Conference Coverage

Women with endometriosis have a much higher risk of being diagnosed with several psychiatric disorders during the postpartum period according to an oral abstract presented at the American Society for Reproductive Medicine’s 2024 Scientific Congress and Expo in Denver, Colorado.

Researchers compared rates of postpartum depression, anxiety, mood disturbance (temporary low or anxious mood requiring no treatment), and obsessive-compulsive disorder (OCD) diagnoses among over 200 million adult women from 67 healthcare organizations who had a child between 2005 and 2023.

Within a year after giving birth, women with prepregnancy endometriosis were 25% more likely to be diagnosed with postpartum depression, 85% more likely to be diagnosed with postpartum mood disturbance, 44% more likely to be diagnosed with anxiety, and 1.26 times more likely to be diagnosed with OCD.

About 75% of women studied had no preexisting depression. This population had a 17% higher risk of receiving a postpartum depression diagnosis, a 95% higher risk of receiving an OCD diagnosis, a 72% higher risk of receiving a postpartum mood disturbance diagnosis, and a 38% risk of receiving an anxiety diagnosis.

Among women without preexisting depression, the risk increased by 64% for OCD, 42% for postpartum mood disturbance, and 25% for anxiety, while the risk for postpartum depression was negligible, indicating that women already experiencing depression likely have a higher baseline risk for worsening symptoms postpartum, said the study’s lead author Tina Yi-Jin Hsieh, MD, MPH, biomedical researcher at Harvard Medical School in Boston, Massachusetts.

“We think that because preexisting depression is the more dominant risk factor, it doesn’t really matter if you have another additional risk factor like endometriosis to really change the risk of postpartum depression,” said Hsieh.

Endometriosis is a debilitating condition in which tissue similar to uterine lining grows on the outside of the uterus, causing chronic pain and infertility. It affects between 6% and 10% of women worldwide and takes an average of between 4 and 11 years to be diagnosed. It has been linked to depression and anxiety disorders, yet the study authors say there’s little research examining its impact on women in the year after giving birth.

“Endometriosis is a complex condition that can affect both physical and mental health over much of a person’s life,” said Anna Modest, PhD, assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and a study author. “Perinatal and maternal mental health can have a huge impact on children and their family — we need to better understand who is at risk for challenges in the postpartum period.”

“Most chronic medical illnesses, particularly those causing pain, have been shown to increase the risk of mood disorders,” said Ripal Shah, MD, MPH, clinical associate professor of Psychiatry and Behavioral Sciences at Stanford Medicine in California. Shah specializes in reproductive psychiatry and was not associated with the study.

“What’s interesting about endometriosis though is that genome-wide association studies have shown that there may be a genetic predisposition for some women to develop both endometriosis and a mood disorder,” said Shah.

A 2023 study suggested that endometriosis, anxiety, and depression may be connected through a shared genetic basis.

But the experience patients with endometriosis go through also lends itself to the development of mood disorders, said Daniel Ginn, DO, assistant clinical professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles. Ginn specializes in the treatment of endometriosis and was not a part of the study.

Beyond postpartum depression, Ginn wasn’t surprised by the association of endometriosis with anxiety or OCD because what he hears from patients “on a daily basis is the telling of a history that has been hallmarked by not being listened to, not being believed, and not having symptoms managed well.”

As a result, he said many patients focus heavily on learning about their condition, coming into office visits with binders full of test results and information in an effort to understand and manage it themselves. This “does lead to a certain sense of a need to grasp for control because no one else is helping them [treat their condition effectively].”

He added: “I find it hard to believe that anxiety and OCD were preexisting of the conditions rather than the consequence of a long-term suboptimally managed disease.”

The authors reported no disclosures or sources of funding.

A version of this article first appeared on Medscape.com.

Women with endometriosis have a much higher risk of being diagnosed with several psychiatric disorders during the postpartum period according to an oral abstract presented at the American Society for Reproductive Medicine’s 2024 Scientific Congress and Expo in Denver, Colorado.

Researchers compared rates of postpartum depression, anxiety, mood disturbance (temporary low or anxious mood requiring no treatment), and obsessive-compulsive disorder (OCD) diagnoses among over 200 million adult women from 67 healthcare organizations who had a child between 2005 and 2023.

Within a year after giving birth, women with prepregnancy endometriosis were 25% more likely to be diagnosed with postpartum depression, 85% more likely to be diagnosed with postpartum mood disturbance, 44% more likely to be diagnosed with anxiety, and 1.26 times more likely to be diagnosed with OCD.

About 75% of women studied had no preexisting depression. This population had a 17% higher risk of receiving a postpartum depression diagnosis, a 95% higher risk of receiving an OCD diagnosis, a 72% higher risk of receiving a postpartum mood disturbance diagnosis, and a 38% risk of receiving an anxiety diagnosis.

Among women without preexisting depression, the risk increased by 64% for OCD, 42% for postpartum mood disturbance, and 25% for anxiety, while the risk for postpartum depression was negligible, indicating that women already experiencing depression likely have a higher baseline risk for worsening symptoms postpartum, said the study’s lead author Tina Yi-Jin Hsieh, MD, MPH, biomedical researcher at Harvard Medical School in Boston, Massachusetts.

“We think that because preexisting depression is the more dominant risk factor, it doesn’t really matter if you have another additional risk factor like endometriosis to really change the risk of postpartum depression,” said Hsieh.

Endometriosis is a debilitating condition in which tissue similar to uterine lining grows on the outside of the uterus, causing chronic pain and infertility. It affects between 6% and 10% of women worldwide and takes an average of between 4 and 11 years to be diagnosed. It has been linked to depression and anxiety disorders, yet the study authors say there’s little research examining its impact on women in the year after giving birth.

“Endometriosis is a complex condition that can affect both physical and mental health over much of a person’s life,” said Anna Modest, PhD, assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and a study author. “Perinatal and maternal mental health can have a huge impact on children and their family — we need to better understand who is at risk for challenges in the postpartum period.”

“Most chronic medical illnesses, particularly those causing pain, have been shown to increase the risk of mood disorders,” said Ripal Shah, MD, MPH, clinical associate professor of Psychiatry and Behavioral Sciences at Stanford Medicine in California. Shah specializes in reproductive psychiatry and was not associated with the study.

“What’s interesting about endometriosis though is that genome-wide association studies have shown that there may be a genetic predisposition for some women to develop both endometriosis and a mood disorder,” said Shah.

A 2023 study suggested that endometriosis, anxiety, and depression may be connected through a shared genetic basis.

But the experience patients with endometriosis go through also lends itself to the development of mood disorders, said Daniel Ginn, DO, assistant clinical professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles. Ginn specializes in the treatment of endometriosis and was not a part of the study.

Beyond postpartum depression, Ginn wasn’t surprised by the association of endometriosis with anxiety or OCD because what he hears from patients “on a daily basis is the telling of a history that has been hallmarked by not being listened to, not being believed, and not having symptoms managed well.”

As a result, he said many patients focus heavily on learning about their condition, coming into office visits with binders full of test results and information in an effort to understand and manage it themselves. This “does lead to a certain sense of a need to grasp for control because no one else is helping them [treat their condition effectively].”

He added: “I find it hard to believe that anxiety and OCD were preexisting of the conditions rather than the consequence of a long-term suboptimally managed disease.”

The authors reported no disclosures or sources of funding.

A version of this article first appeared on Medscape.com.

Women with endometriosis have a much higher risk of being diagnosed with several psychiatric disorders during the postpartum period according to an oral abstract presented at the American Society for Reproductive Medicine’s 2024 Scientific Congress and Expo in Denver, Colorado.

Researchers compared rates of postpartum depression, anxiety, mood disturbance (temporary low or anxious mood requiring no treatment), and obsessive-compulsive disorder (OCD) diagnoses among over 200 million adult women from 67 healthcare organizations who had a child between 2005 and 2023.

Within a year after giving birth, women with prepregnancy endometriosis were 25% more likely to be diagnosed with postpartum depression, 85% more likely to be diagnosed with postpartum mood disturbance, 44% more likely to be diagnosed with anxiety, and 1.26 times more likely to be diagnosed with OCD.

About 75% of women studied had no preexisting depression. This population had a 17% higher risk of receiving a postpartum depression diagnosis, a 95% higher risk of receiving an OCD diagnosis, a 72% higher risk of receiving a postpartum mood disturbance diagnosis, and a 38% risk of receiving an anxiety diagnosis.

Among women without preexisting depression, the risk increased by 64% for OCD, 42% for postpartum mood disturbance, and 25% for anxiety, while the risk for postpartum depression was negligible, indicating that women already experiencing depression likely have a higher baseline risk for worsening symptoms postpartum, said the study’s lead author Tina Yi-Jin Hsieh, MD, MPH, biomedical researcher at Harvard Medical School in Boston, Massachusetts.

“We think that because preexisting depression is the more dominant risk factor, it doesn’t really matter if you have another additional risk factor like endometriosis to really change the risk of postpartum depression,” said Hsieh.

Endometriosis is a debilitating condition in which tissue similar to uterine lining grows on the outside of the uterus, causing chronic pain and infertility. It affects between 6% and 10% of women worldwide and takes an average of between 4 and 11 years to be diagnosed. It has been linked to depression and anxiety disorders, yet the study authors say there’s little research examining its impact on women in the year after giving birth.

“Endometriosis is a complex condition that can affect both physical and mental health over much of a person’s life,” said Anna Modest, PhD, assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and a study author. “Perinatal and maternal mental health can have a huge impact on children and their family — we need to better understand who is at risk for challenges in the postpartum period.”

“Most chronic medical illnesses, particularly those causing pain, have been shown to increase the risk of mood disorders,” said Ripal Shah, MD, MPH, clinical associate professor of Psychiatry and Behavioral Sciences at Stanford Medicine in California. Shah specializes in reproductive psychiatry and was not associated with the study.

“What’s interesting about endometriosis though is that genome-wide association studies have shown that there may be a genetic predisposition for some women to develop both endometriosis and a mood disorder,” said Shah.

A 2023 study suggested that endometriosis, anxiety, and depression may be connected through a shared genetic basis.

But the experience patients with endometriosis go through also lends itself to the development of mood disorders, said Daniel Ginn, DO, assistant clinical professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California, Los Angeles. Ginn specializes in the treatment of endometriosis and was not a part of the study.

Beyond postpartum depression, Ginn wasn’t surprised by the association of endometriosis with anxiety or OCD because what he hears from patients “on a daily basis is the telling of a history that has been hallmarked by not being listened to, not being believed, and not having symptoms managed well.”

As a result, he said many patients focus heavily on learning about their condition, coming into office visits with binders full of test results and information in an effort to understand and manage it themselves. This “does lead to a certain sense of a need to grasp for control because no one else is helping them [treat their condition effectively].”

He added: “I find it hard to believe that anxiety and OCD were preexisting of the conditions rather than the consequence of a long-term suboptimally managed disease.”

The authors reported no disclosures or sources of funding.

A version of this article first appeared on Medscape.com.

Patients with chronic spontaneous urticaria (CSU) experienced early and sustained improvements in symptom scores on treatment with barzolvolimab, during the 52-week follow-up of an ongoing phase 2 study.

Moreover, in the study, barzolvolimab, an anti-KIT monoclonal antibody that inhibits the activation of and depletes mast cells, induced comparable responses in a subset of patients who had taken omalizumab, an anti–immunoglobulin E monoclonal antibody approved by the Food and Drug Administration for treating CSU.

The findings were presented at the annual European Academy of Dermatology and Venereology (EADV) 2024 Congress. Barzolvolimab is being developed by Celldex Therapeutics.

“Barzolvolimab treatment resulted in rapid, profound, and durable improvement in UAS7 [weekly Urticaria Activity Score 7],” said presenter Martin Metz, MD, professor of dermatology, Institute of Allergology, Charité – Universitätsmedizin Berlin in Germany, “with a deepening of response over 52 weeks in patients with antihistamine-refractory CSU.”

“Similar robust improvement was seen in patients previously treated with omalizumab, including refractory patients,” he added.

Because barzolvolimab was well tolerated over the course of the follow-up period, Metz said, it “has the potential to be an important new treatment option,” noting that patients are now being enrolled in global phase 3 studies of barzolvolimab.
 

Sustained Symptom Relief

Ana M. Giménez-Arnau, MD, PhD, associate professor of dermatology, Autonomous University and Pompeu Fabra University, Barcelona, Spain, told Medscape Medical News that the results are important, as they showed people who switched from placebo to the active drug also saw a long-term benefit.

What is “remarkable” about barzolvolimab, continued Giménez-Arnau, who was not involved in the study, is that it is the first drug to target the KIT receptor on mast cells and interfere with stimulating growth factors, thus making the cells that drive the development of CSU “disappear.”

The study included three different barzolvolimab regimens, with the 150-mg dose every 4 weeks and the 300-mg dose every 8 weeks achieving similar results, noted Giménez-Arnau.

For her, there are important questions to answer around the pharmacokinetic and pharmacodynamic profiles of the two regimens that remain, but she underlined that for the patient, the choice of regimen could have an impact on their quality of life.

“If we give 300 mg every 8 weeks,” she said, it appears “you can achieve disease control” while halving the frequency of subcutaneous injections.

She said that it would be “interesting to know” if 300 mg every 8 weeks is given as two 150-mg injections every 2 months or one 300-mg injection. If it is the former, Giménez Arnau said, “This is potentially an important benefit for the patient.”
 

Sustained Benefits at 1 Year

The study enrolled 208 patients with antihistamine-refractory CSU at sites in 10 countries, randomizing them to one of four arms: Subcutaneous injections of barzolvolimab 75 mg or 150 mg every 4 weeks, 300 mg every 8 weeks, or placebo every 4 weeks.

The mean age in each arm was between 42 and 47 years, and around 75% were women. Across the arms, 64%-76% had severe disease, as measured on the UAS7, at a mean score of 30.0-31.3. Around 20% had previously been treated with omalizumab.

Patients were treated for 16 weeks, during which time they completed daily and weekly diaries and attended six clinic visits at weeks 0, 2, 4, 8, 12, and 16. Results from the trial published earlier this year demonstrated that both the regimens (150 mg every 4 weeks and 300 mg every 8 weeks) achieved clinically meaningful and statistically significant improvement in UAS7, the primary endpoint, vs placebo at 12 weeks.

Participants in the barzolvolimab 75 mg and placebo arms were then randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, and those who had been in the 150-mg and 300-mg treatment arms continued with that treatment for a further 36 weeks. (The remaining patients have been continued on a further 24-week follow-up, but the data are not yet available.)

By the 52-week follow-up, 25% of patients who started in each of the barzolvolimab arms had discontinued treatment, as well as 16% first randomized to the placebo arm.

Metz reported that the improvements in UAS7 scores, observed as early as week 1, were sustained through week 52 in patients in both the ongoing 150-mg and 300-mg arms. Patients who initially started in the placebo and the barzolvolimab 75-mg groups caught up with those who had started on the higher doses, so that by week 52, there were no significant differences in urticaria activity, hives, or itch scores between the arms.

By week 52, the proportion of patients achieving well-controlled disease, defined as a UAS7 score ≤ 6, was 73.7% in the barzolvolimab 150 mg every 4-week arm and 68.2% in the 300 mg barzolvolimab every 8-week arm.

Notably, just 12.8% of patients in the placebo arm had achieved well-controlled CSU by week 16, but after switching to barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, 63% reached that target at week 52.

“Maybe even more striking and very interesting to look at,” said Metz, was the complete control of symptoms, meaning “not one single wheal and no itch.” By week 52, 52% of those on 300 mg every 8 weeks and 71.1% of those on 150 mg every 4 weeks had a complete response, with no itch/hives (UAS7 of 0).

Importantly, complete responses with barzolvolimab were observed early and were sustained or improved to week 52, Metz said, with, again, placebo and former barzolvolimab 75 mg patients catching up with those who started on 150 mg every 4 weeks and 300 mg every 8 weeks once they switched at week 16.

“This is the best data for chronic spontaneous urticaria that we have so far seen,” he said, adding that the responses were seen regardless of prior experience with omalizumab.
 

Changes in Hair Color, Skin Pigmentation

As for safety, during the first 16 weeks, 66% of those on active treatment and 39% on placebo experienced at least one adverse event. There were no treatment-related serious adverse events, compared with two among those who received treatment for the full 52 weeks.

The most common adverse events with active treatment were hair color changes (14% in the first 16 weeks and 26% among those treated for the full 52 weeks), neutropenia/reduced neutrophil count (9% in the first 16 weeks and 17% among those treated for the full 52 weeks), and skin hypopigmentation (1% in the first 16 weeks, 13% among those treated for the full 52 weeks, and 19% among those who switched from placebo to active treatment at 36 weeks). Urticaria was reported by 10% among patients on active treatment and 10% among those on placebo in the first 16 weeks, and by 15% of those treated for the full 52 weeks.

In the post-presentation discussion, Metz explained that the hypopigmentation appears to start around the hair follicle and is diffuse, so tends to look like vitiligo.

He suggested that the melanocytes around the hair follicle “seem to be the ones that are more stressed, maybe because of the hair follicle cycling,” adding that the effect is reversible and does not appear to be dose dependent.

The study was funded by Celldex Therapeutics. Metz declared relationships with AbbVie, ALK-Abelló, Almirall, Amgen, argenx, AstraZeneca, Astria, Attovia Therapeutics, Celldex, Celltrion, Escient Pharmaceuticals, Galen, Galderma, GSK, Incyte, Jasper, Lilly, Novartis, Pfizer, Pharvaris, Regeneron, Sanofi, Teva, Third Harmonic Bio, and Vifor.

A version of this article first appeared on Medscape.com.

Patients with chronic spontaneous urticaria (CSU) experienced early and sustained improvements in symptom scores on treatment with barzolvolimab, during the 52-week follow-up of an ongoing phase 2 study.

Moreover, in the study, barzolvolimab, an anti-KIT monoclonal antibody that inhibits the activation of and depletes mast cells, induced comparable responses in a subset of patients who had taken omalizumab, an anti–immunoglobulin E monoclonal antibody approved by the Food and Drug Administration for treating CSU.

The findings were presented at the annual European Academy of Dermatology and Venereology (EADV) 2024 Congress. Barzolvolimab is being developed by Celldex Therapeutics.

“Barzolvolimab treatment resulted in rapid, profound, and durable improvement in UAS7 [weekly Urticaria Activity Score 7],” said presenter Martin Metz, MD, professor of dermatology, Institute of Allergology, Charité – Universitätsmedizin Berlin in Germany, “with a deepening of response over 52 weeks in patients with antihistamine-refractory CSU.”

“Similar robust improvement was seen in patients previously treated with omalizumab, including refractory patients,” he added.

Because barzolvolimab was well tolerated over the course of the follow-up period, Metz said, it “has the potential to be an important new treatment option,” noting that patients are now being enrolled in global phase 3 studies of barzolvolimab.
 

Sustained Symptom Relief

Ana M. Giménez-Arnau, MD, PhD, associate professor of dermatology, Autonomous University and Pompeu Fabra University, Barcelona, Spain, told Medscape Medical News that the results are important, as they showed people who switched from placebo to the active drug also saw a long-term benefit.

What is “remarkable” about barzolvolimab, continued Giménez-Arnau, who was not involved in the study, is that it is the first drug to target the KIT receptor on mast cells and interfere with stimulating growth factors, thus making the cells that drive the development of CSU “disappear.”

The study included three different barzolvolimab regimens, with the 150-mg dose every 4 weeks and the 300-mg dose every 8 weeks achieving similar results, noted Giménez-Arnau.

For her, there are important questions to answer around the pharmacokinetic and pharmacodynamic profiles of the two regimens that remain, but she underlined that for the patient, the choice of regimen could have an impact on their quality of life.

“If we give 300 mg every 8 weeks,” she said, it appears “you can achieve disease control” while halving the frequency of subcutaneous injections.

She said that it would be “interesting to know” if 300 mg every 8 weeks is given as two 150-mg injections every 2 months or one 300-mg injection. If it is the former, Giménez Arnau said, “This is potentially an important benefit for the patient.”
 

Sustained Benefits at 1 Year

The study enrolled 208 patients with antihistamine-refractory CSU at sites in 10 countries, randomizing them to one of four arms: Subcutaneous injections of barzolvolimab 75 mg or 150 mg every 4 weeks, 300 mg every 8 weeks, or placebo every 4 weeks.

The mean age in each arm was between 42 and 47 years, and around 75% were women. Across the arms, 64%-76% had severe disease, as measured on the UAS7, at a mean score of 30.0-31.3. Around 20% had previously been treated with omalizumab.

Patients were treated for 16 weeks, during which time they completed daily and weekly diaries and attended six clinic visits at weeks 0, 2, 4, 8, 12, and 16. Results from the trial published earlier this year demonstrated that both the regimens (150 mg every 4 weeks and 300 mg every 8 weeks) achieved clinically meaningful and statistically significant improvement in UAS7, the primary endpoint, vs placebo at 12 weeks.

Participants in the barzolvolimab 75 mg and placebo arms were then randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, and those who had been in the 150-mg and 300-mg treatment arms continued with that treatment for a further 36 weeks. (The remaining patients have been continued on a further 24-week follow-up, but the data are not yet available.)

By the 52-week follow-up, 25% of patients who started in each of the barzolvolimab arms had discontinued treatment, as well as 16% first randomized to the placebo arm.

Metz reported that the improvements in UAS7 scores, observed as early as week 1, were sustained through week 52 in patients in both the ongoing 150-mg and 300-mg arms. Patients who initially started in the placebo and the barzolvolimab 75-mg groups caught up with those who had started on the higher doses, so that by week 52, there were no significant differences in urticaria activity, hives, or itch scores between the arms.

By week 52, the proportion of patients achieving well-controlled disease, defined as a UAS7 score ≤ 6, was 73.7% in the barzolvolimab 150 mg every 4-week arm and 68.2% in the 300 mg barzolvolimab every 8-week arm.

Notably, just 12.8% of patients in the placebo arm had achieved well-controlled CSU by week 16, but after switching to barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, 63% reached that target at week 52.

“Maybe even more striking and very interesting to look at,” said Metz, was the complete control of symptoms, meaning “not one single wheal and no itch.” By week 52, 52% of those on 300 mg every 8 weeks and 71.1% of those on 150 mg every 4 weeks had a complete response, with no itch/hives (UAS7 of 0).

Importantly, complete responses with barzolvolimab were observed early and were sustained or improved to week 52, Metz said, with, again, placebo and former barzolvolimab 75 mg patients catching up with those who started on 150 mg every 4 weeks and 300 mg every 8 weeks once they switched at week 16.

“This is the best data for chronic spontaneous urticaria that we have so far seen,” he said, adding that the responses were seen regardless of prior experience with omalizumab.
 

Changes in Hair Color, Skin Pigmentation

As for safety, during the first 16 weeks, 66% of those on active treatment and 39% on placebo experienced at least one adverse event. There were no treatment-related serious adverse events, compared with two among those who received treatment for the full 52 weeks.

The most common adverse events with active treatment were hair color changes (14% in the first 16 weeks and 26% among those treated for the full 52 weeks), neutropenia/reduced neutrophil count (9% in the first 16 weeks and 17% among those treated for the full 52 weeks), and skin hypopigmentation (1% in the first 16 weeks, 13% among those treated for the full 52 weeks, and 19% among those who switched from placebo to active treatment at 36 weeks). Urticaria was reported by 10% among patients on active treatment and 10% among those on placebo in the first 16 weeks, and by 15% of those treated for the full 52 weeks.

In the post-presentation discussion, Metz explained that the hypopigmentation appears to start around the hair follicle and is diffuse, so tends to look like vitiligo.

He suggested that the melanocytes around the hair follicle “seem to be the ones that are more stressed, maybe because of the hair follicle cycling,” adding that the effect is reversible and does not appear to be dose dependent.

The study was funded by Celldex Therapeutics. Metz declared relationships with AbbVie, ALK-Abelló, Almirall, Amgen, argenx, AstraZeneca, Astria, Attovia Therapeutics, Celldex, Celltrion, Escient Pharmaceuticals, Galen, Galderma, GSK, Incyte, Jasper, Lilly, Novartis, Pfizer, Pharvaris, Regeneron, Sanofi, Teva, Third Harmonic Bio, and Vifor.

A version of this article first appeared on Medscape.com.

Patients with chronic spontaneous urticaria (CSU) experienced early and sustained improvements in symptom scores on treatment with barzolvolimab, during the 52-week follow-up of an ongoing phase 2 study.

Moreover, in the study, barzolvolimab, an anti-KIT monoclonal antibody that inhibits the activation of and depletes mast cells, induced comparable responses in a subset of patients who had taken omalizumab, an anti–immunoglobulin E monoclonal antibody approved by the Food and Drug Administration for treating CSU.

The findings were presented at the annual European Academy of Dermatology and Venereology (EADV) 2024 Congress. Barzolvolimab is being developed by Celldex Therapeutics.

“Barzolvolimab treatment resulted in rapid, profound, and durable improvement in UAS7 [weekly Urticaria Activity Score 7],” said presenter Martin Metz, MD, professor of dermatology, Institute of Allergology, Charité – Universitätsmedizin Berlin in Germany, “with a deepening of response over 52 weeks in patients with antihistamine-refractory CSU.”

“Similar robust improvement was seen in patients previously treated with omalizumab, including refractory patients,” he added.

Because barzolvolimab was well tolerated over the course of the follow-up period, Metz said, it “has the potential to be an important new treatment option,” noting that patients are now being enrolled in global phase 3 studies of barzolvolimab.
 

Sustained Symptom Relief

Ana M. Giménez-Arnau, MD, PhD, associate professor of dermatology, Autonomous University and Pompeu Fabra University, Barcelona, Spain, told Medscape Medical News that the results are important, as they showed people who switched from placebo to the active drug also saw a long-term benefit.

What is “remarkable” about barzolvolimab, continued Giménez-Arnau, who was not involved in the study, is that it is the first drug to target the KIT receptor on mast cells and interfere with stimulating growth factors, thus making the cells that drive the development of CSU “disappear.”

The study included three different barzolvolimab regimens, with the 150-mg dose every 4 weeks and the 300-mg dose every 8 weeks achieving similar results, noted Giménez-Arnau.

For her, there are important questions to answer around the pharmacokinetic and pharmacodynamic profiles of the two regimens that remain, but she underlined that for the patient, the choice of regimen could have an impact on their quality of life.

“If we give 300 mg every 8 weeks,” she said, it appears “you can achieve disease control” while halving the frequency of subcutaneous injections.

She said that it would be “interesting to know” if 300 mg every 8 weeks is given as two 150-mg injections every 2 months or one 300-mg injection. If it is the former, Giménez Arnau said, “This is potentially an important benefit for the patient.”
 

Sustained Benefits at 1 Year

The study enrolled 208 patients with antihistamine-refractory CSU at sites in 10 countries, randomizing them to one of four arms: Subcutaneous injections of barzolvolimab 75 mg or 150 mg every 4 weeks, 300 mg every 8 weeks, or placebo every 4 weeks.

The mean age in each arm was between 42 and 47 years, and around 75% were women. Across the arms, 64%-76% had severe disease, as measured on the UAS7, at a mean score of 30.0-31.3. Around 20% had previously been treated with omalizumab.

Patients were treated for 16 weeks, during which time they completed daily and weekly diaries and attended six clinic visits at weeks 0, 2, 4, 8, 12, and 16. Results from the trial published earlier this year demonstrated that both the regimens (150 mg every 4 weeks and 300 mg every 8 weeks) achieved clinically meaningful and statistically significant improvement in UAS7, the primary endpoint, vs placebo at 12 weeks.

Participants in the barzolvolimab 75 mg and placebo arms were then randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, and those who had been in the 150-mg and 300-mg treatment arms continued with that treatment for a further 36 weeks. (The remaining patients have been continued on a further 24-week follow-up, but the data are not yet available.)

By the 52-week follow-up, 25% of patients who started in each of the barzolvolimab arms had discontinued treatment, as well as 16% first randomized to the placebo arm.

Metz reported that the improvements in UAS7 scores, observed as early as week 1, were sustained through week 52 in patients in both the ongoing 150-mg and 300-mg arms. Patients who initially started in the placebo and the barzolvolimab 75-mg groups caught up with those who had started on the higher doses, so that by week 52, there were no significant differences in urticaria activity, hives, or itch scores between the arms.

By week 52, the proportion of patients achieving well-controlled disease, defined as a UAS7 score ≤ 6, was 73.7% in the barzolvolimab 150 mg every 4-week arm and 68.2% in the 300 mg barzolvolimab every 8-week arm.

Notably, just 12.8% of patients in the placebo arm had achieved well-controlled CSU by week 16, but after switching to barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks, 63% reached that target at week 52.

“Maybe even more striking and very interesting to look at,” said Metz, was the complete control of symptoms, meaning “not one single wheal and no itch.” By week 52, 52% of those on 300 mg every 8 weeks and 71.1% of those on 150 mg every 4 weeks had a complete response, with no itch/hives (UAS7 of 0).

Importantly, complete responses with barzolvolimab were observed early and were sustained or improved to week 52, Metz said, with, again, placebo and former barzolvolimab 75 mg patients catching up with those who started on 150 mg every 4 weeks and 300 mg every 8 weeks once they switched at week 16.

“This is the best data for chronic spontaneous urticaria that we have so far seen,” he said, adding that the responses were seen regardless of prior experience with omalizumab.
 

Changes in Hair Color, Skin Pigmentation

As for safety, during the first 16 weeks, 66% of those on active treatment and 39% on placebo experienced at least one adverse event. There were no treatment-related serious adverse events, compared with two among those who received treatment for the full 52 weeks.

The most common adverse events with active treatment were hair color changes (14% in the first 16 weeks and 26% among those treated for the full 52 weeks), neutropenia/reduced neutrophil count (9% in the first 16 weeks and 17% among those treated for the full 52 weeks), and skin hypopigmentation (1% in the first 16 weeks, 13% among those treated for the full 52 weeks, and 19% among those who switched from placebo to active treatment at 36 weeks). Urticaria was reported by 10% among patients on active treatment and 10% among those on placebo in the first 16 weeks, and by 15% of those treated for the full 52 weeks.

In the post-presentation discussion, Metz explained that the hypopigmentation appears to start around the hair follicle and is diffuse, so tends to look like vitiligo.

He suggested that the melanocytes around the hair follicle “seem to be the ones that are more stressed, maybe because of the hair follicle cycling,” adding that the effect is reversible and does not appear to be dose dependent.

The study was funded by Celldex Therapeutics. Metz declared relationships with AbbVie, ALK-Abelló, Almirall, Amgen, argenx, AstraZeneca, Astria, Attovia Therapeutics, Celldex, Celltrion, Escient Pharmaceuticals, Galen, Galderma, GSK, Incyte, Jasper, Lilly, Novartis, Pfizer, Pharvaris, Regeneron, Sanofi, Teva, Third Harmonic Bio, and Vifor.

A version of this article first appeared on Medscape.com.

AMSTERDAM — Children with short stature related to severe atopic dermatitis not only can have their condition effectively treated with 16 weeks of dupilumab but also may experience improved growth, bringing them back toward standard height curves, revealed a post hoc trial analysis.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.

It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”

He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”

Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”

“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.

“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”

Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
 

Post Hoc Analysis 

In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.

Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.

For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.

They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.

Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”

Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.

After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).

“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”

Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).

Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.

“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”
 

‘Convincing’ Data

Overall, Kirkorian said in the interview, the data are “convincing” and support her view that severe atopic dermatitis is a “terrible chronic disease that we really underappreciate.” Atopic dermatitis, she added, “should get the respect that any severe chronic illness would have, whether that be arthritis, diabetes, or cardiac disease, because it is a systemic disorder that … profoundly affects quality of life, every minute of every day.”

However, “we don’t get all the referrals we should, until the child has suffered for years and years, and the family has suffered,” as there is a bias that it can be outgrown — although not everybody does — and it “doesn’t look as conspicuous as other chronic skin disorders,” such as psoriasis.

“Now with this study,” Kirkorian said, “it gives us a really compelling point to make to parents, to the community, and to insurers that not only are we affecting the quality of life from the itch standpoint [with dupilumab] but we may have long profound effects on growth and bone health.”

The research was sponsored by Sanofi and Regeneron Pharmaceuticals. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome. Kirkorian declared relationships with Dermavant, Verrica Pharmaceuticals, Pfizer, and Incyte.
 

A version of this article first appeared on Medscape.com.

AMSTERDAM — Children with short stature related to severe atopic dermatitis not only can have their condition effectively treated with 16 weeks of dupilumab but also may experience improved growth, bringing them back toward standard height curves, revealed a post hoc trial analysis.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.

It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”

He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”

Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”

“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.

“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”

Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
 

Post Hoc Analysis 

In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.

Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.

For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.

They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.

Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”

Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.

After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).

“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”

Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).

Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.

“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”
 

‘Convincing’ Data

Overall, Kirkorian said in the interview, the data are “convincing” and support her view that severe atopic dermatitis is a “terrible chronic disease that we really underappreciate.” Atopic dermatitis, she added, “should get the respect that any severe chronic illness would have, whether that be arthritis, diabetes, or cardiac disease, because it is a systemic disorder that … profoundly affects quality of life, every minute of every day.”

However, “we don’t get all the referrals we should, until the child has suffered for years and years, and the family has suffered,” as there is a bias that it can be outgrown — although not everybody does — and it “doesn’t look as conspicuous as other chronic skin disorders,” such as psoriasis.

“Now with this study,” Kirkorian said, “it gives us a really compelling point to make to parents, to the community, and to insurers that not only are we affecting the quality of life from the itch standpoint [with dupilumab] but we may have long profound effects on growth and bone health.”

The research was sponsored by Sanofi and Regeneron Pharmaceuticals. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome. Kirkorian declared relationships with Dermavant, Verrica Pharmaceuticals, Pfizer, and Incyte.
 

A version of this article first appeared on Medscape.com.

AMSTERDAM — Children with short stature related to severe atopic dermatitis not only can have their condition effectively treated with 16 weeks of dupilumab but also may experience improved growth, bringing them back toward standard height curves, revealed a post hoc trial analysis.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.

It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”

He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”

Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”

“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.

“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”

Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
 

Post Hoc Analysis 

In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.

Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.

For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.

They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.

Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”

Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.

After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).

“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”

Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).

Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.

“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”
 

‘Convincing’ Data

Overall, Kirkorian said in the interview, the data are “convincing” and support her view that severe atopic dermatitis is a “terrible chronic disease that we really underappreciate.” Atopic dermatitis, she added, “should get the respect that any severe chronic illness would have, whether that be arthritis, diabetes, or cardiac disease, because it is a systemic disorder that … profoundly affects quality of life, every minute of every day.”

However, “we don’t get all the referrals we should, until the child has suffered for years and years, and the family has suffered,” as there is a bias that it can be outgrown — although not everybody does — and it “doesn’t look as conspicuous as other chronic skin disorders,” such as psoriasis.

“Now with this study,” Kirkorian said, “it gives us a really compelling point to make to parents, to the community, and to insurers that not only are we affecting the quality of life from the itch standpoint [with dupilumab] but we may have long profound effects on growth and bone health.”

The research was sponsored by Sanofi and Regeneron Pharmaceuticals. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAI, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome. Kirkorian declared relationships with Dermavant, Verrica Pharmaceuticals, Pfizer, and Incyte.
 

A version of this article first appeared on Medscape.com.

The monoclonal antibody nemolizumab offers long-term efficacy and safety, as well as quality-of-life benefits, in the management of adolescents and adults with moderate to severe atopic dermatitis (AD), revealed an interim analysis of the ARCADIA open-label extension study.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The results showed nemolizumab was associated with “ongoing clinically meaningful improvements in itch, skin lesions, and sleep disturbance,” said study presenter Diamant Thaçi, MD, PhD, of the Comprehensive Center for Inflammation Medicine, University of Lü̈beck in Germany.

Moreover, “patient-reported outcomes, including quality of life ... continued to improve over 56 weeks of treatment.” In addition, Thaçi added, the “safety data support the long-term use of nemolizumab for the treatment of adolescent and adult patients with moderate to severe atopic dermatitis.”

He explained that interleukin (IL) 31 is a key neuroimmune cytokine in AD, triggering itch, skin barrier disruption, and exacerbation of inflammation via its receptor. Nemolizumab inhibits IL-31 receptor binding and was shown in the ARCADIA 1 and ARCADIA 2 trials to provide, along with background topical corticosteroids, clinically meaningful improvements in itch, skin lesions, and sleep for up to weeks 48 of follow-up in adolescents and adults with moderate to severe AD.

The current open-label long-term extension study involved patients who were enrolled in both ARCADIA 1 and 2 trials, as well as those from four phase 2 and 2b studies, a phase 3b study, and adolescents who had not been included in a trial but who met the criteria for the extension study. All patients, whether they started on placebo plus background topical corticosteroids in a prior study, were treated with nemolizumab 30 mg subcutaneously every 4 weeks along with topical corticosteroids.

The interim analysis included all efficacy and safety data up to the cutoff of September 30, 2022, on 723 patients who had completed 56 weeks of treatment among the 1751 patients initially enrolled in the extension study.

The results showed that, regardless of whether patients were nemolizumab naive at enrollment or had previously taken the drug, there were increases in the proportion of patients with an Investigator Global Assessment (IGA) score of 0/1 and an Eczema Area and Severity Index (EASI) score of at least 75 (EASI-75) over the 56 weeks of the study.

In those naive to nemolizumab, the increase in the proportion with an IGA score of 0/1 increased from 17.7% at baseline to 49.0% at 56 weeks, while the proportion with an EASI-75 increased from 24.0% to 78.7%.

The increase in the proportion of patients with an IGA score 0/1 among those who had previously received nemolizumab increased from 28.5% at baseline to 47.1% at 56 weeks. The proportion with an EASI-75 was 38.1% at baseline, rising to 73.0% at 56 weeks.

Increases in the proportion of patients with an EASI score of at least 50 and at least 90 were also seen with nemolizumab, as were increases in the proportion of patients with an improvement of at least four points on the SCORing Atopic Dermatitis Pruritus visual analogue scale and Sleep loss scores.

Similarly, the proportion of patients with a reduction in Dermatology Life Quality Index of at least four points increased over the study period.

Regarding safety, Thaçi said, there appeared to be fewer adverse events than had been previously reported with nemolizumab. “We don’t see any signs of conjunctivitis,” he continued, or significant risk of infection apart from for COVID-19, but he pointed out that the study was conducted during the pandemic, which was “a very difficult time.”

The most common treatment-related adverse events were, aside from COVID-19, nasopharyngitis in about 10%-11% of patients, upper respiratory tract infection in about 6% to almost 7%, and headache in about 5%.

Among the adverse events of special interest, newly diagnosed asthma or worsening of asthma occurred in 4.7%-4.8% of patients, while peripheral edema was seen in 0.8%-1.7%.

“Besides this, the study results are really looking very good,” he said, adding: “It means, in a long-term study, we can say today that nemolizumab has revealed the [same] safety profile that was shown in the ARCADIA 1 and 2 trials.”

Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin in Ireland, who was not involved in the study, underlined that the current interim assessment does not represent the complete dataset and is based on observed cases rather than a more rigorous methodology, such as net reclassification improvement analysis.

“So it makes it a little harder to interpret when you don’t know how many people are dropping out and why they’re dropping out,” he told this news organization. “That said, those who remain on drug out to 56 weeks do experience ongoing improvement in disease control.”

Consequently, “the most reliable message you can take from this interim analysis of long-term data is that there were no new safety signals,” and nemolizumab looks “safe and well-tolerated.”

Where nemolizumab would fit into the treatment pathway for moderate to severe AD remains an open question, Irvine said, although he believes that IL-13 pathway inhibitors such as dupilumab, tralokinumab, and lebrikizumab “will remain the treatment of choice for the immediate future due to prescriber familiarity and good efficacy data.”

However, for patients who are unsuitable for IL-13 inhibitors and/or Janus kinase inhibitors such as abrocitinib and upadacitinib, nemolizumab “could be an interesting alternative.”

“That’s probably where it is going to start,” Irvine said, “and then obviously that will change over time and as the data mature and prescribers become more familiar with the drug in the real world.”

Nemolizumab (Nemluvio) is approved for treating prurigo nodularis (PN) in the United States and in Japan and is under Food and Drug Administration review for treating AD. It is also under review for PN and AD in Europe, Canada, the United Kingdom, and several other countries, according to Galderma. It is also approved for treating pruritus associated with AD in pediatric, adolescent, and adult patients in Japan.

The study was funded by Galderma. Thaçi declared relationships with AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oréal, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, Target RWE, and UCB. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAl, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome.

A version of this article first appeared on Medscape.com.

The monoclonal antibody nemolizumab offers long-term efficacy and safety, as well as quality-of-life benefits, in the management of adolescents and adults with moderate to severe atopic dermatitis (AD), revealed an interim analysis of the ARCADIA open-label extension study.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The results showed nemolizumab was associated with “ongoing clinically meaningful improvements in itch, skin lesions, and sleep disturbance,” said study presenter Diamant Thaçi, MD, PhD, of the Comprehensive Center for Inflammation Medicine, University of Lü̈beck in Germany.

Moreover, “patient-reported outcomes, including quality of life ... continued to improve over 56 weeks of treatment.” In addition, Thaçi added, the “safety data support the long-term use of nemolizumab for the treatment of adolescent and adult patients with moderate to severe atopic dermatitis.”

He explained that interleukin (IL) 31 is a key neuroimmune cytokine in AD, triggering itch, skin barrier disruption, and exacerbation of inflammation via its receptor. Nemolizumab inhibits IL-31 receptor binding and was shown in the ARCADIA 1 and ARCADIA 2 trials to provide, along with background topical corticosteroids, clinically meaningful improvements in itch, skin lesions, and sleep for up to weeks 48 of follow-up in adolescents and adults with moderate to severe AD.

The current open-label long-term extension study involved patients who were enrolled in both ARCADIA 1 and 2 trials, as well as those from four phase 2 and 2b studies, a phase 3b study, and adolescents who had not been included in a trial but who met the criteria for the extension study. All patients, whether they started on placebo plus background topical corticosteroids in a prior study, were treated with nemolizumab 30 mg subcutaneously every 4 weeks along with topical corticosteroids.

The interim analysis included all efficacy and safety data up to the cutoff of September 30, 2022, on 723 patients who had completed 56 weeks of treatment among the 1751 patients initially enrolled in the extension study.

The results showed that, regardless of whether patients were nemolizumab naive at enrollment or had previously taken the drug, there were increases in the proportion of patients with an Investigator Global Assessment (IGA) score of 0/1 and an Eczema Area and Severity Index (EASI) score of at least 75 (EASI-75) over the 56 weeks of the study.

In those naive to nemolizumab, the increase in the proportion with an IGA score of 0/1 increased from 17.7% at baseline to 49.0% at 56 weeks, while the proportion with an EASI-75 increased from 24.0% to 78.7%.

The increase in the proportion of patients with an IGA score 0/1 among those who had previously received nemolizumab increased from 28.5% at baseline to 47.1% at 56 weeks. The proportion with an EASI-75 was 38.1% at baseline, rising to 73.0% at 56 weeks.

Increases in the proportion of patients with an EASI score of at least 50 and at least 90 were also seen with nemolizumab, as were increases in the proportion of patients with an improvement of at least four points on the SCORing Atopic Dermatitis Pruritus visual analogue scale and Sleep loss scores.

Similarly, the proportion of patients with a reduction in Dermatology Life Quality Index of at least four points increased over the study period.

Regarding safety, Thaçi said, there appeared to be fewer adverse events than had been previously reported with nemolizumab. “We don’t see any signs of conjunctivitis,” he continued, or significant risk of infection apart from for COVID-19, but he pointed out that the study was conducted during the pandemic, which was “a very difficult time.”

The most common treatment-related adverse events were, aside from COVID-19, nasopharyngitis in about 10%-11% of patients, upper respiratory tract infection in about 6% to almost 7%, and headache in about 5%.

Among the adverse events of special interest, newly diagnosed asthma or worsening of asthma occurred in 4.7%-4.8% of patients, while peripheral edema was seen in 0.8%-1.7%.

“Besides this, the study results are really looking very good,” he said, adding: “It means, in a long-term study, we can say today that nemolizumab has revealed the [same] safety profile that was shown in the ARCADIA 1 and 2 trials.”

Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin in Ireland, who was not involved in the study, underlined that the current interim assessment does not represent the complete dataset and is based on observed cases rather than a more rigorous methodology, such as net reclassification improvement analysis.

“So it makes it a little harder to interpret when you don’t know how many people are dropping out and why they’re dropping out,” he told this news organization. “That said, those who remain on drug out to 56 weeks do experience ongoing improvement in disease control.”

Consequently, “the most reliable message you can take from this interim analysis of long-term data is that there were no new safety signals,” and nemolizumab looks “safe and well-tolerated.”

Where nemolizumab would fit into the treatment pathway for moderate to severe AD remains an open question, Irvine said, although he believes that IL-13 pathway inhibitors such as dupilumab, tralokinumab, and lebrikizumab “will remain the treatment of choice for the immediate future due to prescriber familiarity and good efficacy data.”

However, for patients who are unsuitable for IL-13 inhibitors and/or Janus kinase inhibitors such as abrocitinib and upadacitinib, nemolizumab “could be an interesting alternative.”

“That’s probably where it is going to start,” Irvine said, “and then obviously that will change over time and as the data mature and prescribers become more familiar with the drug in the real world.”

Nemolizumab (Nemluvio) is approved for treating prurigo nodularis (PN) in the United States and in Japan and is under Food and Drug Administration review for treating AD. It is also under review for PN and AD in Europe, Canada, the United Kingdom, and several other countries, according to Galderma. It is also approved for treating pruritus associated with AD in pediatric, adolescent, and adult patients in Japan.

The study was funded by Galderma. Thaçi declared relationships with AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oréal, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, Target RWE, and UCB. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAl, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome.

A version of this article first appeared on Medscape.com.

The monoclonal antibody nemolizumab offers long-term efficacy and safety, as well as quality-of-life benefits, in the management of adolescents and adults with moderate to severe atopic dermatitis (AD), revealed an interim analysis of the ARCADIA open-label extension study.

The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

The results showed nemolizumab was associated with “ongoing clinically meaningful improvements in itch, skin lesions, and sleep disturbance,” said study presenter Diamant Thaçi, MD, PhD, of the Comprehensive Center for Inflammation Medicine, University of Lü̈beck in Germany.

Moreover, “patient-reported outcomes, including quality of life ... continued to improve over 56 weeks of treatment.” In addition, Thaçi added, the “safety data support the long-term use of nemolizumab for the treatment of adolescent and adult patients with moderate to severe atopic dermatitis.”

He explained that interleukin (IL) 31 is a key neuroimmune cytokine in AD, triggering itch, skin barrier disruption, and exacerbation of inflammation via its receptor. Nemolizumab inhibits IL-31 receptor binding and was shown in the ARCADIA 1 and ARCADIA 2 trials to provide, along with background topical corticosteroids, clinically meaningful improvements in itch, skin lesions, and sleep for up to weeks 48 of follow-up in adolescents and adults with moderate to severe AD.

The current open-label long-term extension study involved patients who were enrolled in both ARCADIA 1 and 2 trials, as well as those from four phase 2 and 2b studies, a phase 3b study, and adolescents who had not been included in a trial but who met the criteria for the extension study. All patients, whether they started on placebo plus background topical corticosteroids in a prior study, were treated with nemolizumab 30 mg subcutaneously every 4 weeks along with topical corticosteroids.

The interim analysis included all efficacy and safety data up to the cutoff of September 30, 2022, on 723 patients who had completed 56 weeks of treatment among the 1751 patients initially enrolled in the extension study.

The results showed that, regardless of whether patients were nemolizumab naive at enrollment or had previously taken the drug, there were increases in the proportion of patients with an Investigator Global Assessment (IGA) score of 0/1 and an Eczema Area and Severity Index (EASI) score of at least 75 (EASI-75) over the 56 weeks of the study.

In those naive to nemolizumab, the increase in the proportion with an IGA score of 0/1 increased from 17.7% at baseline to 49.0% at 56 weeks, while the proportion with an EASI-75 increased from 24.0% to 78.7%.

The increase in the proportion of patients with an IGA score 0/1 among those who had previously received nemolizumab increased from 28.5% at baseline to 47.1% at 56 weeks. The proportion with an EASI-75 was 38.1% at baseline, rising to 73.0% at 56 weeks.

Increases in the proportion of patients with an EASI score of at least 50 and at least 90 were also seen with nemolizumab, as were increases in the proportion of patients with an improvement of at least four points on the SCORing Atopic Dermatitis Pruritus visual analogue scale and Sleep loss scores.

Similarly, the proportion of patients with a reduction in Dermatology Life Quality Index of at least four points increased over the study period.

Regarding safety, Thaçi said, there appeared to be fewer adverse events than had been previously reported with nemolizumab. “We don’t see any signs of conjunctivitis,” he continued, or significant risk of infection apart from for COVID-19, but he pointed out that the study was conducted during the pandemic, which was “a very difficult time.”

The most common treatment-related adverse events were, aside from COVID-19, nasopharyngitis in about 10%-11% of patients, upper respiratory tract infection in about 6% to almost 7%, and headache in about 5%.

Among the adverse events of special interest, newly diagnosed asthma or worsening of asthma occurred in 4.7%-4.8% of patients, while peripheral edema was seen in 0.8%-1.7%.

“Besides this, the study results are really looking very good,” he said, adding: “It means, in a long-term study, we can say today that nemolizumab has revealed the [same] safety profile that was shown in the ARCADIA 1 and 2 trials.”

Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin in Ireland, who was not involved in the study, underlined that the current interim assessment does not represent the complete dataset and is based on observed cases rather than a more rigorous methodology, such as net reclassification improvement analysis.

“So it makes it a little harder to interpret when you don’t know how many people are dropping out and why they’re dropping out,” he told this news organization. “That said, those who remain on drug out to 56 weeks do experience ongoing improvement in disease control.”

Consequently, “the most reliable message you can take from this interim analysis of long-term data is that there were no new safety signals,” and nemolizumab looks “safe and well-tolerated.”

Where nemolizumab would fit into the treatment pathway for moderate to severe AD remains an open question, Irvine said, although he believes that IL-13 pathway inhibitors such as dupilumab, tralokinumab, and lebrikizumab “will remain the treatment of choice for the immediate future due to prescriber familiarity and good efficacy data.”

However, for patients who are unsuitable for IL-13 inhibitors and/or Janus kinase inhibitors such as abrocitinib and upadacitinib, nemolizumab “could be an interesting alternative.”

“That’s probably where it is going to start,” Irvine said, “and then obviously that will change over time and as the data mature and prescribers become more familiar with the drug in the real world.”

Nemolizumab (Nemluvio) is approved for treating prurigo nodularis (PN) in the United States and in Japan and is under Food and Drug Administration review for treating AD. It is also under review for PN and AD in Europe, Canada, the United Kingdom, and several other countries, according to Galderma. It is also approved for treating pruritus associated with AD in pediatric, adolescent, and adult patients in Japan.

The study was funded by Galderma. Thaçi declared relationships with AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, L’Oréal, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, Target RWE, and UCB. Irvine declared relationships with AbbVie, Arena Pharmaceuticals, BenevolentAl, Chugai Pharmaceutical, Dermavant, Eli Lily, Genentech, LEO Pharma, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, UCB, DS Biopharma, and Inflazome.

A version of this article first appeared on Medscape.com.

Treatment with ruxolitinib cream (1.5%) achieved rapid and marked reductions in the clinical signs and symptoms of cutaneous lichen planus, including itch and skin pain, both when given twice daily and as needed, according to data from a phase 2 trial.

The research, presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress, involved 64 patients older than 18 years. Ruxolitinib cream (Opzelura) is a topical formulation of a Janus kinase (JAK)1/JAK2 inhibitor, approved by the Food and Drug Administration (FDA) for treating mild to moderate atopic dermatitis and for nonsegmental vitiligo in adults and children aged 12 years or older.

 

Courtesy Dr. Aaron Mangold

Ruxolitinib cream twice daily resulted in “significant improvements in cutaneous lichen planus disease severity vs vehicle” after 16 weeks of treatment, said the study presenter, Aaron R. Mangold, MD, a dermatologist at Mayo Clinic, Scottsdale, Arizona.

Further improvements were seen during another 16 weeks of additional open-label, as-needed application, he added, and the topical treatment was “generally well tolerated.”

Consequently, “ruxolitinib cream represents a promising potential treatment for cutaneous lichen planus,” Mangold concluded.

Asked to comment on the results, Adam Friedman, MD, Professor and Chair of Dermatology, George Washington University, Washington, DC, who was not involved with the study, said that in keeping with the characterization of lichen planus using the four Ps — purple, polygonal, pruritic, papules — it is “Pretty common, Predictably disabling and disfiguring, and Passed over again and again in the drug development world.”

He said in an interview that this chronic inflammatory skin condition, which affects roughly 2% of the population, also “lacks consensus on work-up and management, likely in part owing to the absence of sizable clinical trial data.”

A recent survey conducted at a meeting indicated that dermatologists “heavily lean on topical therapies for the management of all severity levels,” noted Friedman, one of the survey authors. “Therefore, the phase 2 data presented at EADV is a welcome addition to the mix.”
 

Phase 2 Study Results 

At the meeting, Mangold said that a previous proof-of-concept single-arm study in 12 patients suggested that topical ruxolitinib was highly effective in treating cutaneous lichen planus.

The current phase 2 trial enrolled 64 patients with predominantly cutaneous disease who had an Investigator’s Global Assessment (IGA) score of 3 or 4 and an Itch Numeric Rating Scale (NRS) score of ≥ 4. Their median age was 57 years, and 71.9% were women. Nearly 63% were White, 28.1% were Black, and 6.3% were Asian. The median duration of disease was 4.9 years, and 90.6% had received prior treatment for their lichen planus.

They were randomized to receive 1.5% ruxolitinib cream or a vehicle cream twice daily for 16 weeks, and following a primary endpoint assessment, they were transferred to an open-label extension period, during which they used ruxolitinib cream as needed for another 16 weeks. There was an additional 30-day safety follow-up period.

At week 16, significantly more patients treated with the ruxolitinib cream (50.0%) vs vehicle cream (21.9%) achieved IGA treatment success (the primary endpoint), defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline (odds ratio, 4.04; P = .0129).

In the open-label extension, when all patients used the active cream as needed, the proportion achieving IGA treatment success increased to 60% among the patients originally treated with ruxolitinib cream and 60.9% among those who switched from the vehicle cream.

A similar pattern was seen with Itch NRS scores. At 16 weeks, 57.7% of those treated with the ruxolitinib cream and 19.2% of those given the vehicle cream achieved an Itch NRS score of ≥ 4 (P < .01), rising to 84.2% and 73.3%, respectively, during the open-label extension.

The time to achievement of an Itch NRS of ≥ 4 was also significantly shorter with the ruxolitinib cream than with the vehicle cream (median days, 17 vs 97; hazard ratio, 2.85; P = .0008).

In both treatment groups, Skin Pain NRS scores decreased by a mean of 3.0 with ruxolitinib cream and 1.3 with the vehicle cream at week 16. By the end of the open-label extension, scores dropped by 4.3 among those who continued on active treatment and by 3.5 among those who switched from vehicle to topical ruxolitinib.

There were few treatment-emergent adverse events, with just three ruxolitinib patients affected during the randomized phase of the trial. There was one grade ≥ 3 event considered unrelated to the study drug, and no serious treatment-emergent adverse events were reported.

The most common adverse events during the randomized period were nasopharyngitis, hypertension, and contusion, all experienced by fewer than 10% of patients, whereas sinusitis, increased blood cholesterol levels, and increased blood creatine phosphokinase were most common in the open-label extension, experienced by no more than 5% of patients.

In the interview, Friedman commented that “these data provide hope that one day soon, there will be an FDA-approved, effective, and well-tolerated approach for this condition, validating the patient and supporting the dermatologist with an evidence-based option.”

The study was funded by Incyte. Mangold declared relationships with Argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Clarivate, Incyte Corporation, Janssen, Nuvig Therapeutics, Pfizer, Regeneron Pharmaceuticals, Soligenix, Tourmaline Bio, AbbVie, Corbus, Eli Lilly, Kyowa, Merck, miRagen Therapeutics, Palvella Therapeutics, Priovant Therapeutics, and Adelphi Values. Friedman declared a relationship with Incyte, but it is not related to this topic.

A version of this article first appeared on Medscape.com.

Treatment with ruxolitinib cream (1.5%) achieved rapid and marked reductions in the clinical signs and symptoms of cutaneous lichen planus, including itch and skin pain, both when given twice daily and as needed, according to data from a phase 2 trial.

The research, presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress, involved 64 patients older than 18 years. Ruxolitinib cream (Opzelura) is a topical formulation of a Janus kinase (JAK)1/JAK2 inhibitor, approved by the Food and Drug Administration (FDA) for treating mild to moderate atopic dermatitis and for nonsegmental vitiligo in adults and children aged 12 years or older.

 

Courtesy Dr. Aaron Mangold

Ruxolitinib cream twice daily resulted in “significant improvements in cutaneous lichen planus disease severity vs vehicle” after 16 weeks of treatment, said the study presenter, Aaron R. Mangold, MD, a dermatologist at Mayo Clinic, Scottsdale, Arizona.

Further improvements were seen during another 16 weeks of additional open-label, as-needed application, he added, and the topical treatment was “generally well tolerated.”

Consequently, “ruxolitinib cream represents a promising potential treatment for cutaneous lichen planus,” Mangold concluded.

Asked to comment on the results, Adam Friedman, MD, Professor and Chair of Dermatology, George Washington University, Washington, DC, who was not involved with the study, said that in keeping with the characterization of lichen planus using the four Ps — purple, polygonal, pruritic, papules — it is “Pretty common, Predictably disabling and disfiguring, and Passed over again and again in the drug development world.”

He said in an interview that this chronic inflammatory skin condition, which affects roughly 2% of the population, also “lacks consensus on work-up and management, likely in part owing to the absence of sizable clinical trial data.”

A recent survey conducted at a meeting indicated that dermatologists “heavily lean on topical therapies for the management of all severity levels,” noted Friedman, one of the survey authors. “Therefore, the phase 2 data presented at EADV is a welcome addition to the mix.”
 

Phase 2 Study Results 

At the meeting, Mangold said that a previous proof-of-concept single-arm study in 12 patients suggested that topical ruxolitinib was highly effective in treating cutaneous lichen planus.

The current phase 2 trial enrolled 64 patients with predominantly cutaneous disease who had an Investigator’s Global Assessment (IGA) score of 3 or 4 and an Itch Numeric Rating Scale (NRS) score of ≥ 4. Their median age was 57 years, and 71.9% were women. Nearly 63% were White, 28.1% were Black, and 6.3% were Asian. The median duration of disease was 4.9 years, and 90.6% had received prior treatment for their lichen planus.

They were randomized to receive 1.5% ruxolitinib cream or a vehicle cream twice daily for 16 weeks, and following a primary endpoint assessment, they were transferred to an open-label extension period, during which they used ruxolitinib cream as needed for another 16 weeks. There was an additional 30-day safety follow-up period.

At week 16, significantly more patients treated with the ruxolitinib cream (50.0%) vs vehicle cream (21.9%) achieved IGA treatment success (the primary endpoint), defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline (odds ratio, 4.04; P = .0129).

In the open-label extension, when all patients used the active cream as needed, the proportion achieving IGA treatment success increased to 60% among the patients originally treated with ruxolitinib cream and 60.9% among those who switched from the vehicle cream.

A similar pattern was seen with Itch NRS scores. At 16 weeks, 57.7% of those treated with the ruxolitinib cream and 19.2% of those given the vehicle cream achieved an Itch NRS score of ≥ 4 (P < .01), rising to 84.2% and 73.3%, respectively, during the open-label extension.

The time to achievement of an Itch NRS of ≥ 4 was also significantly shorter with the ruxolitinib cream than with the vehicle cream (median days, 17 vs 97; hazard ratio, 2.85; P = .0008).

In both treatment groups, Skin Pain NRS scores decreased by a mean of 3.0 with ruxolitinib cream and 1.3 with the vehicle cream at week 16. By the end of the open-label extension, scores dropped by 4.3 among those who continued on active treatment and by 3.5 among those who switched from vehicle to topical ruxolitinib.

There were few treatment-emergent adverse events, with just three ruxolitinib patients affected during the randomized phase of the trial. There was one grade ≥ 3 event considered unrelated to the study drug, and no serious treatment-emergent adverse events were reported.

The most common adverse events during the randomized period were nasopharyngitis, hypertension, and contusion, all experienced by fewer than 10% of patients, whereas sinusitis, increased blood cholesterol levels, and increased blood creatine phosphokinase were most common in the open-label extension, experienced by no more than 5% of patients.

In the interview, Friedman commented that “these data provide hope that one day soon, there will be an FDA-approved, effective, and well-tolerated approach for this condition, validating the patient and supporting the dermatologist with an evidence-based option.”

The study was funded by Incyte. Mangold declared relationships with Argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Clarivate, Incyte Corporation, Janssen, Nuvig Therapeutics, Pfizer, Regeneron Pharmaceuticals, Soligenix, Tourmaline Bio, AbbVie, Corbus, Eli Lilly, Kyowa, Merck, miRagen Therapeutics, Palvella Therapeutics, Priovant Therapeutics, and Adelphi Values. Friedman declared a relationship with Incyte, but it is not related to this topic.

A version of this article first appeared on Medscape.com.

Treatment with ruxolitinib cream (1.5%) achieved rapid and marked reductions in the clinical signs and symptoms of cutaneous lichen planus, including itch and skin pain, both when given twice daily and as needed, according to data from a phase 2 trial.

The research, presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress, involved 64 patients older than 18 years. Ruxolitinib cream (Opzelura) is a topical formulation of a Janus kinase (JAK)1/JAK2 inhibitor, approved by the Food and Drug Administration (FDA) for treating mild to moderate atopic dermatitis and for nonsegmental vitiligo in adults and children aged 12 years or older.

 

Courtesy Dr. Aaron Mangold

Ruxolitinib cream twice daily resulted in “significant improvements in cutaneous lichen planus disease severity vs vehicle” after 16 weeks of treatment, said the study presenter, Aaron R. Mangold, MD, a dermatologist at Mayo Clinic, Scottsdale, Arizona.

Further improvements were seen during another 16 weeks of additional open-label, as-needed application, he added, and the topical treatment was “generally well tolerated.”

Consequently, “ruxolitinib cream represents a promising potential treatment for cutaneous lichen planus,” Mangold concluded.

Asked to comment on the results, Adam Friedman, MD, Professor and Chair of Dermatology, George Washington University, Washington, DC, who was not involved with the study, said that in keeping with the characterization of lichen planus using the four Ps — purple, polygonal, pruritic, papules — it is “Pretty common, Predictably disabling and disfiguring, and Passed over again and again in the drug development world.”

He said in an interview that this chronic inflammatory skin condition, which affects roughly 2% of the population, also “lacks consensus on work-up and management, likely in part owing to the absence of sizable clinical trial data.”

A recent survey conducted at a meeting indicated that dermatologists “heavily lean on topical therapies for the management of all severity levels,” noted Friedman, one of the survey authors. “Therefore, the phase 2 data presented at EADV is a welcome addition to the mix.”
 

Phase 2 Study Results 

At the meeting, Mangold said that a previous proof-of-concept single-arm study in 12 patients suggested that topical ruxolitinib was highly effective in treating cutaneous lichen planus.

The current phase 2 trial enrolled 64 patients with predominantly cutaneous disease who had an Investigator’s Global Assessment (IGA) score of 3 or 4 and an Itch Numeric Rating Scale (NRS) score of ≥ 4. Their median age was 57 years, and 71.9% were women. Nearly 63% were White, 28.1% were Black, and 6.3% were Asian. The median duration of disease was 4.9 years, and 90.6% had received prior treatment for their lichen planus.

They were randomized to receive 1.5% ruxolitinib cream or a vehicle cream twice daily for 16 weeks, and following a primary endpoint assessment, they were transferred to an open-label extension period, during which they used ruxolitinib cream as needed for another 16 weeks. There was an additional 30-day safety follow-up period.

At week 16, significantly more patients treated with the ruxolitinib cream (50.0%) vs vehicle cream (21.9%) achieved IGA treatment success (the primary endpoint), defined as an IGA score of 0 or 1 with ≥ 2-grade improvement from baseline (odds ratio, 4.04; P = .0129).

In the open-label extension, when all patients used the active cream as needed, the proportion achieving IGA treatment success increased to 60% among the patients originally treated with ruxolitinib cream and 60.9% among those who switched from the vehicle cream.

A similar pattern was seen with Itch NRS scores. At 16 weeks, 57.7% of those treated with the ruxolitinib cream and 19.2% of those given the vehicle cream achieved an Itch NRS score of ≥ 4 (P < .01), rising to 84.2% and 73.3%, respectively, during the open-label extension.

The time to achievement of an Itch NRS of ≥ 4 was also significantly shorter with the ruxolitinib cream than with the vehicle cream (median days, 17 vs 97; hazard ratio, 2.85; P = .0008).

In both treatment groups, Skin Pain NRS scores decreased by a mean of 3.0 with ruxolitinib cream and 1.3 with the vehicle cream at week 16. By the end of the open-label extension, scores dropped by 4.3 among those who continued on active treatment and by 3.5 among those who switched from vehicle to topical ruxolitinib.

There were few treatment-emergent adverse events, with just three ruxolitinib patients affected during the randomized phase of the trial. There was one grade ≥ 3 event considered unrelated to the study drug, and no serious treatment-emergent adverse events were reported.

The most common adverse events during the randomized period were nasopharyngitis, hypertension, and contusion, all experienced by fewer than 10% of patients, whereas sinusitis, increased blood cholesterol levels, and increased blood creatine phosphokinase were most common in the open-label extension, experienced by no more than 5% of patients.

In the interview, Friedman commented that “these data provide hope that one day soon, there will be an FDA-approved, effective, and well-tolerated approach for this condition, validating the patient and supporting the dermatologist with an evidence-based option.”

The study was funded by Incyte. Mangold declared relationships with Argenx, Boehringer Ingelheim, Bristol-Myers Squibb, Clarivate, Incyte Corporation, Janssen, Nuvig Therapeutics, Pfizer, Regeneron Pharmaceuticals, Soligenix, Tourmaline Bio, AbbVie, Corbus, Eli Lilly, Kyowa, Merck, miRagen Therapeutics, Palvella Therapeutics, Priovant Therapeutics, and Adelphi Values. Friedman declared a relationship with Incyte, but it is not related to this topic.

A version of this article first appeared on Medscape.com.

Janus kinase inhibitors (JAKis) do not appear to increase the risk for major adverse cardiovascular events (MACE) among people with atopic dermatitis (AD) treated in a real-world setting, suggested the results of a large, US-based, retrospective cohort study.

This holds true even in individuals aged 50 years or older, whose age puts them at increased cardiovascular (CV) risk, said Amina El Ayadi, PhD, of the University of Texas Medical Branch at Galveston. He presented the findings at the recent European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Specifically, the analysis looked at treatment with the oral JAK1 inhibitors upadacitinib (Rinvoq) and abrocitinib (Cibinqo), both approved for treating AD in the United States, and found that the relative risk for MACE, such as acute myocardial infarction, cardiac arrest, stroke, or acute deep vein thrombosis, was ≤ 1.0 compared with those not treated with a JAKi.

Similarly, the relative risk for other CV safety endpoints, such as having an abnormal ECG or pericardial effusion, was also around 1.0. There was a slight increase in the relative risk for arrhythmias, peripheral edema, angina pectoris, or heart failure, but no value went > 1.6 and CIs spanned 1.0, indicating the results lack statistical significance.
 

Reassurance for Dermatologists?

“This suggests that oral administration of these drugs to the patient with atopic dermatitis does not increase the risk of major adverse cardiac events, and dermatologists, based on our data, can safely consider JAK inhibitors for treating moderate to severe dermatitis, even in patients with high risk for these diseases,” El Ayadi said during a late-breaking news session at the meeting.

Yolanda Gilaberte Calzada, MD, PhD, head of the Dermatology Department at Miguel Servet University Hospital in Zaragoza, Spain, who was one of the chairs for the session, said that this was “very good news for us.”

Gilaberte Calzada, president of the Spanish Academy of Dermatology and Venereology, asked if there were any data on the duration of treatment with the two JAKis included in the analysis. El Ayadi said that this was something that would be looked at in future data analyses.

Gilaberte Calzada also observed that because the CIs were wide, with more time, “we will have more defined data.”
 

Analyses Overview

For the two analyses — one in the overall population of patients with AD and the other in those aged 50 years or older — electronic medical record (EMR) data from the TriNetX Research Network were used. This is a global, federated health research network that contains EMRs for more than 275 million patients from over 120 healthcare organizations, El Ayadi explained.

To perform the analyses, the research team queried the TriNetX database to find all patients diagnosed with AD via the International Classification of Diseases, Tenth Revision code L20. They then determined if patients had been treated with JAKi or not, and specifically, with upadacitinib or abrocitinib. Those who had not received any JAKi treatment were the control population.

For the first analysis, no age-specific filter was applied. The investigators identified 1674 people with AD who had been treated with the JAKis and around 1.2 million who had not. Propensity score matching, based on age at diagnosis, biologic sex, and CV comorbidities, was performed to give a total of 1674 patients who had and 1674 who had not been treated with these medications.

In the second analysis, only those aged 50 years or older were considered; 875 patients who had received JAKi treatment were identified and around 250,000 who had not. Propensity score matching based on the same variables gave two groups of 875 people who had or had not taken a JAKi.

Queried over the age cutoff used, El Ayadi noted, “We did an analysis looking at patients 65 and older. However, we came up with lower patient numbers. … We do have this data, and we did not see any significant risk.”

The study was independently supported. El Ayadi and Gilaberte Calzada reported no conflicts of interest in relation to the presented findings.

A version of this article first appeared on Medscape.com.

Janus kinase inhibitors (JAKis) do not appear to increase the risk for major adverse cardiovascular events (MACE) among people with atopic dermatitis (AD) treated in a real-world setting, suggested the results of a large, US-based, retrospective cohort study.

This holds true even in individuals aged 50 years or older, whose age puts them at increased cardiovascular (CV) risk, said Amina El Ayadi, PhD, of the University of Texas Medical Branch at Galveston. He presented the findings at the recent European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Specifically, the analysis looked at treatment with the oral JAK1 inhibitors upadacitinib (Rinvoq) and abrocitinib (Cibinqo), both approved for treating AD in the United States, and found that the relative risk for MACE, such as acute myocardial infarction, cardiac arrest, stroke, or acute deep vein thrombosis, was ≤ 1.0 compared with those not treated with a JAKi.

Similarly, the relative risk for other CV safety endpoints, such as having an abnormal ECG or pericardial effusion, was also around 1.0. There was a slight increase in the relative risk for arrhythmias, peripheral edema, angina pectoris, or heart failure, but no value went > 1.6 and CIs spanned 1.0, indicating the results lack statistical significance.
 

Reassurance for Dermatologists?

“This suggests that oral administration of these drugs to the patient with atopic dermatitis does not increase the risk of major adverse cardiac events, and dermatologists, based on our data, can safely consider JAK inhibitors for treating moderate to severe dermatitis, even in patients with high risk for these diseases,” El Ayadi said during a late-breaking news session at the meeting.

Yolanda Gilaberte Calzada, MD, PhD, head of the Dermatology Department at Miguel Servet University Hospital in Zaragoza, Spain, who was one of the chairs for the session, said that this was “very good news for us.”

Gilaberte Calzada, president of the Spanish Academy of Dermatology and Venereology, asked if there were any data on the duration of treatment with the two JAKis included in the analysis. El Ayadi said that this was something that would be looked at in future data analyses.

Gilaberte Calzada also observed that because the CIs were wide, with more time, “we will have more defined data.”
 

Analyses Overview

For the two analyses — one in the overall population of patients with AD and the other in those aged 50 years or older — electronic medical record (EMR) data from the TriNetX Research Network were used. This is a global, federated health research network that contains EMRs for more than 275 million patients from over 120 healthcare organizations, El Ayadi explained.

To perform the analyses, the research team queried the TriNetX database to find all patients diagnosed with AD via the International Classification of Diseases, Tenth Revision code L20. They then determined if patients had been treated with JAKi or not, and specifically, with upadacitinib or abrocitinib. Those who had not received any JAKi treatment were the control population.

For the first analysis, no age-specific filter was applied. The investigators identified 1674 people with AD who had been treated with the JAKis and around 1.2 million who had not. Propensity score matching, based on age at diagnosis, biologic sex, and CV comorbidities, was performed to give a total of 1674 patients who had and 1674 who had not been treated with these medications.

In the second analysis, only those aged 50 years or older were considered; 875 patients who had received JAKi treatment were identified and around 250,000 who had not. Propensity score matching based on the same variables gave two groups of 875 people who had or had not taken a JAKi.

Queried over the age cutoff used, El Ayadi noted, “We did an analysis looking at patients 65 and older. However, we came up with lower patient numbers. … We do have this data, and we did not see any significant risk.”

The study was independently supported. El Ayadi and Gilaberte Calzada reported no conflicts of interest in relation to the presented findings.

A version of this article first appeared on Medscape.com.

Janus kinase inhibitors (JAKis) do not appear to increase the risk for major adverse cardiovascular events (MACE) among people with atopic dermatitis (AD) treated in a real-world setting, suggested the results of a large, US-based, retrospective cohort study.

This holds true even in individuals aged 50 years or older, whose age puts them at increased cardiovascular (CV) risk, said Amina El Ayadi, PhD, of the University of Texas Medical Branch at Galveston. He presented the findings at the recent European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Specifically, the analysis looked at treatment with the oral JAK1 inhibitors upadacitinib (Rinvoq) and abrocitinib (Cibinqo), both approved for treating AD in the United States, and found that the relative risk for MACE, such as acute myocardial infarction, cardiac arrest, stroke, or acute deep vein thrombosis, was ≤ 1.0 compared with those not treated with a JAKi.

Similarly, the relative risk for other CV safety endpoints, such as having an abnormal ECG or pericardial effusion, was also around 1.0. There was a slight increase in the relative risk for arrhythmias, peripheral edema, angina pectoris, or heart failure, but no value went > 1.6 and CIs spanned 1.0, indicating the results lack statistical significance.
 

Reassurance for Dermatologists?

“This suggests that oral administration of these drugs to the patient with atopic dermatitis does not increase the risk of major adverse cardiac events, and dermatologists, based on our data, can safely consider JAK inhibitors for treating moderate to severe dermatitis, even in patients with high risk for these diseases,” El Ayadi said during a late-breaking news session at the meeting.

Yolanda Gilaberte Calzada, MD, PhD, head of the Dermatology Department at Miguel Servet University Hospital in Zaragoza, Spain, who was one of the chairs for the session, said that this was “very good news for us.”

Gilaberte Calzada, president of the Spanish Academy of Dermatology and Venereology, asked if there were any data on the duration of treatment with the two JAKis included in the analysis. El Ayadi said that this was something that would be looked at in future data analyses.

Gilaberte Calzada also observed that because the CIs were wide, with more time, “we will have more defined data.”
 

Analyses Overview

For the two analyses — one in the overall population of patients with AD and the other in those aged 50 years or older — electronic medical record (EMR) data from the TriNetX Research Network were used. This is a global, federated health research network that contains EMRs for more than 275 million patients from over 120 healthcare organizations, El Ayadi explained.

To perform the analyses, the research team queried the TriNetX database to find all patients diagnosed with AD via the International Classification of Diseases, Tenth Revision code L20. They then determined if patients had been treated with JAKi or not, and specifically, with upadacitinib or abrocitinib. Those who had not received any JAKi treatment were the control population.

For the first analysis, no age-specific filter was applied. The investigators identified 1674 people with AD who had been treated with the JAKis and around 1.2 million who had not. Propensity score matching, based on age at diagnosis, biologic sex, and CV comorbidities, was performed to give a total of 1674 patients who had and 1674 who had not been treated with these medications.

In the second analysis, only those aged 50 years or older were considered; 875 patients who had received JAKi treatment were identified and around 250,000 who had not. Propensity score matching based on the same variables gave two groups of 875 people who had or had not taken a JAKi.

Queried over the age cutoff used, El Ayadi noted, “We did an analysis looking at patients 65 and older. However, we came up with lower patient numbers. … We do have this data, and we did not see any significant risk.”

The study was independently supported. El Ayadi and Gilaberte Calzada reported no conflicts of interest in relation to the presented findings.

A version of this article first appeared on Medscape.com.

The Janus kinase inhibitor delgocitinib may be a better or comparable choice for treating hand eczema than some more established therapies, suggested the results of two separate studies presented during the late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

In the 24-week, phase 3 DELTA FORCE trial, topical delgocitinib was compared head to head with oral alitretinoin for managing chronic hand eczema (CHE). Results showed that greater improvements from baseline to week 12 in Hand Eczema Severity Index (HECSI) scores could be achieved with delgocitinib cream than with alitretinoin capsules.

And in another analysis, which involved patients with the atopic subtype of CHE only, the application of topical delgocitinib was found to be as good as treatment with subcutaneous dupilumab (Dupixent) at improving both HECSI scores and the Investigator Global Assessment for CHE response (IGA-CHE).
 

Potentially a ‘Highly Impactful’ Therapy

“Chronic hand eczema is a common yet burdensome skin condition that poses a considerable challenge for dermatologists. Diversity in morphologic presentation and clinical etiology has been a key limitation for the development of a safe, targeted, one-size-fits-all therapeutic approach,” Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University of Medicine and Science, and the founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, said in an interview.

“These data show that delgocitinib cream is poised to be a novel and highly impactful topical therapy for the treatment of CHE,” said Chovatiya.

DELTA FORCE showed that the efficacy and safety of delgocitinib cream was “superior to alitretinoin, the only approved oral option for CHE,” he said. And the other study, a comparative analysis, showed that delgocitinib’s efficacy was “comparable to the biologic dupilumab specifically for the treatment of atopic hand eczema,” said Chovatiya, one of the authors of that study. He was not an author of the DELTA FORCE study.
 

DELTA FORCE

While it remains an investigational drug in the United States, where it is under Food and Drug Administration review for CHE, delgocitinib cream (Anzupgo) was recently approved by the European Commission for use in adults with moderate to severe hand eczema who do not respond to or who are unable to use topical corticosteroids. Approval was based on data from two phase 3 studies , DELTA 1 and DELTA 2, which compared delgocitinib cream against a cream vehicle, as well as an open-label, long-term extension study, DELTA 3.

In the DELTA FORCE study, 513 adults with severe CHE (IGA-CHE score of 4) were recruited at 102 clinical centers in Europe and North America and randomly allocated to topical treatment with delgocitinib cream, 20 mg/g applied twice daily, or alitretinoin capsules, 30 mg once daily. Treatment with delgocitinib was for 16 weeks, and treatment with alitretinoin was for 12 weeks. The latter’s dose could be reduced to 10 mg in the event of intolerability, and both treatments could be reintroduced if necessary, with a final follow-up at 24 weeks.

Study investigator Ana Maria Giménez-Arnau, MD, PhD, of the Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain, who presented the findings, noted that alitretinoin (Toctino) is an oral systemic retinoid approved in a few European countries, Canada, Israel, and South Korea for the treatment of severe CHE.

The mean age of the participants was 45 years, almost two thirds were women, and the majority (93%) were White; 90% of patients had been recruited in Europe. The median duration of CHE was 4 years.

At baseline, the median HECSI score was recorded as 79.5 in the delgocitinib arm and 80.0 in the alitretinoin arm. At 12 weeks, the least squares mean change in HECSI score from baseline was –67.6 in the delgocitinib arm and –51.5 in the alitretinoin arm, giving a significant difference of –16.1 between the two groups (P < .001).

Giménez-Arnau reported that delgocitinib also outperformed alitretinoin for all other endpoints assessed, including the following: ≥ 90% improvement in HECSI (HECSI-90), IGA-CHE treatment success (defined as a score of 0/1 indicating clear/almost clear skin), changes in Hand Eczema Symptom Diary (HESD) itch and HESD pain scores, area under the curve for HECSI-90, change in Dermatology Life Quality Index score — which were all assessed at 12 weeks — and change in HECSI from baseline to week 24.

There was “significant improvement in the reduction of the HECSI from the first week” of treatment, Giménez-Arnau said at the meeting. Notably, that the effect increased to 12 weeks and then was sustained. A similar pattern was seen for IGA-CHE treatment success and for HESD pain. This is important as “chronic hand eczema is really painful,” she said.

As for safety, 49.4% of patients in the delgocitinib arm vs 76.1% of patients in the alitretinoin arm experienced any type of adverse event (AE). Serious AEs occurred in 2% and 4.9% of patients in each group, respectively, with fewer AEs leading to trial drug discontinuation observed in the delgocitinib arm (1.2% vs 10.1%). The proportion of AEs “probably or possibly” related to the trial drug was 9.5% in the delgocitinib group vs 54.3% in the alitretinoin group.
 

Comparison With Dupilumab in Another Trial

Delgocitinib is no longer just an investigational medication, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said during a separate late-breaking presentation at the EADV 2024 meeting. “I think it’s big news because now we have an important topical option for our patients with chronic hand eczema.”

Armstrong presented a matched-adjusted indirect comparison (MAIC) of delgocitinib vs dupilumab for the treatment of moderate to severe atopic hand eczema, which she described as “the next best thing” to a head-to-head trial.

MAICs are where patient level data from one or more clinical trials evaluating drug “A” are compared with aggregate data from one or more clinical trials evaluating drug “B.” In this case, individual patient data from the DELTA 1 and DELTA 2 trials of delgocitinib were compared with published aggregate data from the phase 3 LIBERTY-AD-HAFT trial of dupilumab.

A total of 201 patients with atopic hand eczema in the DELTA 1 and DELTA 2 trials were matched to 133 patients in the LIBERTY-AD-HAFT trial. Of these, 128 had been treated with delgocitinib cream, 73 with a cream vehicle, 67 with subcutaneous dupilumab, and 66 with a subcutaneous placebo.

“We’re trying to compare as much as possible apples to apples here in terms of the etiology of hand eczema,” Armstrong said. She noted that after matching and weighting based on age, sex, race, and baseline HECSI score, baseline characteristics in the two groups of patients were similar. The mean age was about 35.8 years in the two active treatment arms and 33.4 years in the two placebo arms, and mean baseline HESCI scores were about 79-80.

The endpoints compared were ≥ 75% improvement in HECSI; HECSI-90, HECSI percentage improvement, and IGA-CHE in the DELTA 1 and DELTA 2 trials; or a Hand and Foot IGA score of 0/1.

“The key message to take away from this is that there were no statistically significant differences between topical delgocitinib twice daily vs subcutaneous injection of dupilumab by week 16 in the treatment of patients with atopic hand dermatitis,” Armstrong reported. Odds ratios varied between 1.1 and 1.3 for the various endpoints.

Menno de Rie, MD, PhD, professor of dermatology and immunology at Amsterdam University Medical Center in the Netherlands, who cochaired the session, said that “I appreciate very much that you took the effort to compare these totally different compounds and showed us the methodology that you did. It’s really very impressive.”
 

Topical, Systemic, or Both?

Armstrong was questioned on how to manage someone with atopic hand dermatitis who developed lesions elsewhere on the body.

“I would take a really individualized approach to this patient,” she responded. If the eczema has been limited to the hands and has been there for a while, then perhaps delgocitinib would be her choice, but if they developed lesions elsewhere on the body, then a systemic treatment such as dupilumab may be preferable.

“The good thing is that this study shows that you can offer the patient either of those options and really engage the patient in a shared decision-making process.”

And with regards to whether the two might possibly be used together, Armstrong acknowledged insurance coverage restrictions could be a limiting factor in the United States, but elsewhere — and from a scientific point of view — this could make sense.

“If we have a patient, for example, who has moderate to severe atopic dermatitis involving the body, but also very severe hand eczema as well, one may possibly consider a combination of a systemic medication that’s helpful for the extensive area of involvement on the body ... and now you have a topical therapy, delgocitinib, where you can use it locally, have very deep efficacy locally, to kind of help augment that disease phenotype in that patient population.”

The studies were funded by Leo Pharma. Chovatiya, Giménez-Arnau, and Armstrong acknowledged ties to LEO Pharma, among other pharmaceutical companies.

A version of this article first appeared on Medscape.com.

The Janus kinase inhibitor delgocitinib may be a better or comparable choice for treating hand eczema than some more established therapies, suggested the results of two separate studies presented during the late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

In the 24-week, phase 3 DELTA FORCE trial, topical delgocitinib was compared head to head with oral alitretinoin for managing chronic hand eczema (CHE). Results showed that greater improvements from baseline to week 12 in Hand Eczema Severity Index (HECSI) scores could be achieved with delgocitinib cream than with alitretinoin capsules.

And in another analysis, which involved patients with the atopic subtype of CHE only, the application of topical delgocitinib was found to be as good as treatment with subcutaneous dupilumab (Dupixent) at improving both HECSI scores and the Investigator Global Assessment for CHE response (IGA-CHE).
 

Potentially a ‘Highly Impactful’ Therapy

“Chronic hand eczema is a common yet burdensome skin condition that poses a considerable challenge for dermatologists. Diversity in morphologic presentation and clinical etiology has been a key limitation for the development of a safe, targeted, one-size-fits-all therapeutic approach,” Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University of Medicine and Science, and the founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, said in an interview.

“These data show that delgocitinib cream is poised to be a novel and highly impactful topical therapy for the treatment of CHE,” said Chovatiya.

DELTA FORCE showed that the efficacy and safety of delgocitinib cream was “superior to alitretinoin, the only approved oral option for CHE,” he said. And the other study, a comparative analysis, showed that delgocitinib’s efficacy was “comparable to the biologic dupilumab specifically for the treatment of atopic hand eczema,” said Chovatiya, one of the authors of that study. He was not an author of the DELTA FORCE study.
 

DELTA FORCE

While it remains an investigational drug in the United States, where it is under Food and Drug Administration review for CHE, delgocitinib cream (Anzupgo) was recently approved by the European Commission for use in adults with moderate to severe hand eczema who do not respond to or who are unable to use topical corticosteroids. Approval was based on data from two phase 3 studies , DELTA 1 and DELTA 2, which compared delgocitinib cream against a cream vehicle, as well as an open-label, long-term extension study, DELTA 3.

In the DELTA FORCE study, 513 adults with severe CHE (IGA-CHE score of 4) were recruited at 102 clinical centers in Europe and North America and randomly allocated to topical treatment with delgocitinib cream, 20 mg/g applied twice daily, or alitretinoin capsules, 30 mg once daily. Treatment with delgocitinib was for 16 weeks, and treatment with alitretinoin was for 12 weeks. The latter’s dose could be reduced to 10 mg in the event of intolerability, and both treatments could be reintroduced if necessary, with a final follow-up at 24 weeks.

Study investigator Ana Maria Giménez-Arnau, MD, PhD, of the Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain, who presented the findings, noted that alitretinoin (Toctino) is an oral systemic retinoid approved in a few European countries, Canada, Israel, and South Korea for the treatment of severe CHE.

The mean age of the participants was 45 years, almost two thirds were women, and the majority (93%) were White; 90% of patients had been recruited in Europe. The median duration of CHE was 4 years.

At baseline, the median HECSI score was recorded as 79.5 in the delgocitinib arm and 80.0 in the alitretinoin arm. At 12 weeks, the least squares mean change in HECSI score from baseline was –67.6 in the delgocitinib arm and –51.5 in the alitretinoin arm, giving a significant difference of –16.1 between the two groups (P < .001).

Giménez-Arnau reported that delgocitinib also outperformed alitretinoin for all other endpoints assessed, including the following: ≥ 90% improvement in HECSI (HECSI-90), IGA-CHE treatment success (defined as a score of 0/1 indicating clear/almost clear skin), changes in Hand Eczema Symptom Diary (HESD) itch and HESD pain scores, area under the curve for HECSI-90, change in Dermatology Life Quality Index score — which were all assessed at 12 weeks — and change in HECSI from baseline to week 24.

There was “significant improvement in the reduction of the HECSI from the first week” of treatment, Giménez-Arnau said at the meeting. Notably, that the effect increased to 12 weeks and then was sustained. A similar pattern was seen for IGA-CHE treatment success and for HESD pain. This is important as “chronic hand eczema is really painful,” she said.

As for safety, 49.4% of patients in the delgocitinib arm vs 76.1% of patients in the alitretinoin arm experienced any type of adverse event (AE). Serious AEs occurred in 2% and 4.9% of patients in each group, respectively, with fewer AEs leading to trial drug discontinuation observed in the delgocitinib arm (1.2% vs 10.1%). The proportion of AEs “probably or possibly” related to the trial drug was 9.5% in the delgocitinib group vs 54.3% in the alitretinoin group.
 

Comparison With Dupilumab in Another Trial

Delgocitinib is no longer just an investigational medication, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said during a separate late-breaking presentation at the EADV 2024 meeting. “I think it’s big news because now we have an important topical option for our patients with chronic hand eczema.”

Armstrong presented a matched-adjusted indirect comparison (MAIC) of delgocitinib vs dupilumab for the treatment of moderate to severe atopic hand eczema, which she described as “the next best thing” to a head-to-head trial.

MAICs are where patient level data from one or more clinical trials evaluating drug “A” are compared with aggregate data from one or more clinical trials evaluating drug “B.” In this case, individual patient data from the DELTA 1 and DELTA 2 trials of delgocitinib were compared with published aggregate data from the phase 3 LIBERTY-AD-HAFT trial of dupilumab.

A total of 201 patients with atopic hand eczema in the DELTA 1 and DELTA 2 trials were matched to 133 patients in the LIBERTY-AD-HAFT trial. Of these, 128 had been treated with delgocitinib cream, 73 with a cream vehicle, 67 with subcutaneous dupilumab, and 66 with a subcutaneous placebo.

“We’re trying to compare as much as possible apples to apples here in terms of the etiology of hand eczema,” Armstrong said. She noted that after matching and weighting based on age, sex, race, and baseline HECSI score, baseline characteristics in the two groups of patients were similar. The mean age was about 35.8 years in the two active treatment arms and 33.4 years in the two placebo arms, and mean baseline HESCI scores were about 79-80.

The endpoints compared were ≥ 75% improvement in HECSI; HECSI-90, HECSI percentage improvement, and IGA-CHE in the DELTA 1 and DELTA 2 trials; or a Hand and Foot IGA score of 0/1.

“The key message to take away from this is that there were no statistically significant differences between topical delgocitinib twice daily vs subcutaneous injection of dupilumab by week 16 in the treatment of patients with atopic hand dermatitis,” Armstrong reported. Odds ratios varied between 1.1 and 1.3 for the various endpoints.

Menno de Rie, MD, PhD, professor of dermatology and immunology at Amsterdam University Medical Center in the Netherlands, who cochaired the session, said that “I appreciate very much that you took the effort to compare these totally different compounds and showed us the methodology that you did. It’s really very impressive.”
 

Topical, Systemic, or Both?

Armstrong was questioned on how to manage someone with atopic hand dermatitis who developed lesions elsewhere on the body.

“I would take a really individualized approach to this patient,” she responded. If the eczema has been limited to the hands and has been there for a while, then perhaps delgocitinib would be her choice, but if they developed lesions elsewhere on the body, then a systemic treatment such as dupilumab may be preferable.

“The good thing is that this study shows that you can offer the patient either of those options and really engage the patient in a shared decision-making process.”

And with regards to whether the two might possibly be used together, Armstrong acknowledged insurance coverage restrictions could be a limiting factor in the United States, but elsewhere — and from a scientific point of view — this could make sense.

“If we have a patient, for example, who has moderate to severe atopic dermatitis involving the body, but also very severe hand eczema as well, one may possibly consider a combination of a systemic medication that’s helpful for the extensive area of involvement on the body ... and now you have a topical therapy, delgocitinib, where you can use it locally, have very deep efficacy locally, to kind of help augment that disease phenotype in that patient population.”

The studies were funded by Leo Pharma. Chovatiya, Giménez-Arnau, and Armstrong acknowledged ties to LEO Pharma, among other pharmaceutical companies.

A version of this article first appeared on Medscape.com.

The Janus kinase inhibitor delgocitinib may be a better or comparable choice for treating hand eczema than some more established therapies, suggested the results of two separate studies presented during the late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

In the 24-week, phase 3 DELTA FORCE trial, topical delgocitinib was compared head to head with oral alitretinoin for managing chronic hand eczema (CHE). Results showed that greater improvements from baseline to week 12 in Hand Eczema Severity Index (HECSI) scores could be achieved with delgocitinib cream than with alitretinoin capsules.

And in another analysis, which involved patients with the atopic subtype of CHE only, the application of topical delgocitinib was found to be as good as treatment with subcutaneous dupilumab (Dupixent) at improving both HECSI scores and the Investigator Global Assessment for CHE response (IGA-CHE).
 

Potentially a ‘Highly Impactful’ Therapy

“Chronic hand eczema is a common yet burdensome skin condition that poses a considerable challenge for dermatologists. Diversity in morphologic presentation and clinical etiology has been a key limitation for the development of a safe, targeted, one-size-fits-all therapeutic approach,” Raj Chovatiya, MD, PhD, clinical associate professor at Chicago Medical School, Rosalind Franklin University of Medicine and Science, and the founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, said in an interview.

“These data show that delgocitinib cream is poised to be a novel and highly impactful topical therapy for the treatment of CHE,” said Chovatiya.

DELTA FORCE showed that the efficacy and safety of delgocitinib cream was “superior to alitretinoin, the only approved oral option for CHE,” he said. And the other study, a comparative analysis, showed that delgocitinib’s efficacy was “comparable to the biologic dupilumab specifically for the treatment of atopic hand eczema,” said Chovatiya, one of the authors of that study. He was not an author of the DELTA FORCE study.
 

DELTA FORCE

While it remains an investigational drug in the United States, where it is under Food and Drug Administration review for CHE, delgocitinib cream (Anzupgo) was recently approved by the European Commission for use in adults with moderate to severe hand eczema who do not respond to or who are unable to use topical corticosteroids. Approval was based on data from two phase 3 studies , DELTA 1 and DELTA 2, which compared delgocitinib cream against a cream vehicle, as well as an open-label, long-term extension study, DELTA 3.

In the DELTA FORCE study, 513 adults with severe CHE (IGA-CHE score of 4) were recruited at 102 clinical centers in Europe and North America and randomly allocated to topical treatment with delgocitinib cream, 20 mg/g applied twice daily, or alitretinoin capsules, 30 mg once daily. Treatment with delgocitinib was for 16 weeks, and treatment with alitretinoin was for 12 weeks. The latter’s dose could be reduced to 10 mg in the event of intolerability, and both treatments could be reintroduced if necessary, with a final follow-up at 24 weeks.

Study investigator Ana Maria Giménez-Arnau, MD, PhD, of the Hospital del Mar Research Institute, Pompeu Fabra University, Barcelona, Spain, who presented the findings, noted that alitretinoin (Toctino) is an oral systemic retinoid approved in a few European countries, Canada, Israel, and South Korea for the treatment of severe CHE.

The mean age of the participants was 45 years, almost two thirds were women, and the majority (93%) were White; 90% of patients had been recruited in Europe. The median duration of CHE was 4 years.

At baseline, the median HECSI score was recorded as 79.5 in the delgocitinib arm and 80.0 in the alitretinoin arm. At 12 weeks, the least squares mean change in HECSI score from baseline was –67.6 in the delgocitinib arm and –51.5 in the alitretinoin arm, giving a significant difference of –16.1 between the two groups (P < .001).

Giménez-Arnau reported that delgocitinib also outperformed alitretinoin for all other endpoints assessed, including the following: ≥ 90% improvement in HECSI (HECSI-90), IGA-CHE treatment success (defined as a score of 0/1 indicating clear/almost clear skin), changes in Hand Eczema Symptom Diary (HESD) itch and HESD pain scores, area under the curve for HECSI-90, change in Dermatology Life Quality Index score — which were all assessed at 12 weeks — and change in HECSI from baseline to week 24.

There was “significant improvement in the reduction of the HECSI from the first week” of treatment, Giménez-Arnau said at the meeting. Notably, that the effect increased to 12 weeks and then was sustained. A similar pattern was seen for IGA-CHE treatment success and for HESD pain. This is important as “chronic hand eczema is really painful,” she said.

As for safety, 49.4% of patients in the delgocitinib arm vs 76.1% of patients in the alitretinoin arm experienced any type of adverse event (AE). Serious AEs occurred in 2% and 4.9% of patients in each group, respectively, with fewer AEs leading to trial drug discontinuation observed in the delgocitinib arm (1.2% vs 10.1%). The proportion of AEs “probably or possibly” related to the trial drug was 9.5% in the delgocitinib group vs 54.3% in the alitretinoin group.
 

Comparison With Dupilumab in Another Trial

Delgocitinib is no longer just an investigational medication, April W. Armstrong, MD, MPH, professor and chief of dermatology, University of California, Los Angeles, said during a separate late-breaking presentation at the EADV 2024 meeting. “I think it’s big news because now we have an important topical option for our patients with chronic hand eczema.”

Armstrong presented a matched-adjusted indirect comparison (MAIC) of delgocitinib vs dupilumab for the treatment of moderate to severe atopic hand eczema, which she described as “the next best thing” to a head-to-head trial.

MAICs are where patient level data from one or more clinical trials evaluating drug “A” are compared with aggregate data from one or more clinical trials evaluating drug “B.” In this case, individual patient data from the DELTA 1 and DELTA 2 trials of delgocitinib were compared with published aggregate data from the phase 3 LIBERTY-AD-HAFT trial of dupilumab.

A total of 201 patients with atopic hand eczema in the DELTA 1 and DELTA 2 trials were matched to 133 patients in the LIBERTY-AD-HAFT trial. Of these, 128 had been treated with delgocitinib cream, 73 with a cream vehicle, 67 with subcutaneous dupilumab, and 66 with a subcutaneous placebo.

“We’re trying to compare as much as possible apples to apples here in terms of the etiology of hand eczema,” Armstrong said. She noted that after matching and weighting based on age, sex, race, and baseline HECSI score, baseline characteristics in the two groups of patients were similar. The mean age was about 35.8 years in the two active treatment arms and 33.4 years in the two placebo arms, and mean baseline HESCI scores were about 79-80.

The endpoints compared were ≥ 75% improvement in HECSI; HECSI-90, HECSI percentage improvement, and IGA-CHE in the DELTA 1 and DELTA 2 trials; or a Hand and Foot IGA score of 0/1.

“The key message to take away from this is that there were no statistically significant differences between topical delgocitinib twice daily vs subcutaneous injection of dupilumab by week 16 in the treatment of patients with atopic hand dermatitis,” Armstrong reported. Odds ratios varied between 1.1 and 1.3 for the various endpoints.

Menno de Rie, MD, PhD, professor of dermatology and immunology at Amsterdam University Medical Center in the Netherlands, who cochaired the session, said that “I appreciate very much that you took the effort to compare these totally different compounds and showed us the methodology that you did. It’s really very impressive.”
 

Topical, Systemic, or Both?

Armstrong was questioned on how to manage someone with atopic hand dermatitis who developed lesions elsewhere on the body.

“I would take a really individualized approach to this patient,” she responded. If the eczema has been limited to the hands and has been there for a while, then perhaps delgocitinib would be her choice, but if they developed lesions elsewhere on the body, then a systemic treatment such as dupilumab may be preferable.

“The good thing is that this study shows that you can offer the patient either of those options and really engage the patient in a shared decision-making process.”

And with regards to whether the two might possibly be used together, Armstrong acknowledged insurance coverage restrictions could be a limiting factor in the United States, but elsewhere — and from a scientific point of view — this could make sense.

“If we have a patient, for example, who has moderate to severe atopic dermatitis involving the body, but also very severe hand eczema as well, one may possibly consider a combination of a systemic medication that’s helpful for the extensive area of involvement on the body ... and now you have a topical therapy, delgocitinib, where you can use it locally, have very deep efficacy locally, to kind of help augment that disease phenotype in that patient population.”

The studies were funded by Leo Pharma. Chovatiya, Giménez-Arnau, and Armstrong acknowledged ties to LEO Pharma, among other pharmaceutical companies.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – The addition of bezlotoxumab to fecal microbiota transplantation (FMT) does not provide any clear added benefit in patients with inflammatory bowel disease (IBD) and recurrent Clostridioides difficile infection (rCDI), according to a randomized controlled trial.

“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.

Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).

Brigham and Women&#039;s Hospital

Common and Deadly

CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.

Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.

FMT has been shown to be safe and effective in patients with IBD and rCDI.

Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.

However, there is only limited data on the value of combining these two strategies.

Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.

They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.

Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.

A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).

Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.

With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34). 

Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).

While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.

Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.

FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.

“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.

“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – The addition of bezlotoxumab to fecal microbiota transplantation (FMT) does not provide any clear added benefit in patients with inflammatory bowel disease (IBD) and recurrent Clostridioides difficile infection (rCDI), according to a randomized controlled trial.

“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.

Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).

Brigham and Women&#039;s Hospital

Common and Deadly

CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.

Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.

FMT has been shown to be safe and effective in patients with IBD and rCDI.

Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.

However, there is only limited data on the value of combining these two strategies.

Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.

They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.

Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.

A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).

Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.

With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34). 

Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).

While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.

Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.

FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.

“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.

“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.

A version of this article first appeared on Medscape.com.

PHILADELPHIA – The addition of bezlotoxumab to fecal microbiota transplantation (FMT) does not provide any clear added benefit in patients with inflammatory bowel disease (IBD) and recurrent Clostridioides difficile infection (rCDI), according to a randomized controlled trial.

“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.

Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).

Brigham and Women&#039;s Hospital

Common and Deadly

CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.

Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.

FMT has been shown to be safe and effective in patients with IBD and rCDI.

Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.

However, there is only limited data on the value of combining these two strategies.

Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.

They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.

Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.

A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).

Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.

With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34). 

Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).

While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.

Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.

FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.

“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.

“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.

A version of this article first appeared on Medscape.com.