OA16 Clinical and biochemical improvement following daratumumab therapy for anti-MDA5 antibody positive dermatomyositis with rapidly progressive interstitial lung disease: a case report

Abstract Background/Aims Anti-melanoma differentiation-associated 5 gene autoantibody (anti-MDA5) positive dermatomyositis (DM) with rapidly progressive interstitial lung disease (RP-ILD) represents the most severe and difficult-to-treat form of autoimmune myositis with unfavourable 6-month survival rates despite intensive treatment strategies of combination therapy with glucocorticoids, cyclophosphamide, calcineurin inhibitors, mycophenolate mofetil and rituximab. We describe a case of anti-MDA5 positive DM with RP-ILD that was refractory to intensive combination therapy, requiring courses of rescue plasmapheresis, before eventually responding to intravenous daratumumab. Methods A 30-year-old non-smoking Chinese man who was previously well was hospitalised after 3 weeks of intermittent pyrexia, non-productive cough, lethargy, rashes and myalgia. Examination revealed typical cutaneous changes of dermatomyositis, bilateral mid-to-lower zone inspiratory crepitations in his chest with no proximal muscle weakness or synovitis. Initial investigations demonstrated elevations in creatine kinase, C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, ferritin and neutrophil-to-lymphocyte ratio. Although an initial chest radiograph was normal, CT thorax 4 days later showed non-specific ground-glass opacities with consolidation in both lower lobes. Anti-MDA5 antibodies were strongly positive on EUROLINE Inflammatory Myopathies 16 Ag (IgG) commercial line immunoblot. He was transferred to our centre for further care one week after hospitalisation and was intubated on arrival for type I respiratory failure. He was initiated on combination therapy of intravenous methylprednisolone, intravenous rituximab, hydroxychloroquine, tofacitinib and was also treated with plasmapheresis to remove pathogenic anti-MDA5 antibodies. Although his condition improved initially with successful extubation within one week, the disease remained active in the following months with several admissions for infection-related issues and progression of RP-ILD. Despite various combinations of immunosuppressives and further courses of plasmapheresis, at 6 months post-diagnosis he continued to require a minimum daily prednisolone dose of 45mg (0.625mg/kg/day), remaining positive for anti-MDA5 antibodies on the immunoblot assay, with persistently elevated serum ferritin and transaminases. As such, he was treated with four doses of intravenous daratumumab in an attempt to deplete the long-lasting plasma cells that may be driving the disease. Results Following daratumumab treatment, the anti-MDA5 antibody turned negative on the immunoblot assay with normalisation of ferritin and transaminases, with corresponding improvement in lung function tests and chest radiograph findings. 3 months post-daratumumab, he remains clinically well on hydroxychloroquine, tofacitinib and nintedanib, with successful continuing taper of prednisolone. Conclusion Daratumumab is an anti-CD38 monoclonal antibody licensed for the treatment of multiple myeloma which has been used off-label for other refractory autoimmune conditions such as SLE. It is postulated that besides CD19/20 positive B cells, CD38 positive long-lived autoantibody-secreting plasma cells are essential drivers of chronic inflammation in these autoimmune diseases. In our patient with anti-MDA5 DM and RP-ILD, the use of daratumumab was well-tolerated and led to definite clinical and biochemical improvement. Disclosure L. Koh: None. G. Chai: None. M. Manghani: None. X. Lim: None. B.P.L. Leung: None. C. Chua: None.