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In DMARD-naïve patients with early RA, higher MTX dosage was not beneficial
In patients with early RA who have never taken disease-modifying antirheumatic drugs and initiated methotrexate treatment, clinical outcomes did not appear to be better with a higher starting dose of methotrexate vs. low methotrexate doses, according to findings.
In the systematic literature search, researchers queried databases for studies of patients diagnosed with recent-onset RA and who were DMARD naïve. Studies were also required to have MTX as part of the initial treatment strategy, either as monotherapy or combination therapy, and to include information about the exact dose of study medications, study results within 6 months of treatment and treatment effect data. Outcomes were assessed for the following four treatment regimens: MTX monotherapy; MTX combined with synthetic (cs) DMARDs; biologic (b) DMARDs; or glucocorticoids. A total of 31 studies (n=5,589) were identified and included in the analysis.
for the health assessment questionnaire (HAQ) revealed increasing doses of MTX were not linked to higher efficacy in MTX monotherapy. A small, but statistically positive association was seen between MTX dose and combination therapy with glucocorticoids, as well as MTX dose and combination therapy with bDMARDs.
The meta-regression analysis of the DAS28 also revealed a small, statistically significant positive correlation between MTX dose in combination therapy with bDMARDs, but not in combination with glucocorticoids. Results for the DAS/DAS28 also showed a small, statistically significant positive association with MTX dose in combination therapy with bDMARDs, but not with glucocorticoids.
According to the researchers, there were not enough treatment groups using combination therapy with csDMARDs to perform meta-regression analyses on this regimen.
Combination therapy with glucocorticoids demonstrated a worse HAQ outcome with a higher MTX dose, but not worse DAS/DAS28 or erythrocyte sedimentation rate/C-reactive protein levels. In combination therapy with bDMARDs, a higher MTX dose yielded a higher (worse) outcome HAQ and DAS/DAS28, but not an elevated ESR/CRP level. Effect sizes were considered trivial.
“We saw a trend in clinical trials, as well as in daily practice, for rheumatologists to prescribe methotrexate in combination therapy in the same high doses as recommended for monotherapy,” study author Sytske Anne Bergstra, MSc, told Healio Rheumatology. “However, we hypothesized that in combination with other effective antirheumatic drugs, at least on the short term, methotrexate in lower doses might be equally effective as higher doses. Based on the results of the systematic review, we concluded that for DMARD-naïve RA patients, there was no additional benefit of starting with a high vs. a lower MTX dose within 3 [months] to 6 months from the start of treatment. We therefore suggest that rheumatologists may consider starting MTX at a lower dose, in particular when prescribed in combination with a bDMARD or a glucocorticoid, and increase or change therapy in the setting of a treat-to-target protocol as recommended.” -by Jennifer Byrne
Disclosures: The researchers report no relevant disclosures.