Sliver of hope for hand OA

4 minute read

Australian research presented at the 2023 EULAR Congress investigates the potential use of methotrexate in hand osteoarthritis.

Patients who have hand osteoarthritis characterised by synovial inflammation reported a moderate but potentially clinically relevant reduction in pain after six months of weekly methotrexate therapy, according to an Australian oral abstract presentation at EULAR.

Alfred Hospital head of rheumatology Professor Flavia Cicuttini presented the highly anticipated results of the METHODS trial, which looked at methotrexate as treatment for hand osteoarthritis with synovitis.

Around one in five Australians over the age of 55 has symptomatic hand osteoarthritis, and OA itself is the leading cause of disability in older adults.

Emerging evidence points to localised joint swelling as a key factor driving pain and disease progression in hand OA.

It’s a common clinical phenotype of the disease, with imaging studies identifying synovitis in around 50% of symptomatic hand OA cases.

Despite the prevalence of hand OA, there are very few effective treatments.

Recommendations in the EULAR guidelines, last updated in 2018, include improving education in joint protection, exercises to improve function, the use of splints and when to consider intra-articular glucocorticoid injections and trapeziectomy.

Topical NSAIDs are recommended as the first-line pharmacological treatment, followed by oral NSAIDs.

EULAR specifically recommends against treating hand OA with conventional or biological disease-modifying antirheumatic drugs, following several unsuccessful trials of cs/bDMARDs for the disease.

“Trials investigating the efficacy of hydroxychloroquine, different TNF-inhibitors and anti-interleukin-1 could not demonstrate efficacy of these antirheumatic drugs in patients with hand OA,” the guidelines note.

“Trials investigating methotrexate, sulfasalazine or colchicine have not been performed.”

The double-blinded, placebo-controlled METHODS trial sought to fill this gap by assessing the use of methotrexate in people with the synovitis hand OA phenotype.

“One of the things that’s attractive about the idea of using methotrexate is that we’re very used to using it for rheumatoid arthritis,” Professor Cicuttini told Rheumatology Republic.

The 96 participants were recruited from four Australian cities and were randomly allocated to receive either methotrexate 20mg or placebo once weekly for six months.

At baseline, the patients were, on average, 61 years of age and were predominantly female across both the intervention and placebo groups.

The primary outcome was reduced pain, and secondary outcomes included changes in physical function and quality of life.

In the trial methodology, the METHODS researchers argue that previous efforts to examine anti-inflammatory therapies in hand OA have been limited by the fact that they include all clinical phenotypes of the disease or were too short in duration.

They also cited two successful one-year randomised control trials of etanercept and adalimumab in patients with erosive inflammatory hand OA as a proof-of-concept in support of targeting synovitis.

“Based on the histology of the synovium in hand OA, there is no biological rationale why specific therapies targeting one inflammatory pathway, such as tumour necrosis factor antagonists, provide effective treatments for hand OA with synovitis,” the researchers said.

“Less specific therapies may offer greater disease modification, since multiple pre-inflammatory cytokines are targeted.”

The results, as presented by Professor Cicuttini at EULAR on Wednesday, revealed a -9.9mm between-group difference in pain at six months, measured via the Visual Analogue pain rating scale.

This puts the effect size at 0.45, indicating a moderate effect.

“For it to be clinically significant, we needed 15 millimetres out of 100,” she said.

“We’ve had an effective 10 – having said that, though, when we compared the data to our own population, the effect was of moderate significance.”

Between-group differences did not emerge until three months into the trial, and the methotrexate was well tolerated.

Because it took time for any effect on pain to emerge, Professor Cicuttini said she held hope that the methotrexate may have a disease-modifying effect.

“If it was [just working on pain] like a Panadol, you’d have an effect early,” she told RR.

“The effect follows what we expect to see from a true action of methotrexate.”

The logical next step, Professor Cicuttini said, would be to extend the trial to two or three years.

EULAR 2023 runs from 31 May to 3 June at the MiCo Convention Centre in Milan.

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