A randomized, double-blind, placebo-controlled 12-week trial of infliximab in patients with juvenile-onset spondyloarthritis

Abstract

Objective: To assess the efficacy and safety of infliximab versus placebo in the treatment of patients with juvenile-onset spondyloarthritis (JoSpA).

Methods: Phase III, randomized, double-blind, placebo-controlled trial of 12 weeks that included patients ≤ 18 years old with JoSpA not responding to nonsteroidal anti-inflammatory drugs, sulfasalazine, or methotrexate. Patients were randomly assigned 1:1 to the infusion of infliximab 5mg/kg or placebo; completers entered then an open-label extension (OLE) period of 42 weeks. The primary endpoint was the number of active joints. Secondary outcomes included the assessment of disease activity, tender entheses, spinal mobility, serum C-reactive protein (CRP), the Bath Ankylosing Spondylitis Disease Activity and Functional Index, and the Childhood Health Assessment Questionnaire (CHAQ).

Results: We randomized 12 patients to infliximab and 14 to placebo. No significant differences were found between groups at baseline. At week 12, the mean number of active joints was 1.4 (SD 2.4) in the infliximab group and 4.1 (SD 3.0) in the placebo group (p = 0.0002). A repeated-measures mixed model analysis that included all endpoints in the study demonstrated sustained favourable outcomes of infliximab for active joints, tender joints, swollen joints, and tender enthesis counts, as well as for CHAQ and CRP (p < 0.01). Adverse events were more frequent in the infliximab group, including infections and infusion reactions, but none of them was serious.

Conclusion: Infliximab is efficacious for patients with JoSpA with an inadequate response to conventional treatment. No serious adverse events with the use of infliximab were observed.

Keywords: Active joint counts; Infliximab; Juvenile SpA; Open-label study; Randomized trial; Spondyloarthritis.

Fig. 1

CONSORT flowchart of the infliximab in juvenile-onset SpA trial

Fig. 2

Mean active joint counts, swollen joint counts, tender joint counts, and tender enthesis counts registered during the entire duration of the study (RCT + OLE phases) by treatment group according to randomization. A Mean active joint count (primary outcome). B–D Mean number of swollen joints, tender joints, and tender enthesis, respectively. All comparisons showed a significant difference between infliximab and placebo by week 12. In the open-label extension, in which all patients received infliximab, the mean of each outcome showed a sustained response to infliximab

Fig. 3

Mean level of high-sensitive C-reactive protein (hsCRP) and Childhood Health Assessment Questionnaire score (CHAQ) registered during the entire duration of the study (RCT + OLE phases) by treatment group according to randomization. A Mean hsCRP serum levels in milligrammes per decilitre. B Mean CHAQ scores. Lines showed a significant and sustained positive effect of infliximab over time

Fig. 4

Percentage of patients reaching the American College of Rheumatology (ACR) Paediatric 30 (Pedi 30), 50, 70, 90, and 100 response criteria per treatment group at week 12 (end RCT phase)

Fig. 5

Percentage of patients reaching the Assessment of Spondyloarthritis international Society (ASAS) 20, 40, partial remission, and 5/6 response criteria per treatment group at week 12 (end RCT phase)