Murthy, Sanjay K.

Abstract Background & Aims Crohn’s disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. Methods We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. Results The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Conclusions Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Background and Aims: Clostridium difficile infection (CDI) has been associated with an increased mortality risk among patients with inflammatory bowel disease (IBD) in multiple observational studies. We performed a systematic review and meta-analysis to help clearly define the magnitude of risk in IBD patients with and without CDI, and to assess the risk in individual IBD subtypes. Methods: A systematic search of multiple electronic databases was conducted for observational studies reporting the risk of mortality in IBD, stratified by the presence of CDI. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. Results: Ten observational studies were identified (8 from North America and 2 from Europe) and included 40,700 IBD patients with CDI and 1,320,764 IBD controls without CDI. Overall, IBD patients with CDI had a higher risk of mortality compared with IBD patients without CDI [odds ratios (OR), 4.39; 95% confidence interval (CI), 3.56-5.42; I 2=93%]. The results were stable in high-quality studies and in hospitalized patients. When patients were stratified by IBD type, CDI was associated with increased mortality in patients with ulcerative colitis (7 studies) (OR, 4.39; 95% CI, 3.44-5.61; I 2), but not in patients with Crohn’s disease (4 studies) (OR, 2.21; 95% CI, 0.84-5.77; I 2). Individual studies were limited by an inability to control for IBD disease activity and therapeutic interventions. Conclusions: On the basis of 10 observational studies with at least moderate quality, CDI seems to increase mortality risk in IBD, particularly in ulcerative colitis. These findings are a cause for concern and suggest that CDI should be managed aggressively in patients with IBD.

SummaryBackgroundClostridium difficile infection (CDI) is associated with increased mortality in inflammatory bowel disease (IBD), but the risk of colectomy is variable and has not been adequately studied.AimTo perform a systematic review and meta‐analysis to assess the impact of CDI on colectomy risk in IBD.MethodsMultiple databases were searched systematically for observational studies reporting colectomy risk in IBD, stratified by the presence of CDI, and the duration of follow‐up (short term 3 months, and long term at least 1 year). Weighted summary estimates were calculated using generalised inverse variance with random‐effects model. Study quality was assessed using the Newcastle–Ottawa scale.ResultsTwelve observational studies were identified and included 35 057 IBD patients with CDI, and 929 259 without CDI. CDI did not increase the short‐term colectomy risk in IBD patients overall (10 studies) (OR: 1.35; 95% CI: 0.68–2.67), or in patients with ulcerative colitis (nine studies) (OR: 1.20; 95% CI: 0.39–3.76). In contrast, CDI was associated with higher long‐term colectomy risk in patients with IBD overall (five studies) (OR: 2.23; 95% CI: 1.18–4.21), and in patients with ulcerative colitis (four studies) (OR: 2.96; 95% CI: 1.19–7.34). The results were stable in subgroups stratified by recruitment period, hospitalisation status and geographical location. All studies were at least of moderate quality. The results were limited in the ability to compare IBD severity and the type of anti‐microbial therapy.ConclusionBased on 12 observational studies with at least moderate quality, Clostridium difficile infection appears to increase colectomy risk in IBD in the long‐ but not short‐ term.