Background and Aims Mucosal healing is an important treatment end-point in inflammatory bowel disease, and achieving mucosal healing has been demonstrated to improve disease-related outcomes. ...Considerable uncertainty exists, however, regarding the optimal approach for the assessment of mucosal healing. Aims: to compare currently available diagnostic tools for the assessment of mucosal healing and outline the ideal approach to integrating these tools into clinical trials and clinical practice. Methods Review article. Results Endoscopy represents the criterion standard for the assessment of mucosal healing, and frequent endoscopic assessment is associated with a higher rate of achieving mucosal healing. The use of mucosal biopsy allows for the identification of persistent histologic disease activity, but the incremental clinical benefit of achieving histologic healing is yet to be determined. Magnetic resonance enterography has a high sensitivity for ulcer healing in endoscopically inaccessible disease activity. However, the presence of mucosal lesions cannot be reliably excluded based on this modality alone, and further small-bowel endoscopy should be considered in symptomatic patients. Video capsule endoscopy or device-assisted enteroscopy can be used, with device-assisted enteroscopy being preferred in stricturing Crohn’s disease because of the risk of capsule retention or in patients in whom small-bowel malignancy is a possibility. Conclusions Endoscopy remains the criterion standard for the assessment of mucosal healing. Several alternative diagnostic modalities have become available that can be of value in specific clinical circumstances, particularly in patients with small-bowel involvement.
Summary Background Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be ...a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease. Methods In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov , number NCT01030809. Findings This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66·0% SD 14·0 and 61·9% 16·9; adjusted difference 2·5%, 95% CI −5·2% to 10·2%, p=0·5169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (27·7% and 35·1%, absolute difference AD 7·3%, hazard ratio HR: 0·73, 95% CI 0·62 to 0·86, p=0·0003). There were no differences in serious drug-related adverse events. Interpretation Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. Funding AbbVie Pharmaceuticals.
Abstract Purpose To compare the benefits and harms of anti–tumor necrosis factor (TNF)-α and anti-integrin agents as induction and maintenance therapy in adult patients with Crohn’s disease. Methods ...We searched MEDLINE and the Cochrane Central Register of Controlled Trials from inception through July 2015 for randomized clinical trials in patients with Crohn’s disease who reported response or remission with anti–TNF-α or anti-integrin agents administered as induction and/or maintenance therapy. Data on the study population, interventions, outcome measures, adverse events, and study methods were extracted independently by 2 authors. Findings Among 2503 citations identified, 23 met the eligibility criteria. Random-effects model meta-analyses and network meta-analyses were performed. No statistically significant difference was observed between anti–TNF-α and anti-integrin agents with respect to induction and maintenance of response (odds ratio OR = 1.20 95% CI, 0.73–1.96 from 14 trials and OR = 1.23 95% CI, 0.50–3.03 from 8 trials, respectively) or remission (OR = 1.13 95% CI, 0.72–1.76 from 17 trials and OR = 1.18 95% CI, 0.55–2.50 from 9 trials, respectively). No difference was observed in the indirect comparison of trials that reported results on the subgroup of anti–TNF-α naive patients. The proportions of patients with adverse events, infections, and treatment discontinuations were similar between the agents. Implications Our indirect treatment comparisons did not find a statistically significant difference between anti–TNF-α and anti-integrin agents for induction or maintenance therapy. In the absence of head-to-head comparisons, it remains unclear which patient is more likely to respond better to any of these agents.
Anti-tumor necrosis factor-α agents are key therapeutic options for the treatment of ulcerative colitis. Their efficacy and safety have been shown in large randomized controlled trials. The key ...evidence gained from these trials of infliximab, adalimumab, and golimumab is reviewed along with their effect on mucosal healing and long-term outcomes. Also reviewed are methods for optimizing their effectiveness, including therapeutic drug monitoring and treat-to-target strategies. Finally, remaining unresolved questions regarding their role and effectiveness are considered including how these may be addressed in future clinical trials.
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