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ABX464 (obefazimod) is a small molecule that selectively upregulates miR-124 in immune cells. We aimed to assess ABX464 as a treatment for patients with moderate-to-severe, active ulcerative colitis.In this phase 2b, double-blind, randomised, placebo-controlled induction trial, patients were recruited from 95 centres (hospitals and health-care centres) in 16 countries. Eligible patients were aged 18-75 years, with a diagnosis of moderate-to-severe, active ulcerative colitis and a modified Mayo Score (MMS) of 5 points or higher, and a documented non-response or intolerance to previous treatment. Enrolled patients were randomly assigned (1:1:1:1) via an interactive voice and web response system to receive once daily oral ABX464 100 mg, ABX464 50 mg, ABX464 25 mg, or matched placebo. Randomisation was stratified according to study site (US vs non-US) and to whether the patient had previous exposure to second-line treatment with biologics or JAK inhibitors. The primary endpoint was the change from baseline in MMS at week 8. The primary efficacy analysis was done in the full analysis set (FAS), defined as all randomly assigned patients who received at least one dose of study treatment and had baseline data for at least one efficacy variable, and was analysed according to the principles of intention-to-treat. Safety analyses included patients who had been randomly assigned and who received at least one dose of study treatment. The 96 week open-label extension is ongoing. This study is registered with ClinicalTrials.gov, NCT04023396.Between Aug 13, 2019, and April 16, 2021, 254 patients were randomly allocated to ABX464 100 mg (n=64), ABX464 50 mg (n=63), ABX464 25 mg (n=63), or placebo (n=64). Two patients, both in the ABX464 25 mg group, were excluded from the FAS. In the FAS at week 8, the least squares mean (LSM) change from baseline in MMS was -2·9 (95% CI -3·4 to -2·5) for the ABX464 100 mg group, -3·2 (-3·7 to -2·7) for the ABX464 50 mg group, -3·1 (-3·6 to -2·6) for the ABX464 25 mg group, and -1·9 (-2·4 to -1·5) for placebo group; the magnitude of the difference in MMS from baseline was significantly greater in all three ABX464 groups compared with placebo (p=0·0039 for ABX464 100 mg vs placebo, p=0·0003 for ABX464 50 mg vs placebo, and p=0·0010 for ABX464 25 mg vs placebo). The most frequently reported adverse event was headache, which was reported for 27 (42%) of 64 patients in the ABX464 100 mg group, 19 (30%) of 63 in the 50 mg group, 13 (21%) of 62 in the 25 mg group, and five (8%) of 64 in the placebo group. Severe (grade 3) headache was reported for three (5%) patients in the ABX464 group 100 mg group, two (3%) in the ABX464 50 mg group, one (2%) in the ABX464 25 mg group, and none in the placebo group. The only serious adverse event reported for two or more patients in any group was ulcerative colitis (one in each of the ABX464 100 mg and 50 mg groups, and three [5%] in the placebo group).All doses of ABX464 significantly improved moderate-to-severe, active ulcerative colitis compared with placebo, as measured by changes in MMS from baseline to week 8. A phase 3 clinical programme is ongoing.Abivax.

Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present integrated analyses of nonmelanoma skin cancer (NMSC) incidence in the tofacitinib UC clinical program. Methods Nonmelanoma skin cancer events were evaluated from 3 randomized, placebo-controlled studies: 2 identical, 8-week induction studies (NCT01465763, NCT01458951), a 52-week maintenance study (NCT01458574), and an open-label, long-term extension study (NCT01470612). Cohorts analyzed were: Induction, Maintenance, and Overall (patients receiving ≥1 dose of tofacitinib 5 mg or 10 mg twice daily [BID]). An independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique patients with events per 100 patient-years of exposure) for NMSC were evaluated. A Cox proportional hazards model was used for risk factor analysis. Results Nonmelanoma skin cancer was evaluated for 1124 patients (2576.4 patient-years of tofacitinib exposure; ≤6.8 years’ treatment). In the Induction Cohort, NMSC IR was 0.00 for placebo and 1.26 for 10 mg BID. Nonmelanoma skin cancer IR was 0.97 for placebo, 0.00 for 5 mg BID and 1.91 for 10 mg BID in the Maintenance Cohort, and 0.73 (n = 19) in the Overall Cohort. No NMSC was metastatic or led to discontinuation. In the Overall Cohort, Cox regression identified prior NMSC (hazard ratio [HR], 9.09; P = 0.0001), tumor necrosis factor inhibitor (TNFi) failure (3.32; P = 0.0363), and age (HR per 10-year increase, 2.03; P = 0.0004) as significant independent NMSC risk factors. Conclusions For patients receiving tofacitinib, NMSC occurred infrequently. Older age, prior NMSC, and TNFi failure, which are previously reported NMSC risk factors in patients with UC, were associated with increased NMSC risk.

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of patients achieve clinical remission at the end of a year, prompting the exploration of new treatment modalities. This review explores novel therapeutic approaches to UC, including promising drugs in various stages of development, efforts to maximize the efficacy of currently available treatment options, and non-medication-based modalities. Treatment approaches which show promise in impacting the future of UC management are highlighted.

Background Inflammatory bowel disease (IBD) is a complex disease with variable presentation, progression, and response to therapies. Current disease classification is based on subjective clinical phenotypes. The peripheral blood immunophenome can reflect local inflammation, and thus we measured 39 circulating immune cell types in a large cohort of IBD and control subjects and performed immunotype:phenotype associations. Methods We performed fluorescence-activated cell sorting or CyTOF analysis on blood from 728 Crohn’s disease, 464 ulcerative colitis, and 334 non-IBD patients, with available demographics, endoscopic and clinical examinations and medication use. Results We observed few immune cell types commonly affected in IBD (lowered natural killer cells, B cells, and CD45RA– CD8 T cells). Generally, the immunophenome was distinct between ulcerative colitis and Crohn’s disease. Within disease subtype, there were further distinctions, with specific immune cell types associating with disease duration, behavior, and location. Thiopurine monotherapy altered abundance of many cell types, often in the same direction as disease association, while anti-tumor necrosis factor (anti-TNF) monotherapy demonstrated an opposing pattern. Concomitant use of an anti-TNF and thiopurine was not synergistic, but rather was additive. For example, thiopurine monotherapy use alone or in combination with anti-TNF was associated with a dramatic reduction in major subclasses of B cells. Conclusions We present a peripheral map of immune cell changes in IBD related to disease entity and therapies as a resource for hypothesis generation. We propose the changes in B cell subsets could affect antibody formation and potentially explain the mechanism behind the superiority of combination therapy through the impact of thiopurines on pharmacokinetics of anti-TNFs., Graphical abstract

ObjectiveMirikizumab, a monoclonal antibody targeting the interleukin-23 p19 subunit, was effective in a Phase 2 study (NCT02589665) of moderately-to-severely active ulcerative colitis (UC). We studied mirikizumab’s impact on health-related quality of life (HRQoL).DesignHRQoL was evaluated using the Inflammatory Bowel Disease Questionnaire (IBDQ) and 36-Item Short Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS). Mixed effects models for repeated measures compared score changes between mirikizumab and placebo groups. Additional analyses evaluated associations between HRQoL score changes and achievement of efficacy endpoints at weeks 12 and 52.ResultsAt week 12, IBDQ improved compared with placebo for all mirikizumab groups except mirikizumab 50 mg (50 mg, p=0.073; 200 mg, pConclusionMirikizumab improved HRQoL in patients with moderately-to-severely active UC.

We evaluated the value of post-induction fecal calprotectin (FCP) concentration as a biomarker in patients with ulcerative colitis (UC) treated with a biologic.This post hoc analysis of the GEMINI 1/GEMINI LTS (N = 620) and VARSITY (N = 771) trials evaluated the cross-sectional accuracy of post-induction FCP in identifying endoscopic activity and histologic inflammation, and the prognostic performance of FCP in identifying patients most likely to achieve endoscopic and histologic remission or require colectomy and UC-related hospitalization.The cross-sectional accuracy of FCP in identifying endoscopic activity and histologic inflammation was modest (63%-79%). However, a post-induction FCP concentration of ≤250 μg/g vs250 μg/g was associated with a substantially higher probability of achieving clinical remission (odds ratio [OR], 4.03; 95% confidence interval [CI], 2.78-5.85), endoscopic remission (OR, 4.26; 95% CI, 2.83-6.40), and histologic remission (Robarts Histopathology Index: OR, 5.54; 95% CI, 3.77-8.14; Geboes grade: OR, 6.42; 95% CI, 4.02-10.26) at week 52 and a lower probability of colectomy over 7 years (hazard ratio, 0.296; 95% CI, 0.130-0.677) and UC-related hospitalization (hazard ratio, 0.583; 95% CI, 0.389-0.874). The association with colectomy was significant even among patients in symptomatic remission or with endoscopic improvement post-induction, and among patients with elevated FCP at baseline.Although FCP had only modest cross-sectional accuracy in identifying disease activity, an FCP concentration of ≤250 μg/g vs250 μg/g was associated with increased probability of achieving long-term clinical, endoscopic, and histologic remission, and reduced probability of colectomy and UC-related hospitalization (ClinicalTrials.gov: NCT00783718, NCT00790933, NCT02497469).

Background Differences in autonomic nervous system function, measured by heart rate variability (HRV), have been observed between patients with inflammatory bowel disease and healthy control patients and have been associated in cross-sectional studies with systemic inflammation. High HRV has been associated with low stress. Methods Patients with ulcerative colitis (UC) were followed for 9 months. Their HRV was measured every 4 weeks using the VitalPatch, and blood was collected at baseline and every 12 weeks assessing cortisol, adrenocorticotropin hormone, interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein (CRP). Stool was collected at enrollment and every 6 weeks for fecal calprotectin. Surveys assessing symptoms, stress, resilience, quality of life, anxiety, and depression were longitudinally collected. Results Longitudinally evaluated perceived stress was significantly associated with systemic inflammation (CRP, P = 0.03) and UC symptoms (P = 0.02). There was a significant association between HRV and stress (low-frequency to high-frequency power [LFHF], P = 0.04; root mean square of successive differences [RMSSD], P = 0.04). The HRV was associated with UC symptoms (LFHF, P = 0.03), CRP (high frequency, P < 0.001; low frequency, P < 0.001; RMSSD, P < 0.001), and fecal calprotectin (high frequency, P < 0.001; low frequency, P < 0.001; RMSSD, P < 0.001; LFHF, P < 0.001). Significant changes in HRV indices from baseline developed before the identification of a symptomatic or inflammatory flare (P < 0.001). Conclusions Longitudinally evaluated HRV was associated with UC symptoms, inflammation, and perceived and physiological measures of stress. Significant changes in HRV were observed before the development of symptomatic or inflammatory flare.

BACKGROUND & AIMS: Ustekinumab induces and maintains histologic improvement in patients with ulcerative colitis (UC). The clinical relevance of this endpoint alone, and in combination with endoscopic improvement, is unknown. METHODS: Histologic disease activity was evaluated in 2630 colonic biopsy samples from patients with UC treated in the UNIFI phase 3 UC clinical studies of ustekinumab. We evaluated associations between histologic improvement (defined as the composite of neutrophil infiltration in less than 5% of crypts and no crypt destruction, erosions, ulcerations, or granulation tissue) and clinical endpoints at the end of induction (week 8 and 16) and maintenance (week 44) periods. We assessed the validity of a combined histologic and endoscopic (Mayo endoscopy subscore, 0 or 1) improvement endpoint, which we called histo-endoscopic mucosal healing (or histo-endoscopic mucosal improvement). RESULTS: Histologic improvement was significantly (P < .0001) associated with clinical remission, lower mean disease activity scores, and greater improvement in disease activity at the end of induction and maintenance studies. Ustekinumab induced and maintained significantly higher rates of histologic improvement at induction week 8 and maintenance week 44 than placebo when more stringent definitions of histologic improvement were used. Histologic improvement and endoscopic improvement following induction were associated with 10% to 20% higher rates of histo-endoscopic mucosal healing, clinical remission, and corticosteroid-free remission at week 44 (all P < .05) in patients who received ustekinumab maintenance therapy. At week 44, 61% of patients (56/92) with histo-endoscopic mucosal healing after induction therapy achieved clinical remission, versus 39% of patients (9/23, P = .0983) and 34% of patients (24/71, P = .0009) with endoscopic or histologic improvement alone after induction, respectively. CONCLUSION: Data from the UNIFI program of ustekinumab in patients with UC treated with ustekinumab indicated the achievement of histo-endoscopic mucosal healing after induction therapy is associated with lower disease activity at the end of maintenance therapy than either histologic or endoscopic improvement alone. ClinicalTrials.gov number: NCT02407236. ispartof: GASTROENTEROLOGY vol:159 issue:6 ispartof: location:United States status: published

Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults.Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters.The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life.In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients.UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We present an updated analysis of non-melanoma skin cancer (NMSC) events in the tofacitinib UC clinical programme, including final data from the open-label, long-term extension (OLE) study (as of 24 Aug 2020). Methods NMSC events were evaluated from 3 randomised, placebo (PBO)-controlled studies (2 Phase [P]3 induction studies [NCT01465763; NCT01458951]; 1 P3 maintenance study [NCT01458574]) and an OLE study (NCT01470612), as 3 cohorts: Induction (P3 induction studies [patients (pts) receiving tofacitinib 10 mg twice daily (BID) or PBO]); Maintenance (P3 maintenance study [pts receiving tofacitinib 5 or 10 mg BID or PBO]); Overall (pts receiving tofacitinib 5 or 10 mg BID in P3 or OLE studies). Analysis was by predominant dose (PD) 5 or 10 mg BID, based on average daily dose Results 1124 pts were evaluated for NMSC (2809.4 pt-years of tofacitinib exposure; up to 7.8 years of treatment; median duration 685.5 days). NMSC events in Induction and Maintenance were previously reported (Table 1).1 In Overall, NMSC occurred in 21 pts (IR 0.73 [95% confidence interval (CI) 0.45, 1.12]): PD tofacitinib 5 mg BID n=5, IR 0.63 (0.21, 1.48); PD tofacitinib 10 mg BID n=16, IR 0.77 (0.44, 1.25) (Table 1); 2 new cases since May 2019.1 Eleven pts had squamous cell carcinoma and 15 pts had basal cell carcinoma; 5 pts had both. No NMSC was metastatic or led to discontinuation. IRs by time interval and subgroup are reported (Table 2). Prior NMSC (hazard ratio [HR] 12.08 [95% CI 4.20, 34.76]) and age (per 10-year increase, HR 2.01 [1.38, 2.93]) were significant risk factors for NMSC in the multivariable analysis. Prior immunosuppressant use was not a significant risk factor in either the multivariable or univariate analyses. Conclusion In this analysis, NMSC IRs for tofacitinib were similar to those in pts with UC treated with biologics2 and those previously reported in the tofacitinib UC clinical programme.1 NMSC events were more likely to occur in pts with recognised NMSC risk factors: prior NMSC and increasing age.3 Dose dependency of NMSC IR could not be concluded here, as dose changes were permitted. NMSC IRs remained stable over time, up to 7.8 years of exposure. References

Background Ustekinumab (UST) is an IL-12/23p40 antagonist used to treat pts with moderate-to-severe ulcerative colitis (UC). The ongoing UNIFI long-term extension (LTE) evaluates subcutaneous (SC) 90mg UST maintenance therapy, with efficacy (wk152) and safety (wk156) results reported here. Methods 523 intravenous UST induction responders were randomized to SC maintenance therapy (175 SC placebo [PBO]; 172 UST 90mg every 12 weeks [q12w]; 176 UST 90mg q8w). 284 UST pts who completed wk44 entered the LTE. PBO pts were discontinued after wk44 unblinding. Starting at wk56, randomized pts with UC worsening could adjust to q8w. Symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0) was evaluated in randomized pts. Safety was evaluated for all 588 pts treated in the LTE, including the randomized and nonrandomized populations; 188 received PBO and 457 received UST. The nonrandomized population included responders to PBO induction and UST induction nonresponders at wk8 who received SC UST, responded 8 wks later and received UST 90mg q8w. Results Among all pts randomized to UST at maintenance baseline (intent-to-treat population with nonresponder imputation for missing data and treatment failure criteria), 55.2% were in symptomatic remission at wk152 (biologic naïve, 66.1%; biologic failures, 43.5%; Table 1); 96.4% (185/192) of pts in symptomatic remission at wk152 were corticosteroid-free. Overall, 20.1% (39/149 biologic failure, 16/149 biologic naïve) of pts who were randomized to UST and treated in the LTE discontinued treatment between wks44 and 156. Among randomized pts treated with UST in the LTE, 67.6% were in symptomatic remission at wk152; 76.4% of those in clinical remission at wk44 were in symptomatic remission at wk152; and 84.1% of pts with observed data at wk152 were in symptomatic remission. From maintenance wk0-156, combined UST and PBO pts had 1281.6 and 425.0 pt-years of follow-up, respectively; and safety events per 100 pt-years of follow-up for combined UST vs PBO were AEs: 235.81 vs 204.48, SAEs: 7.73 vs 7.53, and serious infections: 2.34 vs 2.35 (Table 2). From wks96-156, there were no reported deaths or major adverse cardiovascular events. One UST-treated pt with fair skin and a prior history of basal cell carcinoma (BCC) reported 2 BCC. One 90 mg q8w UST pt receiving concomitant 6-MP reported SAEs of neutropenic sepsis and oral herpes SAE; the latter events were considered potential opportunistic infections. The dose of 6-MP was reduced, pt recovered and continued UST. Conclusion The efficacy of UST in pts with UC was sustained through 3 years. No new safety signals were observed.

Wearable devices are designed to capture health-related and physiological data. They may be able to improve inflammatory bowel disease management and address evolving research needs. Little is known about patient perceptions for their use in the study and management of inflammatory bowel disease. The aim of this survey study is to understand patient preferences and interest in wearable technology. Consecutive adult patients who self-reported having inflammatory bowel disease were approached at the Susan and Leonard Feinstein Inflammatory Bowel Disease Center at the Mount Sinai Hospital to complete a 28-question survey. Reponses were analyzed with descriptive statistics. The Pearson Chi-square test and Fischer’s exact test were used to determine the association between demographic and disease-related features and survey responses. Four hundred subjects completed the survey. 42.7% of subjects reported prior or current use of wearable devices. 89.0% of subjects believed that wearable devices can provide important information about their health, while 93.8% reported that they would use a wearable device if it could help their doctor manage their IBD. Subjects identified wrist-worn devices as the preferred device type and a willingness to wear these devices at least daily. Patients with inflammatory bowel disease believe that wearable devices can provide important information about their health and report a willingness to wear them frequently in research studies and as part the routine management of inflammatory bowel disease.

Background When compared with younger patients, much less is known regarding inflammatory bowel disease (IBD)-related medications in the elderly (>65 years) patients. This analysis uses a large cohort of patients with IBD to describe the distribution of patient characteristics and patterns of medication use. Methods TARGET-IBD is a longitudinal cohort of patients with IBD receiving usual care at community and academic practices in the US. Patients with IBD enrolled between July 2017 and May 2019 were included in this analysis. The prevalence of medication use by drug class at the time of enrolment among patients with both ulcerative colitis (UC) and Crohn’s disease (CD) was estimated. Age was stratified into the following categories: 65 years. Proportions and means of patient characteristics were compared using tests of association. The odds of biologic use at enrolment was modelled as was the 95% CI by patient characteristics using logistics regression. Results 681 patients with UC and 979 patients with CD were included in the analysis. At enrolment, mesalamine was the most common medication used among patients with CD >65 years (34%) and among patients with UC across all age categories (58%–77%, Table 1). The use of mesalamine generally increased with advancing age. Patients with CD >65 years were more than twice as likely to be users of mesalamine at enrolment than patients 65 years compared with patients 65 at enrolment, use of a 5-ASA derivative, anti-TNF, steroid, or thiopurine did not differ by established and newly diagnosed patients. There was no association between age, type of IBD, insurance, gender, race or cardiovascular disease and the odds of biologic use in patients >65 years (Figure 1). Conclusion Elderly patients with IBD, whether those with new diagnoses or individuals with the longstanding disease make up a substantial portion of the IBD population. Given that elderly patients demonstrate significant differences in medication use patterns compared with younger patients with IBD, studies of efficacy and adverse events specific to this population are warranted.

Background Crohn’s disease recurrence after ileocolic resection is common and graded with the Rutgeerts score. There is controversy whether anastomotic ulcers represent disease recurrence and should be included in the grading system. The aim of this study was to determine the impact of anastomotic ulcers on Crohn’s disease recurrence in patients with prior ileocolic resections. Secondary aims included defining the prevalence of anastomotic ulcers, risk factors for development, and their natural history. Methods We conducted a retrospective cohort study of patients undergoing an ileocolic resection between 2008 and 2017 at a large academic center, with a postoperative colonoscopy assessing the neoterminal ileum and ileocolic anastomosis. The primary outcome was disease recurrence defined as endoscopic recurrence (>5 ulcers in the neoterminal ileum) or need for another ileocolic resection among patients with or without an anastomotic ulcer in endoscopic remission. Results One hundred eighty-two subjects with Crohn’s disease and an ileocolic resection were included. Anastomotic ulcers were present in 95 (52.2%) subjects. No factors were associated with anastomotic ulcer development. One hundred eleven patients were in endoscopic remission on the first postoperative colonoscopy. On multivariable analysis, anastomotic ulcers were associated with disease recurrence (adjusted hazard ratio [aHR] 3.64; 95% CI, 1.21–10.95; P = 0.02). Sixty-six subjects with anastomotic ulcers underwent a second colonoscopy, with 31 patients (79.5%) having persistent ulcers independent of medication escalation. Conclusion Anastomotic ulcers occur in over half of Crohn’s disease patients after ileocolic resection. No factors are associated with their development. They are associated with Crohn’s disease recurrence and are persistent.

Background and Aims The UNIFI long-term extension [LTE] study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through 3 years of maintenance therapy. Methods Patients randomised to ustekinumab every 12 weeks [q12w] or every 8 weeks [q8w] at maintenance baseline [N = 348] and randomised ustekinumab-treated patients in the LTE [N = 284] were evaluated. Symptomatic remission [Mayo stool frequency = 0/1, rectal bleeding = 0] was assessed. Safety included all LTE patients [N = 188 placebo and N = 457 ustekinumab]. Results Among patients randomised to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at Week 152, respectively. Overall, 20% of patients discontinued ustekinumab, 10% of biologic-naïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at Year 3, 94.6% and 98.0% of patients were also corticosteroid free, respectively. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at Week 152, respectively. Remission rates were higher for biologic-naïve patients than for those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased C-reactive protein and faecal calprotectin measurements over 3 years. From Weeks 96 to 156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis, and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma [BCC] reported two BCCs. One patient in the q8w ustekinumab group, who was receiving concomitant 6-mercaptopurine, experienced serious adverse events of neutropenic sepsis and oral herpes. Conclusions Efficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed.

Women with inflammatory bowel disease (IBD) face difficult decisions regarding treatment during pregnancy: while the majority of IBD medications are safe, there is substantial societal pressure to avoid exposures during pregnancy. However, discontinuation of IBD medications risks a disease flare occurring during pregnancy.This study quantified women's knowledge about pregnancy and IBD and their willingness to accept the risks of adverse pregnancy outcomes to avoid disease activity or medication use during pregnancy.Women with IBD recruited from four centers completed an online discrete-choice experiment stated-preference study including eight choice tasks and the Crohn's and Colitis Pregnancy Knowledge questionnaire. Random-parameters logit was used to estimate preferences for both the respondent personally and what the respondent thought most women would prefer. We also tested for systematically different preferences among individuals with different demographic and personal characteristics, including IBD knowledge. The primary outcome was the maximum acceptable risk of premature birth, birth defects, or miscarriage that women with IBD were willing to accept to avoid (1) taking an IBD medication or (2) having a disease flare during pregnancy.Among 230 respondents, women would accept, on average, up to a 4.9% chance of miscarriage to avoid a disease flare. On average, there were no statistically significant differences in women's preferences for continuing versus avoiding medication in the absence of a flare. However, prior understanding of IBD and pregnancy significantly affected preferences for IBD medication use during pregnancy: women with "poor knowledge" would accept up to a 6.4% chance of miscarriage to avoid IBD medication use during pregnancy, whereas women with "adequate knowledge" would accept up to a 5.1% chance of miscarriage in order to remain on their medication. Respondents' personal treatment preferences did not differ from their assessment of other women's preferences.Women with IBD demonstrated a strong preference for avoiding disease activity during pregnancy. Knowledge regarding pregnancy and IBD was a strong modifier of preferences for continuation of IBD medications during pregnancy. These findings point to an important opportunity for intervention to improve disease control through education to increase medication adherence and alleviate unnecessary fears about IBD medication use during pregnancy.

BACKGROUND: Endoscopy is routine in trials of ulcerative colitis therapies. AIM: To investigate agreement between central and local Mayo endoscopic subscore (MES) reads in the OCTAVE programme METHODS: Flexible sigmoidoscopy was performed in tofacitinib induction (OCTAVE Induction 1&2, NCT01465763 and NCT01458951), maintenance (OCTAVE Sustain, NCT01458574) and open-label, long-term extension (OCTAVE Open, NCT01470612) studies. Kappa statistics and Bowker's tests evaluated agreement/disagreement between centrally and locally read MES, with potential determinants of differences analysed by logistic regression. RESULTS: Moderate-to-substantial agreement was observed between central and local reads at screening (77.1% agreement; kappa 0.62 [95% confidence interval 0.59-0.66]), OCTAVE Induction 1&2 week (Wk) 8 (63.8%; 0.62 [0.59-0.66]), OCTAVE Sustain Wk 52 (55.6%; 0.56 [0.50-0.62]) and for induction non-responders at OCTAVE Open month 2 (59.9%; 0.54 [0.48-0.60]). Where disagreements occurred, local reads were systematically lower than central reads at OCTAVE Induction 1&2 Wk 8, OCTAVE Sustain Wk 52 and OCTAVE Open month 2 (Bowker's P

Rapid symptomatic relief is an important treatment goal for patients with ulcerative colitis (UC). We aimed to characterize early response with ustekinumab in patients with moderate-to-severe UC during the initial 16 weeks of treatment.We performed a post hoc analysis of data from A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis trial. Patients (N = 961) were randomized (1:1:1) to receive intravenous 130 mg ustekinumab, approximately 6 mg/kg ustekinumab, or placebo at week 0. Symptomatic remission, absolute stool number, Mayo stool frequency and rectal bleeding subscores, partial Mayo score, C-reactive protein, and fecal calprotectin were assessed in the overall population and for patients in the biologic-naïve or prior biologic failure subgroups.A significantly greater percentage of patients in the 130-mg ustekinumab (20.0%; P = .015) or approximately 6-mg/kg ustekinumab (20.2%; P = .012) groups achieved symptomatic remission at week 2 vs placebo (12.9%). Mean [SD] changes from baseline in daily stool number on day 7 were greater in the ustekinumab groups (-1.1 [2.6] in 130 mg [P = .065] and -1.2 [2.5] in ∼6 mg/kg [P = .017]) vs placebo (-0.7 [2.7]). The percentage of patients with Mayo stool frequency subscore of 1 or less and rectal bleeding subscore of 0 increased from baseline through week 16 for both ustekinumab groups. Significant improvements in partial Mayo scores were observed by week 2 in both ustekinumab groups vs placebo (P ≤ .001). Significantly more patients in the ustekinumab groups had normalized C-reactive protein levels from week 2 to week 8 vs placebo (P ≤ .05). Similar results were observed with normalized fecal calprotectin levels between week 2 and week 4 (P ≤ .05).Ustekinumab improved symptoms in patients with UC compared with placebo in as early as 7 days, indicating rapid onset of effect after induction.ClinicalTrials.gov: NCT02407236.

Background Inflammatory bowel disease (IBD) treatment paradigms recommend objective disease activity assessment and reactive therapeutic drug monitoring (TDM) prior to changes in biologic therapy. We aimed to describe objective marker and TDM assessment in routine clinical practice prior to biologic therapeutic changes in adult IBD patients. Methods TARGET-IBD is a prospective longitudinal cohort of over 2100 IBD patients receiving usual care at 34 US academic or community centers enrolled between June 2017 and October 2019 who received biologic therapy and had a dose change or biologic discontinuation for lack of efficacy. Objective markers of disease activity within 12 weeks prior included fecal calprotectin, C-reactive protein (CRP), endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). TDM data for infliximab or adalimumab was obtained. Results 525 patients (71.4% Crohn’s disease [CD], 28.6% ulcerative colitis [UC]) receiving biologic therapy underwent dose change (55.6%) or discontinuation (44.4%) for lack of efficacy. The majority were Caucasian (85.7%), 18–39 years old (52.2%), privately insured (81.5%), and at academic centers (73.7%). For dose changes, 67.5% had at least one objective disease activity assessment or TDM in the 12 weeks prior (CD 67.9%, UC 66.2%; P = 0.79). The most common objective marker was CRP in both CD (39.1%) and UC (54.5%). CRP and calprotectin were used significantly more in UC (P = 0.02 and P = 0.03). TDM was obtained in 30.7% (28.8% UC, 31.4% CD; P = 0.72) prior to dose change. For biologic discontinuation, 79.4% patients underwent objective assessment or TDM prior. In CD, CRP (46.3%) was most common, and CT (P = 0.03) and MRI (P P = 0.49) prior to discontinuation. Among all participants with dose change or discontinuation, endoscopy was performed in 29.3% with CD and 31.3% with UC. Academic care setting was associated with objective assessment before therapy change (OR 1.59, 95% CI 1.01–2.50). Conclusion Nearly one-third of patients undergoing a biologic dose change or discontinuation do not undergo objective disease activity assessment or TDM. Assessment choice differs by disease. Future studies assessing the impact of such practices on long-term outcomes are needed.

ObjectiveIBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less invasive assessments.DesignTranscriptome analysis on 712 endoscopically defined inflamed (Inf) and 1778 non-inflamed (Non-Inf) intestinal biopsies (n=498 Crohn’s disease, n=421 UC and 243 controls) in the Mount Sinai Crohn’s and Colitis Registry were used to identify genes differentially expressed between Inf and Non-Inf biopsies and to generate a molecular inflammation score (bMIS) via gene set variance analysis. A circulating MIS (cirMIS) score, reflecting intestinal molecular inflammation, was generated using blood transcriptome data. bMIS/cirMIS was validated as indicators of intestinal inflammation in four independent IBD cohorts.ResultsbMIS/cirMIS was strongly associated with clinical, endoscopic and histological disease activity indices. Patients with the same histologic score of inflammation had variable bMIS scores, indicating that bMIS describes a deeper range of inflammation. In available clinical trial data sets, both scores were responsive to IBD treatment. Despite similar baseline endoscopic and histologic activity, UC patients with lower baseline bMIS levels were more likely treatment responders compared with those with higher levels. Finally, among patients with UC in endoscopic and histologic remission, those with lower bMIS levels were less likely to have a disease flare over time.ConclusionTranscriptionally based scores provide an alternative objective and deeper quantification of intestinal inflammation, which could augment current clinical assessments used for disease monitoring and have potential for predicting therapeutic response and patients at higher risk of disease flares.

Background & Aims Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in a dose-ranging phase 2 induction trial, 3 phase 3 randomized, placebo-controlled trials (OCTAVE Induction 1 and 2; and OCTAVE Sustain), and an ongoing, open-label, long-term extension trial (OCTAVE Open) in patients with moderately to severely active UC. Here, we assessed short- and long-term efficacy and safety of extended induction (16 weeks) with tofacitinib 10 mg twice daily (BID) in patients who failed to respond to initial induction (8 weeks) treatment. Methods In patients who achieved a clinical response following extended induction (delayed responders), the efficacy and safety of tofacitinib were evaluated up to Month 36 of OCTAVE Open. Results 52.2% of patients who did not achieve clinical response to 8 weeks’ treatment with tofacitinib 10 mg BID in the induction studies achieved a clinical response following extended induction (delayed responders). At Month 12 of OCTAVE Open, 70.3%, 56.8%, and 44.6% of delayed responders maintained clinical response and achieved endoscopic improvement and remission, respectively. Corresponding values at Month 36 were 56.1%, 52.0%, and 44.6%. The safety profile of the subsequent 8 weeks was similar to the initial 8 weeks. Conclusions Overall, the majority of patients achieved a clinical response after 8 or 16 weeks’ induction therapy with tofacitinib 10 mg BID. Tofacitinib 10 mg BID, administered as induction therapy for up to 16 weeks, had a comparable safety profile to 8 weeks’ induction therapy. Most delayed responders at Month 36 were in remission. ClinicalTrials.gov: NCT00787202 ; NCT01465763 ; NCT01458951 ; and NCT01470612.

Genome-wide association studies (GWAS) have identified hundreds of loci associated with Crohns disease (CD), however, as with all complex diseases, deriving pathogenic mechanisms from these non-coding GWAS discoveries has been challenging. To complement GWAS and better define actionable biological targets, we analysed sequenced data from more than 30,000 CD patients and 80,000 population controls. We observe rare coding variants in established CD susceptibility genes as well as ten genes where coding variation directly implicates the gene in disease risk for the first time.

BACKGROUND The COVID-19 pandemic has resulted in a high degree of psychological distress among health care workers (HCWs). There is a need to characterize which HCWs are at an increased risk of developing psychological effects from the pandemic. Given the differences in the response of individuals to stress, an analysis of both the perceived and physiological consequences of stressors can provide a comprehensive evaluation of its impact. OBJECTIVE This study aimed to determine characteristics associated with longitudinal perceived stress in HCWs and to assess whether changes in heart rate variability (HRV), a marker of autonomic nervous system function, are associated with features protective against longitudinal stress. METHODS HCWs across 7 hospitals in New York City, NY, were prospectively followed in an ongoing observational digital study using the custom Warrior Watch Study app. Participants wore an Apple Watch for the duration of the study to measure HRV throughout the follow-up period. Surveys measuring perceived stress, resilience, emotional support, quality of life, and optimism were collected at baseline and longitudinally. RESULTS A total of 361 participants (mean age 36.8, SD 10.1 years; female: n=246, 69.3%) were enrolled. Multivariate analysis found New York City’s COVID-19 case count to be associated with increased longitudinal stress (P=.008). Baseline emotional support, quality of life, and resilience were associated with decreased longitudinal stress (P<.001). A significant reduction in stress during the 4-week period after COVID-19 diagnosis was observed in the highest tertial of emotional support (P=.03) and resilience (P=.006). Participants in the highest tertial of baseline emotional support and resilience had a significantly different circadian pattern of longitudinally collected HRV compared to subjects in the low or medium tertial. CONCLUSIONS High resilience, emotional support, and quality of life place HCWs at reduced risk of longitudinal perceived stress and have a distinct physiological stress profile. Our findings support the use of these characteristics to identify HCWs at risk of the psychological and physiological stress effects of the pandemic.

Background Data on care patterns for inflammatory bowel disease (IBD) from large-scale, diverse clinical cohorts in real-world practice are sparse. We developed a real-world cohort of patients receiving care at academic and community sites, for comparative study of therapies and natural history of IBD. Methods We describe novel methodology of central abstraction of clinical data into a real-world IBD registry with patient reported outcomes (PROs). Baseline demographics, clinical characteristics, healthcare utilization, and disease metrics were assessed. Bivariate statistics were used to compare demographic and clinical data by Crohn disease (CD) or ulcerative colitis (UC) and site of care (academic, community). Results In 1 year, 1343 IBD patients (60.1% CD, 38.9% UC) were recruited from 27 academic (49.5%) and community (50.5%) sites, exceeding expectations (110% enrolled). Most participants also consented to provide PROs (59.5%) or biosamples (85.7%). Overall, 48.7% of the cohort provided a baseline PRO, and 62.6% provided a biosample. Compared to UC, CD subjects had higher prior (34.1% CD vs 7.7% UC; P < 0.001) and current (72.1% vs 47.9%; P < 0.001) biologic utilization. CD participants from academic sites had more complicated disease than those from community sites (62.5% vs 46.8% stricturing/penetrating; 33.5% vs 27% perianal; 36.8% vs 14.5% prior biologic, respectively). Nearly all (90.4%) participants had endoscopic data of whom 37.7% were in remission. One-year retention was 98.4%. Conclusions Centralized data abstraction and electronic PRO capture provided efficient recruitment into a large real-world observational cohort. This novel platform provides a resource for clinical outcomes and comparative effectiveness research in IBD.

International audience; Background: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD.Methods: Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale.Results: In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn's disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth.Conclusions: STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.

Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of UC. In data analysed from a large, ongoing (data cut-off February 2019 [a]; database unlocked; data may be subject to change), post-authorisation safety study in patients with RA (≥50 years; ≥1 cardiovascular risk factor; enrolled on a stable dose of MTX), the incidence rate (IRs; unique patients with events per 100 pt-years [PY]) of pulmonary embolism (PE) in patients treated with tofacitinib 10mg BID (0.54 [95% CI] 0.32, 0.87]) was numerically higher compared with 5 mg BID (0.27 [0.12, 0.52]) and statistically different from TNFi (0.09 [0.02, 0.26]). Corresponding IRs for deep vein thrombosis (DVT) were 0.38 (0.20, 0.67), 0.30 (0.14, 0.55) and 0.18 (0.07, 0.39).1 UC is a known risk factor for DVT and PE. Subsequently, updates to the tofacitinib prescribing information have been made, with venous thromboembolism added as a warning and adverse drug reaction. Here, we provide an update on the incidence of DVT and PE in the tofacitinib UC clinical development programme, as of May 2019.2 Methods DVT and PE events were evaluated from 4 randomised placebo-controlled studies (Phase [P]2/P3 induction studies and P3 maintenance study) and an ongoing, open-label, long-term extension (OLE) study.3,4 Three cohorts were analysed: Induction, Maintenance and Overall (patients receiving tofacitinib 5 or 10mg BID in P2/P3/OLE studies; patients were categorised based on the average daily dose: predominant dose [PD] 5 or 10 mg BID). Results 1157 patients were evaluated for DVT and PE, with 2581 PY of tofacitinib exposure and up to 6.8 years’ treatment. In the Induction and Maintenance Cohorts, 2 patients had DVT and 2 had PE; all were receiving placebo at the time of the event (tables). In the Overall Cohort, DVT occurred in 1 pt and PE in 4 patients during the OLE study, after ≥7 months of treatment; all patients had received PD 10 mg BID (83% of Overall Cohort received PD 10 mg BID) and had other (non-UC) risk factors for venous thrombosis (tables). Conclusion IRs in the Overall Cohort have remained stable since the previously reported data cut.2 All of the events in tofacitinib patients (PD 10 mg BID) occurred during the OLE study and all had other (non-UC) risk factors for thromboembolic events. This analysis is limited by sample size and duration of drug exposure; further study is needed. [a] The tofacitinib 10mg BID arm of the study was discontinued in February 2019 and patients who re-consented and chose to remain in the study were switched to the 5 mg BID arm. References

Background Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn’s disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. Methods We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014–June 2015 (Era 1) and July 2015–June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. Results A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease–related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. Conclusion Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later., There has been a shift in utilization of vedolizumab in both Crohn’s disease and ulcerative colitis toward earlier use in the treatment sequencing algorithm. This shift in utilization is associated with improvements in response and disease outcomes.

Background and Aims Cross-sectional studies on sexual function in men with inflammatory bowel disease (IBD) yield mixed results. Using a prospective incidence cohort, we aimed to describe sexual function at baseline and over time and to identify factors associated with impaired sexual function in men with IBD. Methods Men 18 years and older enrolled between April 2008 and January 2013 in the Ocean State Crohn’s and Colitis Area Registry (OSCCAR) with a minimum of 2 years of follow-up were eligible for study. Male sexual function was assessed using the International Index of Erectile Function (IIEF), a self-administered questionnaire that assesses 5 dimensions of sexual function over the most recent 4 weeks. To assess changes in the IIEF per various demographic and clinical factors, linear mixed effects models were used. Results Sixty-nine of 82 eligible men (84%) completed the questionnaire (41 Crohn’s disease, 28 ulcerative colitis). The mean age (SD) of the cohort at diagnosis was 43.4 (19.2) years. At baseline, 39% of men had global sexual dysfunction, and 94% had erectile dysfunction. Independent factors associated with erectile dysfunction are older age and lower physical and mental component summary scores on the Short Form Health Survey (SF-36). Conclusion In an incident cohort of IBD patients, most men had erectile dysfunction. Physicians should be aware of the high prevalence of erectile dysfunction and its associated risk factors among men with newly diagnosed IBD to direct multidisciplinary treatment planning.

In order to identify the practical implications for both health care practitioners and patients in understanding differences between the results of trials assessing therapies for ulcerative colitis [UC], we reviewed clinical trials of therapies for moderate to severe UC, with a focus on trial design. Over time, patient populations in UC trials have become more refractory, reflecting that patients are failing treatment with additional and different classes of drug, including conventional therapies, immunosuppressant drugs, and anti-tumour necrosis factor therapies. Outcomes used to measure efficacy have become increasingly stringent in order to meet the expectations of patients and physicians, and the requirements of regulatory bodies. Trial design has also evolved to integrate induction and maintenance therapy phases, so as to facilitate patient recruitment and to answer clinically important questions such as how efficacious therapies are in specific subpopulations of patients and during long-term use. As UC clinical trial design continues to evolve, and with limited head-to-head trials and real-world comparative effectiveness studies evaluating UC therapies, careful judgment is required to appreciate the differences and similarities in trial designs, and to understand how these variances may affect the observed efficacy and safety outcomes.

BACKGROUND The literature provides conflicting data on sexual function in women with inflammatory bowel disease (IBD). We aim to describe sexual function at baseline and over time in a prospective inception cohort of adult women with IBD. METHODS Women age 18 years or older enrolled in the Ocean State Crohn's & Colitis Area Registry (OSCCAR) with 2 years of prospective follow-up were included in the study. All subjects were enrolled within 1 year of IBD diagnosis. Female sexual function was assessed using the Female Sexual Function Index (FSFI). Linear mixed effects models were used to assess changes in FSFI by various demographic and clinical factors. RESULTS One hundred sixteen of 130 eligible women (89%) were included in the study. Ninety-seven percent of women had sexual dysfunction, defined as an FSFI score of