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

Recent guidelines within the dermatology literature have indicated that a methotrexate test dose may not be needed for patients at lower risk of toxicity. However, few clinical studies have specifically examined the utility of a test dose with regard to detecting or preventing significant laboratory abnormalities. Other specialties, such as rheumatology, do not mention methotrexate test doses within their guidelines.

To determine the frequency of laboratory abnormalities in patients initiating low-dose, oral methotrexate with and without a test dose.

We conducted a retrospective cohort analysis of patients greater than or equal to 18 years of age initiating methotrexate, prescribed by a dermatology or rheumatology provider within the Kaiser Permanente Mid-Atlantic States health plan. A methotrexate test dose was defined as any initial dose less than or equal to 15 mg with one or more laboratory tests within 3 to 10 days after dispensing. Patients were assigned to either the test dose or the non-test dose group. The rate of any grade 2 and higher laboratory abnormality (leukopenia, anemia, thrombocytopenia, elevated aspartate aminotransferase, elevated alanine aminotransferase) over 4 months of treatment was compared between the two groups. For the test dose group, the rate of any grade 2 and higher laboratory abnormality occurring between 3 to 10 days after initial methotrexate dispensing was reported.

2,575 patients were included; 220 in the test dose group and 2,355 in the non-test dose group, with rheumatology patients making up 91.92% (2,367/2,575). Over 4 months, 6.82% (15/220) of patients in the test dose group had at least one grade 2 or higher laboratory abnormality, compared to 4.34% (91/2,097) in the non-test dose group (P=0.09). Within the test dose group, 2.73% (6/220) of patients had a grade 2 or higher laboratory abnormality occurring between 3 to 10 days after initiating treatment.

When initiating methotrexate in dermatology and rheumatology patients, the use of a test dose may be of limited value in detecting or preventing significant laboratory abnormalities. These findings provide support for evolving guidelines and consensus statements in dermatology regarding methotrexate test dose use.  .