Background/Purpose: Methotrexate (MTX) is considered as the anchor disease modifying antirheumatic drug (DMARD) in treatment of rheumatoid arthritis (RA). However, there is no advice concerning individualized dosing. We aimed to study whether the initial dose of MTX/weight is predictive for disease activity and remission over the first 6 months in early RA patients in usual care.  

Methods: Patients with DMARD-naive newly diagnosed inflammatory arthritis were recruited in 5 Finnish sites for a longitudinal follow-up (FIN-ERA) study. Patients fulfilling ACR/EULAR classification criteria for RA and positive for rheumatoid factor (RF) were divided by tertiles of MTX dose/weight. The linearity for baseline characteristics was tested and a multivariate regression analysis was adjusted for age, sex and positivity for anti citrullinated antibodies (AntiCCP). Repeated measures were analyzed using mixed models approach with appropriate distribution and link function.  

Results: Out of 611 recruited patients, 336 patients who started with MTX at baseline (65% F, mean age[SD] at diagnosis 57[15] yrs) were analyzed. The baseline characteristics are depicted in Table 1. Males had lower mean(SD) dose/kg of MTX than females (0.24[0.09] vs 0.22[0.07] mg/kg, P=0.007). Both heavier males and females received lower dose/weight of MTX. A concomitant therapy with hydroxychloroquine (HCQ), and combination with sulphasalazine and HCQ were more common in patients receiving higher dose of MTX/weight. Patients with higher dose/weight of MTX met lower disease activity early and higher DAS28-3 remission rates at 6 months than patients with lower dose after adjusting by confounding variables (Figure 1).  

Conclusion: The initial dose of methotrexate per weight is determinant of disease activity and early remission of DMARD-naive early, RF positive RA patients in usual care.             

  Table 1. Baseline characteristics of 336 DMARD-naive early RA patients divided by tertiles of weight-based dose (mg/kg) of methotrexate. The change of treatment strategy was defined as a change from DMARD monotherapy to a combination therapy or vice versa, start of a biologic DMARD, start/stop of prednisolone, or change of MTX to leflunomide (P for linearity). ^aSulphasalazine ^bHydroxychloroquine *MTX+SSZ+HCQ              

Figure 1. Proportions of DAS28-3 remissions during the first 6 months of DMARD therapy in DMARD-naive early RA patients divided by 3 tertiles of MTX dose/weight. White ball: MTX<0.19mg/kg, Black pyramid: MTX 0.19-0.26 mg/kg, Black square: MTX>0.27mg/kg (P for linearity).