Analysis Of Clinical Efficacy And Safety Of Ustekinumab In The Treatment Of Crohn’s Disease

Objective:We aimed to study the clinical efficacy and safety of Ustekinumab(UST)in patients with Crohn’s disease(CD),including clinical,endoscopic response and remission rates and changes in biochemical parameters.Methods:We collected retrospectively the clinical data in CD patients who received UST treatment in the inflammatory bowel disease(IBD)center of the First Affiliated Hospital of Dalian Medical University from August 2020 to December 2022.The baseline demographics and clinical data were collected.Clinical information including the Crohn’s disease activity index(CDAI),the simple endoscopic score for Crohn’s disease(SES-CD),laboratory parameters[C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),Body Mass Index(BMI),albumin(ALB),and hemoglobin(Hb)],perianal diseases and extraintestinal manifestations were recorded during every follow up.Clinical disease activity and the clinical efficacy of UST were assessed by the CDAI,and the endoscopic disease activity and efficacy of mucosal healing were assessed by the SES-CD.The observational parameters were the clinical,endoscopic remission and response rates at week 8 and week 32 post UST treatment.In addition,we also analyzed the changes in laboratory parameters between the baseline and week 8,week 32 of UST treatment,and the efficacy in patients with perianal diseases and extraintestinal manifestations.All the adverse events during the UST therapy were recorded in detail.Results:1.General clinical data:Thirty CD patients were enrolled in this study.There were13 male(43.3%)and 17 female(56.7%)patients,with a median age of 32.5(25.0,56.0)years and median disease duration of 15.0(6.0,30.0)months.According to the Montreal classification,ileocolonic diseases were documented in 17 patients(56.7%)and complex disease phenotype(B2-B3)were documented in 18 patients(60.0%).In total,6 patients(20.0%)had active perianal diseases,6 patients(20.0%)had extra-intestinal manifestations,24 patients were na?ve to biologicals and 6 patients were bio-experienced.At baseline,mild clinical disease activity was observed in 6 patients(20.0%)and moderate to severe clinical disease activity was observed in 24 patients(80.0%).2.Clinical and endoscopic efficacy:The CDAI scores were 308.5±96.3 at baseline,167.5±59.7 at week 8,and 152.6±63.5 at week 32.Compared with the baseline values,the CDAI scores decreased significantly after UST treatment(P<0.05).The clinical remission and response rates were 33.3%and 56.7%at week 8,43.3%and 80.0%at week 32.A total of 20 CD patients underwent the colonoscopy re-examinations.The SES-CD scores decreased significantly after UST treatment,from 9.8±5.4 at baseline to5.4±4.1 at week 32(P<0.05).The endoscopic remission and response rates were 20.0%and 55.0%at week 32.3.Laboratory parameters:(1)CRP and ESR:The median CRP levels were 22.6(9.1,58.2)mg/L at baseline,5.6(3.13,15.4)mg/L at week 8,and 5.8(3.13,15.2)mg/L at week 32.Compared with the baseline values,the median CRP levels at week 8 and week 32 decreased significantly after UST treatment(P<0.05).Compared with the baseline values,the median ESR levels decreased,but there were no significant differences in ESR levels(P>0.05).(2)Hb and ALB:The mean Hb levels were 105.9±27.6 g/L at baseline,119.4±20.8 g/L at week 8,and 123.7±18.7 g/L at week 32.Compared with the baseline values,the mean Hb levels at week 8 and week 32 increased significantly after UST treatment(P<0.05).The mean ALB levels were 34.9±6.1 g/L at baseline,40.6±4.5 g/L at week8,and 41.2±4.3 g/L at week 32.Compared with the baseline values,the mean ALB levels at week 8 and week 32 increased significantly after UST treatment(P<0.05).(3)BMI and weight:The mean BMI levels were 20.6±4.5 kg/m~2 at baseline,21.3±4.1 kg/m~2 at week 8,and 21.9±3.8 kg/m~2 at week 32.Compared with the baseline values,the mean BMI levels at week 8 and week 32 increased significantly after UST treatment(P<0.05).The mean weight levels were 60.2±13.7 kg at baseline,62.2±12.7 kg at week 8,and 64.2±12.8 kg at week 32.Compared with the baseline values,the mean weight levels at week 8 and week 32 increased significantly after UST treatment(P<0.05).4.Perianal diseases and extraintestinal manifestations:A total of 6 patients had active perianal diseases,including perianal fistula in 5 patients and anal fissure in 1patient.After 32 weeks of UST therapy,4 patients(66.7%)responded to the therapy,2patients(33.3%)achieved fistula healing,and the patient with anal fissure achieved obvious reduction in perianal pain.6 CD patients had combined extraintestinal manifestations,including recurrent oral ulcers in 3 patients,arthritis in 2 patients,and pyoderma gangrenosum in 1 patient.All the extraintestinal manifestations were disappeared after UST treatment.5.Safety:We conducted a safety analysis in 30 patients with CD treated by UST treatment,and found that 3 patients experienced adverse events of zoster virus infection in 2 patients and skin rash in 1 patient.Tuberculosis infection,sepsis,severe infections,or other adverse events were not observed during the follow-up period.And the incidence rate of adverse events was 10.0%.Conclusions:UST therapy could achieve satisfactory efficacy with high clinical and endoscopic remission rates in patients with CD.Such therapy could also relieve the perianal diseases and extraintestinal manifestations,reduce the inflammatory parameters,improve the anemia,and hypoalbuminemia states.Overall,UST is an effective and safe therapeutic option for patients with CD.