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Methotrexate inhibits progressive joint damage in hand OA, fails to improve pain, function
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ATLANTA — Methotrexate significantly reduced the progression of joint damage among patients with erosive hand osteoarthritis, but demonstrated no significant improvement in pain or function over placebo, according to a presentation at the 2019 ACR/ARP Annual Meeting.
“The prevalence of osteoarthritis is approximately 8-10% in patients older than 60, with a frequency that increases with age — 40% of [these] patients will eventually move to erosive hand osteoarthritis, which is a more painful form of the disease, with more disability,” Christian Roux, MD, PhD, from the department of rheumatology at the University of Cote d’Azur in France, said during a press conference. “The problem with erosive hand osteoarthritis is that we lack an effective treatment.”
“We treat patients with analgesics, NSAIDs or steroid injections, but don’t have a treatment that is very effective in this disease,” Roux added. “Given this, some doctors have attempted to use different treatments previously used in rheumatoid arthritis. Recent clinical and imaging studies have shown us the importance of inflammation in erosive hand osteoarthritis, with similarities to other inflammatory rheumatic diseases, such as rheumatoid arthritis.”
To assess the impact of an inflammatory arthritis treatment mainstay — methotrexate — on pain and structural progression, Roux and colleagues conducted a 1-year prospective, monocentric, randomized, double-blind, placebo-controlled study among patients with symptomatic erosive hand OA.
The 64 enrolled participants were randomized to receive either 10 mg of methotrexate per week or placebo, with 32 patients in each group. The primary outcome was pain assessment at 3 months, with secondary outcomes including clinical features — with pain measured on a Visual Analogue Scale (VAS) — radiographic features and MRI at 12 months.
According to study results, at 3 months, there was no significant variation in the mean decrease of the VAS pain score between the two groups (methotrexate: 17.5 decreased from 28.4 vs. placebo: 8.4 decreased from 25.2; P = .2).
However, Roux and colleagues found that erosive joints progressed significantly more to a remodeling phase in the methotrexate group (27%) vs. the placebo group (15%; P = .03). Additionally, joints with joint space loss appeared to have eroded less in the methotrexate group (8%) than in the placebo group (29%). The researchers also noted that, at baseline, interleukin-6 level (P < .0001) and synovitis findings on MRI (P = .02) were predictive factors for erosive structural evolution of non-erosive joints.
Although the researchers found no evidence of superior efficacy of methotrexate over placebo for pain and function evolution at 3 and 12 months, they determined that methotrexate greatly reduced the progression of joint damage vs. placebo, with methotrexate apparently facilitating bone remodeling.
“Our study did not show any superiority of methotrexate on pain at 3 months between the two groups,” Roux said. “There are different hypotheses on the failure of our study to achieve [improved pain] outcomes: The first may be the low doses of methotrexate and the second may be the importance of the placebo effect, which is very important in osteoarthritis disease.”
“[However,] it is interesting to note that in the methotrexate group, we saw less erosion progression and more remodeling effect,” he added. “Our hypothesis for these results is that erosive hand osteoarthritis is an inflammatory disease [and that] methotrexate has an effect on the inflammatory phase of the disease – a factor that may improve the healing process.”– by Robert Stott
Reference:
Ferrero S. Abstract #1759. Methotrexate in patients with hand erosive osteoarthritis refractory to usual treatments: A randomized, double-blind, placebo-controlled trial. Presented at ACR/ARP Annual Meeting, Nov. 8-13, 2019; Atlanta.
Disclosure: Roux reports no relevant financial disclosures.