Skip to main content
Log in

Indirect comparisons of the efficacy of biological agents in patients with active ankylosing spondylitis: a systematic review and meta-analysis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Patients with ankylosing (AS) often do not have a satisfactory response to, or could not tolerate, non-steroidal anti-inflammatory drugs (NSAIDs). Several biologic agents are available for such patients. However, the comparative efficacy of these treatments remains unknown as head-to-head randomized controlled trials (RCTs) are not available. RCTs examining the efficacy of biologic agents in patients with AS who had inadequate response to, or could not tolerate, NSAIDs were identified. If at least two RCTs were available for a given biologic agent, the pooled odds ratio (OR) and 95% confidence interval (CI) of achieving 20% improvement according to the Ankylosing Spondylitis Assessment Study group response criteria 20 (ASAS20) across trials were calculated. The pooled OR for each biologic agent was then compared to each other using the indirect comparison technique. A total of 14 RCTs of older TNF inhibitors, two RCTs of secukinumab, one RCT of certolizumab, and one RCT of tofacitinib were identified. No significant difference in any indirect comparisons was observed with the p values ranging from 0.12 to 0.74. The likelihood of achieving the ASAS20 response in patients AS who failed or could not tolerate NSAIDs was not significantly different between older TNF inhibitors, secukinumab, certolizumab, and tofacitinib. However, the analysis is limited by the small sample size with only one RCT for certolizumab and tofacitinib.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. EL Mouraghi I, Ouarour A, Ghozlani I, Collantes E, Solana R, El Maghraoui A (2015) Polymorphisms of HLA-A, -B, -Cw and DRB1 antigens in Moroccan patients with ankylosing spondylitis and a comparison of clinical features with frequencies of HLA-B*27. Tissue Antigens 85:108–116

    Article  CAS  PubMed  Google Scholar 

  2. Golder V, Schachna L (2013) Ankylosing spondylitis: an update. Aust Fam Physician 42:780–784

    PubMed  Google Scholar 

  3. Dean LE, Jones GT, MacDonald AG et al (2014) Global prevalence of ankylosing spondylitis. Rheumatology (Oxford) 53:650–657

    Article  Google Scholar 

  4. El Maghraoui A (2011) Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications. Eur J Int Med 22:554–560

    Article  Google Scholar 

  5. Zochling J (2008) Assessment and treatment of ankylosing spondylitis: current status and future directions. Curr Opin Rheumatol 20:398–403

    Article  PubMed  Google Scholar 

  6. Song IH, Poddubnyy DA, Rudwaleit M, Sieper J (2008) Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs. Arthritis Rheum 58:929–938

    Article  CAS  PubMed  Google Scholar 

  7. Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL (2015) Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: a systematic review and meta-analysis of observational studies. Eur J Int Med 26:285–291

    Article  CAS  Google Scholar 

  8. Ungprasert P, Srivali N, Thongprayoon C (2016) Nonsteroidal anti-inflammatory drugs and risk of incident heart failure: a systematic review and meta-analysis of observational studies. Clin Cardiol 39:111–118

    Article  PubMed  Google Scholar 

  9. Castellsague J, Riera-Guardia N, Calingaert B (2012) Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf 35:1127–1146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen J, Veras MM, Liu C, Lin J (2013) Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev 28:CD004524

    Google Scholar 

  11. Clegg DO, Reda DJ, Abdellatif M (1999) Comparison of sulfasalazine and placebo for the treatment of axial and peripheral articular manifestations of the seronegative spondyloarthropathies: a Department of Veteran Affairs cooperative study. Arthritis Rheum 42:2325–2329

    Article  CAS  PubMed  Google Scholar 

  12. Ward MM, Deodhar A, Akl EA et al (2016) American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheum 68:282–298

    Article  Google Scholar 

  13. Maxwell LJ, Zochling J, Boonen A et al (2015) TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev 18:CD005468

    Google Scholar 

  14. Landewe R, van Tubergen A (2015) Clinical tools to assess and monitor spondyloarthritis. Curr Rheumatol Rep 17:47

    Article  PubMed  PubMed Central  Google Scholar 

  15. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR (2009) Introduction to meta-analysis. John Wiley & Sons, West Sussex

    Book  Google Scholar 

  16. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50:683–691

    Article  CAS  PubMed  Google Scholar 

  18. Song F, Altman DG, Glenny AM, Deeks JJ (2003) Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 326:472

    Article  PubMed  PubMed Central  Google Scholar 

  19. Pathan E, Abraham S, Van Rossen E et al (2013) Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis. Ann Rheum Dis 72:1475–1480

    Article  CAS  PubMed  Google Scholar 

  20. Braun J, Brandt J, Listing J et al (2002) Treatment of active ankylosing spondylitis with infliximab: a randomized controlled multicentre trial. Lancet 359:1187–1193

    Article  CAS  PubMed  Google Scholar 

  21. van der Heijde D, Dijkmans B, Geusens P et al (2005) Efficacy and safety of infliximab in patients with ankylosing spondylitis. Arthritis Rheum 52:582–591

    Article  PubMed  Google Scholar 

  22. Marzo-Ortega H, McGonagle D, Jarrett S et al (2005) Infliximab in combination with methotrexate in active ankylosing spondylitis: a clinical and imaging study. Ann Rheum Dis 64:1568–1575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Inman RD, Maksymowych WP (2010) A double-blind, placebo-controlled trial of low dose infliximab in ankylosing spondylitis. J Rheumatol 37:1203–1210

    Article  PubMed  Google Scholar 

  24. Maksymowych WP, Salonen D, Inman PD, Rahman P, Lambert RGW (2010) Low-dose infliximab (3mg/kg) significantly reduces spinal inflammation on magnetic resonance imaging in patients with ankylosing spondylitis: a randomized placebo-controlled study. J Rheumatol 37:1728–1734

    Article  CAS  PubMed  Google Scholar 

  25. van der Heijde D, Kivitz A, Schiff MH et al (2006) Efficacy and safety of adalimumab in patients with ankylosing spondylitis. Arthritis Rheum 54:2136–2146

    Article  PubMed  Google Scholar 

  26. Lambert RGW, Salonen D, Rahman P et al (2007) Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 56:4005–4014

    Article  CAS  PubMed  Google Scholar 

  27. Huang F, Gu J, Zhu P et al (2014) Efficacy and safety of adalimumab in Chinese adults with active ankylosing spondylitis: results of a randomised, controlled trial. Ann Rheum Dis 73:587–594

    Article  CAS  PubMed  Google Scholar 

  28. Inman RD, Davis JC, van der Heijde D et al (2008) Efficacy and safety of golimumab in patients with ankylosing spondylitis. Arthritis Rheum 58:3401–3412

    Article  Google Scholar 

  29. Bao C, Huang F, Khan MA et al (2014) Safety and efficacy of golimumab in Chinese patients with active ankylosing spondylitis: 1-year results of a multicentre, randomized, double-blind, placebo-controlled phase III trial. Rheumatology 53:1654–1663

    Article  CAS  PubMed  Google Scholar 

  30. Davis JC, van der Heijde D, Braun J et al (2003) Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 48:3230–3236

    Article  CAS  PubMed  Google Scholar 

  31. Calin A, Dijkmans BAC, Emery P et al (2004) Outcomes of multicentre randomized clinical trial of etanercept to treat ankylosing spondylitis. Ann Rheum Dis 63:1594–1600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. van der Heijde D, Da Silva JC, Dougados M et al (2006) Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis. Ann Rheum Dis 65:1572–1577

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dougados M, Braun J, Szanto S et al (2011) Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomized double-blind placebo-controlled study (SPINE). Ann Rheum Dis 70:799–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Baeten D, Sieper J, Braun J et al (2015) Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med 373:2534–2548

    Article  CAS  PubMed  Google Scholar 

  35. Sieper J, Deodhar A, Marzo-Ortega H et al (2017) Secukinumab efficacy in anti-TNF-naïve and anti-TNF-experienced subjects with active ankylosing spondylitis: results from the MEASURE 2 study. Ann Rheum Dis 76:571–592

    Article  PubMed  Google Scholar 

  36. Landewe R, Braun J, Deodhar A et al (2014) Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of double-blind randomized placebo-controlled phase 3 study. Ann Rheum Dis 73:39–47

    Article  CAS  PubMed  Google Scholar 

  37. van der Heijde D, Deodhar A, Wei JC et al (2017) Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomized placebo-controlled, dose-ranging study. Ann Rheum Dis

  38. Jain A, Singh JA (2013) Harms of TNF inhibitors in rheumatic diseases: a focused review of the literature. Immunotherapy 5:265–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yildiz A, Vieta E, Correll CU, Nikodem M, Baldessarini RJ (2014) Critical issues on the use of network meta-analysis in psychiatry. Harv Rev Psychiatry 22:367–372

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Patompong Ungprasert: Study design, literature search, statistical analysis, and writing manuscript.

Patricia J. Erwin: Literature search and approval of manuscript.

Matthew J. Koster: Study design, literature search, and approval of manuscript.

Corresponding author

Correspondence to Patompong Ungprasert.

Ethics declarations

Funding

This study was supported by a grant (CTSA Grant Number UL1 TR000135) from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosures

None.

Electronic supplementary material

ESM 1

(DOCX 16.1 kb)

Supplementary figure 1:

Funnel plot of older TNF inhibitors (BMP 1240 kb)

Supplementary figure 2:

Risk of bias for individual study (green, low; yellow, unclear; red, high) (BMP 1562 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ungprasert, P., Erwin, P.J. & Koster, M.J. Indirect comparisons of the efficacy of biological agents in patients with active ankylosing spondylitis: a systematic review and meta-analysis. Clin Rheumatol 36, 1569–1577 (2017). https://doi.org/10.1007/s10067-017-3693-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-017-3693-7

Keywords

Navigation