Treatment Landscape for Dermatomyositis Is Evolving

After years of inactivity, therapeutic development for dermatomyositis has begun to move forward with several new therapies and therapeutic strategies.

“This is a very exciting time for the field because we’re finally going to get some new treatments, and I think it will be helpful in our paraneoplastic patients as well,” said Victoria Werth, MD, of Penn Medicine in Philadelphia, during the European Academy of Dermatology and Venereology meeting in Vienna.

Traditional treatments still form the basis of first-line therapy for dermatomyositis with skin involvement, including broad-spectrum sunscreens with SPF rating ≥70 and topical steroids. For patients with scalp involvement, topical steroids are still widely recommended and widely used. Topical Janus kinase (JAK) inhibitors offer an off-label alternative to topical steroids but are often difficult for patients to obtain.

Werth also uses antimalarials, including hydroxychloroquine, quinacrine, and chloroquine, noting that “about 20% of my patients get better with them, and I can avoid having to escalate to other things like methotrexate or mycophenolate mofetil. You have to warn them that they might get a rash, and that’s annoying. But the patients tend to be grateful when they don’t have to escalate therapy.”

Dermatologists often turn to immunosuppressive therapies for second-line treatment, including methotrexate, mycophenolate mofetil, azathioprine, cyclosporine, and tacrolimus. Use of immunosuppressives can be concerning for patients with paraneoplastic disease.

“I talk to oncologists and they often seem a little less concerned with methotrexate,” said Werth. “Many of these patients are getting treated for malignancy, which may help with their dermatomyositis.”

“With a lot of those patients, I’m going to use IVIG [intravenous immunoglobulins; Octagam 10%] before I’m going to use a lot of the immunosuppressives, just to avoid the immunosuppression,” she added.

When using an immunosuppressive, clinicians should keep in mind that patients who respond tend to do so over time.

“If you have somebody who is getting better, you might want to be really patient because they often do continue to get better,” said Werth. “We tend to use a lot of methotrexate and mycophenolate mofetil in [the skin-predominant] population.”

The first approved therapy for dermatomyositis, IVIG was evaluated in a pivotal trial of patients with muscle-predominant dermatomyositis. Some patients had skin manifestations, which also improved with the monoclonal antibody. Nonetheless, “it became harder to get this drug for our skin patients,” Werth noted. “One of my jobs seems to be to advocate for including skin patients in studies so they can access drugs readily.”

Oral steroids also are frequently used in second line, but the goal should be to wean the patients off as quickly as possible, particularly those with skin disease, said Werth. JAK inhibitors might be appropriate for some patients but not those with paraneoplastic disease.

“You’re not going to be giving that to somebody with paraneoplastic dermatomyositis,” she added. “I have questions sometimes about patients who have previous malignancies. Do you really want to give them a JAK inhibitor? Are you going to give them another cancer? We don’t know that the risk is so low.”

Rituximab has some evidence to support its use in patients with muscle involvement but not skin or bone.

Help for patients with dermatomyositis skin lesions arrived recently with FDA approval of the oral TYK2/JAK1 inhibitor brepocitinib (Lisraya). Principal support for the approval came from a phase III trial reported earlier this year at the American Academy of Dermatology meeting, which showed significant overall improvement in disease status, as well as multiple secondary endpoints. A subsequent report on patients with skin involvement also showed significant improvement, which occurred soon after treatment initiation and proved durable.

A substantial proportion of patients with moderate/severe skin disease at baseline had a Cutaneous Dermatomyositis Disease and Area Severity Index score ≤5 at 52 weeks, which “is like not having anything in your skin,” said Werth.

Looking ahead, several dermatomyositis therapy candidates have shown promise in clinical evaluations. The type I interferon receptor antagonist anifrolumab (Saphnelo), currently approved for systemic lupus erythematosus, is being evaluated in ongoing trials of patients with dermatomyositis. A case report on three patients with treatment-resistant or refractory skin dermatomyositis showed “remarkable improvement,” and all three were able to taper systemic steroids and other therapies.

Dazukibart, an investigational anti-interferon beta monoclonal antibody, was evaluated in a placebo-controlled phase II trial of 75 patients with skin- or muscle-predominant dermatomyositis. Two different doses of dazukibart resulted in a “pronounced reduction in disease activity” and were well tolerated.

Efgartigimod, a human IgG1 antibody fragment targeting the neonatal Fc receptor, was evaluated in a phase II/III placebo-controlled trial involving 89 patients with three myositis subtypes, including dermatomyositis. Patients allocated to the antibody had significant improvement in the Myositis Total Improvement Score (TIS) versus placebo, as well as across all six core measures.

Initial results from a phase III placebo-controlled trial of efgartigimod also showed statistically significant and clinically meaningful improvement in the TIS in the overall study population, which included different myositis subgroups. The improvement in the dermatomyositis subgroup did not achieve statistical significance but was considered clinically meaningful.

Chimeric antigen receptor (CAR) T-cell therapy is also getting a look as a potential therapy for dermatomyositis, specifically for patients with significant myositis and anti-synthetase syndrome.

“I think we’re going to have a lot more options for our patients, whether or not they have underlying malignancy,” said Werth.