Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica

• DOI: 10.1093/rap/rkae033
• Publication Date: 2024-03-22T03:18:14Z
• Authors: Juan Pablo Vinicki; Alejandra Cusa; Daniela Domingo; José Luis Velasco...; Sebastián Magri; Alejandro Brigante; Maria Marcela Schmid; Paola Ávila; Natalia Zamora; Laura Sorrentino; Anabella M Rodriguez; Miguel Linarez; Cecilia Pisoni; Carolina Costi; Gustavo Rodriguez...; María Andrea Spin...; Vanesa Ursula Paris; Natalia Perrotta; María del Rosario...; Oscar Rillo; Claudia Pena; Julio Got; Javier Cavallasca; Maximiliano Macha...; Carolina Iturralde; María Victoria Ma...; Romina Tessel; N Saravia Chocobar; Graciela Alarcon
• Keywords: Pulmonary and Respiratory Medicine; Vasculitis; Diagnosis and Management of Urticaria; Logistic regression; 0302 clinical medicine; Classification and Management of Vasculitides; Glomerulonephritis; Rheumatology; Health Sciences; Genetics; Disease; Hereditary Angioedema: Molecular Mechanisms and Clinical Management; Internal medicine; Giant cell arteritis; Polymyalgia rheumatica; Confidence interval; Odds ratio; Methotrexate; FOS: Biological sciences; Medicine; Prednisone; Original Article; Interquartile range; Leflunomide

Abstract

Objectives The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to assess the effectiveness and safety of methotrexate (MTX) and of leflunomide (LEF) in daily clinical practice in PMR patients from Argentina.

Methods A multicentre and observational study (medical records review) of PMR patients seen between 2007 and 2023, who had at least three months of follow-up after starting a GCSD, either MTX or LEF, was performed. Results are expressed as medians and interquartile ranges [25th–75th (IQR)] for continuous variables and percentages for categorical ones. The two treatment groups were compared using χ2 test for categorical variables, Mann–Whitney U test for continuous variables and the log-rank test for time-to-event data. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. In all cases, a p-value <0.05 was considered statistically significant.

Results One-hundred and eighty-six patients (79% female) with a median age of 72 years (IQR, 65–77 years) were included. One-hundred and forty-three patients (77%) were prescribed MTX (15, IQR 10–15) and 43 (23%) LEF (20 mg, fixed dose). Flare-ups (relapses and recurrences) occurred in 13 patients (7%) and were comparable between both groups. Persistent GCSD intake was observed in 145 patients (78%). Glucocorticoid (GC) withdrawal was achieved in 67 of these 145 patients (46%) and this occurred more frequently in the LEF group (P = 0.001). Furthermore, time until prednisone discontinuation was shorter in the LEF-treated patients (4.7 months, IQR 3–20 on LEF versus 31.8 months, IQR 10–82 on MTX, P = 0.000). Remission was found more frequently in the LEF group (P = 0.003). In the multivariate analysis, the probability of remission was higher with LEF therapy (P = 0.010) and this finding persisted in the subgroup analysis who were followed up < 40 months (OR 3.12, 95% CI = 1.30–7.47, P = 0.011).

Conclusions This study demonstrated the clinical effectiveness of LEF and even its superiority in achieving remission when compared with MTX as GCSD in PMR patients. Further research is needed to support these findings.