Subcutaneous golimumab for children with active polyarticular-course juvenile idiopathic arthritis: results of a multicentre, double-blind, randomised-withdrawal trial

Abstract

Objective: This report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA).

Methods: In this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0-16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16-48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety.

Results: Among 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with <1% of all injections. PK analysis confirmed adequate golimumab dosing for polyJIA.

Conclusion: Although the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred.

Clinical trial registration: NCT01230827; Results.

Keywords: anti-tumour necrosis factor; biologics; golimumab; juvenile idiopathic arthritis.

Conflict of interest statement

Competing interests: HIB has served as a consultant and steering committee member for Janssen Research & Development, a consultant for AstraZeneca, Pfizer and Takeda and received research support from Novartis, Roche and UCB. NR served on the speaker’s bureau and as a consultant for AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, F. Hoffmann-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda and UCB Biosciences GmbH. DJL has served as a consultant for Boehringer Ingelheim, Celgene, Janssen Research & Development and Novartis, as a trial investigator for AbbVie, Bristol-Myers Squibb, Janssen Research & Development, Roche, Pfizer and UBC and received research support from the National Institutes of Health. NRP received fees from AbbVie and Roche. FS received research support from Janssen. KM received research support from Pfizer, AbbVie, Roche and Deutsche Kinder-Rheumastiftung and fees from AbbVie, Genzyme, Medac, Pfizer and Pharm-Allergan. IN received fees from AbbVie, Bristol-Myers Squibb, Novartis, Pfizer and Roche and grants from Pfizer and Roche. EA received research support from AbbVie, Bristol-Myers Squibb, Janssen, Novartis, Pfizer and Roche and fees from AbbVie, Bristol-Myers Squibb, Medac, Merck Sharp & Dohme, Novartis, Pfizer and Roche. KEG, ZX, JHL, LK, SLL and MJL are employees of Janssen Research & Development, LLC and own stock in Johnson & Johnson. AM received speaking and consulting fees from AbbVie, Boehringer, Celgene, CrescendoBio, Janssen, MedImmune, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Vertex and Servier. Nothing to disclose: NT, GH, VGC, CAM, AR, DJK, EDS, VP, MRMV, ES, MB, ARK, VK, RJ, WE, IF, BRL.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Patient disposition.

Figure 2

Proportions of enrolled patients with a JIA ACR30/50/70/90 response and inactive disease through week 16 (A), and the mean per cent improvement in the JIA core response variables at week 16 (B). JIA ACR30/50/70/90, ≥30%/50%/70%/90% improvement in the American College of Rheumatology juvenile idiopathic arthritis response criteria. CHAQ, Children’s Health Assessment Questionnaire; JIA ACR, juvenile idiopathic arthritis American College of Rheumatology; VAS, visual analogue scale.

Figure 3

(A) Kaplan-Meier plot of JIA flare events starting Part 2 of the study. (B) Proportions of randomised patients with a JIA ACR30/50/70/90 response and clinical remission at week 48 as compared with baseline (week 0). (C) Mean change in JADAS71-ESR through week 48. (D) The proportion of patients who flared during the trial. Flare rates remained relatively stable over time among patients who continued with golimumab after week 16 and remained relatively similar regardless of the baseline CRP levels. However, among patients receiving placebo in Part 2, the proportion of patients who flared in Part 2 increased depending on CRP levels at baseline: for example, for patients with baseline CRP levels ≥0.02 mg/dL, the flare rate was 48.6% (35/72) and for those with baseline CRP levels ≥1.0 mg/dL, the flare rate was 86.7% (13/15). JIA ACR30/50/70/90, ≥30%/50%/70%/90% improvement in the American College of Rheumatology juvenile idiopathic arthritis response criteria; CRP, C reactive protein; JADAS71-ESR, Juvenile Arthritis Disease Activity Score using erythrocyte sedimentation rate; JIA, juvenile idiopathic arthritis.