Background/Purpose: Limited data are available on the efficacy of anti-TNF agents in non-radiographic axial spondyloarthritis (nr-axSpA). The objective of this analysis is to compare the efficacy and safety of etanercept (ETN) vs placebo after 12 weeks of double-blind treatment and an additional 12 weeks of open-label ETN treatment in patients with nr-axSpA who had an insufficient response to NSAIDs.

Methods: Enrolled patients satisfied ASAS criteria for axSpA, had been exhibiting symptoms between 3 months-5 years, failed ≥2 NSAIDs (including current one), and a BASDAI score ≥4 despite current NSAID use. Patients were blinded and randomized to ETN 50 mg weekly (QW) or placebo and continued NSAIDs for 12 weeks followed by open-label ETN 50 mg QW for an additional 12 weeks (weeks 12-24). Efficacy outcomes were assessed at week 12 and 24 and safety monitored throughout the study. Analyses used ANCOVA models with baseline score, treatment, region and sacroiliac joints status at baseline (MRI) as variables. LOCF imputation was used for missing data.

Results: 215 patients were randomized and included in the mITT population (ETN=106; placebo=109); mean age at baseline was 32 years (range, 18–49 years); 61% were male; and mean disease duration was 2.4 years (range, 0-16.0 years; median, 2.3 years). At week 12, 208 patients (ETN=102; placebo=106) enrolled in the open-label phase. ASAS40 at 12 weeks was achieved by a significantly greater proportion of patients receiving ETN vs placebo (32.4% vs 15.7%, respectively; P=0.006).  At week 12, there were substantial differences in clinical outcomes between the ETN and placebo groups, but the differences largely disappeared when placebo patients were treated with ETN in the open-label phase (table). As compared to week 12, an increased proportion of patients achieved all efficacy outcomes at week 24, after the switch to open label ETN. The percentages of patients (safety population) with any adverse events were 57% (63/111) vs 46% (52/113) at week 12 and 34% (35/102) vs 50% (53/106) at week 24 in the ETN vs placebo groups, respectively.

Conclusion: In this population of patients with early, active nr-axSpA who had an inadequate response to ≥2 NSAIDs, etanercept was more effective than placebo during the first 12 weeks. Clinical outcomes were similar after all patients were treated with ETN (weeks 12-24). No new safety signals were reported.