To assess whether persistence to treatment with methotrexate (MTX) in early rheumatoid arthritis (RA) is shared among first-degree relatives with RA and to estimate any underlying heritability. First-degree relative pairs diagnosed with RA 1999–2018 and starting MTX (in monotherapy) as their first disease-modifying anti-rheumatic drug (DMARD) treatment were identified by linking the Swedish Rheumatology Quality Register to national registers. Short- and long-term persistence to MTX was defined as remaining on treatment at 1 and 3 years, respectively, with no additional DMARDs added. We assessed familial aggregation through relative risks (RR) using log-binomial regression with robust standard errors and estimated heritability using tetrachoric correlations. We also explored the familial aggregation of EULAR treatment response after 3 and 6 months. To mimic the clinical setting, we also tested the association between having a family history of MTX persistence and persistence within the index patient. Familial persistence was not associated with persistence at 1 (RR=1.02, 95% CI 0.87–1.20), only at 3 (RR=1.41, 95% CI 1.14–1.74) years. Heritability at 1 and 3 years was estimated to be 0.08 (95% CI 0–0.43) and 0.58 (95% CI 0.27–0.89), respectively. No significant associations were found between family history and EULAR response at 3 and 6 months, neither overall nor in the clinical setting analysis. Our findings imply a familial component, including a possible genetic element, within the long-term persistence to MTX following RA diagnosis. Whether this component is reflective of characteristics of the underlying RA disease or determinants for sustained response to MTX in itself will require further investigation.

中文翻译：

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早期类风湿性关节炎持续使用甲氨蝶呤治疗是否具有家族性成分？

评估在早期类风湿关节炎 (RA) 中持续使用甲氨蝶呤 (MTX) 治疗是否在 RA 一级亲属之间共享，并估计任何潜在的遗传性。通过将瑞典风湿病学质量登记册与国家登记册联系起来，确定了 1999-2018 年被诊断为 RA 并开始 MTX（单药治疗）作为其首个缓解疾病的抗风湿药 (DMARD) 治疗的一级亲属对。对 MTX 的短期和长期持续性分别定义为分别在 1 年和 3 年时继续治疗，没有添加额外的 DMARD。我们使用具有稳健标准误差的对数二项式回归通过相对风险 (RR) 评估家族聚集，并使用四环相关性估计遗传力。我们还探讨了 3 个月和 6 个月后 EULAR 治疗反应的家族聚集情况。为了模拟临床环境，我们还测试了 MTX 持久性家族史与指数患者体内持久性之间的关联。家族持久性与第 1 年的持久性无关（RR=1.02, 95% CI 0.87-1.20），仅在第 3 年（RR=1.41, 95% CI 1.14-1.74）年。1 年和 3 年的遗传力估计分别为 0.08（95% CI 0-0.43）和 0.58（95% CI 0.27-0.89）。在 3 个月和 6 个月时，无论是总体上还是在临床环境分析中，都没有发现家族史与 EULAR 反应之间存在显着关联。我们的研究结果暗示了一个家族成分，包括可能的遗传因素，在 RA 诊断后长期持续使用 MTX。