Pharmacogenetics of Leflunomide in the RA Management
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- DAS Score Measurement
研究概览
简要总结
- Patients taking leflunomide as the only disease-modifying anti-rheumatic drug (DMARD) will be recruited after consent.
- Blood sample for DNA extraction will be taken The patient will be followed up till two visits 3 months apart, and efficacy and toxicity will be checked using DAS28, ultrasonography, and blood tests for ESR, CRP, anti-CCP, liver function tests, etc. The data form for toxicity will be filled.
- DNA will be extracted in the laboratory, and SNP will be identified.
- The efficacy and toxicity data will be studied against the SNPs found
- An algorithm will be constructed for Pakistani RA patients taking leflunomide.
详细描述
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Its prevalence in Pakistan is approximately 0.5% of the general population. Early introduction of disease-modifying anti-rheumatic drugs (DMARDs) along with appropriate intensification of DMARDs (the treat-to-target approach) is the most effective treatment strategy. Leflunomide, a prodrug, is a second-line DMARD used in the treatment of RA. The active metabolite of teriflunomide inhibits dihydroorotate dehydrogenase (DHODH) enzyme This prevents de novo synthesis of pyrimidines. Hence, T-cell proliferation that is characteristic of RA is inhibited. Pharmacogenetic studies specify the relationship of single nucleotide polymorphisms (SNPs) to the variability in LEF serum levels with potential relevance to effectiveness and tolerability in individual RA patients.
As a single agent in RA the efficacy of leflunomide is second line. Almost 30% of patients quit methotrexate in the first year of treatment, and leflunomide is less expensive than biologic DMARD & has fewer A/E. However, it has shown an efficacy rate of almost 68% in active RA. Trials show that 58.1% of patients experience one adverse effect due to leflunomide & 29% withdraw therapy due to them. Thus, the "Treat-to-target" approach can fail, and permanent joint damage occurs, leading to disability Thus, a prospective study of RA patients in Pakistani population taking Leflunomide as a single DMARD (with or without steroids) analyzing variations in the genes encoding DHODH and ABCG2 with outcomes of the treatment, studying both efficacy and toxicity.
Hypothesis: There is a significant relationship between DHODH, ABCG2 gene polymorphisms with clinical effects and the toxicity of leflunomide.
The aim of this study is to determine whether polymorphism in DHODH, ABCG2 genes is associated with responsiveness to leflunomide treatment in patients with RA.
OBJECTIVES To determine the frequency of genes polymorphism in DHODH, ABCG2 in Pakistani patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At baseline, all patients should fulfill the revised ACR/EULAR criteria for RA10
- •Pakistani individuals
- •between ages of 20-75 years
- •New cases started on Leflunomide/ those already taking for less than a month and their biochemical and clinical data is available
排除标准
- •Patients not willing to participate/ consent not given
- •Patients below the age of 20
- •Non- Pakistani origin
- •Taking another DMARD simultaneously
- •Compromised renal and hepatic functions
- •Cognitive impairment, neurological disease
- •Pregnant/ lactating patients
- •Patients having inflammatory bowel disease/ Irritable bowel syndrome
- •Patients with active infective diseases -Patients who fail to complete 3 months of leflunomide therapy-
研究组 & 干预措施
RA patients taking Leflunomide
RA patients in Pakistani population taking Leflunomide as a single DMARD
干预措施: Study for the correlation of SNPs with efficacy and toxicity of Leflunomide in RA patients (Drug)
结局指标
主要结局
DAS Score Measurement
时间窗: 2 years
The Disease Activity Score (DAS28) is calculated by assessing 28 tender/swollen joints, blood inflammatory markers (ESR or CRP), and patient global health (VAS), with scores \<2.6 indicating remission and \>5.1 indicating high disease activity. It is primarily computed using specialised calculators for Rheumatoid Arthritis. We will take this score at the start of leflunomide therapy, at three-month intervals and at 6 months. The significant outcome will be a 10% decrease from the baseline and will be correlated with the SNP identified.
次要结局
- SNP identification in DHOD gene(2 years)
- Measurement of Hepatotoxicity of Leflunomide(2 years)