Reducing Blood Monitoring Frequency in MTX Monotherapy and Combination Therapy

Lab equipment centrifuging blood. Concept image of a blood test.3d rendering.Lab equipment centrifuging blood. Concept image of a blood test.3d rendering.
In a real-world setting, researchers found evidence that supports the frequency of blood monitoring for alanine aminotransferase levels to 12-week intervals for patients being treated with methotrexate and less frequent blood monitoring for patients on combination disease-modifying antirheumatic drugs.

Reduced frequency of blood monitoring is safe for patients treated with either methotrexate (MTX) monotherapy or combination therapy, according to a letter to the editor published in Rheumatology.

Researchers set out to determine the possibility of reducing the frequency of blood monitoring in patients on stable doses of MTX. Blood monitoring intervals were extended from monthly to 12-week intervals, and investigators examined whether this change would compromise patient safety in terms of missed signs or late detection of transaminitis or neutropenia.

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Between June 2016 and July 2017, investigators reviewed monthly neutrophil count and liver function test results for 1964 patients on MTX (mean treatment duration 122 weeks). Within the cohort, 771 patients were treated with MTX monotherapy while the rest were treated with MTX combination therapy — 775 patients with 1 concomitant disease-modifying antirheumatic drug (DMARD), 82 with 2 concomitant DMARDs, and 396 with biologics.

Those with a neutrophil count <2.0×10⁹/l or alanine aminotransferase (ALT) >34 U/I were categorized as either isolated, persistent, or intermittent (1 abnormal result, at least 2 consecutive abnormal results, or more than 1 abnormal result separated by 1 normal result, respectively).

Patients with neutropenia <1.6×10⁹/I or ALT >100 U/I were selected for medical record review. Of those patients, 112 (5.7%) had neutrophils <1.6×10⁹/I; 67 cases were persistent, 24 were intermittent, and 21 were isolated. A total of 36 patients were recommended to temporarily withhold MTX treatment for a mean duration of 2 weeks. Five patients permanently discontinued MTX treatment as a result of neutropenic sepsis.

Ten patients (0.51%) had ALT >100 U/I; 8 cases were persistent, 1 was intermittent, and 1 was isolated. One patient permanently discontinued MTX treatment due to fatty liver disease. Forty-eight patients had at least 1 ALT rise of 35 U/I to 100 U/I, but no treatment alteration was necessary.

Among all patients with abnormal ALT or neutropenia, elevated levels persisted beyond 12 weeks. Therefore, the researchers noted, “12-week interval blood monitoring would have reliably detected [these] abnormalities.”

Among those with intermittent or isolated ALT or neutropenia, there were “no concerning features requiring cessation of MTX. This suggests that although a portion of neutropenia or ALT rises would not have been captured on 12-week blood monitoring intervals, isolated and intermittent rises are unlikely to pose harm to patients.”

The researchers of the study concluded that less frequent blood monitoring would be an effective use of resources while remaining safe for patients treated with methotrexate monotherapy or combination therapy. Additionally, the data suggest that this reduced frequency is possible among patients being treated with DMARD combination therapy.

Malley T, Corfield G, Fung P, Heneghan D, Kitchen J. Transaminitis and neutropenia are rare in patients on methotrexate: evidence from a large cohort of inflammatory arthritis patients [published online May 12, 2019]. Rheumatology. doi: 10.1093/rheumatology/kez168