Best of 2024: Pain Reduction with Methotrexate in Knee Osteoarthritis Save

The Annals of Internal Medicine reports that oral, low dose, weekly methotrexate significantly reduced knee osteoarthritis (KOA) pain, stiffness, and function in a randomized controlled trial.

 

A multicenter, randomized, double-blind, placebo-controlled trial done performed in the the United Kingdom (June 2014 to October 2017), enrolled 207 adult patients with symptomatic, radiographic KOA and knee pain (severity ≥4 out of 10) on most days in the past 3 months, after an inadequate response to analgesic medications. 

 

Participants were randomized to either placebo or oral weekly methotrexate (6-week escalation 10 to 25 mg) over 12 months and continued usual analgesia. The primary end point was average knee pain (numerical rating scale [NRS] 0 to 10) at 6 months. 

 

A total of 155 participants (64% women; mean age, 60.9 years; 50% Kellgren–Lawrence grade 3 to 4) were randomly assigned to methotrexate (n = 77) or placebo (n = 78).  6 month data and follow-up was available on 86% (n = 134; methotrexate: 66, placebo: 68).  Changes in knee pain scores (0 - 10 numeric scale) at 6 months were:

 

There was a statistically significant pain reduction of 0.79 points favoring methotrexate (P = 0.030), and also significant improvement favoring MTX for WOMAC stiffness (0.60 points [CI, 0.01 to 1.18]; P = 0.045) and function (5.01 points [CI, 1.29 to 8.74]; P = 0.008) scores. There were 4unrelated serious AEs (equal between groups).

 

Treatments for osteoarthritis are limited. These findings, albeit encouraging, merit a larger, more conclusive trial of methotrexate in knee OA.