Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation

To assess the comparative clinical effectiveness and cost-effectiveness of adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis (AS). Major electronic databases were searched up to November 2005. Unpublished evidence such as conference abstracts, reviews of published economic evaluations, and company submissions to the National Institute for Health and Clinical Excellence (NICE) were also reviewed. The assessment was conducted according to accepted procedures for conducting and reporting systematic reviews and economic evaluations. Full economic evaluations that compared two or more options for treatment and considered both costs and consequences were eligible for inclusion in the economic literature review. Nine placebo controlled randomised controlled trials (RCTs) were included in the review of clinical effects. These included two studies of adalimumab, five of etanercept and two of infliximab in comparison with placebo (along with conventional management). No RCTs directly comparing anti-tumour necrosis factor-alpha (TNF-alpha) agents were identified. Meta-analyses were conducted for data on Assessment in Ankylosing Spondylitis (ASAS) (20, 50 and 70% improvement), mean change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and mean change in Bath Ankylosing Spondylitis Functional Index (BASFI) at 12 weeks following initiation of anti-TNF-alpha therapy or placebo for all three drugs. Meta-analyses were also conducted at 24 weeks for etanercept and infliximab. Each meta-analysis of anti-TNF-alpha therapy demonstrated statistically significant advantages over placebo, although there was no significant difference between individual anti-TNF-alpha agents. At 12 weeks, ASAS 50% responses were 3.6-fold more likely with anti-TNF-alpha treatment than placebo. Compared with baseline, BASDAI scores were reduced by close to 2 points at 12 weeks. Functional scores (BASFI) were reduced at 12 weeks. Six full economic evaluations (two peer-reviewed published papers, four abstracts) were included in the review. The conclusions among economic evaluations were mixed, although the balance of evidence indicates that over short time-frames anti-TNF-alpha therapies are unlikely to be considered cost-effective. The limitations of the clinical outcome data impose restrictions on the economic assessment of cost-effectiveness. Direct unbiased RCT evidence is only available in the short term. Current assessment tools are limited and at