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Clinical Trial
. 2014 Jan;73(1):95-100.
doi: 10.1136/annrheumdis-2013-203559. Epub 2013 Jun 13.

Assessment of Short-Term Symptomatic Efficacy of Tocilizumab in Ankylosing Spondylitis: Results of Randomised, Placebo-Controlled Trials

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Free PMC article
Clinical Trial

Assessment of Short-Term Symptomatic Efficacy of Tocilizumab in Ankylosing Spondylitis: Results of Randomised, Placebo-Controlled Trials

Joachim Sieper et al. Ann Rheum Dis. .
Free PMC article

Abstract

Objectives: BUILDER-1 and BUILDER-2 aimed to assess the efficacy and safety of tocilizumab (TCZ) in patients with ankylosing spondylitis (AS).

Methods: BUILDER-1 was a two part, phase II-III parallel-group trial in patients with AS naive to antitumour necrosis factor (aTNF) treatment. Patients in part 1 received TCZ 8 mg/kg or placebo for 12 weeks. In part 2 (beginning after part 1 enrolment ended), newly enrolled patients received TCZ 4 or 8 mg/kg or placebo for 24 weeks. The same treatment arms were used in BUILDER-2, a phase III study in aTNF-inadequate responders. The primary endpoint for both studies was the proportion of patients achieving 20% improvement in the Assessments in Axial SpondyloArthritis international Society (ASAS). Secondary and exploratory endpoints included ASAS40 response rates, Bath Ankylosing Spondylitis Disease Activity Index improvement, changes in joint counts, enthesitis score and C reactive protein (CRP).

Results: 102 patients were randomised in BUILDER-1 part 1; 99 (48 TCZ, 51 placebo) completed 12 weeks. Week 12 ASAS20 response rates were 37.3% and 27.5% in the TCZ and placebo arms, respectively (p=0.2823). Secondary and exploratory endpoints did not differ between treatment arms. CRP levels declined with TCZ treatment, suggesting adequate IL-6 receptor blockade. As a result, BUILDER-1 part 2 and BUILDER-2 were terminated. TCZ safety results were consistent with previous observations in rheumatoid arthritis, except for a cluster of anaphylactic and hypersensitivity events at Bulgarian study sites. No apparent explanation for this clustering could be found.

Conclusions: BUILDER-1 failed to demonstrate TCZ efficacy in treating aTNF-naive patients with AS.

Trial registration: ClinicalTrials.gov NCT01209689 NCT01209702.

Keywords: Ankylosing Spondylitis; Inflammation; Treatment.

Figures

Figure 1
Figure 1
Patient disposition for BUILDER-1 parts 1 and 2 at 12 and 24 weeks. TCZ, tocilizumab.
Figure 2
Figure 2
(A) ASAS20 and (B) ASAS40 response rates at week 12 in BUILDER-1 part 1 (intention-to-treat population; significance was determined using a logistic regression adjusted for region) for the entire group and (C) by CRP levels at baseline. ASAS20, 20% improvement in the Assessments in Ankylosing Spondylitis Response Criteria; CRP, C reactive protein; TCZ, tocilizumab; ULN, upper limit of normal.
Figure 3
Figure 3
BASDAI total score over time in BUILDER-1 part 1 (intention-to-treat population). Error bars represent 95% CIs. Missing components were imputed using last observation carried forward. BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; TCZ, tocilizumab.
Figure 4
Figure 4
Median change in CRP levels from baseline to week 12 in BUILDER-1 part 1 (intention-to-treat population). Error bars represent IQRs. CRP, C reactive protein; TCZ, tocilizumab.

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