ATLANTA – , according to results from the small, prospective, double-blind, randomized, placebo-controlled .
“Our study failed to show the superiority of methotrexate over placebo on pain evolution, but our results on structural evolution and the presence of inflammatory parameters as predictors of erosive evolution in nonerosive diseases may lead us to discuss the place of methotrexate in early steps of the disease evolution, and underlines the importance of the part played by the interaction between synovitis and subchondral bone in erosive progression,” Christian Roux, MD, PhD, of the department of rheumatology at Côte d’Azur University, Nice, France, said in his presentation at the annual meeting of the American College of Rheumatology.
Dr. Roux and colleagues enrolled 64 patients in the ADEM trial, where patients with symptomatic erosive hand osteoarthritis (EHOA) were randomized to receive 10 mg of methotrexate (MTX) per week or placebo. At 3 months, researchers assessed patients for pain using the Visual Analog Scale (VAS) score for hand pain, and secondary outcome measures at 12 months included VAS score for hand pain, radiographic progression using Verbruggen-Veys Anatomical Phase Score and Gent University Scoring System, and MRI.
Patients were included in the study if they were between 45 and 85 years old with a VAS pain score greater than 40, had failed classic therapeutics (acetaminophen, topical NSAIDs, and symptomatic slow-acting drugs), and had at least one erosive lesion. At baseline, the MTX and placebo groups were not significantly different with regard to gender (91% vs. 97% female), mean body mass index (24.6 kg/m2 vs. 24.2 kg/m2) and mean age (67.5 years vs. 64.9 years). Radiologic data showed joint loss, erosive, and erosive plus remodeling measurements were also similar between groups at baseline.
The mean VAS score for patients in the MTX group decreased from 65.7 at baseline to 48.2 at 3 months (–17.5; P = .07), compared with a decrease from 63.9 to 55.5 (–8.4; P = .002). At 12 months, VAS scores for patients in the MTX group decreased to 47.5, compared with a decrease in the placebo group to 48.2. However, the between-group differences for VAS scores were not significant at 3 months (P = .2) and at 12 months (P = .6).
“We have different hypotheses on the failure of our study on our main outcome, which was pain,” he said. “The first is a low-dose of methotrexate, and the second may be ... a placebo effect, which is very, very important in osteoarthritis.”