Apremilast Was Associated with an Acceptable Safety Profile in ESTEEM Trials

Toni Rizzo

doi:10.1177/155989771437002

Summary

Two phase 3 randomized controlled trials were performed to evaluate the safety and efficacy of oral apremilast (CC-10004) in patients with moderate to severe plaque psoriasis. This article discusses the safety analysis from the pooled data of the ESTEEM 1 [NCT01194219] and ESTEEM 2 trials [NCT01232283].

Skin Diseases
Dermatology Clinical Trials

Skin Diseases
Dermatology
Dermatology Clinical Trials

Two phase 3 randomized controlled trials were performed to evaluate the safety and efficacy of oral apremilast (CC-10004) in patients with moderate to severe plaque psoriasis. Kristian Reich, MD, Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany, presented the safety analysis from the pooled data of the ESTEEM 1 [NCT01194219] and ESTEEM 2 trials [NCT01232283].

Patients (n = 1255) with moderate to severe plaque psoriasis were randomized 2:1 to treatment with the selective phosphodiesterase 4 inhibitor apremilast (30 mg, BID; n = 836) or placebo (n = 419) for 16 weeks. At week 16, patients treated with placebo were switched to apremilast, and all patients received apremilast through week 32. At week 32, patients entered a randomized treatment withdrawal phase through week 52. Thus, a total of 1184 patients had received apremilast at 1 year. Adverse events (AEs) were assessed for weeks 0 to 16 (the placebo-controlled period) and weeks 0 to 52 (the apremilast exposure period). Baseline characteristics were similar between the placebo and apremilast groups.

Most AEs were mild to moderate in severity for all treatment durations. Long-term data did not indicate an increase in AEs, based on exposure-adjusted incidence rates (EAIRs) per 100 patient-years. The incidence of serious AEs was similar between the apremilast (2.0%) and placebo (2.6%) groups (Table 1).

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Table 1.

Overview of Adverse Events

The most frequently reported AEs in all treatment periods were diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension headache, and headache (Table 2). Discontinuations due to AEs were low for weeks 0 to 16 and did not increase with longer apremilast exposure, based on EAIRs per 100 patient-years.

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Table 2.

Adverse Events ≥ 5% in Any Treatment Group

No serious diarrhea or nausea AEs were reported in any treatment group for any treatment period. During the apremilast exposure period, discontinuation rates due to diarrhea or nausea were 0.9% and 1.4%, respectively. Diarrhea and nausea were mostly mild, with the highest incidence during the first 2 weeks of treatment. Rates of major and potential major adverse cardiac events, malignancies, and serious infections were similar between the groups.

At week 16, the mean change in weight from baseline was −1.51 kg with apremilast and +0.01 kg with placebo. At week 52, the mean change in weight from baseline was −1.99 kg with apremilast. Weight loss associated with apremilast did not lead to overt medical complications. There was no association between weight loss and diarrhea or nausea.

Based on EAIRs per 100 patient-years, there was no evidence of an increased incidence of depression or suicidality with longer apremilast treatment. At week 16, depression had occurred in 1.2% of patients treated with apremilast and 0.5% of patients treated with placebo; suicide was attempted by 1 patient (0.1%) treated with apremilast and was completed by 1 patient (0.2%) treated with placebo. No clinically relevant effects of apremilast on laboratory measurements were observed.

The investigators concluded that apremilast (30 mg, BID) demonstrated an acceptable safety profile and was generally well tolerated for > 52 weeks.

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