Background/Purpose: Efficacy of anti–tumor necrosis factor (TNF) therapy in patients with axial spondyloarthritis (SpA) has been tested only in patients who are refractory to NSAIDs.

Objectives: To determine whether combination infliximab (IFX)+NSAID therapy is superior to NSAID monotherapy for achieving better clinical outcomes in patients with early, active axial SpA who were naïve to NSAIDs or had a submaximal dose of NSAIDs.

Methods: The INFAST trial was a double-blind, randomized controlled trial of IFX in biologic-naïve patients 18–48 years of age with early, active axial SpA (ASAS criteria, disease duration ≤3 years with chronic back pain and active inflammatory lesions of the sacroiliac [SI] joints on MRI). Patients naïve to NSAIDs or treated with a submaximal dose of NSAIDs were randomized (2:1) to receive 28 weeks of treatment with either IV IFX 5 mg/kg (weeks 0, 2, 6, 12, 18, and 24)+naproxen (NPX) 1000 mg/d or IV placebo (PBO)+NPX 1000 mg/d. The primary endpoint was the percentage of subjects meeting ASAS partial remission criteria at week 28. Treatment group differences were analyzed using Fisher exact tests or analysis of covariance.

Results: 106 patients were randomized to IFX+NPX and 52 to PBO+NPX. At baseline, mean BASDAI scores (100 mm VAS) were 64.4 (SD=15.37) mm and 63.0 (SD=15.43) mm and HLA-B27–positive statuses were 82.1% and 90.4% in the IFX+NPX and PBO+NPX groups, respectively. The primary endpoint, ASAS partial remission at week 28, was achieved by more patients treated with IFX+NPX (61.9%) than PBO+NPX (35.3%), P=0.0021. Partial remission rates increased steadily through weeks 2, 6, 16, and 28 in both the IFX+NPX group (28.6%, 41%, 51.4%, and 61.9%) and the PBO+NPX group (11.8%, 15.7%, 25.5%, 35.3%), with greater partial remission in the IFX+NPX group at each visit (all P <0.05). Improvements in BASDAI, ASDAS, and ESR were considerable and were significantly greater in the IFX+NPX group than the PBO+NPX group (Table 1). The observed CRP decrease was greater in the IFX+NPX group than the PBO+NPX group, but did not reach statistical significance. A greater number of patients in the IFX+NPX group (51.4%) than the PBO+NPX group (19.6%), P=0.0001, achieved inactive disease, defined as ASDAS-CRP <1.3.

Table 1. Change in Efficacy Outcomes from Baseline to Week 28 by Treatment Group

Serious adverse events were reported in 5 (4.8%) patients in the IFX+NPX group (possibly related to study medication in 3 [2.9%] patients) and 3 (5.8%) patients in the PBO+NPX group (possibly related in 2 [3.8%] patients). No deaths occurred.

Conclusion: Patients with early, active axial SpA who were treated with IFX+NPX had greater rates of ASAS partial remission and were more likely to have lower or inactive disease (as measured by BASDAI and ASDAS) than those treated with PBO+NPX. Patients who were treated with PBO+NPX had good response but still had moderately active disease. The safety profile was consistent with that of other anti-TNF biologics.