Dataset Information

Low-dose Methotrexate has Similar Outcomes to High-dose Methotrexate in Combination with Anti-TNF Therapy in Inflammatory Bowel Diseases.

ABSTRACT: BACKGROUND AND AIMS:Methotrexate [MTX] is a well-known immunomodulator in the treatment of inflammatory bowel disease [IBD] and is often combined with biologic agents. The ideal MTX dose for combination therapy has not been determined. This study aimed to investigate the effect of varying doses of MTX on efficacy and safety outcomes when used with anti-TNF agents in IBD. METHODS:This study included patients with Crohn's disease [CD] or ulcerative colitis [UC] receiving care between January 2005 and June 2018. Low-dose MTX was defined as ?12.5 mg/week and high-dose as >12.5 mg/week. The primary efficacy outcome was a composite of need for IBD-related hospitalization or surgery, steroid initiation, or change of biologic agent within 1 year. Safety outcomes included side effects related to MTX, serious infections, malignancy, and need to discontinue MTX therapy within 1 year. Multivariable logistic regression models adjusting for relevant covariates were used to assess independent association between MTX dose and outcomes. RESULTS:Our study included 222 patients with IBD [163 CD, 59 UC]. Just under a third were receiving low-dose MTX [28%]. The primary efficacy composite outcome was noted in 75 patients [47%] in the high-dose MTX group compared with 23 patients [37%] in the low-dose MTX group [p = 0.15]. We found no significant associations between MTX dose and any side effect [odds ratio 1.59, 95% confidence interval 0.77-3.31, p = 0.21] or development of serious infections [odds ratio 1.19, 95% confidence interval 0.41-3.45, p = 0.76]. CONCLUSIONS:Low-dose and high-dose MTX combination therapy were equally effective, and no difference in infection or malignancy rates was observed.

SUBMITTER: Borren NZ

PROVIDER: S-EPMC6692531 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Low-dose Methotrexate has Similar Outcomes to High-dose Methotrexate in Combination with Anti-TNF Therapy in Inflammatory Bowel Diseases.

Borren Nienke Z NZ Luther Jay J Colizzo Francis P FP Garber John G JG Khalili Hamed H Ananthakrishnan Ashwin N AN

Journal of Crohn's & colitis 20190801 8

<h4>Background and aims</h4>Methotrexate [MTX] is a well-known immunomodulator in the treatment of inflammatory bowel disease [IBD] and is often combined with biologic agents. The ideal MTX dose for combination therapy has not been determined. This study aimed to investigate the effect of varying doses of MTX on efficacy and safety outcomes when used with anti-TNF agents in IBD.<h4>Methods</h4>This study included patients with Crohn's disease [CD] or ulcerative colitis [UC] receiving care betwee ...[more]

PMID: 30888405

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Project description:OBJECTIVE:Severe myelosuppression is a serious concern in the management of rheumatic disease patients receiving methotrexate (MTX) therapy. This study was intended to explore factors associated with the development of MTX-related myelosuppression and its disease severity. METHODS:We retrospectively examined a total of 40 cases of MTX-related myelosuppression that had been filed in the registries of participating rheumatology and hematology divisions. Data before onset were compared with those of 120 controls matched for age and sex. Cytopenia was graded according to the National Cancer Institute criteria for adverse events. Data before and at onset were compared between the severe and non-severe groups. RESULTS:Non-use of folic acid supplements, concurrent medications, and low renal function were significantly associated with the development of myelosuppression (p < 0.001, p < 0.001, and p = 0.002, respectively). In addition, significantly lower MTX dosages, higher blood cell counts, and lower hemoglobin levels were seen in the myelosuppression group (p < 0.001). No patients exhibited leukocytopenia, neutropenia, or thrombocytopenia in routine blood monitoring taken within the past month. One-fourth developed myelosuppression within the first two months (an early-onset period). Myelosuppression was severe in approximately 40% of patients. Hypoalbuminemia and non-use of folic acid supplements were significantly associated with the severity of pancytopenia (p = 0.001 and 0.008, respectively). Besides these two factors, early onset and the use of lower doses of MTX were significantly associated with the severity of neutropenia (p = 0.003, 0.007, 0.003, and 0.002, respectively). CONCLUSIONS:Myelosuppression can occur abruptly at any time during low-dose MTX therapy, but severe neutropenia is more likely to occur in the early-onset period of this therapy. Contrary to our expectations, disease severity was not dependent on MTX doses. Serum albumin levels and folic acid supplementation are the important factors affecting the severity of MTX-related pancytopenia and neutropenia.

Project description:BackgroundPersonalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient.AimTo identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis.MethodsWe performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis.ResultsA functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis.ConclusionsThere are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.

Project description:Utilization trends and health effects of infliximab and adalimumab in inflammatory bowel disease (IBD) are incompletely understood. We aimed to describe utilization trends of these 2 anti-tumor necrosis factor (TNF) agents, determine the correlation between utilization with rates of hospitalization and surgery and describe differences in use between adults and children.Longitudinal data were analyzed for drug utilization, hospitalization, and abdominal surgery. Descriptive statistics were used to show trends, and utilization quotients were compared for standardization. Multivariate logistic regression analysis assessed the association between drug use and rates of hospitalization and surgery.Four hundred thirty-eight pediatric and 2514 adult patients with IBD generated a total of 51,882 inpatient and outpatient encounters, representing 1185 Crohn's disease, 1531 ulcerative colitis, and 236 indeterminate colitis patients. From 2007 through 2012, utilization quotients declined for hospitalization but remained unchanged for surgery; adalimumab saw a 3-fold increase, despite continued dominance of infliximab. Median band and mean fitted plots showed downward hospitalization trends from 2006 to 2012. Utilization of infliximab peaked in 2008, Q4 with gradual decline to 2012, Q2; and adalimumab showed moderate increased utilization since 2007, Q1. Use of infliximab (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.70-0.83) and adalimumab (OR, 0.79; 95% CI, 0.72-0.87) was associated with decreased hospitalization risk but not associated with reduced abdominal surgery risk. Children had increased hospitalization (OR, 2.68; 95% CI, 2.49-2.88) but decreased risk for abdominal surgery (OR, 0.57; 95% CI, 0.46-0.70).Current infliximab use remains substantially greater than adalimumab use, despite recent increased use of adalimumab. Although trends for hospitalization for IBD are decreasing, it is not reflected in abdominal surgery rates in a tertiary IBD referral center.

Dataset Information

Low-dose Methotrexate has Similar Outcomes to High-dose Methotrexate in Combination with Anti-TNF Therapy in Inflammatory Bowel Diseases.

Publications

Low-dose Methotrexate has Similar Outcomes to High-dose Methotrexate in Combination with Anti-TNF Therapy in Inflammatory Bowel Diseases.

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