Citation

Mease PJ, Gladman DD, Gomez-Reino JJ, Hall S, Kavanaugh A, Lespessailles E, Schett G, Paris M, Delev N, Teng L, Wollenhaupt J. ACR Open Rheumatol. 2020; 2(8): 459-470.

Copyright

(Copyright © 2020, John Wiley and Sons)

DOI

10.1002/acr2.11156

PMID

unavailable

Abstract

OBJECTIVE: Psoriatic arthritis (PsA) requires long-term treatment, yet safety concerns and monitoring requirements make maintenance a challenge. This analysis of pooled Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) 1, 2, and 3 data describes 3-year apremilast safety and tolerability in PsA.

METHODS: Patients with active PsA were randomized (1:1:1) to placebo, apremilast 30 mg twice daily, or apremilast 20 mg twice daily. Placebo patients were re-randomized to apremilast 30 mg twice daily or 20 mg twice daily at week 16 (early escape) or 24. Double-blind treatment continued to week 52; patients could continue apremilast during an open-label, long-term treatment phase.

RESULTS: In total, 1493 patients received at least one dose of study medication and were included in the safety population (placebo: n = 495; apremilast 30 mg: n = 497; apremilast 20 mg: n = 501). Among patients receiving apremilast, 53.2% (767/1441) completed 3 years of treatment. Greater rates of adverse events (AEs) were reported with apremilast (61.1%; exposure-adjusted incidence rate [EAIR]/100 patient-years, 265.1) versus placebo (47.5%; EAIR/100 patient-years, 200.7) in the placebo-controlled period. During weeks 0 to ≤52, the most common AEs occurring in apremilast-exposed patients were diarrhea (13.9%; EAIR/100 patient-years, 18.6), nausea (12.3%; EAIR/100 patient-years, 16.0), headache (9.4%; EAIR/100 patient-years, 12.1), upper respiratory tract infection (9.1%; EAIR/100 patient-years, 11.5), and nasopharyngitis (6.2%; EAIR/100 patient-years, 7.7). Most AEs were mild/moderate with apremilast exposure ≤156 weeks. Rates of depression remained low (EAIR/100 patient-years, 1.8). Major adverse cardiac events (EAIR/100 patient-years, 0.5), malignancies (EAIR/100 patient-years, 0.9), and serious opportunistic infections (EAIR/100 patient-years, 0.0) were infrequent over the 3-year exposure period. Discontinuation rates due to AEs were low (<7.5%) across all apremilast-exposure periods. Incidences of clinically meaningful abnormalities in postbaseline laboratory values was low; most values returned to baseline levels with continued treatment and without intervention.

CONCLUSION: Apremilast demonstrated a favorable safety profile and was well tolerated up to 156 weeks. © 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

Language: en

Keywords

adult; human; female; male; incidence; depression; randomized controlled trial; suicide attempt; heart failure; C reactive protein; comorbidity; major clinical study; controlled study; double blind procedure; headache; phase 3 clinical trial; middle aged; drug safety; cerebrovascular accident; nonsteroid antiinflammatory agent; drug efficacy; diarrhea; drug tolerability; nausea; multicenter study; hypercholesterolemia; corticosteroid; hypertension; alanine aminotransferase; aspartate aminotransferase; creatinine; leukocyte count; calcium channel blocking agent; brain ischemia; Article; methotrexate; gastroesophageal reflux; Clinical Global Impression scale; prednisone; leflunomide; psoriatic arthritis; salazosulfapyridine; rhinopharyngitis; neutrophil count; upper abdominal pain; tumor necrosis factor; Psoriasis Area and Severity Index; sudden cardiac death; DAS28; apremilast