Methotrexate Test Dose Use and Frequency of Laboratory Abnormalities in Patients Initiating Treatment

Dermatology providers have traditionally used a test dose (TD) of methotrexate when initiating treatment to assess a patient’s predisposition to severe adverse events, particularly myelosuppression.¹ Although not standardized, a TD is usually administered as a single, often subtherapeutic dose ranging from 2.5 to 10.0 mg.^2-6 Laboratory tests are obtained several days after the TD, and if no significant abnormalities are seen, subsequent weekly doses are increased to therapeutic values.¹ More recent guidelines and research within the dermatology literature state that a TD may only be needed in certain populations with a higher risk for methotrexate hematologic toxicity, including patients with impaired renal function and the elderly.^2,7 Other specialties such as rheumatology do not mention the use of a TD within their guidelines, and providers instead initiate treatment within a therapeutic dosing range, with laboratory tests obtained 2 to 4 weeks after beginning treatment.⁸ Because of these varying prescribing practices and due to a paucity of data supporting evolving TD use recommendations in dermatology, we sought to compare the frequency of laboratory abnormalities in patients initiating methotrexate with and without a TD to guide its utility.

Study Design and Cohort Selection
We conducted a retrospective cohort study of outpatient electronic health records and pharmacy dispensing records from Kaiser Permanente Mid-Atlantic States (KPMAS) between January 2003 to December 2020. Patients ≥18 years of age who had a newly dispensed methotrexate prescription from either a dermatology or rheumatology provider were included. Individuals with concomitant use of other immunomodulatory medications within 30 days prior to and 120 days after the