Rheumatoid arthritis (RA) is the most common inflammatory arthropathy, with a prevalence of 0.5-1% in the adult population. In 2026, the therapeutic goal is sustained clinical remission according to ACR/EULAR criteria, achievable in 40-60% of patients with available therapies.
Diagnosis and serological markers
The ACR/EULAR 2010 classification criteria remain the diagnostic standard. The most relevant serological biomarkers are rheumatoid factor (RF, sensitivity 70-80%, specificity 85%) and anti-citrullinated protein antibodies (ACPA/anti-CCP, sensitivity 70-75%, specificity 95-98%). Double seropositivity (RF+ and ACPA+) predicts more severe disease and greater probability of joint erosion, justifying more aggressive treatment from the outset.
Methotrexate: the cornerstone
Methotrexate (MTX) remains the first-line synthetic disease-modifying antirheumatic drug (sDMARD) in RA. The optimal dose is 20-25 mg weekly (oral or subcutaneous), with folic acid supplementation. The subcutaneous route has greater bioavailability and better digestive tolerability than oral at equal doses.
Biological DMARDs after MTX failure
When MTX fails to achieve remission or low activity within 3-6 months, EULAR 2023 guidelines recommend adding a biological DMARD or JAK inhibitor. Available families include anti-TNF (adalimumab, certolizumab, etanercept, golimumab, infliximab), anti-IL-6 (tocilizumab, sarilumab), abatacept (T-cell co-stimulation modulator), and rituximab (anti-CD20).
JAK inhibitors: efficacy and safety debate
JAK inhibitors (baricitinib, upadacitinib, tofacitinib, filgotinib) are oral small molecules that block JAK1/JAK2/JAK3/TYK2 kinases. Their efficacy is comparable or superior to anti-TNF agents. The ORAL SURVEILLANCE trial raised concerns about increased MACE and malignancies with tofacitinib versus anti-TNF in high-risk patients. EULAR 2023 guidelines recommend using JAK inhibitors with caution in patients over 65, smokers, or with cardiovascular risk factors or malignancy history.
Treat-to-Target strategy
The Treat-to-Target (T2T) strategy — assessing disease activity every 1-3 months and adjusting treatment until remission or low activity is achieved — has demonstrated reduced radiological joint damage and improved long-term function. DAS28-CRP <2.6 defines remission; CDAI ≤2.8 and SDAI ≤3.3 are more stringent alternatives.
