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Dermatomyositis

Emerging Therapies

Julie Paik, MD, MHS 
Reviewed on February 14, 2025
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Emerging Therapeutic Options

Since patients with refractory Dermatomyositis (DM) may not respond to existing treatment options, there remains an unmet medical need for more therapeutic alternatives. There are now several drug targets being explored as viable therapeutic options in phase 2 and phase 3 clinical trials.

JAK/STAT Inhibitors

The Janus kinase (JAK)/signal transduction and activator of transcription (STAT) signaling pathway interacts with various mediators and cytokines involved in the pathogenesis of inflammatory and autoimmune diseases, including the interferon pathway. JAK/STAT inhibitors are a promising option to prevent and manage severe complications of DM, such as RP-ILD or calcinosis. JAK inhibitors implicated in treating DM include tofacitinib, baricitinib and ruxolitinib,. Treatment with a JAK inhibitor has been shown in small uncontrolled clinical trials to significantly improve or resolve symptoms of disease for patients with DM and juvenile DM with cutaneous or…

Emerging Therapeutic Options

Since patients with refractory Dermatomyositis (DM) may not respond to existing treatment options, there remains an unmet medical need for more therapeutic alternatives. There are now several drug targets being explored as viable therapeutic options in phase 2 and phase 3 clinical trials.

JAK/STAT Inhibitors

The Janus kinase (JAK)/signal transduction and activator of transcription (STAT) signaling pathway interacts with various mediators and cytokines involved in the pathogenesis of inflammatory and autoimmune diseases, including the interferon pathway. JAK/STAT inhibitors are a promising option to prevent and manage severe complications of DM, such as RP-ILD or calcinosis. JAK inhibitors implicated in treating DM include tofacitinib, baricitinib and ruxolitinib,. Treatment with a JAK inhibitor has been shown in small uncontrolled clinical trials to significantly improve or resolve symptoms of disease for patients with DM and juvenile DM with cutaneous or muscle disease or with ILD. There is not yet robust randomized clinical trials to determine the efficacy of these agents in patients with DM.

Active phase 3 multicenter trials evaluating efficacy and safety of JAK inhibitors for treating adult DM include the VALOR trial on brepocitinib (a dual TYK2/JAK1 inhibitor) and the BIRD trial of baricitinib (a dual JAK1/JAK2 inhibitor), and the GALARISSO trial evaluating GLPG3667 (a selective TYK2 inhibitor).

Abatacept

Abatacept is a promising new treatment option based on data from smaller trials, and may be promising in treatment of refractory DM and sparing steroid use. However, there is not as much evidence as other treatment options, and well-designed clinical studies are needed.

Subcutaneous Efgartigimod

Subcutaneous efgartigimod is a human IgG1 antibody fragment that reduces pathogenic IgG antibodies by blocking the IgG recycling process and is the first-approved FcRn blocker globally. It is being investigated in the ongoing Phase 2/3 ALKIVIA study in adults with idiopathic inflammatory myopathies, including DM. The efficacy results from the ALKIVIA study demonstrated a statistically significant treatment effect in mean total improvement score (TIS) at Week 24 in favor of efgartigimod SC compared to placebo, with no new safety signals.

Apremilast

Apremilast is a phosphodiesterase-4 (PDE-4) inhibitor commonly used in the treatment of psoriasis, psoriatic arthritis, and Behçet disease that has shown efficacy in patients with refractory cutaneous DM without underlying malignancies. Apremilast may inhibit immune pathways that play a fundamental role in DM, such as decreasing expression of proinflammatory cytokines. Apremilast may be also an option to evaluate in patients with refractory cutaneous DM with severe pruritus.

Drugs targeting the IFN pathway may target the immune regulatory pathways in DM. Dazukibart (PF-06823859), an anti-IFNβ monoclonal antibody is an emerging DM therapy that has shown efficacy in treating skin and muscle symptoms. A Phase 2 trial examining dazukibart revealed a pronounced reduction in disease activity and acceptable safety, suggesting that IFNβ inhibition can be a highly promising therapeutic strategy in adults with dermatomyositis. [Fioentino2025] Sifalimumab is another investigational anti-IFN-α monoclonal antibody that has been studied in clinical trials for use in DM.

Future potential options for treatment

Future potential options for treatment of DM include blockers of the lymphotoxin signaling pathway, third-generation anti-B cell therapy, anti-interferon-alpha, anti-cytokine therapies, and anti-chemokine therapy.

Chimeric antigen receptor (CAR) T cell therapy has been investigated in patients with inflammatory myopathy in a patient with anti-synthetase syndrome refractory to other therapies. CAR-T therapy is thought to work by depleting CD19-expressing B-cell lineage in blood and tissue, and is currently being studied in patients with DM.

References

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