Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis

Abstract

Background and aims: Tofacitinib is a Janus kinase inhibitor (JAKi) recently approved for the treatment of moderate to severe ulcerative colitis (UC) based on robust efficacy and safety data derived from OCTAVE clinical trials. Evidence on the outcomes of tofacitinib therapy in real-world UC patients is needed, as a number of these patients would be deemed ineligible for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe UC patients. Methods: We searched the PubMed, EMBASE, Scopus, Web of Science and Cochrane databases for observational studies on the use of tofacitinib in UC patients, published between 30 May 2018 and 24 January 2021. Pooled induction (8–14 weeks) and maintenance (16–26 weeks) clinical response and remission rates were calculated, as well as the proportion of reported adverse events using random effects models. Results: Nine studies were included, comprising 830 patients, of which 81% were previously treated with anti-tumour necrosis factor (TNF) and 57% with vedolizumab. Induction of clinical response and remission were achieved in 51% (95% confidence interval, 41–60%) and 37% (26–45%) of patients, after a median follow-up of 8 weeks. At the end of a median follow-up of 24 weeks, maintenance of clinical response and remission were met in 40% (31–50%) and 29% (23–36%) of patients, respectively. Thirty-two percent of the patients had at least one adverse event, the most commonly reported being mild infection (13%) and worsening of UC, requiring colectomy (13%). A third of the patients (35%) discontinued tofacitinib, most frequently due to primary non-response (51%). Conclusion: Tofacitinib is a safe and effective therapy in real-world UC patients, as previously reported by clinical trials.

Research trends in ulcerative colitis: A bibliometric and visualized study from 2011 to 2021

“…As part of the comprehensive search strategy, we searched meta-analysis studies and scientometric and bibliometric analyses. Based on the search strategies employed in these studies ( Connelly et al, 2016 ; Schöffel et al, 2016 ; Nguyen et al, 2018 ; Lucaciu et al, 2021 ; Schöffel et al, 2021 ), we used advanced search to identify publications relevant to UC with the following query: TOPIC: [(ulcerativ* AND colitis) OR (ulcerativ* AND enteritis) OR (colitis ulcerosa) OR (enteritis ulcerosa) OR (idiopathic proctocolitis) OR (colitis gravis) OR (colitis chronica purulenta) OR (colitis polyposa) OR (gastroenteritis ulcerosa) OR (backwash ileitis)] AND Language: (English). Timespan: 2011–2012.…”

“…As part of the comprehensive search strategy, we searched meta-analysis studies and scientometric and bibliometric analyses. Based on the search strategies employed in these studies (Connelly et al, 2016;Schöffel et al, 2016;Nguyen et al, 2018;Lucaciu et al, 2021;Schöffel et al, 2021), we used advanced search to identify publications relevant to UC with the following query: TOPIC: [(ulcerativ* AND colitis) OR (ulcerativ* AND enteritis) OR (colitis ulcerosa) OR (enteritis ulcerosa) OR (idiopathic proctocolitis) OR (colitis gravis) OR (colitis chronica purulenta) OR (colitis polyposa) OR (gastroenteritis ulcerosa) OR (backwash ileitis)] AND Language: (English). Timespan: 2011Timespan: -2012 This study focused, for the purpose of this analysis, on articles (document types) that included original research articles, case reports, and case series out of the different types of documents indexed in the database (article, proceedings paper, review, meeting abstract, correction, letter, editorial material, note, book chapter, news item, and correction addition).…”

“…In the early years from 2011 to 2013, UC research began to focus on (Actis et al, 2019) cystic fibrosis, asthma, breast cancer, and osteoporosis (Kaplan, 2015); primary sclerosing cholangitis, rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis (Wilks, 1859); celiac disease, pouchitis, and familial adenomatous polyposis (Viola et al, 2021); abnormal motility, colonic permeability, and enteric nervous system (Nguyen et al, 2018); adipose tissue (Lucaciu et al, 2021); epidemiology, gene polymorphism, susceptibility loci, drug delivery, and activity index (Connelly et al, 2016); dextran sulfate sodium (DSS) and acetic acid (Schöffel et al, 2021); guinea pig (Schöffel et al, 2016); N-acetylcysteine, fish oil, and vitamin D (Chen, 2006); 5-aminosalicylic acid (5-ASA), sulfasalazine, olsalazine, and chitosan (Van Eck and Waltman, 2010); cyclosporin, 6-mercaptopurine, methotrexate, and azathioprine (Aksnes, 2003); certolizumab pegol, infliximab, etanercept, adalimumab, and tacrolimus (Bardeesi et al, 2021); Adacolumn, leukocytapheresis, and apheresis (Freeman, 1977); probiotics, antibiotic therapy, curcumin, traditional Chinese medicine, and electroacupuncture (Cobo et al, 2011); colectomy, ileostomy, and ileal pouch-anal anastomosis; (Kessler, 1963); liver transplantation (Marshakova, 1973); confocal laser endomicroscopy and PillCam colon capsule endoscopy (Small, 1973); C-reactive protein, lactoferrin, and fecal calprotectin (Sandborn et al, 2012a); E-cadherin (Sandborn et al, 2017); Epstein-Barr virus and cytomegalovirus infection (Feagan et al, 2013); Helicobacter pylori, gut microbiota, Escherichia coli, and Clostridium difficile infection (Kleinberg, 2003); short-chain fatty acids, butyrate, and bile acid (Cohen et al, 2010); innate immunity (Ng et al, 2017); regulatory T (T reg ) cell, T helper 17 (Th17) cell, natural killer T cell, and mast cell (Burisch et al, 2020); enterochromaffin cell (Livas et al, 2021); antineutrophil cytoplasmic antibody and anti-Saccharomyces cerevisiae antibody (Glänzel and Thijs, 2004); angiogenesis...…”

Managing IBD in patients with previous cancers

“…The first reported serious adverse event rate in the analysed studies of 4.4%; however, the number of malignant events was not further described 50. The second identified one case of malignancy (metastatic breast cancer) among the reported adverse events over a median follow-up of 31 weeks 51. This case was attributed to high prior immunosupressive load 52.…”

“…Of note, the real-world IBD tofacitinib studies and trial data encapsulated a younger population (mean age approx. 40) 48 51…”