Journal Club Review: Effectiveness of Methotrexate and Leflunomide as Corticoid-Sparing Drugs

In this episode, Danielle Gatti Palumbo, PharmD, clinical pharmacist, RhAPP faculty member, and RhAPP Board member, explores a pivotal study evaluating the effectiveness of Methotrexate (MTX) and Leflunomide as steroid-sparing agents in Polymyalgia Rheumatica (PMR). Published in Rheumatology Advances in Practice, this multicenter observational study examines data from 23 rheumatology clinics across Argentina, shedding light on alternative treatment options for patients struggling with prolonged steroid use and associated side effects.Polymyalgia Rheumatica is traditionally managed with glucocorticoids, but long-term steroid use presents significant risks, especially in patients with diabetes, osteoporosis, or cardiovascular disease. The ACR and EULAR guidelines suggest using Methotrexate as a steroid-sparing agent in patients at high risk of relapse or those requiring prolonged treatment. However, due to limited clinical trial data and conflicting results regarding Methotrexate’s impact on disease progression, Leflunomide is emerging as a potential alternative for steroid reduction and long-term disease control.This study followed 186 PMR patients from 2007 to 2023, examining treatment outcomes in those prescribed Methotrexate (10-15 mg weekly) or Leflunomide (20 mg daily). While flare rates remained comparable between both treatment groups, the study found that Leflunomide demonstrated a significantly higher remission rate and faster steroid discontinuation compared to Methotrexate. Patients treated with Leflunomide achieved steroid withdrawal within 4.7 months, while those on Methotrexate required an average of 31.8 months. Additionally, Leflunomide patients exhibited a higher probability of sustained remission up to 40 months post-treatment.The findings of this study suggest that Leflunomide may be a superior steroid-sparing option in PMR, particularly for patients who struggle with Methotrexate tolerability or require faster tapering of glucocorticoids. Although the study had limitations, including its observational design and the relatively low Methotrexate dosing range of 10-15 mg weekly, it provides important clinical insights for rheumatology providers seeking alternative treatment strategies.With the growing need for effective, steroid-sparing therapies in PMR management, Leflunomide presents a viable option that warrants further research and consideration in clinical practice.Visit the RhAPP website or explore additional educational content on the RhAPP ACE App.