While the use of methotrexate in RA is well supported by evidence, the same cannot be said for its use in psoriatic arthritis (PsA), an Australian led Cochrane Review has shown.
The first systematic review of the evidence for the conventional synthetic DMARD (csDMARD) in PsA has found only low-quality evidence from one trial showing that low dose MTX might be slightly more effective than placebo when taken for six months.
The review, conducted by South Australian rheumatologists Dr Tom Wilsdon and Dr Sam Whittle, found eight randomised trials that compared MTX to placebo or other DMARDs but only one placebo-controlled trial was considered to have a low risk of bias.
The single study involving 221 participants used to inform the review showed that MTX in doses of 15mg or less per week had a modest benefit in patients with PsA.
In terms of disease response as measured by PsARC the risk ratio was 1.76 for placebo compared to MTX, which equated to an absolute difference of 16% more responders with MTX compared to placebo (37 vs 21 out of 100 people responding for MTX and placebo respectively). Effects sizes for outcomes such as function, pain and global assessments of disease activity were small.
Overall, the number needed to treat with MTX for an additional beneficial outcomes was six, and the absolute improvement in function was 10%.
The review also showed that none of the randomised controlled trials had reported the effects of MTX on health-related quality of life, radiographic progression, enthsitis, dactylitis and fatigue.
For safety and tolerability, only low quality evidence was available showing similar rates of serious adverse events and withdrawals due to adverse events for MTX and placebo.
Speaking to the limbic, study lead author Dr Wilsdon said the findings would probably not be a surprise to most rheumatologists, who will have some patients with psoriatic arthritis who experience a marked improvement taking MTX.
“The outcomes of our systematic review indicate that methotrexate might not provide clinically meaningful benefits to patients with psoriatic arthritis. If it is used, consideration should be given to escalation to an alternative therapeutic agent if there is an inadequate response,” he said.
The findings tended to support new American College of Rheumatology (ACR) and National Psoriasis Foundation 2018 guidelines that recommend a bDMARD as first-line therapy in patients with severe psoriatic arthritis who are treatment naive, and methotrexate in mild disease.
In contrast, in EULAR guidelines from 2015, the general approach to therapy is to start with a csDMARD, such as MTX, as first-line therapy before progressing to a bDMARD.
“There is a greater body of evidence showing evidence of benefit for bDMARDs in psoriatic arthritis patients compared to methotrexate. We believe there might be a case for earlier biologic use, particularly for patients with severe disease,” said Dr Wilsdon.
However he noted that in Australia, it is not possible to access PBS-subsidised biologic DMARDs (such as TNFi) without a trial of MTX at a dose of at least 20mg per week and at least one other DMARD for 3 months.