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Conventional synthetic DMARD (csDMARD) therapy in patients with axial spondyloarthritis (SpA) is a matter of continuous debate. Part of this discussion is a dispute about methotrexate (MTX) comedication in patients with axial SpA treated with tumour necrosis factor inhibitors biologicals (TNFi). The dispute seems to be based on perceptions rather than scientific evidence and may have been fuelled by one of the European League Against Rheumatism task force on the management of rheumatoid arthritis (RA) recommendations. This recommendation states that in RA, TNFi-biologicals should be used in combination with MTX,1 which finds its justification in the results of multiple randomised clinical trials and careful posthoc analyses thereof.
According to the Assessment in SpondyloArthritis International Society (ASAS), however, axial SpA is not a disease in which csDMARDs including MTX should be prescribed.2 This bold conclusion has been framed by thorough systematic literature research that has failed to find evidence for efficacy of csDMARDs in axial SpA.3
Guidelines and recommendations are supposedly clear and unequivocal. However, clinicians prefer to manage ‘several shades of grey’ rather than ‘think in black and white’. They may argue that absence of evidence (for the efficacy of csDMARDs in axial SpA) does not necessarily mean evidence for the absence of such an effect. In fact, and in spite of current recommendations prescribing the opposite, many do treat patients with axial SpA with csDMARDs occasionally.
It must be easier to digest disobedience with guidelines if plausible scientific explanations can be employed to justify non-commitment: immunogenicity of TNF-inhibiting biologicals is one of those attractive theories that scientists may bring up in order to explain why combinations of MTX and a TNFi-biological work better in RA than monotherapy with a biological: MTX may prevent the formation of TNFi-neutralising antibodies, which in turn could be responsible for loss …
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