Background/Purpose: Apremilast, a PDE-4 inhibitor, is commonly indicated for patients with psoriasis as well as Behçet’s disease. Although this medication is generally well tolerated, numerous adverse events have been reported, and these are among the leading causes of treatment discontinuation. This study aims to identify and describe the most common adverse effects of apremilast and to explore their relationship with underlying comorbidities, particularly cardiovascular and gastrointestinal conditions, to support more personalized and appropriate treatment selection.

Methods: The United States Food and Drug Administration Adverse Event Report System (FAERS) was searched for adverse reactions related to apremilast use. Detailed analysis of cardiac arrhythmias (Tachycardia, bradycardia, atrial fibrillation, QRS complex abnormalities, QT interval abnormalities, bundle branch block (BBB), atrioventricular blocks (AV blocks) and supraventricular tachycardia (SVT)) and gastrointestinal disorders associated with the use of apremilast were reported. Data were reported as frequencies, percentages, and as reporting odds ratios (ROR) with a 95% confidence interval (95% CI).

Results: We analyzed 30,179,725 adverse event reports from the FAERS database, of which 133,748 were associated with the use of apremilast. Among these, 62.91% of the cases involved females, while 4.08% had an unspecified sex. The most reported reaction group among apremilast users was gastrointestinal disorders, documented in 48,652 reports.When gastrointestinal side effects were analyzed in more detail, diarrhea was the most frequently reported, occurring in 23,163 patients. Patients using apremilast had significantly higher reporting odds of diarrhea compared to users of other drugs (ROR 10.12; 95% CI: 9.98–10.27). Nausea was the second most reported gastrointestinal side effect (20,700 reports) (Figure 1), followed by abdominal discomfort (7,058 reports), with RORs of 6.91 and 11.29, respectively (Figure 2).In contrast, when evaluating apremilast for its association with cardiac arrhythmias, none were found to have significantly increased reporting odds compared to other drug users. However, among all arrhythmias reported, the most common were tachycardia (51.6%) and atrial fibrillation (43.0%) (Table 1).

Conclusion: This FAERS analysis reveals key findings on apremilast side effects. Cardiovascular issues like tachycardia and atrial fibrillation were reported but showed no significant outcomes, reassuring for cardiac comorbidities, though careful monitoring is advised. Gastrointestinal side effects, particularly diarrhea and nausea, were the most common. Pre-existing gastrointestinal and cardiovascular comorbidities should be considered, highlighting the need for early recognition and management of side effects to improve adherence. Further studies are needed to assess the impact of these adverse events on treatment discontinuation and disease control.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tolerability-of-apremilast-gastrointestinal-side-effects-dominate-while-cardiac-safety-remains-reassuring/