MDedge Dermatology

To the Editor:

Although biologics provide major therapeutic benefits for dermatologic conditions, they also come with a substantial cost, making them among the most expensive medications available. Medicare and Medicaid spending on biologics for dermatologic conditions increased by 320% from 2012 to 2018, reaching a staggering $10.6 billion in 2018 alone.¹ Biosimilars show promise in reducing health care spending for dermatologic conditions; however, their utilization has been limited due to multiple factors, including delayed market entry from patent thickets, exclusionary formulary contracts, and prescriber skepticism regarding their safety and efficacy.² For instance, a national survey of 1201 US physicians in specialties that are high prescribers of biologics reported that 55% doubted the safety and appropriateness of biosimilars.³

US Food and Drug Administration approval of biosimilars for adalimumab and etanercept offers the potential to reduce health care spending for dermatologic conditions. However, this cost reduction is dependent on utilization rates among dermatologists. In this national cross-sectional review of Medicare data, we predicted the impact of these biosimilars on dermatologic Medicare costs and demonstrated how differing utilization rates among dermatologists can influence potential savings.

To model 2023 utilization and cost reduction from biosimilars, we analyzed Medicare Part D data from 2020 on existing biosimilars, including granulocyte colony–stimulating factors, erythropoiesis-stimulating agents, and tumor necrosis factor α inhibitors.⁴ Methods in line with a 2021 report from the US Department of Health and Human Services⁵ as well as those of Yazdany et al⁶ were used. For each class, we calculated the 2020 distribution of biosimilar and originator drug claims as well as biosimilar cost reduction per 30-day claim. We utilized 2018-2021 annual growth rates for branded adalimumab and etanercept to estimate 30-day claims for 2023 and the cost of these branded agents in the absence of biosimilars. The hypothetical 2023 cost reduction from adalimumab and etanercept biosimilars was estimated by assuming 2020 biosimilar utilization rates and mean cost reduction per claim. This study utilized publicly available or aggregate summary data (not attributable to specific patients) and did not qualify as human subject research; therefore, institutional review board approval was not required.

In 2020, biosimilar utilization proportions ranged from 6.4% (tumor necrosis factor α inhibitors) to 82.7% (granulocyte colony–stimulating factors), with a mean across all classes of 35.7%. On average, the cost per 30-day claim of biosimilars was 66.8% of originator agents (Table 1). In 2021, we identified 57,868 30-day claims for branded adalimumab and etanercept submitted by dermatologists. From 2018 to 2021, 30-day branded adalimumab claims increased by 1.27% annually (cost + 10.62% annually), while claims for branded etanercept decreased by 13.0% annually (cost + 5.68% annually). Assuming these trends, the cost of branded adalimumab and etanercept was estimated to be $539 million in 2023. Applying the aforementioned 35.7% utilization, the introduction of biosimilars in dermatology would yield a cost reduction of approximately $118 million (21.9%). A high utilization rate (82.7%) of biosimilars among dermatologists would increase cost savings to $199 million (36.9%)(Table 2).

We found that the extent of savings from biosimilars was dependent on the utilization rates among dermatologists, with the highest utilization rate almost doubling the total savings of average utilization rates. Given the impact of high utilization and the wide variation observed, understanding the factors that have influenced uptake of biosimilars is important to increasing utilization as these medications become integrated into dermatology. For instance, limited uptake of infliximab initially may have been influenced by concerns about efficacy and increased adverse events.^8,9 In contrast, the high utilization of filgrastim biosimilars (82.7%) may be attributed to its longevity in the market and familiarity to prescribers, as filgrastim was the first biosimilar to be approved in the United States.¹⁰

Promoting reasonable utilization of biosimilars may require prescriber education on their safety and approval processes, which could foster increased utilization and reduce skepticism.⁴ Under the Biologics Price Competition and Innovation Act, the US Food and Drug Administration approves biosimilars only when they exhibit “high similarity” and show no “clinically meaningful differences” compared to the reference biologic, with no added safety risks or reduced efficacy.¹¹ Moreover, a 2023 systematic review of 17 studies found no major difference in efficacy and safety between biosimilars and originators of etanercept, infliximab, and other biologics.¹² Understanding these findings may reassure dermatologists and patients about the reliability and safety of biosimilars.

A limitation of our study is that it solely assesses Medicare data and estimates derived from existing (separate) biologic classes. It also does not account for potential expenditure shifts to newer biologic agents (eg, IL-12/17/23 inhibitors) or changes in manufacturer behavior or promotions. Nevertheless, it indicates notable financial savings from new biosimilar agents in dermatology; along with their compelling efficacy and safety profiles, this could represent a substantial benefit to patients and the health care system.

To the Editor:

Although biologics provide major therapeutic benefits for dermatologic conditions, they also come with a substantial cost, making them among the most expensive medications available. Medicare and Medicaid spending on biologics for dermatologic conditions increased by 320% from 2012 to 2018, reaching a staggering $10.6 billion in 2018 alone.¹ Biosimilars show promise in reducing health care spending for dermatologic conditions; however, their utilization has been limited due to multiple factors, including delayed market entry from patent thickets, exclusionary formulary contracts, and prescriber skepticism regarding their safety and efficacy.² For instance, a national survey of 1201 US physicians in specialties that are high prescribers of biologics reported that 55% doubted the safety and appropriateness of biosimilars.³

US Food and Drug Administration approval of biosimilars for adalimumab and etanercept offers the potential to reduce health care spending for dermatologic conditions. However, this cost reduction is dependent on utilization rates among dermatologists. In this national cross-sectional review of Medicare data, we predicted the impact of these biosimilars on dermatologic Medicare costs and demonstrated how differing utilization rates among dermatologists can influence potential savings.

To model 2023 utilization and cost reduction from biosimilars, we analyzed Medicare Part D data from 2020 on existing biosimilars, including granulocyte colony–stimulating factors, erythropoiesis-stimulating agents, and tumor necrosis factor α inhibitors.⁴ Methods in line with a 2021 report from the US Department of Health and Human Services⁵ as well as those of Yazdany et al⁶ were used. For each class, we calculated the 2020 distribution of biosimilar and originator drug claims as well as biosimilar cost reduction per 30-day claim. We utilized 2018-2021 annual growth rates for branded adalimumab and etanercept to estimate 30-day claims for 2023 and the cost of these branded agents in the absence of biosimilars. The hypothetical 2023 cost reduction from adalimumab and etanercept biosimilars was estimated by assuming 2020 biosimilar utilization rates and mean cost reduction per claim. This study utilized publicly available or aggregate summary data (not attributable to specific patients) and did not qualify as human subject research; therefore, institutional review board approval was not required.

In 2020, biosimilar utilization proportions ranged from 6.4% (tumor necrosis factor α inhibitors) to 82.7% (granulocyte colony–stimulating factors), with a mean across all classes of 35.7%. On average, the cost per 30-day claim of biosimilars was 66.8% of originator agents (Table 1). In 2021, we identified 57,868 30-day claims for branded adalimumab and etanercept submitted by dermatologists. From 2018 to 2021, 30-day branded adalimumab claims increased by 1.27% annually (cost + 10.62% annually), while claims for branded etanercept decreased by 13.0% annually (cost + 5.68% annually). Assuming these trends, the cost of branded adalimumab and etanercept was estimated to be $539 million in 2023. Applying the aforementioned 35.7% utilization, the introduction of biosimilars in dermatology would yield a cost reduction of approximately $118 million (21.9%). A high utilization rate (82.7%) of biosimilars among dermatologists would increase cost savings to $199 million (36.9%)(Table 2).

We found that the extent of savings from biosimilars was dependent on the utilization rates among dermatologists, with the highest utilization rate almost doubling the total savings of average utilization rates. Given the impact of high utilization and the wide variation observed, understanding the factors that have influenced uptake of biosimilars is important to increasing utilization as these medications become integrated into dermatology. For instance, limited uptake of infliximab initially may have been influenced by concerns about efficacy and increased adverse events.^8,9 In contrast, the high utilization of filgrastim biosimilars (82.7%) may be attributed to its longevity in the market and familiarity to prescribers, as filgrastim was the first biosimilar to be approved in the United States.¹⁰

Promoting reasonable utilization of biosimilars may require prescriber education on their safety and approval processes, which could foster increased utilization and reduce skepticism.⁴ Under the Biologics Price Competition and Innovation Act, the US Food and Drug Administration approves biosimilars only when they exhibit “high similarity” and show no “clinically meaningful differences” compared to the reference biologic, with no added safety risks or reduced efficacy.¹¹ Moreover, a 2023 systematic review of 17 studies found no major difference in efficacy and safety between biosimilars and originators of etanercept, infliximab, and other biologics.¹² Understanding these findings may reassure dermatologists and patients about the reliability and safety of biosimilars.

A limitation of our study is that it solely assesses Medicare data and estimates derived from existing (separate) biologic classes. It also does not account for potential expenditure shifts to newer biologic agents (eg, IL-12/17/23 inhibitors) or changes in manufacturer behavior or promotions. Nevertheless, it indicates notable financial savings from new biosimilar agents in dermatology; along with their compelling efficacy and safety profiles, this could represent a substantial benefit to patients and the health care system.

To the Editor:

Although biologics provide major therapeutic benefits for dermatologic conditions, they also come with a substantial cost, making them among the most expensive medications available. Medicare and Medicaid spending on biologics for dermatologic conditions increased by 320% from 2012 to 2018, reaching a staggering $10.6 billion in 2018 alone.¹ Biosimilars show promise in reducing health care spending for dermatologic conditions; however, their utilization has been limited due to multiple factors, including delayed market entry from patent thickets, exclusionary formulary contracts, and prescriber skepticism regarding their safety and efficacy.² For instance, a national survey of 1201 US physicians in specialties that are high prescribers of biologics reported that 55% doubted the safety and appropriateness of biosimilars.³

US Food and Drug Administration approval of biosimilars for adalimumab and etanercept offers the potential to reduce health care spending for dermatologic conditions. However, this cost reduction is dependent on utilization rates among dermatologists. In this national cross-sectional review of Medicare data, we predicted the impact of these biosimilars on dermatologic Medicare costs and demonstrated how differing utilization rates among dermatologists can influence potential savings.

To model 2023 utilization and cost reduction from biosimilars, we analyzed Medicare Part D data from 2020 on existing biosimilars, including granulocyte colony–stimulating factors, erythropoiesis-stimulating agents, and tumor necrosis factor α inhibitors.⁴ Methods in line with a 2021 report from the US Department of Health and Human Services⁵ as well as those of Yazdany et al⁶ were used. For each class, we calculated the 2020 distribution of biosimilar and originator drug claims as well as biosimilar cost reduction per 30-day claim. We utilized 2018-2021 annual growth rates for branded adalimumab and etanercept to estimate 30-day claims for 2023 and the cost of these branded agents in the absence of biosimilars. The hypothetical 2023 cost reduction from adalimumab and etanercept biosimilars was estimated by assuming 2020 biosimilar utilization rates and mean cost reduction per claim. This study utilized publicly available or aggregate summary data (not attributable to specific patients) and did not qualify as human subject research; therefore, institutional review board approval was not required.

In 2020, biosimilar utilization proportions ranged from 6.4% (tumor necrosis factor α inhibitors) to 82.7% (granulocyte colony–stimulating factors), with a mean across all classes of 35.7%. On average, the cost per 30-day claim of biosimilars was 66.8% of originator agents (Table 1). In 2021, we identified 57,868 30-day claims for branded adalimumab and etanercept submitted by dermatologists. From 2018 to 2021, 30-day branded adalimumab claims increased by 1.27% annually (cost + 10.62% annually), while claims for branded etanercept decreased by 13.0% annually (cost + 5.68% annually). Assuming these trends, the cost of branded adalimumab and etanercept was estimated to be $539 million in 2023. Applying the aforementioned 35.7% utilization, the introduction of biosimilars in dermatology would yield a cost reduction of approximately $118 million (21.9%). A high utilization rate (82.7%) of biosimilars among dermatologists would increase cost savings to $199 million (36.9%)(Table 2).

We found that the extent of savings from biosimilars was dependent on the utilization rates among dermatologists, with the highest utilization rate almost doubling the total savings of average utilization rates. Given the impact of high utilization and the wide variation observed, understanding the factors that have influenced uptake of biosimilars is important to increasing utilization as these medications become integrated into dermatology. For instance, limited uptake of infliximab initially may have been influenced by concerns about efficacy and increased adverse events.^8,9 In contrast, the high utilization of filgrastim biosimilars (82.7%) may be attributed to its longevity in the market and familiarity to prescribers, as filgrastim was the first biosimilar to be approved in the United States.¹⁰

Promoting reasonable utilization of biosimilars may require prescriber education on their safety and approval processes, which could foster increased utilization and reduce skepticism.⁴ Under the Biologics Price Competition and Innovation Act, the US Food and Drug Administration approves biosimilars only when they exhibit “high similarity” and show no “clinically meaningful differences” compared to the reference biologic, with no added safety risks or reduced efficacy.¹¹ Moreover, a 2023 systematic review of 17 studies found no major difference in efficacy and safety between biosimilars and originators of etanercept, infliximab, and other biologics.¹² Understanding these findings may reassure dermatologists and patients about the reliability and safety of biosimilars.

A limitation of our study is that it solely assesses Medicare data and estimates derived from existing (separate) biologic classes. It also does not account for potential expenditure shifts to newer biologic agents (eg, IL-12/17/23 inhibitors) or changes in manufacturer behavior or promotions. Nevertheless, it indicates notable financial savings from new biosimilar agents in dermatology; along with their compelling efficacy and safety profiles, this could represent a substantial benefit to patients and the health care system.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

To the Editor:

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome—a severe cutaneous adverse drug reaction—is characterized by a cutaneous rash and systemic upset in the form of various internal organ and hematologic disturbances. This delayed and idiosyncratic syndrome went by several names, including anticonvulsant hypersensitivity syndrome, before Bocquet et al¹ proposed the term DRESS syndrome.

Phenytoin, a hydantoin derivative used in neurology, was implicated in 41% of cases of DRESS syndrome in a study of 100 patients conducted in southern India.^2,3 While DRESS syndrome is a newer name, the clinical picture of DRESS secondary to phenytoin use remains similar in that it manifests with a morbilliform rash and systemic upset. We sought to describe the clinical and laboratory characteristics of phenytoin-induced DRESS syndrome in this case series.

The analysis included 23 patients with DRESS syndrome secondary to phenytoin use who presented to a tertiary care institution in North India between July 2021 and December 2022, satisfied the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria,⁴ and achieved a DRESS diagnostic score of more than 1. The mean age of the patients was 44 years (range, 14–74 years). There was a slight female predominance with a male to female ratio of 0.9:1. More than half of the patients (52.2% [12/23]) presented directly to the dermatology outpatient department; the remaining patients were referred from other departments (47.8% [11/23]). Patients primarily were receiving phenytoin for neurologic indications. Specific reasons included antiseizure prophylaxis following a traffic accident (34.8% [8/23]); epilepsy (26.1% [6/23]); and neoplastic (17.4% [4/23]), vascular (17.4% [4/23]), and infectious (4.3% [1/23]) causes. The mean latency period from drug intake to symptom onset was 29 days (range, 6–62 days), and the mean illness duration was 9 days (range, 1–45 days).

The majority of patients experienced pruritus (91.3% [21/23]) and fever (74.0% [17/23]), and all initially had a rash. Maculopapular morphology was seen in all patients. Erythema multiforme–like (17.4% [4/23]), erythrodermic (17.4% [4/23]), and vesicular (13.0% [3/23]) rashes also were documented (Figure 1). The trunk (100% [23/23]) and extremities (95.7% [22/23]) were involved most often, followed by the palms and soles (56.5% [13/23]). The mean total body surface area affected was 73.65%. Only 7 patients (30.4%) had mucosal ­involvement; nonhemorrhagic cheilitis was the most common manifestation.

THE DIAGNOSIS: Ectopic (Accessory) Breast Tissue

Ectopic (accessory) breast tissue (EBT) is a phenomenon caused by failed regression of one or more components of the embryonic mammary ridges— paired ectodermal thickenings that eventually develop into definitive breast tissue including the nipples, areolae, and parenchyma. Ectopic breast tissue is more common in women than men and is believed to be sporadic, although an autosomal-dominant inheritance mechanism with incomplete penetrance has been proposed for some cases.¹ The reported incidence of EBT varies greatly among racial and ethnic groups but is most common in individuals of Asian descent. The incidence across all types of EBT is estimated at 0.25% to 6% in the general population.²

Observed clinical variations of EBT range from simple polythelia (additional nipple[s] without associated parenchyma) to complete polymastia (organized and differentiated accessory breasts). Some types of EBT are rarer than others: One report of gynecologic cancer screenings in 1660 patients found polymastia and polythelia incidences of 0.12% and 5.48%, respectively.³ Of the symptomatic variations, isolated parenchymal EBT without a nipple or areolar complex is the most common and may manifest clinically as unilateral or bilateral tender, mildly erythematous nodules or masses often located in the axillae. Ectopic breast tissue generally is observed along the milk line, a developmental regional designation corresponding to the embryologic mammary ridge and extending linearly from the anterior axilla to the inguinal fold on both sides of the body; however, there have been rare reports of EBT manifesting in areas outside the milk line, such as the face, neck, back, vulva, and extremities.^2,3

Given that the underlying elements of EBT usually are hormone responsive (as with normal breast tissue), the initial symptom onset and subsequent manifestation frequently coincide with pubertal milestones, pregnancy, or lactation. Furthermore, some patients with EBT may experience symptom fluctuations in concordance with monthly menstrual phases. Many cases of EBT are selflimited and resolve within weeks to months after the end of a pregnancy or lactation, but some cases may persist. Continued observation and follow-up are advisable in all patients, as EBT symptoms often recur and the tissue is susceptible to the same disease processes that affect normal breasts, the most concerning of which is malignancy.⁴ Although the true incidence is limited by available data, primary ectopic breast malignancy has been estimated to account for 0.3% to 3.8% of diagnosed breast malignancies.² Cases of malignancy arising from EBT often are of higher grade and poorer prognosis, a finding that may be attributable to diagnostic delays caused by oversight or misdiagnosis of EBT rather than inherent differences in the biologic profile of the tumors.^2,4 Patients with a documented history of EBT may benefit from having their routine breast cancer screenings expanded to include areas with EBT foci.

Potential misdiagnoses for EBT include subcutaneous lipoma, axillary lymphadenopathy, abscess, hidradenitis suppurativa, or malignancy. Features that are suggestive of EBT include symptom association with hormone fluctuations (eg, menstrual phases), absence of fever, and lactescent rather than purulent drainage. Among reported EBT cases, spontaneous lactation rarely is described and, if present, often is associated with a history of prior trauma (eg, core needle biopsy or local abscess formation).⁵ This trauma creates an aberrant connection known as a milk fistula between the underlying parenchyma and the skin surface. Interestingly, our patient denied any history of axillary trauma, but she was noted to be lactating from an apparent milk fistula rather than an organized secretory duct system.

Though a patient history and clinical examination may be sufficient to diagnose EBT cases that are more physically apparent and well correlated with hormone fluctuations, many cases require additional diagnostic studies for confirmation. Of the tools available, ultrasonography generally is considered first-line due to its noninvasive nature, low cost, minimal risk, and high diagnostic value.² Ultrasonography quickly differentiates between abscesses and cystlike processes, which may appear as discrete areas of decreased echogenicity, and breast tissue, which manifests with fibroglandular tissue and lobules of fat.^2,6 Additionally, ultrasonography may demonstrate the secretion of milk through ducts or fistulae, if present. Should examination with ultrasonography prove inconclusive, follow-up studies using conventional radiographic mammography or magnetic resonance imaging may be warranted. Biopsy of EBT foci generally is not indicated unless first-line noninvasive studies fail to yield a conclusive diagnosis; however, biopsy also may be warranted if initial imaging is suggestive of malignancy arising from EBT.²

Management of EBT generally is conservative, and symptoms often resolve without intervention.⁴ Symptomatic relief may be achieved through techniques such as application of warm/cold compresses, avoidance of mechanical stimulation, and use of over-the-counter pain medicine. In cases that are persistent, frequently recurrent, or associated with severe symptoms or that cause considerable cosmetic impact, management with surgical excision and/or liposuction may be warranted.⁷ In our patient, the symptoms were not bothersome enough to warrant surgical intervention, so she was managed conservatively and did not return for follow-up.

THE DIAGNOSIS: Ectopic (Accessory) Breast Tissue

Ectopic (accessory) breast tissue (EBT) is a phenomenon caused by failed regression of one or more components of the embryonic mammary ridges— paired ectodermal thickenings that eventually develop into definitive breast tissue including the nipples, areolae, and parenchyma. Ectopic breast tissue is more common in women than men and is believed to be sporadic, although an autosomal-dominant inheritance mechanism with incomplete penetrance has been proposed for some cases.¹ The reported incidence of EBT varies greatly among racial and ethnic groups but is most common in individuals of Asian descent. The incidence across all types of EBT is estimated at 0.25% to 6% in the general population.²

Observed clinical variations of EBT range from simple polythelia (additional nipple[s] without associated parenchyma) to complete polymastia (organized and differentiated accessory breasts). Some types of EBT are rarer than others: One report of gynecologic cancer screenings in 1660 patients found polymastia and polythelia incidences of 0.12% and 5.48%, respectively.³ Of the symptomatic variations, isolated parenchymal EBT without a nipple or areolar complex is the most common and may manifest clinically as unilateral or bilateral tender, mildly erythematous nodules or masses often located in the axillae. Ectopic breast tissue generally is observed along the milk line, a developmental regional designation corresponding to the embryologic mammary ridge and extending linearly from the anterior axilla to the inguinal fold on both sides of the body; however, there have been rare reports of EBT manifesting in areas outside the milk line, such as the face, neck, back, vulva, and extremities.^2,3

Given that the underlying elements of EBT usually are hormone responsive (as with normal breast tissue), the initial symptom onset and subsequent manifestation frequently coincide with pubertal milestones, pregnancy, or lactation. Furthermore, some patients with EBT may experience symptom fluctuations in concordance with monthly menstrual phases. Many cases of EBT are selflimited and resolve within weeks to months after the end of a pregnancy or lactation, but some cases may persist. Continued observation and follow-up are advisable in all patients, as EBT symptoms often recur and the tissue is susceptible to the same disease processes that affect normal breasts, the most concerning of which is malignancy.⁴ Although the true incidence is limited by available data, primary ectopic breast malignancy has been estimated to account for 0.3% to 3.8% of diagnosed breast malignancies.² Cases of malignancy arising from EBT often are of higher grade and poorer prognosis, a finding that may be attributable to diagnostic delays caused by oversight or misdiagnosis of EBT rather than inherent differences in the biologic profile of the tumors.^2,4 Patients with a documented history of EBT may benefit from having their routine breast cancer screenings expanded to include areas with EBT foci.

Potential misdiagnoses for EBT include subcutaneous lipoma, axillary lymphadenopathy, abscess, hidradenitis suppurativa, or malignancy. Features that are suggestive of EBT include symptom association with hormone fluctuations (eg, menstrual phases), absence of fever, and lactescent rather than purulent drainage. Among reported EBT cases, spontaneous lactation rarely is described and, if present, often is associated with a history of prior trauma (eg, core needle biopsy or local abscess formation).⁵ This trauma creates an aberrant connection known as a milk fistula between the underlying parenchyma and the skin surface. Interestingly, our patient denied any history of axillary trauma, but she was noted to be lactating from an apparent milk fistula rather than an organized secretory duct system.

Though a patient history and clinical examination may be sufficient to diagnose EBT cases that are more physically apparent and well correlated with hormone fluctuations, many cases require additional diagnostic studies for confirmation. Of the tools available, ultrasonography generally is considered first-line due to its noninvasive nature, low cost, minimal risk, and high diagnostic value.² Ultrasonography quickly differentiates between abscesses and cystlike processes, which may appear as discrete areas of decreased echogenicity, and breast tissue, which manifests with fibroglandular tissue and lobules of fat.^2,6 Additionally, ultrasonography may demonstrate the secretion of milk through ducts or fistulae, if present. Should examination with ultrasonography prove inconclusive, follow-up studies using conventional radiographic mammography or magnetic resonance imaging may be warranted. Biopsy of EBT foci generally is not indicated unless first-line noninvasive studies fail to yield a conclusive diagnosis; however, biopsy also may be warranted if initial imaging is suggestive of malignancy arising from EBT.²

Management of EBT generally is conservative, and symptoms often resolve without intervention.⁴ Symptomatic relief may be achieved through techniques such as application of warm/cold compresses, avoidance of mechanical stimulation, and use of over-the-counter pain medicine. In cases that are persistent, frequently recurrent, or associated with severe symptoms or that cause considerable cosmetic impact, management with surgical excision and/or liposuction may be warranted.⁷ In our patient, the symptoms were not bothersome enough to warrant surgical intervention, so she was managed conservatively and did not return for follow-up.

THE DIAGNOSIS: Ectopic (Accessory) Breast Tissue

Ectopic (accessory) breast tissue (EBT) is a phenomenon caused by failed regression of one or more components of the embryonic mammary ridges— paired ectodermal thickenings that eventually develop into definitive breast tissue including the nipples, areolae, and parenchyma. Ectopic breast tissue is more common in women than men and is believed to be sporadic, although an autosomal-dominant inheritance mechanism with incomplete penetrance has been proposed for some cases.¹ The reported incidence of EBT varies greatly among racial and ethnic groups but is most common in individuals of Asian descent. The incidence across all types of EBT is estimated at 0.25% to 6% in the general population.²

Observed clinical variations of EBT range from simple polythelia (additional nipple[s] without associated parenchyma) to complete polymastia (organized and differentiated accessory breasts). Some types of EBT are rarer than others: One report of gynecologic cancer screenings in 1660 patients found polymastia and polythelia incidences of 0.12% and 5.48%, respectively.³ Of the symptomatic variations, isolated parenchymal EBT without a nipple or areolar complex is the most common and may manifest clinically as unilateral or bilateral tender, mildly erythematous nodules or masses often located in the axillae. Ectopic breast tissue generally is observed along the milk line, a developmental regional designation corresponding to the embryologic mammary ridge and extending linearly from the anterior axilla to the inguinal fold on both sides of the body; however, there have been rare reports of EBT manifesting in areas outside the milk line, such as the face, neck, back, vulva, and extremities.^2,3

Given that the underlying elements of EBT usually are hormone responsive (as with normal breast tissue), the initial symptom onset and subsequent manifestation frequently coincide with pubertal milestones, pregnancy, or lactation. Furthermore, some patients with EBT may experience symptom fluctuations in concordance with monthly menstrual phases. Many cases of EBT are selflimited and resolve within weeks to months after the end of a pregnancy or lactation, but some cases may persist. Continued observation and follow-up are advisable in all patients, as EBT symptoms often recur and the tissue is susceptible to the same disease processes that affect normal breasts, the most concerning of which is malignancy.⁴ Although the true incidence is limited by available data, primary ectopic breast malignancy has been estimated to account for 0.3% to 3.8% of diagnosed breast malignancies.² Cases of malignancy arising from EBT often are of higher grade and poorer prognosis, a finding that may be attributable to diagnostic delays caused by oversight or misdiagnosis of EBT rather than inherent differences in the biologic profile of the tumors.^2,4 Patients with a documented history of EBT may benefit from having their routine breast cancer screenings expanded to include areas with EBT foci.

Potential misdiagnoses for EBT include subcutaneous lipoma, axillary lymphadenopathy, abscess, hidradenitis suppurativa, or malignancy. Features that are suggestive of EBT include symptom association with hormone fluctuations (eg, menstrual phases), absence of fever, and lactescent rather than purulent drainage. Among reported EBT cases, spontaneous lactation rarely is described and, if present, often is associated with a history of prior trauma (eg, core needle biopsy or local abscess formation).⁵ This trauma creates an aberrant connection known as a milk fistula between the underlying parenchyma and the skin surface. Interestingly, our patient denied any history of axillary trauma, but she was noted to be lactating from an apparent milk fistula rather than an organized secretory duct system.

Though a patient history and clinical examination may be sufficient to diagnose EBT cases that are more physically apparent and well correlated with hormone fluctuations, many cases require additional diagnostic studies for confirmation. Of the tools available, ultrasonography generally is considered first-line due to its noninvasive nature, low cost, minimal risk, and high diagnostic value.² Ultrasonography quickly differentiates between abscesses and cystlike processes, which may appear as discrete areas of decreased echogenicity, and breast tissue, which manifests with fibroglandular tissue and lobules of fat.^2,6 Additionally, ultrasonography may demonstrate the secretion of milk through ducts or fistulae, if present. Should examination with ultrasonography prove inconclusive, follow-up studies using conventional radiographic mammography or magnetic resonance imaging may be warranted. Biopsy of EBT foci generally is not indicated unless first-line noninvasive studies fail to yield a conclusive diagnosis; however, biopsy also may be warranted if initial imaging is suggestive of malignancy arising from EBT.²

Management of EBT generally is conservative, and symptoms often resolve without intervention.⁴ Symptomatic relief may be achieved through techniques such as application of warm/cold compresses, avoidance of mechanical stimulation, and use of over-the-counter pain medicine. In cases that are persistent, frequently recurrent, or associated with severe symptoms or that cause considerable cosmetic impact, management with surgical excision and/or liposuction may be warranted.⁷ In our patient, the symptoms were not bothersome enough to warrant surgical intervention, so she was managed conservatively and did not return for follow-up.

This transcript has been edited for clarity. 

What do we do if we don’t like patients? We take the Hippocratic Oath as young students in Glasgow. We do that just before our graduation ceremony; we hold our hands up and repeat the Hippocratic Oath: “First, do no harm,” and so on.

What happens if we intensely dislike a patient? Is it possible to offer them the very best care? I was thinking back over a long career. I’ve been a cancer doctor for 40 years and I quite like saying that.

I can only think genuinely over a couple of times in which I’ve acted reflexively when a patient has done something awful. The couple of times it happened, it was just terrible racist comments to junior doctors who were with me. Extraordinarily dreadful things such as, “I don’t want to be touched by ...” or something of that sort.

Without really thinking about it, you react as a normal citizen and say, “That’s absolutely awful. Apologize immediately or leave the consultation room, and never ever come back again.” 

I remember that it happened once in Glasgow and once when I was a young professor in Birmingham, and it’s just an automatic gut reaction. The patient got a fright, and I immediately apologized and groveled around. In that relationship, we hold all the power, don’t we? Rather than being gentle about it, I was genuinely angry because of these ridiculous comments. 

Otherwise, I think most of the doctor-patient relationships are predicated on nonromantic love. I think patients want us to love them as one would a son, mother, father, or daughter, because if we do, then we will do better for them and we’ll pull out all the stops. “Placebo” means “I will please.” I think in the vast majority of cases, at least in our National Health Service (NHS), patients come with trust and a sense of wanting to build that relationship. That may be changing, but not for me. 

What about putting the boot on the other foot? What if the patients don’t like us rather than vice versa? As part of our accreditation appraisal process, from time to time we have to take patient surveys as to whether the patients felt that, after they had been seen in a consultation, they were treated with dignity, the quality of information given was appropriate, and they were treated with kindness. 

It’s an excellent exercise. Without bragging about it, patients objectively, according to these measures, appreciate the service that I give. It’s like getting five-star reviews on Trustpilot, or whatever these things are, that allow you to review car salesmen and so on. I have always had five-star reviews across the board. 

That, again, I thought was just a feature of that relationship, of patients wanting to please. These are patients who had been treated, who were in the outpatient department, who were in the midst of battle. Still, the scores are very high. I speak to my colleagues and that’s not uniformly the case. Patients actually do use these feedback forms, I think in a positive rather than negative way, reflecting back on the way that they were treated.

It has caused some of my colleagues to think quite hard about their personal style and approach to patients. That sense of feedback is important. 

What about losing trust? If that’s at the heart of everything that we do, then what would be an objective measure of losing trust? Again, in our healthcare system, it has been exceedingly unusual for a patient to request a second opinion. Now, that’s changing. The government is trying to change it. Leaders of the NHS are trying to change it so that patients feel assured that they can seek second opinions.

Again, in all the years I’ve been a cancer doctor, it has been incredibly infrequent that somebody has sought a second opinion after I’ve said something. That may be a measure of trust. Again, I’ve lived through an NHS in which seeking second opinions was something of a rarity. 

I’d be really interested to see what you think. In your own sphere of healthcare practice, is it possible for us to look after patients that we don’t like, or should we be honest and say, “I don’t like you. Our relationship has broken down. I want you to be seen by a colleague,” or “I want you to be nursed by somebody else”?

Has that happened? Is that something that you think is common or may become more common? What about when trust breaks down the other way? Can you think of instances in which the relationship, for whatever reason, just didn’t work and the patient had to move on because of that loss of trust and what underpinned it? I’d be really interested to know. 

I seek to be informed rather than the other way around. Can we truly look after patients that we don’t like or can we rise above it as Hippocrates might have done? 

Thanks for listening, as always. For the time being, over and out.

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

What do we do if we don’t like patients? We take the Hippocratic Oath as young students in Glasgow. We do that just before our graduation ceremony; we hold our hands up and repeat the Hippocratic Oath: “First, do no harm,” and so on.

What happens if we intensely dislike a patient? Is it possible to offer them the very best care? I was thinking back over a long career. I’ve been a cancer doctor for 40 years and I quite like saying that.

I can only think genuinely over a couple of times in which I’ve acted reflexively when a patient has done something awful. The couple of times it happened, it was just terrible racist comments to junior doctors who were with me. Extraordinarily dreadful things such as, “I don’t want to be touched by ...” or something of that sort.

Without really thinking about it, you react as a normal citizen and say, “That’s absolutely awful. Apologize immediately or leave the consultation room, and never ever come back again.” 

I remember that it happened once in Glasgow and once when I was a young professor in Birmingham, and it’s just an automatic gut reaction. The patient got a fright, and I immediately apologized and groveled around. In that relationship, we hold all the power, don’t we? Rather than being gentle about it, I was genuinely angry because of these ridiculous comments. 

Otherwise, I think most of the doctor-patient relationships are predicated on nonromantic love. I think patients want us to love them as one would a son, mother, father, or daughter, because if we do, then we will do better for them and we’ll pull out all the stops. “Placebo” means “I will please.” I think in the vast majority of cases, at least in our National Health Service (NHS), patients come with trust and a sense of wanting to build that relationship. That may be changing, but not for me. 

What about putting the boot on the other foot? What if the patients don’t like us rather than vice versa? As part of our accreditation appraisal process, from time to time we have to take patient surveys as to whether the patients felt that, after they had been seen in a consultation, they were treated with dignity, the quality of information given was appropriate, and they were treated with kindness. 

It’s an excellent exercise. Without bragging about it, patients objectively, according to these measures, appreciate the service that I give. It’s like getting five-star reviews on Trustpilot, or whatever these things are, that allow you to review car salesmen and so on. I have always had five-star reviews across the board. 

That, again, I thought was just a feature of that relationship, of patients wanting to please. These are patients who had been treated, who were in the outpatient department, who were in the midst of battle. Still, the scores are very high. I speak to my colleagues and that’s not uniformly the case. Patients actually do use these feedback forms, I think in a positive rather than negative way, reflecting back on the way that they were treated.

It has caused some of my colleagues to think quite hard about their personal style and approach to patients. That sense of feedback is important. 

What about losing trust? If that’s at the heart of everything that we do, then what would be an objective measure of losing trust? Again, in our healthcare system, it has been exceedingly unusual for a patient to request a second opinion. Now, that’s changing. The government is trying to change it. Leaders of the NHS are trying to change it so that patients feel assured that they can seek second opinions.

Again, in all the years I’ve been a cancer doctor, it has been incredibly infrequent that somebody has sought a second opinion after I’ve said something. That may be a measure of trust. Again, I’ve lived through an NHS in which seeking second opinions was something of a rarity. 

I’d be really interested to see what you think. In your own sphere of healthcare practice, is it possible for us to look after patients that we don’t like, or should we be honest and say, “I don’t like you. Our relationship has broken down. I want you to be seen by a colleague,” or “I want you to be nursed by somebody else”?

Has that happened? Is that something that you think is common or may become more common? What about when trust breaks down the other way? Can you think of instances in which the relationship, for whatever reason, just didn’t work and the patient had to move on because of that loss of trust and what underpinned it? I’d be really interested to know. 

I seek to be informed rather than the other way around. Can we truly look after patients that we don’t like or can we rise above it as Hippocrates might have done? 

Thanks for listening, as always. For the time being, over and out.

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

What do we do if we don’t like patients? We take the Hippocratic Oath as young students in Glasgow. We do that just before our graduation ceremony; we hold our hands up and repeat the Hippocratic Oath: “First, do no harm,” and so on.

What happens if we intensely dislike a patient? Is it possible to offer them the very best care? I was thinking back over a long career. I’ve been a cancer doctor for 40 years and I quite like saying that.

I can only think genuinely over a couple of times in which I’ve acted reflexively when a patient has done something awful. The couple of times it happened, it was just terrible racist comments to junior doctors who were with me. Extraordinarily dreadful things such as, “I don’t want to be touched by ...” or something of that sort.

Without really thinking about it, you react as a normal citizen and say, “That’s absolutely awful. Apologize immediately or leave the consultation room, and never ever come back again.” 

I remember that it happened once in Glasgow and once when I was a young professor in Birmingham, and it’s just an automatic gut reaction. The patient got a fright, and I immediately apologized and groveled around. In that relationship, we hold all the power, don’t we? Rather than being gentle about it, I was genuinely angry because of these ridiculous comments. 

Otherwise, I think most of the doctor-patient relationships are predicated on nonromantic love. I think patients want us to love them as one would a son, mother, father, or daughter, because if we do, then we will do better for them and we’ll pull out all the stops. “Placebo” means “I will please.” I think in the vast majority of cases, at least in our National Health Service (NHS), patients come with trust and a sense of wanting to build that relationship. That may be changing, but not for me. 

What about putting the boot on the other foot? What if the patients don’t like us rather than vice versa? As part of our accreditation appraisal process, from time to time we have to take patient surveys as to whether the patients felt that, after they had been seen in a consultation, they were treated with dignity, the quality of information given was appropriate, and they were treated with kindness. 

It’s an excellent exercise. Without bragging about it, patients objectively, according to these measures, appreciate the service that I give. It’s like getting five-star reviews on Trustpilot, or whatever these things are, that allow you to review car salesmen and so on. I have always had five-star reviews across the board. 

That, again, I thought was just a feature of that relationship, of patients wanting to please. These are patients who had been treated, who were in the outpatient department, who were in the midst of battle. Still, the scores are very high. I speak to my colleagues and that’s not uniformly the case. Patients actually do use these feedback forms, I think in a positive rather than negative way, reflecting back on the way that they were treated.

It has caused some of my colleagues to think quite hard about their personal style and approach to patients. That sense of feedback is important. 

What about losing trust? If that’s at the heart of everything that we do, then what would be an objective measure of losing trust? Again, in our healthcare system, it has been exceedingly unusual for a patient to request a second opinion. Now, that’s changing. The government is trying to change it. Leaders of the NHS are trying to change it so that patients feel assured that they can seek second opinions.

Again, in all the years I’ve been a cancer doctor, it has been incredibly infrequent that somebody has sought a second opinion after I’ve said something. That may be a measure of trust. Again, I’ve lived through an NHS in which seeking second opinions was something of a rarity. 

I’d be really interested to see what you think. In your own sphere of healthcare practice, is it possible for us to look after patients that we don’t like, or should we be honest and say, “I don’t like you. Our relationship has broken down. I want you to be seen by a colleague,” or “I want you to be nursed by somebody else”?

Has that happened? Is that something that you think is common or may become more common? What about when trust breaks down the other way? Can you think of instances in which the relationship, for whatever reason, just didn’t work and the patient had to move on because of that loss of trust and what underpinned it? I’d be really interested to know. 

I seek to be informed rather than the other way around. Can we truly look after patients that we don’t like or can we rise above it as Hippocrates might have done? 

Thanks for listening, as always. For the time being, over and out.

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

A new serum containing 2-mercaptonicotinoyl glycine (Melasyl) as its main ingredient was at least as good as, if not better than, cysteamine 5% cream in treating facial melasma in a randomized controlled study presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

“Melasyl is a new potent melanogenesis inhibitor that exhibits a unique mode of action while preserving melanocyte integrity,” Mukta Sachdev, MD, head of the Department of Dermatology at Manipal Hospital in Bangalore, India, said at a late-breaking news session.

Both the serum and the cysteamine cream lightened participants’ skin to a similar extent, according to the modified Melasma Area and Severity Index (mMASI), with respective reductions of 4.19 and 3.81 points over a period of 4 months from baseline values of 11.15 and 10.93. 

Toa55/iStock/Getty Images

The mMASI score ranges from 0 to 24, with the lowest score representing the least and the highest score the most severe hyperpigmentation of the skin.

But the serum performed better than the cream by another measure. Judged by investigators blinded to which preparation study participants had been using, there was a significantly higher reduction in the Investigator Global Assessment (IGA) score from baseline among those treated with the serum than among those treated with the cream (−51.85% vs −39.06%; P = .0163). 

Moreover, after 4 months of treatment, there were significantly more participants with clear or almost clear skin with the serum than with the cream (17.46% vs 7.81%; P = .0163), Sachdev reported.

Other skin parameters relative to melasma, such as the brightness of skin tone and evenness of the improvement, improved more in the participants using the serum vs cream, she said. 

With “no side effects, no local skin reactions,” Sachdev said, “quality of life improved significantly and similarly, and almost all subjects in both groups were very satisfied with their treatment options.”
 

Active Ingredients

Margarida Gonçalo, MD, PhD, professor of dermatology at the University of Coimbra, in Portugal, who co-chaired the late-breaking news session, commented: “It’s really nice to have new products to treat such a devastating disease.”

Session co-chair, Lidia Rudnicka, MD, head of the Department of Dermatology, Medical University of Warsaw, in Poland, and president of the Polish Dermatological Society, wanted to know more about the active ingredients of the serum and the study’s design. 

Sachdev replied that the serum also contains other ingredients that provide “antioxidant protection” and moisturization. These include retinyl palmitate, which works on the dermal-epidermal junction, and hyaluronic acid, as well as “soothing agents,” such as the medicinal herb Centella asiatica, she said.
 

Study Design

Conducted at a single center in India, the study involved 127 adults aged 20-50 years with melasma. For inclusion, the participants had to have facial epidermal or mixed melasma (phototypes III-V) for more than 1 year; those with dermal melasma were excluded. 

Participants were randomly allocated to receive either the serum, which was applied topically to the areas of interest twice a day in the morning and then at bedtime (n = 63), or cysteamine cream (n = 64), which was applied once a day in addition to a neutral moisturizer. Treatment was for 4 months, with an on-site visit every month. 

All participants were supplied with the same sunscreen/ultraviolet protector applied twice a day (once in the morning and again at midday) and a neutral hydrating cleanser that was used in the morning and evening. 
 

Practical Implications

Over 4 months, both products showed significant improvement in melasma without reaching a plateau, Sachdev reported, with the serum demonstrating superior efficacy and tolerability, as judged by the investigators. 

The study suggests that the serum is a promising non-hydroquinone treatment for melasma, she said. Hydroquinone-containing topical preparations are used to depigment the skin, but their long-term use can be limited for safety reasons. 

“When products like this demonstrate improvement, it is something for the dermatologist to think about because we now have newer ingredients, which are safer and well tolerated,” she continued, noting that there appeared to be no risk for exogenous ochronosis, which can occur with long-term application of hydroquinone.

“So, I think the armamentarium of non-hydroquinone products for the treatment of melasma is rapidly expanding, and there are studies now with clinically proven efficacy,” Sachdev concluded. 

The study was supported by L’Oréal France La Roche-Posay, which launched Melasyl in March 2024. Sachdev reported receipt of research support and honoraria from the company. Gonçalo and Rudnicka were not involved in the study and had no relevant conflicts of interest to report. 
 

A version of this article appeared on Medscape.com.

A new serum containing 2-mercaptonicotinoyl glycine (Melasyl) as its main ingredient was at least as good as, if not better than, cysteamine 5% cream in treating facial melasma in a randomized controlled study presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

“Melasyl is a new potent melanogenesis inhibitor that exhibits a unique mode of action while preserving melanocyte integrity,” Mukta Sachdev, MD, head of the Department of Dermatology at Manipal Hospital in Bangalore, India, said at a late-breaking news session.

Both the serum and the cysteamine cream lightened participants’ skin to a similar extent, according to the modified Melasma Area and Severity Index (mMASI), with respective reductions of 4.19 and 3.81 points over a period of 4 months from baseline values of 11.15 and 10.93. 

Toa55/iStock/Getty Images

The mMASI score ranges from 0 to 24, with the lowest score representing the least and the highest score the most severe hyperpigmentation of the skin.

But the serum performed better than the cream by another measure. Judged by investigators blinded to which preparation study participants had been using, there was a significantly higher reduction in the Investigator Global Assessment (IGA) score from baseline among those treated with the serum than among those treated with the cream (−51.85% vs −39.06%; P = .0163). 

Moreover, after 4 months of treatment, there were significantly more participants with clear or almost clear skin with the serum than with the cream (17.46% vs 7.81%; P = .0163), Sachdev reported.

Other skin parameters relative to melasma, such as the brightness of skin tone and evenness of the improvement, improved more in the participants using the serum vs cream, she said. 

With “no side effects, no local skin reactions,” Sachdev said, “quality of life improved significantly and similarly, and almost all subjects in both groups were very satisfied with their treatment options.”
 

Active Ingredients

Margarida Gonçalo, MD, PhD, professor of dermatology at the University of Coimbra, in Portugal, who co-chaired the late-breaking news session, commented: “It’s really nice to have new products to treat such a devastating disease.”

Session co-chair, Lidia Rudnicka, MD, head of the Department of Dermatology, Medical University of Warsaw, in Poland, and president of the Polish Dermatological Society, wanted to know more about the active ingredients of the serum and the study’s design. 

Sachdev replied that the serum also contains other ingredients that provide “antioxidant protection” and moisturization. These include retinyl palmitate, which works on the dermal-epidermal junction, and hyaluronic acid, as well as “soothing agents,” such as the medicinal herb Centella asiatica, she said.
 

Study Design

Conducted at a single center in India, the study involved 127 adults aged 20-50 years with melasma. For inclusion, the participants had to have facial epidermal or mixed melasma (phototypes III-V) for more than 1 year; those with dermal melasma were excluded. 

Participants were randomly allocated to receive either the serum, which was applied topically to the areas of interest twice a day in the morning and then at bedtime (n = 63), or cysteamine cream (n = 64), which was applied once a day in addition to a neutral moisturizer. Treatment was for 4 months, with an on-site visit every month. 

All participants were supplied with the same sunscreen/ultraviolet protector applied twice a day (once in the morning and again at midday) and a neutral hydrating cleanser that was used in the morning and evening. 
 

Practical Implications

Over 4 months, both products showed significant improvement in melasma without reaching a plateau, Sachdev reported, with the serum demonstrating superior efficacy and tolerability, as judged by the investigators. 

The study suggests that the serum is a promising non-hydroquinone treatment for melasma, she said. Hydroquinone-containing topical preparations are used to depigment the skin, but their long-term use can be limited for safety reasons. 

“When products like this demonstrate improvement, it is something for the dermatologist to think about because we now have newer ingredients, which are safer and well tolerated,” she continued, noting that there appeared to be no risk for exogenous ochronosis, which can occur with long-term application of hydroquinone.

“So, I think the armamentarium of non-hydroquinone products for the treatment of melasma is rapidly expanding, and there are studies now with clinically proven efficacy,” Sachdev concluded. 

The study was supported by L’Oréal France La Roche-Posay, which launched Melasyl in March 2024. Sachdev reported receipt of research support and honoraria from the company. Gonçalo and Rudnicka were not involved in the study and had no relevant conflicts of interest to report. 
 

A version of this article appeared on Medscape.com.

A new serum containing 2-mercaptonicotinoyl glycine (Melasyl) as its main ingredient was at least as good as, if not better than, cysteamine 5% cream in treating facial melasma in a randomized controlled study presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

“Melasyl is a new potent melanogenesis inhibitor that exhibits a unique mode of action while preserving melanocyte integrity,” Mukta Sachdev, MD, head of the Department of Dermatology at Manipal Hospital in Bangalore, India, said at a late-breaking news session.

Both the serum and the cysteamine cream lightened participants’ skin to a similar extent, according to the modified Melasma Area and Severity Index (mMASI), with respective reductions of 4.19 and 3.81 points over a period of 4 months from baseline values of 11.15 and 10.93. 

Toa55/iStock/Getty Images

The mMASI score ranges from 0 to 24, with the lowest score representing the least and the highest score the most severe hyperpigmentation of the skin.

But the serum performed better than the cream by another measure. Judged by investigators blinded to which preparation study participants had been using, there was a significantly higher reduction in the Investigator Global Assessment (IGA) score from baseline among those treated with the serum than among those treated with the cream (−51.85% vs −39.06%; P = .0163). 

Moreover, after 4 months of treatment, there were significantly more participants with clear or almost clear skin with the serum than with the cream (17.46% vs 7.81%; P = .0163), Sachdev reported.

Other skin parameters relative to melasma, such as the brightness of skin tone and evenness of the improvement, improved more in the participants using the serum vs cream, she said. 

With “no side effects, no local skin reactions,” Sachdev said, “quality of life improved significantly and similarly, and almost all subjects in both groups were very satisfied with their treatment options.”
 

Active Ingredients

Margarida Gonçalo, MD, PhD, professor of dermatology at the University of Coimbra, in Portugal, who co-chaired the late-breaking news session, commented: “It’s really nice to have new products to treat such a devastating disease.”

Session co-chair, Lidia Rudnicka, MD, head of the Department of Dermatology, Medical University of Warsaw, in Poland, and president of the Polish Dermatological Society, wanted to know more about the active ingredients of the serum and the study’s design. 

Sachdev replied that the serum also contains other ingredients that provide “antioxidant protection” and moisturization. These include retinyl palmitate, which works on the dermal-epidermal junction, and hyaluronic acid, as well as “soothing agents,” such as the medicinal herb Centella asiatica, she said.
 

Study Design

Conducted at a single center in India, the study involved 127 adults aged 20-50 years with melasma. For inclusion, the participants had to have facial epidermal or mixed melasma (phototypes III-V) for more than 1 year; those with dermal melasma were excluded. 

Participants were randomly allocated to receive either the serum, which was applied topically to the areas of interest twice a day in the morning and then at bedtime (n = 63), or cysteamine cream (n = 64), which was applied once a day in addition to a neutral moisturizer. Treatment was for 4 months, with an on-site visit every month. 

All participants were supplied with the same sunscreen/ultraviolet protector applied twice a day (once in the morning and again at midday) and a neutral hydrating cleanser that was used in the morning and evening. 
 

Practical Implications

Over 4 months, both products showed significant improvement in melasma without reaching a plateau, Sachdev reported, with the serum demonstrating superior efficacy and tolerability, as judged by the investigators. 

The study suggests that the serum is a promising non-hydroquinone treatment for melasma, she said. Hydroquinone-containing topical preparations are used to depigment the skin, but their long-term use can be limited for safety reasons. 

“When products like this demonstrate improvement, it is something for the dermatologist to think about because we now have newer ingredients, which are safer and well tolerated,” she continued, noting that there appeared to be no risk for exogenous ochronosis, which can occur with long-term application of hydroquinone.

“So, I think the armamentarium of non-hydroquinone products for the treatment of melasma is rapidly expanding, and there are studies now with clinically proven efficacy,” Sachdev concluded. 

The study was supported by L’Oréal France La Roche-Posay, which launched Melasyl in March 2024. Sachdev reported receipt of research support and honoraria from the company. Gonçalo and Rudnicka were not involved in the study and had no relevant conflicts of interest to report. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

The Fracture Risk Assessment Tool (FRAX), with bone mineral density, predicts the risk for major osteoporotic fractures and hip fractures in patients with cancer, but FRAX without bone mineral density slightly overestimates these risks, a new analysis found.

METHODOLOGY:

• Cancer-specific guidelines recommend using FRAX to assess fracture risk, but its applicability in patients with cancer remains unclear.
• This retrospective cohort study included 9877 patients with cancer (mean age, 67.1 years) and 45,875 matched control individuals without cancer (mean age, 66.2 years). All participants had dual-energy x-ray absorptiometry (DXA) scans.
• Researchers collected data on bone mineral density and fractures. The 10-year probabilities of major osteoporotic fractures and hip fractures were calculated using FRAX, and the observed 10-year probabilities of these fractures were compared with FRAX-derived probabilities.
• Compared with individuals without cancer, patients with cancer had a shorter mean follow-up duration (8.5 vs 7.6 years), a slightly higher mean body mass index, and a higher percentage of parental hip fractures (7.0% vs 8.2%); additionally, patients with cancer were more likely to have secondary causes of osteoporosis (10% vs 38.4%) and less likely to receive osteoporosis medication (9.9% vs 4.2%).

TAKEAWAY:

• Compared with individuals without cancer, patients with cancer had a significantly higher incidence rate of major fractures (12.9 vs 14.5 per 1000 person-years) and hip fractures (3.5 vs 4.2 per 1000 person-years).
• FRAX with bone mineral density exhibited excellent calibration for predicting major osteoporotic fractures (slope, 1.03) and hip fractures (0.97) in patients with cancer, regardless of the site of cancer diagnosis. FRAX without bone mineral density, however, underestimated the risk for both major (0.87) and hip fractures (0.72).
• In patients with cancer, FRAX with bone mineral density findings were associated with incident major osteoporotic fractures (hazard ratio [HR] per SD, 1.84) and hip fractures (HR per SD, 3.61).
• When models were adjusted for FRAX with bone mineral density, patients with cancer had an increased risk for both major osteoporotic fractures (HR, 1.17) and hip fractures (HR, 1.30). No difference was found in the risk for fracture between patients with and individuals without cancer when the models were adjusted for FRAX without bone mineral density, even when considering osteoporosis medication use.

IN PRACTICE:

“This retrospective cohort study demonstrates that individuals with cancer are at higher risk of fracture than individuals without cancer and that FRAX, particularly with BMD [bone mineral density], may accurately predict fracture risk in this population. These results, along with the known mortality risk of osteoporotic fractures among cancer survivors, further emphasize the clinical importance of closing the current osteoporosis care gap among cancer survivors,” the authors wrote.

SOURCE:

This study, led by Carrie Ye, MD, MPH, University of Alberta, Edmonton, Alberta, Canada, was published online in JAMA Oncology.

LIMITATIONS:

This study cohort included a selected group of cancer survivors who were referred for DXA scans and may not represent the general cancer population. The cohort consisted predominantly of women, limiting the generalizability to men with cancer. Given the heterogeneity of the population, the findings may not be applicable to all cancer subgroups. Information on cancer stage or the presence of bone metastases at the time of fracture risk assessment was lacking, which could have affected the findings.

DISCLOSURES:

This study was funded by the CancerCare Manitoba Foundation. Three authors reported having ties with various sources, including two who received grants from various organizations.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The Fracture Risk Assessment Tool (FRAX), with bone mineral density, predicts the risk for major osteoporotic fractures and hip fractures in patients with cancer, but FRAX without bone mineral density slightly overestimates these risks, a new analysis found.

METHODOLOGY:

• Cancer-specific guidelines recommend using FRAX to assess fracture risk, but its applicability in patients with cancer remains unclear.
• This retrospective cohort study included 9877 patients with cancer (mean age, 67.1 years) and 45,875 matched control individuals without cancer (mean age, 66.2 years). All participants had dual-energy x-ray absorptiometry (DXA) scans.
• Researchers collected data on bone mineral density and fractures. The 10-year probabilities of major osteoporotic fractures and hip fractures were calculated using FRAX, and the observed 10-year probabilities of these fractures were compared with FRAX-derived probabilities.
• Compared with individuals without cancer, patients with cancer had a shorter mean follow-up duration (8.5 vs 7.6 years), a slightly higher mean body mass index, and a higher percentage of parental hip fractures (7.0% vs 8.2%); additionally, patients with cancer were more likely to have secondary causes of osteoporosis (10% vs 38.4%) and less likely to receive osteoporosis medication (9.9% vs 4.2%).

TAKEAWAY:

• Compared with individuals without cancer, patients with cancer had a significantly higher incidence rate of major fractures (12.9 vs 14.5 per 1000 person-years) and hip fractures (3.5 vs 4.2 per 1000 person-years).
• FRAX with bone mineral density exhibited excellent calibration for predicting major osteoporotic fractures (slope, 1.03) and hip fractures (0.97) in patients with cancer, regardless of the site of cancer diagnosis. FRAX without bone mineral density, however, underestimated the risk for both major (0.87) and hip fractures (0.72).
• In patients with cancer, FRAX with bone mineral density findings were associated with incident major osteoporotic fractures (hazard ratio [HR] per SD, 1.84) and hip fractures (HR per SD, 3.61).
• When models were adjusted for FRAX with bone mineral density, patients with cancer had an increased risk for both major osteoporotic fractures (HR, 1.17) and hip fractures (HR, 1.30). No difference was found in the risk for fracture between patients with and individuals without cancer when the models were adjusted for FRAX without bone mineral density, even when considering osteoporosis medication use.

IN PRACTICE:

“This retrospective cohort study demonstrates that individuals with cancer are at higher risk of fracture than individuals without cancer and that FRAX, particularly with BMD [bone mineral density], may accurately predict fracture risk in this population. These results, along with the known mortality risk of osteoporotic fractures among cancer survivors, further emphasize the clinical importance of closing the current osteoporosis care gap among cancer survivors,” the authors wrote.

SOURCE:

This study, led by Carrie Ye, MD, MPH, University of Alberta, Edmonton, Alberta, Canada, was published online in JAMA Oncology.

LIMITATIONS:

This study cohort included a selected group of cancer survivors who were referred for DXA scans and may not represent the general cancer population. The cohort consisted predominantly of women, limiting the generalizability to men with cancer. Given the heterogeneity of the population, the findings may not be applicable to all cancer subgroups. Information on cancer stage or the presence of bone metastases at the time of fracture risk assessment was lacking, which could have affected the findings.

DISCLOSURES:

This study was funded by the CancerCare Manitoba Foundation. Three authors reported having ties with various sources, including two who received grants from various organizations.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The Fracture Risk Assessment Tool (FRAX), with bone mineral density, predicts the risk for major osteoporotic fractures and hip fractures in patients with cancer, but FRAX without bone mineral density slightly overestimates these risks, a new analysis found.

METHODOLOGY:

• Cancer-specific guidelines recommend using FRAX to assess fracture risk, but its applicability in patients with cancer remains unclear.
• This retrospective cohort study included 9877 patients with cancer (mean age, 67.1 years) and 45,875 matched control individuals without cancer (mean age, 66.2 years). All participants had dual-energy x-ray absorptiometry (DXA) scans.
• Researchers collected data on bone mineral density and fractures. The 10-year probabilities of major osteoporotic fractures and hip fractures were calculated using FRAX, and the observed 10-year probabilities of these fractures were compared with FRAX-derived probabilities.
• Compared with individuals without cancer, patients with cancer had a shorter mean follow-up duration (8.5 vs 7.6 years), a slightly higher mean body mass index, and a higher percentage of parental hip fractures (7.0% vs 8.2%); additionally, patients with cancer were more likely to have secondary causes of osteoporosis (10% vs 38.4%) and less likely to receive osteoporosis medication (9.9% vs 4.2%).

TAKEAWAY:

• Compared with individuals without cancer, patients with cancer had a significantly higher incidence rate of major fractures (12.9 vs 14.5 per 1000 person-years) and hip fractures (3.5 vs 4.2 per 1000 person-years).
• FRAX with bone mineral density exhibited excellent calibration for predicting major osteoporotic fractures (slope, 1.03) and hip fractures (0.97) in patients with cancer, regardless of the site of cancer diagnosis. FRAX without bone mineral density, however, underestimated the risk for both major (0.87) and hip fractures (0.72).
• In patients with cancer, FRAX with bone mineral density findings were associated with incident major osteoporotic fractures (hazard ratio [HR] per SD, 1.84) and hip fractures (HR per SD, 3.61).
• When models were adjusted for FRAX with bone mineral density, patients with cancer had an increased risk for both major osteoporotic fractures (HR, 1.17) and hip fractures (HR, 1.30). No difference was found in the risk for fracture between patients with and individuals without cancer when the models were adjusted for FRAX without bone mineral density, even when considering osteoporosis medication use.

IN PRACTICE:

“This retrospective cohort study demonstrates that individuals with cancer are at higher risk of fracture than individuals without cancer and that FRAX, particularly with BMD [bone mineral density], may accurately predict fracture risk in this population. These results, along with the known mortality risk of osteoporotic fractures among cancer survivors, further emphasize the clinical importance of closing the current osteoporosis care gap among cancer survivors,” the authors wrote.

SOURCE:

This study, led by Carrie Ye, MD, MPH, University of Alberta, Edmonton, Alberta, Canada, was published online in JAMA Oncology.

LIMITATIONS:

This study cohort included a selected group of cancer survivors who were referred for DXA scans and may not represent the general cancer population. The cohort consisted predominantly of women, limiting the generalizability to men with cancer. Given the heterogeneity of the population, the findings may not be applicable to all cancer subgroups. Information on cancer stage or the presence of bone metastases at the time of fracture risk assessment was lacking, which could have affected the findings.

DISCLOSURES:

This study was funded by the CancerCare Manitoba Foundation. Three authors reported having ties with various sources, including two who received grants from various organizations.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

AMSTERDAM — Prurigo nodularis (PN), an itchy, highly symptomatic disease that can cause severe impairments in quality of life, may gain a third therapy if promising data on povorcitinib presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress are further validated.

“We now have a pipeline of clinical studies in PN. Who would have even thought that a few years ago,” said Shawn Kwatra, MD, professor and chair, Department of Dermatology, University of Maryland School of Medicine, Baltimore. That is a remarkable turn of events for a difficult disease, he added.

Dr. Kwatra

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin (IL)–4 and IL-13, was the first treatment approved for PN by the Food and Drug Administration 2 years ago. Approval of nemolizumab, a monoclonal antibody that targets IL-31, a cytokine strongly implicated in the itch response, followed in August 2024. Povorcitinib, which targets Janus kinase 1 (JAK1), is on track to be the third.

New data on both nemolizumab and povorcitinib were presented in late breaking news sessions at EADV.

For povorcitinib, a JAK inhibitor, Dr. Kwatra presented extended phase 2 results through 40 weeks at a late-breaker session at the EADV meeting. They follow 16-week data from a randomized study presented earlier this year.

Of the 146 patients followed in the original 16-week randomized trial, which compared 15, 45, and 75 mg of oral povorcitinib once daily against placebo, 126 entered an extension in which all patients were treated with active therapy. In this single-blind phase, those who were responders at 16 weeks received 45 mg povorcitinib, and those who were nonresponders received 75 mg povorcitinib.

At 16 weeks, all doses were superior to placebo in achieving at least a 4-point reduction on the Itch Numerical Rating Scale (NRS4) and the Investigator Global Assessment (IGA) score 0 or 1 (clear or almost clear), as well as in a composite endpoint of both. However, even though the lowest dose of povorcitinib was active, there was a “very clear dose response” demonstrated in speed of response and proportion of responders, according to Dr. Kwatra.

On the 75-mg dose, the time to improvement was a median of 19 days, while the median times to improvement were 35 days on the 45-mg dose and 58 days on the 15-mg dose.

Among povorcitinib responders, 96% had met the NRS4 response at the time they entered the extension study. During the extension study, the proportion of responders who maintained this level of itch control hovered around 90% for the duration. The proportion was 89% at week 40.

The proportion of responders at 16 weeks achieving IGA 0/1, signifying clear or almost clear, was 93%. Again, the rate hovered around 90% for the full 40 weeks. At week 40, the proportion at this outcome was also 89%. The composite outcome among responders persisted at about 80% for most of the follow-up but fell to 63% at the last follow-up.

Among nonresponders who transitioned to 75 mg povorcitinib for the extension period, the NSR4 response rates climbed within 4 weeks to approximately 60% and reached 70% at week 40. For the endpoint of IGA 0/1, rates rose incrementally among the nonresponders over time, reaching 51% at week 40. The composite endpoint was reached at 40 weeks by 41% of nonresponders switched to 75 mg during the 24-week extension.

The results at 40 weeks were highly encouraging, according to Dr. Kwatra, who reported there were no surprises in regard to safety during the extension period. He reported some transient reductions in hemoglobin and infections that resolved, but there were no cardiac events or other more serious events that have been previously associated with JAK inhibitors during the 40-week study period.

When asked if there might be an advantage for povorcitinib relative to the monoclonal antibodies in regard to speed of onset, Dr. Kwatra said that there are no comparative data. Like previous experience with dupilumab, some patients responded rapidly with povorcitinib, but others took longer to achieve benefit.

This variability in response is consistent with the growing evidence that PN is a heterogeneous disease, according to Dr. Kwatra. With multiple up-regulated cytokines implicated in the pathogenesis of PN, he suggested that more treatment options would be useful. When it comes to the multiple molecular pathways involved in the pathogenesis of PN, he said, “patients can be at a different edge of a spectrum.”

In other evidence suggesting that more options are needed, another late-breaking news study at the 2024 EADV congress underlined the fact that PN is a chronic disease. Presented by Franz J. Legat, MD, professor of dermatology at the Medical University of Graz, Graz, Austria, the data involved a withdrawal evaluation nested in a long-term extension (LTE) of the OLYMPIA pivotal trials with nemolizumab.

After 52 weeks in the LTE, 34 patients entered the OLYMPIA DURABILITY study, in which they were randomized to withdrawal or to continue on nemolizumab on an every 4-week dosing schedule.

The relapse rate over 24 weeks was 16.7% (3 of 18 patients) in the continuous nemolizumab arm and 75% (12 of 16 patients) in the withdrawal arm. The median time to relapse was 112.5 days for those in the withdrawal arm and was not reached during follow-up in the nemolizumab arm.

Praising the patients who were willing to risk PN relapse by entering this randomized trial, Dr. Legat said that the study shows a relatively high risk for relapse within months of treatment withdrawal even after good PN control over a period of 52 weeks.

“These data clearly support continuous nemolizumab beyond 52 weeks,” he said.

Dr. Kwatra reported financial relationships with AbbVie, Arcutis, Biotherapeutics, Aslan, Celldex, Galderma, Genzada, Johnson & Johnson, Novartis, Pfizer, Regeneron, Sanofi, and Incyte, which is developing povorcitinib for PN. Dr. Legat reported financial relationships with Almirall, Celgene, Eli Lilly, Menlo Therapeutics, Novartis, Pfizer, Trevi, Vifor, and Galderma, which provided funding for the nemolizumab studies.

A version of this article appeared on Medscape.com.

AMSTERDAM — Prurigo nodularis (PN), an itchy, highly symptomatic disease that can cause severe impairments in quality of life, may gain a third therapy if promising data on povorcitinib presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress are further validated.

“We now have a pipeline of clinical studies in PN. Who would have even thought that a few years ago,” said Shawn Kwatra, MD, professor and chair, Department of Dermatology, University of Maryland School of Medicine, Baltimore. That is a remarkable turn of events for a difficult disease, he added.

Dr. Kwatra

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin (IL)–4 and IL-13, was the first treatment approved for PN by the Food and Drug Administration 2 years ago. Approval of nemolizumab, a monoclonal antibody that targets IL-31, a cytokine strongly implicated in the itch response, followed in August 2024. Povorcitinib, which targets Janus kinase 1 (JAK1), is on track to be the third.

New data on both nemolizumab and povorcitinib were presented in late breaking news sessions at EADV.

For povorcitinib, a JAK inhibitor, Dr. Kwatra presented extended phase 2 results through 40 weeks at a late-breaker session at the EADV meeting. They follow 16-week data from a randomized study presented earlier this year.

Of the 146 patients followed in the original 16-week randomized trial, which compared 15, 45, and 75 mg of oral povorcitinib once daily against placebo, 126 entered an extension in which all patients were treated with active therapy. In this single-blind phase, those who were responders at 16 weeks received 45 mg povorcitinib, and those who were nonresponders received 75 mg povorcitinib.

At 16 weeks, all doses were superior to placebo in achieving at least a 4-point reduction on the Itch Numerical Rating Scale (NRS4) and the Investigator Global Assessment (IGA) score 0 or 1 (clear or almost clear), as well as in a composite endpoint of both. However, even though the lowest dose of povorcitinib was active, there was a “very clear dose response” demonstrated in speed of response and proportion of responders, according to Dr. Kwatra.

On the 75-mg dose, the time to improvement was a median of 19 days, while the median times to improvement were 35 days on the 45-mg dose and 58 days on the 15-mg dose.

Among povorcitinib responders, 96% had met the NRS4 response at the time they entered the extension study. During the extension study, the proportion of responders who maintained this level of itch control hovered around 90% for the duration. The proportion was 89% at week 40.

The proportion of responders at 16 weeks achieving IGA 0/1, signifying clear or almost clear, was 93%. Again, the rate hovered around 90% for the full 40 weeks. At week 40, the proportion at this outcome was also 89%. The composite outcome among responders persisted at about 80% for most of the follow-up but fell to 63% at the last follow-up.

Among nonresponders who transitioned to 75 mg povorcitinib for the extension period, the NSR4 response rates climbed within 4 weeks to approximately 60% and reached 70% at week 40. For the endpoint of IGA 0/1, rates rose incrementally among the nonresponders over time, reaching 51% at week 40. The composite endpoint was reached at 40 weeks by 41% of nonresponders switched to 75 mg during the 24-week extension.

The results at 40 weeks were highly encouraging, according to Dr. Kwatra, who reported there were no surprises in regard to safety during the extension period. He reported some transient reductions in hemoglobin and infections that resolved, but there were no cardiac events or other more serious events that have been previously associated with JAK inhibitors during the 40-week study period.

When asked if there might be an advantage for povorcitinib relative to the monoclonal antibodies in regard to speed of onset, Dr. Kwatra said that there are no comparative data. Like previous experience with dupilumab, some patients responded rapidly with povorcitinib, but others took longer to achieve benefit.

This variability in response is consistent with the growing evidence that PN is a heterogeneous disease, according to Dr. Kwatra. With multiple up-regulated cytokines implicated in the pathogenesis of PN, he suggested that more treatment options would be useful. When it comes to the multiple molecular pathways involved in the pathogenesis of PN, he said, “patients can be at a different edge of a spectrum.”

In other evidence suggesting that more options are needed, another late-breaking news study at the 2024 EADV congress underlined the fact that PN is a chronic disease. Presented by Franz J. Legat, MD, professor of dermatology at the Medical University of Graz, Graz, Austria, the data involved a withdrawal evaluation nested in a long-term extension (LTE) of the OLYMPIA pivotal trials with nemolizumab.

After 52 weeks in the LTE, 34 patients entered the OLYMPIA DURABILITY study, in which they were randomized to withdrawal or to continue on nemolizumab on an every 4-week dosing schedule.

The relapse rate over 24 weeks was 16.7% (3 of 18 patients) in the continuous nemolizumab arm and 75% (12 of 16 patients) in the withdrawal arm. The median time to relapse was 112.5 days for those in the withdrawal arm and was not reached during follow-up in the nemolizumab arm.

Praising the patients who were willing to risk PN relapse by entering this randomized trial, Dr. Legat said that the study shows a relatively high risk for relapse within months of treatment withdrawal even after good PN control over a period of 52 weeks.

“These data clearly support continuous nemolizumab beyond 52 weeks,” he said.

Dr. Kwatra reported financial relationships with AbbVie, Arcutis, Biotherapeutics, Aslan, Celldex, Galderma, Genzada, Johnson & Johnson, Novartis, Pfizer, Regeneron, Sanofi, and Incyte, which is developing povorcitinib for PN. Dr. Legat reported financial relationships with Almirall, Celgene, Eli Lilly, Menlo Therapeutics, Novartis, Pfizer, Trevi, Vifor, and Galderma, which provided funding for the nemolizumab studies.

A version of this article appeared on Medscape.com.

AMSTERDAM — Prurigo nodularis (PN), an itchy, highly symptomatic disease that can cause severe impairments in quality of life, may gain a third therapy if promising data on povorcitinib presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress are further validated.

“We now have a pipeline of clinical studies in PN. Who would have even thought that a few years ago,” said Shawn Kwatra, MD, professor and chair, Department of Dermatology, University of Maryland School of Medicine, Baltimore. That is a remarkable turn of events for a difficult disease, he added.

Dr. Kwatra

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin (IL)–4 and IL-13, was the first treatment approved for PN by the Food and Drug Administration 2 years ago. Approval of nemolizumab, a monoclonal antibody that targets IL-31, a cytokine strongly implicated in the itch response, followed in August 2024. Povorcitinib, which targets Janus kinase 1 (JAK1), is on track to be the third.

New data on both nemolizumab and povorcitinib were presented in late breaking news sessions at EADV.

For povorcitinib, a JAK inhibitor, Dr. Kwatra presented extended phase 2 results through 40 weeks at a late-breaker session at the EADV meeting. They follow 16-week data from a randomized study presented earlier this year.

Of the 146 patients followed in the original 16-week randomized trial, which compared 15, 45, and 75 mg of oral povorcitinib once daily against placebo, 126 entered an extension in which all patients were treated with active therapy. In this single-blind phase, those who were responders at 16 weeks received 45 mg povorcitinib, and those who were nonresponders received 75 mg povorcitinib.

At 16 weeks, all doses were superior to placebo in achieving at least a 4-point reduction on the Itch Numerical Rating Scale (NRS4) and the Investigator Global Assessment (IGA) score 0 or 1 (clear or almost clear), as well as in a composite endpoint of both. However, even though the lowest dose of povorcitinib was active, there was a “very clear dose response” demonstrated in speed of response and proportion of responders, according to Dr. Kwatra.

On the 75-mg dose, the time to improvement was a median of 19 days, while the median times to improvement were 35 days on the 45-mg dose and 58 days on the 15-mg dose.

Among povorcitinib responders, 96% had met the NRS4 response at the time they entered the extension study. During the extension study, the proportion of responders who maintained this level of itch control hovered around 90% for the duration. The proportion was 89% at week 40.

The proportion of responders at 16 weeks achieving IGA 0/1, signifying clear or almost clear, was 93%. Again, the rate hovered around 90% for the full 40 weeks. At week 40, the proportion at this outcome was also 89%. The composite outcome among responders persisted at about 80% for most of the follow-up but fell to 63% at the last follow-up.

Among nonresponders who transitioned to 75 mg povorcitinib for the extension period, the NSR4 response rates climbed within 4 weeks to approximately 60% and reached 70% at week 40. For the endpoint of IGA 0/1, rates rose incrementally among the nonresponders over time, reaching 51% at week 40. The composite endpoint was reached at 40 weeks by 41% of nonresponders switched to 75 mg during the 24-week extension.

The results at 40 weeks were highly encouraging, according to Dr. Kwatra, who reported there were no surprises in regard to safety during the extension period. He reported some transient reductions in hemoglobin and infections that resolved, but there were no cardiac events or other more serious events that have been previously associated with JAK inhibitors during the 40-week study period.

When asked if there might be an advantage for povorcitinib relative to the monoclonal antibodies in regard to speed of onset, Dr. Kwatra said that there are no comparative data. Like previous experience with dupilumab, some patients responded rapidly with povorcitinib, but others took longer to achieve benefit.

This variability in response is consistent with the growing evidence that PN is a heterogeneous disease, according to Dr. Kwatra. With multiple up-regulated cytokines implicated in the pathogenesis of PN, he suggested that more treatment options would be useful. When it comes to the multiple molecular pathways involved in the pathogenesis of PN, he said, “patients can be at a different edge of a spectrum.”

In other evidence suggesting that more options are needed, another late-breaking news study at the 2024 EADV congress underlined the fact that PN is a chronic disease. Presented by Franz J. Legat, MD, professor of dermatology at the Medical University of Graz, Graz, Austria, the data involved a withdrawal evaluation nested in a long-term extension (LTE) of the OLYMPIA pivotal trials with nemolizumab.

After 52 weeks in the LTE, 34 patients entered the OLYMPIA DURABILITY study, in which they were randomized to withdrawal or to continue on nemolizumab on an every 4-week dosing schedule.

The relapse rate over 24 weeks was 16.7% (3 of 18 patients) in the continuous nemolizumab arm and 75% (12 of 16 patients) in the withdrawal arm. The median time to relapse was 112.5 days for those in the withdrawal arm and was not reached during follow-up in the nemolizumab arm.

Praising the patients who were willing to risk PN relapse by entering this randomized trial, Dr. Legat said that the study shows a relatively high risk for relapse within months of treatment withdrawal even after good PN control over a period of 52 weeks.

“These data clearly support continuous nemolizumab beyond 52 weeks,” he said.

Dr. Kwatra reported financial relationships with AbbVie, Arcutis, Biotherapeutics, Aslan, Celldex, Galderma, Genzada, Johnson & Johnson, Novartis, Pfizer, Regeneron, Sanofi, and Incyte, which is developing povorcitinib for PN. Dr. Legat reported financial relationships with Almirall, Celgene, Eli Lilly, Menlo Therapeutics, Novartis, Pfizer, Trevi, Vifor, and Galderma, which provided funding for the nemolizumab studies.

A version of this article appeared on Medscape.com.

AMSTERDAM — For patients with atopic dermatitis (AD) who responded to the anti–interleukin (IL)–13 monoclonal antibody lebrikizumab in the pivotal trials, the level of response, including 90% skin clearance, has generally remained unchanged among those followed up for an additional 2 years, according to the latest data from an extension study. 

At the end of the maintenance phase of the pivotal trials at 12 months, 84% of the patients enrolled into the extension had clear or almost clear skin, as per the Investigator Global Assessment (IGA). This overall figure as well as the proportion with even better responses have persisted unchanged, reported Diamant Thaçi, MD, PhD, professor and head of the Comprehensive Center for Inflammatory Medicine, University of Lübeck in Germany. 
 

Responses at 3 Years Maintained

“This is really quite remarkable,” Dr. Thaçi said. “Roughly all the patients maintained their response.” These results became even more remarkable when patients were assessed for their use of adjunctive therapy to control flares. 

“Over the whole follow-up, 90% had no need for topical corticosteroids or any other rescue therapy,” Dr. Thaçi reported, providing data from the ADjoin lebrikizumab extension study during a late-breaking news session at the annual meeting of the European Academy of Dermatology and Venereology. 

The patients in ADjoin were enrolled from the pivotal phase 3 ADvocate 1 and 2 trials completed almost 2 years ago and published together in March 2023. Lebrikizumab was approved in the United States in September 2024 for moderate to severe AD in patients aged ≥ 12 years, following previous approvals in Europe in 2023 and in Japan in January 2024.

In these two identical trials with a total of 564 patients, the primary endpoint was an IGA of 0 or 1, signifying clear or almost clear skin. At nearly 40%, the proportion of patients reaching this outcome at 16 weeks was about threefold greater (P < .001) on lebrikizumab than on placebo. The benefit was similar on secondary endpoints, such as 75% improvement in the Eczema Area and Severity Index (EASI75) score. 

At the end of the double-blind, placebo-controlled 16-week phase of the ADvocate 1 and 2 trials, which enrolled adults and adolescents aged ≥ 12 years, responders were enrolled into a maintenance phase in which they were rerandomized to 250 mg lebrikizumab every 2 weeks (Q2W) or every 4 weeks (Q4W). The latter is the approved maintenance dose. 

At the end of the maintenance phase, which lasted another 32 weeks (total exposure of 52 weeks for those initially randomized to lebrikizumab), patients were invited into the ADjoin extension. The only exclusions from the extension were serious adverse events related to lebrikizumab and noncompliance. 
 

Response Curves Appear as Straight Lines

Over the next 2 years of ADjoin, response curves appeared as straight lines not only for the overall response but when patients were stratified for different levels of response at the extension study entry. Specifically, 81.5% and 83.3% had an IGA score of 0 or 1 in the Q2W and Q4W arms at completion of the ADvocate 16-week double-blind phase. At 3 years, the rates were 84.0% and 82.9%, respectively. 

For the subgroup who entered ADjoin with an EASI75 or an EASI90 response, the persistence of this level of response over 2 years was similar, although there was some gain observed among those who entered the trial with an EASI75 response. 

“Not only did these patients maintain their response, but the response on average slowly improved, so that there were more patients with an EASI90 response at the 3-year timepoint,” Dr. Thaçi said.

Of the 181 patients in the ADjoin extension, 82 patients were maintained on Q2W dosing and 99 were maintained on Q4W lebrikizumab. Their mean age was about 35 years, more than half were women, and nearly 40% had severe AD at the time they enrolled in the ADvocate trials. There was essentially no difference in response rates among those in the Q2W and Q4W arms over time in ADjoin. 
 

Side Effect Profile Essentially Unchanged

The side effect and tolerability profiles, which were favorable in the original 16-week placebo-controlled study, have remained unchanged over the subsequent maintenance phase and through the additional 2 years of the ADjoin extension.

“There continued to be reports of conjunctivitis, which is very specific for anti–IL-13 therapies,” Dr. Thaçi said. However, he said that the incidence did not increase over time, and because it was easy to treat, “most patients do not discontinue lebrikizumab for this reason.” Moreover, he said the impression was that “the number of patients experiencing adverse effects has been decreasing over time.” 

Calling these long-term results “very exciting,” Dr. Thaçi called lebrikizumab “a very valuable option for long-term AD care.” 

Asked for his perspective on the results, Jonathan I. Silverberg, MD, PhD, Director of Clinical Research, Department of Dermatology, George Washington University, Washington, DC, said that it is important to study long-term efficacy, and these results are positive. Without direct comparisons to other biologics available for AD, nothing can be implied about the relative efficacy of monoclonal antibodies approved for AD. 

“These data are important both from an efficacy and safety perspective” for those advising patients who need chronic AD treatment, said Dr. Silverberg, who was the principal investigator of the ADvocate trials. 

Earlier this year, 5-year follow-up data were published for dupilumab. Of 326 patients who remained on therapy this long, 220 (67%) maintained an IGA of 0 or 1 at the end of the study. There were no unexpected adverse events, which were generally stable or declined throughout the study. 

Dr. Thaçi has financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Leo Pharma, L’Oreal, Janssen-Cilag, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sun Pharma, UCB, and Vichy. Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies including those that make drugs for AD.

A version of this article appeared on Medscape.com.

AMSTERDAM — For patients with atopic dermatitis (AD) who responded to the anti–interleukin (IL)–13 monoclonal antibody lebrikizumab in the pivotal trials, the level of response, including 90% skin clearance, has generally remained unchanged among those followed up for an additional 2 years, according to the latest data from an extension study. 

At the end of the maintenance phase of the pivotal trials at 12 months, 84% of the patients enrolled into the extension had clear or almost clear skin, as per the Investigator Global Assessment (IGA). This overall figure as well as the proportion with even better responses have persisted unchanged, reported Diamant Thaçi, MD, PhD, professor and head of the Comprehensive Center for Inflammatory Medicine, University of Lübeck in Germany. 
 

Responses at 3 Years Maintained

“This is really quite remarkable,” Dr. Thaçi said. “Roughly all the patients maintained their response.” These results became even more remarkable when patients were assessed for their use of adjunctive therapy to control flares. 

“Over the whole follow-up, 90% had no need for topical corticosteroids or any other rescue therapy,” Dr. Thaçi reported, providing data from the ADjoin lebrikizumab extension study during a late-breaking news session at the annual meeting of the European Academy of Dermatology and Venereology. 

The patients in ADjoin were enrolled from the pivotal phase 3 ADvocate 1 and 2 trials completed almost 2 years ago and published together in March 2023. Lebrikizumab was approved in the United States in September 2024 for moderate to severe AD in patients aged ≥ 12 years, following previous approvals in Europe in 2023 and in Japan in January 2024.

In these two identical trials with a total of 564 patients, the primary endpoint was an IGA of 0 or 1, signifying clear or almost clear skin. At nearly 40%, the proportion of patients reaching this outcome at 16 weeks was about threefold greater (P < .001) on lebrikizumab than on placebo. The benefit was similar on secondary endpoints, such as 75% improvement in the Eczema Area and Severity Index (EASI75) score. 

At the end of the double-blind, placebo-controlled 16-week phase of the ADvocate 1 and 2 trials, which enrolled adults and adolescents aged ≥ 12 years, responders were enrolled into a maintenance phase in which they were rerandomized to 250 mg lebrikizumab every 2 weeks (Q2W) or every 4 weeks (Q4W). The latter is the approved maintenance dose. 

At the end of the maintenance phase, which lasted another 32 weeks (total exposure of 52 weeks for those initially randomized to lebrikizumab), patients were invited into the ADjoin extension. The only exclusions from the extension were serious adverse events related to lebrikizumab and noncompliance. 
 

Response Curves Appear as Straight Lines

Over the next 2 years of ADjoin, response curves appeared as straight lines not only for the overall response but when patients were stratified for different levels of response at the extension study entry. Specifically, 81.5% and 83.3% had an IGA score of 0 or 1 in the Q2W and Q4W arms at completion of the ADvocate 16-week double-blind phase. At 3 years, the rates were 84.0% and 82.9%, respectively. 

For the subgroup who entered ADjoin with an EASI75 or an EASI90 response, the persistence of this level of response over 2 years was similar, although there was some gain observed among those who entered the trial with an EASI75 response. 

“Not only did these patients maintain their response, but the response on average slowly improved, so that there were more patients with an EASI90 response at the 3-year timepoint,” Dr. Thaçi said.

Of the 181 patients in the ADjoin extension, 82 patients were maintained on Q2W dosing and 99 were maintained on Q4W lebrikizumab. Their mean age was about 35 years, more than half were women, and nearly 40% had severe AD at the time they enrolled in the ADvocate trials. There was essentially no difference in response rates among those in the Q2W and Q4W arms over time in ADjoin. 
 

Side Effect Profile Essentially Unchanged

The side effect and tolerability profiles, which were favorable in the original 16-week placebo-controlled study, have remained unchanged over the subsequent maintenance phase and through the additional 2 years of the ADjoin extension.

“There continued to be reports of conjunctivitis, which is very specific for anti–IL-13 therapies,” Dr. Thaçi said. However, he said that the incidence did not increase over time, and because it was easy to treat, “most patients do not discontinue lebrikizumab for this reason.” Moreover, he said the impression was that “the number of patients experiencing adverse effects has been decreasing over time.” 

Calling these long-term results “very exciting,” Dr. Thaçi called lebrikizumab “a very valuable option for long-term AD care.” 

Asked for his perspective on the results, Jonathan I. Silverberg, MD, PhD, Director of Clinical Research, Department of Dermatology, George Washington University, Washington, DC, said that it is important to study long-term efficacy, and these results are positive. Without direct comparisons to other biologics available for AD, nothing can be implied about the relative efficacy of monoclonal antibodies approved for AD. 

“These data are important both from an efficacy and safety perspective” for those advising patients who need chronic AD treatment, said Dr. Silverberg, who was the principal investigator of the ADvocate trials. 

Earlier this year, 5-year follow-up data were published for dupilumab. Of 326 patients who remained on therapy this long, 220 (67%) maintained an IGA of 0 or 1 at the end of the study. There were no unexpected adverse events, which were generally stable or declined throughout the study. 

Dr. Thaçi has financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Leo Pharma, L’Oreal, Janssen-Cilag, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sun Pharma, UCB, and Vichy. Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies including those that make drugs for AD.

A version of this article appeared on Medscape.com.

AMSTERDAM — For patients with atopic dermatitis (AD) who responded to the anti–interleukin (IL)–13 monoclonal antibody lebrikizumab in the pivotal trials, the level of response, including 90% skin clearance, has generally remained unchanged among those followed up for an additional 2 years, according to the latest data from an extension study. 

At the end of the maintenance phase of the pivotal trials at 12 months, 84% of the patients enrolled into the extension had clear or almost clear skin, as per the Investigator Global Assessment (IGA). This overall figure as well as the proportion with even better responses have persisted unchanged, reported Diamant Thaçi, MD, PhD, professor and head of the Comprehensive Center for Inflammatory Medicine, University of Lübeck in Germany. 
 

Responses at 3 Years Maintained

“This is really quite remarkable,” Dr. Thaçi said. “Roughly all the patients maintained their response.” These results became even more remarkable when patients were assessed for their use of adjunctive therapy to control flares. 

“Over the whole follow-up, 90% had no need for topical corticosteroids or any other rescue therapy,” Dr. Thaçi reported, providing data from the ADjoin lebrikizumab extension study during a late-breaking news session at the annual meeting of the European Academy of Dermatology and Venereology. 

The patients in ADjoin were enrolled from the pivotal phase 3 ADvocate 1 and 2 trials completed almost 2 years ago and published together in March 2023. Lebrikizumab was approved in the United States in September 2024 for moderate to severe AD in patients aged ≥ 12 years, following previous approvals in Europe in 2023 and in Japan in January 2024.

In these two identical trials with a total of 564 patients, the primary endpoint was an IGA of 0 or 1, signifying clear or almost clear skin. At nearly 40%, the proportion of patients reaching this outcome at 16 weeks was about threefold greater (P < .001) on lebrikizumab than on placebo. The benefit was similar on secondary endpoints, such as 75% improvement in the Eczema Area and Severity Index (EASI75) score. 

At the end of the double-blind, placebo-controlled 16-week phase of the ADvocate 1 and 2 trials, which enrolled adults and adolescents aged ≥ 12 years, responders were enrolled into a maintenance phase in which they were rerandomized to 250 mg lebrikizumab every 2 weeks (Q2W) or every 4 weeks (Q4W). The latter is the approved maintenance dose. 

At the end of the maintenance phase, which lasted another 32 weeks (total exposure of 52 weeks for those initially randomized to lebrikizumab), patients were invited into the ADjoin extension. The only exclusions from the extension were serious adverse events related to lebrikizumab and noncompliance. 
 

Response Curves Appear as Straight Lines

Over the next 2 years of ADjoin, response curves appeared as straight lines not only for the overall response but when patients were stratified for different levels of response at the extension study entry. Specifically, 81.5% and 83.3% had an IGA score of 0 or 1 in the Q2W and Q4W arms at completion of the ADvocate 16-week double-blind phase. At 3 years, the rates were 84.0% and 82.9%, respectively. 

For the subgroup who entered ADjoin with an EASI75 or an EASI90 response, the persistence of this level of response over 2 years was similar, although there was some gain observed among those who entered the trial with an EASI75 response. 

“Not only did these patients maintain their response, but the response on average slowly improved, so that there were more patients with an EASI90 response at the 3-year timepoint,” Dr. Thaçi said.

Of the 181 patients in the ADjoin extension, 82 patients were maintained on Q2W dosing and 99 were maintained on Q4W lebrikizumab. Their mean age was about 35 years, more than half were women, and nearly 40% had severe AD at the time they enrolled in the ADvocate trials. There was essentially no difference in response rates among those in the Q2W and Q4W arms over time in ADjoin. 
 

Side Effect Profile Essentially Unchanged

The side effect and tolerability profiles, which were favorable in the original 16-week placebo-controlled study, have remained unchanged over the subsequent maintenance phase and through the additional 2 years of the ADjoin extension.

“There continued to be reports of conjunctivitis, which is very specific for anti–IL-13 therapies,” Dr. Thaçi said. However, he said that the incidence did not increase over time, and because it was easy to treat, “most patients do not discontinue lebrikizumab for this reason.” Moreover, he said the impression was that “the number of patients experiencing adverse effects has been decreasing over time.” 

Calling these long-term results “very exciting,” Dr. Thaçi called lebrikizumab “a very valuable option for long-term AD care.” 

Asked for his perspective on the results, Jonathan I. Silverberg, MD, PhD, Director of Clinical Research, Department of Dermatology, George Washington University, Washington, DC, said that it is important to study long-term efficacy, and these results are positive. Without direct comparisons to other biologics available for AD, nothing can be implied about the relative efficacy of monoclonal antibodies approved for AD. 

“These data are important both from an efficacy and safety perspective” for those advising patients who need chronic AD treatment, said Dr. Silverberg, who was the principal investigator of the ADvocate trials. 

Earlier this year, 5-year follow-up data were published for dupilumab. Of 326 patients who remained on therapy this long, 220 (67%) maintained an IGA of 0 or 1 at the end of the study. There were no unexpected adverse events, which were generally stable or declined throughout the study. 

Dr. Thaçi has financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Galderma, Leo Pharma, L’Oreal, Janssen-Cilag, New Bridge, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sun Pharma, UCB, and Vichy. Dr. Silverberg reported financial relationships with more than 40 pharmaceutical companies including those that make drugs for AD.

A version of this article appeared on Medscape.com.

AMSTERDAM — For frontal fibrosing alopecia (FFA), a disease with no approved therapies, topical delgocitinib attenuated inflammation and generated hair regrowth in women in a controlled phase 2a trial.

“This is an exciting avenue for FFA if the data are recapitulated in a larger population. It could be an important new treatment option,” said Maryanne Senna, MD, director at Lahey Hospital & Medical Center’s Hair Loss Center of Excellence, Burlington, Massachusetts, and assistant dermatology professor at Harvard Medical School, Boston, Massachusetts.

In a design characterized as “exploratory,” the trial had two parts: a randomized, double-blind, vehicle-controlled intervention for 12 weeks, followed by an open-label extension of topical delgocitinib for all participants for another 12 weeks. 

The primary efficacy endpoint was change in the molecular signature of FFA inflammation at 12 weeks. Clinical improvement was monitored with both trichoscopic images capturing the numbers of hairs and follicular units at 12 weeks and clinical severity scores through week 24. In a topical cream formulation, the Janus kinase inhibitor (JAKi) delgocitinib was associated with favorable activity for both. 
 

Some Hair Regrowth for All

“At 24 weeks, all patients achieved some degree of hair regrowth and a stabilization of disease based on hairline measurements,” Senna reported in a late-breaking news session at the 2024 European Academy of Dermatology and Venereology (EADV) Congress. 

On the clinical endpoints, Senna noted an upward trajectory in clinical improvement at the completion of the study.

The 30 participants were randomly assigned in a 1:1 ratio to receive delgocitinib cream in a concentration of 20 mg/g or vehicle cream applied twice daily for 12 weeks. At the end of this double-blind period, patients on vehicle were crossed over to the active therapy, and all patients were monitored for another 12 weeks in an open-label extension. 

The change from baseline in FFA biomarkers was selected as the primary endpoint based on previous work showing up-regulation in the expression of the Th1 biomarkers CXCL9, CXCL10, and interferon gamma in lesional vs nonlesional scalp in patients with FFA. 

When biopsies at the end of 12 weeks in the double-blind phase of the study were compared with the baseline biopsies, researchers found a decrease in expression of the three local inflammation markers in all patients receiving the JAKi, but not in those receiving the vehicle cream. In this small patient sample, only the reduction in expression of CXCL9, a cytokine known for differentiation and promotion of leukocytes, reached statistical significance (P < .05).

But in an analysis involving the expression of multiple genes, “lesions treated with delgocitinib had a 4% improvement in normalization toward a nonlesional transcriptomic profile, while patients treated with vehicle had a 33% worsening,” Senna reported. The difference was highly significant (P < .001).

Furthermore, the decrease in total Lichen Planopilaris Activity Index and FFA severity scores were numerically and statistically greater (P = .023) in the active-treatment arm than in the vehicle arm by the end of the double-blind part of the trial, she said.

On trichoscopy, there was an increased number of hairs and follicular units at 12 weeks relative to baseline among those treated with topical delgocitinib but a reduction in those treated with vehicle.
 

JAKi Patients Gained Hair, Vehicle Patients Lost Hair

On the basis of hair count per square centimeter from baseline, delgocitinib-treated patients gained on average of seven hairs whereas vehicle recipients lost an average of 11 hairs at 24 weeks, Senna reported.

Patients originally treated with vehicle did improve in most outcome measures in the open-label extension of the experimental treatment after crossover, but they did not catch up to those initially randomized to delgocitinib because of further accrual of favorable changes in the active-treatment group over time.

“There were no adverse events associated with active therapy or vehicle, including application-site reactions,” Senna said. The one between-group difference was a higher rate of COVID-19, but this was greater in the control arm.

All 30 of the participants in this study were women, and all had moderate to severe disease at enrollment. The median age was 64 years. Because of the predominant population at the hair loss center, all but one of the participants were White, and one participant was Asian. 

Characterizing FFA as “devastating and disfiguring,” Senna, who specializes in the care of alopecia, noted that this a difficult disease to control with the off-label strategies that are now used. The slow progress to identify treatments for FFA is illustrated by the fact that only one other double-blind and randomized trial has ever been conducted in FFA, she said.
 

Exploratory Study Supports Anecdotal Experience

On the basis of prior anecdotal experience with JAKi treatment for FFA, Senna said, “I do think that it is possible to get largely clear skin with this therapy.” However, she is now hoping for definitive trials to better characterize the efficacy and safety of oral and topical therapies, perhaps used sequentially to maintain clinical improvement.

In light of the limited current options, Menno de Rie, MD, PhD, professor of dermatology at the University of Amsterdam in the Netherlands, called these data “very inspiring and hopeful.” He suggested the promise of this therapy was reinforced by the upward trajectory of the biomarkers and clinical improvement over the study period. 

“Any improvement in treatment options would be welcome, because we do not [have] any reliable therapies for this condition,” de Rie, who was not an investigator, said in an interview after the presentation. 

Ultimately, Senna said, once effective therapy is established, the goal will be to start as early as possible in the disease process. She noted that there is evidence that prompt therapy can reverse the disorder, not just prevent progression.

“If you can get to the hair follicles before the point of no return, there is [a] chance [of] follicular rescue,” she said.

Delgocitinib cream (Anzupgo) was approved in Europe for treating chronic hand eczema in late September and is under review for the same indication in the United States. 

Senna has financial relationships with Arena, Concert, Eli Lilly, Pfizer, and Leo Pharma, which provided funding for this study. de Rie reported no potential conflicts of interest.

A version of this article appeared on Medscape.com.

AMSTERDAM — For frontal fibrosing alopecia (FFA), a disease with no approved therapies, topical delgocitinib attenuated inflammation and generated hair regrowth in women in a controlled phase 2a trial.

“This is an exciting avenue for FFA if the data are recapitulated in a larger population. It could be an important new treatment option,” said Maryanne Senna, MD, director at Lahey Hospital & Medical Center’s Hair Loss Center of Excellence, Burlington, Massachusetts, and assistant dermatology professor at Harvard Medical School, Boston, Massachusetts.

In a design characterized as “exploratory,” the trial had two parts: a randomized, double-blind, vehicle-controlled intervention for 12 weeks, followed by an open-label extension of topical delgocitinib for all participants for another 12 weeks. 

The primary efficacy endpoint was change in the molecular signature of FFA inflammation at 12 weeks. Clinical improvement was monitored with both trichoscopic images capturing the numbers of hairs and follicular units at 12 weeks and clinical severity scores through week 24. In a topical cream formulation, the Janus kinase inhibitor (JAKi) delgocitinib was associated with favorable activity for both. 
 

Some Hair Regrowth for All

“At 24 weeks, all patients achieved some degree of hair regrowth and a stabilization of disease based on hairline measurements,” Senna reported in a late-breaking news session at the 2024 European Academy of Dermatology and Venereology (EADV) Congress. 

On the clinical endpoints, Senna noted an upward trajectory in clinical improvement at the completion of the study.

The 30 participants were randomly assigned in a 1:1 ratio to receive delgocitinib cream in a concentration of 20 mg/g or vehicle cream applied twice daily for 12 weeks. At the end of this double-blind period, patients on vehicle were crossed over to the active therapy, and all patients were monitored for another 12 weeks in an open-label extension. 

The change from baseline in FFA biomarkers was selected as the primary endpoint based on previous work showing up-regulation in the expression of the Th1 biomarkers CXCL9, CXCL10, and interferon gamma in lesional vs nonlesional scalp in patients with FFA. 

When biopsies at the end of 12 weeks in the double-blind phase of the study were compared with the baseline biopsies, researchers found a decrease in expression of the three local inflammation markers in all patients receiving the JAKi, but not in those receiving the vehicle cream. In this small patient sample, only the reduction in expression of CXCL9, a cytokine known for differentiation and promotion of leukocytes, reached statistical significance (P < .05).

But in an analysis involving the expression of multiple genes, “lesions treated with delgocitinib had a 4% improvement in normalization toward a nonlesional transcriptomic profile, while patients treated with vehicle had a 33% worsening,” Senna reported. The difference was highly significant (P < .001).

Furthermore, the decrease in total Lichen Planopilaris Activity Index and FFA severity scores were numerically and statistically greater (P = .023) in the active-treatment arm than in the vehicle arm by the end of the double-blind part of the trial, she said.

On trichoscopy, there was an increased number of hairs and follicular units at 12 weeks relative to baseline among those treated with topical delgocitinib but a reduction in those treated with vehicle.
 

JAKi Patients Gained Hair, Vehicle Patients Lost Hair

On the basis of hair count per square centimeter from baseline, delgocitinib-treated patients gained on average of seven hairs whereas vehicle recipients lost an average of 11 hairs at 24 weeks, Senna reported.

Patients originally treated with vehicle did improve in most outcome measures in the open-label extension of the experimental treatment after crossover, but they did not catch up to those initially randomized to delgocitinib because of further accrual of favorable changes in the active-treatment group over time.

“There were no adverse events associated with active therapy or vehicle, including application-site reactions,” Senna said. The one between-group difference was a higher rate of COVID-19, but this was greater in the control arm.

All 30 of the participants in this study were women, and all had moderate to severe disease at enrollment. The median age was 64 years. Because of the predominant population at the hair loss center, all but one of the participants were White, and one participant was Asian. 

Characterizing FFA as “devastating and disfiguring,” Senna, who specializes in the care of alopecia, noted that this a difficult disease to control with the off-label strategies that are now used. The slow progress to identify treatments for FFA is illustrated by the fact that only one other double-blind and randomized trial has ever been conducted in FFA, she said.
 

Exploratory Study Supports Anecdotal Experience

On the basis of prior anecdotal experience with JAKi treatment for FFA, Senna said, “I do think that it is possible to get largely clear skin with this therapy.” However, she is now hoping for definitive trials to better characterize the efficacy and safety of oral and topical therapies, perhaps used sequentially to maintain clinical improvement.

In light of the limited current options, Menno de Rie, MD, PhD, professor of dermatology at the University of Amsterdam in the Netherlands, called these data “very inspiring and hopeful.” He suggested the promise of this therapy was reinforced by the upward trajectory of the biomarkers and clinical improvement over the study period. 

“Any improvement in treatment options would be welcome, because we do not [have] any reliable therapies for this condition,” de Rie, who was not an investigator, said in an interview after the presentation. 

Ultimately, Senna said, once effective therapy is established, the goal will be to start as early as possible in the disease process. She noted that there is evidence that prompt therapy can reverse the disorder, not just prevent progression.

“If you can get to the hair follicles before the point of no return, there is [a] chance [of] follicular rescue,” she said.

Delgocitinib cream (Anzupgo) was approved in Europe for treating chronic hand eczema in late September and is under review for the same indication in the United States. 

Senna has financial relationships with Arena, Concert, Eli Lilly, Pfizer, and Leo Pharma, which provided funding for this study. de Rie reported no potential conflicts of interest.

A version of this article appeared on Medscape.com.

AMSTERDAM — For frontal fibrosing alopecia (FFA), a disease with no approved therapies, topical delgocitinib attenuated inflammation and generated hair regrowth in women in a controlled phase 2a trial.

“This is an exciting avenue for FFA if the data are recapitulated in a larger population. It could be an important new treatment option,” said Maryanne Senna, MD, director at Lahey Hospital & Medical Center’s Hair Loss Center of Excellence, Burlington, Massachusetts, and assistant dermatology professor at Harvard Medical School, Boston, Massachusetts.

In a design characterized as “exploratory,” the trial had two parts: a randomized, double-blind, vehicle-controlled intervention for 12 weeks, followed by an open-label extension of topical delgocitinib for all participants for another 12 weeks. 

The primary efficacy endpoint was change in the molecular signature of FFA inflammation at 12 weeks. Clinical improvement was monitored with both trichoscopic images capturing the numbers of hairs and follicular units at 12 weeks and clinical severity scores through week 24. In a topical cream formulation, the Janus kinase inhibitor (JAKi) delgocitinib was associated with favorable activity for both. 
 

Some Hair Regrowth for All

“At 24 weeks, all patients achieved some degree of hair regrowth and a stabilization of disease based on hairline measurements,” Senna reported in a late-breaking news session at the 2024 European Academy of Dermatology and Venereology (EADV) Congress. 

On the clinical endpoints, Senna noted an upward trajectory in clinical improvement at the completion of the study.

The 30 participants were randomly assigned in a 1:1 ratio to receive delgocitinib cream in a concentration of 20 mg/g or vehicle cream applied twice daily for 12 weeks. At the end of this double-blind period, patients on vehicle were crossed over to the active therapy, and all patients were monitored for another 12 weeks in an open-label extension. 

The change from baseline in FFA biomarkers was selected as the primary endpoint based on previous work showing up-regulation in the expression of the Th1 biomarkers CXCL9, CXCL10, and interferon gamma in lesional vs nonlesional scalp in patients with FFA. 

When biopsies at the end of 12 weeks in the double-blind phase of the study were compared with the baseline biopsies, researchers found a decrease in expression of the three local inflammation markers in all patients receiving the JAKi, but not in those receiving the vehicle cream. In this small patient sample, only the reduction in expression of CXCL9, a cytokine known for differentiation and promotion of leukocytes, reached statistical significance (P < .05).

But in an analysis involving the expression of multiple genes, “lesions treated with delgocitinib had a 4% improvement in normalization toward a nonlesional transcriptomic profile, while patients treated with vehicle had a 33% worsening,” Senna reported. The difference was highly significant (P < .001).

Furthermore, the decrease in total Lichen Planopilaris Activity Index and FFA severity scores were numerically and statistically greater (P = .023) in the active-treatment arm than in the vehicle arm by the end of the double-blind part of the trial, she said.

On trichoscopy, there was an increased number of hairs and follicular units at 12 weeks relative to baseline among those treated with topical delgocitinib but a reduction in those treated with vehicle.
 

JAKi Patients Gained Hair, Vehicle Patients Lost Hair

On the basis of hair count per square centimeter from baseline, delgocitinib-treated patients gained on average of seven hairs whereas vehicle recipients lost an average of 11 hairs at 24 weeks, Senna reported.

Patients originally treated with vehicle did improve in most outcome measures in the open-label extension of the experimental treatment after crossover, but they did not catch up to those initially randomized to delgocitinib because of further accrual of favorable changes in the active-treatment group over time.

“There were no adverse events associated with active therapy or vehicle, including application-site reactions,” Senna said. The one between-group difference was a higher rate of COVID-19, but this was greater in the control arm.

All 30 of the participants in this study were women, and all had moderate to severe disease at enrollment. The median age was 64 years. Because of the predominant population at the hair loss center, all but one of the participants were White, and one participant was Asian. 

Characterizing FFA as “devastating and disfiguring,” Senna, who specializes in the care of alopecia, noted that this a difficult disease to control with the off-label strategies that are now used. The slow progress to identify treatments for FFA is illustrated by the fact that only one other double-blind and randomized trial has ever been conducted in FFA, she said.
 

Exploratory Study Supports Anecdotal Experience

On the basis of prior anecdotal experience with JAKi treatment for FFA, Senna said, “I do think that it is possible to get largely clear skin with this therapy.” However, she is now hoping for definitive trials to better characterize the efficacy and safety of oral and topical therapies, perhaps used sequentially to maintain clinical improvement.

In light of the limited current options, Menno de Rie, MD, PhD, professor of dermatology at the University of Amsterdam in the Netherlands, called these data “very inspiring and hopeful.” He suggested the promise of this therapy was reinforced by the upward trajectory of the biomarkers and clinical improvement over the study period. 

“Any improvement in treatment options would be welcome, because we do not [have] any reliable therapies for this condition,” de Rie, who was not an investigator, said in an interview after the presentation. 

Ultimately, Senna said, once effective therapy is established, the goal will be to start as early as possible in the disease process. She noted that there is evidence that prompt therapy can reverse the disorder, not just prevent progression.

“If you can get to the hair follicles before the point of no return, there is [a] chance [of] follicular rescue,” she said.

Delgocitinib cream (Anzupgo) was approved in Europe for treating chronic hand eczema in late September and is under review for the same indication in the United States. 

Senna has financial relationships with Arena, Concert, Eli Lilly, Pfizer, and Leo Pharma, which provided funding for this study. de Rie reported no potential conflicts of interest.

A version of this article appeared on Medscape.com.

AMSTERDAM — A proteomics study designed to determine why some patients with atopic dermatitis (AD) respond quickly to dupilumab, others respond more slowly, and the remainder do not respond at all demonstrated that molecular responses in these three groups are very different.

A discovery that could lead to personalizing therapies, the data identified “distinct systemic biomarker profiles,” according to Ester Del Duca, MD, an instructor in the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York City.

The study was conducted with 67 patients with AD and 16 healthy controls. Serum was collected at two timepoints: An average of 20 weeks after starting dupilumab, then at a mean interval of about 9 months later. At these timepoints, called follow-up 1 and 2, a panel of more than 600 proteins, including unique markers for immunologic, cardiovascular, and neurologic activity, were evaluated.

The criterion for differentiating the three response groups was an Investigator Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (or at least a 2-point IGA reduction from baseline). Early responders were those who met the criterion at both follow-ups, late responders were those who met this criterion only at the second follow-up, and nonresponders never met the criterion.

“There were no significant differences at baseline in clinical severity, past medical history, or patient characteristics,” said Del Duca, who presented these data in a late breaking news session at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Of the 67 patients with AD, 39 were early responders, 11 were late responders, and 17 were nonresponders.

The differences in proteomics were marked. For early responders, there was an early normalization of the proteome, reported Del Duca, illustrating the differences in the proteome of the three groups with a color-coded chart of protein up-regulation and down-regulation relative to healthy controls. The normalization of the proteome persisted in early responders when assessed at the second follow-up.

In the late responders, the proteome dysregulation was substantial relative to healthy controls at the first follow-up, but there was considerable improvement by the second follow-up. Although the change at the second follow-up was still not as robust as that seen in the early responders at either follow-up, Del Duca described the proteomic profile as a 45% improvement from the first follow-up.

In contrast, nonresponders showed worsening in their blood proteome from follow-up 1 to 2. Nonresponders at first follow-up showed up-regulation relative to healthy controls for many proteins associated with the Th1 response, such as interferon gamma, CXCL9, and CXCL10, and Th2 response, such as interleukin-4 and Th17/22, and these did not normalize or worsen by the second follow-up.

“Uniquely to nonresponders, key Th1 biomarkers remained significantly up-regulated relative to controls at both follow-up 1 and 2,” with a P value < .05, Del Duca reported.

To achieve normalization of the proteome as defined by healthy controls, both up-regulation and down-regulation of protein activity were required, although more up-regulations than down-regulations were observed.

When evaluating the proteome changes most implicated in immunoregulation, the investigators were able to show a correlation between worsening in the proteome and greater severity of AD as defined by IGA, Eczema Area and Severity Index, and body surface area involvement.

“Spearman analysis revealed strong and positive correlations between improvements in biomarkers at follow-up 1 and 2 with improvements in clinical markers,” Del Duca said. As examples, she noted favorable changes in biomarkers specifically associated with T cells, dendritic cells, and natural killer cells as clinical outcomes improved.

Conversely, the worsening in T-cell activation among nonresponders, particularly Th1 biomarkers, also tracked with increasing AD symptoms over time.

The implications of the research are broad, and most importantly, it shows that therapeutic targets are likely to differ between patients with AD, according to Del Duca. Although proteomic studies have not yet been conducted with other treatments, these might provide further insight about how patients with AD differ in response across other drugs.

This is important work, according to Brigitte Dréno, MD, PhD, head of the Department of Dermatology, Nantes University Hospital in France. As moderator of the late-breaking news session, she suggested that there are many potential messages from these data, not least that treatment of AD likely involves targeting cytokines beyond those affected by dupilumab in at least some patients.

When Dréno asked Del Duca about what could be surmised about changes from baseline before treatment to the first follow-up, Del Duca said that the study was retrospective, so baseline data were not available.

This is an important missing piece of this investigation, according to Dréno.

“As you move this work forward,” she said that it would be “very important” to determine “if there are predictive markers for evaluating which patients will respond.”

This is a small study with many additional variables to consider in order to develop a clinically useful tool, Del Duca noted. However, this work not only has the potential to guide treatment selection but the biomarkers up-regulated in nonresponders are already “suggesting potential targets for refining therapeutic strategies,” she said.

The study received funding from Bristol-Myers Squibb. Del Duca reported no financial relationships with industry. Dréno reported financial relationships with La Roche–Posay, Pierre Fabré, and Galderma.

A version of this article appeared on Medscape.com.

AMSTERDAM — A proteomics study designed to determine why some patients with atopic dermatitis (AD) respond quickly to dupilumab, others respond more slowly, and the remainder do not respond at all demonstrated that molecular responses in these three groups are very different.

A discovery that could lead to personalizing therapies, the data identified “distinct systemic biomarker profiles,” according to Ester Del Duca, MD, an instructor in the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York City.

The study was conducted with 67 patients with AD and 16 healthy controls. Serum was collected at two timepoints: An average of 20 weeks after starting dupilumab, then at a mean interval of about 9 months later. At these timepoints, called follow-up 1 and 2, a panel of more than 600 proteins, including unique markers for immunologic, cardiovascular, and neurologic activity, were evaluated.

The criterion for differentiating the three response groups was an Investigator Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (or at least a 2-point IGA reduction from baseline). Early responders were those who met the criterion at both follow-ups, late responders were those who met this criterion only at the second follow-up, and nonresponders never met the criterion.

“There were no significant differences at baseline in clinical severity, past medical history, or patient characteristics,” said Del Duca, who presented these data in a late breaking news session at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Of the 67 patients with AD, 39 were early responders, 11 were late responders, and 17 were nonresponders.

The differences in proteomics were marked. For early responders, there was an early normalization of the proteome, reported Del Duca, illustrating the differences in the proteome of the three groups with a color-coded chart of protein up-regulation and down-regulation relative to healthy controls. The normalization of the proteome persisted in early responders when assessed at the second follow-up.

In the late responders, the proteome dysregulation was substantial relative to healthy controls at the first follow-up, but there was considerable improvement by the second follow-up. Although the change at the second follow-up was still not as robust as that seen in the early responders at either follow-up, Del Duca described the proteomic profile as a 45% improvement from the first follow-up.

In contrast, nonresponders showed worsening in their blood proteome from follow-up 1 to 2. Nonresponders at first follow-up showed up-regulation relative to healthy controls for many proteins associated with the Th1 response, such as interferon gamma, CXCL9, and CXCL10, and Th2 response, such as interleukin-4 and Th17/22, and these did not normalize or worsen by the second follow-up.

“Uniquely to nonresponders, key Th1 biomarkers remained significantly up-regulated relative to controls at both follow-up 1 and 2,” with a P value < .05, Del Duca reported.

To achieve normalization of the proteome as defined by healthy controls, both up-regulation and down-regulation of protein activity were required, although more up-regulations than down-regulations were observed.

When evaluating the proteome changes most implicated in immunoregulation, the investigators were able to show a correlation between worsening in the proteome and greater severity of AD as defined by IGA, Eczema Area and Severity Index, and body surface area involvement.

“Spearman analysis revealed strong and positive correlations between improvements in biomarkers at follow-up 1 and 2 with improvements in clinical markers,” Del Duca said. As examples, she noted favorable changes in biomarkers specifically associated with T cells, dendritic cells, and natural killer cells as clinical outcomes improved.

Conversely, the worsening in T-cell activation among nonresponders, particularly Th1 biomarkers, also tracked with increasing AD symptoms over time.

The implications of the research are broad, and most importantly, it shows that therapeutic targets are likely to differ between patients with AD, according to Del Duca. Although proteomic studies have not yet been conducted with other treatments, these might provide further insight about how patients with AD differ in response across other drugs.

This is important work, according to Brigitte Dréno, MD, PhD, head of the Department of Dermatology, Nantes University Hospital in France. As moderator of the late-breaking news session, she suggested that there are many potential messages from these data, not least that treatment of AD likely involves targeting cytokines beyond those affected by dupilumab in at least some patients.

When Dréno asked Del Duca about what could be surmised about changes from baseline before treatment to the first follow-up, Del Duca said that the study was retrospective, so baseline data were not available.

This is an important missing piece of this investigation, according to Dréno.

“As you move this work forward,” she said that it would be “very important” to determine “if there are predictive markers for evaluating which patients will respond.”

This is a small study with many additional variables to consider in order to develop a clinically useful tool, Del Duca noted. However, this work not only has the potential to guide treatment selection but the biomarkers up-regulated in nonresponders are already “suggesting potential targets for refining therapeutic strategies,” she said.

The study received funding from Bristol-Myers Squibb. Del Duca reported no financial relationships with industry. Dréno reported financial relationships with La Roche–Posay, Pierre Fabré, and Galderma.

A version of this article appeared on Medscape.com.

AMSTERDAM — A proteomics study designed to determine why some patients with atopic dermatitis (AD) respond quickly to dupilumab, others respond more slowly, and the remainder do not respond at all demonstrated that molecular responses in these three groups are very different.

A discovery that could lead to personalizing therapies, the data identified “distinct systemic biomarker profiles,” according to Ester Del Duca, MD, an instructor in the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York City.

The study was conducted with 67 patients with AD and 16 healthy controls. Serum was collected at two timepoints: An average of 20 weeks after starting dupilumab, then at a mean interval of about 9 months later. At these timepoints, called follow-up 1 and 2, a panel of more than 600 proteins, including unique markers for immunologic, cardiovascular, and neurologic activity, were evaluated.

The criterion for differentiating the three response groups was an Investigator Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (or at least a 2-point IGA reduction from baseline). Early responders were those who met the criterion at both follow-ups, late responders were those who met this criterion only at the second follow-up, and nonresponders never met the criterion.

“There were no significant differences at baseline in clinical severity, past medical history, or patient characteristics,” said Del Duca, who presented these data in a late breaking news session at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Of the 67 patients with AD, 39 were early responders, 11 were late responders, and 17 were nonresponders.

The differences in proteomics were marked. For early responders, there was an early normalization of the proteome, reported Del Duca, illustrating the differences in the proteome of the three groups with a color-coded chart of protein up-regulation and down-regulation relative to healthy controls. The normalization of the proteome persisted in early responders when assessed at the second follow-up.

In the late responders, the proteome dysregulation was substantial relative to healthy controls at the first follow-up, but there was considerable improvement by the second follow-up. Although the change at the second follow-up was still not as robust as that seen in the early responders at either follow-up, Del Duca described the proteomic profile as a 45% improvement from the first follow-up.

In contrast, nonresponders showed worsening in their blood proteome from follow-up 1 to 2. Nonresponders at first follow-up showed up-regulation relative to healthy controls for many proteins associated with the Th1 response, such as interferon gamma, CXCL9, and CXCL10, and Th2 response, such as interleukin-4 and Th17/22, and these did not normalize or worsen by the second follow-up.

“Uniquely to nonresponders, key Th1 biomarkers remained significantly up-regulated relative to controls at both follow-up 1 and 2,” with a P value < .05, Del Duca reported.

To achieve normalization of the proteome as defined by healthy controls, both up-regulation and down-regulation of protein activity were required, although more up-regulations than down-regulations were observed.

When evaluating the proteome changes most implicated in immunoregulation, the investigators were able to show a correlation between worsening in the proteome and greater severity of AD as defined by IGA, Eczema Area and Severity Index, and body surface area involvement.

“Spearman analysis revealed strong and positive correlations between improvements in biomarkers at follow-up 1 and 2 with improvements in clinical markers,” Del Duca said. As examples, she noted favorable changes in biomarkers specifically associated with T cells, dendritic cells, and natural killer cells as clinical outcomes improved.

Conversely, the worsening in T-cell activation among nonresponders, particularly Th1 biomarkers, also tracked with increasing AD symptoms over time.

The implications of the research are broad, and most importantly, it shows that therapeutic targets are likely to differ between patients with AD, according to Del Duca. Although proteomic studies have not yet been conducted with other treatments, these might provide further insight about how patients with AD differ in response across other drugs.

This is important work, according to Brigitte Dréno, MD, PhD, head of the Department of Dermatology, Nantes University Hospital in France. As moderator of the late-breaking news session, she suggested that there are many potential messages from these data, not least that treatment of AD likely involves targeting cytokines beyond those affected by dupilumab in at least some patients.

When Dréno asked Del Duca about what could be surmised about changes from baseline before treatment to the first follow-up, Del Duca said that the study was retrospective, so baseline data were not available.

This is an important missing piece of this investigation, according to Dréno.

“As you move this work forward,” she said that it would be “very important” to determine “if there are predictive markers for evaluating which patients will respond.”

This is a small study with many additional variables to consider in order to develop a clinically useful tool, Del Duca noted. However, this work not only has the potential to guide treatment selection but the biomarkers up-regulated in nonresponders are already “suggesting potential targets for refining therapeutic strategies,” she said.

The study received funding from Bristol-Myers Squibb. Del Duca reported no financial relationships with industry. Dréno reported financial relationships with La Roche–Posay, Pierre Fabré, and Galderma.

A version of this article appeared on Medscape.com.