ABSTRACT
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that encompasses two major conditions: Crohn's disease (CD) and ulcerative colitis (UC). Historically, IBD has been primarily reported in western countries, but over the past decades, its prevalence is rapidly increasing, especially in lower and middle-income countries (LMICs) such as India and China and also in Sub-Saharan Africa. The prevalence of IBD in LMICs has been the subject of growing concern due to the impact of access to public healthcare and the burden it places on healthcare resources. The classical thiopurines face significant challenges due to cessation of therapy in approximately half of patients within one year due to side effects or ineffectiveness. In this article, we highlight innovating thiopurine treatment for IBD patients in downregulating side effects and improving efficacy.
Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Purines , Sulfhydryl Compounds , Humans , Inflammatory Bowel Diseases/drug therapy , Crohn Disease/drug therapy , Colitis, Ulcerative/drug therapy , Mercaptopurine , Azathioprine/therapeutic use , Immunosuppressive Agents/adverse effectsABSTRACT
We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10â»8). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
Subject(s)
Crohn Disease/genetics , Genetic Loci/genetics , Genetic Predisposition to Disease , Genome, Human/genetics , Genome-Wide Association Study , Computational Biology , Crohn Disease/etiology , Genetic Linkage , Genetic Variation , Humans , Reproducibility of ResultsABSTRACT
BACKGROUND & AIMS: Mycobacterium avium subspecies paratuberculosis has been proposed as a cause of Crohn's disease. We report a prospective, parallel, placebo-controlled, double-blind, randomized trial of 2 years of clarithromycin, rifabutin, and clofazimine in active Crohn's disease, with a further year of follow-up. METHODS: Two hundred thirteen patients were randomized to clarithromycin 750 mg/day, rifabutin 450 mg/day, clofazimine 50 mg/day or placebo, in addition to a 16-week tapering course of prednisolone. Those in remission (Crohn's Disease Activity Index Subject(s)
Anti-Bacterial Agents/administration & dosage
, Clarithromycin/administration & dosage
, Clofazimine/administration & dosage
, Crohn Disease/drug therapy
, Crohn Disease/microbiology
, Mycobacterium Infections/complications
, Mycobacterium avium/classification
, Rifabutin/administration & dosage
, Adult
, Anti-Bacterial Agents/adverse effects
, Anti-Bacterial Agents/therapeutic use
, Clarithromycin/adverse effects
, Clarithromycin/therapeutic use
, Clofazimine/adverse effects
, Clofazimine/therapeutic use
, Double-Blind Method
, Drug Administration Schedule
, Drug Therapy, Combination
, Female
, Glucocorticoids/administration & dosage
, Glucocorticoids/therapeutic use
, Humans
, Male
, Middle Aged
, Patient Compliance
, Prednisolone/administration & dosage
, Prednisolone/therapeutic use
, Rifabutin/adverse effects
, Rifabutin/therapeutic use
, Treatment Failure
