Methotrexate in early rheumatoid arthritis: Is the anchor drug still holding?

Treat-to-target (T2T) is currently the most fashionable strategy for treatment-naive, early rheumatoid arthritis (RA) patients. A T2T approach can lead to a complete and drug-free disease remission, whereas failure to obtain remission leads to damage early in the disease course. Hence, one should try to achieve high remission rates as early as possible, implementing the best therapeutic strategies available. Methotrexate (MTX) combined with glucocorticoid bridging is the mainstay of T2T. However, MTX is often used suboptimally in RA patients for many reasons, including poor tolerability, low compliance, and safety issues. Recent evidence has suggested that novel targeted synthetic DMARDs (tsDMARDs) such as the Janus-kinase (JAK) inhibitors in combination with glucocorticoids yielded better outcomes in early RA than conventional treatment. Such an approach may have advantages in terms of patients' outcomes, though some concerns about serious adverse events need to be addressed.