Endpoint Of Clinical Remission Research Articles

Ustekinumab for Ulcerative Colitis

Ustekinumab for Ulcerative Colitis

Efficacy of JAK inhibitors in Crohn's Disease.

Inhibition of Janus kinases [JAKs] in Crohn’s disease [CD] patients has shown conflicting results in clinical trials. Tofacitinib, a pan-JAK inhibitor, showed efficacy in ulcerative colitis [UC] and has been approved for the treatment of patients with moderate to severe UC. In contrast, studies in CD patients were disappointing and the primary end point of clinical remission could not be met in the respective phase II induction and maintenance trials. Subsequently, the clinical development of tofacitinib was discontinued in CD. In contrast, efficacy of filgotinib, a selective JAK1 inhibitor, in CD patients was demonstrated in the randomized, double-blinded, placebo-controlled phase II FITZROY study. Upadacitinib also showed promising results in a phase II trial in moderate to severe CD. Subsequently, phase III programmes in CD have been initiated for both substances, which are still ongoing. Several newer molecules of this class of orally administrated immunosuppressants are being tested in clinical programmes. The concern of side effects of systemic JAK inhibition is addressed by either exclusively intestinal action or higher selectivity [Tyk2 inhibitors]. In general, JAK inhibitors constitute a new promising class of drugs for the treatment of CD.

59 Immunohistochemical Evidence of Inflammation Is Similar in Patients With Eosinophilic Esophagitis and PPI-Responsive Esophageal Eosinophilia: A Prospective Cohort Study

Introduction: At least one third of patients with clinical, endoscopic and histological findings suggestive of eosinophilic esophagitis (EoE) achieve clinicopathologic remission after proton pump inhibitor (PPI) therapy. This new condition is termed PPI-responsive esophageal eosinophilia (PPI-REE). The durability and long-term efficacy of PPI therapy for these patients is unknown. Methods: Observational study in a cohort of adult patients with PPI-REE, defined by baseline symptoms of esophageal dysfunction (dysphagia/food impaction) and esophageal eosinophilia (> 15 eos/HPF), both resolved (clinical remission and < 15 eos/ HPF) after a course of PPI therapy for at least 8 weeks. PPI dosage was defined as: quadruple (e.g. omeprazole 40 mg bid or its equivalent), double (omeprazole 40 mg/day) and single (omeprazole 20mg/day). After initial PPI response, acid suppressive therapywas progressively tapered based on clinical symptoms and maintained at the lowest dose with the target endpoint of clinical remission. Follow-up endoscopy was performed at 12 months or longer on PPI maintenance dose with histologic examination of both the distal and proximal esophagus. Results: 40 PPI-REE patients have been included to date with a median followup time of 27 months (12-79). Baseline characteristics: 88% males, median age 39 yearsold (19-71), heartburn and/or regurgitation (49%), reflux esophagitis (14%), pH monitoring in 7 patients (4 normal/3 pathological). PPI dosage in the initial PPI trial for diagnosing PPI-REE was quadruple-dose in 18 patients and double-dose in 22 patients. Regarding the step-down process, 19 patients were maintained on double-dose PPI and 21 on single-dose PPI. Overall, 26 out of 40 (63%) maintained clinical and histologic (< 15 eos/HPF) remission during follow-up. Among the 14 relapsers, 8 occurred on double-dose and 6 on single-dose PPI. In 10/14 of the relapsers, esophageal eosinophilia recurred exclusively at the distal esophagus, but not at proximal esophagus. Intensification to quadruple-dose PPI was carried out in 8 out of these 10 distal relapsers, all of whom achieved clinical and histological remission. Conclusions: Sustained clinico-histological remission on low-dose maintenance PPI therapy was observed in 64% of adult PPI-REE patients. A majority of relapsers showed recurrent eosinophilic inflammation limited to the distal esophagus, which resolved after PPI-dose intensification. It is rare for adult PPI-REE patients to fully lose PPI response and be reclassified as EoE.

A meta-analysis of randomized controlled trials comparing antibacterial therapy with placebo in Crohn’s disease

Antibacterial therapy has been investigated in several randomized, clinical trials compared with placebo for the management of Crohn's disease. Evidences for the efficacy of intervention are increasingly required. To conduct a meta-analysis of randomized trials to compare the effects of antibacterial therapy versus placebo in patients with Crohn's disease. A systematic literature search of Pubmed, EMBASE, Cochrane Library (April 1966 to July 2009) was conducted using specific search terms. Eligible studies were randomized controlled trials comparing antibacterial (antimycobacterial and broad-spectrum antibiotic) therapy with placebo. Studies were reviewed to determine the number of participants, mean follow-up, and the odds ratios (OR) for primary end point of clinical remission and clinical response were also abstracted. The meta-analysis was performed using a fixed-effects model or a randomized-effects model according to the degree of heterogeneity. Eleven randomized placebo-controlled clinical trials with 668 participants (364 patients in the treatment group and, 304 patients in the placebo group) were identified. Antimycobacterial agents were used in four of the trials and broad-spectrum antibiotics were used in the other seven trials. Pooled analysis showed no significant differences in the rates of clinical remission [OR = 1.28, 95% confidence interval (CI): 0.87-1.90, P = 0.214] and clinical response (OR = 1.52, 95% CI: 0.91-2.55, P = 0.108) after receiving antibacterial treatment for 3 months or longer. In this meta-analysis, no evidence of benefit for antibiotics in patients with Crohn's disease was found.