Skip to main content
Log in

Comparison of the Efficacy and Safety of Tofacitinib and Apremilast in Patients with Active Psoriatic Arthritis: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

  • Systematic Review
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

A Correction to this article was published on 13 June 2019

This article has been updated

Abstract

Background

Tofacitinib and apremilast have shown considerable efficacy in placebo-controlled trials of active psoriatic arthritis, but the relative efficacy and safety remain unclear because of a lack of head-to-head comparisons.

Objective

The aim of this study was to assess the relative efficacy and safety of tofacitinib and apremilast at different doses in patients with active psoriatic arthritis.

Method

We performed a Bayesian network meta-analysis to combine evidence from randomized controlled trials for examination of the efficacy and safety of tofacitinib 10 mg, tofacitinib 5 mg, apremilast 30 mg, and apremilast 20 mg in psoriatic arthritis.

Results

Eight randomized controlled trials including 3086 patients met the inclusion criteria. There were ten pairwise comparisons including six direct comparisons of five interventions. All the interventions achieved a significant American College of Rheumatology 20 response compared with placebo. Tofacitinib 10 mg and apremilast 30 mg were among the most effective treatments for active psoriatic arthritis, followed by tofacitinib 5 mg, and apremilast 20 mg. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tofacitinib 10 mg had the highest probability of being the best treatment in terms of the American College of Rheumatology 20 response rate (SUCRA = 0.785). This was followed by apremilast 30 mg (SUCRA = 0.670), tofacitinib 5 mg (SUCRA = 0.596), apremilast 20 mg (SUCRA = 0.448), and placebo (SUCRA = 0.001). We observed no significant differences in the incidence of serious adverse events after treatment with tofacitinib 10 mg, apremilast 30 mg, tofacitinib 5 mg, apremilast 20 mg, or placebo.

Conclusions

In patients with active psoriatic arthritis, tofacitinib 10 mg and apremilast 30 mg were the most efficacious interventions and were not associated with a significant risk of serious adverse events.

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
Fig. 4

Similar content being viewed by others

Change history

  • 13 June 2019

    The original version of this article unfortunately contained a mistake. The corresponding author was incorrect.

References

  1. Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64(Suppl. 2):ii14–7.

    PubMed  Google Scholar 

  2. Ash Z, Gaujoux-Viala C, Gossec L, et al. A systematic literature review of drug therapies for the treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR recommendations for the management of psoriatic arthritis. Ann Rheum Dis. 2012;71:319–26.

    Article  CAS  PubMed  Google Scholar 

  3. Gossec L, Smolen JS, Gaujoux-Viala C, et al. European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis. 2012;71:4–12.

    Article  CAS  PubMed  Google Scholar 

  4. Changelian PS, Flanagan ME, Ball DJ, et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science. 2003;302:875–8.

    Article  CAS  PubMed  Google Scholar 

  5. Chrencik JE, Patny A, Leung IK, et al. Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6. J Mol Biol. 2010;400:413–33.

    Article  CAS  PubMed  Google Scholar 

  6. Meyer DM, Jesson MI, Li X, et al. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis. J Inflamm (Lond). 2010;7:41.

    Article  CAS  PubMed Central  Google Scholar 

  7. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583–90.

    Article  CAS  PubMed  Google Scholar 

  8. Houslay MD, Schafer P, Zhang KY. Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today. 2005;10:1503–19.

    Article  CAS  PubMed  Google Scholar 

  9. Conti M, Beavo J. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu Rev Biochem. 2007;76:481–511.

    Article  CAS  PubMed  Google Scholar 

  10. Mease P, Hall S, FitzGerald O, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med. 2017;377:1537–50.

    Article  CAS  PubMed  Google Scholar 

  11. Gladman D, Rigby W, Azevedo VF, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med. 2017;377:1525–36.

    Article  CAS  PubMed  Google Scholar 

  12. Nash P, Ohson K, Walsh J, et al. Early and sustained efficacy with apremilast monotherapy in biological-naive patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE). Ann Rheum Dis. 2018;77:690–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wells AF, Edwards CJ, Kivitz AJ, et al. Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial. Rheumatology (Oxford). 2018;57:1253–63.

    Article  CAS  PubMed Central  Google Scholar 

  14. Cutolo M, Myerson GE, Fleischmann RM, et al. A phase III, randomized, controlled trial of apremilast in patients with psoriatic arthritis: results of the PALACE 2 trial. J Rheumatol. 2016;43:1724–34.

    Article  PubMed  Google Scholar 

  15. Edwards CJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016;75:1065–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. 2014;73:1020–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schett G, Wollenhaupt J, Papp K, et al. Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012;64:3156–67.

    Article  CAS  PubMed  Google Scholar 

  18. Kim D, Cho S-K, Nam SW, et al. Cardiovascular and gastrointestinal effects of etoricoxib in the treatment of osteoarthritis: a systematic review and network meta-analysis. J Rheum Dis. 2017;24:293–302.

    Article  Google Scholar 

  19. Catala-Lopez F, Tobias A, Cameron C, Moher D, Hutton B. Network meta-analysis for comparing treatment effects of multiple interventions: an introduction. Rheumatol Int. 2014;34:1489–96.

    Article  PubMed  Google Scholar 

  20. Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ. 2005;331:897–900.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lee YH, Song GG. Comparative efficacy and safety of secukinumab and adalimumab in patients with active ankylosing spondylitis: a Bayesian network meta-analysis of randomized controlled trials. J Rheum Dis. 2017;24:211–9.

    Article  Google Scholar 

  22. Lee YH, Bae SC, Song GG. Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis. Arch Med Res. 2012;43:356–62.

    Article  CAS  PubMed  Google Scholar 

  23. Lee YH, Bae SC, Song GG. Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti-tumor necrosis factor therapy. Clin Exp Rheumatol. 2013;31:118–21.

    PubMed  Google Scholar 

  24. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.

    Article  CAS  PubMed  Google Scholar 

  25. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.

    Article  PubMed  Google Scholar 

  26. Brown S, Hutton B, Clifford T, et al. A Microsoft-Excel-based tool for running and critically appraising network meta-analyses: an overview and application of NetMetaXL. Syst Rev. 2014;3:110.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2011;64:163–71.

    Article  PubMed  Google Scholar 

  28. Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE. Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making. 2013;33:641–56.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Higgins JP, Jackson D, Barrett JK, Lu G, Ades AE, White IR. Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Methods. 2012;3:98–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. van Valkenhoef G, Lu G, de Brock B, Hillege H, Ades AE, Welton NJ. Automating network meta-analysis. Res Synth. Methods. 2012;3:285–99.

    Google Scholar 

  31. Asahina A, Etoh T, Igarashi A, et al. Oral tofacitinib efficacy, safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: a randomized, double-blind, phase 3 study. J Dermatol. 2016;43:869–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Thaci D, Kimball A, Foley P, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, improves patient-reported outcomes in the treatment of moderate to severe psoriasis: results of two phase III randomized, controlled trials. J Eur Acad Dermatol Venereol. 2017;31:498–506.

    Article  CAS  PubMed  Google Scholar 

  33. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Longterm (52-week) results of a phase III randomized, controlled trial of apremilast in patients with psoriatic arthritis. J Rheumatol. 2015;42:479–88.

    Article  CAS  PubMed  Google Scholar 

  34. Kawalec P, Holko P, Mocko P, Pilc A. Comparative effectiveness of abatacept, apremilast, secukinumab and ustekinumab treatment of psoriatic arthritis: a systematic review and network meta-analysis. Rheumatol Int. 2018;38:189–201.

    Article  CAS  PubMed  Google Scholar 

  35. Wu D, Yue J, Tam LS. Efficacy and safety of biologics targeting interleukin-6, -12/23 and -17 pathways for peripheral psoriatic arthritis: a network meta-analysis. Rheumatology (Oxford). 2018;57:563–71.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gwan Gyu Song.

Ethics declarations

Funding

No sources of funding were received for the preparation of this article or conduct of the study.

Conflict of Interest

Gwan Gyu Song and Young Ho Lee have no conflicts of interest that are directly relevant to the content of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, G.G., Lee, Y.H. Comparison of the Efficacy and Safety of Tofacitinib and Apremilast in Patients with Active Psoriatic Arthritis: A Bayesian Network Meta-Analysis of Randomized Controlled Trials. Clin Drug Investig 39, 421–428 (2019). https://doi.org/10.1007/s40261-019-00765-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-019-00765-w

Navigation