Written by Babatunde Carew
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In patients with knee OA refractory to usual analgesics, methotrexate (MTX) decreased pain over six months compared to placebo; however, these benefits were not sustained at twelve months.
Synopsis
This study assessed the effect of oral methotrexate on knee osteoarthritis (KOA) pain in a multicenter, double-blind, randomized, placebo-controlled trial. Conducted at 15 UK clinics with 207 participants, it tested weekly methotrexate (10-25 mg) or placebo over 12 months, with a primary focus on pain reduction after six months. Results showed that methotrexate reduced knee pain by an average of 0.79 points on a 10-point scale (p=0.030), with statistically significant improvements in knee stiffness and function as well. However, these benefits decreased by time of 12-month follow-up. [AI-generated]
Methotrexate for knee pain…where’s the inflammation?
In Global Burden of Disease studies, knee osteoarthritis is consistently ranked among the leading contributors to years lived with disability. Patients with knee osteoarthritis (KOA) often have symptoms that persist despite physical therapy, multimodal pain regimen, and joint injections. More effective treatments for KOA are needed. The PROMOTE trial explores use of MTX in patients with symptomatic KOA and inadequate response to usual analgesics. At 6 months, MTX – combined with usual analgesics – reduced overall knee pain compared to placebo. However, this pain reduction was modest and relatively short lived, as pain reduction was not sustained at 12 months. More patients in the methotrexate group withdrew due to adverse events, and there was a mean decrease in MTX dose from 6 to 12 months due to tolerability. The combination of a dose decrease and study withdrawal may have affected the 12-month outcome. Interestingly, a post hoc analysis revealed that patients with baseline hsCRP levels ≥ 2 mg/L experienced a sustained reduction in overall knee pain with MTX treatment compared to placebo, while patients with baseline hsCRP < 2 mg/L had no difference in treatment response compared to placebo.
How will this change my practice?
While I don’t think I will be reaching for MTX for treatment of KOA anytime soon, this trial highlights the need for larger studies assessing efficacy and tolerability of MTX in treatment of refractory KOA. It also underscores a potential foundation for future research, emphasizing that not all KOA cases are the same.
Source
Pain Reduction With Oral Methotrexate in Knee Osteoarthritis : A Randomized, Placebo-Controlled Clinical Trial. Ann Intern Med. 2024 Sep;177(9):1145-1156. doi: 10.7326/M24-0303. Epub 2024 Jul 30. PMID: 39074374
