Novel Treatments with Small Molecules in Psoriatic Arthritis
- 1.1k Downloads
Current treatment options for patients with active psoriatic arthritis (PsA) include synthetic disease-modifying antirheumatic drugs and biologic agents. Propelled by increased understanding of immunopathogenesis of PsA, new therapeutic agents targeting different biologic pathways have been evaluated. This article discusses novel small-molecule, orally available treatments that are currently in clinical development for the treatment of psoriasis and PsA. This includes the phosphodiesterase 4 inhibitor apremilast and Janus kinase (JAK) inhibitors. Apremilast has demonstrated significant improvements in patients with moderate to severe psoriasis and PsA in phase II and III clinical trials and has recently been approved for the treatment of PsA. Tofacitinib, an oral inhibitor of JAK3, JAK1, and, to a lesser degree, JAK2, approved for the treatment of rheumatoid arthritis in several countries, has demonstrated positive results in psoriasis in phase II studies. Studies in PsA are ongoing. With these new developments, treatment options will continue to improve in the future.
KeywordsPsoriasis Psoriatic arthritis Apremilast Janus kinase inhibitors
Compliance with Ethics Guidelines
Conflict of Interest
Renata Baronaite Hansen declares no conflict of interest.
Arthur Kavanaugh reports grants from Amgen, AbbVie, Celgene, and Janssen, outside the submitted work.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 4.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(3):319–26.PubMedCrossRefGoogle Scholar
- 17.Papp KA, Kaufmann R, Thaci D, Hu C, Sutherland D, Rohane P. Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison study. J Eur Acad Dermatol Venereol. 2013;27(3):e376–83.PubMedCrossRefGoogle Scholar
- 18.•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(10):3156–67. Important article describing a phase II study showing efficacy of apremilast in joint symptoms in patients with PsA.PubMedCrossRefGoogle Scholar
- 20.••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. Important article describing a phase III study on apremilast in 504 patients with PsA. Apremilast demonstrated efficacy in improving skin and joint symptoms, as well as enthesitis and dactylitis. Google Scholar
- 21.••Cutolo M, Myerson GE, Fleischmann RM, et al. Long-term (52-week) results of a Phase 3, randomized, controlled trial of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis (PALACE 2) [abstract]. Arthritis Rheum. 2013;65(Suppl):S346. This abstract describes efficacy of a apremilast in improving joint symptoms, the Health assessment questionnaire disability index, Medical Outcomes Survey Short form-36 Physical Functioning and skin at 52 weeks of treatment in a phase III study of 484 patients with PsA.Google Scholar
- 22.Edwards CJ, Blanco FJ, Crowley J, et al. Long-term (52-week) results of a Phase 3, randomized, controlled trial of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement (PALACE 3) [abstract]. Arthritis Rheum. 2013;65(Suppl):S132.Google Scholar
- 23.••Gladman DD, Mease PJ, Kavanaugh A, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, is associated with long-term (52-week) improvements in enthesitis and dactylitis in patients with psoriatic arthritis: pooled results from three Phase 3, randomized, controlled trials [abstract]. Arthritis Rheum. 2013;65(Suppl):S347. This article provides a description of the efficacy of apremilast in improving dactylitis and enthesitis in PsA patients in three phase III studies.Google Scholar
- 24.•Mease PJ, Kavanaugh A, Gladman DD, et al. Long-term safety and tolerability of apremilast, an oral phospho- diesterase 4 inhibitor, in patients with psoriatic arthritis: pooled safety analysis of three Phase 3, randomized, controlled trials [abstract]. Arthritis Rheum. 2013;65(Suppl):S131. This article provides a describtion of adverse events of apremilast from three phase III studies.Google Scholar
- 25.Mease PJ, Kavanaugh A, Adebajo AO, et al. Laboratory abnormalities in patients with psoriatic arthritis receiving apremilast, an oral phosphodiesterase 4 inhibitor: pooled safety analysis of three Phase 3, randomized, controlled trials [abstract]. Arthritis Rheum. 2013;65(Suppl):S151.Google Scholar
- 27.Meyer SC, Levine RL. Molecular pathways: molecular basis for sensitivity and resistance to JAK kinase inhibitors. Clin Cancer Res. 2014;20:2051-9.Google Scholar
- 28.•Papp KA, Menter A, Strober B, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol. 2012;167(3):668–77. This study describes the efficacy of JAK inhibitor tofacitinib in improving skin symptoms in a phase II study in patients with psoriasis.PubMedCrossRefGoogle Scholar
- 29.•Mamolo C, Harness J, Tan H, et al. Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, improves patient-reported outcomes in a phase 2b, randomized, double-blind, placebo-controlled study in patients with moderate-to-severe psoriasis. J Eur Acad Dermatol Venereol. 2013.doi: 10.1111/jdv.12081. This article describes the efficacy of JAK inhibitor tofacitinib in improving patient-reported outcomes in phase II study in patients with psoriasis.
- 30.Burmester GR, Blanco R, Charles-Schoeman C, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013;381(9865):451–60.PubMedCrossRefGoogle Scholar
- 33.•Gaujoux-Viala C, Nam J, Ramiro S, et al. Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2014;73(3):510–5. A good review of adverse events of tofacitinib in RA patients.PubMedCrossRefPubMedCentralGoogle Scholar
- 34.Macfarlane LA, Todd DJ. Kinase inhibitors: the next generation of therapies in the treatment of rheumatoid arthritis. Int J Rheum Dis. 2014;17(4):359-68.Google Scholar
- 37.Menter A, Papp K, Janes J, et al. A Phase 2b trial of baricitinib, an oral JAK inhibitor, in patients with moderate-to-severe psoriasis [abstract]. J Am Acad Dermatol. 2014;70(5):AB162.Google Scholar