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. 2023 Sep;24(5):809-820.
doi: 10.1007/s40257-023-00783-7. Epub 2023 Jun 14.

Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behçet's Syndrome

Philip J Mease  1 , Gülen Hatemi  2 , Maria Paris  3 , Sue Cheng  3 , Peter Maes  3 , Wendy Zhang  3 , Rebecca Shi  3 , Andrea Flower  3 , Hernan Picard  3 , Linda Stein Gold  4
Affiliations

Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behçet's Syndrome

Philip J Mease et al. Am J Clin Dermatol. 2023 Sep.

Abstract

Background: Since US FDA approval in 2014, apremilast has consistently demonstrated a favorable benefit-risk profile in 706,585 patients (557,379 patient-years of exposure) worldwide across approved indications of plaque psoriasis, psoriatic arthritis, and Behçet's syndrome; however, long-term exposure across these indications has not been reported.

Objective: The aim of this study was to conduct a pooled analysis of apremilast data from 15 clinical studies with open-label extension phases, focusing on long-term safety.

Methods: We analyzed longer-term safety and tolerability of apremilast 30 mg twice daily across three indications for up to 5 years, focusing on adverse events of special interest, including thrombotic events, malignancies, major adverse cardiac events (MACE), serious infections, and depression. Data were pooled across 15 randomized, placebo-controlled studies and divided into placebo-controlled or all-apremilast-exposure groups. Treatment-emergent adverse events (TEAEs) were assessed.

Results: Overall, 4183 patients were exposed to apremilast (6788 patient-years). Most TEAEs were mild to moderate in the placebo-controlled period (96.6%) and throughout all apremilast exposure (91.6%). TEAE rates of special interest were similar between treatment groups in the placebo-controlled period and remained low throughout all apremilast exposure. Exposure-adjusted incidence rates per 100 patient-years during all apremilast exposure were MACE, 0.30; thrombotic events, 0.10; malignancies, 1.0; serious infections, 1.10; serious opportunistic infections, 0.21; and depression, 1.78. Safety findings were consistent across indications and regions. No new safety signals were identified.

Conclusions: The incidence of serious TEAEs and TEAEs of special interest was low despite long-term exposure, further establishing apremilast as a safe oral option for long-term use across indications with a favorable benefit-risk profile.

Clinical trial registration: NCT00773734, NCT01194219, NCT01232283, NCT01690299, NCT01988103, NCT02425826, NCT03123471, NCT03721172, NCT01172938, NCT01212757, NCT01212770, NCT01307423, NCT01925768, NCT00866359, NCT02307513.

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Conflict of interest statement

Philip J. Mease: AbbVie, Amgen Inc., Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, and UCB—grant/research support and consultant; Boehringer Ingelheim, GlaxoSmithKline—consultant; AbbVie, Amgen Inc., Eli Lilly, Janssen, Novartis, Pfizer, and UCB—speakers bureau. Gülen Hatemi: AbbVie, Amgen Inc., and Celgene Corporation—grant/research support; AbbVie, Boehringer Ingelheim, Novartis, and UCB Pharma—speaker. Maria Paris, Sue Cheng, Peter Maes, Wendy Zhang, Rebecca Shi, Andrea Flower, Hernan Picard: Amgen Inc.—employees and stockholders. Linda Stein Gold: AbbVie, Amgen, Arcutis, Celgene Corporation, Dermira, Dermavant, Eli Lilly, Galderma, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi Genzyme, UCB, and Valeant—honoraria, grants, and/or research funding as a speaker, investigator, and/or advisory board member.

References

    1. Otezla [package insert]. Thousand Oaks, CA: Amgen, Inc.; 2021. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/O....
    1. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83(12):1583–1590. doi: 10.1016/j.bcp.2012.01.001. - DOI - PubMed
    1. US FDA. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. 2021. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warn.... Accessed 10 Dec 2021.
    1. European Medicines Agency. Otezla Summary of Opinion (post authorisation). 2020. https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summ.... Accessed 20 April 2020.
    1. European Medicines Agency. Otezla EPAR summary for the public. 2015. https://www.ema.europa.eu/en/documents/overview/otezla-epar-summary-publ.... Accessed 10 Dec 2021.

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