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ORLANDO, FLORIDA — Advances in treating medical conditions rarely emerge in a straight line. Oftentimes, progress comes in fits and starts, and therapies to treat cutaneous lupus erythematosus (CLE) and dermatomyositis are no exception.
Beyond approved treatments that deserve more attention, like belimumab, approved by the Food and Drug Administration (FDA) for systemic lupus erythematosus (SLE) in 2011, and Octagam 10%, an intravenous immune globulin (IVIG) preparation approved for dermatomyositis in 2021, anticipation is growing for emerging therapies and their potential to provide relief to patients, Anthony Fernandez, MD, PhD, said at the ODAC Dermatology, Aesthetic & Surgical Conference. The tyrosine kinase 2 (TYK2) inhibitor deucravacitinib, Janus kinase (JAK) inhibitors brepocitinib and baricitinib, and the monoclonal antibody anifrolumab, he noted, are prime examples.
“. In my opinion, this is the start of what will be the most exciting decade in the history of these two diseases,” said Dr. Fernandez, director of medical dermatology at the Cleveland Clinic.
Emerging Treatments for Cutaneous Lupus
Although SLE can involve many organ systems, the skin is one of the most affected. There are specific cutaneous lesions categorized as either acute cutaneous lupus, subacute cutaneous lupus, or chronic cutaneous lupus.
The oral TYK2 inhibitor deucravacitinib, for example, should be able to dampen interleukin responses in people with CLE, Dr. Fernandez said. Deucravacitinib was approved by the FDA to treat psoriasis in September 2022.
A phase 2 study published in 2023 focused on this agent for relief of systemic lupus. Improvements in cutaneous disease were a secondary endpoint. The trial demonstrated that the patients treated with deucravacitinib achieved a 56%-70% CLASI-50 response, depending on dosing, compared with a 17% response among those on placebo at week 48.
Based on the trial results, recruitment has begun for a phase 2 trial to evaluate deucravacitinib, compared with placebo, in patients with discoid and/or subacute cutaneous lupus. “This may be another medicine we have available to give to any of our patients with cutaneous lupus,” Dr. Fernandez said.
Anifrolumab Appears Promising
The FDA approval of anifrolumab, a type I interferon (IFN) receptor antagonist, for treating moderate to severe SLE in July 2021, for example, is good news for dermatologists and their patients, added Dr. Fernandez. “Almost immediately after approval, case studies showed marked improvement in patients with refractory cutaneous lupus.” While the therapy was approved for treating systemic lupus, it allows for off-label treatment of the cutaneous predominant form of the disease, he said.
Furthermore, the manufacturer of anifrolumab, AstraZeneca, is launching the LAVENDER clinical trial to assess the monoclonal antibody specifically for treating CLE. “This is a big deal because we may be able to prescribe anifrolumab for our cutaneous lupus patients who don’t have systemic lupus,” Dr. Fernandez said.
Phase 3 data supported use the of anifrolumab in systemic lupus, including the TULIP-2 trial, which demonstrated its superiority to placebo for reducing severity of systemic disease and lowering corticosteroid use. A study published in March 2023 of 11 patients showed that they had a “very fast response” to the agent, Dr. Fernandez said, with a 50% or greater improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score reached by all participants at week 16. Improvements of 50% or more in this scoring system are considered clinically meaningful, he added.
Upcoming Dermatomyositis Treatments
Why highlight emerging therapies for CLE and dermatomyositis in the same ODAC presentation? Although distinct conditions, these autoimmune conditions are both mediated by type 1 IFN inflammation.
Dermatomyositis is a relatively rare immune-mediated disease that most commonly affects the skin and muscle. Doctors score disease presentation, activity, and clinical improvements on a scale similar to CLASI for cutaneous lupus, the CDASI or Cutaneous Dermatomyositis Disease Area and Severity Index. Among people with CDASI activity scores of at least 14, which is the threshold for moderate to severe disease, a 20% improvement is clinically meaningful, Dr. Fernandez said. In addition, a 40% or greater improvement correlates with significant improvements in quality of life.
There is now more evidence for the use of IVIG to treat dermatomyositis. “Among those of us who treat dermatomyositis on a regular basis, we believe IVIG is the most potent treatment. We’ve known that for a long time,” Dr. Fernandez said.
Despite this tenet, for years, there was only one placebo-controlled trial, published in 1993, that evaluated IVIG treatment for dermatomyositis, and it included only 15 participants. That was until October 2022, he said, when the New England Journal of Medicine published a study comparing a specific brand of IVIG (Octagam) with placebo in 95 people with dermatomyositis.
In the study, 79% of participants treated with IVIG had a total improvement score of at least 20 (minimal improvement), the primary endpoint, at 16 weeks, compared with 44% of those receiving a placebo. Those treated with IVIG also had significant improvements in the CDASI score, a secondary endpoint, compared with those on placebo, he said.
Based on results of this trial, the FDA approved Octagam 10% for dermatomyositis in adults. Dr. Fernandez noted the approval is restricted to the brand of IVIG in the trial, not all IVIG products. However, “the FDA approval is most important to us because it gives us ammunition to fight for insurers to approve IVIG when we feel our patients with dermatomyositis need it,” regardless of the brand.
The Potential of JAK1 Inhibitors
An open-label study of the JAK inhibitor tofacitinib, published in December 2020, showed that mean changes in CDASI activity scores at 12 weeks were statistically significant compared with baseline in 10 people with dermatomyositis. “The importance of this study is that it is proof of concept that JAK inhibition can be effective for treating dermatomyositis, especially with active skin disease,” Dr. Fernandez said.
In addition, two large phase 3 trials are evaluating JAK inhibitor safety and efficacy for treating dermatomyositis. One is the VALOR trial, currently recruiting people with recalcitrant dermatomyositis to evaluate treatment with brepocitinib. Researchers in France are looking at another JAK inhibitor, baricitinib, for treating relapsing or treatment-naive dermatomyositis. Recruitment for the BIRD clinical trial is ongoing.
Monoclonal Antibody Showing Promise
“When it comes to looking specifically at dermatomyositis cutaneous disease, it’s been found that the levels of IFN beta correlate best with not only lesional skin type 1 IFN inflammatory signatures but also overall clinical disease activity,” Dr. Fernandez said. This correlation is stronger than for any other IFN-1-type cytokine active in the disorder.
“Perhaps blocking IFN beta might be best way to get control of dermatomyositis activity,” he added.
With that in mind, a phase 2 trial of dazukibart presented at the American Academy of Dermatology 2023 annual meeting highlighted the promise of this agent that targets type 1 IFN beta.
The primary endpoint was improvement in CDASI at 12 weeks. “This medication has remarkable efficacy,” Dr. Fernandez said. “We were one of the sites for this trial. Despite being blinded, there was no question about who was receiving drug and who was receiving placebo.”
“A minimal clinical improvement in disease activity was seen in more than 90%, so almost every patient who received this medication had meaningful improvement,” he added.
Based on the results, the manufacturer, Pfizer, is recruiting participants for a phase 3 trial to further assess dazukibart in dermatomyositis and polymyositis. Dr. Fernandez said, “This is a story you should pay attention to if you treat any dermatomyositis patients at all.”
Regarding these emerging therapies for CLE and dermatomyositis, “This looks very much like the early days of psoriasis, in the early 2000s, when there was a lot of activity developing treatments,” Dr. Fernandez said. “I will predict that within 10 years, we will have multiple novel agents available that will probably work better than anything we have today.”
Dr. Fernandez reported receiving grant and/or research support from Alexion, Incyte, Mallinckrodt Pharmaceuticals, Novartis, Pfizer, and Priovant Therapeutics; acting as a consultant or advisory board member for AbbVie, Biogen, Mallinckrodt Pharmaceuticals; and being a member of the speaker bureau or receiving honoraria for non-CME from AbbVie, Kyowa Kirin, and Mallinckrodt Pharmaceuticals.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — Advances in treating medical conditions rarely emerge in a straight line. Oftentimes, progress comes in fits and starts, and therapies to treat cutaneous lupus erythematosus (CLE) and dermatomyositis are no exception.
Beyond approved treatments that deserve more attention, like belimumab, approved by the Food and Drug Administration (FDA) for systemic lupus erythematosus (SLE) in 2011, and Octagam 10%, an intravenous immune globulin (IVIG) preparation approved for dermatomyositis in 2021, anticipation is growing for emerging therapies and their potential to provide relief to patients, Anthony Fernandez, MD, PhD, said at the ODAC Dermatology, Aesthetic & Surgical Conference. The tyrosine kinase 2 (TYK2) inhibitor deucravacitinib, Janus kinase (JAK) inhibitors brepocitinib and baricitinib, and the monoclonal antibody anifrolumab, he noted, are prime examples.
“. In my opinion, this is the start of what will be the most exciting decade in the history of these two diseases,” said Dr. Fernandez, director of medical dermatology at the Cleveland Clinic.
Emerging Treatments for Cutaneous Lupus
Although SLE can involve many organ systems, the skin is one of the most affected. There are specific cutaneous lesions categorized as either acute cutaneous lupus, subacute cutaneous lupus, or chronic cutaneous lupus.
The oral TYK2 inhibitor deucravacitinib, for example, should be able to dampen interleukin responses in people with CLE, Dr. Fernandez said. Deucravacitinib was approved by the FDA to treat psoriasis in September 2022.
A phase 2 study published in 2023 focused on this agent for relief of systemic lupus. Improvements in cutaneous disease were a secondary endpoint. The trial demonstrated that the patients treated with deucravacitinib achieved a 56%-70% CLASI-50 response, depending on dosing, compared with a 17% response among those on placebo at week 48.
Based on the trial results, recruitment has begun for a phase 2 trial to evaluate deucravacitinib, compared with placebo, in patients with discoid and/or subacute cutaneous lupus. “This may be another medicine we have available to give to any of our patients with cutaneous lupus,” Dr. Fernandez said.
Anifrolumab Appears Promising
The FDA approval of anifrolumab, a type I interferon (IFN) receptor antagonist, for treating moderate to severe SLE in July 2021, for example, is good news for dermatologists and their patients, added Dr. Fernandez. “Almost immediately after approval, case studies showed marked improvement in patients with refractory cutaneous lupus.” While the therapy was approved for treating systemic lupus, it allows for off-label treatment of the cutaneous predominant form of the disease, he said.
Furthermore, the manufacturer of anifrolumab, AstraZeneca, is launching the LAVENDER clinical trial to assess the monoclonal antibody specifically for treating CLE. “This is a big deal because we may be able to prescribe anifrolumab for our cutaneous lupus patients who don’t have systemic lupus,” Dr. Fernandez said.
Phase 3 data supported use the of anifrolumab in systemic lupus, including the TULIP-2 trial, which demonstrated its superiority to placebo for reducing severity of systemic disease and lowering corticosteroid use. A study published in March 2023 of 11 patients showed that they had a “very fast response” to the agent, Dr. Fernandez said, with a 50% or greater improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score reached by all participants at week 16. Improvements of 50% or more in this scoring system are considered clinically meaningful, he added.
Upcoming Dermatomyositis Treatments
Why highlight emerging therapies for CLE and dermatomyositis in the same ODAC presentation? Although distinct conditions, these autoimmune conditions are both mediated by type 1 IFN inflammation.
Dermatomyositis is a relatively rare immune-mediated disease that most commonly affects the skin and muscle. Doctors score disease presentation, activity, and clinical improvements on a scale similar to CLASI for cutaneous lupus, the CDASI or Cutaneous Dermatomyositis Disease Area and Severity Index. Among people with CDASI activity scores of at least 14, which is the threshold for moderate to severe disease, a 20% improvement is clinically meaningful, Dr. Fernandez said. In addition, a 40% or greater improvement correlates with significant improvements in quality of life.
There is now more evidence for the use of IVIG to treat dermatomyositis. “Among those of us who treat dermatomyositis on a regular basis, we believe IVIG is the most potent treatment. We’ve known that for a long time,” Dr. Fernandez said.
Despite this tenet, for years, there was only one placebo-controlled trial, published in 1993, that evaluated IVIG treatment for dermatomyositis, and it included only 15 participants. That was until October 2022, he said, when the New England Journal of Medicine published a study comparing a specific brand of IVIG (Octagam) with placebo in 95 people with dermatomyositis.
In the study, 79% of participants treated with IVIG had a total improvement score of at least 20 (minimal improvement), the primary endpoint, at 16 weeks, compared with 44% of those receiving a placebo. Those treated with IVIG also had significant improvements in the CDASI score, a secondary endpoint, compared with those on placebo, he said.
Based on results of this trial, the FDA approved Octagam 10% for dermatomyositis in adults. Dr. Fernandez noted the approval is restricted to the brand of IVIG in the trial, not all IVIG products. However, “the FDA approval is most important to us because it gives us ammunition to fight for insurers to approve IVIG when we feel our patients with dermatomyositis need it,” regardless of the brand.
The Potential of JAK1 Inhibitors
An open-label study of the JAK inhibitor tofacitinib, published in December 2020, showed that mean changes in CDASI activity scores at 12 weeks were statistically significant compared with baseline in 10 people with dermatomyositis. “The importance of this study is that it is proof of concept that JAK inhibition can be effective for treating dermatomyositis, especially with active skin disease,” Dr. Fernandez said.
In addition, two large phase 3 trials are evaluating JAK inhibitor safety and efficacy for treating dermatomyositis. One is the VALOR trial, currently recruiting people with recalcitrant dermatomyositis to evaluate treatment with brepocitinib. Researchers in France are looking at another JAK inhibitor, baricitinib, for treating relapsing or treatment-naive dermatomyositis. Recruitment for the BIRD clinical trial is ongoing.
Monoclonal Antibody Showing Promise
“When it comes to looking specifically at dermatomyositis cutaneous disease, it’s been found that the levels of IFN beta correlate best with not only lesional skin type 1 IFN inflammatory signatures but also overall clinical disease activity,” Dr. Fernandez said. This correlation is stronger than for any other IFN-1-type cytokine active in the disorder.
“Perhaps blocking IFN beta might be best way to get control of dermatomyositis activity,” he added.
With that in mind, a phase 2 trial of dazukibart presented at the American Academy of Dermatology 2023 annual meeting highlighted the promise of this agent that targets type 1 IFN beta.
The primary endpoint was improvement in CDASI at 12 weeks. “This medication has remarkable efficacy,” Dr. Fernandez said. “We were one of the sites for this trial. Despite being blinded, there was no question about who was receiving drug and who was receiving placebo.”
“A minimal clinical improvement in disease activity was seen in more than 90%, so almost every patient who received this medication had meaningful improvement,” he added.
Based on the results, the manufacturer, Pfizer, is recruiting participants for a phase 3 trial to further assess dazukibart in dermatomyositis and polymyositis. Dr. Fernandez said, “This is a story you should pay attention to if you treat any dermatomyositis patients at all.”
Regarding these emerging therapies for CLE and dermatomyositis, “This looks very much like the early days of psoriasis, in the early 2000s, when there was a lot of activity developing treatments,” Dr. Fernandez said. “I will predict that within 10 years, we will have multiple novel agents available that will probably work better than anything we have today.”
Dr. Fernandez reported receiving grant and/or research support from Alexion, Incyte, Mallinckrodt Pharmaceuticals, Novartis, Pfizer, and Priovant Therapeutics; acting as a consultant or advisory board member for AbbVie, Biogen, Mallinckrodt Pharmaceuticals; and being a member of the speaker bureau or receiving honoraria for non-CME from AbbVie, Kyowa Kirin, and Mallinckrodt Pharmaceuticals.
A version of this article appeared on Medscape.com.
ORLANDO, FLORIDA — Advances in treating medical conditions rarely emerge in a straight line. Oftentimes, progress comes in fits and starts, and therapies to treat cutaneous lupus erythematosus (CLE) and dermatomyositis are no exception.
Beyond approved treatments that deserve more attention, like belimumab, approved by the Food and Drug Administration (FDA) for systemic lupus erythematosus (SLE) in 2011, and Octagam 10%, an intravenous immune globulin (IVIG) preparation approved for dermatomyositis in 2021, anticipation is growing for emerging therapies and their potential to provide relief to patients, Anthony Fernandez, MD, PhD, said at the ODAC Dermatology, Aesthetic & Surgical Conference. The tyrosine kinase 2 (TYK2) inhibitor deucravacitinib, Janus kinase (JAK) inhibitors brepocitinib and baricitinib, and the monoclonal antibody anifrolumab, he noted, are prime examples.
“. In my opinion, this is the start of what will be the most exciting decade in the history of these two diseases,” said Dr. Fernandez, director of medical dermatology at the Cleveland Clinic.
Emerging Treatments for Cutaneous Lupus
Although SLE can involve many organ systems, the skin is one of the most affected. There are specific cutaneous lesions categorized as either acute cutaneous lupus, subacute cutaneous lupus, or chronic cutaneous lupus.
The oral TYK2 inhibitor deucravacitinib, for example, should be able to dampen interleukin responses in people with CLE, Dr. Fernandez said. Deucravacitinib was approved by the FDA to treat psoriasis in September 2022.
A phase 2 study published in 2023 focused on this agent for relief of systemic lupus. Improvements in cutaneous disease were a secondary endpoint. The trial demonstrated that the patients treated with deucravacitinib achieved a 56%-70% CLASI-50 response, depending on dosing, compared with a 17% response among those on placebo at week 48.
Based on the trial results, recruitment has begun for a phase 2 trial to evaluate deucravacitinib, compared with placebo, in patients with discoid and/or subacute cutaneous lupus. “This may be another medicine we have available to give to any of our patients with cutaneous lupus,” Dr. Fernandez said.
Anifrolumab Appears Promising
The FDA approval of anifrolumab, a type I interferon (IFN) receptor antagonist, for treating moderate to severe SLE in July 2021, for example, is good news for dermatologists and their patients, added Dr. Fernandez. “Almost immediately after approval, case studies showed marked improvement in patients with refractory cutaneous lupus.” While the therapy was approved for treating systemic lupus, it allows for off-label treatment of the cutaneous predominant form of the disease, he said.
Furthermore, the manufacturer of anifrolumab, AstraZeneca, is launching the LAVENDER clinical trial to assess the monoclonal antibody specifically for treating CLE. “This is a big deal because we may be able to prescribe anifrolumab for our cutaneous lupus patients who don’t have systemic lupus,” Dr. Fernandez said.
Phase 3 data supported use the of anifrolumab in systemic lupus, including the TULIP-2 trial, which demonstrated its superiority to placebo for reducing severity of systemic disease and lowering corticosteroid use. A study published in March 2023 of 11 patients showed that they had a “very fast response” to the agent, Dr. Fernandez said, with a 50% or greater improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score reached by all participants at week 16. Improvements of 50% or more in this scoring system are considered clinically meaningful, he added.
Upcoming Dermatomyositis Treatments
Why highlight emerging therapies for CLE and dermatomyositis in the same ODAC presentation? Although distinct conditions, these autoimmune conditions are both mediated by type 1 IFN inflammation.
Dermatomyositis is a relatively rare immune-mediated disease that most commonly affects the skin and muscle. Doctors score disease presentation, activity, and clinical improvements on a scale similar to CLASI for cutaneous lupus, the CDASI or Cutaneous Dermatomyositis Disease Area and Severity Index. Among people with CDASI activity scores of at least 14, which is the threshold for moderate to severe disease, a 20% improvement is clinically meaningful, Dr. Fernandez said. In addition, a 40% or greater improvement correlates with significant improvements in quality of life.
There is now more evidence for the use of IVIG to treat dermatomyositis. “Among those of us who treat dermatomyositis on a regular basis, we believe IVIG is the most potent treatment. We’ve known that for a long time,” Dr. Fernandez said.
Despite this tenet, for years, there was only one placebo-controlled trial, published in 1993, that evaluated IVIG treatment for dermatomyositis, and it included only 15 participants. That was until October 2022, he said, when the New England Journal of Medicine published a study comparing a specific brand of IVIG (Octagam) with placebo in 95 people with dermatomyositis.
In the study, 79% of participants treated with IVIG had a total improvement score of at least 20 (minimal improvement), the primary endpoint, at 16 weeks, compared with 44% of those receiving a placebo. Those treated with IVIG also had significant improvements in the CDASI score, a secondary endpoint, compared with those on placebo, he said.
Based on results of this trial, the FDA approved Octagam 10% for dermatomyositis in adults. Dr. Fernandez noted the approval is restricted to the brand of IVIG in the trial, not all IVIG products. However, “the FDA approval is most important to us because it gives us ammunition to fight for insurers to approve IVIG when we feel our patients with dermatomyositis need it,” regardless of the brand.
The Potential of JAK1 Inhibitors
An open-label study of the JAK inhibitor tofacitinib, published in December 2020, showed that mean changes in CDASI activity scores at 12 weeks were statistically significant compared with baseline in 10 people with dermatomyositis. “The importance of this study is that it is proof of concept that JAK inhibition can be effective for treating dermatomyositis, especially with active skin disease,” Dr. Fernandez said.
In addition, two large phase 3 trials are evaluating JAK inhibitor safety and efficacy for treating dermatomyositis. One is the VALOR trial, currently recruiting people with recalcitrant dermatomyositis to evaluate treatment with brepocitinib. Researchers in France are looking at another JAK inhibitor, baricitinib, for treating relapsing or treatment-naive dermatomyositis. Recruitment for the BIRD clinical trial is ongoing.
Monoclonal Antibody Showing Promise
“When it comes to looking specifically at dermatomyositis cutaneous disease, it’s been found that the levels of IFN beta correlate best with not only lesional skin type 1 IFN inflammatory signatures but also overall clinical disease activity,” Dr. Fernandez said. This correlation is stronger than for any other IFN-1-type cytokine active in the disorder.
“Perhaps blocking IFN beta might be best way to get control of dermatomyositis activity,” he added.
With that in mind, a phase 2 trial of dazukibart presented at the American Academy of Dermatology 2023 annual meeting highlighted the promise of this agent that targets type 1 IFN beta.
The primary endpoint was improvement in CDASI at 12 weeks. “This medication has remarkable efficacy,” Dr. Fernandez said. “We were one of the sites for this trial. Despite being blinded, there was no question about who was receiving drug and who was receiving placebo.”
“A minimal clinical improvement in disease activity was seen in more than 90%, so almost every patient who received this medication had meaningful improvement,” he added.
Based on the results, the manufacturer, Pfizer, is recruiting participants for a phase 3 trial to further assess dazukibart in dermatomyositis and polymyositis. Dr. Fernandez said, “This is a story you should pay attention to if you treat any dermatomyositis patients at all.”
Regarding these emerging therapies for CLE and dermatomyositis, “This looks very much like the early days of psoriasis, in the early 2000s, when there was a lot of activity developing treatments,” Dr. Fernandez said. “I will predict that within 10 years, we will have multiple novel agents available that will probably work better than anything we have today.”
Dr. Fernandez reported receiving grant and/or research support from Alexion, Incyte, Mallinckrodt Pharmaceuticals, Novartis, Pfizer, and Priovant Therapeutics; acting as a consultant or advisory board member for AbbVie, Biogen, Mallinckrodt Pharmaceuticals; and being a member of the speaker bureau or receiving honoraria for non-CME from AbbVie, Kyowa Kirin, and Mallinckrodt Pharmaceuticals.
A version of this article appeared on Medscape.com.
FROM ODAC 2024