Optimizing the Start Time of Biologics in Polyarticular Juvenile Idiopathic Arthritis: A Comparative Effectiveness Study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans

Abstract

Objective: The optimal time to start biologics in polyarticular juvenile idiopathic arthritis (JIA) remains uncertain. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed 3 consensus treatment plans (CTPs) for untreated polyarticular JIA to compare strategies for starting biologics.

Methods: Start Time Optimization of Biologics in Polyarticular JIA (STOP-JIA) was a prospective, observational, CARRA Registry study comparing the effectiveness of 3 CTPs: 1) the step-up plan (initial nonbiologic disease-modifying antirheumatic drug [DMARD] monotherapy, adding a biologic if needed, 2) the early combination plan (DMARD and biologic started together), and 3) the biologic first plan (biologic monotherapy). The primary outcome measure was clinically inactive disease according to the provisional American College of Rheumatology (ACR) criteria, without glucocorticoids, at 12 months. Secondary outcome measures included Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and mobility scores, inactive disease as defined by the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS-10), and the ACR Pediatric 70 criteria (Pedi 70).

Results: Of 400 patients enrolled, 257 (64%) began the step-up plan, 100 (25%) the early combination plan, and 43 (11%) the biologic first plan. After propensity score weighting and multiple imputation, clinically inactive disease according to the ACR criteria was achieved in 37% of those on the early combination plan, 32% on the step-up plan, and 24% on the biologic first plan (P = 0.17). Inactive disease according to the clinical JADAS-10 (score ≤2.5) was also achieved in more patients on the early combination plan than the step-up plan (59% versus 43%; P = 0.03), as was ACR Pedi 70 (81% versus 62%; P = 0.008), but generalizability was limited by missing data. PROMIS measures improved in all groups, but without significant differences. Twenty serious adverse events were reported (mostly infections).

Conclusion: Achievement of clinically inactive disease without glucocorticoids did not significantly differ between groups at 12 months. While there was a significantly higher likelihood of early combination therapy achieving inactive disease according to the clinical JADAS-10 and ACR Pedi 70, these results require further exploration.

Trial registration: ClinicalTrials.gov NCT02593006.

Figure 1

Disposition of the study patients. A total of 444 participants were screened, and 401 were enrolled. One patient was determined not to have polyarticular juvenile idiopathic arthritis (JIA) and was excluded from the analysis. Of the 400 analyzable participants at baseline, 257 (64%) were started on the step‐up consensus treatment plan (CTP), 100 (25%) on the early combination CTP, and 43 (11%) on the biologic first CTP. Eighteen participants were lost to follow‐up: 2 withdrew consent and 16 moved to a non‐participating clinical site. Of the patients lost to follow‐up, 2 patients were lost to follow‐up after the baseline visit, 2 patients after the 3 month visit, 2 patients after the 6 month visit, and 12 patients after the 9 month visit, leaving 382 participants with at least 12 months of follow‐up data available (250 in the step‐up CTP group, 94 in the early combination CTP group, and 38 in the biologic first CTP group). Of these 382 participants, 44 missed the 12‐month primary end point visit, leaving a total of 338 evaluable CTP participants for the primary end point (222 in the step‐up CTP group, 81 in the early combination CTP group, and 35 in the biologic first CTP group). CID = clinically inactive disease.

Figure 2

Percentage of patients with polyarticular juvenile idiopathic arthritis in the step‐up consensus treatment plan (CTP) group, early combination CTP group, and biologic first CTP group with inactive disease (ID), low disease activity, moderate disease activity, and high disease activity, according to the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS‐10), throughout the study period.

Figure 3

Patient‐Reported Outcomes Measurement Information System pain interference (A) and mobility (B) T scores over time in patients with juvenile idiopathic arthritis in the step‐up consensus treatment plan (CTP) group, early combination CTP group, and biologic first CTP group. Shaded areas indicate the mean and expected SD (50 ± 10) in the healthy population. Higher T scores indicate more pain or improved mobility. For both measures, all groups improved over time. There were no significant differences between the CTP groups.