The paradigm for treatment for ulcerative colitis (UC) is shifting from resolving symptoms toward objective measures such as mucosal healing (MH). However, it is unclear whether MH is associated with ...improved long-term outcomes. We performed a systematic review and meta-analysis to identify and analyze studies comparing long-term outcomes of patients with MH with those without MH.
We performed a systematic search of 3 large databases to identify prospective studies of patients with active UC that included outcomes of patients found to have MH at the first endoscopic evaluation after initiation of UC therapy (MH1) compared with those without MH1. The primary outcome was clinical remission after at least 52 weeks. Secondary outcomes included proportions of patients who were free of colectomy or corticosteroids and rate of MH after at least 52 weeks.
We analyzed 13 studies comprising 2073 patients with active UC. Patients with MH1 had pooled odds ratio of 4.50 for achieving long-term (after at least 52 weeks) clinical remission (95% confidence interval CI, 2.12-9.52), 4.15 for remaining free of colectomy (95% CI, 2.53-6.81), 8.40 for achieving long-term MH (95% CI, 3.13-22.53), and 9.70 for achieving long-term corticosteroid-free clinical remission (95% CI, 0.94-99.67), compared with patients without MH1. We found no difference in outcomes if patients achieved MH1 while receiving biologic versus non-biologic therapy.
In a meta-analysis, we associated MH with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission. MH is therefore appropriate goal of UC therapy.
Here, we present the reported incidence rates of inflammatory bowel disease (IBD) in patients receiving treatment with secukinumab for psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing ...spondylitis (AS), in a pooled analysis of 21 clinical trials.
Data from all patients who had received at least one dose of secukinumab were included. Safety analyses were conducted to evaluate cumulative IBD rates as well as per-year rates, by indication. Crohn's disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) events were analysed using exposure-adjusted incidence rates (patient incidence rates per 100 patient-years (PY)).
A total of 7355 patients with a cumulative exposure of 16 226.9 PY were included in the pooled analysis. Among 5181 patients with PsO, there were 14 cases of UC, 5 cases of CD and 1 case of IBDU, with exposure adjusted incidence rates (EAIRs) of 0.13, 0.05 and 0.01, respectively. Of these 20 cases, 14 were new-onset. In 1380 patients with PsA, there were 3 cases of UC, 3 cases of CD and 2 cases of IBDU (EAIRs 0.08, 0.08 and 0.05); 7 of these represented new-onset cases. Among 794 patients with AS, there were 4 cases of UC, 8 cases of CD and 1 case of IBDU (EAIRs 0.2, 0.4 and 0.1); 9 were new-onset cases. In the per year analysis, the EAIRs for each indication did not increase over time with secukinumab treatment.
In this pooled secukinumab safety analysis of 7355 patients across 21 clinical trials, cases of IBD events (including CD, UC and IBDU) were uncommon.
Eosinophilic oesophagitis (EoO) and IBD are immune-mediated diseases of the gastrointestinal tract with possible overlapping pathogenic mechanisms. Our aim was to define the epidemiology and clinical ...implications of concurrent EoO and IBD diagnoses.
We conducted a prospective cohort analysis using the Truven MarketScan database (2009-2016) to estimate the incidence and prevalence of EoO in patients with Crohn's disease (CD) or UC and vice versa. Cox proportional hazards and Kaplan-Meier methods were used to estimate the risk of EoO-related or IBD-related complications among patients with concurrent diagnoses.
Among 134 013 536 individuals, the incidence of EoO, CD and UC were 23.1, 51.2 and 55.2 per 100 000 person-years, respectively. The risk of EoO was higher among patients with CD (incidence rate ratio IRR 5.4, p<0.01; prevalence ratio (PR) 7.8, p<0.01) or UC (IRR 3.5, p<0.01; PR 5.0, p<0.01), while the risk of IBD was higher among patients with EoO (CD: IRR 5.7, p<0.01; PR 7.6, p<0.01; UC: IRR 3.4, p<0.01; PR 4.9, p<0.01) versus individuals without either diagnosis. Concurrent diagnosis of EoO and IBD was associated with greater composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.09, p=0.01; UC: aHR 1.10, p=0.04) but lower composite risk of EoO-related complications (aHR 0.59; p<0.01).
Based on a population-based prospective cohort analysis, the risk of EoO is significantly higher among patients with IBD and vice versa. Concurrent diagnoses might modify the risk of IBD-related and EoO-related complications. Studies defining the mechanisms underlying these observations are needed.
Background & Aims Subcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-α (TNFα), was evaluated as maintenance therapy in TNFα antagonist-naive adults with ...moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy. Methods We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT). Patients who responded to induction therapy with golimumab (n = 464) were assigned randomly to groups given placebo or injections of 50 or 100 mg golimumab every 4 weeks through week 52. Patients who responded to placebo in the induction study continued to receive placebo. Nonresponders in the induction study received 100 mg golimumab. The primary end point was clinical response maintained through week 54; secondary end points included clinical remission and mucosal healing at both weeks 30 and 54. Results Clinical response was maintained through week 54 in 47.0% of patients receiving 50 mg golimumab, 49.7% of patients receiving 100 mg golimumab, and 31.2% of patients receiving placebo ( P = .010 and P < .001, respectively). At weeks 30 and 54, a higher percentage of patients who received 100 mg golimumab were in clinical remission and had mucosal healing (27.8% and 42.4%) than patients given placebo (15.6% and 26.6%; P = .004 and P = .002, respectively) or 50 mg golimumab (23.2% and 41.7%, respectively). Percentages of serious adverse events were 7.7%, 8.4%, and 14.3% among patients given placebo, 50 mg, or 100 mg golimumab, respectively; percentages of serious infections were 1.9%, 3.2%, and 3.2%, respectively. Among all patients given golimumab in the study, 3 died (from sepsis, tuberculosis, and cardiac failure, all in patients who received 100 mg golimumab) and 4 developed active tuberculosis. Conclusions Golimumab (50 mg or 100 mg) maintained clinical response through week 54 in patients who responded to induction therapy with golimumab and had moderate-to-severe active ulcerative colitis; patients who received 100 mg golimumab had clinical remission and mucosal healing at weeks 30 and 54. Safety was consistent with that reported for other TNFα antagonists and golimumab in other approved indications. ClinicalTrials.gov number: NCT00488631.
Tumor necrosis factor-α (TNFα) antagonists have advanced the management of inflammatory bowel diseases patients leading to an improvement of patient's quality of life with the reduction of number of ...surgeries and hospitalizations. Despite these advances, many patients do not respond to the induction therapy (primary non-response-PNR) or lose response during the treatment (secondary loss of response-LOR). In this paper we will provide an overview of the definition, epidemiology and risk factors for PNR and LOR, as well as discuss the therapeutic options for managing LOR.
There is a great unmet need for new therapeutics with novel mechanisms of action for patients with Crohn's disease. The ADVANCE and MOTIVATE studies showed that intravenous risankizumab, a selective ...p19 anti-interleukin (IL)-23 antibody, was efficacious and well tolerated as induction therapy. Here, we report the efficacy and safety of subcutaneous risankizumab as maintenance therapy.
FORTIFY is a phase 3, multicentre, randomised, double-blind, placebo-controlled, maintenance withdrawal study across 273 clinical centres in 44 countries across North and South America, Europe, Oceania, Africa, and the Asia-Pacific region that enrolled participants with clinical response to risankizumab in the ADVANCE or MOTIVATE induction studies. Patients in ADVANCE or MOTIVATE were aged 16–80 years with moderately to severely active Crohn's disease. Patients in the FORTIFY substudy 1 were randomly assigned again (1:1:1) to receive either subcutaneous risankizumab 180 mg, subcutaneous risankizumab 360 mg, or withdrawal from risankizumab to receive subcutaneous placebo (herein referred to as withdrawal subcutaneous placebo). Treatment was given every 8 weeks. Patients were stratified by induction dose, post-induction endoscopic response, and clinical remission status. Patients, investigators, and study personnel were masked to treatment assignments. Week 52 co-primary endpoints were clinical remission (Crohn's disease activity index CDAI in the US protocol, or stool frequency and abdominal pain score in the non-US protocol) and endoscopic response in patients who received at least one dose of study drug during the 52-week maintenance period. Safety was assessed in patients receiving at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03105102.
712 patients were initially assessed and, between April 9, 2018, and April 24, 2020, 542 patients were randomly assigned to either the risankizumab 180 mg group (n=179), the risankizumab 360 mg group (n=179), or the placebo group (n=184). Greater clinical remission and endoscopic response rates were reached with 360 mg risankizumab versus placebo (CDAI clinical remission was reached in 74 (52%) of 141 patients vs 67 (41%) of 164 patients, adjusted difference 15% 95% CI 5–24; stool frequency and abdominal pain score clinical remission was reached in 73 (52%) of 141 vs 65 (40%) of 164, adjusted difference 15% 5–25; endoscopic response 66 (47%) of 141 patients vs 36 (22%) of 164 patients, adjusted difference 28% 19–37). Higher rates of CDAI clinical remission and endoscopic response (but not stool frequency and abdominal pain score clinical remission p=0·124) were also reached with risankizumab 180 mg versus withdrawal (subcutaneous placebo; CDAI clinical remission reached in 87 55% of 157 patients, adjusted difference 15% 95% CI 5–24; endoscopic response 74 47% of 157, adjusted difference 26% 17–35). Results for more stringent endoscopic and composite endpoints and inflammatory biomarkers were consistent with a dose–response relationship. Maintenance treatment was well tolerated. Adverse event rates were similar among groups, and the most frequently reported adverse events in all treatment groups were worsening Crohn's disease, arthralgia, and headache.
Subcutaneous risankizumab is a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active Crohn's disease and offers a new therapeutic option for a broad range of patients by meeting endpoints that might change the future course of disease.
AbbVie.
Summary
Background
Accumulating data support a protective role of Helicobacter pylori against inflammatory bowel diseases (IBD), which might be mediated by strain‐specific constituents, specifically ...cagA expression.
Aim
To perform a systematic review and meta‐analysis to more clearly define the association between CagA seropositivity and IBD.
Methods
We identified comparative studies that included sufficient detail to determine the odds or risk of IBD, Crohn's disease (CD) or ulcerative colitis (UC) amongst individuals with vs without evidence of cagA expression (eg CagA seropositivity). Estimates were pooled using a random effects model.
Results
Three clinical studies met inclusion criteria. cagA expression was represented by CagA seropositivity in all studies. Compared to CagA seronegativity overall, CagA seropositivity was associated with lower odds of IBD (OR 0.31, 95% CI 0.21‐0.44) and CD (OR 0.25, 95% CI 0.17‐0.38), and statistically nonsignificant lower odds for UC (OR 0.68, 95% CI 0.35‐1.32). Similarly, compared to H pylori non‐exposed individuals, H pylori exposed, CagA seropositive individuals had lower odds of IBD (OR 0.26, 95% CI 0.16‐0.41) and CD (OR 0.23, 95% CI 0.15‐0.35), but not UC (OR 0.66, 0.34‐1.27). However, there was no significant difference in the odds of IBD, CD or UC between H pylori exposed, CagA seronegative and H pylori non‐exposed individuals.
Conclusion
We found evidence for a significant association between CagA seropositive H pylori exposure and reduced odds of IBD, particularly CD, but not for CagA seronegative H pylori exposure. Additional studies are needed to confirm these findings and define underlying mechanisms.
Summary
Background
There appear to be differences in risk factor profiles for IBD between Asia‐Pacific and Western populations, which might suggest idiosyncrasies in pathogenesis. Recently, sex‐based ...differences in IBD according to the age of diagnosis have been described in Western populations.
Aim
To identify whether sex‐based differences in IBD incidence similarly exist across the age spectrum for Asia‐Pacific populations.
Methods
We identified Asia‐Pacific population‐based cohorts where IBD incidence data stratified by sex were available for the full age spectrum. Cohorts were included only if IBD diagnoses were confirmed and validated. We calculated incidence rate ratios of Crohn's disease (CD) and ulcerative colitis (UC) according to age and compared differences between males and females using random‐effects meta‐analysis.
Results
Among 567.8 million people from 11 Asia‐Pacific countries/provinces/nations, we identified 10 553 incident CD cases (7060 males; 3493 females) and 16 946 incident UC cases (9754 males; 7192 females). Starting in early adolescence until age 50 years, there was a 36%‐64% higher incidence of CD in males vs females (P < 0.001). UC incidence ranged from 20%‐42% higher in males vs females in the age groups between 15 and 65 years (P < 0.05).
Conclusions
In a pooled analysis of population‐based studies from the Asia‐Pacific region, we found a male predominance of both CD and UC for the majority of the age spectrum from adolescence to middle/late‐middle age. Additional studies are needed to clarify biological and nonbiological determinants of sex differences in IBD, which might be distinct between Asia‐Pacific and Western populations.
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