PO:11:171 | Subcutaneous tocilizumab use in a young-onset mixed connective tissue disease patient with multiple treatment failures

Rhaysa Araujo Mousinho¹, Elide Lupi², Massimiliano Limonta² | ¹Clinica di Reumatologia, Dipartimento di Medicina and ²Istituto di Anatomia Patologica, Dipartimento di Medicina di Laboratorio, Osp. S. M. della Misericordia, Università di Udine, Italy

Background. Mixed Connective Tissue Disease (MCTD) is a systemic autoimmune disorder characterized by the presence of anti-U1 ribonucleoprotein (U1-RNP) antibodies associated with clinical features commonly observed in systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis (RA), and polymyositis/dermatomyositis. The pediatric-onset form of the disease is among the rarest entities in pediatric rheumatology.

Case Report. We present the case of a 21-year-old Pakistani woman diagnosed with MCTD at the age of 11 (2015), with onset characterized by Raynaud’s phenomenon (scleroderma capillaroscopic pattern), polyarthritis, and recurrent parotitis. Laboratory findings showed ANA 1:640 speckled pattern, anti-U1-RNP 643 U/mL, rheumatoid factor (RF) 1750 IU/mL, and elevated ESR and CRP. She was treated in the pediatric setting with oral corticosteroids, hydroxychloroquine (HCQ) 300 mg/day, and methotrexate (MTX) up to 20 mg/week. In 2021, due to partial disease control, mycophenolate mofetil (MMF) 1.5 g/day was added, achieving a good response. At age 18 (2022), upon transfer to our care, she presented with active arthritis and elevated inflammatory markers. Instrumental assessment ruled out cardiac and pulmonary involvement. In December 2022, arthritis of the hands and wrists persisted, with ESR 120 mm/h and CRP 2.3 mg/dL (normal <1 mg/dL). Prednisone (PDN) was increased up to 12.5 mg/day and MMF to 2 g/day (in combination with MTX 20 mg/week and HCQ 300 mg/day). Throughout 2023, she experienced recurrent episodes of painful left parotid swelling without fever (ESR 120, CRP 4.5 mg/dL), which responded to tapered corticosteroid therapy (PDN 25 mg/day). In early 2024, she developed progressive fatigue, worsening arthritis of hands and feet, bilateral parotid swelling, and persistently elevated inflammatory markers. MTX was replaced with azathioprine for approximately four months, without clinical improvement (MMF 2 g + HCQ 200 mg + PDN 15 mg/day). In April 2024, azathioprine was discontinued and therapy with rituximab (1 g at T0 and T15) was initiated but suspended after the second infusion due to a mucocutaneous allergic reaction. In October 2024 (ESR 138, CRP 3.1 mg/dL), off-label use of subcutaneous tocilizumab 162 mg weekly was requested and approved (in combination with MTX 10 mg/week and HCQ 200 mg/day). After five months of treatment, the disease is well controlled. The patient no longer presents active arthritis or acute parotitis episodes, prednisone was tapered to 5 mg/day, and inflammatory markers improved (ESR 84 mm/h, CRP 0 mg/dL).

Conclusions. Tocilizumab is a humanized monoclonal antibody targeting the IL-6 receptor, approved for use in RA, juvenile idiopathic arthritis, and giant cell arteritis. Only a few reports in the literature describe tocilizumab use in MCTD, all in pediatric cases with articular involvement. Given its proven efficacy in juvenile idiopathic arthritis, we decided to usetocilizumab in this patient, obtaining a favorable response on arthritis, systemic disease activity, and parotitis. This therapy requires careful clinical and laboratory monitoring.