Skip to main content

Advertisement

Log in

The Changing Face of Clinical Trials in Psoriatic Arthritis

  • Psoriatic Arthritis (J Scher, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of the Review

We will address current treatment and unmet needs in psoriatic arthritis (PsA), examine existing randomized controlled trials (RCTs), and consider options for new trial designs and challenges in their implementation.

Recent Findings

While therapeutic options for PsA have rapidly increased, there continues to be a need for clinical trials to test new therapies and establish optimal treatment strategies in order to improve the care for patients with PsA. In addition, more data is needed on how to select the best therapy for a given patient in clinical practice. Consideration of alternative outcome measures is also needed.

Summary

Despite the rapid expansion in the number of therapy options available, there is still much to be learned about how to treat the individual patient with PsA.

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.

Similar content being viewed by others

References

Papers of particular interest, published recently have been highlighted as: • Of importance •• Of major importance

  1. Nash P, Thaci D, Behrens F, Falk F, Kaltwasser JP. Leflunomide improves psoriasis in patients with psoriatic arthritis: an in-depth analysis of data from the TOPAS study. Dermatology (Basel, Switzerland). 2006;212(3):238–49. doi:10.1159/000091251.

    Article  CAS  Google Scholar 

  2. Mease PJ, Kivitz AJ, Burch FX, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50(7):2264–72. doi:10.1002/art.20335.

    Article  CAS  PubMed  Google Scholar 

  3. Mease PJ, Gladman DD, Ritchlin CT, et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005;52(10):3279–89. doi:10.1002/art.21306.

    Article  CAS  PubMed  Google Scholar 

  4. Antoni C, Krueger GG, de Vlam K, et al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. 2005;64(8):1150–7. doi:10.1136/ard.2004.032268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kavanaugh A, van der Heijde D, McInnes IB, et al. Golimumab in psoriatic arthritis: one-year clinical efficacy, radiographic, and safety results from a phase III, randomized, placebo-controlled trial. Arthritis Rheum. 2012;64(8):2504–17. doi:10.1002/art.34436.

    Article  CAS  PubMed  Google Scholar 

  6. Kavanaugh A, McInnes I, Mease P, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum. 2009;60(4):976–86. doi:10.1002/art.24403.

    Article  CAS  PubMed  Google Scholar 

  7. Mease PJ, Fleischmann R, Deodhar AA, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014;73(1):48–55. doi:10.1136/annrheumdis-2013-203696.

    Article  CAS  PubMed  Google Scholar 

  8. McInnes IB, Kavanaugh A, Gottlieb AB, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet (London, England). 2013;382(9894):780–9. doi:10.1016/s0140-6736(13)60594-2.

    Article  CAS  Google Scholar 

  9. Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73(6):990–9. doi:10.1136/annrheumdis-2013-204655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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(6):1020–6. doi:10.1136/annrheumdis-2013-205056.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329–39. doi:10.1056/NEJMoa1412679.

    Article  CAS  PubMed  Google Scholar 

  12. McInnes IB, Mease PJ, Kirkham B, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (London, England). 2015;386(9999):1137–46. doi:10.1016/s0140-6736(15)61134-5.

    Article  CAS  Google Scholar 

  13. Mease PJ, van der Heijde D, Ritchlin CT, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2016. doi:10.1136/annrheumdis-2016-209709.

    Google Scholar 

  14. Gladman D, Rigby W, Azevedo VF, Behrens F, Blanco R, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in patients with active psoriatic arthritis and an inadequate response to tumor necrosis factor inhibitors: OPAL Beyond, a randomized, double blind, placebo-controlled, phase 3 trial [abstract 10L]. Arthritis Rheumatol (Hoboken, NJ). 2016;68(Suppl 10).

  15. Mease P, Hall S, FitzGerald O, van der Heijde D, Merola J, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, or adalimumab in patients with active psoriatic arthritis and an inadequate response to conventional synthetic dmards: a randomized, placebo‑controlled, phase 3 trial [abstract 2983]. Arthritis Rheumatol (Hoboken, NJ). 2016;68(Suppl 10).

  16. Mease P, Gottlieb A, van der Heijde D, FitzGerald O, Johnsen A, et al. Abatacept in the treatment of active psoriatic arthritis: 24-week results from a phase III study [abstract 1041]. Arthritis Rheumatol (Hoboken, NJ). 2016;68(Suppl 10).

  17. Deodhar A, Gottlieb A, Boehncke W, Dong B, Wang Y, et al. Efficacy and safety results of guselkumab, an anti-IL23 monoclonal antibody, in patients with active psoriatic arthritis over 24 weeks: a phase 2a, randomized, double-blind, placebo-controlled study [abstract 4L]. Arthritis Rheumatol (Hoboken, NJ). 2016;68(Suppl 10).

  18. •• Mease PJ. Biologic therapy for psoriatic arthritis. Rheum Dis Clin N Am. 2015;41(4):723–38. doi:10.1016/j.rdc.2015.07.010. Comprehensive review of recent clinical trials, the results of the trials, and the mechanism of action of drugs tested.

    Article  Google Scholar 

  19. Mease PJ, Heckaman M, Kary S, Kupper H. Application and modifications of minimal disease activity measures for patients with psoriatic arthritis treated with adalimumab: subanalyses of ADEPT. J Rheumatol. 2013;40(5):647–52. doi:10.3899/jrheum.120970.

    Article  CAS  PubMed  Google Scholar 

  20. • Coates LC, Moverley AR, McParland L, et al. Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial. Lancet (London, England). 2015;386(10012):2489–98. doi:10.1016/s0140-6736(15)00347-5. This is the first and only treatment strategy trial published in PsA.

    Article  Google Scholar 

  21. Ogdie A, Eder L. Improving cardiovascular health and metabolic comorbidities in patients with psoriatic arthritis. Int J Clin Rheumatol. 2015;10(6):451–9. doi:10.2217/ijr.15.45.

    Article  CAS  Google Scholar 

  22. • Di Minno MN, Peluso R, Iervolino S, et al. Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumour necrosis factor alpha blockers. Ann Rheum Dis. 2014;73(6):1157–62. doi:10.1136/annrheumdis-2012-202812. This RCT is among the few trials assessing the benefits of non-pharmacologic therapies in PsA.

    Article  PubMed  Google Scholar 

  23. Russolillo A, Iervolino S, Peluso R, et al. Obesity and psoriatic arthritis: from pathogenesis to clinical outcome and management. Rheumatology (Oxford, England). 2013;52(1):62–7. doi:10.1093/rheumatology/kes242.

    Article  CAS  Google Scholar 

  24. Rankin A, Rivest J. Medicine, monopoly, and the premodern state–early clinical trials. N Engl J Med. 2016;375(2):106–9. doi:10.1056/NEJMp1605900.

    Article  PubMed  Google Scholar 

  25. • Bothwell LE, Greene JA, Podolsky SH, Jones DS. Assessing the gold standard–lessons from the history of RCTs. N Engl J Med. 2016;374(22):2175–81. doi:10.1056/NEJMms1604593. Interesting review of the history of clinical trials in medicine.

    Article  CAS  PubMed  Google Scholar 

  26. Bothwell LE, Podolsky SH. The emergence of the randomized, controlled trial. N Engl J Med. 2016;375(6):501–4. doi:10.1056/NEJMp1604635.

    Article  PubMed  Google Scholar 

  27. •• Woodcock J, Ware J, Miller P, McMurray J, Harrington D, et al. Clinical trials series. N Engl J Med. 2016;374(2167). doi:10.1056/NEJMe1601510. The New England Journal of Medicine (NEJM) recently launched a new series titled “The changing face of clinical trials.” This series of review articles and perspectives addresses methods, designs, and other important issues in RCTs

  28. Ford I, Norrie J. Pragmatic trials. N Engl J Med. 2016;375(5):454–63. doi:10.1056/NEJMra1510059.

    Article  PubMed  Google Scholar 

  29. Gabay C, Emery P, van Vollenhoven R, et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet (London, England). 2013;381(9877):1541–50. doi:10.1016/s0140-6736(13)60250-0.

    Article  CAS  Google Scholar 

  30. Smolen JS, Emery P, Fleischmann R, et al. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet (London, England). 2014;383(9914):321–32. doi:10.1016/s0140-6736(13)61751-1.

    Article  CAS  Google Scholar 

  31. Smolen JS, Nash P, Durez P, et al. Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomised controlled trial. Lancet (London, England). 2013;381(9870):918–29. doi:10.1016/s0140-6736(12)61811-x.

    Article  CAS  Google Scholar 

  32. Landewe RB, Smolen JS, Weinblatt ME, et al. Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example. Ann Rheum Dis. 2014;73(10):1755–60. doi:10.1136/annrheumdis-2014-205821.

    Article  PubMed  Google Scholar 

  33. Kalyoncu U, Ogdie A, Campbell W, et al. Systematic literature review of domains assessed in psoriatic arthritis to inform the update of the psoriatic arthritis core domain set. RMD Open. 2016;2(1), e000217. doi:10.1136/rmdopen-2015-000217.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Orbai AM, de Wit M, Mease P, et al. International patient and physician consensus on a psoriatic arthritis core outcome set for clinical trials. Ann Rheum Dis. 2016. doi:10.1136/annrheumdis-2016-210242.

    PubMed  PubMed Central  Google Scholar 

  35. Ogdie A, Schwartzman S, Husni ME. Recognizing and managing comorbidities in psoriatic arthritis. Curr Opin Rheumatol. 2015;27(2):118–26. doi:10.1097/bor.0000000000000152.

    Article  PubMed  Google Scholar 

  36. George M, Giles J, Katz P, Ibrahim S, Cannon G, et al. C-reactive protein and disease activity in rheumatoid arthritis: impact of obesity and adiposity [abstract 510] Arthritis Rheumatol (Hoboken, NJ). 2016;68(Suppl 10).

  37. Coates LC, FitzGerald O, Gladman DD, et al. Reduced joint counts misclassify patients with oligoarticular psoriatic arthritis and miss significant numbers ofpatients with active disease. Arthritis Rheum. 2013;65(6):1504–9.

    Article  PubMed  Google Scholar 

  38. Coates LC, Helliwell PS. Defining low disease activity states in psoriatic arthritis using novel composite disease instruments. J Rheumatol. 2016;43(2):371–5. doi:10.3899/jrheum.150826.

    Article  CAS  PubMed  Google Scholar 

  39. Helliwell PS, Kavanaugh A. Comparison of composite measures of disease activity in psoriatic arthritis using data from an interventional study with golimumab. Arthritis Care Res. 2014;66(5):749–56. doi:10.1002/acr.22204.

    Article  CAS  Google Scholar 

  40. Schoels MM, Aletaha D, Alasti F, Smolen JS. Disease activity in psoriatic arthritis (PsA): defining remission and treatment success using the DAPSA score. Ann Rheum Dis. 2016;75(5):811–8. doi:10.1136/annrheumdis-2015-207507.

    Article  PubMed  Google Scholar 

  41. Sakkas LI, Alexiou I, Simopoulou T, Vlychou M. Enthesitis in psoriatic arthritis. Semin Arthritis Rheum. 2013;43(3):325–34.

    Article  PubMed  Google Scholar 

  42. Nzeusseu Toukap A, Durnez A, Navarro Guerra P, Stoenoiu M. Which are the ultrasound lesions underlying dactylitis? [abstract 148]. Arthritis Rheumatol (Hoboken, NJ). 2016;68(Suppl 10).

  43. Poddubnyy D, Haibel H, Braun J, Rudwaleit M, Sieper J. Low functional relevance of radiographic spinal progression in patients with early axial spondyloarthritis [abstract]. Arthritis Rheumatol (Hoboken, NJ). 2016;68(Suppl 10).

  44. Orbai AM, Ogdie A. Patient-reported outcomes in psoriatic arthritis. Rheum Dis Clin N Am. 2016;42(2):265–83. doi:10.1016/j.rdc.2016.01.002.

    Article  Google Scholar 

  45. Kane D, Stafford L, Bresnihan B, FitzGerald O. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology (Oxford, England). 2003;42(12):1460–8. doi:10.1093/rheumatology/keg384.

    Article  CAS  Google Scholar 

  46. Cresswell L, Chandran V, Farewell VT, Gladman DD. Inflammation in an individual joint predicts damage to that joint in psoriatic arthritis. Ann Rheum Dis. 2011;70(2):305–8. doi:10.1136/ard.2010.135087.

    Article  PubMed  Google Scholar 

  47. Vashisht P, Sayles H, Cannella AC, Mikuls TR, Michaud K. Generalizability of patients with rheumatoid arthritis in biologic agent clinical trials. Arthritis Care Res. 2016;68(10):1478–88. doi:10.1002/acr.22860.

    Article  CAS  Google Scholar 

  48. Ogdie A, Palmer J, Greenberg J, Harrold L, Solomon D, et al. Predictors of achieving remission among patients with psoriatic arthritis prescribed TNF inhibitors [abstract]. Arthritis Rheumatol (Hoboken, NJ). 2016;68(Suppl 10).

  49. Coates LC, Kavanaugh A, Mease PJ, et al. Group for research and assessment of psoriasis and psoriatic arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis Rheumatol (Hoboken, NJ). 2016;68(5):1060–71. doi:10.1002/art.39573.

    Google Scholar 

  50. Tillett W, McHugh N. Treatment algorithms for early psoriatic arthritis: do they depend on disease phenotypes? Curr Rheumatol Rep. 2012;14(4):334–42.

    Article  PubMed  Google Scholar 

  51. Gossec L, Smolen JS, Ramiro S, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis. 2016;75(3):499–510. doi:10.1136/annrheumdis-2015-208337.

    Article  CAS  PubMed  Google Scholar 

  52. •• Fitzgerald O, Haroon M, Giles JT, Winchester R. Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. Arthritis Care Res. 2015;17(1):115. Review article highlighting the correlation between genetics and phenotype among patients with PsA.

    Article  Google Scholar 

  53. Glintborg B, Ostergaard M, Krogh NS, et al. Clinical response, drug survival, and predictors thereof among 548 patients with psoriatic arthritis who switched tumor necrosis factor alpha inhibitor therapy: results from the Danish Nationwide DANBIO Registry. Arthritis Rheum. 2013;65(5):1213–23. doi:10.1002/art.37876.

    Article  CAS  PubMed  Google Scholar 

  54. Iannone F, Lopriore S, Bucci R, et al. Two-year survival rates of anti-TNF-alpha therapy in psoriatic arthritis (PsA) patients with either polyarticular or oligoarticular PsA. Scand J Rheumatol. 2015;44(3):192–9. doi:10.3109/03009742.2014.962081.

    Article  CAS  PubMed  Google Scholar 

  55. Rusman T, Nurmohamed M, van Denderen JC, Visman I, Van der Horst - Bruinsma IE. Female Gender Is Associated with a Poorer Response to TNF-Inhibitors in Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2016;68(Suppl 10).

  56. Ciurea A, Hebeisen M, Weber U, Tamborrini G, Micheroli R, et al. In contrast to men, women with nonradiographic axial spondyloarthritis have lower response rates to TNF inhibitors than women with ankylosing spondylitis [abstract 699]. Arthritis Rheumatol (Hoboken, NJ). 2016;68(Suppl 10).

  57. Medicine Io. Sharing clinical trial data: maximizing benefits, minimizing risks. Washington DC: The National Academies Press; 2015.

    Google Scholar 

  58. Drazen JM. Sharing individual patient data from clinical trials. N Engl J Med. 2015;372(3):201–2. doi:10.1056/NEJMp1415160.

    Article  CAS  PubMed  Google Scholar 

  59. Warren E. Strengthening research through data sharing. N Engl J Med. 2016;375(5):401–3. doi:10.1056/NEJMp1607282.

    Article  PubMed  Google Scholar 

  60. Krumholz HM, Waldstreicher J. The Yale Open Data Access (YODA) Project—a mechanism for data sharing. N Engl J Med. 2016;375(5):403–5. doi:10.1056/NEJMp1607342.

    Article  PubMed  Google Scholar 

  61. Patel MR, Armstrong PW, Bhatt DL, et al. Sharing data from cardiovascular clinical trials—a proposal. N Engl J Med. 2016;375(5):407–9. doi:10.1056/NEJMp1605260.

    Article  PubMed  Google Scholar 

  62. Fraser AD, van Kuijk AW, Westhovens R, et al. A randomised, double blind, placebo controlled, multicentre trial of combination therapy with methotrexate plus ciclosporin in patients with active psoriatic arthritis. Ann Rheum Dis. 2005;64(6):859–64. doi:10.1136/ard.2004.024463.

    Article  CAS  PubMed  Google Scholar 

  63. Antoni CE, Kavanaugh A, Kirkham B, et al. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum. 2005;52(4):1227–36. doi:10.1002/art.20967.

    Article  CAS  PubMed  Google Scholar 

  64. Mease PJ, Gladman DD, Keystone EC. Alefacept in combination with methotrexate for the treatment of psoriatic arthritis: results of a randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2006;54(5):1638–45. doi:10.1002/art.21870.

    Article  CAS  PubMed  Google Scholar 

  65. Kivitz AJ, Espinoza LR, Sherrer YR, Liu-Dumaw M, West CR. A comparison of the efficacy and safety of celecoxib 200 mg and celecoxib 400 mg once daily in treating the signs and symptoms of psoriatic arthritis. Semin Arthritis Rheum. 2007;37(3):164–73. doi:10.1016/j.semarthrit.2007.03.004.

    Article  CAS  PubMed  Google Scholar 

  66. Sterry W, Ortonne JP, Kirkham B, et al. Comparison of two etanercept regimens for treatment of psoriasis and psoriatic arthritis: PRESTA randomised double blind multicentre trial. BMJ (Clinical research ed). 2010;340:c147. doi:10.1136/bmj.c147.

    Article  Google Scholar 

  67. Baranauskaite A, Raffayova H, Kungurov NV, et al. Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study. Ann Rheum Dis. 2012;71(4):541–8. doi:10.1136/ard.2011.152223.

    Article  CAS  PubMed  Google Scholar 

  68. Kingsley GH, Kowalczyk A, Taylor H, et al. A randomized placebo-controlled trial of methotrexate in psoriatic arthritis. Rheumatology (Oxford, England). 2012;51(8):1368–77. doi:10.1093/rheumatology/kes001.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexis Ogdie.

Ethics declarations

Conflict of Interest

Alexis Ogdie declares the receipt of grant funding from Pfizer and has consulted for Pfizer and Novartis.

Laura Coates declares the receipt of grant funding from Abbvie and Janssen and has received honoraria from Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, and UCB.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the authors.

Additional information

This article is part of the Topical Collection on Psoriatic Arthritis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ogdie, A., Coates, L. The Changing Face of Clinical Trials in Psoriatic Arthritis. Curr Rheumatol Rep 19, 21 (2017). https://doi.org/10.1007/s11926-017-0642-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-017-0642-z

Keywords

Navigation