Atlanta, GA—Methotrexate significantly reduced progression of joint damage in patients with erosive hand osteoarthritis and might facilitate bone remodeling, according to a new study.

A presentation at the recent 2019 American College of Rheumatology/Association of Rheumatology Professional Annual Meeting in Atlanta revealed, however, that methotrexate did not demonstrate superior efficacy over placebo for pain relief or function evolution at 3 and 12 months in those patients.

The French study was touted as the first to evaluate the effect of methotrexate (MTX), a disease-modifying antirheumatic drug, in hand osteoarthritis. The 1-year prospective, monocentric, randomized, double-blind, placebo-controlled study sought to examine the drug’s effect on pain and structural progression in patients with symptomatic erosive hand osteoarthritis.

“Erosive hand OA poses problems in terms of pain, function and disability, but especially given the lack of truly effective therapies. The natural evolution of erosive hand OA is characterized by a succession of erosive phases and remodeling. These rearrangements suggest the involvement of pro-inflammatory cytokine cascades known to cause cartilage degradation and bone resorption,” explained lead author Christian Roux, MD, PhD, head of the joint unit in the rheumatology department at Cote d’ Azur University in France. “In recent years, imaging data have confirmed the presence of inflammation in the joints of these patients. The clinical presentation and imaging data bring this entity closer to inflammatory rheumatism, such as rheumatoid arthritis and psoriatic arthritis. These similarities have justified for some the use of treatments used in inflammatory rheumatism.”

Researchers randomized 64 patients with EHOA into two groups: those receiving 10 mg MTX per week or placebo. Defined as the primary endpoint was pain assessment at 3 months, while secondary endpoints were clinical features (pain on visual analog scale [VAS]), radiographic features (Verbruggen anatomical radiographic score and Gent University Score System), and MRI at 12 months.

Results indicate that, at 3 months, no significant difference in the mean decrease in VAS pain score (mm) was detected; (MTX: 17.5 [28.4] vs. placebo: 8.4 [25.2]; P = 0.2). The study team points out, however, that erosive joints progressed significantly more to a remodeling phase in the MTX group than in the placebo group (27% vs. 15%) (P = 0.03). In fact, the researchers note, joints with joint-space loss appeared to be less eroding in the MTX group than in the placebo group (8% vs. 29%; P = 0.2).

The study notes that interleukin-6 level (P <.0001) and synovitis findings on MRI (P = .02) at baseline were determined to be predictive factors for erosive structural evolution of nonerosive joints. 

“Our study shows that MTX did not demonstrate superior efficacy over placebo on pain and function evolution at 3 and 12 months in subjects with EHOA,” the authors conclude. “However, MTX significantly reduced the progression of joint damage compared to placebo and seems to facilitate bone remodeling. The presence of systemic and local inflammations at baseline were predictors of erosive progression.”

“The study does not demonstrate superior efficacy of MTX over placebo on pain and function in subjects with erosive hand OA. But probably it will be linked to a multifactorial origin of pain in these subjects such as mechanical or inflammatory pain,” Roux emphasized. “It is possible that we have to treat earlier if we want to have an effect on pain. However, our results show a structural effect of the treatment that facilitates bone remodeling and seems to slow the erosive structural progression of digital osteoarthritis with a seemingly more pronounced effect in patients with early lesions. I think this is a major point. The main complaint for people is the deformity linked to structural evolution in this disease. Our study’s results should encourage new studies to be conducted.”

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