POS0202 RELATIONSHIP BETWEEN SERUM INTERFERON-Α LEVELS AND CLINICAL PARAMETERS, TREATMENT RESPONSES, AND OUTCOMES IN PATIENTS WITH ANTI-MELANOMA DIFFERENTIATION-ASSOCIATED GENE 5 ANTIBODY-POSITIVE DERMATOMYOSITIS
Authors: T. Ida, T. Iwamoto, S. Kojima, T. Takahashi, M. Yasui, K. Hasebe, S. Furuta, K. Ikeda, K. Kurasawa, T. Tamachi, K. Hirose, H. Nakajima
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis frequently associated with rapidly progressive interstitial lung disease with a poor prognosis, especially in Asian populations [1]. Therefore, aggressive immunosuppressive therapy in combination with glucocorticoids and multiple immunosuppressants with prompt treatment escalation, depending on the treatment response, is required. Several biomarkers, including anti-MDA5 antibody titers and ferritin levels, have been identified for monitoring disease activity and 3-month prognosis [2, 3], but none of them reflect real-time treatment response or serve as an indicator of treatment sufficiency. Recently, type I interferon (IFN), especially IFN-α, has been suggested to play a potential role in the pathophysiology of MDA5-DM [4]; however, its clinical role as a biomarker for MDA5-DM remains largely unknown. <h3>Objectives:</h3> To determine the relationship between serum IFN-α levels and clinical parameters, treatment responses, and outcomes in Japanese patients with MDA5-DM. <h3>Methods:</h3> This observational exploratory study enrolled 59 patients with MDA5-DM aged ≥20 years. Clinical data, serum IFN-α levels, and clinical outcomes, including the response to initial treatment and 3-month mortality, were evaluated. Serum IFN-α levels were measured in patient sera using a high-sensitivity enzyme-linked immunosorbent assay (S-PLEX immunoassay, Meso Scale Discovery, USA). Eleven healthy subjects were recruited to compare the serum IFN-α levels in patients with MDA5-DM. <h3>Results:</h3> The characteristics of the enrolled MDA5 patients were as follows: median age, 55 years; 57.6%, females; 45.8%, muscle symptoms; 98.3%, interstitial lung disease; and 27.1%, mortality within 3 months of the initial treatment. Serum IFN-α levels at pre-treatment were significantly higher in patients with MDA5-DM than in healthy controls (14.9 pg/mL vs. 0.06 pg/mL, p&lt;0.001). Among patients with MDA5-DM, serum IFN-α levels were higher in those with fever and muscle symptoms. Serum IFN-α levels correlated with serum LDH and anti-MDA5 antibody titers. The optimal cut-off value of the baseline serum IFN-α level for 3-month mortality by the receiver operating characteristic curve was 26.6 pg/mL. The 3-month survival rate was lower in patients with an IFN-α of &gt;26.6pg/mL than in those with an IFN-α of ≤26.6pg/mL (40.0% vs. 79.5%, p=0.004) (Figure 1). Of the nine patients whose serum IFN-α levels could be re-measured 2 weeks after the initiation of initial treatment, five were responders and four were non-responders to the initial treatment. Responders showed a greater reduction in serum IFN-α levels from baseline at 2 weeks than did non-responders (79.6% vs. 51.7%) (Figure 2). One hundred percent (3/3 patients) of the patients with &gt;80% serum IFN-α decrease at 2 weeks and 33.3% (2/6 patients) of the patients with ≤80% serum IFN-α decrease at 2 weeks were responders. <h3>Conclusion:</h3> Baseline serum IFN-α levels were associated with fever, muscle symptoms, and other biomarkers, including LDH and anti-MDA5 antibody titers. High baseline serum IFN-α levels are associated with poor 3-month prognosis. A rapid decrease in serum IFN-α levels after induction treatment could be a potential surrogate marker of treatment response; however, large-scale confirmatory studies are required. <h3>REFERENCES:</h3> [1] Wu W, et al. Clin Rev Allergy Immunol 2021;60:293-304. [2] Matsushita T, et al. Br J Dermatol 2017;176:395-402. [3] Gono T, et al. Rheumatology 2010;49:1713-19. [4] Horai Y, et al. Mod Rheumatol 2015;25:85-9. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Tomoaki Ida: None declared, Taro Iwamoto GSK, AstraZeneca, Shotaro Kojima: None declared, Tatsuro Takahashi: None declared, Masahiro Yasui: None declared, Keisuke Hasebe: None declared, Shunsuke Furuta Asahi Kasei Pharma, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Kissei Pharmaceutical, GSK, and Otsuka Pharmaceutical, Asahi Kasei Pharma, Kei Ikeda Eli Lilly, Abbvie, Eisai, Gilead, AstraZeneca, Asahi Kasei, Mitsubishi-Tanabe, Kazuhiro Kurasawa: None declared, Tomohiro Tamachi: None declared, Koichi Hirose: None declared, Hiroshi Nakajima AstraZeneca.