Roflumilast for Oral Ulcers in Behçet's Disease and Recurrent Aphthous Stomatitis

ABSTRACT Oral aphthous ulcer in Behçet's disease (BD) and recurrent aphthous stomatitis (RAS) is a cause of discomfort for many patients, especially in cases refractory to colchicine or azathioprine. Roflumilast, a phosphodiesterase‐4 (PDE4) inhibitor, may be effective for treating refractory oral ulcers (OUs) in BD and RAS, especially in regions where apremilast is unavailable. In this study, we investigated the efficacy and safety profile of low‐dose roflumilast for refractory OUs in BD and RAS. This single‐center, single‐arm, retrospective observational study included 46 patients screened from the outpatient department from May 2023 to Dec 2023. During the 12‐week study period, the subjects received roflumilast at a dosage of 0.25 mg daily. For those experiencing adverse events (AEs) requiring adjustment, the dose was reduced to 0.125 mg. Objective clinical responses were evaluated as clinician‐assessed treatment categories (complete remission, partial response, or non‐response), based on the absence or presence of new OUs and symptom improvement. Subjective symptoms were evaluated through a patient‐reported questionnaire, and AEs were monitored through the protocol. At week 12, 71.7% of patients showed a positive response to roflumilast, with 30.4% achieving complete remission. AEs were reported in 76.1% of the 46 subjects with follow‐up visits, primarily gastrointestinal (71.7%) and neurological symptoms (17.4%). Among the cohort, 78.3% of patients tolerated roflumilast without discontinuation, including 15.2% with dose reduction, while 21.7% discontinued due to intolerable AEs. Roflumilast demonstrated rapid and sustained efficacy in reducing OUs in BD and RAS. Although AEs were frequent, they were generally tolerable and manageable. While the study has limitations, including its retrospective observational nature and small sample size, it suggests roflumilast as a potential treatment alternative for refractory OUs where apremilast is unavailable, deserving further research.