Singh, S

SummaryBackgroundThe optimal ulcerative colitis biopsy protocol is unclear.AimTo evaluate the number of biopsies required to accurately assess microscopic disease activity in ulcerative colitisMethodsBiopsies from patients with ≥4 rectosigmoid samples, and clinical and endoscopic data, were retrospectively obtained from a prospective biobank. Histology and endoscopic videos were read blindly. A 4‐biopsy Robarts Histopathology Index (RHI) reference score, consisting of the worst item‐level ratings from four biopsies, was compared to 1‐, 2‐ and 3‐biopsy estimates. Agreement was determined using bivariate errors‐in‐variable regression analysis (acceptance interval: ±8.25). Endoscopic activity and disease location subgroup analyses were also performed.ResultsForty‐six patients had ≥4 rectosigmoid biopsies available (N = 287). The 2‐biopsy (tolerance interval: −7.66, 4.79) and 3‐biopsy (tolerance interval: −4.86, 3.46) RHI scores demonstrated acceptable agreement with 4‐biopsy scores. One‐biopsy scores demonstrated unacceptable agreement (tolerance interval: −13.99, 7.78). Mean RHI scores using the 2‐, 3‐ and 4‐biopsy approaches were similar (6.1 ± 9.6 P = 0.36; 6.8 ± 10.5, P = 0.7; 7.5 ± 11.2), whereas the 1‐biopsy estimate was lower (4.4 ± 8.1, P = 0.06). Histological remission rates were identical for the 2‐, 3‐ and 4‐biopsy methods (65.2%, P = 1.0). Subgroup analysis demonstrated that three biopsies were required in patients with endoscopically active disease. Sampling additional colonic locations yielded lower histological remission rates compared to rectosigmoid sampling alone (33.3% vs 61.9%, P = 0.1).ConclusionsA minimum of two — conservatively, three — biopsies are required to reliably assess disease activity in a single colonic segment using the RHI. Further studies are needed of endoscopically active patients and sampling locations. These results have implications for biopsy strategies in clinical trials and practice.

SummaryBackgroundAn association between bariatric surgery and development of de‐novo inflammatory bowel disease (IBD) has been observed.AimTo evaluate further the association among bariatric surgery, weight loss medications, obesity and new‐onset IBD.MethodsUsing Explorys, a population‐based Health Insurance Portability and Accountability Act compliant database, we estimated the prevalence of de‐novo IBD among patients treated with bariatric surgery (Roux‐en‐Y gastrojejunostomy, laparoscopic sleeve gastrectomy or gastric banding) (n = 60 870) or weight loss medications (orlistat, phentermine/topiramate, lorcaserin, bupropion/naltrexone and liraglutide) (n = 193 790) compared with obese controls (n = 5 021 210), between 1999 and 2018.ResultsThe prevalence of de‐novo IBD was lower among obese patients exposed to bariatric surgery (7.72 per 1000 patients) or weight loss medications (7.22 per 1000 patients) compared with patients with persistent obesity not exposed to these interventions (11.66 per 1000 patients, P < 0.0001). The risk reduction for de‐novo IBD was consistent across bariatric surgeries and weight loss medications with the exception of orlistat which was not associated with a reduction in risk for de‐novo IBD compared with the persistent obese control cohort.ConclusionObese patients undergoing treatment with bariatric surgery or weight loss medications are at a lower risk for developing de‐novo IBD compared with persistently obese controls not exposed to these interventions. These data suggest that obesity and ineffective management of obesity are risk factors for de‐novo IBD. Further research is needed to confirm these observations and understand potential mechanisms.

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.

SummaryBackgroundThere are conflicting data on comparative effectiveness of adalimumab and infliximab in patients with Crohn's disease (CD).AimsTo compare the effectiveness and safety of adalimumab and infliximab in biologic‐naïve patients with CD, in a nationwide register‐based propensity score‐matched cohort study in Denmark.MethodsA total of 2908 Danish adults with CD had been treated with adalimumab or infliximab as their first biologic agent between 2005‐2014. By Cox regression, we compared rates of all‐cause hospitalisation, CD‐related hospitalisation, major abdominal surgery and serious infections after variable 2:1 propensity score matching, accounting for baseline disease characteristics, healthcare utilisation and use of CD‐related medications.ResultsAfter propensity‐score matching, we included 315 adalimumab‐ (34.9 ± 12.9 years, 41.9% males) and 512 infliximab‐treated (33.6 ± 12.6 years, 40.8% males) patients, with median disease duration 4.0 years; 36.9% had prior abdominal surgery. Over a median follow‐up 2.3 years after starting biological therapy, there were no significant differences in rate of CD‐related hospitalisation (hazard ratio [HR], 0.81 [95% CI, 0.55‐1.20]) or major abdominal surgery (HR, 1.24 [0.66‐2.33]) between adalimumab‐ and infliximab‐treated patients, though rate of all‐cause hospitalisation was lower in adalimumab‐treated patients (HR, 0.74 [0.56‐0.97]). There was no significant difference in incidence of serious infections requiring hospitalisation (HR, 1.06 [0.26‐4.21]). These results were stable in patients treated with biological monotherapy (all‐cause hospitalisation: HR, 0.75 [0.53‐1.05]; CD‐related hospitalisation: HR, 0.82 [0.51‐1.32], abdominal surgery: HR, 1.47 [0.63‐3.47]) or in combination with immunomodulators (all‐cause hospitalisation: HR, 0.70 [0.44‐1.11]; CD‐related hospitalisation: HR, 0.80 [0.42‐1.52], abdominal surgery: HR, 1.02 [0.39‐2.64]).ConclusionsIn this population‐based, propensity score matched, real‐life cohort study using administrative claims, there was no significant difference in effectiveness and safety of adalimumab and infliximab in biologic‐naïve patients with CD.

SummaryBackgroundThere are limited data to inform positioning of agents for treating moderate‐severe ulcerative colitis (UC).AimTo assess comparative efficacy and safety of different therapies as first‐line (biologic‐naïve) and second‐line (prior exposure to anti‐tumour necrosis factor(TNF)‐α) agents for moderate‐severe UC, through a systematic review and network meta‐analysis, and appraise quality of evidence (QoE) using grading of recommendations, assessment, development and evaluation (GRADE) approach.MethodsWe identified randomised controlled trials (RCTs) in adults with moderate‐severe UC treated with anti‐TNF agents, anti‐integrin agents and janus kinase (JAK) inhibitors, as first‐line or second‐line agents, and compared with placebo or another active agent. Efficacy outcomes were induction/maintenance of remission and mucosal healing; and 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.ResultsIn biologic‐naïve patients (12 trials, no head‐to‐head comparisons), infliximab and vedolizumab were ranked highest for induction of clinical remission (infliximab: odds ratio [OR], 4.10 [95% confidence intervals [CI], 2.58‐6.52]; SUCRA,0.85; vedolizumab:SUCRA,0.82) and mucosal healing (infliximab:SUCRA,0.91; vedolizumab:SUCRA,0.81) (moderate QoE). In patients with prior anti‐TNF exposure (4 trials, no head‐to‐head comparisons), tofacitinib was ranked highest for induction of clinical remission (OR, 11.88 [2.32‐60.89]; SUCRA, 0.96) and mucosal healing (moderate QoE). Differences in trial design limited comparability of trials of maintenance therapy for efficacy. Vedolizumab was ranked safest in terms of serious adverse events (SUCRA, 0.91), and infection (SUCRA, 0.75) in maintenance trials.ConclusionsInfliximab and vedolizumab are ranked highest as first‐line agents, and tofacitinib is ranked highest as second‐line agent, for induction of remission and mucosal healing in patients with moderate‐severe UC, based on indirect comparisons. Head‐to‐head trials are warranted to inform clinical decision‐making with greater confidence.