Tuesday, January 10, 2017

Methotrexate in Knee Osteoarthritis Revisited

There had been an article on methotrexate (MTX) in knee osteoarthritis (OA), which had been published in 2014. As it had been a double-blind, randomized controlled trial, I had had a closer look at the article back then (1). Abou-Raya and colleagues submitted and published: "Methotrexate in the treatment of symptomatic knee osteoarthritis: randomised placebo-controlled trial". I had been critical about the article and the results of the study. Today I revisited the article, as I wanted to know more on subsequent trials.

I was quite surprised that the article had been retracted. The Annals of Rheumatic diseases discussed the decision (2). They listed eight points of “great concern”. And the Investigation Committee’s report concluded: “There is an unintentional mistake in the statistical process, with errors in collection of data in some groups”.

Let’s hope that Sarah R. Kingsbury and colleagues fare better with their study: “Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase III trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial”. (3) Discussion: “The PROMOTE trial is designed to examine whether MTX is an effective analgesic treatment for OA. The MRI substudy will address the relationship between synovitis and symptom change. This will potentially provide a much needed new treatment for knee OA.” The follow-up should have been completed by December 2016, so we should get results during 2017. Allow me already to voice some doubts. MTX is an immunosuppressant and any reduction of pain is due to this mode of action (4). Chronic low-grade inflammation is thought as a major driver of joint degradation in osteoarthritis (5); and it's unclear if MTX suppresses this kind of inflammation. “Despite the clear role of inflammation in OA, recent trials of potent anti-inflammatory therapies, including use of systemic and intra-articular biologic agents to inhibit TNFα and IL-1β, proved disappointing [Hunter, 2008].” 

But let’s wait for the publication of the PROMOTE study, which I’ve just misspelled as PRO MORTE. 


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