THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Juvenile dermatomyositis management to undergo changes

Adam Huber, MD, MSc
Adam Huber, MD, MSc

Significant change is coming to the 
management of juvenile dermatomyositis (JDM) for the first time in decades. Two of the first-ever clinical trials in JDM, new therapeutic agents, and new work in biomarkers suggest that individualized treatment is finally on the way.

“This is an exciting time in JDM because we are moving toward having specific treatments and being able to tailor treatment to individual patient characteristics, which has not been the case up until now,” said Adam Huber, MD, MSc, Professor of Rheumatology at IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada. “We will actually have new things to talk about.”

Dr. Huber will discuss emerging management options during a clinical symposium on Juvenile Dermatomyositis: Updates in Clinical Management & Biomarker Development from 11:00 am – 12:00 pm on Sunday in Room 32 B. Results from the first clinical trials in JDM are pointing to more personalized disease-management approaches.

A European trial compared three first-line treatments, oral steroids versus oral steroids plus either methotrexate or cyclosporine. North American clinicians have traditionally preferred the methotrexate combination, while European rheumatologists usually prefer cyclosporine. The head-to-head trial showed superiority for both combination regimens and similar patient outcomes for the combination regimens. The cyclosporine group had more side effects.

A second trial found that children with dermatomyositis may respond better to rituximab than adults, and patients with myositis-specific autoantibodies appeared to have better outcomes than those who lacked the autoantibodies.

“This is the first inkling that here is a drug we can use in one group of patients and may want to skip in another group,” Dr. Huber said. “This study may lead to the first genuinely personalized management decision we have been able to make.”

Biomarker development continues to advance. Recent work has found differences in autoantibody groups in JDM muscle biopsies.

Claire Deakin, PhD
Claire Deakin, PhD

“Patients with autoantibody Mi2 tended to have more severe muscle biopsies, and patients with MDA5 autoantibody tended to have more mild muscle antibodies,” said Claire Deakin, PhD, Research Fellow at the University College London Great Ormond Street Institute of Child Health in London, UK. “Patients who had Mi2 autoantibodies responded a lot better to treatment, whereas patients with MDA5 did not respond well even though they had much more mild muscle biopsies. For patients who had other myositis-specific autoantibodies or Nil-detectable autoantibodies, a higher muscle biopsy score alone predicted a higher risk of remaining on treatment over time.”

These early results need validation in a larger cohort, Dr. Deakin said, but the findings suggest that the combination of muscle biopsy scores and myositis-specific autoantibodies could predict which patients are likely to need a longer treatment course.

Other researchers have found correlations between the interferon signature in JDM and disease activity. Specific proteins associated with interferon expression are elevated in patients with active disease compared to patients in remission. The potential role of interferon in the pathogenesis of dermatomyositis is attracting growing attention.

“Others have shown that you can calculate a gene score based on the expression of certain interferon stimulated genes and that this score is elevated in active disease,” Dr. Deakin said. “This a very active area of research.”

There is also active interest in new classes of rheumatologic agents, especially JAK (Janus kinase) inhibitors. Tofacitinib has been approved for rheumatoid arthritis and could be useful in JDM, as well.

“The mechanisms of action for tofacitinib have a huge impact on the systems that generate interferon,” Dr. Huber said. “There is active discussion that these agents could be useful in JDM. There could well be a trial on ClinicalTrials.gov in the very near future to test at least one of the JAK inhibitors.”