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

Abstract

ObjectiveThis report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA).MethodsIn 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.ResultsAmong 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.ConclusionAlthough 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 RegistrationNCT01230827; Results.

Population Pharmacokinetics and Exposure‐Response Modeling Analyses of Golimumab in Children With Moderately to Severely Active Ulcerative Colitis

“…The population PK model was developed based on pooled data from children (2‐17 years) with ulcerative colitis (PURSUIT‐PEDS‐PK) and with pJIA (GO‐KIDS; NCT01230827) and from adults with ulcerative colitis following SC administration (PURSUIT‐SC; NCT00487539 and PURSUIT‐M; NCT00488631). The PK data set from children with ulcerative colitis was considered too small to construct a robust population PK model.…”

“…Patients not in clinical response at week 6 were withdrawn from further study agent administration. Data collected through week 52 for the population PK analysis included blood samplings for PK at weeks 0, 4,8,12,16,20,24, and 48 (plus one random sample between weeks 0 and 8 for all patients and additional samples at days 4 and 15 for the first 30 patients), and for immunogenicity at weeks 0, 4, 12, 24, and 48.…”

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non‐Systemic Polyarthritis, Sacroiliitis, and Enthesitis

“…The available evidence addresses combination therapy with methotrexate, with no evidence identified for other DMARDs. There was variability in the quality of supporting evidence for the medications, ranging from very low (etanercept, golimumab) to low (abatacept or tocilizumab) and moderate (adalimumab) (39,(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67). The potential benefit of methotrexate treatment for prevention of antidrug antibodies to adalimumab was included in the discussion for concomitant DMARD use with that medication (61).…”

Learning the hard way: clinical trials in juvenile idiopathic arthritis

“…The future direction of care with multinational collaborations (Paediatric Rheumatology International Trials Organisation (PRINTO), Pediatric Rheumatology Collaborative Study Group (PRCSG), Childhood Arthritis and Rheumatology Research Alliance) and advances in precision medicine will undoubtedly continue to revolutionise our approach to diagnosis, treatment and perhaps ultimately cure of JIA. In Annals of the Rheumatic Diseases , Brunner et al report on the use of subcutaneous golimumab for children with active polyarticular course JIA 1. This trial, no doubt associated with immense direct and indirect costs, produced negative results, as it did not achieve its primary end point.…”

“…In the current golimumab study, members of PRINTO and PRCSG report on the use of golimumab in polyarticular course JIA resistant to treatment with methotrexate 1. The study involved 33 sites in 12 countries for a total enrolment of 173 patients.…”