Ustekinumab IV Reinduction Efficacious in Crohn Disease for Sub-Optimal Response to Maintenance

Patients with Crohn disease (CD) who have partial or complete loss of response to maintenance ustekinumab may be responsive to intravenous reinduction of ustekinumab. These findings, from a multicenter, retrospective cohort study, were published in Journal of the Canadian Association of Gastroenterology.

Patients (N=65) with CD who had sub-optimal response or loss of response to maintenance ustekinumab and received intravenous reinduction were retrospectively reviewed for this study. The primary endpoint was the composite outcome of clinical remission with biochemical and/or endoscopic response. Clinical remission was defined as Harvey Bradshaw Index (HBI) score less than 5 with no corticosteroid use; biochemical remission as fecal calprotectin (FCP) less than 250 mg/g and/or C-reactive protein (CRP) in the standard normal range; endoscopic remission as simple endoscopic score for CD (SES-CD) less than 3; and clinical, biochemical, and endoscopic response as at least 50% decreases in HBI, FCP and CRP, and SES-CD score from baseline, respectively.

The patients had a median age of 38.0 (IQR, 24-44) years at reinduction; 62.9% were diagnosed at 17 to 40 years of age; 54.7% were women; 56.5% had ileocolonic disease; 40.3% had nonstricturing, nonpenetrating disease; 74% had 2 failed biologics; 53.1% had received initial subcutaneous ustekinumab induction; and the median time from ustekinumab induction and reinduction was 15 (IQR, 9-29) months.

Patients required reinduction due to loss of response (47.7%), sub-optimal response (40%), or unknown reason.

At a median of 14 weeks postreinduction, 89% remained on ustekinumab maintenance therapy. The patients who discontinued ustekinumab (n=7) had treatment failure.

The primary composite outcome was achieved by 31.0%.

In addition, among patients with sufficient data, 51.3% were in clinical remission, 10.3% had clinical response, 39.5% had a normalization of CRP, 10.5% had a 50% or higher reduction in CRP, 33.3% had a normalization of FCP, 16.7% had a 50%  or higher reduction in FCP, 30.8% were in endoscopic remission, and 30.8% had endoscopic response.

Stratified by disease behavior, 42.3% of patients with stricturing disease; 22.7% of patients with nonstricturing, nonpenetrating disease; and 16.7% of patients with penetrating disease achieved the primary composite outcome. A similar proportion of patients with perianal disease (30.4%) and nonperianal disease (31.4%) achieved the composite primary outcome.

For patients with prereinduction (n=35) and postreinduction (n=25) therapeutic drug monitoring data, ustekinumab concentrations increased from an average of 3.2±2.0 mg/mL prereinduction to 4.6±2.7 mg/mL postreinduction. The preinduction levels of ustekinumab did not differ significantly between patients who did and did not achieve the primary outcome (mean, 1.73 vs 3.01 mg/mL; P =.32), respectively.

The only safety signal of ustekinumab reinduction was a minor infusion reaction of facial erythema and dyspnea, in which the patient was able to complete the ustekinumab infusion at a lower infusion rate.

“Even in the setting of refractory Crohn’s disease, ustekinumab IV reinduction is a well-tolerated and effective option to induce response and remission in patients with partial response or loss of response to maintenance UST therapy,” the study authors wrote.

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