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Studies validate IL-17 as hidradenitis suppurativa drug target
NEW ORLEANS – In two phase 3 trials, bimekizumab, a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.
“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.
The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.
Patients in both studies were randomized to one of four groups – either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.
In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-2-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
Results at primary endpoint
The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.
At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.
In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-4-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.
In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response – 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.
It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full-dose bimekizumab over starting on placebo.
In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Dr. Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.
“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Dr. Kimball said.
Clinically meaningful secondary endpoint
For HS patients, the secondary endpoint of HiSCR75 might be considered the most meaningful, according to Dr. Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB, developer of bimekizumab.
In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2-week and every-4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every-4-week dose (33.7%) were superior to the 15.6% response in placebo patients.
The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Dr. Kimball said.
Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Dr. Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was less than 4% at 16 weeks.
This is only the third phase 3 trial ever completed in patients with HS. In fact, Dr. Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.
“This is amazing news for our patients,” Dr. Kimball said. HS remains a challenging disease, even with a growing number of options showing benefit in large studies, she said, and the high rate of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
Multiple treatment options important
Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina at Chapel Hill, who publishes frequently about this disease.
“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a majority of patients after the first year,” he said.
Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.
“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF [tumor necrosis factor] antagonists,” he said.
Bimekizumab is not approved for any indication in the United States; it is approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in the EU/EEA, where it is marketed as Bimzelx, according to UCB. Dr. Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Dr. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – In two phase 3 trials, bimekizumab, a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.
“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.
The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.
Patients in both studies were randomized to one of four groups – either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.
In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-2-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
Results at primary endpoint
The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.
At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.
In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-4-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.
In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response – 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.
It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full-dose bimekizumab over starting on placebo.
In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Dr. Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.
“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Dr. Kimball said.
Clinically meaningful secondary endpoint
For HS patients, the secondary endpoint of HiSCR75 might be considered the most meaningful, according to Dr. Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB, developer of bimekizumab.
In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2-week and every-4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every-4-week dose (33.7%) were superior to the 15.6% response in placebo patients.
The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Dr. Kimball said.
Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Dr. Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was less than 4% at 16 weeks.
This is only the third phase 3 trial ever completed in patients with HS. In fact, Dr. Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.
“This is amazing news for our patients,” Dr. Kimball said. HS remains a challenging disease, even with a growing number of options showing benefit in large studies, she said, and the high rate of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
Multiple treatment options important
Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina at Chapel Hill, who publishes frequently about this disease.
“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a majority of patients after the first year,” he said.
Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.
“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF [tumor necrosis factor] antagonists,” he said.
Bimekizumab is not approved for any indication in the United States; it is approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in the EU/EEA, where it is marketed as Bimzelx, according to UCB. Dr. Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Dr. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – In two phase 3 trials, bimekizumab, a monoclonal antibody targeting two types of interleukin-17 — IL-17A and IL-17F — reduced the abscess and inflammatory nodule count better than placebo in the chronic inflammatory skin condition hidradenitis suppurativa (HS), according to results presented together during a late-breaker session at the annual meeting of the American Academy of Dermatology.
“We are very excited to add this data to what we already have around IL-17 inhibition. This clearly validates this target for the control of HS,” reported lead investigator Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston.
The trials, called BE HEARD I and BE HEARD II, enrolled 505 and 509 patients with HS, respectively. About 50% of patients in BE HEARD I and 60% of patients in BE HEARD II had Hurley stage 3 disease, which is the most severe of the three stratifications. The remainder were in Hurley stage 2. The mean duration of HS was 8.3 and 7.1 years, respectively.
Patients in both studies were randomized to one of four groups – either to a dosing regimen of 320 mg of bimekizumab administered by subcutaneous injection or to a placebo group. Both trials comprised double-blind 16-week initial and 32-week maintenance treatment periods.
In one experimental group, bimekizumab was given once every 2 weeks for the full course of the 48-week study (Q2W/Q2W). In another, patients started on the every-2-week schedule for 16 weeks and then were switched to every-4-week dosing (Q2W/Q4W). In the third group, patients started and remained on the every-4-week schedule (Q4W/Q4W). Patients in a fourth group started on placebo and switched at 16 weeks to the every-2-week bimekizumab schedule (placebo/Q2W).
Results at primary endpoint
The primary endpoint was HiSCR50, signifying a 50% reduction from baseline in abscess and inflammatory nodule count on the Hidradenitis Suppurativa Clinical Response (HiSCR) assessment tool. At 16 weeks, the initial Q2W dose in two of the groups outperformed the placebo in both BE HEARD I (47.8% vs. 28.7%) and BE HEARD II (52.0% vs. 32.2%). The response rates in the Q4W arm in BE HEARD I (45.3%) and BE HEARD II (53.8%) were also higher than the placebo, but the difference was only significant in BE HEARD II.
At 48 weeks, the proportion of patients with an HiSCR50 response climbed in all groups in both trials. The patterns were generally the same with slightly higher numerical responses among the groups that received the every-2-week dosing schedule relative to the every-4-week schedule.
In BE HEARD I at 48 weeks, the HiSCR50 response rate was about 60% for those who started and remained on every-2-week bimekizumab (Q2W/Q2W) or were switched at 16 weeks to every-4-week bimekizumab (Q2W/Q4W). For those who started and remained on every-4-week bimekizumab and the group started on placebo and switched to every-2-week bimekizumab, the response rates were 52.7% and 45.3%, respectively.
In BE HEARD II, the HiSCR50 response rates were higher in all groups, including the placebo, and the patterns of response were similar at 48 weeks. Most patients reached the HiSCR50 response – 79.8% (Q2W/Q2W), 78.4% (Q2W/Q4W), 76.7% (Q4W/Q4W), and 65.9 % (placebo/Q2W) of patients.
It is notable that, although there was rapid increase in the proportion of placebo patients reaching HiSCR50 after the switch at 16 weeks, there appeared to be an advantage at 48 weeks for starting on full-dose bimekizumab over starting on placebo.
In this trial, patients were listed as nonresponders if they received antibiotics at any time and for any reason after randomization. This might have concealed an even greater benefit of bimekizumab, Dr. Kimball said, but the study design element was considered necessary to isolate the activity of the study drug.
“In future HS trials, it will be helpful to address the difficulty of handling the impact of antibiotics and pain medications [in assessing results],” Dr. Kimball said.
Clinically meaningful secondary endpoint
For HS patients, the secondary endpoint of HiSCR75 might be considered the most meaningful, according to Dr. Kimball. She said that this higher bar not only documents a higher level of efficacy but correlates with meaningful improvement in quality of life. In the two trials combined, more than 55% of patients on continuous bimekizumab achieved HiSCR75 at week 48 in the observed case analysis, according to a news release from biopharmaceutical company UCB, developer of bimekizumab.
In BE HEARD I, the HiSCR75 rates were 33.4% and 24.7% for the every-2-week and every-4-week bimekizumab doses, respectively. The 33.4% response was statistically superior to placebo (18.4%). In BE HEARD II, both the every-2-week dose (35.7%) and the every-4-week dose (33.7%) were superior to the 15.6% response in placebo patients.
The improvements in quality of life as measured with the Dermatology Life Quality Index (DLQI), reflected the changes in disease activity. Relative to about a 3-point reduction from baseline in the placebo groups of the two trials, the 5-point reduction for either the 2-week or 4-week bimekizumab groups in each clinical trial were highly significant, Dr. Kimball said.
Bimekizumab was relatively well tolerated, although it shares the increased risk for candidiasis observed with this agent when used in psoriasis and with other IL-17 inhibitors, such as secukinumab (Cosentyx), in general. The risk of candidiasis appeared to be dose related, but cases were generally mild and easily managed, according to Dr. Kimball. She noted that only three patients discontinued treatment for this reason. Discontinuations for a treatment-related adverse event overall was less than 4% at 16 weeks.
This is only the third phase 3 trial ever completed in patients with HS. In fact, Dr. Kimball has led all of the phase 3 trials so far, including clinical studies of adalimumab (Humira), published in 2016, and of secukinumab, published earlier this year. All were positive studies.
“This is amazing news for our patients,” Dr. Kimball said. HS remains a challenging disease, even with a growing number of options showing benefit in large studies, she said, and the high rate of response, particularly at the level of HiSCR75, “is a huge milestone for what we can achieve.”
Multiple treatment options important
Her assessment was echoed by other experts, including Christopher J. Sayed, MD, an associate professor of dermatology at the University of North Carolina at Chapel Hill, who publishes frequently about this disease.
“It is incredibly exciting to see the strong phase 3 data on bimekizumab, particularly the deep responses at the HiSCR75 in a majority of patients after the first year,” he said.
Importantly, he does not see the growing array of treatment options as necessarily competitive for a disease with heterogeneous manifestations and variable responses to any one agent.
“While this may be a major step forward, it will still be critical to see more drugs come along for those who do not respond fully enough or have comorbidities that prevent the use of IL-17 and TNF [tumor necrosis factor] antagonists,” he said.
Bimekizumab is not approved for any indication in the United States; it is approved for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in the EU/EEA, where it is marketed as Bimzelx, according to UCB. Dr. Kimball reports financial relationships with AbbVie, Janssen, Kymera, Lilly, Novartis, Pfizer, and UCB. Dr. Sayed reports financial relationships with AbbVie, InflaRx, and UCB.
A version of this article first appeared on Medscape.com.
AT AAD 2023
Melanoma screening: Consensus statement offers greater clarity
That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.
Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.
In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.
“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.
The consensus statement was published online in JAMA Dermatology.
The need for guidance
Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.
In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.
To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.
The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.
Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.
In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”
The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.
In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.
“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.
In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.
The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”
Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.
The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.
A version of this article first appeared on Medscape.com.
That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.
Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.
In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.
“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.
The consensus statement was published online in JAMA Dermatology.
The need for guidance
Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.
In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.
To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.
The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.
Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.
In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”
The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.
In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.
“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.
In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.
The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”
Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.
The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.
A version of this article first appeared on Medscape.com.
That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.
Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.
In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.
“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.
The consensus statement was published online in JAMA Dermatology.
The need for guidance
Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.
In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.
To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.
The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.
Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.
In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”
The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.
In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.
“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.
In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.
The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”
Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.
The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.
A version of this article first appeared on Medscape.com.
FROM JAMA DERMATOLOGY
Novel single-use patch shows promise for primary axillary hyperhidrosis
NEW ORLEANS – , results from a pivotal randomized trial showed.
“This is a new kind of device that is going to be a nice tool to have for treating patients who have hyperhidrosis of the axilla,” the study’s lead investigator, David M. Pariser, MD, who practices dermatology in Norfolk, Va., said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
In a study known as SAHARA, investigators at 11 sites evaluated the efficacy of the targeted alkali thermolysis (TAT) patch, a single-use disposable device. The patch consists of a thin sodium layer on an adhesive overlay. It’s applied to the dry axilla, and as the patient sweats during treatment, the sweat reacts with the sodium. According to Dr. Pariser, this interaction generates precisely targeted thermal energy that targets sweat glands, leading to a reduction in excessive sweat production for up to three months.
The researchers enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 and randomized them to either an active TAT or a sham patch for up to 3 minutes. Their mean age was about 33 years, and slightly more than half were women. “If significant discomfort or pain was noted, [the patch] treatment was halted; otherwise, it was left on for 3 minutes,” said Dr. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk. “The treated area was thoroughly cleaned after treatment, and the TAT patch was deactivated. This process was repeated on the other axilla.”
The HDSS, Gravimetric Sweat Production (GSP), and quality of life assessments for bother and impact were measured through 12 weeks. The quality of life assessments were an exploratory endpoint and scored from 0 to 4, with 4 being extremely bothered or impacted and 0 not being bothered or impacted at all. The primary efficacy endpoint was the proportion of treated patients achieving a 1 or 2 on the HDSS at week 4, compared with sham treatment.
Secondary endpoints included the proportion of patients with an improvement of at least 2 grades from baseline to 4 weeks in HDSS by treatment group; mean improvement in the quality of life scale bother by treatment group; mean improvement in the quality of life scale impact by treatment group; and the proportion of subjects with at least 50% improvement in GSP from baseline to 4 weeks in the active patch group only.
Adverse events (AEs) were divided into 3 categories: AEs at the treatment site (or skin reactions within the treated part of the axilla); procedure-related AEs (those that are the result of treatment, but not in the treated part of the axilla), and non-axillary AEs.
Dr. Pariser reported that at 4 weeks, 63.6% of patients in the active patch group versus 44.2% of those in the sham group improved to an HDSS score of 1 or 2 (P = .0332) and that 43.2% of those in the active patch group versus 16.3% of those in the sham group (P = .0107) achieved a 2-point or greater HDSS improvement. In addition, 9.1% of those in the active patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” he commented.
In other findings, 60.5% of patients in the active patch group showed at least a 50% reduction in GSP, compared with 32.6% of those in the sham group (P = .0102), with mean reductions of 57.3 mg/5min and 18.2 mg/5min, respectively (P = .0036). As for quality-of-life outcome scores, bother associated with hyperhidrosis was reduced by 1.52 points in active versus 0.61 in sham subjects (P = .0005), while impact was reduced by 1.44 in active versus 0.57 in sham subjects (P = .0004).
Adverse events
A total of 13 patients in the active patch group experienced AEs at the treatment site, including six with erythema; four with erosion; two with burning, itching or stinging; and one with underarm odor. “The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” said Dr. Pariser said.
Most adverse events resolved in fewer than 2 weeks, and all were mild to moderate. No serious adverse events occurred. Only five adverse events occurred in the sham group.
The TAT patch is currently undergoing review by the Food and Drug Administration, and according to Dr. Pariser, no other body sites have been treated with the device.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized hyperhidrosis as “an exceedingly common medical condition that is commonly overlooked even though it has a tremendous burden on quality of life. I should know, as both someone who manages a large cohort of these patients but also as someone who suffers from it.”
Treatment options “have historically been limited, many of which are off-label and some which are difficult to access due to cost and/or duration/frequency of treatment,” added Dr. Friedman, who was not involved with the study. “The TAT patch offers a new, targeted, in-office, practical procedure-based approach to treat primary axillary hyperhidrosis. Innovation is certainly welcomed and needed, and I am curious to see how this technology is employed in practice once approved.”
The device is being developed by Candesant Biomedical. Dr. Pariser disclosed that he is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.
Dr. Friedman reported having no relevant disclosures.
NEW ORLEANS – , results from a pivotal randomized trial showed.
“This is a new kind of device that is going to be a nice tool to have for treating patients who have hyperhidrosis of the axilla,” the study’s lead investigator, David M. Pariser, MD, who practices dermatology in Norfolk, Va., said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
In a study known as SAHARA, investigators at 11 sites evaluated the efficacy of the targeted alkali thermolysis (TAT) patch, a single-use disposable device. The patch consists of a thin sodium layer on an adhesive overlay. It’s applied to the dry axilla, and as the patient sweats during treatment, the sweat reacts with the sodium. According to Dr. Pariser, this interaction generates precisely targeted thermal energy that targets sweat glands, leading to a reduction in excessive sweat production for up to three months.
The researchers enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 and randomized them to either an active TAT or a sham patch for up to 3 minutes. Their mean age was about 33 years, and slightly more than half were women. “If significant discomfort or pain was noted, [the patch] treatment was halted; otherwise, it was left on for 3 minutes,” said Dr. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk. “The treated area was thoroughly cleaned after treatment, and the TAT patch was deactivated. This process was repeated on the other axilla.”
The HDSS, Gravimetric Sweat Production (GSP), and quality of life assessments for bother and impact were measured through 12 weeks. The quality of life assessments were an exploratory endpoint and scored from 0 to 4, with 4 being extremely bothered or impacted and 0 not being bothered or impacted at all. The primary efficacy endpoint was the proportion of treated patients achieving a 1 or 2 on the HDSS at week 4, compared with sham treatment.
Secondary endpoints included the proportion of patients with an improvement of at least 2 grades from baseline to 4 weeks in HDSS by treatment group; mean improvement in the quality of life scale bother by treatment group; mean improvement in the quality of life scale impact by treatment group; and the proportion of subjects with at least 50% improvement in GSP from baseline to 4 weeks in the active patch group only.
Adverse events (AEs) were divided into 3 categories: AEs at the treatment site (or skin reactions within the treated part of the axilla); procedure-related AEs (those that are the result of treatment, but not in the treated part of the axilla), and non-axillary AEs.
Dr. Pariser reported that at 4 weeks, 63.6% of patients in the active patch group versus 44.2% of those in the sham group improved to an HDSS score of 1 or 2 (P = .0332) and that 43.2% of those in the active patch group versus 16.3% of those in the sham group (P = .0107) achieved a 2-point or greater HDSS improvement. In addition, 9.1% of those in the active patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” he commented.
In other findings, 60.5% of patients in the active patch group showed at least a 50% reduction in GSP, compared with 32.6% of those in the sham group (P = .0102), with mean reductions of 57.3 mg/5min and 18.2 mg/5min, respectively (P = .0036). As for quality-of-life outcome scores, bother associated with hyperhidrosis was reduced by 1.52 points in active versus 0.61 in sham subjects (P = .0005), while impact was reduced by 1.44 in active versus 0.57 in sham subjects (P = .0004).
Adverse events
A total of 13 patients in the active patch group experienced AEs at the treatment site, including six with erythema; four with erosion; two with burning, itching or stinging; and one with underarm odor. “The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” said Dr. Pariser said.
Most adverse events resolved in fewer than 2 weeks, and all were mild to moderate. No serious adverse events occurred. Only five adverse events occurred in the sham group.
The TAT patch is currently undergoing review by the Food and Drug Administration, and according to Dr. Pariser, no other body sites have been treated with the device.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized hyperhidrosis as “an exceedingly common medical condition that is commonly overlooked even though it has a tremendous burden on quality of life. I should know, as both someone who manages a large cohort of these patients but also as someone who suffers from it.”
Treatment options “have historically been limited, many of which are off-label and some which are difficult to access due to cost and/or duration/frequency of treatment,” added Dr. Friedman, who was not involved with the study. “The TAT patch offers a new, targeted, in-office, practical procedure-based approach to treat primary axillary hyperhidrosis. Innovation is certainly welcomed and needed, and I am curious to see how this technology is employed in practice once approved.”
The device is being developed by Candesant Biomedical. Dr. Pariser disclosed that he is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.
Dr. Friedman reported having no relevant disclosures.
NEW ORLEANS – , results from a pivotal randomized trial showed.
“This is a new kind of device that is going to be a nice tool to have for treating patients who have hyperhidrosis of the axilla,” the study’s lead investigator, David M. Pariser, MD, who practices dermatology in Norfolk, Va., said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
In a study known as SAHARA, investigators at 11 sites evaluated the efficacy of the targeted alkali thermolysis (TAT) patch, a single-use disposable device. The patch consists of a thin sodium layer on an adhesive overlay. It’s applied to the dry axilla, and as the patient sweats during treatment, the sweat reacts with the sodium. According to Dr. Pariser, this interaction generates precisely targeted thermal energy that targets sweat glands, leading to a reduction in excessive sweat production for up to three months.
The researchers enrolled 110 individuals with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 and randomized them to either an active TAT or a sham patch for up to 3 minutes. Their mean age was about 33 years, and slightly more than half were women. “If significant discomfort or pain was noted, [the patch] treatment was halted; otherwise, it was left on for 3 minutes,” said Dr. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk. “The treated area was thoroughly cleaned after treatment, and the TAT patch was deactivated. This process was repeated on the other axilla.”
The HDSS, Gravimetric Sweat Production (GSP), and quality of life assessments for bother and impact were measured through 12 weeks. The quality of life assessments were an exploratory endpoint and scored from 0 to 4, with 4 being extremely bothered or impacted and 0 not being bothered or impacted at all. The primary efficacy endpoint was the proportion of treated patients achieving a 1 or 2 on the HDSS at week 4, compared with sham treatment.
Secondary endpoints included the proportion of patients with an improvement of at least 2 grades from baseline to 4 weeks in HDSS by treatment group; mean improvement in the quality of life scale bother by treatment group; mean improvement in the quality of life scale impact by treatment group; and the proportion of subjects with at least 50% improvement in GSP from baseline to 4 weeks in the active patch group only.
Adverse events (AEs) were divided into 3 categories: AEs at the treatment site (or skin reactions within the treated part of the axilla); procedure-related AEs (those that are the result of treatment, but not in the treated part of the axilla), and non-axillary AEs.
Dr. Pariser reported that at 4 weeks, 63.6% of patients in the active patch group versus 44.2% of those in the sham group improved to an HDSS score of 1 or 2 (P = .0332) and that 43.2% of those in the active patch group versus 16.3% of those in the sham group (P = .0107) achieved a 2-point or greater HDSS improvement. In addition, 9.1% of those in the active patch group achieved a 3-point improvement on the HDSS, compared with none in the sham group. “That’s an amazing improvement; you’re basically going from moderate or severe to none,” he commented.
In other findings, 60.5% of patients in the active patch group showed at least a 50% reduction in GSP, compared with 32.6% of those in the sham group (P = .0102), with mean reductions of 57.3 mg/5min and 18.2 mg/5min, respectively (P = .0036). As for quality-of-life outcome scores, bother associated with hyperhidrosis was reduced by 1.52 points in active versus 0.61 in sham subjects (P = .0005), while impact was reduced by 1.44 in active versus 0.57 in sham subjects (P = .0004).
Adverse events
A total of 13 patients in the active patch group experienced AEs at the treatment site, including six with erythema; four with erosion; two with burning, itching or stinging; and one with underarm odor. “The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” said Dr. Pariser said.
Most adverse events resolved in fewer than 2 weeks, and all were mild to moderate. No serious adverse events occurred. Only five adverse events occurred in the sham group.
The TAT patch is currently undergoing review by the Food and Drug Administration, and according to Dr. Pariser, no other body sites have been treated with the device.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized hyperhidrosis as “an exceedingly common medical condition that is commonly overlooked even though it has a tremendous burden on quality of life. I should know, as both someone who manages a large cohort of these patients but also as someone who suffers from it.”
Treatment options “have historically been limited, many of which are off-label and some which are difficult to access due to cost and/or duration/frequency of treatment,” added Dr. Friedman, who was not involved with the study. “The TAT patch offers a new, targeted, in-office, practical procedure-based approach to treat primary axillary hyperhidrosis. Innovation is certainly welcomed and needed, and I am curious to see how this technology is employed in practice once approved.”
The device is being developed by Candesant Biomedical. Dr. Pariser disclosed that he is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.
Dr. Friedman reported having no relevant disclosures.
AT AAD 2023
CSU in children: Study identifies biomarkers associated with responses to different treatments
NEW ORLEANS – , results from a single-center prospective study showed.
“Given that the majority of CSU cases in adults are due to autoimmunity and there being very [few] studies on biomarkers for CSU in children, our study furthers our current understanding of the role of different biomarkers in treatment response,” lead study author Alex Nguyen, MsC, said in an interview at the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
To identify biomarkers with treatment and disease resolution in children with CSU, Mr. Nguyen, a 4-year medical student at McGill University, Montreal, and colleagues prospectively recruited 109 children from the Montreal Children’s Hospital Allergy and Immunology Clinic who reported hives for at least 6 weeks from 2013 to 2022. They obtained levels of thyroid stimulating hormone (TSH), anti-thyroxine peroxidase (anti-TPO), total immunoglobulin E (IgE), CD63, tryptase, eosinophils, MPV, and platelets; the weekly urticaria activity score (UAS7) was recorded at study entry.
Levels of treatment included antihistamines at standard dose, four times the standard dose, omalizumab, and resolution of treatment. The researchers used univariate and multivariate logistic regressions to determine factors associated with different treatment levels and resolution.
Slightly more than half of the study participants (55%) were female, and their mean age was 9 years. Mr. Nguyen and colleagues observed that elevated MPV was associated with the four times increased dose of antihistamines treatment level (odds ratio = 1.052, 95% confidence interval = 1.004-1.103). Lower age was associated with disease resolution (OR = 0.982, 95% CI = 0.965-0.999).
After adjustment for age, sex, TSH, anti-TPO, total IgE, CD63, eosinophils, MPV, and platelets, elevated tryptase was associated with the antihistamine use at standard dose level (OR = 1.152, 95% CI = 1.019-1.302) and lower tryptase levels with disease resolution (OR = .861, 95% CI = 0.777-0.955).
“We were fascinated when we found that tryptase levels in patients with chronic spontaneous urticaria were associated with standard dose of antihistamines and even disease resolution,” Mr. Nguyen said. “Higher tryptase levels were associated with standard dose antihistamines, which potentially could imply an increase in mast cell activation. Furthermore, we saw that lower tryptase levels were associated with disease resolution likely given if the disease may not have been as severe.”
He acknowledged certain limitations of the study, including a limited sample size and an unbalanced sample size among treatment groups. In the future, he and his colleagues plan to increase the sample size and to include other biomarkers such as interleukin (IL)-6, D-dimer, vitamin D, and matrix mettaloproteinase-9.
“Much as the name suggests, CSU often arises without a clear trigger,” said Raj Chovatiya, MD, PhD, assistant professor in the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study. “Particularly in children, little is known about potential biomarkers that may guide treatment or disease resolution. While a larger, prospective analysis would better characterize temporal trends in serum biomarkers in relation to disease activity, these data suggest that underlying mechanisms of tryptase may be worth an in-depth look in children with CSU.”
The study was recognized as the second-best poster at the meeting. The researchers reported having no financial disclosures. The other study coauthors were Michelle Le MD, Sofianne Gabrielli MSc, Elena Netchiporouk, MD, MSc, and Moshe Ben-Shoshan, MD, MSc. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for several pharmaceutical companies.
NEW ORLEANS – , results from a single-center prospective study showed.
“Given that the majority of CSU cases in adults are due to autoimmunity and there being very [few] studies on biomarkers for CSU in children, our study furthers our current understanding of the role of different biomarkers in treatment response,” lead study author Alex Nguyen, MsC, said in an interview at the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
To identify biomarkers with treatment and disease resolution in children with CSU, Mr. Nguyen, a 4-year medical student at McGill University, Montreal, and colleagues prospectively recruited 109 children from the Montreal Children’s Hospital Allergy and Immunology Clinic who reported hives for at least 6 weeks from 2013 to 2022. They obtained levels of thyroid stimulating hormone (TSH), anti-thyroxine peroxidase (anti-TPO), total immunoglobulin E (IgE), CD63, tryptase, eosinophils, MPV, and platelets; the weekly urticaria activity score (UAS7) was recorded at study entry.
Levels of treatment included antihistamines at standard dose, four times the standard dose, omalizumab, and resolution of treatment. The researchers used univariate and multivariate logistic regressions to determine factors associated with different treatment levels and resolution.
Slightly more than half of the study participants (55%) were female, and their mean age was 9 years. Mr. Nguyen and colleagues observed that elevated MPV was associated with the four times increased dose of antihistamines treatment level (odds ratio = 1.052, 95% confidence interval = 1.004-1.103). Lower age was associated with disease resolution (OR = 0.982, 95% CI = 0.965-0.999).
After adjustment for age, sex, TSH, anti-TPO, total IgE, CD63, eosinophils, MPV, and platelets, elevated tryptase was associated with the antihistamine use at standard dose level (OR = 1.152, 95% CI = 1.019-1.302) and lower tryptase levels with disease resolution (OR = .861, 95% CI = 0.777-0.955).
“We were fascinated when we found that tryptase levels in patients with chronic spontaneous urticaria were associated with standard dose of antihistamines and even disease resolution,” Mr. Nguyen said. “Higher tryptase levels were associated with standard dose antihistamines, which potentially could imply an increase in mast cell activation. Furthermore, we saw that lower tryptase levels were associated with disease resolution likely given if the disease may not have been as severe.”
He acknowledged certain limitations of the study, including a limited sample size and an unbalanced sample size among treatment groups. In the future, he and his colleagues plan to increase the sample size and to include other biomarkers such as interleukin (IL)-6, D-dimer, vitamin D, and matrix mettaloproteinase-9.
“Much as the name suggests, CSU often arises without a clear trigger,” said Raj Chovatiya, MD, PhD, assistant professor in the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study. “Particularly in children, little is known about potential biomarkers that may guide treatment or disease resolution. While a larger, prospective analysis would better characterize temporal trends in serum biomarkers in relation to disease activity, these data suggest that underlying mechanisms of tryptase may be worth an in-depth look in children with CSU.”
The study was recognized as the second-best poster at the meeting. The researchers reported having no financial disclosures. The other study coauthors were Michelle Le MD, Sofianne Gabrielli MSc, Elena Netchiporouk, MD, MSc, and Moshe Ben-Shoshan, MD, MSc. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for several pharmaceutical companies.
NEW ORLEANS – , results from a single-center prospective study showed.
“Given that the majority of CSU cases in adults are due to autoimmunity and there being very [few] studies on biomarkers for CSU in children, our study furthers our current understanding of the role of different biomarkers in treatment response,” lead study author Alex Nguyen, MsC, said in an interview at the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
To identify biomarkers with treatment and disease resolution in children with CSU, Mr. Nguyen, a 4-year medical student at McGill University, Montreal, and colleagues prospectively recruited 109 children from the Montreal Children’s Hospital Allergy and Immunology Clinic who reported hives for at least 6 weeks from 2013 to 2022. They obtained levels of thyroid stimulating hormone (TSH), anti-thyroxine peroxidase (anti-TPO), total immunoglobulin E (IgE), CD63, tryptase, eosinophils, MPV, and platelets; the weekly urticaria activity score (UAS7) was recorded at study entry.
Levels of treatment included antihistamines at standard dose, four times the standard dose, omalizumab, and resolution of treatment. The researchers used univariate and multivariate logistic regressions to determine factors associated with different treatment levels and resolution.
Slightly more than half of the study participants (55%) were female, and their mean age was 9 years. Mr. Nguyen and colleagues observed that elevated MPV was associated with the four times increased dose of antihistamines treatment level (odds ratio = 1.052, 95% confidence interval = 1.004-1.103). Lower age was associated with disease resolution (OR = 0.982, 95% CI = 0.965-0.999).
After adjustment for age, sex, TSH, anti-TPO, total IgE, CD63, eosinophils, MPV, and platelets, elevated tryptase was associated with the antihistamine use at standard dose level (OR = 1.152, 95% CI = 1.019-1.302) and lower tryptase levels with disease resolution (OR = .861, 95% CI = 0.777-0.955).
“We were fascinated when we found that tryptase levels in patients with chronic spontaneous urticaria were associated with standard dose of antihistamines and even disease resolution,” Mr. Nguyen said. “Higher tryptase levels were associated with standard dose antihistamines, which potentially could imply an increase in mast cell activation. Furthermore, we saw that lower tryptase levels were associated with disease resolution likely given if the disease may not have been as severe.”
He acknowledged certain limitations of the study, including a limited sample size and an unbalanced sample size among treatment groups. In the future, he and his colleagues plan to increase the sample size and to include other biomarkers such as interleukin (IL)-6, D-dimer, vitamin D, and matrix mettaloproteinase-9.
“Much as the name suggests, CSU often arises without a clear trigger,” said Raj Chovatiya, MD, PhD, assistant professor in the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study. “Particularly in children, little is known about potential biomarkers that may guide treatment or disease resolution. While a larger, prospective analysis would better characterize temporal trends in serum biomarkers in relation to disease activity, these data suggest that underlying mechanisms of tryptase may be worth an in-depth look in children with CSU.”
The study was recognized as the second-best poster at the meeting. The researchers reported having no financial disclosures. The other study coauthors were Michelle Le MD, Sofianne Gabrielli MSc, Elena Netchiporouk, MD, MSc, and Moshe Ben-Shoshan, MD, MSc. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for several pharmaceutical companies.
AT AAD 2023
JAK inhibitor safety warnings drawn from rheumatologic data may be misleading in dermatology
NEW ORLEANS – , even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.
Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.
The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream.
Basis of boxed warnings
In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m2.
After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.
In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.
Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
Evidence of difference in dermatology
There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.
For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.
When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.
Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.
“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.
Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.
Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”
“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
Risk-benefit considerations in dermatology
This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.
Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.
“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”
George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.
“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.
“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”
Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.
Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.
A version of this article originally appeared on Medscape.com.
NEW ORLEANS – , even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.
Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.
The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream.
Basis of boxed warnings
In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m2.
After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.
In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.
Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
Evidence of difference in dermatology
There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.
For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.
When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.
Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.
“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.
Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.
Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”
“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
Risk-benefit considerations in dermatology
This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.
Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.
“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”
George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.
“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.
“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”
Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.
Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.
A version of this article originally appeared on Medscape.com.
NEW ORLEANS – , even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.
Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.
The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream.
Basis of boxed warnings
In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m2.
After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.
In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.
Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
Evidence of difference in dermatology
There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.
For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.
When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.
Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.
“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.
Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.
Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”
“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
Risk-benefit considerations in dermatology
This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.
Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.
“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”
George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.
“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.
“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”
Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.
Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.
A version of this article originally appeared on Medscape.com.
AT AAD 2023
Lanolin gets nod for Allergen of the Year
Lanolin is a complex and varying mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons, but the allergic components are mainly the free lanolin alcohols, especially alkanediols, said Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, who announced the Allergen of the Year at the society’s annual meeting.
Criteria for selection can include a known allergen with a new twist or increasing frequency or a newly reported allergen with mini-epidemics that may have been missed for years, Dr. Belsito said.
“The prevalence and severity of allergy to ‘lanolin’ have been hotly debated” since a potential case was first reported in the 1920s, wrote Dr. Belsito and Blair A. Jenkins, MD, PhD, a dermatology resident at New York–Presbyterian Hospital, Columbia Campus, in a review published in Dermatitis.
“ ‘Lanolin’ is indeed a paradox allergen,” wrote Dr. Jenkins and Dr. Belsito. “The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results.”
And those who test positive for a lanolin allergy on diseased skin may be able to use lanolin products on normal skin, they wrote.
“From my perspective, this was a timely year to think about lanolin, as there is significant ongoing controversy about whether it is allergenic,” Dr. Jenkins said in an interview. “Numerous companies market lanolin-containing topicals as safe and effective emollients,” she said.
Medical grade and highly purified anhydrous lanolin, which contain less than 2.5% and less than 1.5% of free alcohols, respectively, can still elicit or induce a contact allergy, Dr. Belsito said in his presentation. Hydrogenated lanolin has shown more allergenicity than lanolin alcohol, while lanolin wax, lanolin acid, and lanolin esters possess lower allergenicity than lanolin alcohol, he said.
Notably, modern wool textiles do not contain lanolin, and lanolin-allergic patients need not avoid wool, Dr. Belsito added.
Amerchol L-101, a common trade name on products containing lanolin, contains 10% wool wax alcohols obtained from the hydrolysis of wool fat dissolved in mineral oil at a 1:1 ratio, said Dr. Belsito. He recommended testing lanolin alcohols (in 30% petrolatum) and Amerchol L-101 (in 50% petrolatum) simultaneously with or without other lanolin derivatives and/or the patient’s products in cases of possible allergy, he said.
Consider high-risk groups
Current evidence suggests that the prevalence of contact allergy in the western European population is 0.4%, wrote Dr. Jenkins and Dr. Belsito.
Although the frequency of lanolin allergy is relatively low, certain conditions convey greater risk, such as stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis, they wrote. Older adults and children are at increased risk because they are more likely to have these conditions. Demographic data also suggest that lanolin allergy is more common in non-Hispanic Whites than in non-Hispanic Blacks, they wrote.
Looking ahead, “I think further exploration of allergy across different skin types and ethnicities is warranted,” Dr. Jenkins said. “Further investigation of ideal [lanolin] allergens for patch testing is also needed.”
Dr. Jenkins and Dr. Belsito said they had no relevant financial conflicts to disclose.
Lanolin is a complex and varying mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons, but the allergic components are mainly the free lanolin alcohols, especially alkanediols, said Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, who announced the Allergen of the Year at the society’s annual meeting.
Criteria for selection can include a known allergen with a new twist or increasing frequency or a newly reported allergen with mini-epidemics that may have been missed for years, Dr. Belsito said.
“The prevalence and severity of allergy to ‘lanolin’ have been hotly debated” since a potential case was first reported in the 1920s, wrote Dr. Belsito and Blair A. Jenkins, MD, PhD, a dermatology resident at New York–Presbyterian Hospital, Columbia Campus, in a review published in Dermatitis.
“ ‘Lanolin’ is indeed a paradox allergen,” wrote Dr. Jenkins and Dr. Belsito. “The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results.”
And those who test positive for a lanolin allergy on diseased skin may be able to use lanolin products on normal skin, they wrote.
“From my perspective, this was a timely year to think about lanolin, as there is significant ongoing controversy about whether it is allergenic,” Dr. Jenkins said in an interview. “Numerous companies market lanolin-containing topicals as safe and effective emollients,” she said.
Medical grade and highly purified anhydrous lanolin, which contain less than 2.5% and less than 1.5% of free alcohols, respectively, can still elicit or induce a contact allergy, Dr. Belsito said in his presentation. Hydrogenated lanolin has shown more allergenicity than lanolin alcohol, while lanolin wax, lanolin acid, and lanolin esters possess lower allergenicity than lanolin alcohol, he said.
Notably, modern wool textiles do not contain lanolin, and lanolin-allergic patients need not avoid wool, Dr. Belsito added.
Amerchol L-101, a common trade name on products containing lanolin, contains 10% wool wax alcohols obtained from the hydrolysis of wool fat dissolved in mineral oil at a 1:1 ratio, said Dr. Belsito. He recommended testing lanolin alcohols (in 30% petrolatum) and Amerchol L-101 (in 50% petrolatum) simultaneously with or without other lanolin derivatives and/or the patient’s products in cases of possible allergy, he said.
Consider high-risk groups
Current evidence suggests that the prevalence of contact allergy in the western European population is 0.4%, wrote Dr. Jenkins and Dr. Belsito.
Although the frequency of lanolin allergy is relatively low, certain conditions convey greater risk, such as stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis, they wrote. Older adults and children are at increased risk because they are more likely to have these conditions. Demographic data also suggest that lanolin allergy is more common in non-Hispanic Whites than in non-Hispanic Blacks, they wrote.
Looking ahead, “I think further exploration of allergy across different skin types and ethnicities is warranted,” Dr. Jenkins said. “Further investigation of ideal [lanolin] allergens for patch testing is also needed.”
Dr. Jenkins and Dr. Belsito said they had no relevant financial conflicts to disclose.
Lanolin is a complex and varying mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons, but the allergic components are mainly the free lanolin alcohols, especially alkanediols, said Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, who announced the Allergen of the Year at the society’s annual meeting.
Criteria for selection can include a known allergen with a new twist or increasing frequency or a newly reported allergen with mini-epidemics that may have been missed for years, Dr. Belsito said.
“The prevalence and severity of allergy to ‘lanolin’ have been hotly debated” since a potential case was first reported in the 1920s, wrote Dr. Belsito and Blair A. Jenkins, MD, PhD, a dermatology resident at New York–Presbyterian Hospital, Columbia Campus, in a review published in Dermatitis.
“ ‘Lanolin’ is indeed a paradox allergen,” wrote Dr. Jenkins and Dr. Belsito. “The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results.”
And those who test positive for a lanolin allergy on diseased skin may be able to use lanolin products on normal skin, they wrote.
“From my perspective, this was a timely year to think about lanolin, as there is significant ongoing controversy about whether it is allergenic,” Dr. Jenkins said in an interview. “Numerous companies market lanolin-containing topicals as safe and effective emollients,” she said.
Medical grade and highly purified anhydrous lanolin, which contain less than 2.5% and less than 1.5% of free alcohols, respectively, can still elicit or induce a contact allergy, Dr. Belsito said in his presentation. Hydrogenated lanolin has shown more allergenicity than lanolin alcohol, while lanolin wax, lanolin acid, and lanolin esters possess lower allergenicity than lanolin alcohol, he said.
Notably, modern wool textiles do not contain lanolin, and lanolin-allergic patients need not avoid wool, Dr. Belsito added.
Amerchol L-101, a common trade name on products containing lanolin, contains 10% wool wax alcohols obtained from the hydrolysis of wool fat dissolved in mineral oil at a 1:1 ratio, said Dr. Belsito. He recommended testing lanolin alcohols (in 30% petrolatum) and Amerchol L-101 (in 50% petrolatum) simultaneously with or without other lanolin derivatives and/or the patient’s products in cases of possible allergy, he said.
Consider high-risk groups
Current evidence suggests that the prevalence of contact allergy in the western European population is 0.4%, wrote Dr. Jenkins and Dr. Belsito.
Although the frequency of lanolin allergy is relatively low, certain conditions convey greater risk, such as stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis, they wrote. Older adults and children are at increased risk because they are more likely to have these conditions. Demographic data also suggest that lanolin allergy is more common in non-Hispanic Whites than in non-Hispanic Blacks, they wrote.
Looking ahead, “I think further exploration of allergy across different skin types and ethnicities is warranted,” Dr. Jenkins said. “Further investigation of ideal [lanolin] allergens for patch testing is also needed.”
Dr. Jenkins and Dr. Belsito said they had no relevant financial conflicts to disclose.
FROM ACDS 2023
Study finds quality of topical steroid withdrawal videos on YouTube subpar
NEW ORLEANS –
“Video-sharing platforms such as YouTube are a great place for patients to connect and find community with others dealing with the same conditions,” senior author Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. “There is no doubt tremendous value in viewing the shared experience; however, it is important that medical advice be evidence based and validated. Seeking said advice from a medical professional such as a board-certified dermatologist will no doubt increase the likelihood that said guidance is supported by the literature and most importantly, will do no harm.”
Noting a trend of increased user-created content on social media and Internet sites about topical steroid withdrawal in recent years, Dr. Friedman, first author Erika McCormick, a fourth-year medical student at George Washington University, and colleagues used the keywords “topical steroid withdrawal” on YouTube to search for and analyze the top 10 most viewed videos on the subject.
Two independent reviewers used the modified DISCERN (mDISCERN) tool and the Global Quality Scale (GQS) to assess reliability and quality/scientific accuracy of videos, respectively. Average scores were generated for each video and the researchers used one way ANOVA, unpaired t-tests, and linear regression to analyze the ratings. For mDISCERN criteria, a point is given per each of five criteria for a possible score between 0 and 5. Examples of criteria included “Are the aims clear and achieved?” and “Is the information presented both balanced and unbiased”? For GQS, a score from 1 to 5 is designated based on criteria ranging from “poor quality, poor flow, most information missing” to “excellent quality and flow, very useful for patients.”
The researchers found that the mean combined mDISCERN score of the 10 videos was a 2, which indicates poor reliability and shortcomings. Similarly, the combined mean GQS score was 2.5, which suggests poor to moderate quality of videos, missing discussion of important topics, and limited use to patients. The researchers found no correlation between mDISCERN or GQS scores and length of video, duration on YouTube, or number of views, subscribers, or likes.
“We were disheartened that patient testimonial videos had the poorest quality and reliability of the information sources,” Ms. McCormick said in an interview. “Videos that included medical research and information from dermatologists had significantly higher quality and reliability scores than the remainder of videos.” Accurate information online is essential to help patients recognize topical steroid withdrawal and seek medical care, she continued.
Conversely, wide viewership of unreliable information “may contribute to fear of topical corticosteroids and dissuade use in patients with primary skin diseases that may benefit from this common treatment,” Dr. Friedman said. “Dermatologists must be aware of the content patients are consuming online, should guide patients in appraising quality and reliability of online resources, and must provide valid sources of additional information for their patients.” One such resource he recommended is the National Eczema Association, which has created online content for patients about topical steroid withdrawal.
Doris Day, MD, a New York–based dermatologist who was asked to comment on the study, said that many patients rely on YouTube as a go-to resource, with videos that can be watched at times of their choosing. “Oftentimes, the person on the video is relatable and has some general knowledge but is lacking the information that would be relevant and important for the individual patient,” said Dr. Day, who was not involved with the study. “The downside of this is that the person who takes that advice may not use the prescription properly or for the correct amount of time, which can lead to either undertreating or, even worse, overtreatment, which can have permanent consequences.”
One possible solution is for more doctors to create videos for YouTube, she added, “but that doesn’t guarantee that those would be the ones patients would choose to watch.” Another solution “is to have YouTube add qualifiers indicating that the information being discussed is not medical,” she suggested. “Ideally, patients will get all the information they need while they are in the office and also have clear written instructions and even a video they can review at a later time, made by the office, to help them feel they are getting personalized care and the attention they need.”
Ms. McCormick’s research is funded by a grant from Galderma. Dr. Friedman and Dr. Day had no relevant disclosures to report.
NEW ORLEANS –
“Video-sharing platforms such as YouTube are a great place for patients to connect and find community with others dealing with the same conditions,” senior author Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. “There is no doubt tremendous value in viewing the shared experience; however, it is important that medical advice be evidence based and validated. Seeking said advice from a medical professional such as a board-certified dermatologist will no doubt increase the likelihood that said guidance is supported by the literature and most importantly, will do no harm.”
Noting a trend of increased user-created content on social media and Internet sites about topical steroid withdrawal in recent years, Dr. Friedman, first author Erika McCormick, a fourth-year medical student at George Washington University, and colleagues used the keywords “topical steroid withdrawal” on YouTube to search for and analyze the top 10 most viewed videos on the subject.
Two independent reviewers used the modified DISCERN (mDISCERN) tool and the Global Quality Scale (GQS) to assess reliability and quality/scientific accuracy of videos, respectively. Average scores were generated for each video and the researchers used one way ANOVA, unpaired t-tests, and linear regression to analyze the ratings. For mDISCERN criteria, a point is given per each of five criteria for a possible score between 0 and 5. Examples of criteria included “Are the aims clear and achieved?” and “Is the information presented both balanced and unbiased”? For GQS, a score from 1 to 5 is designated based on criteria ranging from “poor quality, poor flow, most information missing” to “excellent quality and flow, very useful for patients.”
The researchers found that the mean combined mDISCERN score of the 10 videos was a 2, which indicates poor reliability and shortcomings. Similarly, the combined mean GQS score was 2.5, which suggests poor to moderate quality of videos, missing discussion of important topics, and limited use to patients. The researchers found no correlation between mDISCERN or GQS scores and length of video, duration on YouTube, or number of views, subscribers, or likes.
“We were disheartened that patient testimonial videos had the poorest quality and reliability of the information sources,” Ms. McCormick said in an interview. “Videos that included medical research and information from dermatologists had significantly higher quality and reliability scores than the remainder of videos.” Accurate information online is essential to help patients recognize topical steroid withdrawal and seek medical care, she continued.
Conversely, wide viewership of unreliable information “may contribute to fear of topical corticosteroids and dissuade use in patients with primary skin diseases that may benefit from this common treatment,” Dr. Friedman said. “Dermatologists must be aware of the content patients are consuming online, should guide patients in appraising quality and reliability of online resources, and must provide valid sources of additional information for their patients.” One such resource he recommended is the National Eczema Association, which has created online content for patients about topical steroid withdrawal.
Doris Day, MD, a New York–based dermatologist who was asked to comment on the study, said that many patients rely on YouTube as a go-to resource, with videos that can be watched at times of their choosing. “Oftentimes, the person on the video is relatable and has some general knowledge but is lacking the information that would be relevant and important for the individual patient,” said Dr. Day, who was not involved with the study. “The downside of this is that the person who takes that advice may not use the prescription properly or for the correct amount of time, which can lead to either undertreating or, even worse, overtreatment, which can have permanent consequences.”
One possible solution is for more doctors to create videos for YouTube, she added, “but that doesn’t guarantee that those would be the ones patients would choose to watch.” Another solution “is to have YouTube add qualifiers indicating that the information being discussed is not medical,” she suggested. “Ideally, patients will get all the information they need while they are in the office and also have clear written instructions and even a video they can review at a later time, made by the office, to help them feel they are getting personalized care and the attention they need.”
Ms. McCormick’s research is funded by a grant from Galderma. Dr. Friedman and Dr. Day had no relevant disclosures to report.
NEW ORLEANS –
“Video-sharing platforms such as YouTube are a great place for patients to connect and find community with others dealing with the same conditions,” senior author Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. “There is no doubt tremendous value in viewing the shared experience; however, it is important that medical advice be evidence based and validated. Seeking said advice from a medical professional such as a board-certified dermatologist will no doubt increase the likelihood that said guidance is supported by the literature and most importantly, will do no harm.”
Noting a trend of increased user-created content on social media and Internet sites about topical steroid withdrawal in recent years, Dr. Friedman, first author Erika McCormick, a fourth-year medical student at George Washington University, and colleagues used the keywords “topical steroid withdrawal” on YouTube to search for and analyze the top 10 most viewed videos on the subject.
Two independent reviewers used the modified DISCERN (mDISCERN) tool and the Global Quality Scale (GQS) to assess reliability and quality/scientific accuracy of videos, respectively. Average scores were generated for each video and the researchers used one way ANOVA, unpaired t-tests, and linear regression to analyze the ratings. For mDISCERN criteria, a point is given per each of five criteria for a possible score between 0 and 5. Examples of criteria included “Are the aims clear and achieved?” and “Is the information presented both balanced and unbiased”? For GQS, a score from 1 to 5 is designated based on criteria ranging from “poor quality, poor flow, most information missing” to “excellent quality and flow, very useful for patients.”
The researchers found that the mean combined mDISCERN score of the 10 videos was a 2, which indicates poor reliability and shortcomings. Similarly, the combined mean GQS score was 2.5, which suggests poor to moderate quality of videos, missing discussion of important topics, and limited use to patients. The researchers found no correlation between mDISCERN or GQS scores and length of video, duration on YouTube, or number of views, subscribers, or likes.
“We were disheartened that patient testimonial videos had the poorest quality and reliability of the information sources,” Ms. McCormick said in an interview. “Videos that included medical research and information from dermatologists had significantly higher quality and reliability scores than the remainder of videos.” Accurate information online is essential to help patients recognize topical steroid withdrawal and seek medical care, she continued.
Conversely, wide viewership of unreliable information “may contribute to fear of topical corticosteroids and dissuade use in patients with primary skin diseases that may benefit from this common treatment,” Dr. Friedman said. “Dermatologists must be aware of the content patients are consuming online, should guide patients in appraising quality and reliability of online resources, and must provide valid sources of additional information for their patients.” One such resource he recommended is the National Eczema Association, which has created online content for patients about topical steroid withdrawal.
Doris Day, MD, a New York–based dermatologist who was asked to comment on the study, said that many patients rely on YouTube as a go-to resource, with videos that can be watched at times of their choosing. “Oftentimes, the person on the video is relatable and has some general knowledge but is lacking the information that would be relevant and important for the individual patient,” said Dr. Day, who was not involved with the study. “The downside of this is that the person who takes that advice may not use the prescription properly or for the correct amount of time, which can lead to either undertreating or, even worse, overtreatment, which can have permanent consequences.”
One possible solution is for more doctors to create videos for YouTube, she added, “but that doesn’t guarantee that those would be the ones patients would choose to watch.” Another solution “is to have YouTube add qualifiers indicating that the information being discussed is not medical,” she suggested. “Ideally, patients will get all the information they need while they are in the office and also have clear written instructions and even a video they can review at a later time, made by the office, to help them feel they are getting personalized care and the attention they need.”
Ms. McCormick’s research is funded by a grant from Galderma. Dr. Friedman and Dr. Day had no relevant disclosures to report.
AT AAD 2023
Spironolactone: an ‘inexpensive, effective’ option for acne in women
HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.
“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!
An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.
According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.
“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”
A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.
Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.
Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.
In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).
According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”
A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.
The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.
Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.
Medscape and this news organization are owned by the same parent company.
HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.
“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!
An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.
According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.
“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”
A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.
Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.
Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.
In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).
According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”
A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.
The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.
Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.
Medscape and this news organization are owned by the same parent company.
HONOLULU – In the clinical experience of Julie C. Harper, MD, an increasing number of women with acne are turning to off-label, long-term treatment with spironolactone.
“Spironolactone is fairly accessible, inexpensive, and effective for our patients,” Dr. Harper, a dermatologist who practices in Birmingham, Ala., said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!
An aldosterone receptor antagonist commonly used to treat high blood pressure and heart failure, spironolactone also has antiandrogenic properties with a proven track record for treating acne and hirsutism. It reduces androgen production, inhibits 5-alpha reductase, and increases sex hormone binding globulin. The dosing range for treating acne is 25 mg to 200 mg per day, but Dr. Harper prefers a maximum dose of 100 mg per day.
According to a systematic review of its use for acne in adult women, the most common side effect is menstrual irregularity, while other common side effects include breast tenderness/swelling, fatigue, and headaches.
“The higher the dose, the higher the rate of side effects,” she said. Concomitant use of an oral contraceptive lessens menstrual irregularities and prevents pregnancies, to avoid exposure during pregnancy and the hypothetical risk of feminization of the male fetus with exposure late in the first trimester. “Early in my career, I used to say if you’re going to be on spironolactone you’re also going to be on an oral contraceptive. But the longer I’ve practiced, I’ve learned that women who have a contraindication to birth control pills or who don’t want to take it can still benefit from an oral antiandrogen by being on spironolactone.”
A large retrospective analysis of 14-year data concluded that routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne. “If you’re between the ages of 18 and 45, healthy, and not taking other medications where I’m worried about potassium levels, I’m not checking those levels at all,” Dr. Harper said.
Spironolactone labeling includes a boxed warning regarding the potential for tumorigenicity based on rat studies, but the dosages used in those studies were 25-250 times higher than the exposure dose in humans, Dr. Harper said.
Results from a systematic review and meta-analysis of seven studies in the medical literature found no evidence of an increased risk of breast cancer in women with exposure to spironolactone. “However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism,” the study authors wrote.
In a separate study, researchers drew from patients in the Humana Insurance database from 2005 to 2017 to address whether spironolactone is associated with an increased risk of recurrence of breast cancer. Recurrent breast cancer was examined in 29,146 women with continuous health insurance for 2 years after a diagnosis of breast cancer. Of these, 746 were prescribed spironolactone, and the remainder were not. The researchers found that 123 women (16.5%) who were prescribed spironolactone had a breast cancer recurrence, compared with 3,649 women (12.8%) with a breast cancer recurrence who had not been prescribed spironolactone (P = .004). Adjusted Cox regression analysis following propensity matching showed no association between spironolactone and increased breast cancer recurrence (adjusted hazard ratio, 0.966; P = .953).
According to Dr. Harper, spironolactone may take about 3 months to kick in. “Likely this is a long-term treatment, and most of the time we’re going to be using it in combination with other acne treatments such as topical retinoids or topical benzoyl peroxide, oral antibiotics, or even isotretinoin.”
A study of long-term spironolactone use in 403 women found that the most common dose prescribed was 100 mg/day, and 68% of the women were concurrently prescribed a topical retinoid, 2.2% an oral antibiotic, and 40.7% an oral contraceptive.
The study population included 32 patients with a history of polycystic ovarian syndrome, 1 with a history of breast cancer, and 5 were hypercoagulable. Patients took the drug for a mean of 471 days. “As opposed to our antibiotics, where the course for patients is generally 3-4 months, when you start someone on spironolactone, they may end up staying on it,” Dr. Harper said.
Dr. Harper disclosed that she serves as an advisor or consultant for Almirall, Cassiopeia, Cutera, EPI, Galderma, L’Oreal, Ortho Dermatologics, Sol Gel, and Vyne. She also serves as a speaker or member of a speaker’s bureau for Almirall, Cassiopeia, Cutera, EPI, Galderma, Journey Almirall, L’Oreal, Ortho Dermatologics, Sun Pharmaceutical Industries, and Vyne.
Medscape and this news organization are owned by the same parent company.
AT THE MEDSCAPELIVE! HAWAII DERMATOLOGY SEMINAR
Lebrikizumab monotherapy for AD found safe, effective during induction
, researchers reported in the New England Journal of Medicine.
The identically designed, 52-week, randomized, double-blind, placebo-controlled trials enrolled 851 adolescents and adults with moderate to severe AD and included a 16-week induction period followed by a 36-week maintenance period. At week 16, the results “show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” wrote lead author Jonathan Silverberg, MD, PhD, director of clinical research and contact dermatitis, at George Washington University, Washington, and colleagues. “Although 16 weeks of treatment with lebrikizumab is not sufficient to assess its long-term safety, the results from the induction period of these two trials suggest a safety profile that is consistent with findings in previous trials,” they added.
Results presented at the European Academy of Dermatology and Venereology 2022 annual meeting, but not yet published, showed similar efficacy maintained through the end of the trial.
Eligible patients were randomly assigned to receive either lebrikizumab 250 mg (with a 500-mg loading dose given at baseline and at week 2) or placebo, administered subcutaneously every 2 weeks, with concomitant topical or systemic treatments prohibited through week 16 except when deemed appropriate as rescue therapy. In such cases, moderate-potency topical glucocorticoids were preferred as first-line rescue therapy, while the study drug was discontinued if systemic therapy was needed.
In both trials, the primary efficacy outcome – a score of 0 or 1 on the Investigator’s Global Assessment (IGA) – and a reduction of at least 2 points from baseline at week 16, was met by more patients treated with lebrikizumab than with placebo: 43.1% vs. 12.7% respectively in trial 1 (P < .001); and 33.2% vs. 10.8% in trial 2 (P < .001).
Similarly, in both trials, a higher percentage of the lebrikizumab than placebo patients had an EASI-75 response (75% improvement in the Eczema Area and Severity Index score): 58.8% vs. 16.2% (P < .001) in trial 1 and 52.1% vs. 18.1% (P < .001) in trial 2.
Improvement in itch was also significantly better in patients treated with lebrikizumab, compared with placebo. This was measured by a reduction of at least 4 points in the Pruritus NRS from baseline to week 16 and a reduction in the Sleep-Loss Scale score of at least 2 points from baseline to week 16 (P < .001 for both measures in both trials).
A higher percentage of placebo vs. lebrikizumab patients discontinued the trials during the induction phases (14.9% vs. 7.1% in trial 1 and 11.0% vs. 7.8% in trial 2), and the use of rescue medication was approximately three times and two times higher in both placebo groups respectively.
Conjunctivitis was the most common adverse event, occurring consistently more frequently in patients treated with lebrikizumab, compared with placebo (7.4% vs. 2.8% in trial 1 and 7.5% vs. 2.1% in trial 2).
“Although several theories have been proposed for the pathogenesis of conjunctivitis in patients with atopic dermatitis treated with this class of biologic agents, the mechanism remains unclear and warrants further study,” the investigators wrote.
Asked to comment on the new results, Zelma Chiesa Fuxench, MD, who was not involved in the research, said they “continue to demonstrate the superior efficacy and favorable safety profile” of lebrikizumab in adolescents and adults and support the results of earlier phase 2 studies. “The results of these studies thus far continue to offer more hope and the possibility of a better future for our patients with atopic dermatitis who are still struggling to achieve control of their disease.”
Dr. Chiesa Fuxench from the department of dermatology at the University of Pennsylvania, Philadelphia, said she looks forward to reviewing the full study results in which patients who achieved the primary outcomes of interest were then rerandomized to either placebo, or lebrikizumab every 2 weeks or every 4 weeks for the 36-week maintenance period “because we know that there is data for other biologics in atopic dermatitis (such as tralokinumab) that demonstrate that a decrease in the frequency of injections may be possible for patients who achieve disease control after an initial 16 weeks of therapy every 2 weeks.”
The research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Dr. Silverberg disclosed he is a consultant for Dermira and Eli Lilly, as are other coauthors on the paper who additionally disclosed grants from Dermira and other relationships with Eli Lilly such as advisory board membership and having received lecture fees. Three authors are Eli Lilly employees. Dr. Chiesa Fuxench disclosed that she is a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, Abbvie, and Incyte for which she has received honoraria for work related to AD. Dr. Chiesa Fuxench has also been a recipient of research grants from Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.
, researchers reported in the New England Journal of Medicine.
The identically designed, 52-week, randomized, double-blind, placebo-controlled trials enrolled 851 adolescents and adults with moderate to severe AD and included a 16-week induction period followed by a 36-week maintenance period. At week 16, the results “show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” wrote lead author Jonathan Silverberg, MD, PhD, director of clinical research and contact dermatitis, at George Washington University, Washington, and colleagues. “Although 16 weeks of treatment with lebrikizumab is not sufficient to assess its long-term safety, the results from the induction period of these two trials suggest a safety profile that is consistent with findings in previous trials,” they added.
Results presented at the European Academy of Dermatology and Venereology 2022 annual meeting, but not yet published, showed similar efficacy maintained through the end of the trial.
Eligible patients were randomly assigned to receive either lebrikizumab 250 mg (with a 500-mg loading dose given at baseline and at week 2) or placebo, administered subcutaneously every 2 weeks, with concomitant topical or systemic treatments prohibited through week 16 except when deemed appropriate as rescue therapy. In such cases, moderate-potency topical glucocorticoids were preferred as first-line rescue therapy, while the study drug was discontinued if systemic therapy was needed.
In both trials, the primary efficacy outcome – a score of 0 or 1 on the Investigator’s Global Assessment (IGA) – and a reduction of at least 2 points from baseline at week 16, was met by more patients treated with lebrikizumab than with placebo: 43.1% vs. 12.7% respectively in trial 1 (P < .001); and 33.2% vs. 10.8% in trial 2 (P < .001).
Similarly, in both trials, a higher percentage of the lebrikizumab than placebo patients had an EASI-75 response (75% improvement in the Eczema Area and Severity Index score): 58.8% vs. 16.2% (P < .001) in trial 1 and 52.1% vs. 18.1% (P < .001) in trial 2.
Improvement in itch was also significantly better in patients treated with lebrikizumab, compared with placebo. This was measured by a reduction of at least 4 points in the Pruritus NRS from baseline to week 16 and a reduction in the Sleep-Loss Scale score of at least 2 points from baseline to week 16 (P < .001 for both measures in both trials).
A higher percentage of placebo vs. lebrikizumab patients discontinued the trials during the induction phases (14.9% vs. 7.1% in trial 1 and 11.0% vs. 7.8% in trial 2), and the use of rescue medication was approximately three times and two times higher in both placebo groups respectively.
Conjunctivitis was the most common adverse event, occurring consistently more frequently in patients treated with lebrikizumab, compared with placebo (7.4% vs. 2.8% in trial 1 and 7.5% vs. 2.1% in trial 2).
“Although several theories have been proposed for the pathogenesis of conjunctivitis in patients with atopic dermatitis treated with this class of biologic agents, the mechanism remains unclear and warrants further study,” the investigators wrote.
Asked to comment on the new results, Zelma Chiesa Fuxench, MD, who was not involved in the research, said they “continue to demonstrate the superior efficacy and favorable safety profile” of lebrikizumab in adolescents and adults and support the results of earlier phase 2 studies. “The results of these studies thus far continue to offer more hope and the possibility of a better future for our patients with atopic dermatitis who are still struggling to achieve control of their disease.”
Dr. Chiesa Fuxench from the department of dermatology at the University of Pennsylvania, Philadelphia, said she looks forward to reviewing the full study results in which patients who achieved the primary outcomes of interest were then rerandomized to either placebo, or lebrikizumab every 2 weeks or every 4 weeks for the 36-week maintenance period “because we know that there is data for other biologics in atopic dermatitis (such as tralokinumab) that demonstrate that a decrease in the frequency of injections may be possible for patients who achieve disease control after an initial 16 weeks of therapy every 2 weeks.”
The research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Dr. Silverberg disclosed he is a consultant for Dermira and Eli Lilly, as are other coauthors on the paper who additionally disclosed grants from Dermira and other relationships with Eli Lilly such as advisory board membership and having received lecture fees. Three authors are Eli Lilly employees. Dr. Chiesa Fuxench disclosed that she is a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, Abbvie, and Incyte for which she has received honoraria for work related to AD. Dr. Chiesa Fuxench has also been a recipient of research grants from Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.
, researchers reported in the New England Journal of Medicine.
The identically designed, 52-week, randomized, double-blind, placebo-controlled trials enrolled 851 adolescents and adults with moderate to severe AD and included a 16-week induction period followed by a 36-week maintenance period. At week 16, the results “show a rapid onset of action in multiple domains of the disease, such as skin clearance and itch,” wrote lead author Jonathan Silverberg, MD, PhD, director of clinical research and contact dermatitis, at George Washington University, Washington, and colleagues. “Although 16 weeks of treatment with lebrikizumab is not sufficient to assess its long-term safety, the results from the induction period of these two trials suggest a safety profile that is consistent with findings in previous trials,” they added.
Results presented at the European Academy of Dermatology and Venereology 2022 annual meeting, but not yet published, showed similar efficacy maintained through the end of the trial.
Eligible patients were randomly assigned to receive either lebrikizumab 250 mg (with a 500-mg loading dose given at baseline and at week 2) or placebo, administered subcutaneously every 2 weeks, with concomitant topical or systemic treatments prohibited through week 16 except when deemed appropriate as rescue therapy. In such cases, moderate-potency topical glucocorticoids were preferred as first-line rescue therapy, while the study drug was discontinued if systemic therapy was needed.
In both trials, the primary efficacy outcome – a score of 0 or 1 on the Investigator’s Global Assessment (IGA) – and a reduction of at least 2 points from baseline at week 16, was met by more patients treated with lebrikizumab than with placebo: 43.1% vs. 12.7% respectively in trial 1 (P < .001); and 33.2% vs. 10.8% in trial 2 (P < .001).
Similarly, in both trials, a higher percentage of the lebrikizumab than placebo patients had an EASI-75 response (75% improvement in the Eczema Area and Severity Index score): 58.8% vs. 16.2% (P < .001) in trial 1 and 52.1% vs. 18.1% (P < .001) in trial 2.
Improvement in itch was also significantly better in patients treated with lebrikizumab, compared with placebo. This was measured by a reduction of at least 4 points in the Pruritus NRS from baseline to week 16 and a reduction in the Sleep-Loss Scale score of at least 2 points from baseline to week 16 (P < .001 for both measures in both trials).
A higher percentage of placebo vs. lebrikizumab patients discontinued the trials during the induction phases (14.9% vs. 7.1% in trial 1 and 11.0% vs. 7.8% in trial 2), and the use of rescue medication was approximately three times and two times higher in both placebo groups respectively.
Conjunctivitis was the most common adverse event, occurring consistently more frequently in patients treated with lebrikizumab, compared with placebo (7.4% vs. 2.8% in trial 1 and 7.5% vs. 2.1% in trial 2).
“Although several theories have been proposed for the pathogenesis of conjunctivitis in patients with atopic dermatitis treated with this class of biologic agents, the mechanism remains unclear and warrants further study,” the investigators wrote.
Asked to comment on the new results, Zelma Chiesa Fuxench, MD, who was not involved in the research, said they “continue to demonstrate the superior efficacy and favorable safety profile” of lebrikizumab in adolescents and adults and support the results of earlier phase 2 studies. “The results of these studies thus far continue to offer more hope and the possibility of a better future for our patients with atopic dermatitis who are still struggling to achieve control of their disease.”
Dr. Chiesa Fuxench from the department of dermatology at the University of Pennsylvania, Philadelphia, said she looks forward to reviewing the full study results in which patients who achieved the primary outcomes of interest were then rerandomized to either placebo, or lebrikizumab every 2 weeks or every 4 weeks for the 36-week maintenance period “because we know that there is data for other biologics in atopic dermatitis (such as tralokinumab) that demonstrate that a decrease in the frequency of injections may be possible for patients who achieve disease control after an initial 16 weeks of therapy every 2 weeks.”
The research was supported by Dermira, a wholly owned subsidiary of Eli Lilly. Dr. Silverberg disclosed he is a consultant for Dermira and Eli Lilly, as are other coauthors on the paper who additionally disclosed grants from Dermira and other relationships with Eli Lilly such as advisory board membership and having received lecture fees. Three authors are Eli Lilly employees. Dr. Chiesa Fuxench disclosed that she is a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, Abbvie, and Incyte for which she has received honoraria for work related to AD. Dr. Chiesa Fuxench has also been a recipient of research grants from Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Solitary abdominal papule
Dermoscopy revealed an 8-mm scaly brown-black papule that lacked melanocytic features (pigment network, globules, streaks, or homogeneous blue or brown color) but had milia-like cysts and so-called “fat fingers” (short, straight to curved radial projections1). These findings were consistent with a diagnosis of seborrheic keratosis (SK).
SKs go by many names and are often confused with nevi. Some patients might know them by such names as “age spots” or “liver spots.” Patients often have many SKs on their body; the back and skin folds are common locations. Patients may be unhappy about the way they look and may describe occasional discomfort when the SKs rub against clothes and inflammation that occurs spontaneously or with trauma.
Classic SKs have a well-demarcated border and waxy, stuck-on appearance. There are times when it is difficult to distinguish between an SK and a melanocytic lesion. Thus, a biopsy may be necessary. In addition, SKs are so common that collision lesions may occur. (Collision lesions result when 2 histologically distinct neoplasms occur adjacent to each other and cause an unusual clinical appearance with features of each lesion.) The atypical clinical features in a collision lesion may prompt a biopsy to exclude malignancy.
Dermoscopic features of SKs include well-demarcated borders, milia-like cysts (white circular inclusions), comedo-like openings (brown/black circular inclusions), fissures and ridges, hairpin vessels, and fat fingers.
Cryotherapy is a quick and efficient treatment when a patient would like the lesions removed. Curettage or light electrodessication may be less likely to cause post-inflammatory hypopigmentation in patients with darker skin types. These various destructive therapies are often considered cosmetic and are unlikely to be covered by insurance unless there is documentation of significant inflammation or discomfort. In this case, the lesion was not treated.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.
1. Wang S, Rabinovitz H, Oliviero M, et al. Solar lentigines, seborrheic keratoses, and lichen planus-like keratoses. In: Marghoob A, Malvehy J, Braun, R, eds. Atlas of Dermoscopy. 2nd ed. Informa Healthcare; 2012: 58-69.
Dermoscopy revealed an 8-mm scaly brown-black papule that lacked melanocytic features (pigment network, globules, streaks, or homogeneous blue or brown color) but had milia-like cysts and so-called “fat fingers” (short, straight to curved radial projections1). These findings were consistent with a diagnosis of seborrheic keratosis (SK).
SKs go by many names and are often confused with nevi. Some patients might know them by such names as “age spots” or “liver spots.” Patients often have many SKs on their body; the back and skin folds are common locations. Patients may be unhappy about the way they look and may describe occasional discomfort when the SKs rub against clothes and inflammation that occurs spontaneously or with trauma.
Classic SKs have a well-demarcated border and waxy, stuck-on appearance. There are times when it is difficult to distinguish between an SK and a melanocytic lesion. Thus, a biopsy may be necessary. In addition, SKs are so common that collision lesions may occur. (Collision lesions result when 2 histologically distinct neoplasms occur adjacent to each other and cause an unusual clinical appearance with features of each lesion.) The atypical clinical features in a collision lesion may prompt a biopsy to exclude malignancy.
Dermoscopic features of SKs include well-demarcated borders, milia-like cysts (white circular inclusions), comedo-like openings (brown/black circular inclusions), fissures and ridges, hairpin vessels, and fat fingers.
Cryotherapy is a quick and efficient treatment when a patient would like the lesions removed. Curettage or light electrodessication may be less likely to cause post-inflammatory hypopigmentation in patients with darker skin types. These various destructive therapies are often considered cosmetic and are unlikely to be covered by insurance unless there is documentation of significant inflammation or discomfort. In this case, the lesion was not treated.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.
Dermoscopy revealed an 8-mm scaly brown-black papule that lacked melanocytic features (pigment network, globules, streaks, or homogeneous blue or brown color) but had milia-like cysts and so-called “fat fingers” (short, straight to curved radial projections1). These findings were consistent with a diagnosis of seborrheic keratosis (SK).
SKs go by many names and are often confused with nevi. Some patients might know them by such names as “age spots” or “liver spots.” Patients often have many SKs on their body; the back and skin folds are common locations. Patients may be unhappy about the way they look and may describe occasional discomfort when the SKs rub against clothes and inflammation that occurs spontaneously or with trauma.
Classic SKs have a well-demarcated border and waxy, stuck-on appearance. There are times when it is difficult to distinguish between an SK and a melanocytic lesion. Thus, a biopsy may be necessary. In addition, SKs are so common that collision lesions may occur. (Collision lesions result when 2 histologically distinct neoplasms occur adjacent to each other and cause an unusual clinical appearance with features of each lesion.) The atypical clinical features in a collision lesion may prompt a biopsy to exclude malignancy.
Dermoscopic features of SKs include well-demarcated borders, milia-like cysts (white circular inclusions), comedo-like openings (brown/black circular inclusions), fissures and ridges, hairpin vessels, and fat fingers.
Cryotherapy is a quick and efficient treatment when a patient would like the lesions removed. Curettage or light electrodessication may be less likely to cause post-inflammatory hypopigmentation in patients with darker skin types. These various destructive therapies are often considered cosmetic and are unlikely to be covered by insurance unless there is documentation of significant inflammation or discomfort. In this case, the lesion was not treated.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.
1. Wang S, Rabinovitz H, Oliviero M, et al. Solar lentigines, seborrheic keratoses, and lichen planus-like keratoses. In: Marghoob A, Malvehy J, Braun, R, eds. Atlas of Dermoscopy. 2nd ed. Informa Healthcare; 2012: 58-69.
1. Wang S, Rabinovitz H, Oliviero M, et al. Solar lentigines, seborrheic keratoses, and lichen planus-like keratoses. In: Marghoob A, Malvehy J, Braun, R, eds. Atlas of Dermoscopy. 2nd ed. Informa Healthcare; 2012: 58-69.
