scholarly journals Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis in Open-label, Longterm Extension Studies

2014 ◽  
Vol 41 (5) ◽  
pp. 837-852 ◽  
Author(s):  
Jürgen Wollenhaupt ◽  
Joel Silverfield ◽  
Eun Bong Lee ◽  
Jeffrey R. Curtis ◽  
Susan P. Wood ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Incidence Rate ◽  
Kinase Inhibitor ◽  
Safety Data ◽  
Janus Kinase ◽  
Upper Respiratory Tract ◽  
Open Label ◽  
Safety And Efficacy ◽  
Mean Values ◽  
Link Type

Objective.To describe the longterm safety and efficacy profile of tofacitinib in patients with moderate to severe active rheumatoid arthritis (RA).Methods.Data were pooled from 2 open-label studies (NCT00413699, NCT00661661) involving patients who had participated in qualifying phase I, II, or III index studies of tofacitinib. Safety data included over 60 months of observation; efficacy data are reported up to Month 48. Treatment was initiated with tofacitinib 5 or 10 mg twice daily. Primary endpoints were adverse events (AE) and laboratory safety data. Secondary endpoints included American College of Rheumatology (ACR) response rates, and Disease Activity Score (28 joints) (DAS28)-4[erythrocyte sedimentation rate (ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) assessments.Results.Overall, 4102 patients were treated for 5963 patient-years; mean (maximum) treatment duration was 531 (1844) days; 20.8% of patients discontinued treatment over 60 months. The most common AE were nasopharyngitis (12.7%) and upper respiratory tract infection (10.5%). Serious AE were reported in 15.4% of patients with an exposure-estimated incidence rate of 11.1 events/100 patient-years. Serious infections were reported in 4.5% of patients with an exposure-estimated incidence rate of 3.1 events/100 patient-years (95% CI: 2.66–3.55). Mean values for laboratory variables were stable over time and consistent with phase II and III studies. Persistent efficacy was demonstrated through Month 48, as measured by ACR response rate (ACR20/50/70) DAS28-4-ESR, and HAQ-DI. Safety and efficacy were similar for patients receiving tofacitinib as monotherapy or with background nonbiologic disease-modifying antirheumatic drugs.Conclusion.Tofacitinib demonstrated consistent safety and persistent efficacy over 48 months in patients with RA.

scholarly journals P525 Rheumatoid arthritis treatment with filgotinib: Week 156 safety and efficacy data from a phase 2b open-label extension study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S452-S452
Author(s):  
R Besuyen ◽  
A Kavanaugh ◽  
R Westhovens ◽  
K Winthrop ◽  
S Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Inflammatory Diseases ◽  
Day Treatment ◽  
Janus Kinase ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
Grade 3

Abstract Background Filgotinib (FIL) is an oral, selective Janus kinase inhibitor, shown to be effective and well tolerated in patients (pt) with rheumatoid arthritis (RA) and other inflammatory diseases (IBD/AS/PsA). DARWIN 3, an ongoing, open-label, long-term extension of phase 2b studies evaluates the longer-term safety and efficacy of FIL in RA. Methods The study evaluated pt outcomes for methotrexate (MTX) inadequate responders completing the 24-week DARWIN 1 (FIL+MTX) and DARWIN 2 (FIL monotherapy) studies. We present an interim analysis at week 156 following FIL 200 or 100 mg/day treatment. Event rate: total events/total years of exposure of FIL; Exposure: until data cut-off in patients on the study at the time of analysis. Results Eight hundred and seventy-seven patients completed the parent studies. Seven hundred and thirty-nine enrolled in DARWIN 3 (497 DARWIN 1, 242 DARWIN 2); most DARWIN 1 and 2 patients were female (81.5%, 81.8%), white (75.3%, 74.8%); mean age was 53 and 52 years, respectively. Mean baseline MTX dose in the FIL+MTX group: 16.8mg/week. At week 156, 59.9% of patients remained on study. Most common reasons for discontinuation were adverse events (26.5%) and subject request (9.1%). Total exposure to FIL was 2203 pt-years; mean exposure ± standard deviation (SD): 3.04 ± 1.22 years for FIL+MTX and 2.86 ± 1.21 years for FIL monotherapy. Treatment-emergent adverse events (TEAEs): 419 (84.3%) patients on FIL+MTX and 203 (83.9%) patients on FIL monotherapy; serious TEAEs occurred in 45 (9.1%) and 33 (13.6%), respectively. Adverse event of special interest (AESI) rates remained low at week 156 (Table 1). Grade ≥3 toxicities in >1% of patients were decreased lymphocytes (4.2%/1%), decreased neutrophils (1.0/1.2%), increased fasting triglycerides (2.2/0%) and decreased fasting triglycerides (0/3.3%) for FIL+MTX/FIL monotherapy respectively. 5 deaths occurred (FIL+MTX: 2, FIL monotherapy: 3) none after week 132. Clinical efficacy was shown at week 156 in both FIL+MTX and FIL monotherapy groups, using observed cases as measured by ACR20 (87.2% and 89.7%)/ACR50 (72.4 and 63.0)/ACR70 (45.5 and 40.0) DAS28(CRP) ≤3.2 (69.0 and 64.7) and DAS28(CRP) <2.6 (53.4 and 45.6). Conclusion FIL was generally well tolerated; no new safety signals emerged. No safety differences observed in patients receiving FIL+MTX or FIL monotherapy. Efficacy was sustained up to week 156 in both treatment groups.

scholarly journals Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

2014 ◽  
Vol 41 (4) ◽  
pp. 629-639 ◽  
Author(s):  
Mark C. Genovese ◽  
César Pacheco Tena ◽  
Arturo Covarrubias ◽  
Gustavo Leon ◽  
Eduardo Mysler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Incidence Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Link Type

Objective.Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).Methods.The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.Results.Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.Conclusion.These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

scholarly journals P219 Long-term safety of filgotinib in patients with PsA: week 52 safety data from a Phase 2 open-label extension study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Laura Coates ◽  
Philip Mease ◽  
Dafna Gladman ◽  
Filip Van den Bosch ◽  
Anna Rychlewska-Hanczewska ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Safety Data ◽  
Janus Kinase ◽  
Controlled Study ◽  
Stock Ownership ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

Abstract Background Filgotinib (FIL) is an orally administered, selective janus kinase 1 (JAK1) inhibitor in development for psoriatic arthritis (PsA). Efficacy and safety of FIL in patients with active PsA were evaluated in a 16-week phase 2 study (EQUATOR, NCT03101670). After 16 weeks, patients could roll-over to an Open Label Extension (OLE) Study (EQUATOR2, NCT03320876) for the purpose of evaluating long-term safety and efficacy. The aim of this analysis was to assess safety and efficacy through 52 weeks of exposure to filgotinib. Methods Patients who completed the randomised, double-blind, placebo-controlled study were eligible for participation in the OLE, during which all patients received once daily (qd) open-label FIL 200mg. In this interim analysis of OLE, for the safety analysis, all data were included from the screening in the core study up to the data cut of 18 April 2019 in the OLE. For the efficacy analysis, all data until OLE Week 52 visit for each patient were included (observed case analysis). Results Of the 131 patients randomised and dosed in EQUATOR, 124 (95%) completed the study and 122 (93%) enrolled in EQUATOR2; 50% were female and mean age was 50. At this interim analysis, 106/122 (87%) remained in the OLE (premature discontinuations during OLE due to: 4 for safety, 11 withdrew consent, and 1 for other reasons). Cumulative patient years of exposure (PYE) on FIL were 160, median time on FIL was 66 weeks. Key safety data are summarised in Table 1. Key ≥Grade 2 treatment-emergent laboratory abnormalities seen with FIL arm (N = 128) compared with PBO (N = 66) were lymphocyte decrease 11.1% vs 4.5%, neutrophil decrease 5.5% vs 0%, ALT increase 1.6% vs 1.5% and creatinine increase 0.8% vs 0%, respectively. At week 52, 34% of the patients fulfilled criteria for minimal disease activity and 81%, 55%, and 33% of patients, respectively, achieved ACR20/50/70 responses. Conclusion FIL 200mg qd was generally well tolerated and the safety profile in PsA was comparable to that observed in the FIL rheumatoid arthritis studies. The data from this interim analysis suggest that further improvement of the patient condition can be expected beyond 16 weeks of treatment. Disclosures L. Coates: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Lilly, Novartis, Pfizer, Prothena, Sun pharma, and UCB. P. Mease: Other; Received support from Abbvie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN, and UCB. D. Gladman: Other; Received support from Abbvie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB, BMS, and Galapagos. F. Van den Bosch: Other; Received support from Abbvie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, and UCB. A. Rychlewska-Hanczewska: Other; Received support from Galapagos and Gilead Sciences. C. Tasset: Corporate appointments; Employee of Galapagos NV. L. Meuleners: Corporate appointments; Employee of Galapagos NV. M. Trivedi: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc... Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. R. Besuyen: Other; Employee of Galapagos NV. P. Helliwell: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Novartis, Pfizer, and UCB.

Abstract 3732: Long-Term Safety and Efficacy of ABT-335 (Fenofibric Acid) in Combination with Statin Therapy for the Treatment of Patients with Mixed Dyslipidemia

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Harold E. Bays ◽  
Peter H. Jones ◽  
Syed M. Mohiuddin ◽  
Maureen T. Kelly ◽  
Hsiaoming Sun ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Extension Study ◽  
Integrated Analysis ◽  
Upper Respiratory Tract ◽  
Moderate Dose ◽  
Open Label ◽  
Safety And Efficacy ◽  
Mean Values ◽  
Mixed Dyslipidemia

Background: The efficacy and safety of ABT-335 + statin combination therapy was demonstrated in three 12-week, controlled studies of patients with mixed dyslipidemia randomized to ABT-335 (135mg) + low or moderate dose rosuvastatin (R), simvastatin (S), or atorvastatin (A), or ABT-335 or statin monotherapy. A subsequent 52-week open label extension study evaluated the long-term safety and efficacy of ABT-335 combined with statins. Methods: Patients who completed 12 weeks of treatment in the 3 controlled studies were eligible to enroll in the 52-week extension study to receive ABT-335 + the moderate dose statin that was used in their initial study: R 20mg, S 40mg, or A 40mg. This was a pre-specified, integrated analysis of patients receiving ABT-335 + statin in the 12- and 52-week studies. Results: Of the 2715 randomized patients, 2316 completed the 12-week studies and 1911 enrolled in the extension study. A total of 2201 patients received at least 1 dose of ABT-335 + statin for a median duration of 364 days; 1139 patients were treated for ≥52 weeks. The incidence of adverse events (AEs) was similar across all 3 combination therapy groups (Table ). The most common AEs were headache, upper respiratory tract infection, nasopharyngitis, and back pain. Rhabdomyolysis was not reported in any group. Patients who were initially randomized to ABT-335 + statin and continued in the extension study (N=979) had sustained improvements in multiple lipids. After 12 and 52 weeks of treatment, combination therapy resulted in mean percent decreases in TG (−45.7% and −47.5%, respectively) and LDL-C (−32.2% and −37.8%), and increases in HDL-C (17.6% and 23.8%). Mean values at 12 and 52 weeks were: TG 141.2 and 136.3 mg/dL; LDL-C 101.6 and 93.5 mg/dL; and HDL-C 45.0 and 47.1 mg/dL, respectively. Conclusions: Long-term ABT-335 + statin combination therapy was generally well tolerated and resulted in comprehensive and sustained improvements in TG, HDL-C, and LDL-C in adults with mixed dyslipidemia. Summary of safety, n/N (%)

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