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Dafna D Gladman - One of the best experts on this subject based on the ideXlab platform.
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fri0351 does sex or body mass index impact response to therapy in psoriatic arthritis results from a phase 3 double blind randomized trial examining methotrexate and etanercept as monotherapy or in combination for treating psoriatic arthritis
Annals of the Rheumatic Diseases, 2020Co-Authors: P J Mease, Dafna D Gladman, Alexis Ogdie, Joseph F Merola, A Deodhar, David H Collier, Elaine Karis, Lyrica Liu, A KavanaughAbstract:Background: In psoriatic arthritis (PsA), contextual factors such as sex and body mass index (BMI) may affect response to therapy. Objectives: To examine if sex and BMI influenced 24-week (wk) outcomes in a 48-wk PsA trial of methotrexate (MTX) and etanercept (ETN) as monotherapy (mono) or combined.1 Methods: MTX- and biologic-naive adult patients with active PsA were randomized to weekly: MTX 20mg (n=284), ETN 50mg (n=284), or MTX 20mg+ETN 50mg (n=283). Wk-24 outcomes included ACR 20, MDA, VLDA, PASDAS, DAPSA, LDI, SPARCC, BSA, sPGA, and mNAPSI. Descriptive statistics examined outcomes in each treatment arm by sex (male vs female) or BMI (≤30kg/m2 vs >30kg/m2). Modeling analyses also examined sex or BMI effect on outcomes when comparing MTX mono to the ETN-containing arms (analyses were adjusted for any prior use of a nonbiologic disease-modifying antirheumatic drug; the model for the influence of sex also adjusted for baseline BMI status). Nominal P-values are provided. Results: Baseline disease activity was slightly higher in women, especially with MTX+ETN. Descriptive statistics showed men and women had similar results at wk 24 in the MTX mono and ETN mono arms; with MTX+ETN, men had better outcomes for ACR20, MDA, VLDA, and PASDAS. In treatment-interaction analyses, men had more favorable responses at wk 24 with MTX+ETN vs MTX mono for PASDAS, MDA, and LDI (Table). Baseline disease activity was similar in both BMI categories. Descriptive statistics in each treatment arm showed no consistent differences in results at wk 24 between BMI categories. In treatment-interaction analyses, BMI ≤30kg/m2 had a more favorable response at wk 24 with MTX+ETN vs MTX mono for sPGA (Table). Conclusion: Results suggest contextual factors may affect response to therapy in PsA. The treatment-interaction analyses suggest disparate responses to MTX+ETN by sex; BMI only affected skin response. References: [1]Mease et al. Arthritis Rheumatol. 2019;71:1112-24 Disclosure of Interests: Philip J Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/Research Support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Dafna D Gladman Grant/Research Support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/Research Support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Atul Deodhar Grant/Research Support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Alexis Ogdie Grant/Research Support from: Novartis, Pfizer – grant/Research Support, Consultant of: AbbVie, BMS, Eli Lilly, Novartis, Pfizer, Takeda – consultant, David Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc., Elaine Karis Shareholder of: Amgen Inc., Employee of: Amgen Inc., Lyrica Liu Shareholder of: Amgen Inc., Employee of: Amgen Inc., Arthur Kavanaugh Grant/Research Support from: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB
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fri0352 probability of achieving low disease activity or remission with apremilast treatment among dmard naive subjects with active psoriatic arthritis
Annals of the Rheumatic Diseases, 2020Co-Authors: P J Mease, Dafna D Gladman, A Kavanaugh, F Behrens, Alexis Ogdie, Alvin F Wells, Martin J Bergman, S Richter, M Brunori, L TengAbstract:Background: Apremilast (APR) is associated with comparable ACR response rates in DMARD-naive vs DMARD-experienced patients (pts) with psoriatic arthritis (PsA).1,2 A question that remains is if DMARD-naive pts treated with APR have greater chances of achieving treatment targets than DMARD-experienced pts. cDAPSA is a commonly used treatment target. Objectives: To assess the predictive value of baseline (BL) clinical disease status on achieving long-term cDAPSA treatment targets at Wk 52 among DMARD-naive subjects in PALACE 4; to compare these findings vs those recently reported from the PALACE 1-3 studies in subjects with prior exposure to DMARDs; and to provide further evidence that at a group level, achievement of cDAPSA disease targets with APR is associated with no or mild articular and extra-articular disease activity by Wk 52. Methods: This post hoc analysis included subjects assigned to APR 30 mg twice daily at BL who had available cDAPSA data at BL. We calculated the probabilities of shifting across different cDAPSA categories (remission [REM]: ≤4; low disease activity [LDA]: >4 to ≤13; moderate disease activity [Mod]: >13 to ≤27; high disease activity [HDA]: >273) from BL to Wk 52. Mean values of articular and non-articular variables (e.g., PASI, SJC/TJC, MASES, dactylitis) from BL to Wk 52 were assessed by cDAPSA category achieved at Wk 52 to determine the association between achievement of targets and control of articular and non-articular manifestations. Results from the current analyses were compared with the previously reported results from PALACE 1-3. Results: A total of 175 subjects receiving APR were included; at BL, 66.3% were in HDA, 31.4% in Mod, and 2.3% were in LDA. Overall, subjects who achieved treatment targets (LDA or REM) by Wk 52 had lower levels of disease activity at BL, as shown by a lower number of swollen and tender joints and lower presence of enthesitis and dactylitis. Higher prevalence of psoriasis-involved body surface area ≥3% at BL was observed. Subjects in Mod at BL were estimated to be more than twice as likely to achieve REM or LDA at Wk 52 vs subjects in HDA at BL; for subjects in LDA at BL, the estimated probability of achieving cDAPSA treatment targets was 100% (Figure). PALACE 4 subjects with LDA and Mod at BL exhibited higher estimated probabilities of achieving treatment targets (100.0% and 61.7%, respectively) than those observed in the DMARD-experienced population of PALACE 1-3 (71.1% and 46.9%). Subjects in PALACE 4 who achieved REM or LDA by Wk 52 showed no or mild articular and extra-articular disease activity by Wk 52, similar to what was observed in the PALACE 1-3 population.4 Conclusion: DMARD-naive subjects in PALACE 4 who had LDA or Mod at BL had the highest likelihood of achieving treatment targets (cDAPSA REM or LDA) by Wk 52 with continued APR treatment. Results from the current probability analyses revealed higher probability rates than those observed in the DMARD-experienced PALACE 1-3 population; control of articular and extra-articular manifestations was observed in the DMARD-naive and DMARD-experienced populations. References: [1]Wells AF, et al. Rheumatology. 2018;57:1253-63. 2. Kavanaugh A, et al. Arthritis Res Ther. 2019;21:118. 3. Machado PM. Ann Rheum Dis. 2016;75:787-90. 4. Mease PJ, et al. Arthritis Care Res. 2020 Jan 7. Disclosure of Interests: Philip J Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/Research Support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Arthur Kavanaugh Grant/Research Support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB – grant/Research Support, Alexis Ogdie Grant/Research Support from: Novartis, Pfizer – grant/Research Support, Consultant of: AbbVie, BMS, Eli Lilly, Novartis, Pfizer, Takeda – consultant, Alvin F. Wells Grant/Research Support from: AbbVie, Celgene Corporation, Lilly – grant/Research Support, Consultant of: AbbVie, Alexion, Amgen, BMS, Celgene Corporation, Horizon, Lilly, Novartis, UCB – consultant, Speakers bureau: AbbVie, Alexion, Amgen, BMS, Celgene Corporation, Horizon, Lilly, Novartis, UCB – speakers bureau, Martin Bergman Shareholder of: Johnson & Johnson – stockholder, Consultant of: AbbVie, BMS, Celgene Corporation, Genentech, Janssen, Merck, Novartis, Pfizer, Sanofi – consultant, Speakers bureau: AbbVie, Celgene Corporation, Novartis, Pfizer, Sanofi – speakers bureau, Dafna D Gladman Grant/Research Support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/Research Support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Frank Behrens Grant/Research Support from: AbbVie, Chugai, Janssen, Roche, Pfizer – grant/Research Support, Consultant of: AbbVie Biotest, Boehringer Ingelheim, Celgene Corporation, Chugai, Eli Lilly, Genzyme, Janssen, Novartis, Pfizer, Roche, UCB – consultant, Speakers bureau: AbbVie, Biotest, BMS, Celgene Corporation, Chugai, Eli Lilly, Genzyme, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, UCB - speaker, Sven Richter Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Michele Brunori Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Lichen Teng Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Benoit Guerette Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Josef S. Smolen Grant/Research Support from: AbbVie, Eli Lilly, Janssen, Merck Sharp & Dohme, Pfizer, Roche – grant/Research Support, Consultant of: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – consultant, Speakers bureau: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – speaker
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sat0395 responsiveness and clinical trial discrimination of swollen and tender joint counts for the measurement of msk disease activity in psoriatic arthritis
Annals of the Rheumatic Diseases, 2019Co-Authors: Ali Duartegarcia, Dafna D Gladman, Philip J Mease, Lihi Eder, Niti Goel, Maarten De Wit, Oliver Fitzgerald, Ying Ying Leung, Anamaria Orbai, Bev SheaAbstract:Background While tender and swollen joint counts (TJC and SJC) are key instruments for the assessment of peripheral arthritis in PsA, little is known about the psychometric properties of TJC and SJC in randomized controlled trials (RCTs) and how these properties differ among patient subgroups. 1 Objectives To assess the responsiveness and discrimination of TJC and SJC in PsA using RCT datasets and evaluate subgroups of patients with early vs. established disease and 3 or less vs 4 or more active joints. Methods Patient-level data from 8 phase III RCTs and the TIght COntrol of Psoriatic Arthritis (TICOPA) trial were analyzed2. The standardized response mean (SRM, mean difference between baseline and follow up divided by the standard deviation (SD) of the mean difference) and standardized mean differences (SMD, mean difference in the treated group minus the mean difference in the placebo group divided by the pooled SD for the change) were used to address responsiveness and discrimination respectively. TJC28, SJC28, TJC68, and SJC66 were the primary measures of interest but physician and patient global assessments (PhGA and PtGA) and pain were included for comparison. SRMs were calculated in subgroups of patients with less than 3 (TJC68/SJC66 ≤ 3) or more than 3 (TJC68/SJC66) active joints as well as early ( Results In traditional phase III RCTs, TJC and SJC were responsive and had good clinical trial discrimination. SRMs were similar and ranged from -0.8 to -0.4 (‘moderate’ responsiveness) (Figure 1). SMDs were similar among SJC28 and SJC66 and likewise between TJC28 and TJC68 but mostly within the small effect range (-0.2 to -0.5; not shown). PhGA and PtGA had higher SMDs than the joint counts. SRMs were substantially lower for joint counts (and also PtGA) among the low compared with the higher joint count groups (Figure 2). There were no substantial differences in SRMs between patients with early and established disease. Conclusion Joint counts are responsive to change and have reasonable discrimination in RCTs among patients higher disease activity at baseline. However, joint counts may not be ideal outcome measures in oligoarticular disease and have lower responsiveness and discrimination in this subgroup. References [1] Duarte-Garcia et al. J Rheumatol 2019 In Press. [2] Coates et al. Lancet 2016 Acknowledgement Funded by the Rheumatology Research Foundation; We would like to thank Janssen Scientific Affairs LLC, YODA (Yale Open Data Access) Project, UCB, Novartis, and Pfizer for their scientific partnership. Disclosure of Interests Ali Duarte-Garcia: None declared, Lihi Eder Grant/Research Support from: AbbVie, Eli Lilly and Company, Amgen, Celgene, UCB, Janssen, Novartis, and Pfizer, Consultant for: AbbVie, Eli Lilly and Company, Amgen, Celgene, UCB, Janssen, Novartis, and Pfizer, Niti Goel Shareholder of: Own stock options in Kezar Life Sciences., Employee of: Corporate officer of Kezar Life Sciences., Maarten de Wit: None declared, Dafna D Gladman Grant/Research Support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Oliver FitzGerald: None declared, Philip J Mease Grant/Research Support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: AbbVie, Amgen, BMS, Galapagos, Gilead Sciences, Inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Ying Ying Leung Grant/Research Support from: Abbvie, Novartis, Speakers bureau: Abbvie and Novartis, Speakers bureau: Novartis, Ana-Maria Orbai Grant/Research Support from: AbbVie, Celgene, Horizon Pharma, Janssen, Lilly, and Novartis, Consultant for: Lilly, Janssen, Novartis, Pfizer, and UCB, Bev Shea Employee of: Salary partially paid by OMERACT, Vibeke Strand Consultant for: AbbVie, Amgen, Bayer, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo, EMD Serono, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Kezar, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Servier, UCB., Philip Helliwell Grant/Research Support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos, Alisa Stephens-Shields: None declared, William Tillett Grant/Research Support from: AbbVie, Celgene, and Lilly, Consultant for: AbbVie, Celgene, Lilly, Novartis, and Pfizer, Speakers bureau: Abbvie, Celgene, Lilly, Janssen, Novartis, UCB, and Pfizer, Laura C Coates Grant/Research Support from: AbbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead Sciences Inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB, Alexis Ogdie Grant/Research Support from: (To my university) Novartis, Pfizer, Grant/Research Support from: Novartis, Pfizer, Grant/Research Support from: Novartis, Pfizer, Grant/Research Support from: Novartis, Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly and Company, Novartis, Pfizer, and Takeda, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda
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sat0448 apremilast treatment and long term up to 156 weeks improvements in dactylitis and enthesitis in patients with psoriatic arthritis analysis of a large database of the phase iii clinical development program
Annals of the Rheumatic Diseases, 2017Co-Authors: Dafna D Gladman, J Wollenhaupt, Eric Lespessailles, Georg Schett, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, M Mcilraith, Christopher J Edwards, C BirbaraAbstract:Background Dactylitis and enthesitis, hallmark features of psoriatic arthritis (PsA), may be difficult to manage. PALACE 1, 2, and 3 compared the efficacy and safety of apremilast (APR) with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics. Objectives Report the impact of long-term APR 30 mg BID (APR30) treatment on dactylitis and enthesitis in pts with active PsA. Methods Pts were randomized (1:1:1) to PBO, APR30, or APR 20 mg BID (APR20) stratified by baseline (BL) DMARD use (yes/no). After the 24-wk PBO-controlled phase, all pts received APR30 or APR20 and could enroll in long-term follow-up. Data for pts entering the study with pre-existing dactylitis or enthesitis were pooled across PALACE 1–3, as prespecified, to allow for robust analysis. Dactylitis count (number of digits [hands/feet] with dactylitis present [0=absence, 1=presence]; range: 0–20) was used to assess dactylitis improvement. Enthesitis was evaluated based on MASES (range: 0–13), indicating the number of painful entheses out of 13 enthesis sites. Wk 24 analyses used LOCF for missing values and data for early escape pts; Wks 52 and 156 used data as observed. Results Among pts with dactylitis (n=610) or enthesitis (n=915) at BL and ≥1 post-BL value, BL mean dactylitis counts ranged from 3.2 to 3.4 and MASES ranged from 4.4 to 4.8. At Wk 24, mean change in dactylitis count was −1.8 (APR30) vs −1.3 (PBO) ( P =0.0097); more APR30 pts achieved a dactylitis count of 0 vs PBO pts (Table). Mean change in MASES was −1.3 (APR30) vs −0.9 (PBO) ( P =0.0194); more APR30 pts achieved a MASES of 0 vs PBO pts. Significant effect on enthesitis was confirmed in the PSA-006 (ACTIVE) study of APR in pts with a maximum of 1 previous DMARD treatment, in which the Gladman Enthesitis Index was used, focusing on more peripheral sites of activity: significant effect for APR vs PBO was seen as early as Wk 2, and at Wk 24, mean changes were −1.5 vs −0.5 ( P =0.0032, MMRM). Sustained improvements in dactylitis and enthesitis severity were seen in APR pts at Wk 156 in PALACE 1–3 (Table): for dactylitis, 79.6% achieved a count of 0 and the mean percent change was −83.6%; for MASES, 55.0% of APR pts achieved a score of 0 and the mean percent change was −65.2%. Conclusions The majority of pts (63%) in PALACE 1–3 had active enthesitis and 42% had dactylitis at BL. APR30 demonstrated early and long-term benefit (up to 156 wks) in treating dactylitis and enthesitis, including resolution of BL disease in many pts. Disclosure of Interest D. Gladman Grant/Research Support from: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, A. Kavanaugh Grant/Research Support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, J. Gomez-Reino Grant/Research Support from: Roche and Schering-Plough, Consultant for: BMS, Pfizer, Roche, Schering-Plough, UCB, J. Wollenhaupt Grant/Research Support from: Abbott, BMS, MSD, Pfizer, UCB, Consultant for: Abbott, BMS, MSD, Pfizer, UCB, M. Cutolo Grant/Research Support from: Actelion, BMS, Sanofi-Aventis, Consultant for: Actelion, BMS, Sanofi-Aventis, G. Schett Grant/Research Support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, E. Lespessailles Grant/Research Support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, M. McIlraith Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, C. Edwards Grant/Research Support from: Celgene Corporation, Pfizer, Roche, Samsung, Consultant for: Celgene Corporation, Pfizer, Roche, Samsung, Speakers bureau: Abbott, GSK, Pfizer, Roche, C. Birbara Grant/Research Support from: Amgen, BMS, Incyte, Eli Lilly, Merck, Pfizer, P. Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB
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op0169 apremilast an oral phosphodiesterase 4 inhibitor is associated with long term 104 week improvements in enthesitis and dactylitis in patients with psoriatic arthritis pooled results from three phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2015Co-Authors: Dafna D Gladman, J Wollenhaupt, Eric Lespessailles, Georg Schett, Maurizio Cutolo, J J Gomezreino, M Mcilraith, A O Adebajo, A Kavanaugh, Christopher J EdwardsAbstract:Background Apremilast (APR), a PDE4 inhibitor, helps regulate immune responses in psoriatic arthritis (PsA). PALACE 1-3 compared APR efficacy/safety with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics, including efficacy assessment across multiple aspects of disease. Enthesitis and dactylitis are hallmark features of PsA that lead to pain and disability. Objectives Evaluate the impact of APR treatment over 104 wks on enthesitis and dactylitis in a pooled analysis of PALACE 1-3. Methods Pts were randomized (1:1:1) to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline (BL) DMARD use (yes/no). The PBO-controlled phase continued to Wk 24, with an early escape option at Wk 16. Double-blind APR treatment continued to Wk 52; pts could then continue to receive APR for up to an additional 4 years during an open-label extension phase. Data were pooled across PALACE 1-3 to allow for analysis of robust numbers of pts with pre-existing enthesopathy and/or dactylitis. Enthesitis was evaluated based on Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) (range 0-13), which indicates the number of painful entheses out of 13 entheses sites. The dactylitis count (range 0-20) is the number of digits (hands/feet) with dactylitis present; each digit is rated as 0 (none) or 1 (present). Results Long-term improvement in enthesitis and dactylitis severity was seen in pts with enthesitis and/or dactylitis at BL who were receiving APR at 104 weeks, as shown by reductions in MASES and dactylitis counts (Table). Mean changes in MASES were -57.5% (APR30) and -55.1% (APR20) at Wk 104. MASES scores of 0, indicating no pain at any of the entheses assessed, were achieved by 48.7% (APR30) and 51.5% (APR20) of pts. Mean changes in dactylitis count were -80.0% (APR30) and -75.8% (APR20) at Wk 104. Dactylitis counts decreased to 0 in 77.5% (APR30) and 72.9% (APR20) of pts. Over 104 wks, most AEs were mild/moderate in severity; in general, no increase was seen in AE incidence/severity with longer term exposure. Conclusions Over 104 wks, APR continued to demonstrate efficacy in PsA treatment, including improvements in enthesitis and dactylitis. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 104 wks. Disclosure of Interest D. Gladman Grant/Research Support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Kavanaugh Grant/Research Support from: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support from: Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth, J. Wollenhaupt Grant/Research Support from: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/Research Support from: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, Consultant for: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, G. Schett Grant/Research Support from: Abbott, Celgene Corporation, Roche, and UCB, Consultant for: Abbott, Celgene Corporation, Roche, and UCB, E. Lespessailles Grant/Research Support from: Amgen, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, M. McIlraith Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, C. Edwards Grant/Research Support from: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/Research Support from: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and Pfizer Inc, P. Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB,Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB,Celgene Corporation, Novartis, and Roche, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB,
Philip J Mease - One of the best experts on this subject based on the ideXlab platform.
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fri0451 secukinumab provides sustained improvements in the signs and symptoms in psoriatic arthritis final 5 year efficacy and safety results from a phase 3 trial
Annals of the Rheumatic Diseases, 2019Co-Authors: Philip J Mease, A Kavanaugh, Andreas M Reimold, Hasan Tahir, J Rech, Stephen Hall, Piet Geusens, Pascale Pellet, Eumorphia Maria DelichaAbstract:Background Secukinumab (SEC) provided rapid and significant improvements in all key clinical domains of psoriatic arthritis (PsA) in the FUTURE 1 study (NCT01392326) with improvements sustained through 3 years.1 Objectives We present the final 5 year efficacy and safety results of the study. Methods Overall, 606 adults with active PsA were randomised to SEC 10 mg/kg intravenously at baseline, and at weeks (wks) 2 and 4, followed by 150 mg or 75 mg subcutaneously (SC) every 4 wks, or matching placebo. Placebo patients (pts) were re-randomised to SEC 150 mg or 75 mg SC from Wk 16 or 24, depending on clinical response.1 At Wk 104, 460 pts entered the 3-year extension study. Pts could have SEC dose escalated from 150 to 300 mg and from 75 mg to 150/300 mg starting from Wk 156, based on physician’s judgement. Assessments at Wk 260 included ACR20/50/70, PASI 90, HAQ-DI, SF-36 PCS, and resolution of dactylitis and enthesitis and are reported for pts originally randomised to the SEC 150 mg and 75 mg groups (observed data). Safety is reported as exposure adjusted incidence rate/100 patient-years (EAIR) for all pts (n = 587) who received ≥1 dose of study treatment. Results Overall, 132/161 (82%) and 124/147 (84.4%) pts originally randomised to SEC 150/75 mg, respectively, who entered the extension study, completed 260 Wks of treatment. A total of 86/236 (36.4%) pts on SEC 150 mg were escalated to 300 mg, while 180/221 (81.4%) pts on SEC 75 mg were escalated to 150/300 mg. Clinical responses were sustained or further improved through 5 years treatment (Table 1). Over the entire study period (SEC mean exposure of 2320 patient-years), the safety profile of SEC was consistent with previous reports.1 EAIR of selected adverse events for SEC were serious infections (1.8), ulcerative colitis (0.04), Crohn’s disease (0.1), and MACE (0.5). Six deaths (3 in each dose group) were reported in any SEC group through 5 years. Conclusion SEC provided sustained improvements in the signs and symptoms in the major clinical domains of PsA through 5 years. SEC was well tolerated with a safety profile consistent with that previously reported. References [1] Mease PJ, et al. Ann. Rheum. Dis. 2017; 76 (suppl 2): 952. Disclosure of Interests Philip J Mease Grant/Research Support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: AbbVie, Amgen, BMS, Galapagos, Gilead Sciences, Inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Arthur Kavanaugh Grant/Research Support from: UCB Pharma, Andreas Reimold Grant/Research Support from: AbbVie, Hasan Tahir: None declared, Jurgen Rech Grant/Research Support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Stephen Hall Grant/Research Support from: AbbVie Inc, BMS, Lilly, Janssen, Pfizer, UCB, and Novartis, Consultant for: AbbVie Inc, BMS, Lilly, Janssen, Pfizer, UCB, and Novartis , Piet Geusens Grant/Research Support from: Research Support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Grant/Research Support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Consultant for: Research Support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Research Support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Pascale Pellet Shareholder of: Novartis, Employee of: Novartis, Eumorphia Maria Delicha Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Shephard Mpofu Employee of: Novartis
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sat0395 responsiveness and clinical trial discrimination of swollen and tender joint counts for the measurement of msk disease activity in psoriatic arthritis
Annals of the Rheumatic Diseases, 2019Co-Authors: Ali Duartegarcia, Dafna D Gladman, Philip J Mease, Lihi Eder, Niti Goel, Maarten De Wit, Oliver Fitzgerald, Ying Ying Leung, Anamaria Orbai, Bev SheaAbstract:Background While tender and swollen joint counts (TJC and SJC) are key instruments for the assessment of peripheral arthritis in PsA, little is known about the psychometric properties of TJC and SJC in randomized controlled trials (RCTs) and how these properties differ among patient subgroups. 1 Objectives To assess the responsiveness and discrimination of TJC and SJC in PsA using RCT datasets and evaluate subgroups of patients with early vs. established disease and 3 or less vs 4 or more active joints. Methods Patient-level data from 8 phase III RCTs and the TIght COntrol of Psoriatic Arthritis (TICOPA) trial were analyzed2. The standardized response mean (SRM, mean difference between baseline and follow up divided by the standard deviation (SD) of the mean difference) and standardized mean differences (SMD, mean difference in the treated group minus the mean difference in the placebo group divided by the pooled SD for the change) were used to address responsiveness and discrimination respectively. TJC28, SJC28, TJC68, and SJC66 were the primary measures of interest but physician and patient global assessments (PhGA and PtGA) and pain were included for comparison. SRMs were calculated in subgroups of patients with less than 3 (TJC68/SJC66 ≤ 3) or more than 3 (TJC68/SJC66) active joints as well as early ( Results In traditional phase III RCTs, TJC and SJC were responsive and had good clinical trial discrimination. SRMs were similar and ranged from -0.8 to -0.4 (‘moderate’ responsiveness) (Figure 1). SMDs were similar among SJC28 and SJC66 and likewise between TJC28 and TJC68 but mostly within the small effect range (-0.2 to -0.5; not shown). PhGA and PtGA had higher SMDs than the joint counts. SRMs were substantially lower for joint counts (and also PtGA) among the low compared with the higher joint count groups (Figure 2). There were no substantial differences in SRMs between patients with early and established disease. Conclusion Joint counts are responsive to change and have reasonable discrimination in RCTs among patients higher disease activity at baseline. However, joint counts may not be ideal outcome measures in oligoarticular disease and have lower responsiveness and discrimination in this subgroup. References [1] Duarte-Garcia et al. J Rheumatol 2019 In Press. [2] Coates et al. Lancet 2016 Acknowledgement Funded by the Rheumatology Research Foundation; We would like to thank Janssen Scientific Affairs LLC, YODA (Yale Open Data Access) Project, UCB, Novartis, and Pfizer for their scientific partnership. Disclosure of Interests Ali Duarte-Garcia: None declared, Lihi Eder Grant/Research Support from: AbbVie, Eli Lilly and Company, Amgen, Celgene, UCB, Janssen, Novartis, and Pfizer, Consultant for: AbbVie, Eli Lilly and Company, Amgen, Celgene, UCB, Janssen, Novartis, and Pfizer, Niti Goel Shareholder of: Own stock options in Kezar Life Sciences., Employee of: Corporate officer of Kezar Life Sciences., Maarten de Wit: None declared, Dafna D Gladman Grant/Research Support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Oliver FitzGerald: None declared, Philip J Mease Grant/Research Support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: AbbVie, Amgen, BMS, Galapagos, Gilead Sciences, Inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Ying Ying Leung Grant/Research Support from: Abbvie, Novartis, Speakers bureau: Abbvie and Novartis, Speakers bureau: Novartis, Ana-Maria Orbai Grant/Research Support from: AbbVie, Celgene, Horizon Pharma, Janssen, Lilly, and Novartis, Consultant for: Lilly, Janssen, Novartis, Pfizer, and UCB, Bev Shea Employee of: Salary partially paid by OMERACT, Vibeke Strand Consultant for: AbbVie, Amgen, Bayer, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo, EMD Serono, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Kezar, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Servier, UCB., Philip Helliwell Grant/Research Support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos, Alisa Stephens-Shields: None declared, William Tillett Grant/Research Support from: AbbVie, Celgene, and Lilly, Consultant for: AbbVie, Celgene, Lilly, Novartis, and Pfizer, Speakers bureau: Abbvie, Celgene, Lilly, Janssen, Novartis, UCB, and Pfizer, Laura C Coates Grant/Research Support from: AbbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead Sciences Inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB, Alexis Ogdie Grant/Research Support from: (To my university) Novartis, Pfizer, Grant/Research Support from: Novartis, Pfizer, Grant/Research Support from: Novartis, Pfizer, Grant/Research Support from: Novartis, Pfizer, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly and Company, Novartis, Pfizer, and Takeda, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Consultant for: Abbvie, Amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda
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ab0741 achievement of cdapsa low disease activity or remission is associated with control of articular and extra articular manifestations of active psoriatic arthritis in subjects treated with apremilast
Annals of the Rheumatic Diseases, 2019Co-Authors: Laura C Coates, F Behrens, Philip J Mease, Alexis Ogdie, M Brunori, L Teng, Anamaria Orbai, Benoit Guerette, Josef S SmolenAbstract:Background Therapeutic targets for psoriatic arthritis (PsA) include the achievement of remission (REM) or low disease activity (LDA), measured by the Clinical Disease activity index for Psoriatic arthritis (cDAPSA [0-154]), a composite of swollen and tender joints counts (SJC and TJC), Patient’s assessment of Pain (PAP) and Patient’s Global assessment of Disease activity (PtGA). Objectives We examined the trajectories for improvement in cDAPSA, its core components and PsA manifestations not measured by cDAPSA among subjects achieving cDAPSA REM or LDA by Week 52. Methods Pooled analyses of the phase III PALACE 1, 2 and 3 studies were performed for subjects assigned to receive apremilast (APR) 30 mg twice daily at baseline (BL). Subjects with cDAPSA components available to calculate responses at Week 52 were included and grouped according to the cDAPSA categories reached at Week 52 (REM: ≤4; LDA: >4 to ≤13; moderate disease activity: >13 to ≤27; high disease activity: >27). We then traced their mean cDAPSA trajectory from BL to Week 52. Mean disease activity in core PsA domains were reported longitudinally by cDAPSA category reached at Week 52. Results A total of 375 aPR subjects were included in the analyses. Achievement of REM or LDA by Week 52 was associated with lower mean cDAPSA at BL, and these subjects had continuous improvements in disease activity from BL to Week 52 (Figure). Among subjects who achieved REM or LDA by Week 52, most were classified as having LDA (mean cDAPSA: 8.5) or moderate disease activity (mean cDAPSA: 16.6), respectively, at Week 16. Furthermore, subjects who achieved REM or LDA by Week 52 showed early improvement, with no/mild articular and extra-articular disease activity by Week 52 with aPR (Table). Conclusion In the subgroup of subjects who achieved cDAPSA REM or LDA, early improvement was seen in disease activity by Week 16 and sustained to Week 52 with continued treatment. Subjects achieving cDAPSA REM or LDA exhibited no or mild disease activity in enthesitis, dactylitis, function and skin psoriasis by Week 52. Disclosure of interests Laura C Coates Grant/Research Support from: abbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: abbVie, amgen, BMS, Celgene, Galapagos, Gilead Sciences inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB, Philip J Mease Grant/Research Support from: abbVie, amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: abbVie, amgen, BMS, Galapagos, Gilead Sciences, inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: abbVie, amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Frank Behrens Grant/Research Support from: abbVie, Pfizer, Roche, Chugai, Prophylix, Bioline, Novartis, Consultant for: abbVie, Pfizer, Roche, Chugai, UCB, Bristol-Myers Squibb, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Eli Lilly, Speakers bureau: ad board: abbVie, Pfizer, Roche, Chugai, UCB, Bristol-Myers Squibb, Celgene, Novartis, Biotest, Janssen, Genzyme, Eli Lilly, ana-Maria Orbai Grant/Research Support from: abbVie, Celgene, Horizon Pharma, Janssen, Lilly, and Novartis, Consultant for: Lilly, Janssen, Novartis, Pfizer, and UCB, alexis Ogdie Grant/Research Support from: (To my university) Novartis, Pfizer, Grant/Research Support from: Novartis, Pfizer, Grant/Research Support from: Novartis, Pfizer, Grant/Research Support from: Novartis, Pfizer, Consultant for: abbVie, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly and Company, Novartis, Pfizer, and Takeda, Consultant for: abbVie, amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer inc, Takeda, Consultant for: abbvie, amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Consultant for: abbvie, amgen, BMS, Celgene, Corrona, Lilly, Novartis, Pfizer, Takeda, Michele Brunori Employee of: Celgene Corporation, Lichen Teng Employee of: Celgene Corporation, Benoit Guerette Employee of: Celgene Corporation, Josef S. Smolen Grant/Research Support from: abbVie, Eli Lilly, Janssen, MSD, Pfizer, Roche, Consultant for: abbVie, amgen, astra-Zeneca, astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, MedImmune, MSD, Novartis, Pfizer, Roche, Samsun, Sanofi, UDB, Speakers bureau: abbVie, amgen, astra-Zeneca, astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, MedImmune, MSD, Novartis, Pfizer, Roche, Samsun, Sanofi, UDB
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op0078 apremilast an oral phosphodiesterase 4 inhibitor is associated with long term 52 week improvement in measures of disease activity in patients with psoriatic arthritis results from 3 phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: A Kavanaugh, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Georg Schett, Maurizio Cutolo, J J Gomezreino, Philip J Mease, A O Adebajo, R StevensAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. The PALACE 1, 2, and 3 trials compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics. Objectives Evaluate the impact of APR over 52 weeks on PsA disease activity. Methods Patients were randomized 1:1:1 to receive PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients with Results At Week 16, a significantly greater proportion of patients treated with APR achieved a modified ACR20 response vs PBO (primary endpoint). In patients initially randomized to APR and completing 52 weeks, ACR20 response was sustained over 52 weeks. APR20 and APR30 demonstrated improvement in disease activity vs PBO at Week 16, as measured by the DAS-28 (CRP), modified PsARC response, and good or moderate EULAR response. Among patients who were continuously treated with APR through 52 weeks sustained improvements were observed at Week 52 (Table). The most common adverse events reported during the PBO-controlled period (PAL 1-3; pooled) were diarrhea (12.2%), nausea (10.1%), and headache (8.0%). The safety profile of APR through 52 weeks was similar to that observed with APR for up to 24 weeks of treatment (PBO-controlled period). Conclusions APR demonstrated clinically meaningful improvements in measures of PsA disease activity through Week 52. APR demonstrated an acceptable safety profile and was generally well tolerated through 52 weeks. Disclosure of Interest A. Kavanaugh Grant/Research Support: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc., Roche, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, Consultant for: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, P. Mease Grant/Research Support: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc.,Celgene Corporation, Novartis, Roche and UCB, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., Celgene Corporation, Novartis, Roche and UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene corporation, Janssen, Pfizer Inc., Novartis and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene corporation, Janssen, Pfizer Inc., Novartis and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Roche and Schering Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc., Roche, Schering Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering Plough, and Wyeth, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, and UCB, Consultant for: Abbott, Celgene Corporation, Roche, and UCB, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc., Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc., Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc., and Roche, C. Birbara Grant/Research Support: Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and Pfizer Inc. DOI 10.1136/annrheumdis-2014-eular.1827
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ab0746 apremilast an oral phosphodiesterase 4 inhibitor and the impact of baseline weight and bmi on acr20 and haq di response pooled results from 3 phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: Georg Schett, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, Philip J Mease, A O Adebajo, R StevensAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 1, 2, and 3 compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior disease-modifying antirheumatic drugs and/or biologics. Objectives Assess the impact of baseline weight and body mass index (BMI) on clinical response to APR over 24 weeks in a pooled analysis. Methods Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients with Results 1493 patients were randomized, received ≥1 dose of study medication (PBO: n=496; APR20: n=500; APR30: n=497), and were comparable across treatment groups for demographics, disease characteristics, and prior/concurrent therapy. At baseline, mean (SD) weight was 85.7 (20.6) kg and mean (SD) BMI was 29.9 (6.5) kg/m 2 . APR administration resulted in statistically significant and clinically meaningful improvement in ACR20 response (primary endpoint) in all 3 PALACE trials. APR30 was associated with significant improvements in Health Assessment Questionnaire-Disability Index (HAQ-DI) vs PBO at Week 16 (key secondary endpoint) across all 3 trials. At Week 16, similar ACR20 response rates and improvements in HAQ-DI were observed across all weight and BMI ranges (Table). A favorable treatment effect for both APR treatment groups vs PBO was observed, irrespective of baseline body weight or BMI. Overall, the treatment effect was dose-dependent, with greater effects generally observed in APR30 over APR20 patients. These treatment effects were generally maintained at Week 24. Conclusions APR demonstrated a favorable treatment effect in patients with active PsA. Comparable improvements in the signs and symptoms of PsA and physical function were observed across a broad range of baseline weight and BMI values. Results suggest no dose adjustment is required to account for baseline body weight or BMI. Disclosure of Interest G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, P. Mease Grant/Research Support: Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Kavanaugh Consultant for: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth; and has received Research grants from Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/Research Support: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and DOI 10.1136/annrheumdis-2014-eular.1773
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fri0352 probability of achieving low disease activity or remission with apremilast treatment among dmard naive subjects with active psoriatic arthritis
Annals of the Rheumatic Diseases, 2020Co-Authors: P J Mease, Dafna D Gladman, A Kavanaugh, F Behrens, Alexis Ogdie, Alvin F Wells, Martin J Bergman, S Richter, M Brunori, L TengAbstract:Background: Apremilast (APR) is associated with comparable ACR response rates in DMARD-naive vs DMARD-experienced patients (pts) with psoriatic arthritis (PsA).1,2 A question that remains is if DMARD-naive pts treated with APR have greater chances of achieving treatment targets than DMARD-experienced pts. cDAPSA is a commonly used treatment target. Objectives: To assess the predictive value of baseline (BL) clinical disease status on achieving long-term cDAPSA treatment targets at Wk 52 among DMARD-naive subjects in PALACE 4; to compare these findings vs those recently reported from the PALACE 1-3 studies in subjects with prior exposure to DMARDs; and to provide further evidence that at a group level, achievement of cDAPSA disease targets with APR is associated with no or mild articular and extra-articular disease activity by Wk 52. Methods: This post hoc analysis included subjects assigned to APR 30 mg twice daily at BL who had available cDAPSA data at BL. We calculated the probabilities of shifting across different cDAPSA categories (remission [REM]: ≤4; low disease activity [LDA]: >4 to ≤13; moderate disease activity [Mod]: >13 to ≤27; high disease activity [HDA]: >273) from BL to Wk 52. Mean values of articular and non-articular variables (e.g., PASI, SJC/TJC, MASES, dactylitis) from BL to Wk 52 were assessed by cDAPSA category achieved at Wk 52 to determine the association between achievement of targets and control of articular and non-articular manifestations. Results from the current analyses were compared with the previously reported results from PALACE 1-3. Results: A total of 175 subjects receiving APR were included; at BL, 66.3% were in HDA, 31.4% in Mod, and 2.3% were in LDA. Overall, subjects who achieved treatment targets (LDA or REM) by Wk 52 had lower levels of disease activity at BL, as shown by a lower number of swollen and tender joints and lower presence of enthesitis and dactylitis. Higher prevalence of psoriasis-involved body surface area ≥3% at BL was observed. Subjects in Mod at BL were estimated to be more than twice as likely to achieve REM or LDA at Wk 52 vs subjects in HDA at BL; for subjects in LDA at BL, the estimated probability of achieving cDAPSA treatment targets was 100% (Figure). PALACE 4 subjects with LDA and Mod at BL exhibited higher estimated probabilities of achieving treatment targets (100.0% and 61.7%, respectively) than those observed in the DMARD-experienced population of PALACE 1-3 (71.1% and 46.9%). Subjects in PALACE 4 who achieved REM or LDA by Wk 52 showed no or mild articular and extra-articular disease activity by Wk 52, similar to what was observed in the PALACE 1-3 population.4 Conclusion: DMARD-naive subjects in PALACE 4 who had LDA or Mod at BL had the highest likelihood of achieving treatment targets (cDAPSA REM or LDA) by Wk 52 with continued APR treatment. Results from the current probability analyses revealed higher probability rates than those observed in the DMARD-experienced PALACE 1-3 population; control of articular and extra-articular manifestations was observed in the DMARD-naive and DMARD-experienced populations. References: [1]Wells AF, et al. Rheumatology. 2018;57:1253-63. 2. Kavanaugh A, et al. Arthritis Res Ther. 2019;21:118. 3. Machado PM. Ann Rheum Dis. 2016;75:787-90. 4. Mease PJ, et al. Arthritis Care Res. 2020 Jan 7. Disclosure of Interests: Philip J Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/Research Support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Arthur Kavanaugh Grant/Research Support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB – grant/Research Support, Alexis Ogdie Grant/Research Support from: Novartis, Pfizer – grant/Research Support, Consultant of: AbbVie, BMS, Eli Lilly, Novartis, Pfizer, Takeda – consultant, Alvin F. Wells Grant/Research Support from: AbbVie, Celgene Corporation, Lilly – grant/Research Support, Consultant of: AbbVie, Alexion, Amgen, BMS, Celgene Corporation, Horizon, Lilly, Novartis, UCB – consultant, Speakers bureau: AbbVie, Alexion, Amgen, BMS, Celgene Corporation, Horizon, Lilly, Novartis, UCB – speakers bureau, Martin Bergman Shareholder of: Johnson & Johnson – stockholder, Consultant of: AbbVie, BMS, Celgene Corporation, Genentech, Janssen, Merck, Novartis, Pfizer, Sanofi – consultant, Speakers bureau: AbbVie, Celgene Corporation, Novartis, Pfizer, Sanofi – speakers bureau, Dafna D Gladman Grant/Research Support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/Research Support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Frank Behrens Grant/Research Support from: AbbVie, Chugai, Janssen, Roche, Pfizer – grant/Research Support, Consultant of: AbbVie Biotest, Boehringer Ingelheim, Celgene Corporation, Chugai, Eli Lilly, Genzyme, Janssen, Novartis, Pfizer, Roche, UCB – consultant, Speakers bureau: AbbVie, Biotest, BMS, Celgene Corporation, Chugai, Eli Lilly, Genzyme, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, UCB - speaker, Sven Richter Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Michele Brunori Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Lichen Teng Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Benoit Guerette Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Josef S. Smolen Grant/Research Support from: AbbVie, Eli Lilly, Janssen, Merck Sharp & Dohme, Pfizer, Roche – grant/Research Support, Consultant of: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – consultant, Speakers bureau: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – speaker
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fri0451 secukinumab provides sustained improvements in the signs and symptoms in psoriatic arthritis final 5 year efficacy and safety results from a phase 3 trial
Annals of the Rheumatic Diseases, 2019Co-Authors: Philip J Mease, A Kavanaugh, Andreas M Reimold, Hasan Tahir, J Rech, Stephen Hall, Piet Geusens, Pascale Pellet, Eumorphia Maria DelichaAbstract:Background Secukinumab (SEC) provided rapid and significant improvements in all key clinical domains of psoriatic arthritis (PsA) in the FUTURE 1 study (NCT01392326) with improvements sustained through 3 years.1 Objectives We present the final 5 year efficacy and safety results of the study. Methods Overall, 606 adults with active PsA were randomised to SEC 10 mg/kg intravenously at baseline, and at weeks (wks) 2 and 4, followed by 150 mg or 75 mg subcutaneously (SC) every 4 wks, or matching placebo. Placebo patients (pts) were re-randomised to SEC 150 mg or 75 mg SC from Wk 16 or 24, depending on clinical response.1 At Wk 104, 460 pts entered the 3-year extension study. Pts could have SEC dose escalated from 150 to 300 mg and from 75 mg to 150/300 mg starting from Wk 156, based on physician’s judgement. Assessments at Wk 260 included ACR20/50/70, PASI 90, HAQ-DI, SF-36 PCS, and resolution of dactylitis and enthesitis and are reported for pts originally randomised to the SEC 150 mg and 75 mg groups (observed data). Safety is reported as exposure adjusted incidence rate/100 patient-years (EAIR) for all pts (n = 587) who received ≥1 dose of study treatment. Results Overall, 132/161 (82%) and 124/147 (84.4%) pts originally randomised to SEC 150/75 mg, respectively, who entered the extension study, completed 260 Wks of treatment. A total of 86/236 (36.4%) pts on SEC 150 mg were escalated to 300 mg, while 180/221 (81.4%) pts on SEC 75 mg were escalated to 150/300 mg. Clinical responses were sustained or further improved through 5 years treatment (Table 1). Over the entire study period (SEC mean exposure of 2320 patient-years), the safety profile of SEC was consistent with previous reports.1 EAIR of selected adverse events for SEC were serious infections (1.8), ulcerative colitis (0.04), Crohn’s disease (0.1), and MACE (0.5). Six deaths (3 in each dose group) were reported in any SEC group through 5 years. Conclusion SEC provided sustained improvements in the signs and symptoms in the major clinical domains of PsA through 5 years. SEC was well tolerated with a safety profile consistent with that previously reported. References [1] Mease PJ, et al. Ann. Rheum. Dis. 2017; 76 (suppl 2): 952. Disclosure of Interests Philip J Mease Grant/Research Support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: AbbVie, Amgen, BMS, Galapagos, Gilead Sciences, Inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Arthur Kavanaugh Grant/Research Support from: UCB Pharma, Andreas Reimold Grant/Research Support from: AbbVie, Hasan Tahir: None declared, Jurgen Rech Grant/Research Support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Stephen Hall Grant/Research Support from: AbbVie Inc, BMS, Lilly, Janssen, Pfizer, UCB, and Novartis, Consultant for: AbbVie Inc, BMS, Lilly, Janssen, Pfizer, UCB, and Novartis , Piet Geusens Grant/Research Support from: Research Support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Grant/Research Support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Consultant for: Research Support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Research Support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Pascale Pellet Shareholder of: Novartis, Employee of: Novartis, Eumorphia Maria Delicha Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Shephard Mpofu Employee of: Novartis
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sat0448 apremilast treatment and long term up to 156 weeks improvements in dactylitis and enthesitis in patients with psoriatic arthritis analysis of a large database of the phase iii clinical development program
Annals of the Rheumatic Diseases, 2017Co-Authors: Dafna D Gladman, J Wollenhaupt, Eric Lespessailles, Georg Schett, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, M Mcilraith, Christopher J Edwards, C BirbaraAbstract:Background Dactylitis and enthesitis, hallmark features of psoriatic arthritis (PsA), may be difficult to manage. PALACE 1, 2, and 3 compared the efficacy and safety of apremilast (APR) with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics. Objectives Report the impact of long-term APR 30 mg BID (APR30) treatment on dactylitis and enthesitis in pts with active PsA. Methods Pts were randomized (1:1:1) to PBO, APR30, or APR 20 mg BID (APR20) stratified by baseline (BL) DMARD use (yes/no). After the 24-wk PBO-controlled phase, all pts received APR30 or APR20 and could enroll in long-term follow-up. Data for pts entering the study with pre-existing dactylitis or enthesitis were pooled across PALACE 1–3, as prespecified, to allow for robust analysis. Dactylitis count (number of digits [hands/feet] with dactylitis present [0=absence, 1=presence]; range: 0–20) was used to assess dactylitis improvement. Enthesitis was evaluated based on MASES (range: 0–13), indicating the number of painful entheses out of 13 enthesis sites. Wk 24 analyses used LOCF for missing values and data for early escape pts; Wks 52 and 156 used data as observed. Results Among pts with dactylitis (n=610) or enthesitis (n=915) at BL and ≥1 post-BL value, BL mean dactylitis counts ranged from 3.2 to 3.4 and MASES ranged from 4.4 to 4.8. At Wk 24, mean change in dactylitis count was −1.8 (APR30) vs −1.3 (PBO) ( P =0.0097); more APR30 pts achieved a dactylitis count of 0 vs PBO pts (Table). Mean change in MASES was −1.3 (APR30) vs −0.9 (PBO) ( P =0.0194); more APR30 pts achieved a MASES of 0 vs PBO pts. Significant effect on enthesitis was confirmed in the PSA-006 (ACTIVE) study of APR in pts with a maximum of 1 previous DMARD treatment, in which the Gladman Enthesitis Index was used, focusing on more peripheral sites of activity: significant effect for APR vs PBO was seen as early as Wk 2, and at Wk 24, mean changes were −1.5 vs −0.5 ( P =0.0032, MMRM). Sustained improvements in dactylitis and enthesitis severity were seen in APR pts at Wk 156 in PALACE 1–3 (Table): for dactylitis, 79.6% achieved a count of 0 and the mean percent change was −83.6%; for MASES, 55.0% of APR pts achieved a score of 0 and the mean percent change was −65.2%. Conclusions The majority of pts (63%) in PALACE 1–3 had active enthesitis and 42% had dactylitis at BL. APR30 demonstrated early and long-term benefit (up to 156 wks) in treating dactylitis and enthesitis, including resolution of BL disease in many pts. Disclosure of Interest D. Gladman Grant/Research Support from: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, A. Kavanaugh Grant/Research Support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, J. Gomez-Reino Grant/Research Support from: Roche and Schering-Plough, Consultant for: BMS, Pfizer, Roche, Schering-Plough, UCB, J. Wollenhaupt Grant/Research Support from: Abbott, BMS, MSD, Pfizer, UCB, Consultant for: Abbott, BMS, MSD, Pfizer, UCB, M. Cutolo Grant/Research Support from: Actelion, BMS, Sanofi-Aventis, Consultant for: Actelion, BMS, Sanofi-Aventis, G. Schett Grant/Research Support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, E. Lespessailles Grant/Research Support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, M. McIlraith Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, C. Edwards Grant/Research Support from: Celgene Corporation, Pfizer, Roche, Samsung, Consultant for: Celgene Corporation, Pfizer, Roche, Samsung, Speakers bureau: Abbott, GSK, Pfizer, Roche, C. Birbara Grant/Research Support from: Amgen, BMS, Incyte, Eli Lilly, Merck, Pfizer, P. Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB
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op0078 apremilast an oral phosphodiesterase 4 inhibitor is associated with long term 52 week improvement in measures of disease activity in patients with psoriatic arthritis results from 3 phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: A Kavanaugh, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Georg Schett, Maurizio Cutolo, J J Gomezreino, Philip J Mease, A O Adebajo, R StevensAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. The PALACE 1, 2, and 3 trials compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics. Objectives Evaluate the impact of APR over 52 weeks on PsA disease activity. Methods Patients were randomized 1:1:1 to receive PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients with Results At Week 16, a significantly greater proportion of patients treated with APR achieved a modified ACR20 response vs PBO (primary endpoint). In patients initially randomized to APR and completing 52 weeks, ACR20 response was sustained over 52 weeks. APR20 and APR30 demonstrated improvement in disease activity vs PBO at Week 16, as measured by the DAS-28 (CRP), modified PsARC response, and good or moderate EULAR response. Among patients who were continuously treated with APR through 52 weeks sustained improvements were observed at Week 52 (Table). The most common adverse events reported during the PBO-controlled period (PAL 1-3; pooled) were diarrhea (12.2%), nausea (10.1%), and headache (8.0%). The safety profile of APR through 52 weeks was similar to that observed with APR for up to 24 weeks of treatment (PBO-controlled period). Conclusions APR demonstrated clinically meaningful improvements in measures of PsA disease activity through Week 52. APR demonstrated an acceptable safety profile and was generally well tolerated through 52 weeks. Disclosure of Interest A. Kavanaugh Grant/Research Support: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc., Roche, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, Consultant for: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, P. Mease Grant/Research Support: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc.,Celgene Corporation, Novartis, Roche and UCB, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., Celgene Corporation, Novartis, Roche and UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene corporation, Janssen, Pfizer Inc., Novartis and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene corporation, Janssen, Pfizer Inc., Novartis and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Roche and Schering Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc., Roche, Schering Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering Plough, and Wyeth, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, and UCB, Consultant for: Abbott, Celgene Corporation, Roche, and UCB, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc., Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc., Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc., and Roche, C. Birbara Grant/Research Support: Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and Pfizer Inc. DOI 10.1136/annrheumdis-2014-eular.1827
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ab0746 apremilast an oral phosphodiesterase 4 inhibitor and the impact of baseline weight and bmi on acr20 and haq di response pooled results from 3 phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: Georg Schett, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, Philip J Mease, A O Adebajo, R StevensAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 1, 2, and 3 compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior disease-modifying antirheumatic drugs and/or biologics. Objectives Assess the impact of baseline weight and body mass index (BMI) on clinical response to APR over 24 weeks in a pooled analysis. Methods Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients with Results 1493 patients were randomized, received ≥1 dose of study medication (PBO: n=496; APR20: n=500; APR30: n=497), and were comparable across treatment groups for demographics, disease characteristics, and prior/concurrent therapy. At baseline, mean (SD) weight was 85.7 (20.6) kg and mean (SD) BMI was 29.9 (6.5) kg/m 2 . APR administration resulted in statistically significant and clinically meaningful improvement in ACR20 response (primary endpoint) in all 3 PALACE trials. APR30 was associated with significant improvements in Health Assessment Questionnaire-Disability Index (HAQ-DI) vs PBO at Week 16 (key secondary endpoint) across all 3 trials. At Week 16, similar ACR20 response rates and improvements in HAQ-DI were observed across all weight and BMI ranges (Table). A favorable treatment effect for both APR treatment groups vs PBO was observed, irrespective of baseline body weight or BMI. Overall, the treatment effect was dose-dependent, with greater effects generally observed in APR30 over APR20 patients. These treatment effects were generally maintained at Week 24. Conclusions APR demonstrated a favorable treatment effect in patients with active PsA. Comparable improvements in the signs and symptoms of PsA and physical function were observed across a broad range of baseline weight and BMI values. Results suggest no dose adjustment is required to account for baseline body weight or BMI. Disclosure of Interest G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, P. Mease Grant/Research Support: Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Kavanaugh Consultant for: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth; and has received Research grants from Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/Research Support: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and DOI 10.1136/annrheumdis-2014-eular.1773
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sat0448 apremilast treatment and long term up to 156 weeks improvements in dactylitis and enthesitis in patients with psoriatic arthritis analysis of a large database of the phase iii clinical development program
Annals of the Rheumatic Diseases, 2017Co-Authors: Dafna D Gladman, J Wollenhaupt, Eric Lespessailles, Georg Schett, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, M Mcilraith, Christopher J Edwards, C BirbaraAbstract:Background Dactylitis and enthesitis, hallmark features of psoriatic arthritis (PsA), may be difficult to manage. PALACE 1, 2, and 3 compared the efficacy and safety of apremilast (APR) with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics. Objectives Report the impact of long-term APR 30 mg BID (APR30) treatment on dactylitis and enthesitis in pts with active PsA. Methods Pts were randomized (1:1:1) to PBO, APR30, or APR 20 mg BID (APR20) stratified by baseline (BL) DMARD use (yes/no). After the 24-wk PBO-controlled phase, all pts received APR30 or APR20 and could enroll in long-term follow-up. Data for pts entering the study with pre-existing dactylitis or enthesitis were pooled across PALACE 1–3, as prespecified, to allow for robust analysis. Dactylitis count (number of digits [hands/feet] with dactylitis present [0=absence, 1=presence]; range: 0–20) was used to assess dactylitis improvement. Enthesitis was evaluated based on MASES (range: 0–13), indicating the number of painful entheses out of 13 enthesis sites. Wk 24 analyses used LOCF for missing values and data for early escape pts; Wks 52 and 156 used data as observed. Results Among pts with dactylitis (n=610) or enthesitis (n=915) at BL and ≥1 post-BL value, BL mean dactylitis counts ranged from 3.2 to 3.4 and MASES ranged from 4.4 to 4.8. At Wk 24, mean change in dactylitis count was −1.8 (APR30) vs −1.3 (PBO) ( P =0.0097); more APR30 pts achieved a dactylitis count of 0 vs PBO pts (Table). Mean change in MASES was −1.3 (APR30) vs −0.9 (PBO) ( P =0.0194); more APR30 pts achieved a MASES of 0 vs PBO pts. Significant effect on enthesitis was confirmed in the PSA-006 (ACTIVE) study of APR in pts with a maximum of 1 previous DMARD treatment, in which the Gladman Enthesitis Index was used, focusing on more peripheral sites of activity: significant effect for APR vs PBO was seen as early as Wk 2, and at Wk 24, mean changes were −1.5 vs −0.5 ( P =0.0032, MMRM). Sustained improvements in dactylitis and enthesitis severity were seen in APR pts at Wk 156 in PALACE 1–3 (Table): for dactylitis, 79.6% achieved a count of 0 and the mean percent change was −83.6%; for MASES, 55.0% of APR pts achieved a score of 0 and the mean percent change was −65.2%. Conclusions The majority of pts (63%) in PALACE 1–3 had active enthesitis and 42% had dactylitis at BL. APR30 demonstrated early and long-term benefit (up to 156 wks) in treating dactylitis and enthesitis, including resolution of BL disease in many pts. Disclosure of Interest D. Gladman Grant/Research Support from: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, A. Kavanaugh Grant/Research Support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, J. Gomez-Reino Grant/Research Support from: Roche and Schering-Plough, Consultant for: BMS, Pfizer, Roche, Schering-Plough, UCB, J. Wollenhaupt Grant/Research Support from: Abbott, BMS, MSD, Pfizer, UCB, Consultant for: Abbott, BMS, MSD, Pfizer, UCB, M. Cutolo Grant/Research Support from: Actelion, BMS, Sanofi-Aventis, Consultant for: Actelion, BMS, Sanofi-Aventis, G. Schett Grant/Research Support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, E. Lespessailles Grant/Research Support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, M. McIlraith Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, C. Edwards Grant/Research Support from: Celgene Corporation, Pfizer, Roche, Samsung, Consultant for: Celgene Corporation, Pfizer, Roche, Samsung, Speakers bureau: Abbott, GSK, Pfizer, Roche, C. Birbara Grant/Research Support from: Amgen, BMS, Incyte, Eli Lilly, Merck, Pfizer, P. Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB
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op0169 apremilast an oral phosphodiesterase 4 inhibitor is associated with long term 104 week improvements in enthesitis and dactylitis in patients with psoriatic arthritis pooled results from three phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2015Co-Authors: Dafna D Gladman, J Wollenhaupt, Eric Lespessailles, Georg Schett, Maurizio Cutolo, J J Gomezreino, M Mcilraith, A O Adebajo, A Kavanaugh, Christopher J EdwardsAbstract:Background Apremilast (APR), a PDE4 inhibitor, helps regulate immune responses in psoriatic arthritis (PsA). PALACE 1-3 compared APR efficacy/safety with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics, including efficacy assessment across multiple aspects of disease. Enthesitis and dactylitis are hallmark features of PsA that lead to pain and disability. Objectives Evaluate the impact of APR treatment over 104 wks on enthesitis and dactylitis in a pooled analysis of PALACE 1-3. Methods Pts were randomized (1:1:1) to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline (BL) DMARD use (yes/no). The PBO-controlled phase continued to Wk 24, with an early escape option at Wk 16. Double-blind APR treatment continued to Wk 52; pts could then continue to receive APR for up to an additional 4 years during an open-label extension phase. Data were pooled across PALACE 1-3 to allow for analysis of robust numbers of pts with pre-existing enthesopathy and/or dactylitis. Enthesitis was evaluated based on Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) (range 0-13), which indicates the number of painful entheses out of 13 entheses sites. The dactylitis count (range 0-20) is the number of digits (hands/feet) with dactylitis present; each digit is rated as 0 (none) or 1 (present). Results Long-term improvement in enthesitis and dactylitis severity was seen in pts with enthesitis and/or dactylitis at BL who were receiving APR at 104 weeks, as shown by reductions in MASES and dactylitis counts (Table). Mean changes in MASES were -57.5% (APR30) and -55.1% (APR20) at Wk 104. MASES scores of 0, indicating no pain at any of the entheses assessed, were achieved by 48.7% (APR30) and 51.5% (APR20) of pts. Mean changes in dactylitis count were -80.0% (APR30) and -75.8% (APR20) at Wk 104. Dactylitis counts decreased to 0 in 77.5% (APR30) and 72.9% (APR20) of pts. Over 104 wks, most AEs were mild/moderate in severity; in general, no increase was seen in AE incidence/severity with longer term exposure. Conclusions Over 104 wks, APR continued to demonstrate efficacy in PsA treatment, including improvements in enthesitis and dactylitis. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 104 wks. Disclosure of Interest D. Gladman Grant/Research Support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Kavanaugh Grant/Research Support from: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support from: Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth, J. Wollenhaupt Grant/Research Support from: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/Research Support from: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, Consultant for: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, G. Schett Grant/Research Support from: Abbott, Celgene Corporation, Roche, and UCB, Consultant for: Abbott, Celgene Corporation, Roche, and UCB, E. Lespessailles Grant/Research Support from: Amgen, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, M. McIlraith Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, C. Edwards Grant/Research Support from: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/Research Support from: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and Pfizer Inc, P. Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB,Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB,Celgene Corporation, Novartis, and Roche, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB,
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op0078 apremilast an oral phosphodiesterase 4 inhibitor is associated with long term 52 week improvement in measures of disease activity in patients with psoriatic arthritis results from 3 phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: A Kavanaugh, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Georg Schett, Maurizio Cutolo, J J Gomezreino, Philip J Mease, A O Adebajo, R StevensAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. The PALACE 1, 2, and 3 trials compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics. Objectives Evaluate the impact of APR over 52 weeks on PsA disease activity. Methods Patients were randomized 1:1:1 to receive PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients with Results At Week 16, a significantly greater proportion of patients treated with APR achieved a modified ACR20 response vs PBO (primary endpoint). In patients initially randomized to APR and completing 52 weeks, ACR20 response was sustained over 52 weeks. APR20 and APR30 demonstrated improvement in disease activity vs PBO at Week 16, as measured by the DAS-28 (CRP), modified PsARC response, and good or moderate EULAR response. Among patients who were continuously treated with APR through 52 weeks sustained improvements were observed at Week 52 (Table). The most common adverse events reported during the PBO-controlled period (PAL 1-3; pooled) were diarrhea (12.2%), nausea (10.1%), and headache (8.0%). The safety profile of APR through 52 weeks was similar to that observed with APR for up to 24 weeks of treatment (PBO-controlled period). Conclusions APR demonstrated clinically meaningful improvements in measures of PsA disease activity through Week 52. APR demonstrated an acceptable safety profile and was generally well tolerated through 52 weeks. Disclosure of Interest A. Kavanaugh Grant/Research Support: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc., Roche, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, Consultant for: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, P. Mease Grant/Research Support: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc.,Celgene Corporation, Novartis, Roche and UCB, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., Celgene Corporation, Novartis, Roche and UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene corporation, Janssen, Pfizer Inc., Novartis and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene corporation, Janssen, Pfizer Inc., Novartis and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Roche and Schering Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc., Roche, Schering Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering Plough, and Wyeth, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, and UCB, Consultant for: Abbott, Celgene Corporation, Roche, and UCB, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc., Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc., Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc., and Roche, C. Birbara Grant/Research Support: Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and Pfizer Inc. DOI 10.1136/annrheumdis-2014-eular.1827
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ab0746 apremilast an oral phosphodiesterase 4 inhibitor and the impact of baseline weight and bmi on acr20 and haq di response pooled results from 3 phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: Georg Schett, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, Philip J Mease, A O Adebajo, R StevensAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 1, 2, and 3 compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior disease-modifying antirheumatic drugs and/or biologics. Objectives Assess the impact of baseline weight and body mass index (BMI) on clinical response to APR over 24 weeks in a pooled analysis. Methods Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients with Results 1493 patients were randomized, received ≥1 dose of study medication (PBO: n=496; APR20: n=500; APR30: n=497), and were comparable across treatment groups for demographics, disease characteristics, and prior/concurrent therapy. At baseline, mean (SD) weight was 85.7 (20.6) kg and mean (SD) BMI was 29.9 (6.5) kg/m 2 . APR administration resulted in statistically significant and clinically meaningful improvement in ACR20 response (primary endpoint) in all 3 PALACE trials. APR30 was associated with significant improvements in Health Assessment Questionnaire-Disability Index (HAQ-DI) vs PBO at Week 16 (key secondary endpoint) across all 3 trials. At Week 16, similar ACR20 response rates and improvements in HAQ-DI were observed across all weight and BMI ranges (Table). A favorable treatment effect for both APR treatment groups vs PBO was observed, irrespective of baseline body weight or BMI. Overall, the treatment effect was dose-dependent, with greater effects generally observed in APR30 over APR20 patients. These treatment effects were generally maintained at Week 24. Conclusions APR demonstrated a favorable treatment effect in patients with active PsA. Comparable improvements in the signs and symptoms of PsA and physical function were observed across a broad range of baseline weight and BMI values. Results suggest no dose adjustment is required to account for baseline body weight or BMI. Disclosure of Interest G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, P. Mease Grant/Research Support: Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Kavanaugh Consultant for: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth; and has received Research grants from Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/Research Support: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and DOI 10.1136/annrheumdis-2014-eular.1773
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sat0408 long term safety and tolerability of apremilast an oral phosphodiesterase 4 inhibitor in patients with psoriatic arthritis pooled safety analysis of three phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: Philip J Mease, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Georg Schett, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, A O Adebajo, K ShahAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 1, 2, and 3 compared the efficacy and safety of APR with placebo (PBO) in patients with active PsA despite prior conventional DMARDs and/or biologics. Objectives The overall safety and tolerability of APR was assessed in a pooled analysis of PALACE 1, 2, and 3, with APR exposure ≥52 wks. Methods Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline (BL) DMARD use (yes/no). Patients with Results 1,493 patients received study medication (PBO: 495; APR20: 501; APR30: 497) and were included in the safety population. The APR-exposure period included 720 patients treated with APR20 (766.4 patient-yrs) and 721 with APR30 (769.0 patient-yrs). The nature, incidence, and severity of AEs were comparable through the 24-wk and 52-wk periods (Table). The most common AEs were diarrhea (14.3%), nausea (12.6%), headache (10.1%), URTI (10.3%), and nasopharyngitis (7.4%). Most AEs were mild or moderate in severity. Discontinuations due to AEs (APR20: 7.5%; APR30: 8.3%) were low, occurring primarily in the first 24 wks of treatment. Serious AEs (SAEs) occurred in 6.8% (APR20) and 7.2% (APR30) of patients. One death occurred (APR20) due to multiorgan failure not suspected to be treatment-related. Diarrhea and nausea were predominantly mild and occurred at a reduced incidence after the first month of dosing, with the highest incidence reported in the first 2 wks of treatment. Most cases resolved within 30 days despite continued therapy and without medical intervention. Discontinuation due to GI AEs was 4% through Wk 52, with nausea (1.7%) and diarrhea (1.5%) being the most common. There was 1 case of diarrhea and 1 case of nausea reported as an SAE in the 0 to ≥24-wk period, and no additional cases reported in the 0 to ≥52-wk period. Exposure-adjusted incidence rates of major adverse cardiac events, serious infections including systemic opportunistic infection, or malignancies were comparable to PBO. Laboratory abnormalities were infrequent and transient with no trends or patterns observed. Conclusions APR demonstrated an acceptable safety profile and was generally well tolerated through 52 wks; the nature, incidence, and severity of AEs were comparable through the 24-wk and 52-wk periods. These data do not indicate a need for laboratory monitoring. Disclosure of Interest P. Mease Grant/Research Support: Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, A. Kavanaugh Grant/Research Support: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, K. Shah Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/Research Support: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and DOI 10.1136/annrheumdis-2014-eular.5589
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sat0448 apremilast treatment and long term up to 156 weeks improvements in dactylitis and enthesitis in patients with psoriatic arthritis analysis of a large database of the phase iii clinical development program
Annals of the Rheumatic Diseases, 2017Co-Authors: Dafna D Gladman, J Wollenhaupt, Eric Lespessailles, Georg Schett, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, M Mcilraith, Christopher J Edwards, C BirbaraAbstract:Background Dactylitis and enthesitis, hallmark features of psoriatic arthritis (PsA), may be difficult to manage. PALACE 1, 2, and 3 compared the efficacy and safety of apremilast (APR) with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics. Objectives Report the impact of long-term APR 30 mg BID (APR30) treatment on dactylitis and enthesitis in pts with active PsA. Methods Pts were randomized (1:1:1) to PBO, APR30, or APR 20 mg BID (APR20) stratified by baseline (BL) DMARD use (yes/no). After the 24-wk PBO-controlled phase, all pts received APR30 or APR20 and could enroll in long-term follow-up. Data for pts entering the study with pre-existing dactylitis or enthesitis were pooled across PALACE 1–3, as prespecified, to allow for robust analysis. Dactylitis count (number of digits [hands/feet] with dactylitis present [0=absence, 1=presence]; range: 0–20) was used to assess dactylitis improvement. Enthesitis was evaluated based on MASES (range: 0–13), indicating the number of painful entheses out of 13 enthesis sites. Wk 24 analyses used LOCF for missing values and data for early escape pts; Wks 52 and 156 used data as observed. Results Among pts with dactylitis (n=610) or enthesitis (n=915) at BL and ≥1 post-BL value, BL mean dactylitis counts ranged from 3.2 to 3.4 and MASES ranged from 4.4 to 4.8. At Wk 24, mean change in dactylitis count was −1.8 (APR30) vs −1.3 (PBO) ( P =0.0097); more APR30 pts achieved a dactylitis count of 0 vs PBO pts (Table). Mean change in MASES was −1.3 (APR30) vs −0.9 (PBO) ( P =0.0194); more APR30 pts achieved a MASES of 0 vs PBO pts. Significant effect on enthesitis was confirmed in the PSA-006 (ACTIVE) study of APR in pts with a maximum of 1 previous DMARD treatment, in which the Gladman Enthesitis Index was used, focusing on more peripheral sites of activity: significant effect for APR vs PBO was seen as early as Wk 2, and at Wk 24, mean changes were −1.5 vs −0.5 ( P =0.0032, MMRM). Sustained improvements in dactylitis and enthesitis severity were seen in APR pts at Wk 156 in PALACE 1–3 (Table): for dactylitis, 79.6% achieved a count of 0 and the mean percent change was −83.6%; for MASES, 55.0% of APR pts achieved a score of 0 and the mean percent change was −65.2%. Conclusions The majority of pts (63%) in PALACE 1–3 had active enthesitis and 42% had dactylitis at BL. APR30 demonstrated early and long-term benefit (up to 156 wks) in treating dactylitis and enthesitis, including resolution of BL disease in many pts. Disclosure of Interest D. Gladman Grant/Research Support from: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, A. Kavanaugh Grant/Research Support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, J. Gomez-Reino Grant/Research Support from: Roche and Schering-Plough, Consultant for: BMS, Pfizer, Roche, Schering-Plough, UCB, J. Wollenhaupt Grant/Research Support from: Abbott, BMS, MSD, Pfizer, UCB, Consultant for: Abbott, BMS, MSD, Pfizer, UCB, M. Cutolo Grant/Research Support from: Actelion, BMS, Sanofi-Aventis, Consultant for: Actelion, BMS, Sanofi-Aventis, G. Schett Grant/Research Support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, E. Lespessailles Grant/Research Support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, M. McIlraith Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, C. Edwards Grant/Research Support from: Celgene Corporation, Pfizer, Roche, Samsung, Consultant for: Celgene Corporation, Pfizer, Roche, Samsung, Speakers bureau: Abbott, GSK, Pfizer, Roche, C. Birbara Grant/Research Support from: Amgen, BMS, Incyte, Eli Lilly, Merck, Pfizer, P. Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB
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op0169 apremilast an oral phosphodiesterase 4 inhibitor is associated with long term 104 week improvements in enthesitis and dactylitis in patients with psoriatic arthritis pooled results from three phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2015Co-Authors: Dafna D Gladman, J Wollenhaupt, Eric Lespessailles, Georg Schett, Maurizio Cutolo, J J Gomezreino, M Mcilraith, A O Adebajo, A Kavanaugh, Christopher J EdwardsAbstract:Background Apremilast (APR), a PDE4 inhibitor, helps regulate immune responses in psoriatic arthritis (PsA). PALACE 1-3 compared APR efficacy/safety with placebo (PBO) in patients (pts) with active PsA despite prior conventional DMARDs and/or biologics, including efficacy assessment across multiple aspects of disease. Enthesitis and dactylitis are hallmark features of PsA that lead to pain and disability. Objectives Evaluate the impact of APR treatment over 104 wks on enthesitis and dactylitis in a pooled analysis of PALACE 1-3. Methods Pts were randomized (1:1:1) to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline (BL) DMARD use (yes/no). The PBO-controlled phase continued to Wk 24, with an early escape option at Wk 16. Double-blind APR treatment continued to Wk 52; pts could then continue to receive APR for up to an additional 4 years during an open-label extension phase. Data were pooled across PALACE 1-3 to allow for analysis of robust numbers of pts with pre-existing enthesopathy and/or dactylitis. Enthesitis was evaluated based on Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) (range 0-13), which indicates the number of painful entheses out of 13 entheses sites. The dactylitis count (range 0-20) is the number of digits (hands/feet) with dactylitis present; each digit is rated as 0 (none) or 1 (present). Results Long-term improvement in enthesitis and dactylitis severity was seen in pts with enthesitis and/or dactylitis at BL who were receiving APR at 104 weeks, as shown by reductions in MASES and dactylitis counts (Table). Mean changes in MASES were -57.5% (APR30) and -55.1% (APR20) at Wk 104. MASES scores of 0, indicating no pain at any of the entheses assessed, were achieved by 48.7% (APR30) and 51.5% (APR20) of pts. Mean changes in dactylitis count were -80.0% (APR30) and -75.8% (APR20) at Wk 104. Dactylitis counts decreased to 0 in 77.5% (APR30) and 72.9% (APR20) of pts. Over 104 wks, most AEs were mild/moderate in severity; in general, no increase was seen in AE incidence/severity with longer term exposure. Conclusions Over 104 wks, APR continued to demonstrate efficacy in PsA treatment, including improvements in enthesitis and dactylitis. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 104 wks. Disclosure of Interest D. Gladman Grant/Research Support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Kavanaugh Grant/Research Support from: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support from: Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth, J. Wollenhaupt Grant/Research Support from: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/Research Support from: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, Consultant for: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, G. Schett Grant/Research Support from: Abbott, Celgene Corporation, Roche, and UCB, Consultant for: Abbott, Celgene Corporation, Roche, and UCB, E. Lespessailles Grant/Research Support from: Amgen, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, M. McIlraith Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, C. Edwards Grant/Research Support from: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/Research Support from: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and Pfizer Inc, P. Mease Grant/Research Support from: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB,Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, UCB,Celgene Corporation, Novartis, and Roche, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB,
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op0078 apremilast an oral phosphodiesterase 4 inhibitor is associated with long term 52 week improvement in measures of disease activity in patients with psoriatic arthritis results from 3 phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: A Kavanaugh, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Georg Schett, Maurizio Cutolo, J J Gomezreino, Philip J Mease, A O Adebajo, R StevensAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. The PALACE 1, 2, and 3 trials compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics. Objectives Evaluate the impact of APR over 52 weeks on PsA disease activity. Methods Patients were randomized 1:1:1 to receive PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients with Results At Week 16, a significantly greater proportion of patients treated with APR achieved a modified ACR20 response vs PBO (primary endpoint). In patients initially randomized to APR and completing 52 weeks, ACR20 response was sustained over 52 weeks. APR20 and APR30 demonstrated improvement in disease activity vs PBO at Week 16, as measured by the DAS-28 (CRP), modified PsARC response, and good or moderate EULAR response. Among patients who were continuously treated with APR through 52 weeks sustained improvements were observed at Week 52 (Table). The most common adverse events reported during the PBO-controlled period (PAL 1-3; pooled) were diarrhea (12.2%), nausea (10.1%), and headache (8.0%). The safety profile of APR through 52 weeks was similar to that observed with APR for up to 24 weeks of treatment (PBO-controlled period). Conclusions APR demonstrated clinically meaningful improvements in measures of PsA disease activity through Week 52. APR demonstrated an acceptable safety profile and was generally well tolerated through 52 weeks. Disclosure of Interest A. Kavanaugh Grant/Research Support: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc., Roche, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, Consultant for: Actelion, Bristol-Myers Squibb, and Sanofi-Aventis, P. Mease Grant/Research Support: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc.,Celgene Corporation, Novartis, Roche and UCB, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., Celgene Corporation, Novartis, Roche and UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genetech, Janssen, Eli Lilly, Pfizer Inc., and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene corporation, Janssen, Pfizer Inc., Novartis and UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene corporation, Janssen, Pfizer Inc., Novartis and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Roche and Schering Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc., Roche, Schering Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering Plough, and Wyeth, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc., and UCB, G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, and UCB, Consultant for: Abbott, Celgene Corporation, Roche, and UCB, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc., Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc., Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc., and Roche, C. Birbara Grant/Research Support: Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and Pfizer Inc. DOI 10.1136/annrheumdis-2014-eular.1827
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ab0746 apremilast an oral phosphodiesterase 4 inhibitor and the impact of baseline weight and bmi on acr20 and haq di response pooled results from 3 phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: Georg Schett, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, Philip J Mease, A O Adebajo, R StevensAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 1, 2, and 3 compared the efficacy and safety of APR with placebo (PBO) in patients with active psoriatic arthritis (PsA) despite prior disease-modifying antirheumatic drugs and/or biologics. Objectives Assess the impact of baseline weight and body mass index (BMI) on clinical response to APR over 24 weeks in a pooled analysis. Methods Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline DMARD use (yes/no). Patients with Results 1493 patients were randomized, received ≥1 dose of study medication (PBO: n=496; APR20: n=500; APR30: n=497), and were comparable across treatment groups for demographics, disease characteristics, and prior/concurrent therapy. At baseline, mean (SD) weight was 85.7 (20.6) kg and mean (SD) BMI was 29.9 (6.5) kg/m 2 . APR administration resulted in statistically significant and clinically meaningful improvement in ACR20 response (primary endpoint) in all 3 PALACE trials. APR30 was associated with significant improvements in Health Assessment Questionnaire-Disability Index (HAQ-DI) vs PBO at Week 16 (key secondary endpoint) across all 3 trials. At Week 16, similar ACR20 response rates and improvements in HAQ-DI were observed across all weight and BMI ranges (Table). A favorable treatment effect for both APR treatment groups vs PBO was observed, irrespective of baseline body weight or BMI. Overall, the treatment effect was dose-dependent, with greater effects generally observed in APR30 over APR20 patients. These treatment effects were generally maintained at Week 24. Conclusions APR demonstrated a favorable treatment effect in patients with active PsA. Comparable improvements in the signs and symptoms of PsA and physical function were observed across a broad range of baseline weight and BMI values. Results suggest no dose adjustment is required to account for baseline body weight or BMI. Disclosure of Interest G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, P. Mease Grant/Research Support: Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Kavanaugh Consultant for: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth; and has received Research grants from Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/Research Support: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and DOI 10.1136/annrheumdis-2014-eular.1773
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sat0408 long term safety and tolerability of apremilast an oral phosphodiesterase 4 inhibitor in patients with psoriatic arthritis pooled safety analysis of three phase 3 randomized controlled trials
Annals of the Rheumatic Diseases, 2014Co-Authors: Philip J Mease, J Wollenhaupt, Dafna D Gladman, Eric Lespessailles, Georg Schett, Maurizio Cutolo, A Kavanaugh, J J Gomezreino, A O Adebajo, K ShahAbstract:Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 1, 2, and 3 compared the efficacy and safety of APR with placebo (PBO) in patients with active PsA despite prior conventional DMARDs and/or biologics. Objectives The overall safety and tolerability of APR was assessed in a pooled analysis of PALACE 1, 2, and 3, with APR exposure ≥52 wks. Methods Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline (BL) DMARD use (yes/no). Patients with Results 1,493 patients received study medication (PBO: 495; APR20: 501; APR30: 497) and were included in the safety population. The APR-exposure period included 720 patients treated with APR20 (766.4 patient-yrs) and 721 with APR30 (769.0 patient-yrs). The nature, incidence, and severity of AEs were comparable through the 24-wk and 52-wk periods (Table). The most common AEs were diarrhea (14.3%), nausea (12.6%), headache (10.1%), URTI (10.3%), and nasopharyngitis (7.4%). Most AEs were mild or moderate in severity. Discontinuations due to AEs (APR20: 7.5%; APR30: 8.3%) were low, occurring primarily in the first 24 wks of treatment. Serious AEs (SAEs) occurred in 6.8% (APR20) and 7.2% (APR30) of patients. One death occurred (APR20) due to multiorgan failure not suspected to be treatment-related. Diarrhea and nausea were predominantly mild and occurred at a reduced incidence after the first month of dosing, with the highest incidence reported in the first 2 wks of treatment. Most cases resolved within 30 days despite continued therapy and without medical intervention. Discontinuation due to GI AEs was 4% through Wk 52, with nausea (1.7%) and diarrhea (1.5%) being the most common. There was 1 case of diarrhea and 1 case of nausea reported as an SAE in the 0 to ≥24-wk period, and no additional cases reported in the 0 to ≥52-wk period. Exposure-adjusted incidence rates of major adverse cardiac events, serious infections including systemic opportunistic infection, or malignancies were comparable to PBO. Laboratory abnormalities were infrequent and transient with no trends or patterns observed. Conclusions APR demonstrated an acceptable safety profile and was generally well tolerated through 52 wks; the nature, incidence, and severity of AEs were comparable through the 24-wk and 52-wk periods. These data do not indicate a need for laboratory monitoring. Disclosure of Interest P. Mease Grant/Research Support: Celgene Corporation, Novartis, and Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer Inc, and UCB, A. Kavanaugh Grant/Research Support: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer Inc, Roche, and UCB, D. Gladman Grant/Research Support: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis, and UCB, A. Adebajo: None declared, J. Gomez-Reino Grant/Research Support: Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering-Plough, and Wyeth, J. Wollenhaupt Grant/Research Support: Abbott, Bristol-Myers Squibb, MSD, Pfizer Inc, and UCB, M. Cutolo Grant/Research Support: Actelion, Bristol-Myers Squibb, and G. Schett Grant/Research Support: Abbott, Celgene Corporation, Roche, E. Lespessailles Grant/Research Support: Amgen, Eli Lilly, Novartis, and Servier, K. Shah Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, C. Edwards Grant/Research Support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, C. Birbara Grant/Research Support: Amgen, Bristol-Myers Squibb, Incyte, Eli Lilly, Merck, and DOI 10.1136/annrheumdis-2014-eular.5589
