Induction Of Endoscopic Remission Research Articles

Efficacy and Safety of Oral Janus Kinase Inhibitors for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Background: Janus kinase (JAK) inhibitors are novel agents for treatment of inflammatory bowel disease. We aimed to determine the efficacy and safety of Janus kinase (JAK) inhibitors for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Methods: A systematic review and meta-analysis were conducted. PubMed, Embase, and CENTRAL were searched to November 1, 2018 for randomized placebo-controlled trials (RCTs) of JAK inhibitors in adult patients with CD or UC. Clinical, endoscopic, and safety outcomes were extracted and rates relative to placebo were pooled using a random-effects model. Findings: A total of 12 RCTs (5 CD, 7 UC) were included. Patients were randomized to placebo (n=844), tofacitinib (n=1,882), filgotinib (n=130), peficitinib (n=176), upadacitinib (n=387), or TD-1473 (n=31). JAK inhibitor treatment was associated with induction of clinical remission in CD (relative risk RR 1∙38 [95% confidence interval CI 1∙04-1∙83], p=0 ∙025, I2=14%) and UC (RR 3∙07 [95% CI: 2∙03-4∙63], p<0∙001, I2=0%). In UC, JAK inhibitor treatment was associated with induction of endoscopic remission (endoscopic Mayo subscore MCSe=0/1) (RR 2∙43 [95% CI: 1∙64- 3∙59], p<0∙001, I2=27%) and mucosal healing (MCSe=0) (RR 5∙50 [95% CI: 2∙46-12∙32], p<0∙001, I2=0%). JAK inhibitor treatment increased the risk of infection compared to placebo (RR 1∙40 [95% CI: 1∙18-1∙67], p<0∙001, I2=0%), particularly for herpes zoster. All studies were rated as low or unclear risk of bias. Interpretation: JAK inhibitors are effective for induction of clinical and endoscopic remission in CD and UC, although are associated with an increased risk of infectious complications. Funding Statement: There was no funding source for this study. Christopher Ma is supported by a Clinician Fellowship from the Canadian Institutes of Health Research and the Canadian Association of Gastroenterology. Niels Vande Casteele is supported by a Research Scholar Award from the American Gastroenterological Association. Declaration of Interests: Christopher Ma, Jeffrey Lee, Anish Mitra, Anouar Teriaky, and Daksh Choudhary have no conflicts of interest to disclose. Tran Nguyen is an employee of Robarts Clinical Trials, Inc. Niels Vande Casteele has received research support from R-Biopharm and Takeda and consulting fees from Janssen, Pfizer, Progenity, Prometheus, Takeda, and UCB. Reena Khanna has received consulting/speaker fees from AbbVie, Encycle, Janssen, Merck, Pendopharm, Pfizer, Roche, Robarts Clinical Trials, Shire, and Takeda Canada. Remo Panaccione has received scientific advisory board fees from Abbott/AbbVie, Amgen, Janssen, Merck, Pfizer, Prometheus Laboratories, Salix Pharma, Shire, Takeda, and Warner Chilcott, consulting fees from Abbott/AbbVie, Amgen, Aptalis, Astra Zeneca, Baxter, BMS, Centocor, Elan/Biogen, Eisai, Ferring, GSK, Janssen, Merck, Millennium, Pfizer, Proctor & Gamble, Prometheus Therapeutics and Diagnostics, Schering-Plough, Shire, Takeda, UCB Pharma, and Warner Chilcott, research grants from Abbott/AbbVie, Amgen, Aptalis, Astra Zeneca, Baxter, BMS, Centocor, Eisai, Elan/Biogen, Ferring, GSK, Janssen, Merck, Millennium, Pfizer, Proctor & Gamble, Prometheus, Shire, Schering-Plough, Takeda, UCB Pharma, and Warner Chilcott, and speaker’s bureau fees from Abbott/AbbVie, Amgen, Aptalis, Astra Zeneca, Baxter, BMS, Centocor, Eisai, Elan/Biogen, Ferring, GSK, Janssen, Merck, Millennium, Pfizer, Proctor & Gamble, Prometheus, Schering-Plough, Shire, Takeda, UCB Pharma, and Warner Chilcott. Brian Feagan has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc., Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc., Elan/Biogen, Janssen440 Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc., and Sigmoid Pharma; and speaker’s fees from UCB, AbbVie, and J&J/Janssen. Vipul Jairath has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, Celltrion; speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, Pfizer Ethics Approval Statement: PRISMA guidelines referenced.

Systematic review with meta-analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease.

Janus kinase (JAK) inhibitors represent a novel therapeutic class for treatment of inflammatory bowel disease. To determine the efficacy and safety of JAK inhibitors compared to placebo for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). PubMed, Embase and CENTRAL were systematically searched to November 1, 2018. Randomised placebo-controlled trials (RCTs) of JAK inhibitors in adult patients with CD or UC were eligible. Open-label extension studies without a placebo comparator arm were excluded. Clinical, endoscopic, and safety outcomes were extracted and rates relative to placebo were pooled using a random-effects model. A total of 12 RCTs (5 CD, 7 UC) were included. Patients were randomised to placebo (n=844), tofacitinib (n=1882), filgotinib (n=130), peficitinib (n=176), upadacitinib (n=387) or TD-1473 (n=31). JAK inhibitor treatment was associated with induction of clinical remission in CD (RR, relative risk 1.38 [95% confidence interval CI 1.04-1.83], P=0.025, I2 =14%) and UC (RR 3.07 [95% CI 2.03-4.63], P<0.001, I2 =0%). In UC, JAK inhibitor treatment was associated with induction of endoscopic remission (endoscopic Mayo subscore MCSe=0/1) (RR 2.43 [95% CI 1.64-3.59], P<0.001, I2 =27%) and mucosal healing (MCSe=0) (RR 5.50 [95% CI 2.46-12.32], P<0.001, I2 =0%). JAK inhibitor treatment increased the risk of infection compared to placebo (RR 1.40 [95% CI 1.18-1.67], P<0.001, I2 =0%), particularly for herpes zoster. JAK inhibitors are effective for inducing clinical remission in CD and induction of clinical and endoscopic remission in UC, although are associated with an increased risk of infectious complications.

Biologic drugs for induction and maintenance of remission in Crohn's disease: a network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: We aim to conduct a systematic review and meta-analysis of all RCTs that compare biologic drugs (TNF-α antagonists, integrin antagonists, or ustekinumab) against placebo or an active comparator in adults with CD. Using frequentist network meta-analysis, we aim to assess the efficacy of biologic drugs to treat CD and generate a clinically useful ranking of available biological drugs according to efficacy in terms of: 1) Induction and maintenance of clinical remission in CD, defined as a Crohn's Disease Activity Index (CDAI) below 150; 2) Induction and maintenance of clinical response in CD, defined as a drop in the CDAI of at least 70 (CDAI-70) or 100 (CDAI-100) points compared to baseline; and 3) Induction of endoscopic remission in CD, defined as an absence of ulceration.

P039 Mucosal interleukin-33 levels in patients with moderate to severe ulcerative colitis before and after induction of endoscopic remission by infliximab

P039 Mucosal interleukin-33 levels in patients with moderate to severe ulcerative colitis before and after induction of endoscopic remission by infliximab

P040 Mucosal T cell profiles in newly diagnosed, untreated inflammatory bowel disease patients

in acute lesions of inflammation including ulcerative colitis. Its role is not fully understood, especially its importance in wound and mucosal healing in inflammatory bowel disease [1,2]. Methods: We included 57 patients with moderate to severe ulcerative colitis from the University Hospital of North Norway. Patients were treated with infliximab to clinical and endoscopic remission defined by the ulcerative disease activity index as a score of 2 or less and with an endoscopic sub score of 0 or 1. Mucosal gene expression levels of IL-33 and tumour necrosis factor alpha (TNF-a) levels where determined in colon mucosal biopsies prior to infliximab therapy and at endoscopic remission using real-time PCR. Immunohistochemistry analysis was performed for IL-33 in 10 patients and 10 healthy controls. Results: No differences in IL-33 mucosal levels were found for the whole study population when comparing active disease with endoscopic remission, however a significant reduction of IL-33 was found in a subgroup of 17 patients (30%) who achieved normalisation of TNF-a expression (fold change 0.44, p value = 0.039). Infliximab therapy was stopped in 55 patients following endoscopic remission, at 1 year follow up 26 patients (47%) where still in disease remission. Immunohistochemistry showed IL-33 positive cells in the acute disease phase localised in the lamina propria, endothelial cells and also in basalcryptcells, the latter was not seen in endoscopic remission or in the healthy controls. Conclusions: Induction of endoscopic remission by infliximab in patients with ulcerative colitis significantly reduced the mucosal IL-33 levels only when TNF-a was normalised. Our data support the hypothesis of IL-33 as a pivotal mediator of inflammation in ulcerative colitis and is tightly associated to the mucosal expression of TNF-a.