The combination of calcineurin inhibitor with ustekinumab is effective and well-tolerated among patients with steroid-resistant acute severe ulcerative colitis (ASUC), according to study results published in Clinical Gastroenterology and Hepatology.

The multicenter, retrospective study included 10 patients who were hospitalized with ASUC. All participants received an initial infusion of ustekinumab (6 mg/kg), followed by 90 mg subcutaneously every 8 weeks. After 7 days of intravenous (IV) calcineurin inhibitor (ciclosporin 2 mg/kg/d initially, with a blood concentration target of 150 to 250 ng/mL, tacrolimus at 0.05 mg/kg), clinical responders were switched orally with the same blood concentration target. A calcineurin inhibitor administered as bridge therapy was withdrawn within the first 3 months after inclusion.

Study endpoints included clinical response, clinical remission, and biochemical remission at 6 months after inclusion, colectomy free-survival, survival without ustekinumab discontinuation, and safety.


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Participants’ median age was 32 years, and 8 were women.

The median time between ustekinumab initiation and withdrawal of the calcineurin inhibitor was 45 (IQR, 45-60) days. The median time between initiating the calcineurin inhibitor and ustekinumab was 22 (IQR, 6-60) days.

At 6 months, no participants had a colectomy. The median partial Mayo score and C-reactive protein levels significantly decreased (10.6 vs 1.0; P =.005) and 17.5 (IQR, 4.1-38.8) mg/L vs 2.3 (IQR, 1.7-3.2) mg /L (P =.02), respectively.

A patient failed to obtain both clinical response and remission, and 1 patient continued on a steroid at 6 months. After a median follow-up of 9 months (IQR, 5-11), 1 patient discontinued ustekinumab owing to treatment failure. Also, 2 patients required ustekinumab dose optimization after 3 months owing to lack of efficacy. Tolerance to treatment was good, with 1 case of alopecia occurring.

Study limitations included the limited sample of participants, and the follow-up was less than 1 year.

“…[T]he sequence of treatment with induction calcineurin inhibitor followed by maintenance treatment with ustekinumab appears to be effective and well-tolerated,” the study authors wrote. “These encouraging data have to be confirmed in larger cohorts of patients.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Veyrard P, Pellet G, Laharie D, Nachury M, Juillerat P, Roblin X. Efficacy of induction therapy with calcineurin inhibitors in combination with ustekinumab for acute severe ulcerative colitis. Clin Gastroenterol Hepatol. Published online March 17, 2022. doi:10.1016/j.cgh.2022.03.008