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Mark C Genovese - One of the best experts on this subject based on the ideXlab platform.

  • sat0341 efficacy and safety of ixekizumab in patients with active psoriatic arthritis and previous inadequate response to tnf inhibitors 52 week results from a phase 3 study
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Mark C Genovese, Joel M Kremer, David H Adams, Lisa Kerr, Bernard Combe, Peter Nash
    Abstract:

    Background Ixekizumab (IXE) is a high affinity monoclonal antibody that selectively targets interleukin-17A. In patients with active psoriatic arthritis (PsA) who had an inadequate response to tumour necrosis factor inhibitors (TNFi), IXE was superior to placebo (PBO) in improving the signs and symptoms of PsA after 24 weeks of treatment (SPIRIT-P2; NCT02349295).1 Objectives The objective of this study is to report the Week 52 interim efficacy and safety findings of IXE treatment during the Extension Period (EP) of SPIRIT-P2 (Weeks 24–156). Methods SPIRIT-P2 is a Phase 3, multicenter, double-blind study. All 363 patients had an inadequate response to one or two TNFi or were intolerant to TNFi. During the Double-Blind Treatment Period (DBTP; Weeks 0–24), patients were randomly assigned 1:1:1 to subcutaneous administration of either 80 mg IXE every 4 weeks (Q4W; n=122) or every 2 weeks (Q2W; n=123) following a 160 mg starting dose at Week 0, or PBO (n=118). Of these, 310 patients completed the DBTP and entered the EP (Weeks 24–156). Patients randomised to IXE at Week 0 continued the same dose regimen in the EP. PBO patients were re-randomised (1:1) to IXE Q4W or Q2W at Week 16 (inadequate responders) or 24. In this interim analysis, efficacy (up to Week 52) and safety (up to Week 156) were analysed using the EP population, defined as all patients who received at least 1 dose of study drug in the EP. Missing values were considered non-response for categorical data and were imputed by modified baseline observation carried forward for continuous data. Results In the DBTP, a significantly higher percentage of patients achieved ACR20 at Week 24 with IXE Q4W (53%) or Q2W (48%) than with PBO (20%).1 For patients who entered the EP, the mean age was 52 years, 47% were male, the mean time since PsA onset was 12 years, and mean tender and swollen joint counts at baseline (Week 0) were 23 and 12, respectively. For EP patients who were initially randomised to IXE Q4W or Q2W during the DBTP, ACR20 responses at Week 52 were 68% and 59%, respectively. For patients treated with PBO during the DBTP and re-randomised to IXE Q4W or Q2W during the EP, ACR20 responses at Week 52 were 61% and 50%, respectively. Additional efficacy measures are depicted in the Table. The frequency of adverse events (AEs) in the EP is presented in the Table; the majority were mild or moderate in severity. Serious AEs occurred in 15 patients, and one death occurred in the EP population: a myocardial infarction in a PBO/IXE Q2W patient 502 days after starting IXE. Conclusions IXE demonstrated sustained improvement in the signs and symptoms of PsA across treatment groups during the EP. The safety profile of IXE observed in the EP population was consistent with the safety profile of the intent-to-treat population in the DBTP of SPIRIT-P2.1 Reference [1] Nash P, et al. Lancet2017;389:2317–27. Disclosure of Interest M. Genovese Grant/research support from: Eli Lilly and Company, Abbvie, Galapagos, Pfizer, Consultant for: Eli Lilly and Company, Abbvie, Galapagos, Pfizer, B. Combe Grant/research support from: Pfizer, MSD, Roche-Chugai, Consultant for: Pfizer, UCB, Bristol-Myers Squibb, Janssen, Eli Lilly and Company, MSD, Roche-Chugai, AbbVie, Novartis, Speakers bureau: Pfizer, Bristol-Myers Squibb, Eli Lilly and Company, MSD, J. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Novartis, Pfizer, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Novartis, Pfizer, Employee of: Corrona, D. Adams Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, C. Lee Shareholder of: Eli Lilly and Company, L. Kerr Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, P. Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Roche, Sanofi, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Roche, Sanofi, UCB

  • thu0166 safety profile of baricitinib in patients with active ra an integrated analysis
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Josef S Smolen, C. Dickson, Mark C Genovese, Terence Rooney, William L Macias, T Takeuchi, David L Hyslop, L Chen, J Riddle, Tracy E Cardillo
    Abstract:

    Background Baricitinib (bari; an oral JAK 1/JAK 2 inhibitor) is in development for patients (pts) with active RA. Objectives To assess the safety of bari in pts with active RA across 8 completed studies (4 Ph3, 3 Ph2, 1 Ph1b) and 1 ongoing long-term extension (LTE) study. Methods Primary safety analysis was based on 6 studies with bari 4 mg QD and placebo (PBO) arms and dose response assessments on 4 studies with bari 2 and 4 mg QD and PBO arms. In addition, the all-bari RA set included all patients exposed to any bari dose. 2 studies contained active comparators. Results 3464 pts were exposed to bari (4214 pt-yrs (PY); 2166 pts (62.5%) >1 yr; 467 (13.5%) >2 yrs). In controlled periods of the program, no increases in deaths, AEs leading to study drug discontinuation, malignancies, MACE, or serious infections were seen for bari vs PBO/active treatment. Herpes zoster was reported more frequently for bari vs PBO. In randomized, controlled periods of the program, TB was reported in 2 pts: 1 bari 4 mg, 1 adalimumab; in uncontrolled periods, 6 TB events were reported (bari 4 mg: 2 with incomplete TB screening, 3 without organism confirmed). All TB occurred in endemic areas. Two GI perforations were reported (0.05/100 PY). No confirmed opportunistic infections were reported. Bari treatment has been associated with changes in selected hematology/clinical chemistry analytes; few patients ( Conclusions In the context of reported efficacy, 1,2 bari had an acceptable safety profile in pts with moderate-to-severe active RA. References Dougados M. Ann Rheum Dis. 2015;74(S2):79. Taylor PC. Arthritis Rheumatol. 2015;67(suppl 10). Disclosure of Interest J. Smolen Grant/research support from: AbbVie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Celtrion, Glaxo, ILTOO, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, M. Genovese Grant/research support from: AbbVie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, Vertex, Consultant for: AbbVie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, T. Takeuchi Grant/research support from: Chugai Pharmaceutical Co,. Ltd, Eli Lilly and Company, Consultant for: Eli Lilly and Company, D. Hyslop Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, W. Macias Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Rooney Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, L. Chen Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, C. Dickson Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, J. Riddle Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Cardillo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, K. Winthrop Grant/research support from: BMS, Pfizer, Consultant for: BMS, Pfizer, Eli Lilly and Company, Abbvie, Galapagos

  • op0029 baricitinib an oral janus kinase jak 1 jak2 inhibitor in patients with active rheumatoid arthritis ra and an inadequate response to tnf inhibitors results of the phase 3 ra beacon study
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Mark C Genovese, Joel M Kremer, Omid Zamani, Charles Ludivico, Marek Krogulec, Scott D Beattie, A E Koch, Tracy E Cardillo, Terence Rooney, William L Macias
    Abstract:

    Background In ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in patients (pts) with active RA naive to biologic DMARDs (bDMARDs). 1,2 Objectives To report results from a ph 3 study of bari in pts with active RA and an inadequate response or intolerance to ≥1 TNF inhibitor (TNFi). Methods Pts with active RA (TJC & SJC ≥6, hsCRP ≥3mg/L) on conventional DMARDs (cDMARDs) were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD for 24 wks. All bDMARDs were discontinued ≥28d prior to treatment. Primary endpoint was ACR20 response at Wk 12 for bari 4 mg vs. PBO. Results Of 527 randomized pts, 57% had received ≥2 bDMARDs and 38% had received ≥1 non-TNFi bDMARD. Fewer pts discontinued treatment prior to Wk 24 on bari 2 or 4 mg vs. PBO (10%, 11%, 18%, respectively). ACR20 response at Wk 12 was higher with bari 4 mg vs. PBO (55% vs. 27%, p≤0.001). Improvements in ACR20, ACR50, ACR70, DAS28, CDAI, SDAI, and HAQ-DI were seen (Table), many as early as Wk 1. Treatment benefit was sustained through Wk 24 for the 4 mg dose. More TEAEs occurred in pts receiving bari 2 or 4 mg compared to PBO (71%, 77%, 64%, respectively) including infections (44%, 40%, 31%, respectively). SAE rates through 24 wks were similar among pts receiving bari 2 or 4 mg or PBO (4%, 10%, and 7%, respectively) including serious infections (2%, 3%, and 3%, respectively). There were no opportunistic infections, TB, or GI perforations. Two non-melanoma skin cancers and 2 major adverse cardiovascular events, including 1 death (stroke), were seen with bari 4 mg. Lab findings were consistent with ph 2 studies. Abnormalities leading to discontinuation were infrequent. Conclusions In pts with active RA on cDMARDs and an inadequate response to bDMARDs, once daily oral bari was associated with rapid and sustained clinical improvements through 24 wks, with an acceptable safety and tolerability profile. The largest benefit was seen with the 4 mg dose. Additional ph 3 studies in bDMARD-naive pts are ongoing. References Keystone et al. Ann Rheum Dis 2015;24:333-340 Tanaka et al. Arthritis Rheum 2013;65(S10):S765 Disclosure of Interest M. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, Consultant for: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, J. Kremer Grant/research support from: Abbvie, Amgen, BMS, Genentech, Eli Lilly & Company, Pfizer, UCB, Consultant for: Eli Lilly & Company, Employee of: Corrona, O. Zamani Grant/research support from: Eli Lilly & Company, C. Ludivico Grant/research support from: Eli Lilly & Company, M. Krogulec Grant/research support from: Eli Lilly & Company, L. Xie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. Beattie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, A. Koch Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Cardillo Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Rooney Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, W. Macias Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, D. Schlichting Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, J. Smolen Grant/research support from: Abbvie, Janssen, MSD, Pfizer, Roche, UCB, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, Janssen, Eli Lilly & Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB

William L Macias - One of the best experts on this subject based on the ideXlab platform.

  • thu0166 safety profile of baricitinib in patients with active ra an integrated analysis
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Josef S Smolen, C. Dickson, Mark C Genovese, Terence Rooney, William L Macias, T Takeuchi, David L Hyslop, L Chen, J Riddle, Tracy E Cardillo
    Abstract:

    Background Baricitinib (bari; an oral JAK 1/JAK 2 inhibitor) is in development for patients (pts) with active RA. Objectives To assess the safety of bari in pts with active RA across 8 completed studies (4 Ph3, 3 Ph2, 1 Ph1b) and 1 ongoing long-term extension (LTE) study. Methods Primary safety analysis was based on 6 studies with bari 4 mg QD and placebo (PBO) arms and dose response assessments on 4 studies with bari 2 and 4 mg QD and PBO arms. In addition, the all-bari RA set included all patients exposed to any bari dose. 2 studies contained active comparators. Results 3464 pts were exposed to bari (4214 pt-yrs (PY); 2166 pts (62.5%) >1 yr; 467 (13.5%) >2 yrs). In controlled periods of the program, no increases in deaths, AEs leading to study drug discontinuation, malignancies, MACE, or serious infections were seen for bari vs PBO/active treatment. Herpes zoster was reported more frequently for bari vs PBO. In randomized, controlled periods of the program, TB was reported in 2 pts: 1 bari 4 mg, 1 adalimumab; in uncontrolled periods, 6 TB events were reported (bari 4 mg: 2 with incomplete TB screening, 3 without organism confirmed). All TB occurred in endemic areas. Two GI perforations were reported (0.05/100 PY). No confirmed opportunistic infections were reported. Bari treatment has been associated with changes in selected hematology/clinical chemistry analytes; few patients ( Conclusions In the context of reported efficacy, 1,2 bari had an acceptable safety profile in pts with moderate-to-severe active RA. References Dougados M. Ann Rheum Dis. 2015;74(S2):79. Taylor PC. Arthritis Rheumatol. 2015;67(suppl 10). Disclosure of Interest J. Smolen Grant/research support from: AbbVie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Celtrion, Glaxo, ILTOO, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, M. Genovese Grant/research support from: AbbVie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, Vertex, Consultant for: AbbVie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, T. Takeuchi Grant/research support from: Chugai Pharmaceutical Co,. Ltd, Eli Lilly and Company, Consultant for: Eli Lilly and Company, D. Hyslop Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, W. Macias Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Rooney Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, L. Chen Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, C. Dickson Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, J. Riddle Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Cardillo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, K. Winthrop Grant/research support from: BMS, Pfizer, Consultant for: BMS, Pfizer, Eli Lilly and Company, Abbvie, Galapagos

  • op0029 baricitinib an oral janus kinase jak 1 jak2 inhibitor in patients with active rheumatoid arthritis ra and an inadequate response to tnf inhibitors results of the phase 3 ra beacon study
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Mark C Genovese, Joel M Kremer, Omid Zamani, Charles Ludivico, Marek Krogulec, Scott D Beattie, A E Koch, Tracy E Cardillo, Terence Rooney, William L Macias
    Abstract:

    Background In ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in patients (pts) with active RA naive to biologic DMARDs (bDMARDs). 1,2 Objectives To report results from a ph 3 study of bari in pts with active RA and an inadequate response or intolerance to ≥1 TNF inhibitor (TNFi). Methods Pts with active RA (TJC & SJC ≥6, hsCRP ≥3mg/L) on conventional DMARDs (cDMARDs) were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD for 24 wks. All bDMARDs were discontinued ≥28d prior to treatment. Primary endpoint was ACR20 response at Wk 12 for bari 4 mg vs. PBO. Results Of 527 randomized pts, 57% had received ≥2 bDMARDs and 38% had received ≥1 non-TNFi bDMARD. Fewer pts discontinued treatment prior to Wk 24 on bari 2 or 4 mg vs. PBO (10%, 11%, 18%, respectively). ACR20 response at Wk 12 was higher with bari 4 mg vs. PBO (55% vs. 27%, p≤0.001). Improvements in ACR20, ACR50, ACR70, DAS28, CDAI, SDAI, and HAQ-DI were seen (Table), many as early as Wk 1. Treatment benefit was sustained through Wk 24 for the 4 mg dose. More TEAEs occurred in pts receiving bari 2 or 4 mg compared to PBO (71%, 77%, 64%, respectively) including infections (44%, 40%, 31%, respectively). SAE rates through 24 wks were similar among pts receiving bari 2 or 4 mg or PBO (4%, 10%, and 7%, respectively) including serious infections (2%, 3%, and 3%, respectively). There were no opportunistic infections, TB, or GI perforations. Two non-melanoma skin cancers and 2 major adverse cardiovascular events, including 1 death (stroke), were seen with bari 4 mg. Lab findings were consistent with ph 2 studies. Abnormalities leading to discontinuation were infrequent. Conclusions In pts with active RA on cDMARDs and an inadequate response to bDMARDs, once daily oral bari was associated with rapid and sustained clinical improvements through 24 wks, with an acceptable safety and tolerability profile. The largest benefit was seen with the 4 mg dose. Additional ph 3 studies in bDMARD-naive pts are ongoing. References Keystone et al. Ann Rheum Dis 2015;24:333-340 Tanaka et al. Arthritis Rheum 2013;65(S10):S765 Disclosure of Interest M. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, Consultant for: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, J. Kremer Grant/research support from: Abbvie, Amgen, BMS, Genentech, Eli Lilly & Company, Pfizer, UCB, Consultant for: Eli Lilly & Company, Employee of: Corrona, O. Zamani Grant/research support from: Eli Lilly & Company, C. Ludivico Grant/research support from: Eli Lilly & Company, M. Krogulec Grant/research support from: Eli Lilly & Company, L. Xie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. Beattie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, A. Koch Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Cardillo Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Rooney Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, W. Macias Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, D. Schlichting Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, J. Smolen Grant/research support from: Abbvie, Janssen, MSD, Pfizer, Roche, UCB, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, Janssen, Eli Lilly & Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB

Joel M Kremer - One of the best experts on this subject based on the ideXlab platform.

  • thu0071 the combination of rheumatoid factors with antibody systems targeting citrullinated carbamylated and peptidyl arginine deiminase autoantigens distinguishes rheumatoid arthritis
    Annals of the Rheumatic Diseases, 2019
    Co-Authors: Thierry Dervieux, Joel M Kremer, John Conklin, Tyler Omalley, Kelley Brady, Roberta Vezza Alexander, Claudia Ibarra, Michael Mahler, Michael E Weinblatt, Arthur Weinstein
    Abstract:

    Background: Novel antibody systems including anti-Carbamylated Protein Antibody (anti-CarP IgG) and anti-Peptidyl Arginine Deiminase Antibody (anti-PAD4 IgG) are emerging as independent diagnostic and prognostic biomarkers for Rheumatoid Arthritis (RA) (ref, 1-3). As such, these antibody systems may add value to rheumatoid factor (IgM) and anti-citrullinated peptide antibody (ACPA IgG), the hallmark antibodies in RA. Objectives: We evaluated the diagnostic performance of Rheumatoid Factor (RF) with antibody systems targeting citrullinated, carbamylated and PAD4 autoantigens in RA. Methods: The cohort consisted of 638 consenting subjects with RA (fulfilling the 1987 or 2010 ACR classification criteria, mean age: 59.8±0.5 years [SEM], 80% female) and a control group of 775 subjects (mean age: 44.7±0.5 years, 85% females, including Systemic Lupus Erythematosus [n=369], primary Sjogren’s Syndrome [n=64], Primary Fibromyalgia [n=85], other connective tissue diseases [n=63], and a group of normal healthy donors [n=194]). Autoantibodies titers from serum were measured using fluoroenzyme immunoassays (anti-RF [IgM] and anti-CCP [IgG]; Phadia Upsala, Sweden), ELISA (anti-CarP [IgG], research use only [RUO], Inova Diagnostics, San Diego) and bead-based AptivaTM technology (anti-PAD4 [IgG], RUO, Inova Diagnostics) in a clinical laboratory accredited by the College of American Pathologists. For each positive antibody (above each cutoff) a score of 1 was assigned and the cumulative presence of the 4 antibodies was determined [range 0-4]. The ability of the biomarkers to distinguish RA from controls was calculated using sensitivity, specificity and interval likelihood ratio (LR). Positive Predictive Value (PPV) was estimated at 10% pre-test probability. Statistics consisted of Mann-Whitney and Chi-square tests. Results: In this cohort anti-CarP IgG (>20 Units) yielded 33.5% sensitivity and 77.9% specificity. Anti-PAD4 (>1000 Units) yielded 35.0% sensitivity and 95.0% specificity. RF IgM (>5 Units/ml) and anti-CCP (>10 Units/ml) were 67.4% and 66.5% sensitive, respectively (87.5% and 97.0% specific, respectively). RA presented 5-fold higher 4-antibody system scores (2.02±0.05) than controls (0.42±0.02); (p Conclusion: This cumulative combination of antibody systems targeting citrullinated, carbamylated, PAD4 and Fc autoantigens (RF IgM) is highly specific for RA. It may be useful in diagnosing and classifying RA even in symptomatic patients who present early in the course of disease. References: [1] Shi, et al. Proc Natl Acad Sci USA. 2011 108(42):17372-7 [2] Darrah E et al. Sci Transl Med. 2013 2;5186ra65 [3] Verheul, et al. Arthritis Rheumatol. 2018 Nov;70(11):1721-1731 Disclosure of Interests: Thierry Dervieux Shareholder of: Exagen (a diagnostics Company not a pharmaceutical Company), Employee of: Exagen (a diagnostics Company not a pharmaceutical Company), John Conklin Employee of: Exagen (a diagnostics Company not a pharmaceutical Company), Tyler O’Malley Employee of: Exagen (a diagnostics Company not a pharmaceutical Company), Kelley Brady Employee of: Exagen (a diagnostics Company not a pharmaceutical Company), Roberta Alexander Employee of: Exagen (a diagnostics Company not a pharmaceutical Company), Jing Shi Employee of: Exagen (a diagnostics Company not a pharmaceutical Company), Claudia Ibarra Shareholder of: Exagen (a diagnostics Company not a pharmaceutical Company), Employee of: Exagen (a diagnostics Company not a pharmaceutical Company), Michael Mahler Employee of: Inova Diagnostics (Not pharmaceutical, diagnostics Company), Joel Kremer Shareholder of: Corrona, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Genentech, GSK, Lilly, Pfizer, Regeneron and Sanofi, Employee of: Corrona, Michael E. Weinblatt Shareholder of: Stock option: CanFite, Lycera, Scipher, Inmedix, Grant/research support from: Crescendo Bioscience, Bristol Myers Squibb, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, CanFite, Corrona, Crescendo, GlaxoSmithKline, Gilead, Horizon, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Scipher, Set Point, Arthur Weinstein Shareholder of: Exagen (a diagnostics Company not a pharmaceutical Company), Consultant for: Exagen (a diagnostics Company not a pharmaceutical Company)

  • sat0341 efficacy and safety of ixekizumab in patients with active psoriatic arthritis and previous inadequate response to tnf inhibitors 52 week results from a phase 3 study
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Mark C Genovese, Joel M Kremer, David H Adams, Lisa Kerr, Bernard Combe, Peter Nash
    Abstract:

    Background Ixekizumab (IXE) is a high affinity monoclonal antibody that selectively targets interleukin-17A. In patients with active psoriatic arthritis (PsA) who had an inadequate response to tumour necrosis factor inhibitors (TNFi), IXE was superior to placebo (PBO) in improving the signs and symptoms of PsA after 24 weeks of treatment (SPIRIT-P2; NCT02349295).1 Objectives The objective of this study is to report the Week 52 interim efficacy and safety findings of IXE treatment during the Extension Period (EP) of SPIRIT-P2 (Weeks 24–156). Methods SPIRIT-P2 is a Phase 3, multicenter, double-blind study. All 363 patients had an inadequate response to one or two TNFi or were intolerant to TNFi. During the Double-Blind Treatment Period (DBTP; Weeks 0–24), patients were randomly assigned 1:1:1 to subcutaneous administration of either 80 mg IXE every 4 weeks (Q4W; n=122) or every 2 weeks (Q2W; n=123) following a 160 mg starting dose at Week 0, or PBO (n=118). Of these, 310 patients completed the DBTP and entered the EP (Weeks 24–156). Patients randomised to IXE at Week 0 continued the same dose regimen in the EP. PBO patients were re-randomised (1:1) to IXE Q4W or Q2W at Week 16 (inadequate responders) or 24. In this interim analysis, efficacy (up to Week 52) and safety (up to Week 156) were analysed using the EP population, defined as all patients who received at least 1 dose of study drug in the EP. Missing values were considered non-response for categorical data and were imputed by modified baseline observation carried forward for continuous data. Results In the DBTP, a significantly higher percentage of patients achieved ACR20 at Week 24 with IXE Q4W (53%) or Q2W (48%) than with PBO (20%).1 For patients who entered the EP, the mean age was 52 years, 47% were male, the mean time since PsA onset was 12 years, and mean tender and swollen joint counts at baseline (Week 0) were 23 and 12, respectively. For EP patients who were initially randomised to IXE Q4W or Q2W during the DBTP, ACR20 responses at Week 52 were 68% and 59%, respectively. For patients treated with PBO during the DBTP and re-randomised to IXE Q4W or Q2W during the EP, ACR20 responses at Week 52 were 61% and 50%, respectively. Additional efficacy measures are depicted in the Table. The frequency of adverse events (AEs) in the EP is presented in the Table; the majority were mild or moderate in severity. Serious AEs occurred in 15 patients, and one death occurred in the EP population: a myocardial infarction in a PBO/IXE Q2W patient 502 days after starting IXE. Conclusions IXE demonstrated sustained improvement in the signs and symptoms of PsA across treatment groups during the EP. The safety profile of IXE observed in the EP population was consistent with the safety profile of the intent-to-treat population in the DBTP of SPIRIT-P2.1 Reference [1] Nash P, et al. Lancet2017;389:2317–27. Disclosure of Interest M. Genovese Grant/research support from: Eli Lilly and Company, Abbvie, Galapagos, Pfizer, Consultant for: Eli Lilly and Company, Abbvie, Galapagos, Pfizer, B. Combe Grant/research support from: Pfizer, MSD, Roche-Chugai, Consultant for: Pfizer, UCB, Bristol-Myers Squibb, Janssen, Eli Lilly and Company, MSD, Roche-Chugai, AbbVie, Novartis, Speakers bureau: Pfizer, Bristol-Myers Squibb, Eli Lilly and Company, MSD, J. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Novartis, Pfizer, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Novartis, Pfizer, Employee of: Corrona, D. Adams Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, C. Lee Shareholder of: Eli Lilly and Company, L. Kerr Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, P. Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Roche, Sanofi, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Roche, Sanofi, UCB

  • op0029 baricitinib an oral janus kinase jak 1 jak2 inhibitor in patients with active rheumatoid arthritis ra and an inadequate response to tnf inhibitors results of the phase 3 ra beacon study
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Mark C Genovese, Joel M Kremer, Omid Zamani, Charles Ludivico, Marek Krogulec, Scott D Beattie, A E Koch, Tracy E Cardillo, Terence Rooney, William L Macias
    Abstract:

    Background In ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in patients (pts) with active RA naive to biologic DMARDs (bDMARDs). 1,2 Objectives To report results from a ph 3 study of bari in pts with active RA and an inadequate response or intolerance to ≥1 TNF inhibitor (TNFi). Methods Pts with active RA (TJC & SJC ≥6, hsCRP ≥3mg/L) on conventional DMARDs (cDMARDs) were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD for 24 wks. All bDMARDs were discontinued ≥28d prior to treatment. Primary endpoint was ACR20 response at Wk 12 for bari 4 mg vs. PBO. Results Of 527 randomized pts, 57% had received ≥2 bDMARDs and 38% had received ≥1 non-TNFi bDMARD. Fewer pts discontinued treatment prior to Wk 24 on bari 2 or 4 mg vs. PBO (10%, 11%, 18%, respectively). ACR20 response at Wk 12 was higher with bari 4 mg vs. PBO (55% vs. 27%, p≤0.001). Improvements in ACR20, ACR50, ACR70, DAS28, CDAI, SDAI, and HAQ-DI were seen (Table), many as early as Wk 1. Treatment benefit was sustained through Wk 24 for the 4 mg dose. More TEAEs occurred in pts receiving bari 2 or 4 mg compared to PBO (71%, 77%, 64%, respectively) including infections (44%, 40%, 31%, respectively). SAE rates through 24 wks were similar among pts receiving bari 2 or 4 mg or PBO (4%, 10%, and 7%, respectively) including serious infections (2%, 3%, and 3%, respectively). There were no opportunistic infections, TB, or GI perforations. Two non-melanoma skin cancers and 2 major adverse cardiovascular events, including 1 death (stroke), were seen with bari 4 mg. Lab findings were consistent with ph 2 studies. Abnormalities leading to discontinuation were infrequent. Conclusions In pts with active RA on cDMARDs and an inadequate response to bDMARDs, once daily oral bari was associated with rapid and sustained clinical improvements through 24 wks, with an acceptable safety and tolerability profile. The largest benefit was seen with the 4 mg dose. Additional ph 3 studies in bDMARD-naive pts are ongoing. References Keystone et al. Ann Rheum Dis 2015;24:333-340 Tanaka et al. Arthritis Rheum 2013;65(S10):S765 Disclosure of Interest M. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, Consultant for: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, J. Kremer Grant/research support from: Abbvie, Amgen, BMS, Genentech, Eli Lilly & Company, Pfizer, UCB, Consultant for: Eli Lilly & Company, Employee of: Corrona, O. Zamani Grant/research support from: Eli Lilly & Company, C. Ludivico Grant/research support from: Eli Lilly & Company, M. Krogulec Grant/research support from: Eli Lilly & Company, L. Xie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. Beattie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, A. Koch Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Cardillo Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Rooney Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, W. Macias Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, D. Schlichting Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, J. Smolen Grant/research support from: Abbvie, Janssen, MSD, Pfizer, Roche, UCB, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, Janssen, Eli Lilly & Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB

Terence Rooney - One of the best experts on this subject based on the ideXlab platform.

  • thu0166 safety profile of baricitinib in patients with active ra an integrated analysis
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Josef S Smolen, C. Dickson, Mark C Genovese, Terence Rooney, William L Macias, T Takeuchi, David L Hyslop, L Chen, J Riddle, Tracy E Cardillo
    Abstract:

    Background Baricitinib (bari; an oral JAK 1/JAK 2 inhibitor) is in development for patients (pts) with active RA. Objectives To assess the safety of bari in pts with active RA across 8 completed studies (4 Ph3, 3 Ph2, 1 Ph1b) and 1 ongoing long-term extension (LTE) study. Methods Primary safety analysis was based on 6 studies with bari 4 mg QD and placebo (PBO) arms and dose response assessments on 4 studies with bari 2 and 4 mg QD and PBO arms. In addition, the all-bari RA set included all patients exposed to any bari dose. 2 studies contained active comparators. Results 3464 pts were exposed to bari (4214 pt-yrs (PY); 2166 pts (62.5%) >1 yr; 467 (13.5%) >2 yrs). In controlled periods of the program, no increases in deaths, AEs leading to study drug discontinuation, malignancies, MACE, or serious infections were seen for bari vs PBO/active treatment. Herpes zoster was reported more frequently for bari vs PBO. In randomized, controlled periods of the program, TB was reported in 2 pts: 1 bari 4 mg, 1 adalimumab; in uncontrolled periods, 6 TB events were reported (bari 4 mg: 2 with incomplete TB screening, 3 without organism confirmed). All TB occurred in endemic areas. Two GI perforations were reported (0.05/100 PY). No confirmed opportunistic infections were reported. Bari treatment has been associated with changes in selected hematology/clinical chemistry analytes; few patients ( Conclusions In the context of reported efficacy, 1,2 bari had an acceptable safety profile in pts with moderate-to-severe active RA. References Dougados M. Ann Rheum Dis. 2015;74(S2):79. Taylor PC. Arthritis Rheumatol. 2015;67(suppl 10). Disclosure of Interest J. Smolen Grant/research support from: AbbVie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Celtrion, Glaxo, ILTOO, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, M. Genovese Grant/research support from: AbbVie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, Vertex, Consultant for: AbbVie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, T. Takeuchi Grant/research support from: Chugai Pharmaceutical Co,. Ltd, Eli Lilly and Company, Consultant for: Eli Lilly and Company, D. Hyslop Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, W. Macias Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Rooney Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, L. Chen Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, C. Dickson Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, J. Riddle Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Cardillo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, K. Winthrop Grant/research support from: BMS, Pfizer, Consultant for: BMS, Pfizer, Eli Lilly and Company, Abbvie, Galapagos

  • op0029 baricitinib an oral janus kinase jak 1 jak2 inhibitor in patients with active rheumatoid arthritis ra and an inadequate response to tnf inhibitors results of the phase 3 ra beacon study
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Mark C Genovese, Joel M Kremer, Omid Zamani, Charles Ludivico, Marek Krogulec, Scott D Beattie, A E Koch, Tracy E Cardillo, Terence Rooney, William L Macias
    Abstract:

    Background In ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in patients (pts) with active RA naive to biologic DMARDs (bDMARDs). 1,2 Objectives To report results from a ph 3 study of bari in pts with active RA and an inadequate response or intolerance to ≥1 TNF inhibitor (TNFi). Methods Pts with active RA (TJC & SJC ≥6, hsCRP ≥3mg/L) on conventional DMARDs (cDMARDs) were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD for 24 wks. All bDMARDs were discontinued ≥28d prior to treatment. Primary endpoint was ACR20 response at Wk 12 for bari 4 mg vs. PBO. Results Of 527 randomized pts, 57% had received ≥2 bDMARDs and 38% had received ≥1 non-TNFi bDMARD. Fewer pts discontinued treatment prior to Wk 24 on bari 2 or 4 mg vs. PBO (10%, 11%, 18%, respectively). ACR20 response at Wk 12 was higher with bari 4 mg vs. PBO (55% vs. 27%, p≤0.001). Improvements in ACR20, ACR50, ACR70, DAS28, CDAI, SDAI, and HAQ-DI were seen (Table), many as early as Wk 1. Treatment benefit was sustained through Wk 24 for the 4 mg dose. More TEAEs occurred in pts receiving bari 2 or 4 mg compared to PBO (71%, 77%, 64%, respectively) including infections (44%, 40%, 31%, respectively). SAE rates through 24 wks were similar among pts receiving bari 2 or 4 mg or PBO (4%, 10%, and 7%, respectively) including serious infections (2%, 3%, and 3%, respectively). There were no opportunistic infections, TB, or GI perforations. Two non-melanoma skin cancers and 2 major adverse cardiovascular events, including 1 death (stroke), were seen with bari 4 mg. Lab findings were consistent with ph 2 studies. Abnormalities leading to discontinuation were infrequent. Conclusions In pts with active RA on cDMARDs and an inadequate response to bDMARDs, once daily oral bari was associated with rapid and sustained clinical improvements through 24 wks, with an acceptable safety and tolerability profile. The largest benefit was seen with the 4 mg dose. Additional ph 3 studies in bDMARD-naive pts are ongoing. References Keystone et al. Ann Rheum Dis 2015;24:333-340 Tanaka et al. Arthritis Rheum 2013;65(S10):S765 Disclosure of Interest M. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, Consultant for: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, J. Kremer Grant/research support from: Abbvie, Amgen, BMS, Genentech, Eli Lilly & Company, Pfizer, UCB, Consultant for: Eli Lilly & Company, Employee of: Corrona, O. Zamani Grant/research support from: Eli Lilly & Company, C. Ludivico Grant/research support from: Eli Lilly & Company, M. Krogulec Grant/research support from: Eli Lilly & Company, L. Xie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. Beattie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, A. Koch Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Cardillo Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Rooney Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, W. Macias Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, D. Schlichting Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, J. Smolen Grant/research support from: Abbvie, Janssen, MSD, Pfizer, Roche, UCB, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, Janssen, Eli Lilly & Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB

  • lb0001 baricitinib an oral janus kinase jak 1 jak2 inhibitor in patients with active rheumatoid arthritis ra and an inadequate response to cdmard therapy results of the phase 3 ra build study
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: M Dougados, Scott D Beattie, Terence Rooney, D Van Der Heijde, Y C Chen, Maria Greenwald, E Drescher, I De La Torre, D Schlichting, S De Bono
    Abstract:

    Background In ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in patients (pts) with active RA and inadequate response (IR) to conventional DMARDs (cDMARDs). Objectives To report results from a 24-week (Wk) global ph 3 study of bari in pts with active RA and an IR or intolerance to ≥1 cDMARD. Methods Pts with active RA (TJC & SJC≥6 & hsCRP≥3.6 mg/L) with stable background treatment were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD, stratified by region and baseline joint erosion status, with rescue from Wk 16 for nonresponders. Primary endpoint was ACR20 response at Wk 12 for bari 4 mg vs. PBO. Results Of 684 randomized pts, 81% were seropositive with mean baseline DAS28 of 5.55 (-hsCRP) and 6.22 (-ESR). Rescue rates were 9%, 7%, and 24% for bari 2 mg, 4 mg, PBO, respectively. ACR20 response at Wk 12 was 62% with bari 4 mg vs. 40% with PBO (p≤0.001). Improvements in ACR50, ACR70, DAS28, CDAI, SDAI, and HAQ-DI were seen (Table), many as early as Wk 1. Change in mTSS at Wk 24 was lower with bari 2 or 4 mg vs. PBO (p≤0.05, p≤0.01, respectively). TEAE and SAE rates, including serious infections, were similar among pts receiving bari 2 or 4 mg or PBO (SAEs: 3%, 5%, 5%, respectively). There were no GI perforations or opportunistic infections. In the bari 4 mg group, 1 TB case and 1 NMSC case occurred. In the PBO group, 2 deaths and 2 MACE occurred. Lab findings were similar to ph 2; few abnormalities led to discontinuation. Conclusions Once daily oral bari was associated with rapid and sustained clinical improvement and inhibition of radiographic joint damage, with an acceptable safety and tolerability profile. The most robust benefit across measures was seen with the 4 mg dose. Disclosure of Interest M. Dougados Grant/research support from: Eli Lilly and Company, AbbVie, Pfizer, UCB, Bristol-Myers Squibb, Novartis, Sanofi, and Roche, Consultant for: Eli Lilly and Company, AbbVie, Pfizer, UCB, Bristol-Myers Squibb, Novartis, Sanofi, and Roche, D. van der Heijde Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli Lilly and Company, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB, and Vertex, Y.-C. Chen Grant/research support from: Eli Lilly and Company, Speakers bureau: Eli Lilly and Company, AbbVie, Pfizer, and Bristol-Myers Squibb, M. Greenwald Grant/research support from: Eli Lilly and Company, E. Drescher: None declared, J. Liu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Beattie Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, I. de la Torre Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Rooney Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, D. Schlichting Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. de Bono Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, P. Emery Consultant for: Abbott/AbbVie, Bristol-Myers Squibb, Pfizer, UCB, MSD, Roche, Novartis, Samsung, Takeda, and Eli Lilly and Company

Tracy E Cardillo - One of the best experts on this subject based on the ideXlab platform.

  • thu0166 safety profile of baricitinib in patients with active ra an integrated analysis
    Annals of the Rheumatic Diseases, 2016
    Co-Authors: Josef S Smolen, C. Dickson, Mark C Genovese, Terence Rooney, William L Macias, T Takeuchi, David L Hyslop, L Chen, J Riddle, Tracy E Cardillo
    Abstract:

    Background Baricitinib (bari; an oral JAK 1/JAK 2 inhibitor) is in development for patients (pts) with active RA. Objectives To assess the safety of bari in pts with active RA across 8 completed studies (4 Ph3, 3 Ph2, 1 Ph1b) and 1 ongoing long-term extension (LTE) study. Methods Primary safety analysis was based on 6 studies with bari 4 mg QD and placebo (PBO) arms and dose response assessments on 4 studies with bari 2 and 4 mg QD and PBO arms. In addition, the all-bari RA set included all patients exposed to any bari dose. 2 studies contained active comparators. Results 3464 pts were exposed to bari (4214 pt-yrs (PY); 2166 pts (62.5%) >1 yr; 467 (13.5%) >2 yrs). In controlled periods of the program, no increases in deaths, AEs leading to study drug discontinuation, malignancies, MACE, or serious infections were seen for bari vs PBO/active treatment. Herpes zoster was reported more frequently for bari vs PBO. In randomized, controlled periods of the program, TB was reported in 2 pts: 1 bari 4 mg, 1 adalimumab; in uncontrolled periods, 6 TB events were reported (bari 4 mg: 2 with incomplete TB screening, 3 without organism confirmed). All TB occurred in endemic areas. Two GI perforations were reported (0.05/100 PY). No confirmed opportunistic infections were reported. Bari treatment has been associated with changes in selected hematology/clinical chemistry analytes; few patients ( Conclusions In the context of reported efficacy, 1,2 bari had an acceptable safety profile in pts with moderate-to-severe active RA. References Dougados M. Ann Rheum Dis. 2015;74(S2):79. Taylor PC. Arthritis Rheumatol. 2015;67(suppl 10). Disclosure of Interest J. Smolen Grant/research support from: AbbVie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Celtrion, Glaxo, ILTOO, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, M. Genovese Grant/research support from: AbbVie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, Vertex, Consultant for: AbbVie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, T. Takeuchi Grant/research support from: Chugai Pharmaceutical Co,. Ltd, Eli Lilly and Company, Consultant for: Eli Lilly and Company, D. Hyslop Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, W. Macias Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Rooney Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, L. Chen Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, C. Dickson Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, J. Riddle Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, T. Cardillo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, K. Winthrop Grant/research support from: BMS, Pfizer, Consultant for: BMS, Pfizer, Eli Lilly and Company, Abbvie, Galapagos

  • op0029 baricitinib an oral janus kinase jak 1 jak2 inhibitor in patients with active rheumatoid arthritis ra and an inadequate response to tnf inhibitors results of the phase 3 ra beacon study
    Annals of the Rheumatic Diseases, 2015
    Co-Authors: Mark C Genovese, Joel M Kremer, Omid Zamani, Charles Ludivico, Marek Krogulec, Scott D Beattie, A E Koch, Tracy E Cardillo, Terence Rooney, William L Macias
    Abstract:

    Background In ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in patients (pts) with active RA naive to biologic DMARDs (bDMARDs). 1,2 Objectives To report results from a ph 3 study of bari in pts with active RA and an inadequate response or intolerance to ≥1 TNF inhibitor (TNFi). Methods Pts with active RA (TJC & SJC ≥6, hsCRP ≥3mg/L) on conventional DMARDs (cDMARDs) were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD for 24 wks. All bDMARDs were discontinued ≥28d prior to treatment. Primary endpoint was ACR20 response at Wk 12 for bari 4 mg vs. PBO. Results Of 527 randomized pts, 57% had received ≥2 bDMARDs and 38% had received ≥1 non-TNFi bDMARD. Fewer pts discontinued treatment prior to Wk 24 on bari 2 or 4 mg vs. PBO (10%, 11%, 18%, respectively). ACR20 response at Wk 12 was higher with bari 4 mg vs. PBO (55% vs. 27%, p≤0.001). Improvements in ACR20, ACR50, ACR70, DAS28, CDAI, SDAI, and HAQ-DI were seen (Table), many as early as Wk 1. Treatment benefit was sustained through Wk 24 for the 4 mg dose. More TEAEs occurred in pts receiving bari 2 or 4 mg compared to PBO (71%, 77%, 64%, respectively) including infections (44%, 40%, 31%, respectively). SAE rates through 24 wks were similar among pts receiving bari 2 or 4 mg or PBO (4%, 10%, and 7%, respectively) including serious infections (2%, 3%, and 3%, respectively). There were no opportunistic infections, TB, or GI perforations. Two non-melanoma skin cancers and 2 major adverse cardiovascular events, including 1 death (stroke), were seen with bari 4 mg. Lab findings were consistent with ph 2 studies. Abnormalities leading to discontinuation were infrequent. Conclusions In pts with active RA on cDMARDs and an inadequate response to bDMARDs, once daily oral bari was associated with rapid and sustained clinical improvements through 24 wks, with an acceptable safety and tolerability profile. The largest benefit was seen with the 4 mg dose. Additional ph 3 studies in bDMARD-naive pts are ongoing. References Keystone et al. Ann Rheum Dis 2015;24:333-340 Tanaka et al. Arthritis Rheum 2013;65(S10):S765 Disclosure of Interest M. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, Consultant for: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, J. Kremer Grant/research support from: Abbvie, Amgen, BMS, Genentech, Eli Lilly & Company, Pfizer, UCB, Consultant for: Eli Lilly & Company, Employee of: Corrona, O. Zamani Grant/research support from: Eli Lilly & Company, C. Ludivico Grant/research support from: Eli Lilly & Company, M. Krogulec Grant/research support from: Eli Lilly & Company, L. Xie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, S. Beattie Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, A. Koch Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Cardillo Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, T. Rooney Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, W. Macias Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, D. Schlichting Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, J. Smolen Grant/research support from: Abbvie, Janssen, MSD, Pfizer, Roche, UCB, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, Janssen, Eli Lilly & Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB