Marleen Nys

Long-Term Safety and Efficacy of Abatacept in Children With Juvenile Idiopathic Arthritis

OBJECTIVE We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study. METHODS This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >or=21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008. RESULTS Of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient. CONCLUSION Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Abatacept improves health‐related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis

To assess health‐related quality of life (HRQOL) in abatacept‐treated children/adolescents with juvenile idiopathic arthritis (JIA).

Clinical response and tolerability to abatacept in patients with rheumatoid arthritis previously treated with infliximab or abatacept: open-label extension of the ATTEST Study

Objective To assess the efficacy and safety of abatacept in biological-naive patients with rheumatoid arthritis and an inadequate response to methotrexate treated in the long-term extension (LTE) of the ATTEST trial. Methods Patients randomly assigned to abatacept, placebo or infliximab completing the 1-year double-blind period were eligible to receive abatacept ∼10 mg/kg in the open-label LTE. Efficacy to year 2 is presented for patients randomly assigned to abatacept or infliximab who switched to open-label abatacept. Safety data are presented for all patients entering LTE regardless of double-blind treatment. Results Of 431 patients randomly assigned, 79.8% remained on abatacept at year 2. At years 1 and 2, 19.7% and 26.1% of abatacept and 13.3% and 28.6% of infliximab-to-abatacept patients achieved disease activity score 28-defined remission (<2.6). Safety with abatacept during the cumulative study period was consistent with the double-blind experience, with no increase in adverse event incidence following the switch to abatacept. Conclusion In methotrexate-inadequate responders, abatacept efficacy was maintained over 2 years. For infliximab-to-abatacept patients, efficacy improvements were seen in year 2 after patients switched to abatacept. Switching directly from infliximab to abatacept was well tolerated. These data demonstrate that abatacept provides sustained responses and consistent safety, suggesting that switching from infliximab to abatacept is a viable treatment option.

Efficacy and safety of abatacept, a T-cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis

Objectives To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA). Methods This study randomised patients (1:1) with active PsA (~60% with prior exposure to a tumour necrosis factor inhibitor) to blinded weekly subcutaneous abatacept 125 mg (n=213) or placebo (n=211) for 24 weeks, followed by open-label subcutaneous abatacept. Patients without ≥20% improvement in joint counts at week 16 were switched to open-label abatacept. The primary end point was the proportion of patients with ≥20% improvement in the American College of Rheumatology (ACR20) criteria at week 24. Results Abatacept significantly increased ACR20 response versus placebo at week 24 (39.4% vs 22.3%; p<0.001). Although abatacept numerically increased Health Assessment Questionnaire–Disability Index response rates (reduction from baseline ≥0.35) at week 24, this was not statistically significant (31.0% vs 23.7%; p=0.097). The benefits of abatacept were seen in ACR20 responses regardless of tumour necrosis factor inhibitor exposure and in other musculoskeletal manifestations, but significance could not be attributed due to ranking below Health Assessment Questionnaire–Disability Index response in hierarchical testing. However, the benefit on psoriasis lesions was modest. Efficacy was maintained or improved up to week 52. Abatacept was well tolerated with no new safety signals. Conclusions Abatacept treatment of PsA in this phase III study achieved its primary end point, ACR20 response, showed beneficial trends overall in musculoskeletal manifestations and was well tolerated. There was only a modest impact on psoriasis lesions. Trial registration number ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb).

FRI0191 Immunogenicity is low and transient with intravenous abatacept therapy

Background Immunogenicity with therapeutic proteins has been linked to reduction in both efficacy and safety in patients (pts) with RA.1,2 We previously reported in clinical trials that IV abatacept (ABA) demonstrated low (∼3%) and transient immunogenicity that has no apparent impact on efficacy or safety.3 Objectives To evaluate immunogenicity in a large pt group with long-term (up to 8 yrs) IV ABA exposure. Methods Data from 7 ABA RA clinical trials were included in immunogenicity assessments, including double-blind periods from 6 placebo-controlled studies (AIM, ATTEST, ATTAIN, ASSURE, 101 and 100) and 1 non-randomized, open-label study (ARRIVE), and their open-label, long-term extensions. Pts had active RA, inadequate response/intolerance to MTX/DMARDs or biologics and were treated with IV ABA (∼10 mg/kg) every 4 weeks. Anti-ABA antibodies were detected using two ELISA assays: one to whole ABA molecule (CTLA4 and IgG1), and one to CTLA4 “tip” region (T). Positive samples had titers≥400 for anti-ABA or ≥25 for anti-CTLA4-T. Persistent immunogenicity was defined as positive response on ≥2 consecutive visits. Data are as-observed for all ABA-treated pts. Results 3985 pts were included with up to 8 yrs’ ABA exposure. A total of 6.3% of pts demonstrated immunogenicity; titers were low and did not increase with continued treatment. Persistent immunogenicity (2.4%) and immunogenicity with missed doses (3.8% for 1 and 4.6% for ≥2 missed doses) were also low. Serious adverse events (SAEs) attributed as being related to study drug were reported in 32/252 (12.7%) pts who experienced immunogenicity. No relationship was identified between immunogenicity and SAEs, peri-infusional, acute infusional or autoimmune events, or hypersensitivity reactions. No consistent relationship between immunogenicity and efficacy (measured by ACR20) was observed; 83% (55/66) of ACR20 responders maintained ACR20 vs 36% (10/28) of non-responders achieved ACR20 following positive antibody response. Conclusions Abatacept demonstrated low immunogenicity in pts with RA and up to 8 yrs of abatacept exposure. Titers of anti-abatacept and anti-CTLA-4-T antibodies were low and did not persist nor increase with continued treatment. No consistent association was observed between antibody response and clinical efficacy or safety. References Bartelds GM, et al. JAMA 2011;305:1460–8. Pascual-Salcedo D, et al. Rheumatology 2011;50:1445–52. Haggerty HG, et al. J Rheum 2007;34:2365–73. Disclosure of Interest M. Weinblatt Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, M. Genovese Consultant for: Bristol-Myers Squibb, M. Schiff Consultant for: Bristol-Myers Squibb, R. Westhovens Grant/Research support from: Roche, UCB, Inc., Consultant for: Bristol-Myers Squibb, Centocor, Inc., Roche, Schering-Plough, Speakers Bureau: Bristol-Myers Squibb, R. Alten Grant/Research support from: BMS, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, Consultant for: Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, Speakers Bureau: Abbott Laboratories, BMS, Horizon Pharma, Merck Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, I. Delaet Employee of: Bristol-Myers Squibb, M. Nys Employee of: Bristol-Myers Squibb, J. Manning Employee of: Bristol-Myers Squibb, J. Kremer Grant/Research support from: Bristol-Myers Squibb, Speakers Bureau: Bristol-Myers Squibb

Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study

To investigate the pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept treatment over 24 months in patients with polyarticular‐course juvenile idiopathic arthritis (JIA).