Drug Survival of Biologics in Treating Ankylosing Spondylitis: A Systematic Review and Meta-analysis of Real-World Evidence

BioDrugs. 2020 Oct;34(5):669-679. doi: 10.1007/s40259-020-00442-x.

Abstract

Background: The last decade has witnessed the increasing use of biologics for the treatment of ankylosing spondylitis (AS). Drug survival is an outcome incorporating real-world effectiveness and safety. However, the drug survival of biologics in treating AS is unclear.

Objective: The aim was to assess the drug survival of biologics (tumor necrosis factor inhibitors and anti-interleukin-17 monoclonal antibodies) in treating AS.

Methods: We conducted a systematic review and meta-analysis and searched the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases up to 13th May 2020. Studies that analyzed the drug survival of biologics for AS and reported the respective annual data for each biologic for at least 1 year were included. Two authors independently screened and selected studies and assessed their risk of bias. A third author was available for arbitrating discrepancies. The Newcastle-Ottawa Scale was employed to evaluate the risk of bias of included studies. We conducted a random-effects model meta-analysis to obtain pooled drug survival from year 1 to 5. We performed subgroup analyses for biologic-naïve patients, first-line versus second- and third-line biologics, discontinuation due to loss of effectiveness and adverse effects, and high-quality studies.

Results: We included 39 studies with 32,493 patients. The drug survival decreased from 76% at year 1 to 51% at year 5 for etanercept, from 75 to 51% for adalimumab, from 76 to 53% for infliximab, from 72 to 49% for golimumab, and from 63 to 57% for certolizumab pegol. The drug survival rate for secukinumab was 0.77 (95% confidence interval 0.64‒0.90) at year 1. Subgroup analyses on biologic-naïve patients and discontinuation due to adverse effects found no differences in the drug survival of various biologics except for a lower drug survival of infliximab in biologic-naïve patients. The drug survival for first-line biologics was higher than for second- and third-line biologics.

Conclusion: To the best of our knowledge, this study is the first systematic review and meta-analysis on the drug survival of biological therapies for AS patients. The drug survival of all biologics in treating AS appeared comparable, but is higher in first-line biologics than second- and third-line biologics. To date there are scarce data on the drug survival of newly available biologics, for example, anti-interleukin-17 biologics.

Prospero registration no: CRD42018114204.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adalimumab / therapeutic use
  • Antirheumatic Agents* / therapeutic use
  • Biological Products* / therapeutic use
  • Etanercept / therapeutic use
  • Humans
  • Infliximab / therapeutic use
  • Pharmaceutical Preparations*
  • Spondylitis, Ankylosing* / drug therapy

Substances

  • Antirheumatic Agents
  • Biological Products
  • Pharmaceutical Preparations
  • Infliximab
  • Adalimumab
  • Etanercept