The effect of gender on methotrexate prescription attitudes in Italian rheumatoid arthritis patients: the MARI study.

OBJECTIVES: The MARI study investigated the prescription patterns of methotrexate (MTX) in patients presenting with rheumatoid arthritis (RA) in Italy. The primary aims of this cross-sectional analysis from the MARI study were to investigate the effect of gender on the prescription patterns and safety of MTX therapy. METHODS: The study enrolled 1336 patients with RA. Retrospective data included patients' clinical history, previous treatment with MTX and other DMARDs, and MTX modifications in the previous 12-month period. Cross-sectional data included information about current treatment with MTX (dose and route of administration, and adverse events), concomitant medications, disease activity, and modifications of MTX treatment at study entry. The prescription patterns of MTX, rates and causes of MTX modifications were analysed according to gender. RESULTS: There were no significant differences related to gender in the prescription patterns of MTX, either at 6 months after starting MTX or at the time of study entry. In the 12 months prior to study entry, women (4%) were more likely to undergo MTX modifications (dose or route of administration) compared to men (2%, p=0.032), due to subjective intolerance, but this difference was no longer significant after controlling for confounders. At study entry, a higher proportion of women (27%) reported tolerability issues (nausea and weakness) related to MTX compared to men (14%, p=0.001). Although a similar percentage of males and females changed dose or route of administration of MTX at the time of study entry, the reasons for such modifications were dissimilar between genders. Particularly, a higher proportion of women underwent MTX modification due to intolerance (women 6% vs. men 1%, p=0.002). CONCLUSIONS: In Italy, prescription patterns of MTX do not differ between genders. However, women seem to be at higher risk of adverse events leading to MTX modifications.

The Th17 axis in psoriatic disease: pathogenetic and therapeutic implications.

Psoriasis and psoriatic arthritis represent two paradigmatic conditions characterized by chronic inflammation and possibly autoimmunity, despite the absence of known serum autoantibodies. The two diseases, albeit strongly correlated from clinical, genetic, and epidemiogical standpoints, manifest significant differences in terms of etiology and pathogenetic mechanisms. Nonetheless, Th17 cells appear crucial to both diseases, and IL23 is the cytokine involved in determining the fate of naive CD4+ cells to differentiate into a pathogenic phenotype. This basic experimental observation led to a clear understanding of the immune dysfunction causing psoriasis and psoriatic arthritis but, more importantly, also led to new therapeutic approaches. In recent years, monoclonal antibodies directed to IL12/IL23 (ustekinumab) or IL17 (secukinumab, ixekizumab, brodalumab) are being investigated or have proven to be beneficial for patients with psoriatic disease, thus further supporting the view that Th17 cells play a pivotal role in disease onset and perpetuation. These most recent reports indeed represent significant developments that may allow overcoming the TNFα pathway as the major therapeutic target in chronic inflammation.