Objective To develop and validate a prognostic model to inform risk stratified decisions on frequency of monitoring blood tests during long term methotrexate treatment. Design Retrospective cohort study. Setting Electronic health records within the UK’s Clinical Practice Research Datalink (CPRD) Gold and CPRD Aurum. Participants Adults (≥18 years) with a diagnosis of an immune mediated inflammatory disease who were prescribed methotrexate by their general practitioner for six months or more during 2007-19. Main outcome measure Discontinuation of methotrexate owing to abnormal monitoring blood test result. Patients were followed-up from six months after their first prescription for methotrexate in primary care to the earliest of outcome, drug discontinuation for any other reason, leaving the practice, last data collection from the practice, death, five years, or 31 December 2019. Cox regression was performed to develop the risk equation, with bootstrapping used to shrink predictor effects for optimism. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination. Results Data from 13 110 (854 events) and 23 999 (1486 events) participants were included in the development and validation cohorts, respectively. 11 candidate predictors (17 parameters) were included. In the development dataset, the optimism adjusted R2 was 0.13 and the optimism adjusted Royston D statistic was 0.79. The calibration slope and Royston D statistic in the validation dataset for the entire follow-up period was 0.94 (95% confidence interval 0.85 to 1.02) and 0.75 (95% confidence interval 0.67 to 0.83), respectively. The prognostic model performed well in predicting outcomes in clinically relevant subgroups defined by age group, type of immune mediated inflammatory disease, and methotrexate dose. Conclusion A prognostic model was developed and validated that uses information collected during routine clinical care and may be used to risk stratify the frequency of monitoring blood test during long term methotrexate treatment. The study protocol is available from [www.cprd.com][1]. [1]: http://www.cprd.com

中文翻译：

---

免疫介导的炎症性疾病中甲氨蝶呤毒性的风险分层监测：使用英国初级保健数据开发和验证预后模型

目的 开发并验证预后模型，为长期甲氨蝶呤治疗期间监测血液检查频率的风险分层决策提供信息。设计回顾性队列研究。在英国临床实践研究数据链 (CPRD) Gold 和 CPRD Aurum 中设置电子健康记录。参与者 2007-19 年期间被全科医生开出甲氨蝶呤处方 6 个月或更长时间、被诊断患有免疫介导炎症性疾病的成年人（≥18 岁）。主要结局指标 由于血液检测监测结果异常而停用甲氨蝶呤。对患者进行随访，从在初级保健中首次开出甲氨蝶呤处方后六个月开始，到最早出现结果、因任何其他原因停药、离开诊所、最后一次从诊所收集数据、死亡、五年或 2019 年 12 月 31 日为止. 进行 Cox 回归来建立风险方程，并使用引导法来缩小乐观的预测效应。多重插补处理缺失的预测数据。模型性能通过校准和辨别来评估。结果 开发队列和验证队列分别包含 13 110 名（854 项事件）和 23 999 名（1486 项事件）参与者的数据。包括 11 个候选预测变量（17 个参数）。在开发数据集中，乐观度调整后的 R2 为 0.13，乐观度调整后的 Royston D 统计量为 0.79。整个随访期间验证数据集中的校准斜率和 Royston D 统计量分别为 0.94（95% 置信区间 0.85 至 1.02）和 0.75（95% 置信区间 0.67 至 0.83）。该预后模型在预测由年龄组、免疫介导的炎症性疾病类型和甲氨蝶呤剂量定义的临床相关亚组的结果方面表现良好。结论 使用常规临床护理期间收集的信息开发并验证了预后模型，可用于对长期甲氨蝶呤治疗期间监测血液检查的频率进行风险分层。该研究方案可从 [www.cprd.com][1] 获取。[1]：http://www.cprd.com