Dataset Information

Methotrexate treatment efficacy in sarcoidosis might be related to TNF-? polymorphism: real life preliminary study.

ABSTRACT: Introduction:Methotrexate therapy improves lung function in selected sarcoidosis patients. Variation in TNF gene was associated with response to treatment. Aim: To determine the predictive role of-308 G/A, -857C/T, -863 C/A and -1031 T/C TNF-? polymorphism in the efficacy of MTX for progressive pulmonary sarcoidosis. Material and Methods:Twenty-eight sarcoidosis patients treated with MTX (6-24 months) were genotyped for TNF-? polymorphisms: -1031 T/C, -857C/T, -308 G/A and -863 C/A. Pulmonary function test (PFT) were performed every 6 months to determine treatment response, until the drug withdrawal. Results:No correlation between the initial clinical presentation of sarcoidosis and TNF ? polymorphisms was found, neither for every allele nor for combined genotypes distribution. According to PFT evaluation we have discovered 3 types of response to MTX: early (ER), late (LR) and No-response (NR). TNF-?-308 A allele carriers have got significantly higher chance to be LR, p=0.02, RRI:83%. TNF-?-308 GG genotype transferred the 3-fold higher probability of early vs late response to MTX, p=0.02. Combined genotyping allowed to distinguish LR from ER and NR groups. ER and NR patients are genetically similar (-857CC-308GG). LR are "genetically" different group of patients (-857C/T-308GG or -857CC-308A/G) with 5-fold greater probability to be LR than TNF-?-857CC-308GG patients, p=0,005 sensitivity 85%, specificity: 43%, PPV 58%, NPV 75%. TNF-?-308GG-857CC patients have significantly lower chance to be LR comparing to other response type p=0.03 OR=0,075 95% CI=0.07-0.08. Conclusion:Two types of positive response to MTX therapy (early and late) in chronic respiratory sarcoidosis are associated with polymorphic changes in TNF gene.

SUBMITTER: Goljan Geremek A

PROVIDER: S-EPMC7247097 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Methotrexate treatment efficacy in sarcoidosis might be related to TNF-α polymorphism: real life preliminary study.

Goljan Geremek Anna A Puscinska Elzbieta E Czystowska Monika M Skoczylas Agnieszka A Bednarek Michal M Nowinski Adam A Gorecka Dorota D Demkow Urszula U Sliwinski Pawel P

Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG 20190501 4

<h4>Introduction</h4>Methotrexate therapy improves lung function in selected sarcoidosis patients. Variation in TNF gene was associated with response to treatment. <i>Aim:</i> To determine the predictive role of-308 G/A, -857C/T, -863 C/A and -1031 T/C <i>TNF-</i>α polymorphism in the efficacy of MTX for progressive pulmonary sarcoidosis.<h4>Material and methods</h4>Twenty-eight sarcoidosis patients treated with MTX (6-24 months) were genotyped for <i>TNF-</i>α polymorphisms: -1031 T/C, -857C/T, ...[more]

PMID: 32476962

Similar Datasets

Project description:BACKGROUND:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammatory status, joint destruction, disability, and pain. Methotrexate (MTX) has been confirmed to reduce disease activity and delay or stabilize the development of bone erosions. However, major drawbacks are that patients show great interindividual variability in response to MTX and the unpredictable occurrence of side effects. A strategy for personalized MTX treatment to predict its efficacy and toxicity has not yet been determined. To establish personalized MTX therapy in Japanese patients with rheumatoid arthritis, we performed a preliminary study for predicting better methotrexate efficacy including single-nucleotide polymorphisms (SNPs) for MTX-related transporters/enzymes. METHODS:Disease control status (good or poor) was judged by the number of Disease Activity Scores (DAS28) of <2 for 6-12 months. The response index R was calculated by the improved area under the curve (AUC) of the DAS28 score for 0-3 or 0-6 months by dividing the cumulative dose of MTX during 0-3 or 0-6 months, respectively. Genotyping of alleles of RFC1 80G?>?A, RFC1 -43 T?>?C, FPGS 1994G?>?A, GGH 401C?>?T, MTHFR 1298A?>?C, and TYMS 3'-UTR (-6/+6) was performed using the real-time PCR system. RESULTS:Seven of 21 patients were judged as good responders in terms of disease control, and the remainder as poor responders. For 0-3 months after starting MTX administration, the median cumulative dose and improved DAS28 AUC in the good and poor response groups were 96.0 mg and 25.4 and 118.0 mg and 23.4, respectively. For 0-6 months, the median cumulative dose and improved DAS28 AUC in the good and poor response groups were 192.0 mg and 51.0 and 214.0 mg and 47.6, respectively. Statistically significant differences between the 2 groups in the 0-6-month period were observed in DAS28 AUC improvement and index R. A slight tendency for a correlation between G/G genotypes and A allele genotypes in RFC1 80 genotypes was observed, although it did not reach statistical significance. CONCLUSION:This study suggested that aggressive RA treatment with MTX from the early period of administration is necessary to obtain a good response after 6 months, although no SNPs predicting a better treatment response to MTX were identified.

Project description:IntroductionPeripheral inhibition of tumor necrosis factor (TNF)-α, outside of the central nervous system, may result in clinical improvement of Alzheimer's disease (AD) outcomes. TNF-α inhibitors (TNFIs) are effective treatments for various autoimmune conditions and may be effective for preventing and/or treating AD. The objective of this study was to compare the risk of dementia and AD in patients initiating methotrexate versus those initiating TNFIs.MethodsInsurance claims data from databases of commercially insured and Medicare-eligible patients were used to estimate the risk of dementia and AD within patients with rheumatoid arthritis (RA) initiating a TNFI versus initiation of methotrexate. A sensitivity analysis included all patients without the RA diagnosis requirement. The at-risk period spanned from the index date until a diagnosis of the outcome, loss-to-follow-up, or receipt of the comparator drug. Patients were matched 1-to-1 using propensity scores. A Cox proportional hazards model was used to estimate the hazard ratio (HR). Negative controls were used to calibrate the results.ResultsA total of 11,092 new TNFI patients and 44,023 new methotrexate patients were identified, and 8925 from each group were matched. The outcome of dementia occurred in 1.4% of patients in both groups. The calibrated results from the Cox regression found no difference between the two groups (commercially insured database: calibrated HR = 0.69, 95% confidence interval = 0.45 to 1.05; Medicare-only database: 1.14, 0.66 to 1.96). Results were similar in all sensitivity analyses: outcome of AD and including patients without RA.DiscussionNo significant difference for the risk of dementia or AD was seen between patients initiating a TNFI versus methotrexate. Although this study cannot conclude whether use of TNFIs is protective against dementia and AD compared with receiving no treatment, there was no evidence that it is more protective than the active comparator methotrexate.

Dataset Information

Methotrexate treatment efficacy in sarcoidosis might be related to TNF-? polymorphism: real life preliminary study.

Publications

Methotrexate treatment efficacy in sarcoidosis might be related to TNF-α polymorphism: real life preliminary study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets