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The monoclonal antibody ustekinumab (Stelara), which targets interleukin (IL)-12 and IL-23, appeared to be effective for clearing oral ulcers in Behcet's disease in a multicenter open-label study conducted in France.

In a cohort of 30 patients with resistant oral ulcers, 60% of patients showed complete responses at week 12, with no oral ulcers, 33% had partial responses, and three had no response, according to David Saadoun, MD, PhD, of Sorbonne Université in Paris, and colleagues.

And after a median follow-up of 48 weeks, 94% of patients had complete responses and 6% had partial responses, while none of the patients continued to have no response, the investigators reported online in .

Behcet's disease is a vasculitis affecting the mucocutaneous tissues, with additional manifestations in the joints, eyes, vasculature, and central nervous system. Treatment with colchicine is recommended, although the evidence for efficacy on oral ulcers is unclear. Immunosuppressants including azathioprine, thalidomide, and tumor necrosis factor inhibitors have been tried, but have been associated with potentially severe adverse events. "There is still an unmet need for an effective, safe, and well-tolerated treatment for the mucocutaneous manifestations of Behcet's disease," the investigators wrote.

Previous studies have shown that IL-23 plays a central role in the differentiation of Th17 lymphocytes, which are involved in the pathogenesis of Behcet's disease. These cytokines, along with Th1 lymphocytes, also have been shown to correlate with disease activity, and genome-wide association studies have linked IL-23 receptor polymorphisms with Behcet's disease.

"Taken together, these data provide a strong rationale for the use of ustekinumab in Behcet's disease," Saadoun and colleagues stated.

Accordingly, from 2014 to 2018 they recruited patients who had at least two oral ulcers despite treatment with colchicine. Participants were given 90 mg of ustekinumab subcutaneously at weeks 0 and 4 and then every 12 weeks, but the interval between doses could be shortened in patients experiencing a loss of efficacy towards the end of the interval (end-of-dose effect).

Participants were allowed to continue stable doses of colchicine, prednisone, and other immunosuppressive agents.

Patients' mean age was 39, disease duration averaged 8 years, and slightly more than half were men.

Disease manifestations other than oral ulcers included a history of genital ulcers in 90% of patients, joint involvement in 73%, pseudo-folliculitis in 50%, deep vein thrombosis in 20%, uveitis in 20%, and central nervous system involvement in 13%.

At the time of study enrollment, joint manifestations were present in 53% of patients, with a median tender joint count of six, and genital ulcers were present in 33%. Median Behcet's Syndrome Activity Score (BSAS) was 70 out of a possible score of 100.

Prednisone was being taken by 53% of participants, with a median daily dose of 11 mg, and half also continued with colchicine. One patient with pyoderma gangrenosum was also receiving tocilizumab (Actemra) and another with a heart allograft was being given mycophenolate mofetil (CellCept) and everolimus (Afinitor).

At week 12, the median number of oral ulcers had declined from two to zero (P<0.0001).

Also at week 12, only 10% of patients still had genital ulcers, 30% reported arthralgia, and the median BSAS had fallen from 70 to 17.5 (P<0.0001). Three patients (19%) had stopped taking steroids.

At the end of follow-up, which ranged from 6 to 16 months, only one patient still had a genital ulcer, and four continued to experience arthralgia. One patient who had been on morphine for arthralgia was able to stop, and 37% of patients on prednisone at baseline were no longer taking steroids. For those remaining on prednisone, the median daily dose was 7.5 mg.

Adverse events were reported by 23% of patients, with the most common being a headache. None of the adverse events were considered serious.

At the end of follow-up, 87% of patients were still taking ustekinumab. One patient had withdrawn because of a headache, and three because of a Behcet's flare. End-of-dose effects were seen in four patients, and shortening the between-dose interval was effective, similar to what has been seen for ustekinumab in other conditions such as Crohn's disease.

"In conclusion, ustekinumab seems to be effective and safe to treat Behcet's disease patients with colchicine-resistant oral ulcerations," the investigators wrote. "Further prospective placebo-controlled studies are warranted."

Limitations of the study, the team said, included the open-label design and lack of placebo control.

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