0354: Open-label Phase 3 Study of Intravenous Golimumab in Patients with Polyarticular Juvenile Idiopathic Arthritis: Pharmacokinetics, Effectiveness, Safety, and Immunogenicity over 252 Weeks

Nicolino Ruperto¹, Daniel J Lovell², Sarah Ringold³, Xie L. Xu⁴, Jocelyn H. Leu³, Edwin Lam³, Yuhua Wang³, Alberto Martini⁵ and Hermine Brunner⁶, ¹IRCCS Istituto Giannina Gaslini, UOSID Centro Trial, Genova, Italy, ²UC Department of Pediatrics, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH, ³Janssen Research & Development, LLC, Spring House, PA, ⁴Janssen Research & Development, LLC, San Diego, CA, ⁵Universita degli Studi di Genova, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Genova, Italy, ⁶Cincinnati Children's Hospital Medical Center, Division of Rheumatology, Cincinnati, OH

Background/Purpose: The phase 3, Intravenous Golimumab in Pediatric Participants with Active Polyarticular-Course JIA Despite MTX (GO-VIVA) study demonstrated that golimumab (GLM) 80 mg/m² at Week (W) 0, W4 and Q8W thereafter is well-tolerated and effective in children 2 to < 18 years of age with active polyarticular-course juvenile idiopathic arthritis (pcJIA) despite MTX through W52 (NCT02277444). The pharmacokinetics (PK), immunogenicity, efficacy, and safety of GLM in GO-VIVA participants (pts) who continued into the long-term extension (LTE) through W252 are evaluated.

Methods: Pts from GO-VIVA who continued GLM 80 mg/m² IV q8w (max dose 240 mg) after W52 were included. PK and immunogenicity were assessed through W244, and safety was assessed through W252. Efficacy measures included JIA ACR response from baseline (start of GLM), clinical Juvenile Arthritis Disease Activity Score based on 10 joints (cJADAS-10) minimal disease activity (cJADAS-10 MDA), inactive disease (cJADAS-10 ID) and remission (≥ 6 continuous months of cJADAS-10 ID). These were analyzed using an intent-to-treat (ITT) approach through W116, due to a protocol amendment instituted during the LTE that limited efficacy data collected after W116. Non-responder imputation was used for missing data.

Results: Of the 127 pts treated, 112 (88.2%) continued into the LTE, and 69 (54.3%) completed GLM through W244 and had a W252 assessment. The most common reasons for discontinuation of GLM treatment through W244 were adverse event (AE) (19%) and withdrawal of consent (7%). W244 median steady-state trough GLM concentration was 0.61 μg/mL (mean ± SD: 0.66 ± 0.569μg/mL; N=31) vs 0.44 μg/mL (mean ± SD: 0.50 ± 0.455 μg/mL; N=93) at W52, indicating that exposure was maintained over time. Median trough GLM concentrations at W244 were similar across different age categories and body weight quartiles. From W52 to W116, the majority of pts had JIA ACR 30 (72%-77%), JIA ACR 50 (71%-76%), and JIA ACR 70 (62%-68%) responses, and approximately 50% had JIA ACR 90. The majority of pts (≥56%) achieved cJADAS-10 MDA, 41%-49% achieved cJADAS-10 ID, and 28-33% achieved remission. Antibodies to GLM were detected in 56 (44.8%) of pts through W244; the majority of titers were < 1:1000. Of these 56 pts, 35 were positive for neutralizing antibodies (Nab) with an overall incidence of NAb of 31% (35/112). No new or unexpected safety issues were identified through W252. AEs and SAEs were reported in 92.1% and 19.7% of pts, respectively. One death (septic shock) occurred.

Conclusion: PK exposure through the end of the LTE was consistent with that observed through W52. Although analyses were limited by protocol modification, data through W116 suggest a therapeutic benefit with additional treatment and achievement of clinically important endpoints for pts who continued in the LTE. GLM was generally well tolerated with an acceptable long-term safety profile through W252.


N. Ruperto: Ablynx, 2, 6, AstraZeneca-Medimmune, 2, 6, Bayer, 2, 6, Biogen, 2, 6, Boehringer-Ingelheim, 2, 6, Bristol-Myers Squibb (BMS), 2, 5, 6, Celgene, 5, 12, Personal Fees, Non-Financial Support, Eli Lilly, 2, 5, 6, EMD Serono, 2, 6, F. Hoffman-La Roche, 2, 5, 6, GlaxoSmithKlein (GSK), 2, 5, 6, Janssen, 2, 5, 6, Merck/MSD, 2, 6, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, R-Pharma, 2, 6, Sinergie, 2, 6, Sobi, 2, 5, 6, UCB, 2, 5; D. Lovell: Abbott, 2, 6, AbbVie, 2, Amgen, 2, AstraZeneca, 2, Boehringer-Ingelheim, 2, Bristol-Myers Squibb(BMS), 2, Canadian Arthritis Society, 1, Celgene, 2, Forest Research, 1, GlaxoSmithKlein(GSK), 2, Hoffmann-La Roche, 2, Janssen, 2, NIH-NIAMS, 1, Novartis, 2, 6, Pfizer, 2, United Bioscience Corporation, 2, Wyeth, 2; S. Ringold: Janssen, 3; X. Xu: Janssen, 3, 10, 11; J. Leu: Janssen, 3, Johnson & Johnson, 11; E. Lam: Janssen, 3, 11; Y. Wang: Janssen, 3; A. Martini: Boehringer-Ingelheim, 2, Eli Lilly, 2, Janssen, 2, Merck/MSD, 2, Novartis, 2, Pfizer, 2; H. Brunner: AbbVie, 2, AstraZeneca-Medimmune, 2, Biogen, 2, Boehringer-Ingelheim, 2, Bristol-Myers Squibb (BMS), 2, 5, Celgene, 2, Eli Lilly, 2, 5, EMD Serono, 2, F-Hoffman La Roche, 2, 5, GlaxoSmithKlein (GSK), 2, 5, 6, Horizon, 2, 2, Janssen, 5, Merck, 2, Novartis, 2, 5, 6, Pfizer, 2, 5, 6.