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The impact of co-existing immune-mediated diseases on phenotype and outcomes in inflammatory bowel diseases.

ABSTRACT: BACKGROUND:Inflammatory bowel diseases lead to progressive bowel damage and need for surgery. While the increase in prevalence of other immune-mediated diseases in IBD is well recognised, the impact of this on the natural history of IBD is unknown. AIM:To determine the impact of concomitant immune-mediated diseases on phenotypes and outcomes in IBD. METHODS:Patients with IBD enrolled in a prospective registry were queried about the presence of other immune-mediated diseases, defined as those where immune dysregulation plays a role in pathogenesis. Demographics and disease-related information were obtained. Subjects also completed measures of quality of life. Multivariable regression models compared disease phenotype and outcomes of IBD patients with and without other immune-mediated diseases. RESULTS:The cohort included 2145 IBD patients among whom 458 (21%) had another immune-mediated disease. There was no difference in CD phenotype between the two groups. UC patients were more likely to have pancolitis in the presence of another immune-mediated disease (62%) compared to those without (52%, P = 0.02). IBD patients with another immune-mediated disease had higher rates of needing anti-TNF biologics [Odds ratio (OR) 1.31, 95% CI 1.05-1.63] and surgery (OR 1.26, 95% CI 0.99-1.61). The presence of another immune-mediated disease was also associated with lower disease-specific and general physical quality of life. CONCLUSIONS:The presence of another immune-mediated disease in IBD patients was associated with higher likelihood of pancolonic involvement in UC, and a modest increase in need for IBD-related surgery and anti-TNF biological therapy. Such patients also experienced worse quality of life.

SUBMITTER: Conway G

PROVIDER: S-EPMC5315585 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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The impact of co-existing immune-mediated diseases on phenotype and outcomes in inflammatory bowel diseases.

Conway G G Velonias G G Andrews E E Garber J J JJ Yajnik V V Ananthakrishnan A N AN

Alimentary pharmacology & therapeutics 20170120 6

<h4>Background</h4>Inflammatory bowel diseases lead to progressive bowel damage and need for surgery. While the increase in prevalence of other immune-mediated diseases in IBD is well recognised, the impact of this on the natural history of IBD is unknown.<h4>Aim</h4>To determine the impact of concomitant immune-mediated diseases on phenotypes and outcomes in IBD.<h4>Methods</h4>Patients with IBD enrolled in a prospective registry were queried about the presence of other immune-mediated diseases ...[more]

PMID: 28105709

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Project description:IntroductionKidney disease is a well-known extraintestinal manifestation (EIM) associated with inflammatory bowel disease (IBD), with a variety of underlying etiologies. However, little is known about the overall outcomes and predictors.MethodsThis is a retrospective, observational cohort study. Patients with IBD in whom a native kidney biopsy was performed at Mayo Clinic (Rochester, MN) between 1994 and 2022, were included. Demographic, clinical, and histologic characteristics of prognostic interest were collected. The main outcomes were kidney failure, disease remission, kidney function changes at last follow-up, and death.ResultsFrom a total cohort of 318 patients, we selected a study group of 111 patients followed-up with at our institution (45 ulcerative colitis [UC] and 66 Crohn's disease [CD]), with a mean age of 48 ± 17 years (40% females). IgA nephropathy (IgAN), chronic interstitial nephritis (CIN), and acute interstitial nephritis (AIN) were the most common diagnoses (22%, 19%, 13%, respectively). Median estimated glomerular filtration rate (eGFR) at presentation was 30 ml/min per 1.73 m2 (interquartile range [IQR]: 17-54) and urinary protein-to-creatinine ratio [UPCR] 0.8 g/g (0.3-3.4), without differences between IBD types. During a median follow-up of 59 months (12-109), 29 patients (26%) reached kidney failure. By multivariable analysis, the main predictors of kidney failure were age (hazard ratio [HR]: 1.04; P = 0.002), baseline eGFR (HR: 0.94; P = 0.003) and histologic chronicity score (HR: 4.01; P < 0.001). Therapeutic management varied according to underlying etiology. Global survival (kidney failure + death) was significantly better in patients who achieved complete or partial remission, or stabilization or improvement of kidney function.ConclusionOne-fourth of patients with IBD with kidney disease may reach kidney failure, and the main determinants of this outcome is age, baseline eGFR, and degree of chronicity in kidney biopsy.

Project description:BackgroundTherapeutic drug monitoring (TDM) is a decision-making tool for optimizing the use of certain therapies. In this article, the authors review the role of proactive TDM of biological agents in patients with inflammatory bowel disease (IBD) and other immune-mediated inflammatory diseases (IMID). They also discuss the future of TDM as a component of personalized medicine from the clinical laboratory perspective.MethodsThis narrative review originated from proceedings of the fifth biannual Challenges in Therapeutic Drug Monitoring seminar and was supplemented by additional literature identified at various stages of critical review.ResultsProactive TDM aims to achieve adequate concentrations of biological drugs, such that patients attain and maintain an optimal treatment response. Proactive TDM may also have a role in de-escalating anti-tumor necrosis factor therapy in patients in clinical remission and in optimizing infliximab monotherapy as an alternative to combination therapy with an immunomodulator. A major proactive TDM application is in pediatric patients with IBD. Achieving mucosal healing in children with IBD requires that infliximab or adalimumab concentrations are monitored early during induction therapy, with dose modifications guided by the timing (week) of measurement. Recent innovations in biological therapy include international standards for infliximab and adalimumab for the global harmonization of bioactivity and monotest devices with an accuracy equivalent to that of conventional enzyme-linked immunosorbent assays and quicker turnaround times.ConclusionsDespite several knowledge gaps regarding proactive TDM of anti-tumor necrosis factor therapy in patients with IMID, growing evidence suggests that it is associated with better outcomes than empiric optimization and/or reactive TDM in IBD. Enhanced pharmacokinetic modeling to predict drug exposure and patient genotyping for the precise application of proactive TDM are considered key elements to optimize biological therapy in the future.

Project description:BackgroundPatients with Crohn's disease (CD) are at increased risk of co-occurring immune-mediated inflammatory diseases (IMIDs). As discrepancy exists regarding the phenotypic presentation of CD among patients with such co-occurring IMIDs, we aimed to conduct a systematic review with meta-analysis characterizing the phenotype of CD among this subgroup of patients.MethodsPubMed, Embase, and Scopus were searched from their earliest records to October 2019 for studies reporting the behavior and localization of CD according to the Vienna or Montreal Classifications and CD-related surgery in patients with co-occurring IMIDs. These studies were the subject of a random effect meta-analysis.ResultsAfter reviewing 24,413 studies, we identified a total of 23 studies comprising 1572 and 35,043 CD patients with and without co-occurring IMIDs, respectively, that fulfilled our inclusion criteria. Overall, patients with co-occurring IMIDs were more likely to have upper gastrointestinal inflammation than were patients without co-occurring IMIDs [relative risk (RR) = 1.49 (95% confidence interval (CI) 1.09-2.04), p = 0.01, I 2 = 7%]. In addition, presence of primary sclerosing cholangitis (PSC) was associated with a lower occurrence of ileal affection [RR = 0.44 (95% CI 0.24-0.81), p < 0.01, I 2 = 32%], increased occurrence of colonic affection [RR = 1.78 (95% CI 1.33-2.38), p < 0.01, I 2 = 32%] and an increased likelihood of non-stricturing and non-penetrating behavior [RR = 1.43 (95% CI 0.97-2.11), p = 0.07, I 2 = 86%]. The latter reached significance when cumulating different IMIDs [RR = 1.30 (95% CI 1.09-1.55), p < 0.01, I 2 = 88%]. CD patients with PSC also underwent fewer CD-related surgeries [RR = 0.55 (95% CI 0.34-0.88), p = 0.01, I 2 = 0%], irrespective of CD location or behavior.ConclusionThis study emphasizes that CD patients with co-existing PSC are likely to have a unique inflammatory distribution primarily confined to the colon, while patients with IMIDs in general have higher likelihood of affection of upper gastrointestinal tract and a non-stricturing and non-penetrating behavior. As such a phenotype of CD is typically associated with a milder disease course; future studies are needed to confirm these results.

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The impact of co-existing immune-mediated diseases on phenotype and outcomes in inflammatory bowel diseases.

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The impact of co-existing immune-mediated diseases on phenotype and outcomes in inflammatory bowel diseases.

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