TOPLINE:
The antimetabolite and immunosuppressant methotrexate, taken orally and in addition to usual analgesia, alleviates pain in patients with knee osteoarthritis.
METHODOLOGY:
- Investigators conducted a phase 3 randomized controlled trial among 155 patients in the United Kingdom with painful radiographic knee osteoarthritis and an inadequate response to their current medication (PROMOTE trial).
- Patients were assigned to oral methotrexate once weekly (6-week escalation from 10 to 25 mg) or placebo for 12 months, added to usual analgesia.
- The main outcome was average knee pain at 6 months on a numerical rating scale from 0 to 10.
TAKEAWAY:
- At 6 months, mean scores for knee pain had decreased by 1.3 points in the methotrexate group and 0.6 points in the placebo group (difference by intention to treat, 0.79 points; P = .030).
- The former also saw greater benefit in terms of Western Ontario and McMaster Universities Osteoarthritis Index scores for stiffness (difference, 0.60 points; P = .045) and physical function (difference, 5.01 points; P = .008).
- Differences between groups were no longer significant at 12 months.
- Benefit of methotrexate appeared to be dose related.
- The groups were similar with respect to nausea and diarrhea; four serious adverse events (two per group) were deemed unrelated to study treatment.
IN PRACTICE:
“Further work is required to understand adequate methotrexate dosing, whether benefits are greater in those with elevated systemic inflammation levels, and to consider cost-effectiveness before introducing this therapy for a potentially large population,” the authors wrote.
SOURCE:
The study was led by Sarah R. Kingsbury, PhD, University of Leeds and National Institute for Health and Care Research Leeds Biomedical Research Centre, Leeds, England, and was published online in Annals of Internal Medicine.
LIMITATIONS:
Limitations included a decrease in methotrexate dose between 6 and 12 months, nonallowance of switching to subcutaneous drug for intolerance, and a lack of assessment of the effectiveness of blinding.
DISCLOSURES:
The study was funded by Versus Arthritis, a charity that supports people with arthritis. Some authors reported affiliations with Versus Arthritis and/or companies that develop drugs for arthritis.
A version of this article appeared on Medscape.com.