MTX for Knee OA
Trial question
What is the effect of low-dose methotrexate in patients with knee osteoarthritis and effusion-synovitis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
89.0% female
11.0% male
N = 215
215 patients (191 female, 24 male).
Inclusion criteria: patients with knee osteoarthritis and effusion-synovitis.
Key exclusion criteria: inflammatory arthritis or SLE; knee surgery or arthroscopic examinations performed or planned within 1 year; MRI contraindications; intra-articular injection, intramuscular injection, or oral corticosteroid use in the past 4 weeks; other anti-synovitis agents application in the past 3 months; hypersensitivity to methotrexate; pregnancy or lactation.
Interventions
N=108 methotrexate (maximum dose of 15 mg weekly).
N=107 placebo (matching placebo weekly).
Primary outcome
Mean reduction in knee visual analogue scale pain at 52 weeks
29.5 mm
29.8 mm
29.8 mm
22.4 mm
14.9 mm
7.5 mm
0.0 mm
Methotrexate
Placebo
No significant
difference ↔
No significant difference in mean reduction in knee VAS pain at 52 weeks (29.5 mm vs. 29.8 mm; MD -0.3, 95% CI -7.3 to 6.7).
Secondary outcomes
No significant difference in mean reduction in effusion-synovitis maximal area at 52 weeks (0.2 cm² vs. 0.3 cm²; MD -0.1, 95% CI -1 to 0.8).
No significant difference in mean reduction in Western Ontario and McMaster Universities Osteoarthritis Index total score at 52 weeks (459.6 points vs. 441.5 points; MD 18.2, 95% CI -112 to 148.4).
No significant difference in Outcome Measures in Rheumatology Arthritis Clinical Trials-Osteoarthritis Research Society International at 52 weeks (54.6% vs. 56.1%; ARD -1.5, 95% CI -14.32 to 11.32).
Safety outcomes
No significant differences in adverse events, serious adverse events.
Significant difference in liver enzymes > 1.5× ULN (19.4% vs. 9.3%).
Conclusion
In patients with knee osteoarthritis and effusion-synovitis, methotrexate was not superior to placebo with respect to mean reduction in knee VAS pain at 52 weeks.
Reference
Zhaohua Zhu, Qinghong Yu, Xiaomei Leng et al. Low-Dose Methotrexate for the Treatment of Inflammatory Knee Osteoarthritis: A Randomized Clinical Trial. JAMA Intern Med. 2025 Jun 2. Online ahead of print.
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