Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis
Arthur Kavanaugh, Dafna D Gladman, Christopher J Edwards, Georg Schett, Benoit Guerette, Nikolay Delev, Lichen Teng, Maria Paris, Philip J Mease, Arthur Kavanaugh, Dafna D Gladman, Christopher J Edwards, Georg Schett, Benoit Guerette, Nikolay Delev, Lichen Teng, Maria Paris, Philip J Mease
Abstract
Background: The efficacy and safety of apremilast were assessed in patients with psoriatic arthritis (PsA) in three phase III clinical trials with similar designs (PALACE 1, 2, and 3).
Methods: Following a 24-week, randomized (1:1:1 to apremilast 30 mg twice daily, 20 mg twice daily, or placebo), double-blind phase and a 28-week blinded active treatment phase, patients could receive apremilast in open-label extension studies for an additional 4 years. Eligible adult patients had active PsA for ≥ 6 months and three or more swollen joints and three or more tender joints despite prior treatment with disease-modifying anti-rheumatic drugs.
Results: A total of 1493 randomized patients received one or more doses of study medication (placebo: n = 496; apremilast 30 mg twice daily: n = 497; apremilast 20 mg twice daily: n = 500). In patients continuing apremilast treatment, response was sustained without new safety issues. At week 260, 67.2% of remaining patients achieved an ACR20 response, and 44.4% and 27.4% achieved ACR50 and ACR70 responses, respectively. Among patients with baseline enthesitis and dactylitis, 62.4% achieved a Maastricht Ankylosing Spondylitis Enthesitis Score of 0 and 80.9% achieved a dactylitis count of 0, respectively. In patients who had ≥ 3% baseline psoriasis body surface area involvement, 43.6% achieved ≥ 75% reduction from the baseline Psoriasis Area and Severity Index scores. The most commonly reported adverse events (AEs) were diarrhea, nausea, headache, upper respiratory tract infection, and nasopharyngitis, with most diarrhea and nausea AEs occurring within the first 2 weeks of treatment and usually resolving within 4 weeks. Reported rates of depression during the study were low (≤ 1.8%). The majority of patients maintained their weight within 5% of baseline during the study. No new safety concerns or increases in the incidence or severity of AEs were observed over the long term.
Conclusions: Apremilast maintained clinical benefit and a favorable safety profile for up to 5 years among patients with PsA.
Trial registration: ClinicalTrials.gov NCT01172938 , NCT01212757 , NCT01212770.
Keywords: Apremilast; Drug safety; Psoriatic arthritis; Treatment efficacy.
Conflict of interest statement
Ethics approval and consent to participateThe institutional review boards from each participating medical center approved the study protocol for each of the three studies. All patients provided written informed consent before any study-related procedures were conducted.
Consent for publicationNot applicable.
Competing interestsAK has received grant/research support from Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, and UCB. DDG has received grant/research support from and served as a consultant for AbbVie, Amgen, BMS, Celgene Corporation, Gilead, Janssen, Novartis, Pfizer, and UCB. CJE has received grant/research support from and served as a consultant for AbbVie, BMS, Celgene Corporation, Janssen, Pfizer, Roche, Samsung, Sanofi, and UCB. GS has received grant/research support from and served as a consultant for Abbott, Celgene Corporation, Roche, and UCB. BG, ND, LT, and MP are employees of Celgene Corporation. PJM has received grant/research support from and served as a consultant for Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Genentech, Janssen, Novartis, Pfizer, and UCB, and has served on speakers bureaus for Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, and UCB.
Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Figures
References
- Kavanaugh A, Mease PJ, Gomez-Reino JJ, Adebajo AO, Wollenhaupt J, Gladman DD, et al. Treatment of psoriatic arthritis in a phase 3 randomized, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. 2014;73(6):1020–1026. doi: 10.1136/annrheumdis-2013-205056.
- Cutolo M, Myerson GE, Fleischmann R, Liote F, Diaz-Gonzalez F, Van den Bosch F, 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(9):1724–1734. doi: 10.3899/jrheum.151376.
- Edwards CJ, Blanco FJ, Crowley J, Birbara CA, Jaworski J, Aelion 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(6):1065–1073. doi: 10.1136/annrheumdis-2015-207963.
- Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665–2673. doi: 10.1002/art.21972.
- Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38(6):727–735. doi: 10.1002/art.1780380602.
- El Miedany Y. Recent developments in management of psoriatic arthritis. Curr Rheumatol Rev. 2005;1(1):9–19. doi: 10.2174/1573397052954154.
- Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, Landewe R, van ver Tempel H, Mielants H, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis. 2003;62(2):127–132. doi: 10.1136/ard.62.2.127.
- Mease PJ, Woolley JM, Bitman B, Wang BC, Globe DR, Singh A. Minimally important difference of health assessment questionnaire in psoriatic arthritis: relating thresholds of improvement in functional ability to patient-rated importance and satisfaction. J Rheumatol. 2011;38(11):2461–2465. doi: 10.3899/jrheum.110546.
- Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol. 1982;9(5):789–793.
- Mease P, Gladman D, Kavanaugh A, Nakasato P, Guerette B, Teng L, et al. Characterization of clinical benefits in subjects classified as ACR20 non-responders at week 104 of apremilast treatment: subanalysis of 3 long-term, phase III trials [abstract OP0309] Ann Rheum Dis. 2018;77(Suppl 2):201–202.
- Mease PJ, Gladman DD, Kavanaugh A, Nakasato P, Guerette B, Teng L, et al. Characterization of clinical benefits in subjects classified as ACR20 non-responders at week 104 of apremilast treatment: subanalysis of 3 long-term, phase III trials [abstract] Arthritis Rheumatol. 2017;69(Suppl 10):603.
- Gladman DD, Farewell VT, Nadeau C. Clinical indicators of progression in psoriatic arthritis: multivariate relative risk model. J Rheumatol. 1995;22(4):675–679.
Source: PubMed