Indirect comparison of the effects of anti-TNF biological agents in patients with Ankylosing Spondylitis by means of a Mixed Treatment Comparison performed on efficacy data from published randomised, controlled trials

Abstract

Objectives:

To compare ASAS (Assessment in Ankylosing Spondylitis Response Criteria), 20 response patterns between anti-TNF biological agents in patients with ankylosing spondylitis by means of a mixed treatment comparison of different randomized, controlled trials (RCTs) on the efficacy of biological therapies.

Methods:

A systematic review of literature was performed to identify a number of similarly designed double-blind, randomized, placebo-controlled trials investigating the efficacy of the TNF-α inhibitors etanercept, infliximab, and adalimumab in the treatment of ankylosing spondylitis patients, conducted over an 18-year period. The end-point of interest was ASAS20 response criteria at 24 weeks. Results were analyzed simultaneously using Bayesian mixed treatment comparison techniques. Results were expressed as odds ratio (OR) of ASAS20 response and associated 95% credible intervals (CrIs). The probability of being the best treatment was also reported.

Results:

Three RCTs were selected for data extraction and further analysis. By mean of MTC, all anti-TNF agents demonstrated to be more efficacious in inducing an ASAS20 response than placebo. Infliximab shows a 72% probability of being the best treatment of all. Adalimumab and etanercept show probabilities of 13% and 15%, respectively. No differences were observed when comparing directly an anti-TNF-α agent against another. When compared with placebo, Infliximab increases the probability of response by ∼7-times (OR = 6.8), Adalimumab by ∼4-times (OR = 4.4), and Etanercept by 5-times (OR = 4.9). Differences in trials procedures, the use of a fixed-effect model, and the small number of trials included represent limitations of this study

Conclusions:

Even if the mixed treatment comparisons between infliximab, adalimumab, and etanercept did not show a statistically significant difference, this analysis suggests that infliximab, compared to placebo, is expected to provide the highest rate of ASAS20 response in SA patients naive to biologic treatments.

Keywords::

• Ankylosing spondylitis
• Mixed treatment comparison
• Efficacy
• Etanercept
• Adalimumab
• Infliximab

Abbreviations::

• ASAS, Assessment in Ankylosing Spondylitis Response Criteria; CrIs, credible intervals; OR, odds ratio; RCT, randomized controlled trial; MTC, mixed treatment comparison; AS, ankylosing spondylitis; TNFR, TNF receptor; BASDAI, Bath Ankylosing Spondylitis Disease Activity index; ESR, erythro sedimentation rate; CRP, C reactive protein; NSAID, non-steroideal anti-inflammatory drugs; mSASSS, modified Stoke Ankylosing Spondylitis Spine Score.

Transparency

Declaration of funding

This study was performed with unrestricted funds from ANTIAGE (non-lucrative National Association for intra-articular therapy by ultrasound guidance), of which AM is President.

Declaration of interest

The authors declare that no funds were allocated by any sponsors for the execution of this study. AM, BL, and EB have previously received grants as consultants and speakers from Abbott, Pfizer, Merck, Wyeth, andSchering-Plough. JME peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed any relevant financial relationships.