Early change in bone resorption predicts discontinuation of tumor necrosis factor-alpha blocking therapy in patients with ankylosing spondylitis

Abstract

Background In ankylosing spondylitis (AS), objective measurements evaluating the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy are lacking. Objectives To investigate the predictive value of bone turnover markers (BTM) in relation to discontinuation of TNF-α blocking therapy in patients with AS. Methods 111 consecutive AS outpatients from the Medical Center Leeuwarden and the University Medical Center Groningen who started TNF-α blocking therapy (infliximab n=22; etanercept n=71; adalimumab n=18) were included between November 2004 and December 2007. All patients fulfilled the modified New York criteria for AS (n=109) or the ASAS criteria for axial spondyloarthritis (n=2). Patients with recent fractures and/or use of bisphosphonates were excluded. Continuation of TNF-α blocking therapy was based on decrease in Bath AS Disease Activity Index (BASDAI) of at least 50% or 2 units compared with baseline, and/or expert opinion in favor of treatment continuation. Clinical assessments, marker of bone formation bone-specific alkaline phosphatase (BALP), and marker of bone resorption serum collagen-telopeptide (sCTX) were assessed at baseline, 3 and 6 months, and 1, 2, and 3 years. Z-scores of BTM were calculated using matched 10-years-cohorts of a Dutch reference group (200 men or 350 women) to correct for the normal influence that age and gender have on bone turnover. Results Mean age of the 111 AS patients was 42.2 years (SD ± 10.3), median disease duration was 16 years (range 1-49), and 70% were male. Mean BASDAI was 6.1 (SD ± 1.7) and mean AS disease activity index (ASDAS) was 3.8 (SD ± 0.8) at baseline. After 3 years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased BALP Z-score and significantly decreased sCTX Z-score compared to baseline. Baseline to 3 months decrease in sCTX Z-score (HR: 0.513, 95% CI: 0.367-0.717) was inversely associated with time to discontinuation of TNF-α blocking therapy in univariate Cox regression. Multivariate analysis showed that baseline to 3 months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263-0.591), ASDAS (HR: 0.488, 95% CI: 0.317-0.752), and physician’s global disease activity (GDA) (HR: 0.739, 95% CI: 0.600-0.909) were independent inversely related predictors of time to treatment discontinuation. Conclusions In addition to the ASDAS and physician’s GDA, early change in bone resorption marker sCTX after starting treatment can serve as an objective measure in the prediction of long-term continuation of TNF-α blocking therapy in AS. Disclosure of Interest None Declared