Abstract
Objective This study assessed whether the addition of methotrexate (MTX) to glucocorticoid therapy reduces overall glucocorticoid usage in patients with polymyalgia rheumatica (PMR), focusing particularly on those exhibiting glucocorticoid-resistant disease. Methods This retrospective study included 82 patients with PMR treated with glucocorticoids. After applying matching weights, outcomes were compared between weighted populations of 18 patients receiving MTX and 18 receiving glucocorticoid monotherapy. A subgroup analysis was conducted among the 38 patients classified as glucocorticoid-resistant, comparing weighted populations of eight in the MTX group and nine in the non-MTX group after the application of matching weights. Results In the primary analysis (overall cohort), the cumulative glucocorticoid dose at 104 weeks was 4,263 mg in the MTX group and 4,418 mg in the non-MTX group, showing no significant reduction effect from MTX (mean difference, -155 mg; 95% confidence interval (CI), -1003 to 693; P = 0.717). The glucocorticoid discontinuation rate also showed no significant difference between the groups (38.2% vs. 27.8%; risk ratio (RR), 1.37; 95% CI, 0.61 to 3.1; P = 0.442). By contrast, in the subgroup analysis of glucocorticoid-resistant patients, the cumulative glucocorticoid dose in the MTX group was 4,298 mg, which was significantly lower than the 5,618 mg in the non-MTX group, with a mean difference of -1320 mg (95% CI, -2539 to -102; P = 0.035). The glucocorticoid discontinuation rate was also significantly higher in the MTX group than in the non-MTX group (45.5% vs. 4.1%; RR, 11; 95% CI, 2.1 to 57.9; P = 0.0059). Conclusions Although adjunctive MTX therapy did not significantly reduce glucocorticoid exposure in the overall PMR population, our findings suggest a substantial benefit for patients with glucocorticoid-resistant PMR, markedly reducing cumulative glucocorticoid exposure and increasing the rate of discontinuation. These results highlight the critical importance of patient selection when considering MTX for PMR.