Sailish Honap

BACKGROUND: Tofacitinib is a partially selective Janus kinase inhibitor approved for the treatment of refractory moderate to severe ulcerative colitis [UC]. We sought to define the effectiveness and adverse effects of tofacitinib in a real-world cohort. METHODS: We conducted a retrospective observational cohort study of 134 patients with UC [64% male; median age 37 years [range 16-81]; 83% of patients had previously received at least one biologic] treated with tofacitinib from October 2018 to October 2019 in four UK centres. Disease activity was assessed using the Simple Clinical Colitis Activity Index [SCCAI] or partial Mayo score [PMS], depending on study site. Response and remission were defined as a reduction in SCCAI or PMS of ≥3and SCCAI ≤2 or a PMS ≤1, respectively. RESULTS: Overall, 74% (88/119; 95 confidence interval [CI] 65-81%] patients responded to tofacitinib at Week 8 and steroid-free remission was observed in 44% [47/108; 95% CI 3453%] patients at Week 26. Primary non-response was independently associated with younger age [p = 0.014] and higher C-reactive protein [CRP] levels at baseline [p = 0.004]. Only 23% [3/13] of patients who continued tofacitinib in the setting of primary non-response were in steroid-free remission at Week 26. Prior biologic exposure did not influence response or remission rates. Dose escalation, however, recaptured response in approximately half of patients who had lost response. Dyslipidaemia was observed in 20% [27/134; 95% CI 1428%] of patients, but adverse events necessitating drug withdrawal were uncommon and no venous thromboembolic events occurred. CONCLUSIONS: In this multicentre real-world cohort, tofacitinib was well tolerated and clinically effective in a treatment-refractory UC population.

BACKGROUND AND AIMS: The incidence of inflammatory bowel diseases [IBD] has risen over the past decade to become a global issue. The objectives of this review were to describe the incidence and/or prevalence of IBD in the era of advanced therapies, and to describe the association between environmental risk factors and both pathogenesis and disease course across the ages. METHODS: We performed a search of English language publications listed in PubMed regarding the epidemiology of IBD and key environmental factors implicated in IBD from January 2000 to December 2023. RESULTS: Annual incidence rates varied by geographical region with IBD estimates ranging from 10.5 to 46.14 per 100 000 in Europe, 1.37 to 1.5 per 100 000 in Asia and the Middle East, 23.67 to 39.8 per 100 000 in Oceania, 0.21 to 3.67 per 100 000 in South America, and 7.3 to 30.2 per 100 000 in North America. The burden of IBD among children and adolescents, and older people is rising globally. Key environmental factors implicated in IBD pathogenesis include exposure to tobacco smoking, antibiotics, non-steroidal anti-inflammatory drugs, oral contraceptives, infections, and ultra-high processed foods. Breastfeeding and a high-quality diet rich in fruit, vegetables, fish, and other fibre sources are important protective factors. Smoking has consistently been shown to negatively impact disease outcomes for Crohn's disease. CONCLUSION: The epidemiology of IBD has undergone considerable change in recent decades, with an increase in the burden of disease worldwide. Optimally studying and targeting environmental triggers in IBD may offer future opportunities for disease modification.

Inflammatory bowel disease (IBD) commonly requires immunosuppressive treatments to induce and maintain durable remission. Janus kinase inhibitors (JAKis) are a novel group of orally administered, small molecule drugs that work by attenuating multiple cytokine signalling pathways to mediate dysregulated immune responses involved in the pathogenesis of IBD. Tofacitinib, filgotinib and upadacitinib have demonstrated efficacy against placebo and are licensed for the treatment of moderate to severe ulcerative colitis; upadacitinib is the only JAKi also currently approved for the treatment of Crohn's disease. Safety concerns stratified by age have led to class-wide regulatory restrictions for JAKi use across all inflammatory diseases. It is important for gastroenterologists managing patients with IBD to be aware of the key pivotal trial outcomes, to identify appropriate patients in whom to commence a JAKi, and to understand the safety considerations and ways to mitigate these risks in the patients they treat. This review provides a contemporaneous overview of this emerging therapeutic class and provides a practical guide for healthcare practitioners for initiating and monitoring JAKi in IBD.