ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2708

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

Hermine Brunner1, Nikolay Tzaribachev 2, Ingrid Louw 3, Alberto Berman 4, Inmaculada Calvo Penadés 5, Jordi Antón 6, Francisco Ávila-Zapata 7, Rubèn J Cuttica 8, Gerd Horneff 9, Robert Wong 10, Mehmooda Shaikh 11, Johanna Mora 11, Marleen Nys 12, Daniel J. Lovell 13, Alberto Martini 14 and Nicolino Ruperto 15, 1Pediatric Rheumatology Collaborative Study Group (PRCSG), Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany, 3Panorama Medical Centre, Parow, South Africa, 4Universidad Nacional de Tucuman and Centro Médico Privado de Reumatología, Tucuman, Argentina, 5Hospital Univ. La Fe, Valencia, Spain, 6Hospital Sant Joan de Déu, Barcelona, Spain, 7Star Medica Hospital, Merida, Yucatán, Mexico, 8Hospital General de Niños Pedro de Elizalde, Buenos Aires, Argentina, 9Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany, 10Bristol-Myers Squibb, Princeton, 11Bristol-Myers Squibb, Princeton, NJ, 12Bristol-Myers Squibb, Braine L’Alleud, Belgium, 13Pediatric Rheumatology Collaborative Study Group (PRCSG), Cincinnati Children’s Hospital Medical Center, Cincinnati, 14IRCCS Istituto Giannina Gaslini, Università degli Studi di Genova, Genova, Italy, 15Paediatric Rheumatology International Trials Organisation (PRINTO), Genoa, Italy

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: , , ,

Session Information

Date: Tuesday, November 12, 2019

Title: Pediatric Rheumatology – ePoster III: Systemic JIA, Fever, & Vasculitis

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.

References

  1. Doeleman MJH, et al. Rheumatology (Oxford) 2019;pii:kez030.
  2. Brunner HI, et al. Arthritis Rheumatol 2018;70:1144–54.
  3. Ruperto N, et al. Lancet 2008;372:383–91.

Writing support: Katerina Kumpan, Caudex, funded by Bristol-Myers Squibb.

Disclosure: H. Brunner, ., 2, 5, 8, AbbVie, 5, AstraZeneca, 5, Bayer, 5, Bristol-Myers Squibb, 2, 5, EMD Serono, 5, Genentech, 2, 5, 8, GlaxoSmithKline, 5, Janssen, 5, Lilly, 5, Novartis, 5, 8, Pfizer, 2, 5, R-Pharm, 5, Sanofi, 5, UCB, 5; N. Tzaribachev, None; I. Louw, Amgen, 5, Janssen, 5, Novartis, 5, Pfizer, 5, Pfizer Inc, 5, Roche, 5; A. Berman, AbbVie, 2, Abbvie, 2, Amgen, 2, Bristol Myers Squibb, 2, Bristol-Myers Squibb, 2, Eli Lilly, 2, Genentech/Roche, 2, Janssen, 2, Lilly, 2, Merck Serono, 2, MSD, 2, Pfizer, 2, Roche, 2, Sanofi, 2, Servier, 2; I. Calvo Penadés, AbbVie, 2, 5, 8, Bristol-Myers Squibb, 2, Clementia, 2, MSD, 2, Novartis, 2, 5, 8, Pfizer, 2, Roche, 2, 8, Sanofi, 2, SOBI, 8; J. Antón, AbbVie, 2, Bristol-Myers Squibb, 2, Gebro, 2, GlaxoSmithKline, 2, Novartis, 2, Novimmune, 2, Pfizer, 2, Roche, 2, Sobi, 2; F. Ávila-Zapata, None; R. Cuttica, AbbVie, 2, 5, Bristol-Myers Squibb, 2, 5, Lilly, 2, 5, Pfizer, 2, 5, Roche, 2, 5, Sanofi, 2, 5; G. Horneff, Chugai, 5, 8, GlaxoSmithKline, 5, 8, Novartis, 5, 8, Sanofi, 5, 8; R. Wong, Bristol-Myers Squibb, 3, 4; M. Shaikh, Bristol-Myers Squibb, 3; J. Mora, Bristol-Myers Squibb, 3, 4; M. Nys, Bristol-Myers Squibb, 1, 3; D. Lovell, Abbott, 5, 9, AbbVie, 5, 9, Amgen, 5, 9, AstraZeneca, 5, Astra-Zeneca Pharm, 5, Biogen, 5, Boehringer Ingelheim, 5, Boeringher Ingelheim, 5, Bristol-Myers Squibb, 5, 9, Celgene, 5, Forest Research, 9, Forest Research Institute, 5, Genentech, 5, 8, GlaxoSmithKline, 5, Hoffmann-La Roche, 5, 9, Horizon, 5, Jannsen, 5, Janssen, 5, 9, Johnson & Johnson, 5, Novartis, 5, 9, Pfizer, 5, 9, Roche, 5, 9, Takeda, 5, 9, UBC, 5, Wyeth Pharm, 5, 8; A. Martini, EMD Serono, 5, 8, EMD-Serono, 5, 8, Janssen, 5, 8, Novartis, 5, 8, Pfizer, 5, 8; N. Ruperto, AbbVie, 5, 8, Abbvie, 8, Ablynx, 5, 8, Ablynx, AbbVie, Astrazeneca-Medimmune, Biogen, Boehringer, Bristol Myers and Squibb, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, 8, AstraZeneca-Medimmune, 8, Astrazeneca-Medimmune, 8, AstraZeneca-MedImmune, 5, 8, Biogen, 5, 8, BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi., 2, Boehringer, 8, Boehringer Ingelheim, 5, 8, Boeringher Ingelheim, 8, Bristol-Myers Squibb, 2, 5, 8, Eli Lilly, 2, 5, 8, Eli-Lilly, 8, EMD Serono, 5, 8, F Hoffmann-La Roche, 2, 5, 8, GlaxoSmithKline, 2, 5, 8, Hoffmann-La Roche, 8, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, SanofiServier, Sinergie, Sobi and Takeda, 8, Janssen, 2, 5, 8, Merck, 5, 8, Novartis, 2, 5, 8, Pfizer, 2, 5, 8, R-Pharma, 5, 8, SanofiServier, 5, 8, Sinergie, 5, 8, Sobi, 2, 5, 8, 9, Takeda, 5, 8.

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 .

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