Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for ?156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2) - 14/12/17
, Diamant Thaçi, MD b, Pascal Joly, MD c, d, Ketty Peris, MD e, Kim A. Papp, MD, PhD f, Joana Goncalves, MD g, Robert M. Day, PhD g, Rongdean Chen, PhD g, Kamal Shah, MD g, Carlos Ferrándiz, MD h, Jennifer C. Cather, MD iAbstract |
Background |
Randomized, controlled trials demonstrated efficacy and safety of apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis.
Objective |
Assess long-term safety of oral apremilast in psoriasis patients.
Methods |
Safety findings are reported for 0 to ≥156 weeks from the Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2.
Results |
The 0 to ≥156–week apremilast-exposure period included 1184 patients treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to ≤52 weeks, the adverse events (AEs) that occurred in ≥5% of patients included diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache. From 0 to ≥156 weeks, no new AEs (affecting ≥5% of the population) were reported. AEs, serious AEs, and study drug discontinuations caused by AEs did not increase with long-term exposure. During the 0 to ≥156–week period, the rates of major cardiac events (exposure-adjusted incidence rate [EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years), depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100 patient-years) did not increase in comparison with the rates found during the 0 to ≤52–week period. No serious opportunistic infections, reactivation of tuberculosis, or clinically meaningful effects on laboratory measurements were reported.
Limitations |
This study had a high dropout rate (21% of patients ongoing >156 weeks); most were unrelated to safety concerns.
Conclusions |
Apremilast demonstrated an acceptable safety profile and was generally well tolerated for ≥156 weeks.
Le texte complet de cet article est disponible en PDF.Key words : apremilast, clinical trial, ESTEEM, phosphodiesterase 4 inhibitor, psoriasis, psoriatic arthritis, safety
Abbreviations used : AE, EAIR, ESTEEM, GI, PDE4, TB
Plan
| Funding sources: These studies were sponsored by Celgene Corporation. |
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| Conflicts of interest: Dr Crowley has received compensation as a speaker, consultant, and investigator for AbbVie, Amgen, Celgene Corporation, Eli Lilly, and Novartis. He has been an investigator for Merck, Maruho, Janssen, Pfizer, Regeneron, Sun, Boehringer Ingelheim, and Sandoz. Dr Thaçi has received research support from AbbVie, Almirall, Amgen, Astellas, Biogen-Idec, Boehringer Ingelheim, Celgene Corporation, Dignity, Eli Lilly, Forward Pharma, GlaxoSmithKline, LEO Pharma, Janssen-Cilag, Maruho, MSD, Mitsubishi Pharma, Novartis, Pfizer, Roche, and Sandoz and honoraria from AbbVie, Biogen-Idec, Celgene Corporation, Janssen, LEO Pharma, Pfizer, Roche-Posay, Novartis, and Mundipharma. He has acted as a consultant for AbbVie, Biogen-Idec, Celgene Corporation, Dignity, Galapagos, Maruho, Mitsubishi, Novartis, Pfizer, and XenoPort and sat on scientific advisory boards for AbbVie, Amgen, Biogen-Idec, Celgene Corporation, Eli Lilly, GlaxoSmithKline, LEO Pharma, Pfizer, Novartis, Janssen, Mundipharma, and Sandoz. Dr Joly has no financial relationships to disclose. Dr Peris has received honoraria as an advisory board member for Eli Lilly, LEO Pharma, MEDA, and Roche. Dr Papp has received research support from AbbVie, Allergan, Amgen, Anacor, Astellas, Baxalta, Biogen-Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene Corporation, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, Glenmark, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Merck, Merck Serono, Mylan, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis, Stiefel, Takeda, UCB, and Valeant. He has acted as a consultant for AbbVie, Akros, Allergan, Amgen, Anacor, Astellas, AstraZeneca, Baxalta, Baxter, Biogen-Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite BioPharma, Celgene Corporation, Celtic, Cipher, Dermira, Dow Pharma, Eli Lilly, Formycon, Forward Pharma, Funxional Therapeutics, Galderma, Genentech, Genexion, Glenmark, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, Lypanosys, MedImmune, Merck, Merck Serono, Mitsubishi Pharma, Mylan, Novartis, Novommune, Pan Genetics, Pfizer, Regeneron, Roche, Sanofi-Aventis, Stiefel, Sun Pharma, Takeda, UCB, Valeant, Vertex, and Xoma. He is on advisory boards for AbbVie, Amgen, Astellas, AstraZeneca, Baxter, Boehringer Ingelheim, Celgene Corporation, Eli Lilly, Galderma, LEO Pharma, Merck, Merck Serono, Novartis, Pfizer, Regeneron, Sanofi-Aventis, UCB, and Valeant. Dr Goncalves and Dr Chen are employees of Celgene Corporation. Dr Day and Dr Shah were employees of Celgene Corporation at the time of study conduct and own stocks, stock options, and/or restricted stock units in Celgene Corporation. Dr Ferrándiz has participated in advisory boards for AbbVie, Amgen, Celgene Corporation, Eli Lilly, Janssen, LEO Pharma, and Novartis. Dr Cather has received compensation as a speaker, consultant, and investigator for Actelion, AbbVie, Amgen, Celgene Corporation, Janssen, Eli Lilly, and Novartis. She has been an investigator for Boehringer Ingelheim, Merck, Pfizer, and Regeneron, and has participated in advisory boards for Actelion, Celgene Corporation, Eli Lilly, Janssen, and Novartis. |
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Vol 77 - N° 2
P. 310 - août 2017 Retour au numéro
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