Clobetasol solution for oral cGvHD: A phase II trial

Results from a randomized, double-blind, placebo-controlled, phase II (NCT01557517) trial evaluating the efficacy and safety of clobetasol 0.05% oral solution in patients aged ≥12 years with moderate-to-severe oral chronic graft-versus-host disease (cGvHD) were published in Blood Advances by El Jurdi et al. The study consisted of an initial 14-day blinded phase comparing clobetasol vs placebo, followed by an open-label phase in which all patients received clobetasol for a total of 28 days. The primary endpoint was the percentage change in Schubert Oral Mucositis Rating Scale (S-OMRS) score from baseline to Day 28.

Key data: Among the 35 patients who completed 28 days of clobetasol treatment, mean S-OMRS scores improved by 66% from baseline (p < 0.0001) and the overall response rate (ORR) was 91.4% (complete response [CR], 20%; partial response [PR], 71.4%). At Day 14 of the blinded phase, mean S-OMRS scores were lower with clobetasol vs placebo (33.7 vs 45.5; p = 0.02); patient-perceived improvements in oral status also favored clobetasol (p = 0.03). Adrenal insufficiency was observed in 28 of 31 patients evaluated at Day 28, including 14 patients without prior supraphysiologic glucocorticoid exposure. Analysis of paired oral mucosal biopsies showed that clobetasol significantly reduced the frequency of all T cells, as well as non-T cells expressing cytoplasmic interleukin (IL)-17, accompanied by reduced salivary IL-6 and CXCL10. 

Key learning: In this trial, short-term treatment with clobetasol 0.05% oral solution demonstrated promising efficacy in patients with moderate-to-severe oral cGvHD; however, adrenal insufficiency was common. Further evaluation of clobetasol oral solution in larger randomized trials is warranted.