Trends and variation in unsafe prescribing of methotrexate: a cohort study in English NHS primary care.

Objective To describe trends and geographical variation in methotrexate prescribing that breaches national safety recommendations; deaths from methotrexate poisoning; and associated litigation. Methods A retrospective cohort study of English NHS primary care prescribing data, complemented by information obtained through Freedom of Information (FOI) requests. The main outcome measures were: (1) variation in ratio of breaching / adherent prescribing, geographically and over time, between General Practices and Clinical Commissioning Groups; (2) description of responses to FOI requests. Results Out of 7349 NHS General Practices in England, 1689 practices prescribed both 2.5mg and 10mg tablets to individual patients in 2017, breaching national guidance. In April 2018, 697 practices (at the 90th centile and above) prescribed at least 14.3% of all methotrexate as 10mg tablets, breaching national guidance. The 66 practices at the 99th percentile and above gave at least 52.4% of all prescribed methotrexate in the form of 10 mg tablets. The prescribing of 10mg tablets has fallen over 7 years, with 10mg tablets as a proportion of all methotrexate tablets falling from 9.1% to 3.4%. 21 deaths caused by methotrexate poisoning have been reported from 1993-2017. Conclusions The prevalence of unsafe methotrexate prescribing has reduced but it remains common, with substantial variation between organisations. We recommend the NHS invests in better strategies around implementation of safety recommendations. 21 deaths have been attributed to methotrexate poisoning but with no further details easily available: the full coroners reports for these deaths should be reviewed to identify recurring themes.