Background Tumor necrosis factor (TNF) blocking agent has shown to be effective in patients with axial spondyloarthritis (SpA) including ankylosing spondylitis (AS) as up to 60-70%. However, the other 30-40% of patients fails to respond. This non-responsiveness to TNF blocking agent has been suggested as the result of the development of antibodies against it, anti-drug antibodies (ADA), which have been described well in patients with rheumatoid arthritis and Crohn's disease.
Objectives The aim is to assess whether ADA is related to the clinical efficacy in SpA patients on anti-TNF agents.
Methods According to the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA, consecutive patients were recruited at a single tertiary hospital who received treatment with adalimumab (Ada) or infliximab (Ifx): 86 AS, 11 inflammatory bowel disease associated SpA, 3 psoriatic SpA and 2 undifferentiated SpA. Serum samples were collected at the enrolment for the drug and ADA levels, which were measured by ELISA. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at baseline (at the beginning of the current anti-TNF agents), at 3 month and then every 6 months. The reactivation of tuberculosis infections, side-effects or infusion reactions, and the cause for discontinuation of therapy were assessed prospectively.
Results A total of 102 patients were studied (89.2% male; mean age at sampling 35.2±18.0 years; mean disease duration 11.3±7.9 years). HLA-B27 was positive in 65 of 76 patients (85.5%). Among 102 patients, 74 were treated with Ada and 28 with Ifx. Eighteen patients (17.6%) had switched from other kinds of anti-TNF agents including Ada, Ifx and etanercept. Latent tuberculosis (TB) infection was detected in 22 patients (21.6%) before starting anti-TNF agents and the treatment regimen with isoniazid and rifampin was commenced by a TB expert. ADA was demonstrated in 8 patients (7.8%) (5 of Ada and 3 of Ifx) and all of them were anti-TNF naïve patients. Patients who developed ADA had lower levels of the corresponding drugs (Ada level: 0.45±0.68 vs 4.42±2.12, p<0.0001; Ifx level 0.91±1.36 vs 3.38±2.24, p=0.076). At baseline, no differences in BASDAI were found in patients with or without ADA, and neither ESR nor CRP was different. The median period under prospective observation was 15 months (range 0 – 17, mean 12.7±7.8). ADA-positive patients had a significantly higher cumulative drug discontinuation rate due to inefficacy and adverse events (37.5% vs 6.4%, p=0.022). There was no reactivation of tuberculosis during anti-TNF treatment.
Conclusions Our result suggests that in SpA patients the presence of ADA to current Ada or Ifx can predict the drug discontinuation in future due to inefficacy or adverse events.
Disclosure of Interest None declared