Citations

Abstract Background and Aims Patient-reported outcomes are recommended endpoints in Crohn’s disease [CD] trials. The association between patient-reported general well-being relative to symptoms of diarrhoea and abdominal pain [AP] in patients with moderate to severe CD was explored. Methods Patients from three randomized, placebo-controlled, double-blind adalimumab or upadacitinib studies with average daily very soft/liquid stool frequency [SF] ≥4 and/or AP score ≥2 at baseline were included. Using electronic diaries, patients reported general well-being [seven-point Likert scale; 1 = worst; 7 = best] in item 10 of the Inflammatory Bowel Disease Questionnaire [IBDQ]. Changes in well-being and clinical outcomes of SF and AP from baseline to week 12 or 16, and the relationship between well-being and clinical outcomes were evaluated using cumulative distribution function and probability density function curves. Results In total, 858 patients with CD were included [adalimumab, n = 695; upadacitinib, n = 163]. Patients who achieved clinical remission [SF ≤2.8, AP score ≤1.0, neither worse than baseline] were more likely than those not in clinical remission to report IBDQ item 10 response in the 6–7 group category but not IBDQ categories ≤5. Higher IBDQ score for item 10 [6–7] was associated with lower SF and AP score. Greater point increases in IBDQ item 10 were associated with a greater percentage decrease in clinical parameters; a ≥25–30% decrease in SF or AP was associated with a ≥1-point improvement in IBDQ. Conclusions An association between improvements in patient-reported general well-being and clinical remission/response was observed using outcomes of SF and AP, supporting the clinical remission/response endpoint definitions used in clinical studies of CD. Clinical Trial Registrations [ClinicalTrials.gov]: NCT00077779 [CHARM]; NCT00348283 [EXTEND]; NCT02365649 [CELEST].

INTRODUCTION: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown. METHODS: We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied. RESULTS: Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery. DISCUSSION: Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases.

Abstract Background and Aims To report results from VISIBLE 2, a randomised, double-blind, placebo-controlled, phase 3 trial evaluating a new subcutaneous [SC] vedolizumab formulation as maintenance treatment in adults with moderately to severely active Crohn’s disease [CD]. Methods Following open-label vedolizumab 300 mg intravenous induction therapy at Weeks 0 and 2, Week 6 clinical responders (≥70-point decrease in CD Activity Index [CDAI] score from baseline) were randomised 2:1 to receive double-blind maintenance vedolizumab 108 mg SC or placebo every 2 weeks until Week 50. Assessments at Week 52 included clinical remission [primary endpoint; CDAI ≤150], enhanced clinical response [≥100-point decrease in CDAI from baseline], corticosteroid-free clinical remission among patients using a corticosteroid at baseline, clinical remission in anti-tumour necrosis factor [anti-TNF]-naïve patients, and safety. Results Following vedolizumab intravenous induction, 275 patients were randomised to vedolizumab SC and 135 to placebo maintenance. At Week 52, 48.0% of patients receiving vedolizumab SC versus 34.3% receiving placebo were in clinical remission [p = 0.008]. Enhanced clinical response at Week 52 was achieved by 52.0% versus 44.8% of patients receiving vedolizumab SC versus placebo, respectively [p = 0.167]. At Week 52, 45.3% and 18.2% of patients receiving vedolizumab SC and placebo, respectively, were in corticosteroid-free clinical remission, and 48.6% of anti-TNF-naïve patients receiving vedolizumab SC and 42.9% receiving placebo were in clinical remission. Injection site reaction was the only new safety finding observed for vedolizumab SC [2.9%]. Conclusions Vedolizumab SC is an effective and safe maintenance therapy in patients with CD who responded to two infusions of vedolizumab intravenous induction therapy.

Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease (IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1–10 (1 = strongly disagree and 10 = strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous. During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new statements were proposed, and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be used for all biologics for both primary nonresponse and secondary loss of response. It was recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10–15 μg/mL was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti–tumor necrosis factor therapy. It was recommended to perform proactive TDM after induction and at least once during maintenance. Consensus was achieved in most cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti–tumor necrosis factors.

Abstract Background and Aims Bowel urgency and abdominal pain are impactful, yet under-appreciated ulcerative colitis symptoms and not commonly assessed in clinical trials. We evaluated how these symptoms may improve with upadacitinib treatment and correlate with clinical and health-related quality of life [HRQOL] outcomes in the phase 2b U-ACHIEVE study. Methods Patients aged 18–75 years, with moderately to severely active ulcerative colitis, were randomised to receive placebo or upadacitinib (7.5, 15, 30, or 45 mg once daily [QD]). Bowel urgency and abdominal pain were evaluated at baseline and Weeks 2, 4, 6, and 8. Week 8 correlations were evaluated between bowel urgency/abdominal pain with clinical [Mayo subscores and high-sensitivity C-reactive protein and faecal calprotectin measurements] and HRQOL outcomes [Inflammatory Bowel Disease Questionnaire and 36-Item Short Form Health Survey scores]. Results A greater proportion of patients [n = 250] reported no bowel urgency and less abdominal pain with upadacitinib treatment compared with placebo, with improvements observed as early as 2 weeks. At Week 8, patients receiving the 45-mg QD dose had the greatest improvements versus placebo, with 46% reporting no bowel urgency [vs 9%; p ≤ 0.001] and 38% reporting no abdominal pain [vs 13%; p = 0.015]. At Week 8, moderate correlations were found between bowel urgency or abdominal pain and most clinical and HRQOL outcomes. Conclusions Induction treatment with upadacitinib demonstrated significant reductions in bowel urgency and abdominal pain compared with placebo. These symptoms also correlate to clinical and HRQOL outcomes, supporting their use to monitor disease severity and other treatment outcomes.

Abstract Background and Aims There remains a historical misconception that inflammatory bowel disease [IBD] patients are underweight. However, recent data suggest rates of obesity in IBD parallel to those of the general population. The impact obesity has on the natural history of IBD is unclear. We aimed to determine obesity rates at the time of IBD diagnosis in a population-based cohort of ulcerative colitis [UC] patients. Methods Chart review was performed on patients diagnosed with UC over 1970–2010. Data were collected on demographics, body mass index [BMI], disease characteristics, IBD-specific hospitalisations, intestinal resection, and corticosteroid use. The proportion of patients who were obese at the time of their diagnosis was evaluated over time, and survival free of IBD-related complications was assessed using Kaplan-Meier survival analysis. Results A total of 417 adults were diagnosed with UC over 1970–2010, 55.4% of whom were classified as either overweight [34.8%] or obese [20.6%]. The prevalence of obesity increased 2–3-fold over the 40-year study period. Obese patients had a 72% increased risk of hospitalisation (hazard ratio [HR],1.72; 95% confidence interval [CI], 1.10–2.71; p = 0.018) when compared with normal weight patients. Additionally, with each incremental increase in BMI by 1 kg/m2, the risk of hospitalisation increased by 5% [HR,1.05; 95% CI, 1.01–1.08; p = 0.008] and risk of corticosteroid use increased by 2.6% [HR,1.026; 95% CI, 1.00–1.05; p = 0.05]. Conclusions The prevalence of obesity in the UC population is increasing and may have negative prognostic implications, specifically regarding risk of future hospitalisation and corticosteroid use. Additional prospective studies are necessary to more clearly define these associations.

Abstract Background Filgotinib (FIL) is a once-daily, oral, preferential Janus kinase 1 inhibitor in development for the treatment of inflammatory bowel disease. FIL for the treatment of moderately to severely active ulcerative colitis (UC) was evaluated in the phase 2b/3 randomized, double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522). Long-term use of corticosteroids (CS) is associated with significant side effects. The aim of this post hoc analysis was to assess the CS-sparing effects of FIL in the SELECTION study. Methods Patients (18–75 years old) with moderately to severely active UC were randomized (2:2:1) to receive FIL 100 mg (n = 564), FIL 200 mg (n = 507) or PBO (n = 280) once daily orally for up to 11 weeks (induction study). At week 11, FIL induction responders were rerandomized 2:1 to continue their induction FIL dose or to receive PBO (maintenance study). CS use was kept stable up to week 14, at which point mandatory CS tapering occurred. CS could be resumed during the maintenance study; however, if the baseline CS dose was exceeded this was considered treatment failure. In this post hoc analysis, CS-free remission was defined as remission at week 58 (endoscopic subscore ≤ 1, rectal bleeding subscore = 0 and ≥ 1-point decrease in stool frequency subscore to achieve 0 or 1) without systemic or localized CS use that was indicated for UC in the previous 1, 3, 6 or 8 months. Results The baseline characteristics of patients in the maintenance study were similar across treatment groups (Table 1). Of the 92 patients receiving CS at maintenance baseline (week 11; maintenance week 0) who received FIL 200 mg during the maintenance study, 25 (27%) were in remission at week 58 and had been continuously CS-free for at least the previous 6 months (Table 2). The proportion of CS-free remitters in the FIL 200 mg group was consistently higher than with PBO (Table 2). In patients taking CS at maintenance baseline who had continued CS-use post baseline, lower median prednisone dosing was observed with FIL 200 mg than with PBO throughout the maintenance study (maximum difference at week 34 [maintenance week 23]: 5.0 mg vs 13.8 mg) (Figure 1). In SELECTION, a total of 199 patients received FIL 200 mg in the maintenance study, of whom 74 (37.2%) were in remission at week 58; of these 74 patients, 69 (93.2%) were continuously CS-free for at least the previous 6 months (Figure 2). Conclusion In this post hoc analysis of SELECTION maintenance study data, FIL 200 mg was effective in reducing and eliminating CS use through to week 58 in patients with moderately to severely active UC. The vast majority of patients taking FIL 200 mg who were in remission at week 58 had not taken CS in the previous 6 months.