Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study.

BACKGROUND & AIMS: Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). METHODS: This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. RESULTS: In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P = .001), patients treated with vedolizumab (P = .001), patients with moderate endoscopic disease activity (P = .002), and a body mass index <25 kg/m2 (P = .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P = .006). No new safety signals were observed. CONCLUSIONS: Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.

De-escalation of immunomodulator and biological therapy in inflammatory bowel disease.

Treatment strategies for inflammatory bowel disease (IBD) focus on the induction and long-term maintenance of deep remission to avoid complications of active disease and improve long-term outcomes. Medical therapies for IBD, notably the increasingly widespread use of biological therapy, are often effective at controlling disease, but these drugs are associated with substantial adverse events, which together with other factors-including increasing treatment costs and patient preferences-leads to concerns regarding indefinite use of medical therapy. Consequently, the need to consider the safety and feasibility of drug de-escalation once IBD remission has been achieved is clear. Here, we review the current evidence surrounding de-escalation of immunomodulator and biological therapy in Crohn's disease and ulcerative colitis. We discuss strategies for de-escalation, including the selection of patients who are appropriate for treatment de-escalation and the use of proactive drug monitoring, and review the evidence on subsequent optimal follow-up. We conclude by proposing an algorithm to guide de-escalation decisions, and highlight future perspectives, including the potential effect of emerging medication and personalised medicine for these diseases.

Long-term Clinical Effectiveness of Ustekinumab in Patients with Crohn's Disease Who Failed Biologic Therapies: A National Cohort Study.

BACKGROUND: Ustekinumab [UST] was recently approved in Europe for the treatment of moderate to severe Crohn's disease [CD]. Long-term real-world data are currently scarce for CD patients previously exposed to several biologics. METHODS: This is an observational, national, retrospective multicentre study. Patients received intravenous UST ~6 mg/kg at baseline, with 90 mg subcutaneously thereafter every 8 weeks. Response and remission rates were assessed at Weeks 8, 16, and 52. RESULTS: Data from 152 patients were analysed. All patients were exposed to at least one anti-TNFα agent, with 69.7% were exposed to even two anti-TNFα and vedolizumab. After 1 year, 42.1% and 25.7% of patients had experienced clinical response and clinical remission, respectively, and 38.8% and 24.3% had achieved steroid-free clinical response and remission, respectively; 38.8% of patients discontinued therapy during the 12 months of follow-up. Colonic location was predictive of clinical response at 1 year, and low body mass index [BMI] at baseline was a negative predictor of clinical remission. Resolution of arthralgia was associated with clinical response over time. De novo arthralgia was reported by 17.9% of patients at Week 8 and 13.5% of patients at Week 52. No impact of UST on arthralgia was observed in patients with concomitant ankylosing spondylitis [n = 17]. Others adverse events were reported in 7.2% of patients. CONCLUSIONS: This real-world cohort study confirms the effectiveness of UST in CD patients previously exposed to several biologics. Ustekinumab was well tolerated with respect to adverse events. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

The Cost-effectiveness of Biological Therapy Cycles in the Management of Crohn's Disease.

OBJECTIVES: To examine the cost-effectiveness of continued treatment for patients with moderate-severe Crohn's disease in clinical remission, with a combination of anti-tumour necrosis factor alpha [anti-TNFα] [infliximab] and immunomodulator therapy compared with two different withdrawal strategies: [1] withdrawal of the anti-TNFα therapy; and [2] withdrawal of the immunomodulator therapy, respectively. METHODS: A decision-tree model was constructed mimicking three treatment arms: [1] continued combination therapy with infliximab and immunomodulator; [2] withdrawal of infliximab; or [3] withdrawal of the immunomodulator. Relapses in each arm are managed with treatment intensification and re-institution of the de-escalated drug according to a prespecified algorithm. State-dependent relapse risks, remission probabilities, and quality of life weights were collected from previous published studies. RESULTS: Combination therapy was less costly and more efficient than the withdrawal of the immunomodulator, and more costly and more efficient than withdrawal of infliximab. Whether or not combination therapy is cost-effective, compared with the alternatives, depends primarily on current pharmaceutical prices and the willingness-to-pay per additional quality-adjusted life-year [QALY]. CONCLUSIONS: Combination therapy using a combination of anti-TNFα [infliximab] and an immunomodulator is cost-effective in the treatment of Crohn's disease compared with treatment cycles in which the immunomodulator is withdrawn. Combination treatment is cost-effective compared with treatment cycles in which infliximab is withdrawn, at prices of infliximab below€192/100 mg, given a willingness-to-pay threshold at€49 020 [Sweden] per additional QALY.

Integrated Care for Crohn's Disease: A Plea for the Development of Clinical Decision Support Systems.

Evolution in the management of Crohn's disease [CD] has been characterized by recent paradigm changes. First, new biological therapies induce intestinal healing and full disease control in a substantial number of patients, particularly when introduced early in the disease course. However, they are expensive and associated with potentially severe side effects, raising the question of optimal treatment duration. Secondly, progress in biomarkers and medical imaging performance has enabled better refinement of the definition and prediction of remission or relapse of the disease through monitoring [tight control]. This progress may help to improve tailoring treatment in relation to target ['treat-to target' approach], applying patient-centred and collaborative perspectives, consistent with other chronic disease management. Such an approach requires the integration of a potentially large number of parameters coming from different stakeholders. This integration would be difficult based solely on implementation of classical guidelines and the clinician's intuition. To this end, clinical decision support systems should be developed that integrate a combination of various outcomes to facilitate the treatment decision and to share information between patients, primary care specialists, and health insurance companies or health authorities. This should ease complex therapeutic decisions and serve as a basis for continued research into effectiveness of CD management.

The course of anaemia in children and adolescents with Crohn's disease included in a prospective registry.

AIM: The aim of this study is to determine the prevalence and evolution of anaemia in prospectively followed children and adolescents diagnosed with Crohn's disease (CD). METHODS: The BELCRO registry (inclusion May 2008-April 2010), describing current clinical treatment practice of children diagnosed with CD, provided data on age, height, body mass index (BMI), paediatric Crohn's disease activity index (PCDAI), therapy and haemoglobin (Hb) at diagnosis 12 and 24 months follow-up. Anaemia was defined as Hb < -2 sd, while severe anaemia was defined as Hb < -4 sd. Patients were classified as child ≤13 and adolescent >13 years of age. RESULT: Ninety-six were included, 13 dropped out due to insufficient Hb data (37 females/46 males; median age 13.3 years, range 2.2-17.8 years). At diagnosis, the median Hb sd was -2.66 (-8.4; 1.07) and was correlated with the PCDAI (p = 0.013). At diagnosis, 51/83 (61%) were anaemic and all had active disease. Hb z-score significantly improved (p < 0.0001) but 26/68 (38%) remained anaemic at 12 months and 29/76 (38%) at 24 months of follow-up. The correlation to the PCDAI disappeared. At 24 months, children were more likely to be anaemic. There was no difference in iron dose nor duration of iron supplements between children and adolescents. Iron treatment was more readily given to patients presenting with anaemia. Hb did not differ between patients with (n = 28) or without iron supplements. Half of the patients with persisting anaemia were given iron supplements, of which, only three were given intravenously. CONCLUSION: Anaemia remains an important extra-intestinal manifestation of CD in children. Physicians, lacking optimal treatment strategies, undertreat their patients.