Efficacy and safety of ustekinumab in patients with Crohn’s disease in real clinical practice

Background. Currently, there is a need to develop new types of drugs for the treatment of patients with Crohn's disease (CD), which would make it possible to achieve rapid induction of clinical remission, reduce the risk of immunogenicity and other side effects, and reduce the number of side effects. Objective. Retrospective assessment of the efficacy and tolerability of therapy with ustekinumab (UST) in patients with moderate-to-severe CD in real clinical practice. Methods. To assess the efficacy and safety of UST, we included in the study 11 patients with CD who received an induction course of therapy with this drug starting from January 2020. There were 18.2% of men, 81.8% of women, mean age was 34,4±6.8 years, disease duration - 8.4±3.2 years. The vast majority of patients (90.9%) received immunosuppressants and glucocorticosteroids. All patients were previously treated with with genetically engineered biological drugs (GIBD). Results. After induction of UST, 10 patients during the first week showed a decrease in the Crohn's disease activity index (CDAI) by more than 100 points. In 6 (54.5%) patients at 6 weeks of therapy, clinical remission according to CDAI was noted, 4 (36.4%) patients achieved clinical response rates, and 1 (9.1%) patient did not show any positive dynamics. In 2 of 6 patients who achieved clinical remission by the 15th week from the start of the UST administration, there was an increase in the stool frequency with type 6 stool consistency according to the Bristol scale. In this regard, it was decided to reduce the intervals between repeated injections of UST from 12 to 8 weeks. After that, the clinical picture of the disease improved. After 12 weeks, clinical remission was achieved in 8 (72.7%) patients, the clinical response persisted in 2 (18.2%) CD patients. Most patients with clinical remission at 12 weeks have also achieved mucosal healing. At week 12, endoscopic examination was performed in 6 patients, 5 (45.4%) of them were diagnosed with endoscopic remission (SES-CD <,4). After 12 weeks, in all patients who responded to UST therapy, CDAI decreased on average from 425.0±49.3 to 128.6±110.6 points, and the Crohn's disease endoscopic activity index - from 7.8±2.4 to 3.2±1.2points. At the same time, the C-reactive protein level decreased on average from 35.1±34.3 to 6.6±3.8 mg/L. Fecal calprotectin level decreased on average from 1382.0±474.2 to 405.0±47.3 pg/g. At the 48th week of the study, 10 patients were examined, 7 (63.6%) of whom had endoscopic remission (SES-CD <,4) and complete healing of lesions of the intestinal mucosa. In 3 patients, complete clinical and endoscopic remission was not achieved, most of them previously received more than 3 GIBDs - 3 anti-TNF-а drugs registered in the Russian Federation for the treatment of CD, and an a4@7 integrin blocker. It should be noted that 10 (90.9%) patients who achieved clinical remission after the induction course of UST, maintained it by 48 weeks of follow-up by the time of completion of the analysis. Conclusion. This clinical observation of a small group of CD patients, as well as previous multicenter studies, demonstrated the high efficiency of UST in induction and maintenance therapy in a cohort of patients with moderate-to-severe CD resistant to disease-modifying agents and GIBD.

Crohn's disease, inflammatory bowel disease, ustekinumab