A team at Sanjay Gandhi Postgraduate Institute of Medical Sciences in Lucknow, India, initiated methotrexate therapy in 31 patients with active RA who were disease-modifying anti-rheumatic drug (DMARD)-nave at baseline. Twenty-five patients completed the 4-month study.
Baseline methotrexate dose was 10 mg/week. It was increased monthly by 2.5 mg/week. At 4 months, the median methotrexate dose given was 17.5 mg/week. There was significant variation among patients in their response to methotrexate, as well as variation in dosage needed to obtain a therapeutic response.
TNF-alpha, interferon-gamma and interleukin-10 (IL-10) concentrations were estimated by ELISA.
"T cell stimulation resulted in a significant increase in cytokine release, and addition of methotrexate led to a dose-dependent suppression of all three cytokines," lead author Dr. Nigil Haroon and colleagues report in the June issue of the Journal of Rheumatology.
There was a "significant negative correlation" of change in Disease Activity Score (DAS) and the dose required to suppress cytokines by 50% (ID50) and levels of TNF-alpha and IFN-gamma, but not IL-10.
According to criteria from the European League Against Rheumatism (EULAR), 13 patients achieved a moderate response, 4 had a good response and 3 entered remission. ACR20 was seen in 6 patients, ACR50 in 8 patients and ACR70 responses were observed in 3 patients.
The investigators evaluated the sensitivity and specificity of the TNF-alpha assay in predicting methotrexate response. A TNF-alpha ID50 cutoff value of 224 ng/mL "gave the best sensitivity and specificity values for predicting EULAR moderate response. This cutoff predicted patients having moderate EULAR response with 93% sensitivity and 86% specificity," Dr. Haroon's team reports.
"Patients with TNF-alpha ID50 values above and below the cutoff had distinct clinical courses, with a majority of patients with lower ID50 having a better response at 4 months," they note.
"In vitro suppression of TNF-alpha is a novel and efficient assay to predict the clinical response to MTX in patients with RA," the Indian investigators write. "Validation of the assay in a larger cohort is needed to determine its role in clinical decision-making."
J Rheumatol 2008;35:975-978.