Background/Purpose: Anti-MDA5 Abs have been reported to associate with clinically amyopathic and classic dermatomyositis (DM), with severe progressive interstitial lung disease (ILD) and poor prognosis in Japanese pts. The aim of this study was to examine the frequency and characteristics of anti-MDA5 Abs associated with juvenile DM (JDM) in North America.        

Methods: Demographic, clinical, laboratory and outcome features of 37 pts with anti-MDA5 Abs were assessed and compared to those of 60 MSA/MAA negative and 175 anti-p155/140 Ab+ JDM and JCTM/DM pts meeting probable or definite Bohan and Peter criteria. Differences were evaluated by Fisher’s exact and Mann-Whitney tests. Kaplan-Meier and Log-rank tests were used for treatment analysis. Myositis Abs were tested by standard immunoprecipitation (IP) and MDA-5 and p155/140 Abs tested by reverse IP-immunoblot. Significant univariable results were examined in multivariable logistic regression.   

Results:   Anti-MDA5 Abs were identified in 37 (7.9%) pts out of a cohort of 467 JDM and JCTM/DM pts. Characteristics of MDA5+ pts compared to MSA/MAA- and anti-p155/140 Ab JDM and JCTM/DM pts are shown in the Table. MDA5 Ab+ pts had lower serum CK levels. MDA5 Ab+ pts more frequently had fatigue, fever, weight loss, adenopathy, arthralgia, arthritis, abnormal PFTs, dyspnea, and ILD compared to Ab- and p155/140+ pts. The median skeletal, pulmonary and constitutional symptom scores at diagnosis were higher in MDA5 Ab+ pts, but the median overall clinical symptom score at diagnosis was lower compared to Ab- and higher compared to p155/140+ pts (p<0.0001).  There were no differences in gender distribution, delay to diagnosis, and onset severity among the three groups.  Anti-MDA5 Ab + pts did not differ in total number or types of medications received, or in frequency of remission compared to MSA/MAA- or p155/140 Ab+ pts. MDA5+ pts had fewer flares (48% vs. 73%, p=0.014), and shorter time to final steroid discontinuation (30 [IQR 16-66] vs. 53 mths [IQR 26-128], p=0.009) compared to p155/140+ pts. Multivariable analysis revealed weight loss, arthritis and lower serum CK level were significantly associated with anti-MDA5+ vs Ab – pts, whereas, weight loss, arthritis, arthralgia, dyspnea, fever, and slow disease onset speed were significantly associated with anti-MDA5+ vs. p155/140+. There were no differences in disease course, status at most recent evaluation, ACR functional class, and mortality of MDA5+ vs either group.

Conclusion:  Anti-MDA5 Abs are seen in a distinct subset of juvenile myositis with JDM who have frequent arthritis, arthralgia, weight loss, adenopathy, and ILD, but lower serum CK. MDA5+ pts have comparable outcomes, but with the ability to discontinue steroids more rapidly and less frequent flares compared to p155/140+ pts.  

Table.  Characteristics of JDM patients with anti-MDA5 Abs compared to MSA/MAA negative and anti-p155/140 Ab