RESUMO
BACKGROUND AND AIMS: Ustekinumab (UST) is an effective biologic for treatment of inflammatory bowel disease (IBD). However, some patients treated with UST have suboptimal clinical response with standard dosing. The aims of this study were to determine the effectiveness of UST dose intensification (DI), identify factors associated with DI, cumulative incidence of DI and persistence of UST among treated patients. METHODS: Clinical data of patients with Crohn's disease (CD) and ulcerative colitis (UC) who received UST from September 2017 to October 2022 in Singapore General Hospital were collected. Primary outcome was defined as achieving corticosteroid-free clinical remission, biochemical remission, endoscopic healing and/or transmural healing (CD). Statistical analysis was performed to identify factors, which are predictive of UST DI and effectiveness of UST DI. RESULTS: Forty-two patients (34 CD and 8 UC) underwent UST DI to either 6-weekly (n = 19, 45.2%) or 4-weekly (n = 23, 35.9%) and the median time to intensification was 31.1 weeks (17.8-65.7). Presence of perianal disease in CD (HR 4.9; 1.47-16.4) was associated with DI. After DI, 16 (38%) patients achieved primary outcome by week 52. The overall drug persistence rates at 1 year and 2 years were 75.7% (95% CI 62.9-84.6) and 63.5% (95% CI 49.9-74.3), respectively. CONCLUSION: Two third of IBD patients underwent DI while on UST treatment and the median time to DI was about 6 months after induction. CD patients with perianal disease is more likely to undergo DI. More than one third of dose-intensified patients achieved remission by week 52.
RESUMO
OBJECTIVE: Preventing the postoperative recurrence (POR) of Crohn's disease (CD) poses a significant challenge to clinicians. With the advent of biologics, various studies have observed a reduction of recurrence after surgery. Hence, we performed a systematic review and meta-analysis to identify the rate of POR at different time points in the era of biologic use. METHODS: We performed a literature search using Medline and Embase databases for studies investigating biologics in preventing the POR of CD. Data were extracted, and a single-arm meta-analysis with generalized linear mixed model and Clopper-Pearson method for confidence interval (CI) was performed to identify endoscopic, clinical and surgical recurrence rates at 6 months and 1, 2 and 5 years postoperatively. RESULTS: Altogether 24 studies were included in the meta-analysis. The endoscopic, clinical and surgical POR rate with the use of anti-tumor necrosis factor (TNF)-α agents at 1 year was 21.72% (95% CI 16.28%-28.37%), 13.06% (95% CI 8.18%-18.92%) and 3.76% (95% CI 1.37%-9.91%), respectively. The 5-year recurrence rate was 84.21% (95% CI 72.35%-91.57%) and 17.49% (95% CI 9.17%-30.80%) for endoscopic and surgical recurrence, respectively. Subgroup analyses at 1 year for the type of anti-TNF-α agent or the timing of initiation after surgery showed no significant difference in endoscopic, clinical and surgical recurrence rates. CONCLUSIONS: Anti-TNF-α agents are effective at preventing clinical, endoscopic and surgical POR of CD. The timing of initiating biological therapy after surgery has no significant effect on the rate of POR. The efficacy of infliximab and adalimumab for postoperative recurrence prevention is similar.