Thalidomide therapy for refractory mucosal disease: benefit and risks over 10 years

Background The immunomodulatory and antiangiogenic effects of thalidomide have been demonstrated in a number of refractory ulcerative oromucosal conditions, including recurrent aphthous stomatitis (RAS), Behcet disease, erythema multiforme (EM), erosive lichen planus, and orofacial granulomatosis (OFG). Thalidomide acts by modulating the inflammatory cascade, interacting with various cytokines, including tumor necrosis factor-α, interleukin 10, and cyclooxygenase 2. Despite its efficacy, thalidomide is associated with a number of risks, including peripheral neuropathy, thromboembolic disease, and embryofetal toxicity, which limit its clinical use. Methods A retrospective review of the clinical database of the Oral Medicine Department at the Royal National ENT and Eastman Dental Hospitals, UCLH, London, UK, was undertaken to identify patients prescribed thalidomide between 2009 and 2019. Results Sixteen patients (9 men and 7 women) with a mean age of 46 years (range, 20-66 years) were identified in this cohort. Clinical diagnoses included RAS (n = 10), human immunodeficiency virus (HIV)-related oral ulceration (n = 3), EM (n = 2), and OFG (n = 1). All patients, with the exception of HIV-related cases, had proved refractory to systemic corticosteroids and/or immunosuppressive therapy. Patients were treated for a mean of 50 months (range, 1-120 months) with doses ranging from 50 mg every 3 days to 100 mg daily. A complete remission (CR) rate of 56% was noted in this cohort, with CR defined as complete clearing of mucosal disease within 1 month of treatment onset and maintenance of this CR during the second month of treatment. All patients underwent a baseline sensory nerve action potential test before initiating thalidomide. Five of 16 patients subjectively reported transient peripheral neuropathy. There was objective evidence of mild length-dependent axonal sensory neuropathy in 2 of 16 patients, with treatment cessation occurring in an isolated case due to persistent neuropathy. Conclusions Within this cohort, thalidomide demonstrated a favorable efficacy/safety ratio with long-term use. It remains a viable treatment option for cases of refractory oral ulceration. Given the history of adverse effects associated with thalidomide, informed consent with regard to embryofetal toxicity and contraceptive counseling are pivotal to safe prescribing. Counseling with respect to other common adverse effects, including peripheral neuropathy and venous and arterial thromboembolism, is mandatory, and these adverse effects need to be understood.