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Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were evaluated in randomised, placebo-controlled Phase (P)2 (NCT00787202) and P3 (NCT01465763; NCT01458951; NCT01458574) studies, an open-label, long-term extension (OLE) study (NCT01470612) and an ongoing P3b/4 study (NCT03281304). We report updated tofacitinib safety analyses from the tofacitinib UC clinical programme, with inclusion of a 6‑month interim analysis of data from the P3b/4 study, up to 7.8 years of tofacitinib exposure.

This analysis included1157 patients (pts) receiving tofacitinib 5 or 10 mg BID from completed P2/P3/OLE studies, and the ongoing P3b/4 study (as of 20 Feb 2020; Overall+P3b/4 Cohort). Proportions and incidence rates (IRs; unique pts with events/100 pt‑years [PY] of exposure) were evaluated for deaths and adverse events (AEs) of special interest. Opportunistic infections (OIs), malignancies, major adverse cardiovascular events (MACE) and gastrointestinal perforations were adjudicated.

Table 1 shows demographics and clinical characteristics. In the Overall+P3b/4 Cohort, 1157 pts received ≥1 dose of tofacitinib 5 or 10 mg BID; 955 (83%) received a predominant dose of 10 mg BID; 397/1157 (34.3%) pts had received tofacitinib for >4.1 years. Median treatment duration was 623 (range, 1–2850) days (2999.7 PY of exposure). Table 2 shows safety data for AEs of special interest in the Overall+P3b/4 Cohort. IRs (95% confidence intervals) for all tofacitinib doses: deaths, 0.23 (0.09, 0.46); serious infections, 1.69 (1.26, 2.21); herpes zoster (non-serious and serious), 3.30 (2.67, 4.04); OIs, 1.03 (0.70, 1.46); malignancies (excluding non-melanoma skin cancer [NMSC]), 0.84 (0.55, 1.24); NMSC, 0.73 (0.45, 1.10); MACE, 0.29 (0.13, 0.55); deep vein thrombosis, 0.03 (0.00, 0.18); pulmonary embolism, 0.19 (0.07, 0.42); and gastrointestinal perforations, 0.10 (0.02, 0.28). IRs for AEs of special interest were similar to prior Overall Cohort analyses.¹

The safety profile of tofacitinib in pts with UC from the tofacitinib UC clinical programme was generally consistent with that of other UC therapies, including biologics, with the exception of herpes zoster.² IRs for AEs of special interest have remained stable over an extended period of time (up to 7.8 years) with inclusion of final data from the OLE study and an interim analysis of data from the P3b/4 study.^1,3

References:
1. Sandborn WJ et al. United European Gastroenterol J 2021; 9 (Suppl 8): Abstract OP152.
2. Curtis JR et al. Inflamm Bowel Dis 2021; 27: 1394-1408.
3. Sandborn WJ et al. United European Gastroenterol J 2020; 8 (Suppl 8): Abstract OP494.

Bobby Lo discusses his work measuring the impact of IBD on healthcare costs and the wider economy in a Danish cohort and provides some interesting insight into the Danish healthcare model.

Paediatric Inflammatory Bowel Disease (IBD) accounts for 10-15% of all incident cases, while incidence in children under 10 years old is rising most rapidly. Very early-onset inflammatory bowel disease (VEOIBD) is diagnosed before the age of 6 years while infantile IBD occurs before the age of 2 years and may be a clue for monogenic IBD..

It is very important to identify monogenic IBD patients as management may differ from classical IBD. While age of onset is most relevant, specific comorbidity and extraintestinal manifestations also are of particular relevance in identification of monogenic IBD. These conditions are summarized in the following: Young agematters most. Young age onset; Multiple family members and consanguinity; Autoimmunity; Thriving failure; Treatment with conventional medication fails; Endocrine concerns; Recurrent infections or unexplained fever; Severe perianal disease; Macrophage activation syndrome and HLH; Obstruction and atresia of intestine; Skin lesions, dental and hair abnormalities; Tumours. This anagram will be further elucidated.

A diagnostic algorithm of monogenic IBD will be discussed, incorporating multidisciplinary team assessment of genetic results, genetic counselling but also the need for functional assessment of novel gene defects and variants of unknown significance to establish causality. Also, illustrative cases of monogenic IBD such as Interleukin-10 receptor deficiency and XIAP will be incorporated in the presentation.

Avi Dukler describes results from a new serum biomarker panel developed and tested for prediction of endoscopic healing in a cohort study from Leuven, Belgium.

1. To understand the role of dietary patterns in development of CD
2. To review the position of dietary therapy in current ECCO-ESPGHAN guidelines
3. To discuss novel dietary strategies based on recent evidence
4. To show how microbiome and metabolome can affect induction and maintenance of remission

In co-operation with the Crohn's & Colitis Foundation