Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Patients (pts) with polyarticular-course JIA (pJIA) may develop anti-drug antibodies (ADAs) in response to biologics.1 Presence of ADAs has been associated with treatment (tmt) failure and hypersensitivity in pts with pJIA.1 Abatacept (ABA), a fully human co-stimulation modulator, consists of the extracellular domain of cytotoxic T lymphocyte–associated antigen-4 (CTLA-4) linked to Fc portion of IgG1. Here we evaluate immunogenicity (IMG) of SC and IV ABA, and effect of IMG on efficacy, pharmacokinetics (PK) and safety in an open-label (OL), Phase III study of SC ABA (NCT01844518) and in a double-blind, Phase III study of IV ABA (NCT00095173).
Methods: Study design and eligibility criteria for both studies were reported previously.2,3 In the SC study, pts with pJIA and prior DMARD failure were stratified by age cohort (2–5 and 6–17 years [yrs]) to receive weight-tiered SC ABA (10 to < 25 kg [50 mg], 25 to < 50 kg [87.5 mg], ≥50 kg [125 mg]) weekly for 4 months. JIA-ACR30 responders at Month 4 could receive SC ABA for another 20 months.2 ADAs were detected by electrochemiluminescence. In the IV study, pts with pJIA and prior DMARD failure received OL IV ABA (10 mg/kg body weight) for 4 months (Period A); JIA-ACR30 criteria responders at Month 4 were randomized 1:1 to receive IV ABA (10 mg/kg) or placebo (PBO) for 6 months or until flare (Period B). Pts could receive OL ABA in a 5-yr follow-up (Period C).3 ADAs were detected by ELISA.
Results: In the SC study, ADA rate was low in both cohorts (Table 1). In the 2–5-yr cohort, of 3 ADA positive (+) CTLA-4-specific pts, 2 had neutralizing antibodies detected (ADA-NAb+); no 6–17-yr-old pts (of 3 ADA+ CTLA-4-specific) were ADA-NAb+ over 24 months. ADA positivity on tmt did not impact JIA-ACR30 response. ABA steady-state serum trough concentration was similar between ADA+ and ADA negative pts (data not shown). Pts treated with ABA+MTX, but not with ABA alone, developed ADAs in the 2–5- (7/36 [19.4%]) and 6–17-yr (8/135 [5.9%]) cohorts.
In the IV study, ADAs were infrequent for pts who remained on ABA versus those on PBO (Table 2). Of 6 ADA+ pts with ADA-NAb assessments, 3 were ADA-NAb+ in Period C. In Period B, of 7 ABA-treated pts with flare and 47 ABA-treated pts without flare, respectively, 0 and 7 (14.9%) were ADA+ CTLA-4-specific; in the PBO arm, 7/26 (26.9%) and 15/28 (53.6%) pts with and without flare, respectively, were ADA+ CTLA-4-specific. In Period A, 2/140 (1.4%) ABA+MTX-treated pts and 2/49 (4.1%) pts treated with ABA alone developed ADAs. Pts treated with ABA+MTX, but not pts treated with ABA alone, developed ADAs during Period B (7/45 [15.6%]).
No new safety signals, including those suggestive of hypersensitivity were reported in ADA+ pts in either study.
Conclusion: IMG of SC and IV abatacept was low and did not have any impact on the efficacy, PK and safety of abatacept. Contrary to previous reports for other biologics,1 in this study, MTX did not lower the incidence of ADAs when co-dosed with abatacept.
- Doeleman MJH, et al. Rheumatology (Oxford) 2019;pii:kez030.
- Brunner HI, et al. Arthritis Rheumatol 2018;70:1144–54.
- Ruperto N, et al. Lancet 2008;372:383–91.
Writing support: Katerina Kumpan, Caudex, funded by Bristol-Myers Squibb.
To cite this abstract in AMA style:Brunner H, Tzaribachev N, Louw I, Berman A, Calvo Penadés I, Antón J, Ávila-Zapata F, Cuttica R, Horneff G, Wong R, Shaikh M, Mora J, Nys M, Lovell D, Martini A, Ruperto N. Effect of Immunogenicity on Efficacy and Safety of Subcutaneous or Intravenous Abatacept in Pediatric Patients with Polyarticular-Course JIA: Findings from Two Phase III Trials [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/effect-of-immunogenicity-on-efficacy-and-safety-of-subcutaneous-or-intravenous-abatacept-in-pediatric-patients-with-polyarticular-course-jia-findings-from-two-phase-iii-trials/. Accessed October 23, 2020.
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