Background/Purpose: We describe a single-center North American adult cohort of MDA5-positive DM, with emphasis on the subgroup of patients that experience drug-free long-term remission.

Methods: From our entire IIM cohort, 52 patients were included that (1) Met either Bohan and Peter or 2017 American College of Rheumatology/European League Against Rheumatism classification criteria for dermatomyositis and (2) Were positive for anti-MDA5 autoantibodies by two methods: Euroimmun line blot (16 Ag IgG, Germany) and ELISA (MBL, Japan). All patients underwent structured telephone research interviews in 2019-2020 to update clinical status including symptoms and DM-specific therapies. Remission was defined as being off all immunosuppressive and immunomodulatory therapies > 1 year while remaining asymptomatic.

Results: Demographic and disease characteristics for the 52 MDA5-positive DM patients can be found in Table 1. Thirty-eight (73%) of the patients were women with a median age at DM symptom-onset of 47 (IQR 40-54). Twenty-five (48%) percent of patients were white, 16 (30%) were African American, 3 (6%) were Asian and 8 (16%) were other/declined to provide race. All patients had either Heliotrope or Gottron’s sign, 29 (56%) had synovitis, and 18 (35%) had calcinosis. The majority of patients had interstitial lung disease, defined by fibrotic changes on HRCT (83%). With regards to disease severity, 35% of patients required pulse-dose solumedrol at some point in their treatment course, 8% experienced a spontaneous pneumothorax or pneumomediastinum, 12% required intubation, and 10% died.

Over longitudinal follow-up, the median of which was 3.5 years (IQR 1.3-5.9), a total of 9 patients (18%) achieved clinical remission. One patient lost to follow-up could not be reached to ascertain clinical status. For the 9 patients that achieved clinical remission, the median time from DM-symptom onset to clinical remission was 4 years (IQR 2.4-5.0, range 1.8-5.6). The median duration of remission at the time of this study was 3.5 years (range 1.4-7.8). There were no demographic or disease characteristics that were significantly associated with clinical remission. There was no association between baseline MDA5 titer as obtained by MBL ELISA and clinical remission (median MBL MDA5 139 vs 140 units, Wilcoxon rank sum p=0.82). In patients who went into remission, there was no clear association with receiving more immunosuppression: A history of combination therapy use was equally likely in remission and non-remission groups, with a median number of concurrent medications of 3 throughout follow-up. Similarly, patients who went into remission had the same interval between DM-symptom onset to 1^st immune-suppressing medication prescribed (median 0.25 years vs 0.25 years, rank sum p=0.185).

Conclusion: In a single center, tertiary referral population of MDA5+ DM, the largest North American cohort reported to date, approximately 20% of patients experienced long-term drug-free remission. No demographic, clinical sign/symptom or laboratory factors were associated with remission. Future studies investigating other candidate biomarkers are warranted to identify this patient subgroup.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-features-and-prognosis-of-a-large-north-american-cohort-of-adult-mda5-dermatomyositis/