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Indirect Comparison Between Subcutaneous Biologic Agents in Ankylosing Spondylitis

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Abstract

Background and Objective

There are four efficacious subcutaneous anti-tumor necrosis factor alpha (TNF-alpha) agents used for the therapy of ankylosing spondilitis (AS), but apparently little or no differences in their effectiveness was proven. By this study, we aimed to compare Assessment in Ankylosing Spondylitis Response Criteria 20 response patterns (ASAS20) between subcutaneous approved biological agents in patients affected by ankylosing spondylitis by means of a mixed treatment comparison of different randomized controlled trials (RCTs) on the efficacy of biological therapies.

Methods

A search in scientific literature was performed to identify the most complete collection of RCTs available on the selected topic. Similarly designed double-blind, randomized, placebo-controlled trials investigating the efficacy of the subcutaneous and approved TNF-alpha inhibitors such as etanercept, certolizumab pegol, golimumab and adalimumab in the treatment of ankylosing spondylitis patients were identified. The endpoint of interest was ASAS20 response criterium at 12 weeks. Results were analysed simultaneously using Bayesian mixed treatment comparison techniques. Results were expressed as odds ratio (OR) of positive ASAS20 response and associated 95 % credible intervals (CrIs). The probability of being the best treatment was also reported.

Results

Only five RCTs matched the inclusion criteria for consequent data extraction and analysis. Mixed treatment comparison of data from such RCTs demonstrated that all subcutaneous anti-TNF-alpha agents are more effective in inducing an ASAS20 response than placebo. Data from 24 weeks’ follow-up were not taken into account as early escape granted in some of the studies made results at 24 weeks unmatchable. In our analysis, golimumab proved to be the drug that more probably represents the best choice for achieving ASAS20 response at 12 weeks, although no differences were observed when comparing directly every single subcutaneous anti-TNF-alpha agent against another.

Conclusions

Even if the mixed treatment comparisons between adalimumab, golimumab, certolizumab pegol and etanercept did not show a statistically significant difference, this analysis, based on data from only five RCTs, suggests that golimumab, compared to placebo, may be the drug that provides the highest probability of achieving ASAS20 response in AS patients naive to biologic treatments at 12 weeks.

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Competing interests

This study was conducted with unrestricted funds from ANTIAGE (a non profit National Association for ultrasound-guided intra-articular hip therapy) whose President is Prof. Alberto Migliore. Prof. Alberto Migliore and Prof. Bruno Laganà received grants as consultants from Pfizer, Abbvie and Merck for national and international studies.

Authors’ contribution

Prof. Migliore A. and Prof. Laganà B. both contributed to study concept and realisation, Dr Bernardi M. and Prof. Petrella L. contributed providing statistical analysis and Dr Bizzi E. contributed by analysing results and to the development text.

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Correspondence to Emanuele Bizzi.

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Migliore, A., Bizzi, E., Bernardi, M. et al. Indirect Comparison Between Subcutaneous Biologic Agents in Ankylosing Spondylitis. Clin Drug Investig 35, 23–29 (2015). https://doi.org/10.1007/s40261-014-0246-6

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