Pos0984 daratumumab rescue therapy in a patient with anti-mda5 associated ards

Background MDA5-associated dermatomyositis is often associated with rapid progressive interstitial lung disease resulting in acute respiratory distress syndrome (ARDS). Patients that progress to require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) generally have a high mortality despite intensive combined immunosuppressive treatment. (1) Daratumumab, an anti-CD38 monoclonal antibody has been successfully used in the treatment of refractory autoantibody-associated diseases with the intention of targeting autoantibody-producing CD38+ plasma cells. (2) Objectives Rescue treatment of anti-MDA5 antibody associated ARDS with Daratumumab combination therapy. Methods We treated an ECMO-dependent patient with refractory anti-MDA5 dermato-pulmonary syndrome with a combination treatment of four weekly doses of 1800mg daratumumab s.c. as well as tofacitinib, ciclosporin and prednisolone. Results A 55-year-old patient was transferred to our hospital with ARDS of unknown origin combined with a short history of oligoarthritis and Gottron’s papules. She required mechanical ventilation and ECMO. Autoantibodies showed strong positivity for anti-MDA5 and -Ro52, so she was diagnosed with MDA5+ dermatopulmonary syndrome. She initially received treatment with cyclophosphamide, tofacitinib, ciclosporin, intravenous immunoglobulins and high-dose steroids. However, her interstitial lung disease showed no improvement. We escalated the immunosuppressive therapy with daratumumab. The pulmonary function improved approximately four weeks after daratumumab initiation and the patient was consequently weaned from ECMO and respirator. The clinical course was complicated by an ischemic stroke and a blood stream infection with enterococci which would have made a lung transplantation impossible. We were able to discharge the patient to rehabilitative care with only low-flow supplemental oxygen. Conclusion Rescue immunosuppressive therapy of MDA5-antibody associated ARDS with daratumumab in addition to tofacitinib, ciclosporin and prednisolone was associated with remarkable clinical improvement in this case. More clinical data and long-term follow-up are needed to investigate safety and efficacy of this treatment regimen in MDA5-antibody-associated disease. References [1]Vuillard, C. et al. Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study. Ann. Intensive Care 8, 87 (2018). [2]Ostendorf, L. et al. Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus. N Engl J Med 383, 1149–1155 (2020). Acknowledgements We thank the patient and her family for allowing us to present this case. Disclosure of Interests Lennard Ostendorf Speakers bureau: Speaker for Roche, unrelated to the abstract., Frédéric Münch: None declared, Lena Thormählen: None declared, Jens Nee: None declared, Udo Schneider: None declared.