METHOTREXATE DOSE AND OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS

Abstract

Background Methotrexate (MTX) is well known as the anchor drug for treatment of rheumatoid arthritis (RA). It is recommended that MTX should be administered as soon as the diagnosis of RA is made and the dose should be escalated to tolerable adequate higher dose.

Objectives We aimed to investigate the difference in outcomes according to the weekly dose of MTX.

Methods A total of 4,393 patients enrolled in KORONA (Korean Observational Study Network for Arthritis), after excluding 973 patients who were not receiving MTX and 10 patients with inadequate information on their MTX dosage, were assessed for demographic factors, disease outcome measurements (DAS28, HAQ, EQ-5D, fatigue, sleep, pain, general condition, radiographic damage, surgery), comorbidities, medication, and adverse events. A total of 4,361 patients were assessed for outcomes according to MTX dose in relation to body weight after excluding 32 patients with body weight data missing. Patients receiving more or less than 10mg weekly dose of MTX were compared. In patients receiving more than 10mg weekly dose of MTX, patients with more or less than 0.25mg/kg were compared and in those receiving less than 10mg weekly, 0.16mg/kg was the cut-off for comparison.

Results More patients were receiving more than 10mg weekly dose of MTX (62.4%) compared to less than 10mg (37.6%). Patients in the more than 10mg weekly dose group were younger (p<0.01), had shorter disease duration (p<0.01), better general condition (p<0.01), had less hypertension (p<0.01) and other cardiovascular comorbidities (p<0.01), received more steroids (p<0.01) and NSAIDs (p<0.01), and had more radiographic damage at diagnosis and follow up (p<0.01) and surgery (p<0.01). When weekly MTX dose more or less than 0.25mg/kg were compared in the more than 10mg weekly group, the more than 0.25mg/kg group were more female (p<0.01), younger (p<0.01), longer disease duration (p<0.01), higher HAQ score (p<0.01), more pain (p<0.01), lower EQ-5D score (p<0.01), higher DAS28 (p<0.01), less hypertension (p<0.01), other cardiovascular (p<0.01), and gastrointestinal comorbidities (p<0.01), more radiographic damage at diagnosis (p<0.01) and follow up (p<0.01), and more surgery (p<0.01).

Conclusions Higher doses of MTX were used in younger patients with worse prognostic factors at diagnosis. The high-dose group had significantly higher disease activity, more pain, higher HAQ score, lower EQ-5D score, more radiographic damage and surgery, and more gastrointestinal comorbidities. But they had significantly less hypertension and other cardiovascular comorbidities, showed no significant difference in interstitial lung disease and adverse events.