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Philip J Mease - One of the best experts on this subject based on the ideXlab platform.
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Secukinumab efficacy on psoriatic arthritis grappa omeract core domains in patients with or without prior tumor necrosis factor inhibitor use pooled analysis of four phase 3 studies
Rheumatology and therapy, 2021Co-Authors: Ana Maria Orbai, Dafna D Gladman, Elaine M Husni, Ying Ying Leung, Stefan Siebert, William Tillett, M Vis, Olivier Chambenoit, X Meng, Philip J MeaseAbstract:Psoriatic arthritis (PsA) is a chronic, heterogeneous, immune-mediated disease manifesting as a spectrum of possible inflammatory signs and symptoms. Clinicians need therapeutic choices that work across all active PsA disease domains, as well as practical information about efficacy of available treatments for individual domains in specific groups of patients. The objective of this study was to evaluate the effect of prior tumor necrosis factor inhibitor (TNFi) exposure on the efficacy of Secukinumab across PsA core domains. Data were pooled from 2049 participants with PsA in four phase 3 studies (FUTURE 2–5). Efficacy at week 16 was evaluated for each GRAPPA-OMERACT PsA core domain using nonresponder imputation for musculoskeletal disease activity and Psoriasis Area and Severity Index scores or as-observed data for other outcomes. For each measure, comparisons with placebo were made separately in the TNFi-naive and TNFi-inadequate responder/intolerant (TNF-IR) cohorts. Treatment with Secukinumab improved PsA disease activity across all disease domains regardless of previous TNFi use, although TNFi-naive patients experienced numerically greater benefits in most outcomes. Among patients treated with Secukinumab 300 mg, 41.5% and 24.4% of TNFi-naive patients (P < 0.05 vs placebo) and 18.6% and 9.0% of TNF-IR patients (nonsignificant vs placebo) experienced resolution in 66 swollen and 68 tender joint counts, respectively; additionally, 37.2% of TNFi-naive patients and 24.2% of TNF-IR patients achieved complete resolution of psoriasis at week 16 (all P < 0.05 vs placebo). Secukinumab effect sizes were generally larger in TNFi-naive vs TNF-IR patients for musculoskeletal and patient-reported domains. Secukinumab demonstrated efficacy vs placebo across GRAPPA-OMERACT PsA core domains. Higher responses among TNFi-naive vs TNF-IR patients suggest that Secukinumab should be considered for first-line use in PsA. Psoriatic arthritis (PsA) is a long-term disease that can affect a patient’s joints, skin, lower back, physical function, mental health, productivity, and other areas. Drugs called tumor necrosis factor inhibitors (TNFis) can be used to treat PsA, although not all patients benefit from TNFis and many seek other treatment options. These patients, known as TNFi-inadequate responders (TNF-IR), have PsA that is difficult to treat. Another treatment option is Secukinumab, a drug that blocks a molecule called interleukin-17 that is involved in PsA. Doctors need to know how different drugs work for treating PsA signs and symptoms in different groups of patients, including TNF-IR patients and those who have never received TNFis (TNFi-naive patients). This study used data from 2049 patients in four different PsA clinical trials (FUTURE 2–5) to see how well Secukinumab worked at treating different signs and symptoms of PsA in TNFi-naive and TNF-IR patients. After 16 weeks of treatment, patients who took Secukinumab saw greater improvements across all measured PsA signs and symptoms than those who took placebo. This was true for both TNFi-naive and TNF-IR patients. TNFi-naive patients seemed to benefit slightly more than TNF-IR patients—especially in their joint symptoms—although this study was not designed to judge the significance of these differences. These results suggest that Secukinumab would be an effective first treatment option for patients with PsA. Since Secukinumab improves the skin, joints, and other affected areas, it can be useful in treating the whole patient who has psoriatic disease.
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Secukinumab versus adalimumab for treatment of active psoriatic arthritis exceed a double blind parallel group randomised active controlled phase 3b trial
The Lancet, 2020Co-Authors: Iain B Mcinnes, Philip J Mease, Peter Nash, Arthur Kavanaugh, F Behrens, Christopher T Ritchlin, Jordi Gratacos Masmitja, Philippe Goupille, T Korotaeva, Alice B GottliebAbstract:Summary Background Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of Secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response. Methods This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive Secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg Secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov , NCT02745080 . Findings Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive Secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the Secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of Secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the Secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98–1·72; p=0·0719). The safety profiles of Secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the Secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the Secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator. Interpretation Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, Secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis. Funding Novartis Pharma.
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long term efficacy and safety of Secukinumab in patients with psoriatic arthritis 5 year end of study results from the phase 3 future 2 study
The Lancet Rheumatology, 2020Co-Authors: Iain B Mcinnes, Philip J Mease, Peter Nash, J Rech, Bruce Kirkham, Proton Rahman, Alan Kivitz, Philip G Conaghan, Sandra V Navarra, Ashwini D BelsareAbstract:Summary Background Secukinumab is an interleukin-17A inhibitor used in the treatment of patients with active psoriatic arthritis. In the phase 3 FUTURE 2 trial, Secukinumab showed sustained improvement in clinical outcomes over 2 years. Because scarce data exists on the long-term treatment with biological therapies in patients with psoriatic arthritis, we aimed to assess and describe the 5-year (end-of-study) results on the efficacy and safety of Secukinumab 300 mg and 150 mg doses, as well as dose escalation, from the FUTURE 2 study. Methods FUTURE 2 is a phase 3, double-blind, placebo-controlled study done at 76 centres in Asia, Australia, Canada, Europe, and the USA. Patients with active psoriatic arthritis aged 18 years or older were randomly assigned to either Secukinumab (300 mg, 150 mg, or 75 mg) or placebo weekly from baseline and then every 4 weeks from week 4. Secukinumab dose was escalated from 150 mg to 300 mg and from 75 mg to 150 mg or 300 mg starting at week 128, if active signs of disease were observed in patients, on the basis of the physician's assessment, with the escalated dose maintained thereafter. We assessed key efficacy endpoints at week 260 (5 years) for Secukinumab 300 mg and 150 mg, including American College of Rheumatology (ACR) and Psoriasis Area and Severity Index (PASI) responses. The safety analysis included all patients who received one or more doses of Secukinumab. We report data as observed. This study is registered with ClinicalTrials.gov , NCT01752634 . Findings At randomisation, 65% of patients were naive to tumour necrosis factor inhibitors and 47% were receiving concomitant methotrexate. Of 397 patients randomly assigned in FUTURE 2, 248 (62%) completed 5 years of treatment, including 64 (64%) of 100 patients in the original Secukinumab 300 mg group, 65 (65%) of 100 in the 150 mg group, 59 (60%) of 99 in the 75 mg group, and 60 (61%) of 98 in the placebo group. Overall, 127 (52%) of 242 patients required dose escalation during the study. ACR responses at 5 years were 71 (74%; ACR20), 50 (52%; ACR50), and 31 (32%; ACR70) of 96 evaluable patients in the Secukinumab 300 mg group, and 67 (70%; ACR20), 41 (43%; ACR50), and 28 (29%; ACR70) of 96 evaluable patients in the Secukinumab 150 mg group. From 24 to 32 weeks and from 48 to 84 weeks after dose escalation from Secukinumab 150 mg to 300 mg, the proportions of ACR and PASI non-responders decreased, whereas the proportions of ACR and PASI responders increased. During the entire treatment period, the most frequent treatment-emergent serious adverse event was serious infection (exposure-adjusted incidence 1·7, 95% CI 1·1–2·5; n=25) in the any Secukinumab group. No new or unexpected safety signals were reported. Interpretation Secukinumab 300 mg and 150 mg provided sustained improvement in the signs and symptoms of psoriatic arthritis, with consistent safety over 5 years. This study supports the clinical benefit and safety of long-term treatment with Secukinumab in patients with psoriatic arthritis. Funding Novartis.
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long term safety of Secukinumab in patients with moderate to severe plaque psoriasis psoriatic arthritis and ankylosing spondylitis integrated pooled clinical trial and post marketing surveillance data
Arthritis Research & Therapy, 2019Co-Authors: A Deodhar, Xenofon Baraliakos, Brian Porter, Philip J Mease, K Reich, A Blauvelt, I Mcinnes, C Leonardi, Das A Gupta, A WidmerAbstract:Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for Secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of Secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of Secukinumab. A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing Secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to Secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with Secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of Secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions.
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matching adjusted indirect comparison Secukinumab versus infliximab in biologic naive patients with psoriatic arthritis
Journal of Comparative Effectiveness Research, 2019Co-Authors: Vibeke Strand, Iain B Mcinnes, Philip J Mease, Peter Nash, Howard Thom, Chrysostomos Kalyvas, Matthias Hunger, K Gandhi, Luminita Pricop, S M JuglAbstract:Aim: To compare Secukinumab with infliximab in biologic-naive patients with psoriatic arthritis using matching-adjusted indirect comparison. Patients & methods: Individual patient baseline data for Secukinumab were matched to published aggregate data for infliximab by key baseline characteristics, with matching weights determined by logistic regression, and used to recalculate American College of Rheumatology (ACR) responses for Secukinumab, for comparison with infliximab. Results: There were no differences in outcomes between Secukinumab and infliximab at weeks 6/8 and 14/16. At weeks 24 and 54/52, ACR 20 responses were higher with Secukinumab 150 mg than infliximab. At week 54/52, ACR 20/50 responses were higher for Secukinumab 300 mg than infliximab. Conclusion: In the mid to long term, patients receiving Secukinumab were more likely to achieve ACR 20/50 responses than those receiving infliximab.
Shephard Mpofu - One of the best experts on this subject based on the ideXlab platform.
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Secukinumab efficacy on enthesitis in patients with ankylosing spondylitis pooled analysis of four pivotal phase 3 studies
The Journal of Rheumatology, 2021Co-Authors: Georg Schett, Shephard Mpofu, Atul Deodhar, Filip Van Den Bosch, Xenofon Baraliakos, Mikkel Ostergaard, Ayan Das Gupta, Todd Fox, Adam Winseck, Brian PorterAbstract:OBJECTIVE To assess the efficacy of Secukinumab on axial and peripheral enthesitis in patients with ankylosing spondylitis (AS) using pooled data from randomized controlled phase 3 studies. METHODS In this post-hoc analysis, data were pooled from patients originally randomized to Secukinumab 150 mg, 300 mg, or placebo from phase 3 MEASURE 1-4 studies (ClinicalTrials.gov identifiers: NCT01358175, NCT01649375, NCT02008916 and NCT02159053). Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was used for assessments of enthesitis through Week 52. Efficacy outcomes were mean change in MASES score and complete resolution (MASES=0) of enthesitis in patients with baseline MASES>0. RESULTS A total of 693 (71.5%) patients had enthesitis at baseline in Secukinumab 300 mg, 150 mg and placebo groups (58 [76.3%], 355 [70.4%] and 280 [72%]), respectively, out of 969 patients pooled in this analysis. At Week 16, mean change from baseline for overall MASES and enthesitis at axial MASES-sites was: Secukinumab 300 mg (-2.9 [P<0.01] and -2.9 [P<0.01]); 150 mg (-2.4 [P<0.015] and -2.3 [P<0.05]), and placebo (-1.9 and -1.8), with improvements seen through Week 52. More than a third of Secukinumab-treated patients (300 mg, 36.2% and 150 mg, 40.8%) achieved complete resolution of enthesitis at Week 16. CONCLUSION Secukinumab improved enthesitis at overall MASES and axial sites in patients with ankylosing spondylitis.
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minimal disease activity among active psoriatic arthritis patients treated with Secukinumab 2 year results from a multicenter randomized double blind parallel group placebo controlled phase iii study
Arthritis Care and Research, 2018Co-Authors: Laura C Coates, Shephard Mpofu, Philip J Mease, S M Jugl, Laure Gossec, Bruce Kirkham, Bintu Sherif, C Gaillez, C Karyekar, K GandhiAbstract:OBJECTIVE To evaluate minimal disease activity (MDA) among psoriatic arthritis (PsA) patients receiving Secukinumab through 2 years in the FUTURE 2 study. METHODS Patients with active PsA were randomized to receive subcutaneous Secukinumab 300, 150, or 75 mg or placebo. MDA was assessed in the overall population (anti-tumor necrosis factor [anti-TNF]-naive and inadequate responders [anti-TNF-IR]) and in patients stratified by prior anti-TNF exposure and by time since diagnosis at weeks 16, 24, 52, and 104. Function and patient-reported outcomes (PROs), including health-related quality of life (QoL) and work productivity, were assessed in MDA responders versus nonresponders. RESULTS Overall, 28% of patients (27 of 98) and 23% (23 of 100) achieved MDA at week 16 with Secukinumab 300 and 150 mg, respectively, versus 10% (9 of 94) with placebo. In the anti-TNF-naive cohort, a higher proportion of patients achieved MDA at week 16 with Secukinumab 300 and 150 mg (34% and 32%, respectively) versus placebo (13%). The corresponding value in the anti-TNF-IR cohort was 15% and 8% with Secukinumab 300 and 150 mg, respectively, versus with placebo (3%). At week 16, 27.1% of MDA responders (16 of 59) achieved a very low disease activity (VLDA) response, with the percentage being numerically greater with Secukinumab 300 and 150 mg (30% [8 of 27] and 26% [6 of 23], respectively) versus placebo (22% [2 of 9]). The MDA and VLDA responses with Secukinumab 300 and 150 mg were sustained through 2 years. MDA responders showed greater improvements in QoL outcomes compared to nonresponders through 2 years. CONCLUSION A greater proportion of patients achieved MDA with Secukinumab versus placebo at week 16, with response rates sustained through 2 years. MDA was associated with improved PROs, including QoL, through 2 years.
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Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression primary results from the randomised double blind phase iii future 5 study
Annals of the Rheumatic Diseases, 2018Co-Authors: Philip J Mease, Shephard Mpofu, Desiree Van Der Heijde, Hasan Tahir, Proton Rahman, Sandra V Navarra, R Landewe, Atul Singhal, Elke Boettcher, Karin MeiserAbstract:Objectives To evaluate the effect of subcutaneous (s.c.) Secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA). Methods Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. Secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received Secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16. Results Significantly more patients achieved an ACR20 response at week 16 with Secukinumab 300 mg with LD (62.6%), 150 mg with LD (55.5%) or 150 mg without LD (59.5%) than placebo (27.4%) (p 0.01 for 300 mg with LD and 150 mg without LD and p Conclusion S.c. Secukinumab 300 mg and 150 mg with and without LD significantly improved clinical signs and symptoms and inhibited radiographic structural progression versus placebo at week 24 in patients with PsA. Trial registration number NCT02404350; Results.
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efficacy and safety of Secukinumab administration by autoinjector in patients with psoriatic arthritis results from a randomized placebo controlled trial future 3
Arthritis Research & Therapy, 2018Co-Authors: Peter Nash, Iain B Mcinnes, Philip J Mease, Eva Dokoupilova, Mats Andersson, Proton Rahman, Ricardo Blanco, Christopher T Ritchlin, Radhika Kajekar, Shephard MpofuAbstract:The study aimed to assess 52-week efficacy and safety of Secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study ( ClinicalTrials.gov NCT01989468). Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) Secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s.c. Secukinumab 300 or 150 mg at week 16 (nonresponders) or week 24 (responders) and stratified at randomization by prior anti-tumor necrosis factor (TNF) therapy (anti-TNF-naive, 68.1%; intolerant/inadequate response (anti-TNF-IR), 31.9%). The primary endpoint was the proportion of patients achieving at least 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24. Autoinjector usability was evaluated by Self-Injection Assessment Questionnaire (SIAQ). Overall, 92.1% (300 mg), 91.3% (150 mg), and 93.4% (placebo) of patients completed 24 weeks, and 84.9% (300 mg) and 79.7% (150 mg) completed 52 weeks. In the overall population (combined anti-TNF-naive and anti-TNF-IR), ACR20 response rate at week 24 was significantly higher in Secukinumab groups (300 mg, 48.2% (p < 0.0001); 150 mg, 42% (p < 0.0001); placebo, 16.1%) and was sustained through 52 weeks. SIAQ results showed that more than 93% of patients were satisfied/very satisfied with autoinjector usage. Secukinumab was well tolerated with no new or unexpected safety signals reported. Secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. High acceptability of autoinjector was observed. The safety profile was consistent with that reported previously. ClinicalTrials.gov NCT01989468 . Registered 21 November 2013. EudraCT 2013–004002-25 . Registered 17 December 2013.
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Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis 2 year results from the phase 3 future 2 study
Rheumatology, 2017Co-Authors: Iain B Mcinnes, Philip J Mease, Luminita Pricop, Bruce Kirkham, Proton Rahman, Alice B Gottlieb, Christopher T Ritchlin, Radhika Kajekar, Eumorphiamaria Delicha, Shephard MpofuAbstract:Objectives. To assess long-term efficacy, safety and tolerability of Secukinumab up to 104 weeks in patients with active PsA. Methods. Patients with PsA (n = 397) were randomized to s.c. Secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive Secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP, presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures. Results. A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the Secukinumab 300, 150 and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical improvements were observed through week 104 with Secukinumab across other clinically important domains of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-a use. Over the entire treatment period the incidence, type and severity of adverse events were consistent with those reported previously. Conclusion. Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously. Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01752634
Brian Porter - One of the best experts on this subject based on the ideXlab platform.
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Secukinumab efficacy on enthesitis in patients with ankylosing spondylitis pooled analysis of four pivotal phase 3 studies
The Journal of Rheumatology, 2021Co-Authors: Georg Schett, Shephard Mpofu, Atul Deodhar, Filip Van Den Bosch, Xenofon Baraliakos, Mikkel Ostergaard, Ayan Das Gupta, Todd Fox, Adam Winseck, Brian PorterAbstract:OBJECTIVE To assess the efficacy of Secukinumab on axial and peripheral enthesitis in patients with ankylosing spondylitis (AS) using pooled data from randomized controlled phase 3 studies. METHODS In this post-hoc analysis, data were pooled from patients originally randomized to Secukinumab 150 mg, 300 mg, or placebo from phase 3 MEASURE 1-4 studies (ClinicalTrials.gov identifiers: NCT01358175, NCT01649375, NCT02008916 and NCT02159053). Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was used for assessments of enthesitis through Week 52. Efficacy outcomes were mean change in MASES score and complete resolution (MASES=0) of enthesitis in patients with baseline MASES>0. RESULTS A total of 693 (71.5%) patients had enthesitis at baseline in Secukinumab 300 mg, 150 mg and placebo groups (58 [76.3%], 355 [70.4%] and 280 [72%]), respectively, out of 969 patients pooled in this analysis. At Week 16, mean change from baseline for overall MASES and enthesitis at axial MASES-sites was: Secukinumab 300 mg (-2.9 [P<0.01] and -2.9 [P<0.01]); 150 mg (-2.4 [P<0.015] and -2.3 [P<0.05]), and placebo (-1.9 and -1.8), with improvements seen through Week 52. More than a third of Secukinumab-treated patients (300 mg, 36.2% and 150 mg, 40.8%) achieved complete resolution of enthesitis at Week 16. CONCLUSION Secukinumab improved enthesitis at overall MASES and axial sites in patients with ankylosing spondylitis.
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Secukinumab provides sustained reduction in fatigue in patients with ankylosing spondylitis long term results of two phase iii randomized controlled trials
Arthritis Care and Research, 2020Co-Authors: Tore K Kvien, Mikkel Ostergaard, Brian Porter, Vibeke Strand, Laure Gossec, Nicole Williams, Philip G Conaghan, Denis Poddubnyy, Abhijit Shete, I GilloteauAbstract:Objective To investigate the longer-term effects of Secukinumab 150 mg on fatigue in patients with ankylosing spondylitis (AS) in MEASURE 1 (up to 3 years) and MEASURE 2 (up to 2 years). Methods Patients with active AS were randomized to Secukinumab or placebo in MEASURE 1 (10 mg/kg intravenous [IV] followed by 150 mg subcutaneous [SC]) and MEASURE 2 (150 mg SC). Patients were naive to or had an inadequate response/intolerance to tumor necrosis factor inhibitors (anti-TNF-naive/ anti-TNF-IR). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Relationships between fatigue response and baseline characteristics and clinical/laboratory variables were explored. Results Significant improvements in FACIT-F scores from baseline were observed with Secukinumab across both studies versus placebo at week 16 (P Conclusion Secukinumab provided rapid and sustained improvements in fatigue for up to 3 years, regardless of prior anti-TNF exposure.
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long term safety of Secukinumab in patients with moderate to severe plaque psoriasis psoriatic arthritis and ankylosing spondylitis integrated pooled clinical trial and post marketing surveillance data
Arthritis Research & Therapy, 2019Co-Authors: A Deodhar, Xenofon Baraliakos, Brian Porter, Philip J Mease, K Reich, A Blauvelt, I Mcinnes, C Leonardi, Das A Gupta, A WidmerAbstract:Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for Secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of Secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of Secukinumab. A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing Secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to Secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with Secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of Secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions.
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Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis 4 year results from the measure 1 study
Rheumatology, 2019Co-Authors: Jurgen Braun, Atul Deodhar, Xenofon Baraliakos, Paul Emery, Denis Poddubnyy, Eumorphiamaria Delicha, Zsolt Talloczy, Brian PorterAbstract:Objectives:To evaluate the effect of Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, on efficacy, imaging outcomes, and safety through 4 years (208 weeks) in patients with ankylosing spondylitis. Methods:Patients opting to enrol had completed 2 years' treatment in the MEASURE 1 core study with subcutaneous Secukinumab 150 or 75 mg every 4 weeks (q4Wk), following intravenous loading to Week (Wk) 4, or placebo treatment to Wk16/24. Up-titration from Secukinumab 75-150 mg q4Wk was permitted following a protocol amendment. Efficacy is reported for patients originally randomized to Secukinumab. Radiographic changes were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and changes in MRI measures of inflammation using the Berlin scoring method. Safety and tolerability were evaluated. Results:Among 274 extension study participants, 89.7% (78/87) and 93.0% (93/100) originally randomized to Secukinumab 150 and 75 mg, respectively, completed 208Wk. Through Wk208, Assessment of Spondyloarthritis International Society 20/40 (observed) were 79.7%/60.8% (150 mg), 71.0%/43.5% (75 mg) and 80.0%/76% (up-titrators; n = 25). Mean (s.d.) changes in mSASSS were 1.2 (3.91) (150 mg), 1.8 (4.32) (75 mg) and 1.6 (5.67) (up-titrators). No radiographic progression (mSASSS change from Baseline < 2) was observed in 79% of patients receiving either Secukinumab dose. Exposure-adjusted incidence rates per 100 patient-years were: serious infections (1.0), Candida infections (0.4), Crohn's disease (0.6), ulcerative colitis (0.2), and malignant/unspecified tumours (0.5), with no new safety signals. Conclusion:Through 4 years, Secukinumab provided sustained efficacy on signs and symptoms, and MRI outcomes, a low rate of radiographic progression and a consistent safety profile. Trial registration:NCT01863732.
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efficacy safety and tolerability of Secukinumab in patients with active ankylosing spondylitis a randomized double blind phase 3 study measure 3
Arthritis Research & Therapy, 2017Co-Authors: K Pavelka, Luminita Pricop, Eva Dokoupilova, Hasan Tahir, Mats Andersson, Alan Kivitz, Ricardo Blanco, Aimee Readie, Marco Maradiaga, Brian PorterAbstract:Secukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in two phase 3 studies (MEASURE 1 and MEASURE 2). Here, we present 52-week results from the MEASURE 3 study assessing the efficacy and safety of Secukinumab 300 and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen. A total of 226 patients were randomized to intravenous Secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous Secukinumab 300 mg (IV-300 mg) or 150 mg (IV-150 mg) every 4 weeks, or matched placebo. Patients in the placebo group were re-randomized to subcutaneous Secukinumab at a dose of 300 or 150 mg at week 16. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16 in the IV-300 mg or IV-150 mg versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, and ASAS partial remission responses, as well as the change from baseline in high-sensitivity C-reactive protein levels. Statistical analyses followed a predefined hierarchical hypothesis testing strategy to adjust for multiplicity of testing, with non-responder imputation used for binary variables and mixed-model repeated measures for continuous variables. The primary efficacy endpoint was met; the ASAS20 response rate was significantly greater at week 16 in the IV-300 mg (60.5%; P < 0.01) and IV-150 mg (58.1%; P < 0.05) groups versus placebo (36.8%). All secondary endpoints were met at week 16, except ASAS partial remission in the IV-150 mg group. Improvements achieved with Secukinumab in all clinical endpoints at week 16 were also sustained at week 52. Infections, including candidiasis, were more common with Secukinumab than with placebo during the placebo-controlled period. During the entire treatment period, pooled incidence rates of Candida infections and grade 3–4 neutropenia were 1.8% for both of these adverse events in Secukinumab-treated patients. Secukinumab (300 mg and 150 mg dose groups) provided rapid, significant and sustained improvement through 52 weeks in the signs and symptoms of patients with AS. The safety profile was consistent with previous reports, with no new or unexpected findings. ClinicalTrials.gov, NCT02008916 . Registered on 8 December 2013. EUDRACT 2013-001090-24. Registered on 24 October 2013). The study was not retrospectively registered.
Iain B Mcinnes - One of the best experts on this subject based on the ideXlab platform.
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Secukinumab versus adalimumab for treatment of active psoriatic arthritis exceed a double blind parallel group randomised active controlled phase 3b trial
The Lancet, 2020Co-Authors: Iain B Mcinnes, Philip J Mease, Peter Nash, Arthur Kavanaugh, F Behrens, Christopher T Ritchlin, Jordi Gratacos Masmitja, Philippe Goupille, T Korotaeva, Alice B GottliebAbstract:Summary Background Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of Secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response. Methods This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive Secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg Secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov , NCT02745080 . Findings Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive Secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the Secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of Secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the Secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98–1·72; p=0·0719). The safety profiles of Secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the Secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the Secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator. Interpretation Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, Secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis. Funding Novartis Pharma.
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long term efficacy and safety of Secukinumab in patients with psoriatic arthritis 5 year end of study results from the phase 3 future 2 study
The Lancet Rheumatology, 2020Co-Authors: Iain B Mcinnes, Philip J Mease, Peter Nash, J Rech, Bruce Kirkham, Proton Rahman, Alan Kivitz, Philip G Conaghan, Sandra V Navarra, Ashwini D BelsareAbstract:Summary Background Secukinumab is an interleukin-17A inhibitor used in the treatment of patients with active psoriatic arthritis. In the phase 3 FUTURE 2 trial, Secukinumab showed sustained improvement in clinical outcomes over 2 years. Because scarce data exists on the long-term treatment with biological therapies in patients with psoriatic arthritis, we aimed to assess and describe the 5-year (end-of-study) results on the efficacy and safety of Secukinumab 300 mg and 150 mg doses, as well as dose escalation, from the FUTURE 2 study. Methods FUTURE 2 is a phase 3, double-blind, placebo-controlled study done at 76 centres in Asia, Australia, Canada, Europe, and the USA. Patients with active psoriatic arthritis aged 18 years or older were randomly assigned to either Secukinumab (300 mg, 150 mg, or 75 mg) or placebo weekly from baseline and then every 4 weeks from week 4. Secukinumab dose was escalated from 150 mg to 300 mg and from 75 mg to 150 mg or 300 mg starting at week 128, if active signs of disease were observed in patients, on the basis of the physician's assessment, with the escalated dose maintained thereafter. We assessed key efficacy endpoints at week 260 (5 years) for Secukinumab 300 mg and 150 mg, including American College of Rheumatology (ACR) and Psoriasis Area and Severity Index (PASI) responses. The safety analysis included all patients who received one or more doses of Secukinumab. We report data as observed. This study is registered with ClinicalTrials.gov , NCT01752634 . Findings At randomisation, 65% of patients were naive to tumour necrosis factor inhibitors and 47% were receiving concomitant methotrexate. Of 397 patients randomly assigned in FUTURE 2, 248 (62%) completed 5 years of treatment, including 64 (64%) of 100 patients in the original Secukinumab 300 mg group, 65 (65%) of 100 in the 150 mg group, 59 (60%) of 99 in the 75 mg group, and 60 (61%) of 98 in the placebo group. Overall, 127 (52%) of 242 patients required dose escalation during the study. ACR responses at 5 years were 71 (74%; ACR20), 50 (52%; ACR50), and 31 (32%; ACR70) of 96 evaluable patients in the Secukinumab 300 mg group, and 67 (70%; ACR20), 41 (43%; ACR50), and 28 (29%; ACR70) of 96 evaluable patients in the Secukinumab 150 mg group. From 24 to 32 weeks and from 48 to 84 weeks after dose escalation from Secukinumab 150 mg to 300 mg, the proportions of ACR and PASI non-responders decreased, whereas the proportions of ACR and PASI responders increased. During the entire treatment period, the most frequent treatment-emergent serious adverse event was serious infection (exposure-adjusted incidence 1·7, 95% CI 1·1–2·5; n=25) in the any Secukinumab group. No new or unexpected safety signals were reported. Interpretation Secukinumab 300 mg and 150 mg provided sustained improvement in the signs and symptoms of psoriatic arthritis, with consistent safety over 5 years. This study supports the clinical benefit and safety of long-term treatment with Secukinumab in patients with psoriatic arthritis. Funding Novartis.
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matching adjusted indirect comparison Secukinumab versus infliximab in biologic naive patients with psoriatic arthritis
Journal of Comparative Effectiveness Research, 2019Co-Authors: Vibeke Strand, Iain B Mcinnes, Philip J Mease, Peter Nash, Howard Thom, Chrysostomos Kalyvas, Matthias Hunger, K Gandhi, Luminita Pricop, S M JuglAbstract:Aim: To compare Secukinumab with infliximab in biologic-naive patients with psoriatic arthritis using matching-adjusted indirect comparison. Patients & methods: Individual patient baseline data for Secukinumab were matched to published aggregate data for infliximab by key baseline characteristics, with matching weights determined by logistic regression, and used to recalculate American College of Rheumatology (ACR) responses for Secukinumab, for comparison with infliximab. Results: There were no differences in outcomes between Secukinumab and infliximab at weeks 6/8 and 14/16. At weeks 24 and 54/52, ACR 20 responses were higher with Secukinumab 150 mg than infliximab. At week 54/52, ACR 20/50 responses were higher for Secukinumab 300 mg than infliximab. Conclusion: In the mid to long term, patients receiving Secukinumab were more likely to achieve ACR 20/50 responses than those receiving infliximab.
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Secukinumab for psoriatic arthritis comparative effectiveness versus licensed biologics apremilast a network meta analysis
Journal of Comparative Effectiveness Research, 2018Co-Authors: Iain B Mcinnes, Peter Nash, Howard Thom, K Gandhi, Luminita Pricop, Christopher T Ritchlin, Ernest Choy, Steve Kanters, S M JuglAbstract:Aim: A network meta-analysis using randomized controlled trial data compared psoriatic arthritis (PsA) outcomes (American College of Rheumatology [ACR], Psoriasis Area Severity Index [PASI] and Psoriatic Arthritis Response Criteria [PsARC] response rates) at 12-16 weeks for Secukinumab, adalimumab, apremilast, certolizumab, etanercept, golimumab, infliximab and ustekinumab. Patients & methods: Trials were identified by systematic review. Separate networks were developed for the full-study populations, biologic-naive patients and biologic-experienced patients. Results: In the full populations, Secukinumab, adalimumab, golimumab and infliximab demonstrated the highest ACR response rates. Secukinumab and infliximab demonstrated the highest PASI response rates, and infliximab and etanercept demonstrated the highest PsARC response rates. Conclusion: In the full populations, Secukinumab demonstrated good efficacy across all outcomes. All treatments for active PsA included in this comprehensive network meta-analysis demonstrated superiority to placebo.
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Secukinumab provides rapid and sustained pain relief in psoriatic arthritis over 2 years results from the future 2 study
Arthritis Research & Therapy, 2018Co-Authors: Iain B Mcinnes, Georg Schett, Todd Fox, Vibeke Strand, Philip J Mease, Luminita Pricop, S M Jugl, Bruce Kirkham, Nicole Williams, K GandhiAbstract:Pain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of Secukinumab on patient-reported pain in PsA through 104 weeks of treatment. Pain was assessed through week 104 using clinically relevant measures, including change from baseline in a pain visual analog scale (VAS) and Short Form-36 (SF-36) bodily domain scores; proportion of patients reporting improvements equal to or better than minimum clinically meaningful differences in the pain VAS and SF-36 bodily pain domain scores; and proportion of patients with no, moderate, or extreme pain/discomfort measured by the EuroQoL 5-Dimension 3-Level Questionnaire (EQ-5D-3 L) pain item scores. Correlations of pain measures were analyzed using Pearson’s correlation coefficient. Pre-specified analyses of TNF-naive patients and patients who stopped TNF-inhibitors (TNFis) due to inadequate responses or safety/tolerability (TNF-IR patients) were performed using “as-observed data.” Mean improvements from baseline in pain VAS scores were greater with Secukinumab versus placebo by week 3 (− 16.9; P < 0.0001 with Secukinumab 300 mg and − 12.6; P < 0.05 with Secukinumab 150 mg) and sustained through week 104. SF-36 bodily pain domain scores were significantly greater with 300 mg Secukinumab and Secukinumab 150 mg versus placebo by week 4 (16.2 and 16.3, respectively; P < 0.0001 for both), and these changes were maintained through week 104. With both Secukinumab 300 mg and Secukinumab 150 mg, improvements equal to or better than the minimum clinically meaningful differences in pain VAS and SF-36 bodily pain were significant versus placebo at week 3 and week 4, respectively. At week 4, 15%, 9%, and 5% of patients receiving Secukinumab 300 mg, Secukinumab 150 mg, and placebo, respectively, reported “no pain/discomfort” measured by EQ-5D-3 L; these proportions increased to week 104 with both Secukinumab doses. Similarly, improvements in pain measures were significant in both TNF-naive and TNF-IR patients. Secukinumab provided rapid and sustained pain relief in PsA over 2 years of treatment. Improvements in pain were reported regardless of prior exposure to TNFis. ClinicalTrials.gov, NCT01752634 . Registered on 19 December 2012.
Luminita Pricop - One of the best experts on this subject based on the ideXlab platform.
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matching adjusted indirect comparison Secukinumab versus infliximab in biologic naive patients with psoriatic arthritis
Journal of Comparative Effectiveness Research, 2019Co-Authors: Vibeke Strand, Iain B Mcinnes, Philip J Mease, Peter Nash, Howard Thom, Chrysostomos Kalyvas, Matthias Hunger, K Gandhi, Luminita Pricop, S M JuglAbstract:Aim: To compare Secukinumab with infliximab in biologic-naive patients with psoriatic arthritis using matching-adjusted indirect comparison. Patients & methods: Individual patient baseline data for Secukinumab were matched to published aggregate data for infliximab by key baseline characteristics, with matching weights determined by logistic regression, and used to recalculate American College of Rheumatology (ACR) responses for Secukinumab, for comparison with infliximab. Results: There were no differences in outcomes between Secukinumab and infliximab at weeks 6/8 and 14/16. At weeks 24 and 54/52, ACR 20 responses were higher with Secukinumab 150 mg than infliximab. At week 54/52, ACR 20/50 responses were higher for Secukinumab 300 mg than infliximab. Conclusion: In the mid to long term, patients receiving Secukinumab were more likely to achieve ACR 20/50 responses than those receiving infliximab.
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Secukinumab provides sustained pasdas defined remission in psoriatic arthritis and improves health related quality of life in patients achieving remission 2 year results from the phase iii future 2 study
Arthritis Research & Therapy, 2018Co-Authors: Laura C Coates, Vibeke Strand, Peter Nash, Laure Gossec, Tore K Kvien, Dafna D Gladman, Oliver Fitzgerald, A Kavanaugh, Lawrence Rasouliyan, Luminita PricopAbstract:Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2 years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of Secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2 years among patients with PsA in the FUTURE 2 study. PASDAS (cut-off scores: remission ≤ 1.9; LDA > 1.9 and < 3.2; Moderate Disease Activity ≥ 3.2 and < 5.4; and high disease activity [HDA] ≥ 5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naive and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of Secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of Secukinumab (300 and 150 mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures. In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with Secukinumab 300 mg and in 15.2% and 19.2%, respectively, in the Secukinumab 150 mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naive group, a higher proportion of patients achieved remission + LDA at week 16 with Secukinumab 300 and 150 mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with Secukinumab were sustained through 2 years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2 years. Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2 years. Remission/LDA was achieved by both TNFi-naive and TNFi-experienced patients treated with Secukinumab, with higher rates in TNFi-naive patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA. ClinicalTrials.gov, NCT01752634 . Registered on December 19, 2012. EUDRACT, 2012-004439-22 . Registered on December 12, 2012.
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Secukinumab for psoriatic arthritis comparative effectiveness versus licensed biologics apremilast a network meta analysis
Journal of Comparative Effectiveness Research, 2018Co-Authors: Iain B Mcinnes, Peter Nash, Howard Thom, K Gandhi, Luminita Pricop, Christopher T Ritchlin, Ernest Choy, Steve Kanters, S M JuglAbstract:Aim: A network meta-analysis using randomized controlled trial data compared psoriatic arthritis (PsA) outcomes (American College of Rheumatology [ACR], Psoriasis Area Severity Index [PASI] and Psoriatic Arthritis Response Criteria [PsARC] response rates) at 12-16 weeks for Secukinumab, adalimumab, apremilast, certolizumab, etanercept, golimumab, infliximab and ustekinumab. Patients & methods: Trials were identified by systematic review. Separate networks were developed for the full-study populations, biologic-naive patients and biologic-experienced patients. Results: In the full populations, Secukinumab, adalimumab, golimumab and infliximab demonstrated the highest ACR response rates. Secukinumab and infliximab demonstrated the highest PASI response rates, and infliximab and etanercept demonstrated the highest PsARC response rates. Conclusion: In the full populations, Secukinumab demonstrated good efficacy across all outcomes. All treatments for active PsA included in this comprehensive network meta-analysis demonstrated superiority to placebo.
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Secukinumab provides rapid and sustained pain relief in psoriatic arthritis over 2 years results from the future 2 study
Arthritis Research & Therapy, 2018Co-Authors: Iain B Mcinnes, Georg Schett, Todd Fox, Vibeke Strand, Philip J Mease, Luminita Pricop, S M Jugl, Bruce Kirkham, Nicole Williams, K GandhiAbstract:Pain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of Secukinumab on patient-reported pain in PsA through 104 weeks of treatment. Pain was assessed through week 104 using clinically relevant measures, including change from baseline in a pain visual analog scale (VAS) and Short Form-36 (SF-36) bodily domain scores; proportion of patients reporting improvements equal to or better than minimum clinically meaningful differences in the pain VAS and SF-36 bodily pain domain scores; and proportion of patients with no, moderate, or extreme pain/discomfort measured by the EuroQoL 5-Dimension 3-Level Questionnaire (EQ-5D-3 L) pain item scores. Correlations of pain measures were analyzed using Pearson’s correlation coefficient. Pre-specified analyses of TNF-naive patients and patients who stopped TNF-inhibitors (TNFis) due to inadequate responses or safety/tolerability (TNF-IR patients) were performed using “as-observed data.” Mean improvements from baseline in pain VAS scores were greater with Secukinumab versus placebo by week 3 (− 16.9; P < 0.0001 with Secukinumab 300 mg and − 12.6; P < 0.05 with Secukinumab 150 mg) and sustained through week 104. SF-36 bodily pain domain scores were significantly greater with 300 mg Secukinumab and Secukinumab 150 mg versus placebo by week 4 (16.2 and 16.3, respectively; P < 0.0001 for both), and these changes were maintained through week 104. With both Secukinumab 300 mg and Secukinumab 150 mg, improvements equal to or better than the minimum clinically meaningful differences in pain VAS and SF-36 bodily pain were significant versus placebo at week 3 and week 4, respectively. At week 4, 15%, 9%, and 5% of patients receiving Secukinumab 300 mg, Secukinumab 150 mg, and placebo, respectively, reported “no pain/discomfort” measured by EQ-5D-3 L; these proportions increased to week 104 with both Secukinumab doses. Similarly, improvements in pain measures were significant in both TNF-naive and TNF-IR patients. Secukinumab provided rapid and sustained pain relief in PsA over 2 years of treatment. Improvements in pain were reported regardless of prior exposure to TNFis. ClinicalTrials.gov, NCT01752634 . Registered on 19 December 2012.
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efficacy safety and tolerability of Secukinumab in patients with active ankylosing spondylitis a randomized double blind phase 3 study measure 3
Arthritis Research & Therapy, 2017Co-Authors: K Pavelka, Luminita Pricop, Eva Dokoupilova, Hasan Tahir, Mats Andersson, Alan Kivitz, Ricardo Blanco, Aimee Readie, Marco Maradiaga, Brian PorterAbstract:Secukinumab, an anti–interleukin-17A monoclonal antibody, improved the signs and symptoms of ankylosing spondylitis (AS) in two phase 3 studies (MEASURE 1 and MEASURE 2). Here, we present 52-week results from the MEASURE 3 study assessing the efficacy and safety of Secukinumab 300 and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen. A total of 226 patients were randomized to intravenous Secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous Secukinumab 300 mg (IV-300 mg) or 150 mg (IV-150 mg) every 4 weeks, or matched placebo. Patients in the placebo group were re-randomized to subcutaneous Secukinumab at a dose of 300 or 150 mg at week 16. The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response rate at week 16 in the IV-300 mg or IV-150 mg versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, and ASAS partial remission responses, as well as the change from baseline in high-sensitivity C-reactive protein levels. Statistical analyses followed a predefined hierarchical hypothesis testing strategy to adjust for multiplicity of testing, with non-responder imputation used for binary variables and mixed-model repeated measures for continuous variables. The primary efficacy endpoint was met; the ASAS20 response rate was significantly greater at week 16 in the IV-300 mg (60.5%; P < 0.01) and IV-150 mg (58.1%; P < 0.05) groups versus placebo (36.8%). All secondary endpoints were met at week 16, except ASAS partial remission in the IV-150 mg group. Improvements achieved with Secukinumab in all clinical endpoints at week 16 were also sustained at week 52. Infections, including candidiasis, were more common with Secukinumab than with placebo during the placebo-controlled period. During the entire treatment period, pooled incidence rates of Candida infections and grade 3–4 neutropenia were 1.8% for both of these adverse events in Secukinumab-treated patients. Secukinumab (300 mg and 150 mg dose groups) provided rapid, significant and sustained improvement through 52 weeks in the signs and symptoms of patients with AS. The safety profile was consistent with previous reports, with no new or unexpected findings. ClinicalTrials.gov, NCT02008916 . Registered on 8 December 2013. EUDRACT 2013-001090-24. Registered on 24 October 2013). The study was not retrospectively registered.
