Effectiveness of Methotrexate and Leflunomide as Corticoid-Sparing Drugs

In this episode, Danielle Gatti Palumbo, PharmD, clinical pharmacist, RhAPP faculty member, and Board member, discusses a pivotal study on Methotrexate (MTX) and Leflunomide as steroid-sparing agents in Polymyalgia Rheumatica (PMR). Published in Rheumatology Advances in Practice, this multicenter observational study analyzed data from 23 rheumatology clinics in Argentina, offering insights into alternative treatments for patients facing steroid-related risks.

PMR is traditionally managed with glucocorticoids, but long-term use increases risks for diabetes, osteoporosis, and cardiovascular disease. While ACR and EULAR guidelines recommend Methotrexate for steroid reduction, limited trial data has led to interest in Leflunomide as a potential alternative.

Following 186 PMR patients from 2007 to 2023, the study compared outcomes in those treated with Methotrexate (10-15 mg weekly) or Leflunomide (20 mg daily). While flare rates were similar, Leflunomide showed a significantly higher remission rate and faster steroid discontinuation—4.7 months compared to 31.8 months with Methotrexate. Additionally, Leflunomide patients had a higher probability of sustained remission up to 40 months post-treatment.

These findings suggest Leflunomide may be a more effective steroid-sparing option for PMR, especially for patients needing quicker steroid tapering or struggling with Methotrexate tolerability. Although observational in design and limited by Methotrexate’s lower dosing range, the study provides valuable insights for rheumatology providers considering alternative PMR treatments.

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