Upadacitinib in rheumatoid nodules: beyond joint control

Rheumatoid nodules (RN) are a common extra-articular manifestation in rheumatoid arthritis (RA), occurring in up to 30% of patients, and are associated with more severe disease and high-titer rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (ACPA) positivity.They most commonly occur on pressure areas, including elbows, finger joints, or occasionally in internal organs such as the lungs 1,2 .RN may be refractory to disease-modifying antirheumatic drugs (DMARDs) and can paradoxically worsen with methotrexate or leflunomide despite improvement in joint disease activity 3 .Although often asymptomatic, RN may cause pain, functional or aesthetic impairment, and in the lungs, cavitation may lead to complications such as hemoptysis, pleural effusion, or pneumothorax.Their management remains challenging, as evidence of regression with standard RA therapies is limited.However, small case series have suggested that Janus kinase (JAK) inhibitors (JAKi) may be effective in RN treatment, including those affecting the skin and lungs [4][5][6][7][8][9] .In this context, we report two cases of RN that markedly improved following treatment with upadacitinib.The first case concerns a 50-year-old male smoker with recent-onset erosive, seropositive RA (RF and ACPA positive) who developed multiple subcutaneous nodules over the extensor surfaces of the elbows and wrists, leading to severe functional impairment.Because of active hepatitis C virus infection with elevated liver enzymes, sulfasalazine was initiated as first-line therapy, with inadequate arthritis control.After successful antiviral treatment, methotrexate was tried, but RN increased in number and size (the largest measuring 7 cm in diameter).Given this paradoxical progression, methotrexate was discontinued and upadacitinib 15 mg/day was initiated.Four months after treatment, there was >50% reduction in nodule size and complete