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)

• Published in: Journal of the American Academy of Dermatology Vol. 77; no. 2; pp. 310 - 317.e1
• Main Authors: Crowley, Jeffrey, MD, Thaçi, Diamant, MD, Joly, Pascal, MD, Peris, Ketty, MD, Papp, Kim A., MD, PhD, Goncalves, Joana, MD, Day, Robert M., PhD, Chen, Rongdean, PhD, Shah, Kamal, MD, Ferrándiz, Carlos, MD, Cather, Jennifer C., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2017; Elsevier
• Subjects: Adult; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; apremilast; Cardiovascular Diseases - epidemiology; clinical trial; Depression - epidemiology; Dermatology; Diarrhea - chemically induced; ESTEEM; Female; Headache - chemically induced; Human health and pathology; Humans; Immunology; Immunotherapy; Incidence; Life Sciences; Male; Middle Aged; Nasopharyngitis - chemically induced; Nausea - chemically induced; Neoplasms - epidemiology; phosphodiesterase 4 inhibitor; psoriasis; Psoriasis - drug therapy; psoriatic arthritis; Respiratory Tract Infections - chemically induced; Rhumatology and musculoskeletal system; safety; Santé publique et épidémiologie; Suicide, Attempted - statistics & numerical data; Tension-Type Headache - chemically induced; Thalidomide - adverse effects; Thalidomide - analogs & derivatives; Time Factors; clinical trial; Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis; GI; AE; EAIR; PDE4; tuberculosis; adverse event; apremilast; TB; ESTEEM; gastrointestinal; exposure-adjusted incidence rate; phosphodiesterase 4; psoriasis; safety; phosphodiesterase 4 inhibitor; psoriatic arthritis
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2017.01.052

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.