Safety of Reduced Methotrexate Lab Monitoring: a Population-based, Target Trial Emulation Study

- Target trial emulation that will include Incident methotrexate users age ≥18 years in the REP between 1/1/2012-12/31/2022 (to allow at least three years follow-up through analysis date 12/31/2025) with ≥2 preceding codes for rheumatic disease

Treatment strategies:

• Guidelines group: monitor 3+ times in first 0-3 months, 3+ times in 3 to 12 months, and at least once every 4.5 months afterward.
• Reduced group: monitor 1-2 times in first 0-3 months, 1-2 times in 3 to 12 months, and at least once per year afterward (but not more than once every 4.5 months).
• Assignment procedures: We will use clone-censor-weighting (CCW) methods to explore the effect of both treatments in each patient. A negative control outcome such as trauma outcomes to assess for uncontrolled confounding.
• Time zero: start date of incident methotrexate use
• Follow up: Ends at methotrexate discontinuation (defined as not taking methotrexate for ≥6 months), death, loss to follow-up, or three years after baseline, whichever occurs first.

Data: Laboratory and prescription data were electronically available since 1/1/2010 and fully viewable since 1/1/2012. Therefore, this study will include all adults aged ≥18 years with incident low-dose (≤25mg/week) methotrexate use from 1/1/2012 on. To ensure the population would fall under the purview of the ACR methotrexate monitoring guidelines, we also required ≥2 codes (30 days apart) for a rheumatic condition within two years prior to index date of first methotrexate prescription, which we ascertained by prescription data and confirmed by manual chart review. A rheumatologist previously manually abstracted all methotrexate monitoring-related data including frequency as described previously (Reed et al., unpublished).

Outcomes: