Methotrexate in peripheral spondyloarthritis including psoriatic arthritis: a need for further evaluation.

The International Society for Spondyloarthritis [Assessment of SpondyloArthritis (ASAS)] recommends the use of SSZ in the case of active peripheral synovitis with or without concomitant skin psoriasis [1, 2]; MTX is not mentioned in the table that summarizes the recommendation. In the ASAS recommendations, it is stated that ‘Most rheumatologists will try MTX in patients with predominant peripheral spondyloarthritis but no evidence-based recommendation can presently support this’ [2]. The recommendations from other international scientific societies, such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) [3] or the European League Against Rheumatism (EULAR) [4], focus on the management of psoriatic arthritis and propose MTX as a potential first-line DMARD therapy but acknowledge the paucity of evidence. In this issue of Rheumatology, Kingsley et al. [5] report the third negative placebo randomized controlled trial that evaluated MTX in patients suffering from psoriatic arthritis with a relevant sample size and a mode of administration of MTX close to the rheumatological daily practice. Despite this well-conducted, clearly presented and adequately interpreted study, one questions whether such a lack of demonstration of superiority of MTX over placebo in the a priori chosen primary variable will affect rheumatological daily practice. This questioning is based not only on the fact that a negative trial is more frequently exposed to criticisms than a positive trial, but also, and probably more importantly, on the fact that such negative results are not in line with the physicians’ views. From the data, one anticipates that the main criticisms are the inclusion criteria, the choice of the primary variable and the study duration. In this trial, the definition of an active disease required to participate in the trial (e.g. main inclusion criterion) was the presence of only one peripheral joint with active inflammatory synovitis. Since the primary end-point was based on a change in this parameter, perhaps the more appropriate primary end-point is the status of the patient at the end of the trial and not a change. For example, the percentage of patients with no synovitis or the percentage of patients in remission and low disease activity as it is currently done in RA in clinical trials focused on patients with baseline moderate active disease [6]. Moreover, the data presented emphasize and confirm that patient-reported outcomes and patient’s opinion, or both, are more discriminant than objective measures to differentiate an active drug from a placebo [7, 8]. In a trial reported by Kingsley et al. [5], changes in both the patient’s and the assessor’s global assessment clearly showed not only a statistically significant difference, but also a relevant treatment effect in favour of MTX. Finally, perhaps a 7-year time period to enrol patients in a study was too long, with the potential for introducing bias in the characteristics of the recruited patients. Moreover, could such a long period of time be due to the reluctance of the physicians to ask their patients to participate in a placebo controlled trial that evaluates a drug whose efficacy they were already convinced of? Such a difficulty might be resolved by selecting an alternative study design in which patients receive the active drug in a cross-over design or a systematic long-term extension. Apart from the criticisms of this particular trial, the physicians’ reluctance to reconsider their opinion about the benefit of MTX in such patients will be based mainly on their own feeling or experience. Obviously, most rheumatologists are deeply convinced of the benefit of MTX in patients suffering from active inflammatory chronic aseptic synovitis, whatever the underlying disease. On the basis of all the above arguments, it is tempting for clinicians not to consider any change in their daily practice: i.e. the current working practice of rheumatologists to use MTX when prescription is not under strict regulation or supervision by health authorities. However, our younger colleagues follow the evidence-based medicine approach and will be more reluctant to use a drug for a specific disease for which there is a lack of evidence of efficacy. Moreover, this attitude may result in clinicians forgetting that the main objective of a treatment for inflammatory rheumatic disorders nowadays is not only to improve the patient’s existing condition, but also to prevent subsequent deterioration. Regarding the first objective (i.e. to improve the patient’s current condition), the data presented in this trial are in favour of the use of MTX. For the second