Background/Purpose: Coatomer protein complex subunit α (COPA) syndrome is a rare genetic multisystem autoimmune disorder inherited in an autosomal dominant manner. Onset typically occurs in childhood, including pulmonary, musculoskeletal, and renal manifestations. Pulmonary features include cough, dyspnea, and life-threatening diffuse alveolar hemorrhage. Lung involvement is a key negative prognostic factor. Musculoskeletal and renal manifestations can include arthralgias, polyarticular arthritis, and glomerulonephritis. Patients are usually diagnosed with other rheumatologic conditions prior to the discovery of COPA syndrome and are often treatment refractory. Therefore, it remains unclear which immunomodulating drugs are the most beneficial for these patients. We report the demographics, clinical findings, prior medications, and current outcomes for COPA syndrome patients treated with rituximab, including 3 patients not previously reported.

Methods: A retrospective chart review was performed for 11 COPA syndrome patients who were treated with rituximab.

Results: The mean age of symptom onset was 8 years (range 0.5-18). The mean current age is 25 years (range 4-55), with a mean of 16 years (range 2-54) since illness onset. There was a female majority (55%), and patients were white non-Hispanic (55%), white Hispanic (27%), and black (18%). Diagnoses given prior to the discovery of COPA syndrome included mixed connective tissue disease, juvenile idiopathic arthritis, ANCA-associated vasculitis, rheumatoid arthritis, and idiopathic pulmonary hemosiderosis. Patients predominantly carried the p.R233H mutation  (82%). The majority of patients presented with pulmonary symptoms (55%), but some presented with arthritis (27%), renal (9%), and neurologic (9%) manifestations. All patients had interstitial lung disease by chest CT. Other features included pulmonary hemorrhage (27%), arthritis (55%), and renal disease (36%). Laboratory results revealed elevated ESR (82%) and the presence of ANA (82%), ANCA (73%), RF (82%), and ACPA (50%). Prior to rituximab, the majority of patients (55%) failed 5 or more immunomodulatory drugs (mean: 4.5, range 1-9), and 3 patients (27%) were on oxygen therapy at rest. Patients had been treated with corticosteroids (100%), hydroxychloroquine (82%), methotrexate (45%), TNF-inhibitors (45%), azathioprine (36%), mycophenolate mofetil (36%), cyclophosphamide (27%), sulfasalazine (27%), tofacitinib (9%), and anti-IL-6R (9%). At last follow-up after rituximab (mean 2 years, range 1-5), no patients were on oxygen at rest. Chest CT results remained stable or showed improvement of nodules and ground glass opacities. The majority of patients (90%) reported symptomatic respiratory improvement; one patient had an arthritis flare. No patients have required listing for lung or renal transplants. These COPA patients tolerated rituximab without serious adverse events, specifically there were no infectious complications.

Conclusion: The COPA syndrome patients in our cohort had symptomatic improvement, stable or improving chest CT results, and decreased oxygen requirements after rituximab. Rituximab is a potentially promising therapy for patients with COPA syndrome.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/use-of-rituximab-to-treat-copa-syndrome-a-multi-institutional-cohort/