Ustekinumab Safe, Effective for Refractory Crohn Disease as Short- and Long-Term Therapy

Researchers evaluated the safety and efficacy profile of short- and long-term treatment with ustekinumab for patients with Crohn disease.

Ustekinumab is safe and effective as short- and long-term treatment in patients with refractory Crohn disease (CD), according to study findings published in Inflammatory Bowel Diseases.

The retrospective, noninterventional SUSTAIN study included patients who were aged 18 years and older, had active CD (Harvey-Bradshaw Index >4), had received at least 1 initial dose of intravenous ustekinumab 6 months or more before the study, and were followed up by gastroenterologists in the hospital setting. The study was conducted in 61 hospitals in Spain.

The primary outcome was the retention rate of ustekinumab from the beginning of treatment to the last recorded dose.

A total of 463 patients (mean age, 47.1±13.4 years; mean age at diagnosis, 33.4±14.5 years; 50.1% women) were included. Study participants’ mean disease duration was 14.1±9 years, and their mean time until ustekinumab initiation was 12.6±9 years. More than 96% of participants had previously used biologics, most frequently adalimumab and infliximab.

At a median follow-up of 15.5 months, 356 patients (76.9%; 95% CI, 72.8%-80.7%) were still receiving ustekinumab and 107 (23.1%) had discontinued. The incidence of ustekinumab discontinuation was 18.4% per patient-year of follow-up.

Multivariate analysis showed that previous intestinal surgery and concomitant treatment with steroids were associated with an increased risk for ustekinumab discontinuation, and a maintenance schedule of once every 12 weeks was associated with a reduced risk.

Among the cohort, 44.0% and 56.1% of patients achieved clinical remission at weeks 8 and 16, respectively. In addition, 57.6% of participants reached a clinical response at week 8 and 70.2% at week 16.

Among the patients who achieved clinical remission at week 16, the median time of follow-up was 15.7 (IQR, 12.9-19.0) months. The patients also had a median time to loss of response (LoR) of 11.1 (IQR, 7.1-14.7) months, and the incidence of LoR was 29.7% per patient-year of follow-up. At 6, 12, and 18 months, the probability of sustaining remission was 84%, 74%, and 66%, respectively.

A total of 50 adverse events (30.3%) were reported in 39 (8.4%) patients, and 4 of these events were severe. The adverse events resulted in temporary interruption of treatment in 19.6% of patients and treatment suspension in 17.9%.

Study limitations included the retrospective design and potential for missing data in clinical records. Also, the researchers could not evaluate mucosal healing or properly assess the effect of exposure to biologic agents on the effectiveness of ustekinumab.

“To our knowledge, our study has the largest cohort and one of the longest follow-up periods among the published real-world studies of refractory CD patients treated with ustekinumab, including a total of 463 patients and a follow-up of up to 24 months,” the study authors noted. “Our results provide new data regarding the effectiveness and safety of ustekinumab in clinical practice.”

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.


Chaparro M, Baston-Rey I, Fernández-Salgado E, et al. Long-term real-world effectiveness and safety of ustekinumab in Crohn’s disease patients: the SUSTAIN study. Inflamm Bowel Dis. Published online February 15, 2022. doi:10.1093/ibd/izab357