BackgroundDermatomyositis (DM) is an immune-mediated idiopathic inflammatory myopathy (IIM). Two subsets of autoantibodies have been identified in patients with IIM. The first includes myositis-specific antibodies (MSA) such as anti-Jo-1, anti-TIF-1 and anti-MDA-5. The second includes myositis-associated antibodies (MAA) such as anti-PM-SCL, anti-Ku and anti-Ro, which are also found in patients with other autoimmune diseases. MSA are highly specific for IIMs and represent a unique clinical phenotype and prognosis, and have also been associated with the pathogenesis of various subsets of IIM. The ProDERM study recently demonstrated the efficacy and safety of intravenous immunoglobulin (IVIg) in DM patients (1) but the potential role of MSA and MAA in the treatment responses of these patients has not yet been determined.ObjectivesAutoantibody status at baseline and its relationship to treatment response to IVIg were investigated in a post-hoc analysis of the randomized, placebo-controlled ProDERM study.MethodsIn the ProDERM study, dermatomyositis patients received 2 g/kg IVIg treatment (n=47) or placebo (n=48) every 4 weeks for 16 weeks. From week 16 onwards eligible patients (n=91) received IVIg for a further 24 weeks. The primary endpoint was a Total Improvement Score (TIS) of at least 20 (indicating at least minimum improvement) at week 16 and no confirmed deterioration up to week 16. Serum samples were taken at baseline and analysed for MSA (anti-Jo-1, PL-12, SRP, Mi-2, TIF-1, MDA5, MJ, SUMO) and MAA (anti-PM-SCL, Ku, U1RNP, Ro/SSA) by the Oklahoma Medical Research Foundation. Patients were stratified according to their antibody status as MSA-positive (including patients who were also MAA-positive), MAA-positive only, or antibody negative at baseline. The association of antibody status with treatment response measured by TIS was evaluated.ResultsAt baseline, a total of 49 (52%) patients were MSA-positive, 13 (14%) were MAA-positive, and 33 (35%) were antibody negative. Demographics of patients in each group are shown in Table 1. Of patients who were MSA-positive, 10 were also positive for MAA.The numbers of patients from the ProDERM study with each specific MSA and MAA are shown in Figure 1.In the MSA group, 71% (35/49) of patients had TIS response (score ≥20) at week 16, compared to 55% (18/33) in the autoantibody-negative group. In the MSA group 24 patients were randomized to IVIg and of these 83% (20/24) showed TIS response (score ≥20) at week 16 compared to 60% (15/25) in the group of MSA-positive patients receiving placebo. Additional analyses (including results for specific subgroups in the MSA-positive group) will be presented at the EULAR 2023 congress.ConclusionMyositis-specific antibodies were commonly identified in patients with dermatomyositis in the ProDERM study. Further analyses will determine if specific MSA, such as anti-TIF-1 and others, play a role in treatment response to IVIg.Reference[1]Aggarwal R., Charles-Schoeman C., Schessl J., et al. N Engl J Med 2022;387:1264–1278Table 1.Patient demographics and baseline characteristicsMSA-positive* (N=49)MAA-positive** (N=13)Antibody negative (N=33)Mean (range) age, years51 (22–79)54 (33–70)54 (28–77)Mean (range) time since diagnosis, years3.66 (0.16–15.6)5.04 (0.39–18.4)5.8 (0.09–48.7)Sex, n (% female)39 (79.6)11 (84.6)12 (63.6)Race, n (% White)42 (85.7)13 (100.0)32 (97.0)Mean BMI, kg/m229.827.026.5Disease severity, n (%)MildModerateSevere10 (20.4)31 (63.3)8 (16.3)4 (30.8)8 (61.5)1 (7.7)12 (36.4)17 (51.5)4 (12.1)CDASI score≤14>1419 (38.8)30 (61.2)5 (38.5)8 (61.5)20 (60.6)13 (39.4)Randomised treatmentIVIgPlacebo2425491914BMI, body mass index; CDASI, Cutaneous Disease Area and Severity Index; IVIg, intravenous immunoglobulin; MAA, myositis-associated antibodies; MSA, myositis-specific antibodies.*10 patients positive for MSA were also positive for MAA.**MAA-positive group contains only patients with MAA (no MSA).AcknowledgementsAll investigators and patients.Disclosure of InterestsChristina Charles-Schoeman Consultant of: Abbvie, Bristol Myers Squibb, Octapharma, Pfizer, Priovant, Galapagos, Grant/research support from: AbbVie, Bristol Myers Squibb, Pfizer, and CSL Behring, Jochim Schessl Speakers bureau: Pfizer, Consultant of: Octapharma, Elisabeth Clodi Employee of: Octapharma Pharmzeutika Produktionsges.m.b.H., 1100 Vienna, Austria, Rohit Aggarwal Consultant of: Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, EMD Serono, Q32, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim (BI), Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, Actigraph, Scipher, Horizon Therapeutics, Teva, Beigene, ANI Pharmaceuticals, Biogen, Nuvig, Capella Bioscience, CabalettaBio, Grant/research support from: Mallinckrodt, Pfizer, Bristol Myers-Squibb, Q32, EMD Serono, Jansen, Boehringer Ingelheim (BI), and the ProDERM Investigators: None declared.