Clinical Disease Manifestations Associated With Tumor Necrosis Factor Inhibitor Nonresponse in Juvenile Spondyloarthritis

Objective To identify the clinical characteristics associated with initial tumor necrosis factor inhibitor (TNFi) nonresponse in patients with juvenile spondyloarthritis (JSpA).

Methods This is a retrospective analysis of patients with JSpA enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry between July 2015 and January 2019 and their response to their first TNFi agent. The JSpA population included those with enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. Demographic and disease characteristics were compared at baseline visits prior to TNFi start and at the time of initial TNFi nonresponse or the visit closest to 6 months following TNFi start for the responders.

Results Inclusion criteria were met by 286 patients; 168 were TNFi responders and 118 were TNFi nonresponders. Median time to TNFi nonresponse was 8.9 (IQR 5.3-14.2) months. Median age at TNFi start was similar for nonresponders (13.9 years) and responders (13.8 years; P = 0.91). Nonresponders were more likely to be female (61.9% vs 48.2%, P = 0.02) and have a higher BMI (21.6 vs 19.2, P = 0.02) and longer symptom duration (2.2 vs 1.4 years, P = 0.04) compared to responders. Nonresponders had more clinical sacroiliitis and higher patient global assessment (PtGA) at baseline visit compared to responders (P = 0.004 and P = 0.01, respectively). The majority were secondary nonresponders (113/118, 96%). Most patients switched to a second TNFi (60.2%) following initial TNFi nonresponse.

Conclusion Most nonresponders to TNFi had secondary nonresponse. Patients with JSpA who did not respond to initial TNFi were more likely to be female and have longer symptom duration prior to starting a TNFi, clinical sacroiliitis, and a higher BMI and higher PtGA scores at baseline. Patients with these features should be monitored more carefully for treatment response.