A novel selective phosphodiesterase 4 (PDE4) inhibitor, mufemilast, significantly reduced oral ulcer burden, relieved pain, and increased ulcer-free remission rates in patients with Behçet’s syndrome (BS), according to findings published in the Annals of the Rheumatic Diseases. The phase 2 randomized trial also demonstrated an acceptable safety profile, supporting the potential of mufemilast as a new treatment option for mucocutaneous manifestations of the disease.
Behçet’s syndrome is a chronic multisystem inflammatory vasculitis characterized by recurrent oral ulcers that can cause considerable pain and impair quality of life. Although colchicine and the PDE4 inhibitor apremilast are recommended as first-line therapies for mucocutaneous disease, treatment may be limited by gastrointestinal adverse effects, and disease relapse remains common in some patients. Mufemilast, a next-generation selective PDE4 inhibitor, has shown potent anti-inflammatory activity in preclinical studies and is being investigated as an alternative therapeutic option.
The multicenter, randomized, placebo-controlled phase 2 trial enrolled 90 patients with Behçet’s syndrome diagnosed according to the 2013 International Criteria for Behçet’s Disease who had active oral ulcers. Participants were randomly assigned to receive mufemilast 45 mg (n = 29), mufemilast 60 mg (n = 31), or placebo (n = 30) twice daily for 12 weeks.
The primary endpoint was the area under the curve (AUC) for oral ulcer count from baseline to week 12. Compared with placebo, both mufemilast doses significantly reduced oral ulcer burden. The least-squares mean differences in AUC₀–₁₂ were −104.8 (95% confidence interval [CI], −156.3 to −53.2; P < .001) for the 45 mg dose and −142.5 (95% CI, −192.4 to −92.7; P < .001) for the 60 mg dose.
In addition to reducing ulcer counts, mufemilast significantly improved visual analogue scale pain scores and shortened the time to ulcer-free remission compared with placebo (P < .001). The higher 60 mg dose generally demonstrated greater efficacy than the 45 mg dose.
Treatment was well tolerated. PDE4-related adverse events were generally mild, transient, and resolved spontaneously. Discontinuation rates were low, occurring in 7% of patients in each mufemilast group compared with 3% in the placebo group. Importantly, no drug-related serious adverse events were reported during the study.
The investigators concluded that mufemilast effectively reduced oral ulcer burden, alleviated pain, and accelerated ulcer healing in patients with Behçet’s syndrome while maintaining an acceptable safety profile. Ongoing phase 3 studies and long-term follow-up are expected to further define the efficacy and safety of mufemilast and clarify its role in the management of Behçet’s syndrome.
References
- Liu T, Li C, Zheng W, Tang J, et al. Efficacy and safety of mufemilast in patients with Behçet’s syndrome: a phase 2 randomised clinical trial. Ann Rheum Dis. 2026 Jul;85(7):1425-1435.
- Li X, Wu X, Huo A, Zeng G, Jones R, Chen R, Wang H. Safety, Tolerability, and Pharmacokinetics of Mufemilast, a PDE4 Inhibitor, in Healthy Participants: A First-in-Human Phase 1 Study. Clin Pharmacol Drug Dev. 2026 Jan;15(1):e70005.