Fumery, Mathurin

SummaryBackgroundThere are limited data to inform positioning of agents for treating moderate‐severe Crohn's disease (CD).AimWe assessed comparative efficacy and safety of first‐line (biologic‐naïve) and second‐line (prior exposure to anti‐tumour necrosis factor [TNF]‐α) agents) biologic therapy for moderate‐severe CD, through a systematic review and network meta‐analysis, and appraised quality of evidence (QoE) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.MethodsWe identified randomised controlled trials (RCTs) in adults with moderate‐severe CD treated with approved anti‐TNF agents, anti‐integrin agents and anti‐IL12/23 agents, first‐line or second‐line, and compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of clinical remission; safety outcomes were serious adverse events and infections. Network meta‐analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities.ResultsNo head‐to‐head trials were identified. In biologic‐naïve patients, infliximab (SUCRA,0.93) and adalimumab (SUCRA,0.75) were ranked highest for induction of clinical remission (moderate QoE). In patients with prior anti‐TNF exposure, adalimumab (SUCRA, 0.91; low QoE, in patients with prior response or intolerance to anti‐TNF agents) and ustekinumab (SUCRA, 0.71) were ranked highest for induction of clinical remission. In patients with response to induction therapy, adalimumab (SUCRA, 0.97) and infliximab (SUCRA, 0.68) were ranked highest for maintenance of remission. Ustekinumab had lowest risk of serious adverse events (SUCRA, 0.72) and infection (SUCRA, 0.71; along with infliximab, SUCRA, 0.83) in maintenance trials.ConclusionIndirect comparisons suggest that infliximab or adalimumab may be preferred first‐line agents, and ustekinumab a preferred second‐line agent, for induction of remission in patients with moderate‐severe CD. Head‐to‐head trials are warranted.

SummaryBackgroundSubtotal or total colectomy or proctocolectomy with permanent ileostomy (TC‐PI) may be a treatment option for medically refractory colonic Crohn's disease (CD).AimTo perform a systematic review and meta‐analysis to evaluate the rate, risk factors and outcomes of CD recurrence after TC‐PI.MethodsIn a systematic review ending 31 March 2016, we identified 18 cohort studies (1438 adults) who underwent TC‐PI for colonic CD (median follow‐up, 7.4 years; interquartile range, 5.3–9.0). We estimated pooled rates [with 95% confidence interval (CI)] of clinical and surgical recurrence, and risk factors for disease recurrence.ResultsOn meta‐analysis, the risk of clinical recurrence after TC‐PI was 28.0% (95% CI, 21.7–35.3; 14 studies, 260/1004 patients), with a 5 and 10‐year median cumulative rate of 23.5% (range, 7–35) and 40% (range, 11–60) respectively. The risk of surgical recurrence was 16.0% (95% CI, 11.1–22.7; 10 studies; 183/1092 patients), with a 5 and 10‐year median cumulative rate of 10% (range, 3–29) and 18.5% (range, 14–34) respectively. The risk of clinical and surgical recurrence in patients without ileal disease at baseline was 11.5% (95% CI, 7.7–16.8) and 10.4% (95% CI, 4.5–22.5) respectively. History of ileal disease was associated with 3.2 times higher risk of disease recurrence (RR, 3.2; 95% CI, 1.8–5.6). Other inconsistent risk factors for disease recurrence were penetrating disease and young age at disease onset.ConclusionsSmall bowel clinical recurrence occurs in about 28% of patients after total colectomy with permanent ileostomy for colonic Crohn's disease. Disease recurrence risk is 3.2 times higher in patients with history of ileal disease, and continued medical therapy may be advisable in this population. In patients without ileal inflammation at surgery, continued endoscopic surveillance may identify asymptomatic disease recurrence to guide therapy.