Mufemilast offers ulcer relief for people with Behçet syndrome

medwireNews: Mufemilast significantly reduces oral ulcers in patients with Behçet syndrome compared with placebo, suggest findings from a phase 2 trial.

The researchers found that treatment with the selective phosphodiesterase (PDE)4 inhibitor significantly reduced ulcer count, alleviated pain, and accelerated ulcer healing relative to placebo.

They comment that, while there are FDA-approved first-line treatments for mucocutaneous lesions, such as colchicine and apremilast, “adverse events such as gastrointestinal side effects limit their use, and some patients may experience relapse after treatment.”

In the current study, “[m]ufemilast demonstrated a good safety profile without titration,” the investigators point out, and “PDE4-related side effects were transient and resolved spontaneously.”

A total of 90 patients with Behçet syndrome at 29 medical centers in China were randomly assigned to receive oral mufemilast, at a dose of 45 mg (n=29) or 60 mg (n=31), or placebo (n=30) twice daily for 12 weeks.

The patients all had active oral ulcers at the time of screening and at least two oral ulcers at the point they were randomly assigned to treatment. The mean number of ulcers was 3.5, and oral pain, assessed on a 100 mm visual analog scale (VAS), was 49, where higher scores indicate greater pain. The participants had a mean age of 40 years and 61% were women.

During treatment, the patients could continue to take oral and topical analgesics, as well as low-dose corticosteroids (<10 mg/day), as long as they had been taking them for at least 4 weeks before the trial and remained on the same dose throughout.

The primary efficacy outcome was the area under the curve (AUC) for the total number of ulcers from baseline to week 12. This endpoint was chosen “because it reflects the number of oral ulcers over time and more effectively captures the remitting and relapsing course of oral ulcers in [Behçet syndrome] than does the number of ulcers at a single time point,” the study authors explain.

The number of oral ulcers “declined rapidly” during mufemilast treatment and to a significantly greater degree than with placebo, say Zhanguo Li (Peking University People’s Hospital, Beijing, China) and colleagues. At 12 weeks, the least squares mean differences in the AUC for total ulcers versus placebo was  –104.8 and –142.5 for the patients taking mufemilast 45 mg and 65 mg, respectively.

The reduction in the mean number of oral ulcers from baseline to week 12 was 2.8 with mufemilast 45 mg and 2.9 with mufemilast 60 mg versus 1.6 with placebo. The mean reduction in pain on the VAS from baseline was a respective 42.2, 40.5, and 28.5. 

Moreover, the proportion of patients who achieved complete remission of ulcers by week 6 and remained ulcer free for the remaining 6 weeks was 28% and 39% in the mufemilast 45 mg and 60 mg groups, respectively, versus 3% in the placebo group.

The corresponding proportion of patients who were in complete remission at 12 weeks was 38% and 45% versus 17%, and the proportion remaining ulcer free after completing treatment was 35% and 52% versus 38%.

In all, five patients discontinued treatment due to adverse events (AEs), which were considered related to the study drug. These AEs were mild to moderate and included nausea, abdominal discomfort and retching, abdominal pain, vomiting and dizziness, and most resolved without treatment.

Treatment-emergent AEs were also “primarily mild and resolved spontaneously within the first week,” observe the researchers in the Annals of the Rheumatic Diseases, with the most frequent being PDE4-related nausea, headache, diarrhea, upper respiratory tract infection, and vomiting. There were no serious AEs.

The investigators note that they also intended to assess the effect of mufemilast on genital ulcers, skin lesions, and joint involvement, but the numbers of patients with these symptoms were too low.

The treatment effect on these symptoms as well as a longer follow-up on the safety and efficacy of the mufemilast is being conducted in an ongoing phase 3 study, they add.

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Ann Rheum Dis 2026; doi:10.1016/j.ard.2026.01.014