Background Interleukin-6 (IL-6) has been shown to be elevated in patients (pts) with AS and correlates with disease activity.1 Case reports concerning the use of TCZ in pts with AS have been published.2-5 The efficacy and safety of TCZ, an inhibitor of IL-6 receptor signalling, as a treatment for AS have not been evaluated in a placebo-controlled trial.
Objectives To examine the efficacy and safety of TCZ for the treatment of AS.
Methods Study Design: Phase 2, multicentre, randomised, double-blind, placebo-controlled study, 12-week (wk) duration. Patients: Definite diagnoses of AS by the modified New York criteria and Bath AS Disease Activity Index (BASDAI) score ≥4.0; adults who were NSAID inadequate responders (IR) and anti-TNF naive. Study Drugs: TCZ 8 mg/kg or placebo (PBO) IV every 4 wks. Primary Endpoints: 20% improvement in assessment of AS (ASAS20) response and safety at wk 12.
Results Of 102 pts enrolled, 99 (48 TCZ, 51 PBO) completed 12 wks. Pt demographics and disease status were in keeping with the target population (Table). The proportion of pts achieving ASAS20 and ASAS40 at wk 12 was not significantly different for TCZ vs PBO (37% vs 28%, p=0.2823; 12% vs 20%, p=0.2694) (Table). No differences between TCZ and PBO were observed for (1) higher percentage ASAS responses, (2) change in individual ASAS components, (3) BASDAI endpoints. These findings were independent of baseline CRP level. There was a reduction in CRP and in AS Disease Activity Score (ASDAS)–CRP with TCZ but not PBO (difference in median CRP change between arms, –1.2 mg/dl, p<0.0001; difference in mean ASDAS-CRP change between arms, –0.9, p<0.0001). Rates/100 patient-years of adverse events (AEs) for TCZ and PBO were 262.4 and 226.9; rates of serious AEs were 17.5 and 0. No AEs led to withdrawal during this 12-wk study.
Conclusions The study failed to demonstrate the efficacy of TCZ over placebo for the treatment of symptoms of AS, irrespective of baseline CRP level. CRP levels declined with TCZ, suggesting adequate IL-6R blockade. The change in ASDAS-CRP was driven by the decrease in CRP. The safety profile of TCZ in this study was consistent with that seen in RA pts.
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Disclosure of Interest J. Sieper Grant/Research support from: Abbott, Merck, Pfizer, Consultant for: Abbott, Merck, Pfizer, UCB, Roche, Sanofi, Speakers Bureau: Abbott, Merck, Pfizer, B. Porter-Brown Shareholder of: Roche, Employee of: Roche, L. Thompson Shareholder of: Roche, Employee of: Roche, O. Harari Employee of: Roche, M. Dougados Grant/Research support from: Roche, Consultant for: Roche, Speakers Bureau: Roche
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