OBJECTIVES: In 2015, the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program proposed shifting the therapeutic focus on ulcerative colitis (UC) toward altering the natural history of the disease course by regularly monitoring objective measurements of disease activity and tailoring treatment accordingly. The therapeutic paradigm shift was well received in the research community and is often cited. However, new evidence on optimal UC treatment targets continues to accumulate since the time of the STRIDE guidelines. This systematic review summarizes the evidence accrued since the STRIDE UC recommendations, discusses the barriers for adoption of treat-to-target approaches in clinical practice in UC, and suggests directions for future research. METHODS: We systematically reviewed MEDLINE for studies from the time of the STRIDE systematic review up to March 31, 2018, that assessed the potential treatment targets identified by the STRIDE recommendations. RESULTS: Each potential treatment target literature search returned > 200 articles, which were then reviewed by 2 independent investigators for relevant studies. Selected studies of clinical factors, patient-reported outcomes, endoscopy, histology, imaging, and biomarkers and implications on treatment targets are summarized. CONCLUSIONS: It appears that the relative weight given to different therapeutic targets in the development and improvement of UC treatments could be optimized, with an increased emphasis on endoscopic and histological targets over clinical or symptomatic targets. For this evolution to occur, however, new research has to demonstrate that the treat-to-target approach will deliver on the promise of better long-term outcomes compared with current approaches.

Background and AimsMedical management of fistulising Crohn’s disease [CD] is constrained by the limited number of available therapies. We evaluated the efficacy of vedolizumab, a gut-selective α4β7 integrin antagonist approved for treating moderately to severely active CD, in a subpopulation of patients with fistulising CD who participated in the GEMINI 2 trial [NCT00783692].MethodsExploratory analyses of data from the GEMINI 2 trial were conducted in 461 responders to 6-week vedolizumab induction therapy who received maintenance placebo [VDZ/PBO, N = 153] or vedolizumab [VDZ/VDZ, N = 308]. Fistula closure rates were assessed at Weeks 14 and 52, and the time to fistula closure was analysed by the Cox proportional hazards model with adjustments for significant covariates.ResultsAt entry into the maintenance period, 153 [33%] patients had a history of fistulising disease and 57 [12%] patients had ≥1 active draining fistula. By Week 14, 28% of VDZ/VDZ-treated patients compared with 11% of VDZ/PBO-treated patients (95% confidence interval [CI], –11.4 to 43.9) achieved fistula closure. Corresponding rates at Week 52 were 31% and 11% (absolute risk reduction [ARR]: 19.7%; 95% CI, –8.9 to 46.2). Similarly, VDZ/VDZ-treated patients had faster time to fistula closure and were more likely to have fistula closure at Week 52 [33% vs 11%; HR: 2.54; 95% CI, 0.54–11.96]. Prior failure of antibiotic therapy was a negative predictor of fistula closure [HR: 0.217; 95% CI, 0.059–0.795; p = 0.021], whereas trough vedolizumab concentrations did not affect closure rates.ConclusionsOur findings are consistent with the beneficial effect of vedolizumab treatment for fistulising CD.

Primary sclerosing cholangitis (PSC) is a rare obliterative fibrotic condition of the bile ducts. We assessed PSC epidemiology and natural history within the UK Clinical Practice Research Datalink (CPRD).Incidence and natural history of PSC were evaluated in a retrospective cohort study using linkage of CPRD, Hospital Episode Statistics, and Office for National Statistics data. Data from age, sex, and general practice-matched population controls provided a context for the incident PSC patients. Liver disease other than PSC was defined as autoimmune hepatitis, hepatitis, hepatomegaly, liver failure, cirrhosis, portal hypertension, cholangiocarcinoma, or hepatobiliary cancer.The age-standardized incidence of PSC was 0.68 (95% confidence interval [CI] 0.45–0.99) per 100,000 person-years and the age-standardized prevalence was 5.58 (95% CI 4.82–7.35) per 100,000 during 1998 to 2014. In all, 250 incident PSC patients met the inclusion criteria and each was matched with 5 controls (mean age 54 ± 18 years, men 63.2%). A higher percentage of PSC patients had a history of inflammatory bowel disease (54% vs 2%) and liver disease other than PSC (22% vs 1%) than controls (standardized differenceweighted >0.1). During a median follow-up of 5 years, PSC patients were more likely to develop adverse health outcomes. The mortality rate per 1000 person-years was 3-fold higher in PSC than population controls (49.5 vs 16.1; incidence rate ratio 3.1, 95% CI 2.2–4.2).The incidence and prevalence of PSC observed in the UK CPRD were either comparable with or higher than previous studies. Compared with the general population, PSC patients had worse health outcomes including PSC disease progression, complications, and higher mortality.