Background: Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is a specific subtype of idiopathic inflammatory myopathy characterized by prominent interstitial lung disease (ILD) and high mortality with a trait of east Asian dominance. Trying to tackle the IFN-I pathway in MDA5+DM, Janus Kinase inhibitor (JAKi), such as tofacitinib, has demonstrated its efficacy in terms of improving survival among early-stage MDA5+DM-ILD patients. Nevertheless, the management of more advanced-stage MDA5+DM with rapidly progressive ILD (RPILD), i.e., patients who developed respiratory failure within 3-month of the onset of disease, is still a big challenge in practice.

Objectives: Owing to the lack of highly efficacious therapy and the grave prognosis of the disease, plasmapheresis remains to be a viable option for MDA5+DM-RPILD. Immunoadsorption had been proven to be a more efficient and safer treatment than plasma exchange in miscellaneous antibody-mediated autoimmune diseases. Herein, we conducted a large real-world study using Protein A immunoadsorption on top of JAKi, to evaluate the effectiveness of this approach in MDA5+DM with RPILD.

Methods: Based on a large inception cohort of MDA5+DM, patients with RPILD (oxygen index below 300 within the first 3 months of disease duration) were included. Patients who received protein A immunoadsorption plus a JAKi was compared to those treated with JAKi alone. Propensity score matching (PSM) was performed to adjust confounding factors. Survival analysis was conducted to evaluate the efficacy of immunoadsorption add on.

Results: From October 2017 to April 2024, a total of 152 newly diagnosed MDA5+DM patients with RPILD were eligible for analyses. 34 patients underwent immunoadsorption with JAKi (ProJAK group) and 68 patients received JAKi with or without other immunosuppressants combination (JAK group) were compared as control after 1:2 PSM. The 6-month transplantation-free survival was significantly improved from 16.2% in JAK group to 41.2% in ProJAK group (p=0.004). Subgroup analysis suggested ProJAK therapy tended to have a more significant survival gain in OI < 200 patients. Of note, our data showed a hitherto undescribed serendipitous finding that anti-MDA5 antibody titers dramatically declined soon after emergency bilateral lung transplantation and kept decreasing to normal range within 6-month, indicating that anti-MDA5+ antibodies might be actively participated in the process of acute lung injury, and an average of 40% titer reduction by immunoadsorption was relevant to a clinical meaningful outcome improvement. The most common adverse effect of ProJAK was transient immunoglobin decrease, but the infectious rate was similar between two groups.

Conclusion: Immunoadsorption in combination with JAKi might be a promising treatment approach for MDA5+DM patients with RPILD.

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Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.