Conference Coverage

SAN DIEGO — While the concept of zoom dysmorphia is well accepted in today’s clinical practice, diagnostic criteria are lacking, especially in virtual settings, according to George Kroumpouzos, MD, PhD, who, with colleagues, recently proposed a screening tool to help identify patients with zoom dysmorphia.

The term, coined in 2020 by dermatologist Shadi Kourosh, MD, MPH, and colleagues at Harvard Medical School, Boston, refers to an altered or skewed negative perception of one’s body image that results from spending extended amounts of time on video calls. Speaking at the annual meeting of the American Academy of Dermatology, Dr. Kroumpouzos, clinical associate professor of dermatology at Brown University, Providence Rhode Island, explained that most people believe that zoom dysmorphia falls within the spectrum of body dysmorphic disorder (BDD). He described zoom dysmorphia as “a facial dysmorphia triggered or aggravated by frequent virtual meetings. Frequent use of videoconferencing platforms is linked to a distorted perception of facial images, which leads to dysmorphic concerns.”

Dr. Kroumpouzos

Individuals with zoom dysmorphia tend to scrutinize their facial features and fixate on what they think needs to improve, he continued. They experience anxiety about attending video conferences with the camera on and feel pressured to appear perfect before virtual meetings. “They find facial flaws during virtual meetings, and they believe others notice their perceived flaws,” he said. “This all has drastic effects on body dissatisfaction and self-esteem, which leads to a desire to seek cosmetic procedures. It interferes with an individual’s life and can trigger or aggravate body dysmorphic disorder.”

While several tools have been validated in cosmetic settings to screen for BDD, such as the 9-item Body Dysmorphic Disorder Questionnaire–Dermatology questionnaire, the 7-item Body Dysmorphic Disorder Questionnaire–Aesthetic Surgery questionnaire, the Cosmetic Procedure Screening Questionnaire, and the Body Dysmorphic Disorder Symptom Scale, no formal screening tools exist to identify zoom dysmorphia. To complicate matters, “identifying dysmorphic concerns in virtual settings can be challenging,” Dr. Kroumpouzos added. “This makes the recognition of zoom dysmorphia during telehealth visits even more difficult.”

Individuals who may have zoom dysmorphia may fear being misunderstood, judged, or ridiculed because of a perceived flaw in appearance, he said, making establishing rapport and eye contact difficult. “There’s a reticence and silence due to the individual’s avoidant characteristics,” he said. “Patients may become easily distracted or disengaged during telehealth visits in case of technical issues. Psychiatric comorbidities can mask symptoms related to dysmorphic concerns.”

To bridge this gap, Dr. Kroumpouzos and colleagues have proposed a screening tool, a questionnaire related to features of zoom dysmorphia, to facilitate recognition of zoom dysmorphia in virtual settings.

The first component consists of open-ended questions such as “Are you comfortable with being interviewed in a virtual appointment?” and “How do you feel about your appearance during virtual meetings?” Such questions “aim to start the dialogue, to facilitate the discussion with a patient who may be shy or avoidant,” Dr. Kroumpouzos explained.

The second component of the tool consists of questions more specific to screening for zoom dysmorphia, starting with “Are you concerned about facial flaws?” If the patient answers no, they don’t qualify for any others, he said. “But, if they answer yes to that question and yes to at least one more [question], they may have zoom dysmorphia.”

Other questions include, “Do you think that your face is not friendly to the camera?” “Do you hesitate to open the camera?” “Have you tried to hide or camouflage your flaw with your hands, hair, makeup, or clothing?” “Have you sought advice from others to improve your appearance or image?” “Do you often use the filter features of the video conferencing platform?” “Did you consider buying a new camera or equipment that helps improve your image?”

If the clinician deems the patient a candidate for the diagnosis of zoom dysmorphia, the tool recommends asking a BDD-focused question: “In the past month, have you been very concerned that there is something wrong with your physical appearance or the way one or more parts of your body look?” If the patient answers yes, “that individual should be invited to fill out a questionnaire specifically for BDD or come to the office for further evaluation,” Dr. Kroumpouzos said.

In his view, the brevity of the proposed screening tool makes it easy to incorporate into clinical practice, and the “yes or no” questions are practical. “It is crucial to elicit the presence of zoom dysmorphia in its early stage,” he said. “Zoom dysmorphia may trigger an increase in BDD, [so] it is essential to identify the presence of BDD in zoom dysmorphia sufferers and treat it appropriately.”

Dr. Kroumpouzos reported having no relevant financial disclosures.

SAN DIEGO — While the concept of zoom dysmorphia is well accepted in today’s clinical practice, diagnostic criteria are lacking, especially in virtual settings, according to George Kroumpouzos, MD, PhD, who, with colleagues, recently proposed a screening tool to help identify patients with zoom dysmorphia.

The term, coined in 2020 by dermatologist Shadi Kourosh, MD, MPH, and colleagues at Harvard Medical School, Boston, refers to an altered or skewed negative perception of one’s body image that results from spending extended amounts of time on video calls. Speaking at the annual meeting of the American Academy of Dermatology, Dr. Kroumpouzos, clinical associate professor of dermatology at Brown University, Providence Rhode Island, explained that most people believe that zoom dysmorphia falls within the spectrum of body dysmorphic disorder (BDD). He described zoom dysmorphia as “a facial dysmorphia triggered or aggravated by frequent virtual meetings. Frequent use of videoconferencing platforms is linked to a distorted perception of facial images, which leads to dysmorphic concerns.”

Dr. Kroumpouzos

Individuals with zoom dysmorphia tend to scrutinize their facial features and fixate on what they think needs to improve, he continued. They experience anxiety about attending video conferences with the camera on and feel pressured to appear perfect before virtual meetings. “They find facial flaws during virtual meetings, and they believe others notice their perceived flaws,” he said. “This all has drastic effects on body dissatisfaction and self-esteem, which leads to a desire to seek cosmetic procedures. It interferes with an individual’s life and can trigger or aggravate body dysmorphic disorder.”

While several tools have been validated in cosmetic settings to screen for BDD, such as the 9-item Body Dysmorphic Disorder Questionnaire–Dermatology questionnaire, the 7-item Body Dysmorphic Disorder Questionnaire–Aesthetic Surgery questionnaire, the Cosmetic Procedure Screening Questionnaire, and the Body Dysmorphic Disorder Symptom Scale, no formal screening tools exist to identify zoom dysmorphia. To complicate matters, “identifying dysmorphic concerns in virtual settings can be challenging,” Dr. Kroumpouzos added. “This makes the recognition of zoom dysmorphia during telehealth visits even more difficult.”

Individuals who may have zoom dysmorphia may fear being misunderstood, judged, or ridiculed because of a perceived flaw in appearance, he said, making establishing rapport and eye contact difficult. “There’s a reticence and silence due to the individual’s avoidant characteristics,” he said. “Patients may become easily distracted or disengaged during telehealth visits in case of technical issues. Psychiatric comorbidities can mask symptoms related to dysmorphic concerns.”

To bridge this gap, Dr. Kroumpouzos and colleagues have proposed a screening tool, a questionnaire related to features of zoom dysmorphia, to facilitate recognition of zoom dysmorphia in virtual settings.

The first component consists of open-ended questions such as “Are you comfortable with being interviewed in a virtual appointment?” and “How do you feel about your appearance during virtual meetings?” Such questions “aim to start the dialogue, to facilitate the discussion with a patient who may be shy or avoidant,” Dr. Kroumpouzos explained.

The second component of the tool consists of questions more specific to screening for zoom dysmorphia, starting with “Are you concerned about facial flaws?” If the patient answers no, they don’t qualify for any others, he said. “But, if they answer yes to that question and yes to at least one more [question], they may have zoom dysmorphia.”

Other questions include, “Do you think that your face is not friendly to the camera?” “Do you hesitate to open the camera?” “Have you tried to hide or camouflage your flaw with your hands, hair, makeup, or clothing?” “Have you sought advice from others to improve your appearance or image?” “Do you often use the filter features of the video conferencing platform?” “Did you consider buying a new camera or equipment that helps improve your image?”

If the clinician deems the patient a candidate for the diagnosis of zoom dysmorphia, the tool recommends asking a BDD-focused question: “In the past month, have you been very concerned that there is something wrong with your physical appearance or the way one or more parts of your body look?” If the patient answers yes, “that individual should be invited to fill out a questionnaire specifically for BDD or come to the office for further evaluation,” Dr. Kroumpouzos said.

In his view, the brevity of the proposed screening tool makes it easy to incorporate into clinical practice, and the “yes or no” questions are practical. “It is crucial to elicit the presence of zoom dysmorphia in its early stage,” he said. “Zoom dysmorphia may trigger an increase in BDD, [so] it is essential to identify the presence of BDD in zoom dysmorphia sufferers and treat it appropriately.”

Dr. Kroumpouzos reported having no relevant financial disclosures.

SAN DIEGO — While the concept of zoom dysmorphia is well accepted in today’s clinical practice, diagnostic criteria are lacking, especially in virtual settings, according to George Kroumpouzos, MD, PhD, who, with colleagues, recently proposed a screening tool to help identify patients with zoom dysmorphia.

The term, coined in 2020 by dermatologist Shadi Kourosh, MD, MPH, and colleagues at Harvard Medical School, Boston, refers to an altered or skewed negative perception of one’s body image that results from spending extended amounts of time on video calls. Speaking at the annual meeting of the American Academy of Dermatology, Dr. Kroumpouzos, clinical associate professor of dermatology at Brown University, Providence Rhode Island, explained that most people believe that zoom dysmorphia falls within the spectrum of body dysmorphic disorder (BDD). He described zoom dysmorphia as “a facial dysmorphia triggered or aggravated by frequent virtual meetings. Frequent use of videoconferencing platforms is linked to a distorted perception of facial images, which leads to dysmorphic concerns.”

Dr. Kroumpouzos

Individuals with zoom dysmorphia tend to scrutinize their facial features and fixate on what they think needs to improve, he continued. They experience anxiety about attending video conferences with the camera on and feel pressured to appear perfect before virtual meetings. “They find facial flaws during virtual meetings, and they believe others notice their perceived flaws,” he said. “This all has drastic effects on body dissatisfaction and self-esteem, which leads to a desire to seek cosmetic procedures. It interferes with an individual’s life and can trigger or aggravate body dysmorphic disorder.”

While several tools have been validated in cosmetic settings to screen for BDD, such as the 9-item Body Dysmorphic Disorder Questionnaire–Dermatology questionnaire, the 7-item Body Dysmorphic Disorder Questionnaire–Aesthetic Surgery questionnaire, the Cosmetic Procedure Screening Questionnaire, and the Body Dysmorphic Disorder Symptom Scale, no formal screening tools exist to identify zoom dysmorphia. To complicate matters, “identifying dysmorphic concerns in virtual settings can be challenging,” Dr. Kroumpouzos added. “This makes the recognition of zoom dysmorphia during telehealth visits even more difficult.”

Individuals who may have zoom dysmorphia may fear being misunderstood, judged, or ridiculed because of a perceived flaw in appearance, he said, making establishing rapport and eye contact difficult. “There’s a reticence and silence due to the individual’s avoidant characteristics,” he said. “Patients may become easily distracted or disengaged during telehealth visits in case of technical issues. Psychiatric comorbidities can mask symptoms related to dysmorphic concerns.”

To bridge this gap, Dr. Kroumpouzos and colleagues have proposed a screening tool, a questionnaire related to features of zoom dysmorphia, to facilitate recognition of zoom dysmorphia in virtual settings.

The first component consists of open-ended questions such as “Are you comfortable with being interviewed in a virtual appointment?” and “How do you feel about your appearance during virtual meetings?” Such questions “aim to start the dialogue, to facilitate the discussion with a patient who may be shy or avoidant,” Dr. Kroumpouzos explained.

The second component of the tool consists of questions more specific to screening for zoom dysmorphia, starting with “Are you concerned about facial flaws?” If the patient answers no, they don’t qualify for any others, he said. “But, if they answer yes to that question and yes to at least one more [question], they may have zoom dysmorphia.”

Other questions include, “Do you think that your face is not friendly to the camera?” “Do you hesitate to open the camera?” “Have you tried to hide or camouflage your flaw with your hands, hair, makeup, or clothing?” “Have you sought advice from others to improve your appearance or image?” “Do you often use the filter features of the video conferencing platform?” “Did you consider buying a new camera or equipment that helps improve your image?”

If the clinician deems the patient a candidate for the diagnosis of zoom dysmorphia, the tool recommends asking a BDD-focused question: “In the past month, have you been very concerned that there is something wrong with your physical appearance or the way one or more parts of your body look?” If the patient answers yes, “that individual should be invited to fill out a questionnaire specifically for BDD or come to the office for further evaluation,” Dr. Kroumpouzos said.

In his view, the brevity of the proposed screening tool makes it easy to incorporate into clinical practice, and the “yes or no” questions are practical. “It is crucial to elicit the presence of zoom dysmorphia in its early stage,” he said. “Zoom dysmorphia may trigger an increase in BDD, [so] it is essential to identify the presence of BDD in zoom dysmorphia sufferers and treat it appropriately.”

Dr. Kroumpouzos reported having no relevant financial disclosures.

SAN DIEGO — First-line treatment with a combination of cadonilimab, a PD-1/CTLA-4 bispecific immune checkpoint inhibitor, and standard chemotherapy provides a survival advantage over placebo plus chemotherapy in patients with locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma,, according to a new study.

Jiafu Ji, MD, PhD, presented this and other findings of the randomized, double-blind, placebo-controlled phase 3 COMPASSION-15 trial at the annual meeting of the American Association for Cancer Research (AACR).

“The consistent survival benefits across all prespecified PD-L1 expression cutoffs, particularly in patients with low PD-L1 expression, have significant implications for clinical practice by expanding treatment options, improving outcomes for patients with PD-L1–low tumors, influencing guidelines, and stimulating further research in advanced G/GEJ adenocarcinoma treatment,” said Dr. Ji, a principal investigator of this trial, in an interview.

Unmet Need

The incidence of gastric cancer is particularly high in China, but as Dr. Ji discussed in his talk, the treatment options for patients with advanced disease remain limited. Although the Food and Drug Administration (FDA) has approved the combination of PD-L1 inhibitors with chemotherapy for the first-line treatment of advanced gastric cancer, not all patients respond to the treatment, explained Dr. Ji, who is a professor of gastrointestinal surgery and president of Peking University Cancer Hospital and Beijing Institute for Cancer Research in China.

He added that the combination of PD-L1 inhibitors and chemotherapy has not yet been approved for the treatment of advanced gastric cancer in China, leaving chemotherapy as the only treatment option for Chinese patients.

Study Design

To evaluate the efficacy and safety of first-line cadonilimab plus standard chemotherapy in patients with advanced or metastatic gastric cancer, the authors of the COMPASSION-15 trial enrolled 610 patients with unresectable, locally advanced, or metastatic G/GEJ adenocarcinoma who had not received any prior treatments. PD-L1 expression status was not used to exclude patients from the trial.

In a press conference held at AACR 2024, Dr. Ji explained the study rationale, design, and endpoints. He said that patients with tumors without PD-L1 expression typically show little to no benefit from anti–PD-1/PD-L1 inhibitors, and their treatment options are limited to chemotherapy.

“Testing the efficacy of this bispecific antibody in this patient population could provide an alternative treatment approach for them,” he added.

Patients were randomized 1:1 to receive either cadonilimab (10 mg/kg every 3 weeks) plus chemotherapy or placebo plus chemotherapy. The primary endpoint of the study was overall survival (OS) in the intent-to-treat (ITT) population, and secondary efficacy endpoints included OS, progression-free survival (PFS), and objective response rate (ORR) in the ITT population, as well as in patients stratified by PD-L1 expression.

Cadonilimab Plus Standard Chemotherapy Improves OS

Interim analysis, conducted with a median follow-up of 18.69 months, showed a significant improvement in OS for the cadonilimab plus chemotherapy group compared with the chemotherapy-alone group, according to data presented at the press conference. The median OS was 15.0 months in the cadonilimab group versus 10.8 months in the placebo group, representing a 38% reduction in the risk of death (hazard ratio [HR], 0.62; 95% CI, 0.50-0.78, P < .001).

Yelena Y. Janjigian, MD, who not involved in COMPASSION-15, provided critique of the study, during another session at the meeting, in which she discussed the CheckMate 649 trial. She noted that, although the median OS of 15 months in the COMPASSION-15 study was slightly higher than the OS in the CheckMate 649 trial (approximately 14 months), comparing the results of two studies is challenging.

“In the COMPASSION-15 trial, chemotherapy was stopped after [4.5 months], and only 50% of patients received chemotherapy with subsequent treatment — this is not standard and may limit the comparison with other immunotherapy trials,” explained Dr. Janjigian, who is a gastrointestinal oncologist and was a principal investigator in the phase 3 CheckMate 649 immunotherapy trial for advanced gastric cancer.

Importantly, survival benefit with cadonilimab plus chemotherapy was observed across all prespecified PD-L1 expression levels, including in patients with low PD-L1 expression (PD-L1 combined positive score [CPS] less than 5%). In the low PD-L1 expression group (CPS less than 5%), the median OS was 14.8 months in the cadonilimab group compared with 11.8 months in the placebo group (HR, 0.70; 95% CI, 0.51-0.95; P = .011).

“These positive survival outcomes when cadonilimab was combined with chemotherapy may be attributed to synergistic mechanisms of action, enhanced immune responses, modulation of the tumor microenvironment, and careful patient selection based on biomarker assessments,” noted Dr. Ji, during an interview. “Targeting multiple pathways using bispecific antibodies provides potential synergistic effects, enhancing anti-tumor activity and improving treatment outcomes.”

Cadonilimab Plus Standard Chemotherapy Reduces the Risk of Tumor Progression

In addition to prolonging OS, cadonilimab plus chemotherapy also provided superior PFS and ORR compared to placebo plus chemotherapy.

The median PFS was 7.0 months in the cadonilimab plus chemotherapy group, versus 5.3 months in the chemotherapy-only group (HR, 0.53; 95% CI, 0.44-0.65, P < .001), and the ORR was 65.2% versus 48.9%, respectively. Furthermore, the duration of response was longer with cadonilimab plus chemotherapy than with placebo plus chemotherapy (8.8 versus 4.4 months, respectively).

Toxicities Associated With Cadonilimab Plus Standard Chemotherapy Are Manageable

The safety profile of the cadonilimab plus chemotherapy regimen was manageable, with grade 3 or higher treatment-related adverse events occurring in 71.8% of patients in the cadonilimab group and 60.5% of patients in the placebo group. No new safety signals were observed.

During an interview, Dr. Ji said that the most common adverse events were endocrine toxicity, skin toxicity, and lung toxicity. “These adverse events were managed through close monitoring, symptom management, and appropriate interventions based on the severity and nature of the toxicity experienced by patients,” he explained. He added that this toxicity profile of cadonilimab is similar to the toxicity profiles of approved PD-1 and CTLA-4 inhibitors.

Implications — A New Treatment Paradigm for Advanced Gastric Cancer?

According to Dr. Ji, the interim results from the cadonilimab study suggest that this novel PD-1/CTLA-4 bispecific antibody, in combination with chemotherapy, could become a new standard first-line treatment option for patients with advanced G/GEJ adenocarcinoma, offering a significant survival advantage over chemotherapy alone, regardless of PD-L1 status.

“The ability of cadonilimab to improve survival outcomes, regardless of PD-L1 status, is a significant advancement, as we have struggled to find effective treatments for patients with low PD-L1 expression in this setting,” he said, during the interview.

Despite these promising findings, Dr. Janjigian highlighted that patient stratification in the COMPASSION-15 study is currently lacking. She explained that biomarkers such as MSI status, T-reg signatures, and HER-2 are important to consider according to data from the CheckMate 649 trial.

“Hazard ratios for patients with T-reg–high tumors were almost 0.6, independent of inflammatory status. These data suggest that we can maybe even cure some patients with PD-1/CTLA-4 inhibitors,” she noted.

She added that knowing the status of MSI and HER-2 is clinically important as it can inform clinicians whether they can avoid chemotherapy or add trastuzumab.

“Despite the suboptimal comparator arm, the study is very important and offers a rationale for dual PD-1/CTLA-4 blockade,” Dr. Janjigian concluded.

COMPASSION-15 was funded by Akeso Biopharma, Inc. Dr. Ji reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients. Dr. Janjigian lists relationships with AbbVie, AmerisourceBergen Drug Corporation, Arcus Biosciences, Ask-Gene Pharma, Inc., Astellas Pharma, AstraZeneca, Basilea Pharmaceutica Ltd., Bayer, Bristol Myers, Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck, Pfizer, and many other companies, as well as the U.S. Department of Defense, National Cancer Institute, and others.

SAN DIEGO — First-line treatment with a combination of cadonilimab, a PD-1/CTLA-4 bispecific immune checkpoint inhibitor, and standard chemotherapy provides a survival advantage over placebo plus chemotherapy in patients with locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma,, according to a new study.

Jiafu Ji, MD, PhD, presented this and other findings of the randomized, double-blind, placebo-controlled phase 3 COMPASSION-15 trial at the annual meeting of the American Association for Cancer Research (AACR).

“The consistent survival benefits across all prespecified PD-L1 expression cutoffs, particularly in patients with low PD-L1 expression, have significant implications for clinical practice by expanding treatment options, improving outcomes for patients with PD-L1–low tumors, influencing guidelines, and stimulating further research in advanced G/GEJ adenocarcinoma treatment,” said Dr. Ji, a principal investigator of this trial, in an interview.

Unmet Need

The incidence of gastric cancer is particularly high in China, but as Dr. Ji discussed in his talk, the treatment options for patients with advanced disease remain limited. Although the Food and Drug Administration (FDA) has approved the combination of PD-L1 inhibitors with chemotherapy for the first-line treatment of advanced gastric cancer, not all patients respond to the treatment, explained Dr. Ji, who is a professor of gastrointestinal surgery and president of Peking University Cancer Hospital and Beijing Institute for Cancer Research in China.

He added that the combination of PD-L1 inhibitors and chemotherapy has not yet been approved for the treatment of advanced gastric cancer in China, leaving chemotherapy as the only treatment option for Chinese patients.

Study Design

To evaluate the efficacy and safety of first-line cadonilimab plus standard chemotherapy in patients with advanced or metastatic gastric cancer, the authors of the COMPASSION-15 trial enrolled 610 patients with unresectable, locally advanced, or metastatic G/GEJ adenocarcinoma who had not received any prior treatments. PD-L1 expression status was not used to exclude patients from the trial.

In a press conference held at AACR 2024, Dr. Ji explained the study rationale, design, and endpoints. He said that patients with tumors without PD-L1 expression typically show little to no benefit from anti–PD-1/PD-L1 inhibitors, and their treatment options are limited to chemotherapy.

“Testing the efficacy of this bispecific antibody in this patient population could provide an alternative treatment approach for them,” he added.

Patients were randomized 1:1 to receive either cadonilimab (10 mg/kg every 3 weeks) plus chemotherapy or placebo plus chemotherapy. The primary endpoint of the study was overall survival (OS) in the intent-to-treat (ITT) population, and secondary efficacy endpoints included OS, progression-free survival (PFS), and objective response rate (ORR) in the ITT population, as well as in patients stratified by PD-L1 expression.

Cadonilimab Plus Standard Chemotherapy Improves OS

Interim analysis, conducted with a median follow-up of 18.69 months, showed a significant improvement in OS for the cadonilimab plus chemotherapy group compared with the chemotherapy-alone group, according to data presented at the press conference. The median OS was 15.0 months in the cadonilimab group versus 10.8 months in the placebo group, representing a 38% reduction in the risk of death (hazard ratio [HR], 0.62; 95% CI, 0.50-0.78, P < .001).

Yelena Y. Janjigian, MD, who not involved in COMPASSION-15, provided critique of the study, during another session at the meeting, in which she discussed the CheckMate 649 trial. She noted that, although the median OS of 15 months in the COMPASSION-15 study was slightly higher than the OS in the CheckMate 649 trial (approximately 14 months), comparing the results of two studies is challenging.

“In the COMPASSION-15 trial, chemotherapy was stopped after [4.5 months], and only 50% of patients received chemotherapy with subsequent treatment — this is not standard and may limit the comparison with other immunotherapy trials,” explained Dr. Janjigian, who is a gastrointestinal oncologist and was a principal investigator in the phase 3 CheckMate 649 immunotherapy trial for advanced gastric cancer.

Importantly, survival benefit with cadonilimab plus chemotherapy was observed across all prespecified PD-L1 expression levels, including in patients with low PD-L1 expression (PD-L1 combined positive score [CPS] less than 5%). In the low PD-L1 expression group (CPS less than 5%), the median OS was 14.8 months in the cadonilimab group compared with 11.8 months in the placebo group (HR, 0.70; 95% CI, 0.51-0.95; P = .011).

“These positive survival outcomes when cadonilimab was combined with chemotherapy may be attributed to synergistic mechanisms of action, enhanced immune responses, modulation of the tumor microenvironment, and careful patient selection based on biomarker assessments,” noted Dr. Ji, during an interview. “Targeting multiple pathways using bispecific antibodies provides potential synergistic effects, enhancing anti-tumor activity and improving treatment outcomes.”

Cadonilimab Plus Standard Chemotherapy Reduces the Risk of Tumor Progression

In addition to prolonging OS, cadonilimab plus chemotherapy also provided superior PFS and ORR compared to placebo plus chemotherapy.

The median PFS was 7.0 months in the cadonilimab plus chemotherapy group, versus 5.3 months in the chemotherapy-only group (HR, 0.53; 95% CI, 0.44-0.65, P < .001), and the ORR was 65.2% versus 48.9%, respectively. Furthermore, the duration of response was longer with cadonilimab plus chemotherapy than with placebo plus chemotherapy (8.8 versus 4.4 months, respectively).

Toxicities Associated With Cadonilimab Plus Standard Chemotherapy Are Manageable

The safety profile of the cadonilimab plus chemotherapy regimen was manageable, with grade 3 or higher treatment-related adverse events occurring in 71.8% of patients in the cadonilimab group and 60.5% of patients in the placebo group. No new safety signals were observed.

During an interview, Dr. Ji said that the most common adverse events were endocrine toxicity, skin toxicity, and lung toxicity. “These adverse events were managed through close monitoring, symptom management, and appropriate interventions based on the severity and nature of the toxicity experienced by patients,” he explained. He added that this toxicity profile of cadonilimab is similar to the toxicity profiles of approved PD-1 and CTLA-4 inhibitors.

Implications — A New Treatment Paradigm for Advanced Gastric Cancer?

According to Dr. Ji, the interim results from the cadonilimab study suggest that this novel PD-1/CTLA-4 bispecific antibody, in combination with chemotherapy, could become a new standard first-line treatment option for patients with advanced G/GEJ adenocarcinoma, offering a significant survival advantage over chemotherapy alone, regardless of PD-L1 status.

“The ability of cadonilimab to improve survival outcomes, regardless of PD-L1 status, is a significant advancement, as we have struggled to find effective treatments for patients with low PD-L1 expression in this setting,” he said, during the interview.

Despite these promising findings, Dr. Janjigian highlighted that patient stratification in the COMPASSION-15 study is currently lacking. She explained that biomarkers such as MSI status, T-reg signatures, and HER-2 are important to consider according to data from the CheckMate 649 trial.

“Hazard ratios for patients with T-reg–high tumors were almost 0.6, independent of inflammatory status. These data suggest that we can maybe even cure some patients with PD-1/CTLA-4 inhibitors,” she noted.

She added that knowing the status of MSI and HER-2 is clinically important as it can inform clinicians whether they can avoid chemotherapy or add trastuzumab.

“Despite the suboptimal comparator arm, the study is very important and offers a rationale for dual PD-1/CTLA-4 blockade,” Dr. Janjigian concluded.

COMPASSION-15 was funded by Akeso Biopharma, Inc. Dr. Ji reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients. Dr. Janjigian lists relationships with AbbVie, AmerisourceBergen Drug Corporation, Arcus Biosciences, Ask-Gene Pharma, Inc., Astellas Pharma, AstraZeneca, Basilea Pharmaceutica Ltd., Bayer, Bristol Myers, Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck, Pfizer, and many other companies, as well as the U.S. Department of Defense, National Cancer Institute, and others.

SAN DIEGO — First-line treatment with a combination of cadonilimab, a PD-1/CTLA-4 bispecific immune checkpoint inhibitor, and standard chemotherapy provides a survival advantage over placebo plus chemotherapy in patients with locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma,, according to a new study.

Jiafu Ji, MD, PhD, presented this and other findings of the randomized, double-blind, placebo-controlled phase 3 COMPASSION-15 trial at the annual meeting of the American Association for Cancer Research (AACR).

“The consistent survival benefits across all prespecified PD-L1 expression cutoffs, particularly in patients with low PD-L1 expression, have significant implications for clinical practice by expanding treatment options, improving outcomes for patients with PD-L1–low tumors, influencing guidelines, and stimulating further research in advanced G/GEJ adenocarcinoma treatment,” said Dr. Ji, a principal investigator of this trial, in an interview.

Unmet Need

The incidence of gastric cancer is particularly high in China, but as Dr. Ji discussed in his talk, the treatment options for patients with advanced disease remain limited. Although the Food and Drug Administration (FDA) has approved the combination of PD-L1 inhibitors with chemotherapy for the first-line treatment of advanced gastric cancer, not all patients respond to the treatment, explained Dr. Ji, who is a professor of gastrointestinal surgery and president of Peking University Cancer Hospital and Beijing Institute for Cancer Research in China.

He added that the combination of PD-L1 inhibitors and chemotherapy has not yet been approved for the treatment of advanced gastric cancer in China, leaving chemotherapy as the only treatment option for Chinese patients.

Study Design

To evaluate the efficacy and safety of first-line cadonilimab plus standard chemotherapy in patients with advanced or metastatic gastric cancer, the authors of the COMPASSION-15 trial enrolled 610 patients with unresectable, locally advanced, or metastatic G/GEJ adenocarcinoma who had not received any prior treatments. PD-L1 expression status was not used to exclude patients from the trial.

In a press conference held at AACR 2024, Dr. Ji explained the study rationale, design, and endpoints. He said that patients with tumors without PD-L1 expression typically show little to no benefit from anti–PD-1/PD-L1 inhibitors, and their treatment options are limited to chemotherapy.

“Testing the efficacy of this bispecific antibody in this patient population could provide an alternative treatment approach for them,” he added.

Patients were randomized 1:1 to receive either cadonilimab (10 mg/kg every 3 weeks) plus chemotherapy or placebo plus chemotherapy. The primary endpoint of the study was overall survival (OS) in the intent-to-treat (ITT) population, and secondary efficacy endpoints included OS, progression-free survival (PFS), and objective response rate (ORR) in the ITT population, as well as in patients stratified by PD-L1 expression.

Cadonilimab Plus Standard Chemotherapy Improves OS

Interim analysis, conducted with a median follow-up of 18.69 months, showed a significant improvement in OS for the cadonilimab plus chemotherapy group compared with the chemotherapy-alone group, according to data presented at the press conference. The median OS was 15.0 months in the cadonilimab group versus 10.8 months in the placebo group, representing a 38% reduction in the risk of death (hazard ratio [HR], 0.62; 95% CI, 0.50-0.78, P < .001).

Yelena Y. Janjigian, MD, who not involved in COMPASSION-15, provided critique of the study, during another session at the meeting, in which she discussed the CheckMate 649 trial. She noted that, although the median OS of 15 months in the COMPASSION-15 study was slightly higher than the OS in the CheckMate 649 trial (approximately 14 months), comparing the results of two studies is challenging.

“In the COMPASSION-15 trial, chemotherapy was stopped after [4.5 months], and only 50% of patients received chemotherapy with subsequent treatment — this is not standard and may limit the comparison with other immunotherapy trials,” explained Dr. Janjigian, who is a gastrointestinal oncologist and was a principal investigator in the phase 3 CheckMate 649 immunotherapy trial for advanced gastric cancer.

Importantly, survival benefit with cadonilimab plus chemotherapy was observed across all prespecified PD-L1 expression levels, including in patients with low PD-L1 expression (PD-L1 combined positive score [CPS] less than 5%). In the low PD-L1 expression group (CPS less than 5%), the median OS was 14.8 months in the cadonilimab group compared with 11.8 months in the placebo group (HR, 0.70; 95% CI, 0.51-0.95; P = .011).

“These positive survival outcomes when cadonilimab was combined with chemotherapy may be attributed to synergistic mechanisms of action, enhanced immune responses, modulation of the tumor microenvironment, and careful patient selection based on biomarker assessments,” noted Dr. Ji, during an interview. “Targeting multiple pathways using bispecific antibodies provides potential synergistic effects, enhancing anti-tumor activity and improving treatment outcomes.”

Cadonilimab Plus Standard Chemotherapy Reduces the Risk of Tumor Progression

In addition to prolonging OS, cadonilimab plus chemotherapy also provided superior PFS and ORR compared to placebo plus chemotherapy.

The median PFS was 7.0 months in the cadonilimab plus chemotherapy group, versus 5.3 months in the chemotherapy-only group (HR, 0.53; 95% CI, 0.44-0.65, P < .001), and the ORR was 65.2% versus 48.9%, respectively. Furthermore, the duration of response was longer with cadonilimab plus chemotherapy than with placebo plus chemotherapy (8.8 versus 4.4 months, respectively).

Toxicities Associated With Cadonilimab Plus Standard Chemotherapy Are Manageable

The safety profile of the cadonilimab plus chemotherapy regimen was manageable, with grade 3 or higher treatment-related adverse events occurring in 71.8% of patients in the cadonilimab group and 60.5% of patients in the placebo group. No new safety signals were observed.

During an interview, Dr. Ji said that the most common adverse events were endocrine toxicity, skin toxicity, and lung toxicity. “These adverse events were managed through close monitoring, symptom management, and appropriate interventions based on the severity and nature of the toxicity experienced by patients,” he explained. He added that this toxicity profile of cadonilimab is similar to the toxicity profiles of approved PD-1 and CTLA-4 inhibitors.

Implications — A New Treatment Paradigm for Advanced Gastric Cancer?

According to Dr. Ji, the interim results from the cadonilimab study suggest that this novel PD-1/CTLA-4 bispecific antibody, in combination with chemotherapy, could become a new standard first-line treatment option for patients with advanced G/GEJ adenocarcinoma, offering a significant survival advantage over chemotherapy alone, regardless of PD-L1 status.

“The ability of cadonilimab to improve survival outcomes, regardless of PD-L1 status, is a significant advancement, as we have struggled to find effective treatments for patients with low PD-L1 expression in this setting,” he said, during the interview.

Despite these promising findings, Dr. Janjigian highlighted that patient stratification in the COMPASSION-15 study is currently lacking. She explained that biomarkers such as MSI status, T-reg signatures, and HER-2 are important to consider according to data from the CheckMate 649 trial.

“Hazard ratios for patients with T-reg–high tumors were almost 0.6, independent of inflammatory status. These data suggest that we can maybe even cure some patients with PD-1/CTLA-4 inhibitors,” she noted.

She added that knowing the status of MSI and HER-2 is clinically important as it can inform clinicians whether they can avoid chemotherapy or add trastuzumab.

“Despite the suboptimal comparator arm, the study is very important and offers a rationale for dual PD-1/CTLA-4 blockade,” Dr. Janjigian concluded.

COMPASSION-15 was funded by Akeso Biopharma, Inc. Dr. Ji reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients. Dr. Janjigian lists relationships with AbbVie, AmerisourceBergen Drug Corporation, Arcus Biosciences, Ask-Gene Pharma, Inc., Astellas Pharma, AstraZeneca, Basilea Pharmaceutica Ltd., Bayer, Bristol Myers, Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck, Pfizer, and many other companies, as well as the U.S. Department of Defense, National Cancer Institute, and others.

SAN DIEGO — In his role as chief medical officer for Ascension Medical Group–Texas, which employs about 1,000 physicians across every medical specialty, dermatologist Jason S. Reichenberg, MD, MBA, has heard his share of stories about patients who treat medical staff aggressively, incessantly complain, or threaten to file lawsuits for the care or treatment they’ve received.

At the annual meeting of the American Academy of Dermatology, Dr. Reichenberg, professor of dermatology at the University of Texas at Austin, shared several tips for managing such difficult patients:

Look for ‘red flags’ that raise concerns. This may include patients’ unrealistic expectations for a cure, “which could be because of their cultural or educational background,” he said. Difficult patients also may view physicians as enemies.

Dr. Reichenberg

“They may quote legal jargon or threaten consequences if there is a bad outcome,” he explained. “They may say, ‘I’m a great reviewer on Yelp and I look forward to giving you a great Yelp review when we finish today.’ They may also have previously sued physicians, or they may tell you that their last physician was horrible.”

Shift into robot mode. In other words, don’t stray from your practice’s protocol by offering special treatment to difficult patients. For example, if a difficult patient shows up 15 minutes late and the office has a policy that patients should be rescheduled if they arrive 10 minutes late, “do not break that policy no matter what, because that’s your protocol,” he advised. “You also do not promise anything you don’t know or that nobody could know. If a difficult patient asks, ‘what is the statistical chance that I’ll get better with this treatment,’ you either say, ‘studies have shown that this is the exact percentage,’ or ‘I don’t know. We’re going to do our best.’”

Set expectations at the outset. “If I walk into the room and the nurse has been in there for 25 minutes doing the intake and I know it’s going to be a long visit, I’ll start by saying, ‘I have 8 minutes to see you today,’ ” Dr. Reichenberg said. “ ‘Whatever we don’t finish today we’ll have to do during a follow-up visit, so let’s please prioritize what we need to do.’ ” Sometimes he sets his smartphone alarm to 8 minutes and when the timer goes off, he’ll say, “I’m so sorry, but I have to go.” For talkative patients, he continued, “I’ll ask, ‘is it okay if I interrupt you if I have a clarifying question?’ That gives you permission to interrupt.”

Blame a third “party” or policy. When patients express anger, find an “enemy” that you can be angry at together. “You might say something like, ‘I’m as frustrated as you are; I can’t believe how broken our health care system is that I have only 8 minutes with you today,’ ” he advised. “Show that you’re on the same side as them.” You could also blame a policy by saying something like, “I’m sorry; I can’t do that for you. My practice has strict rules about that. I’m as frustrated as you are.”

Practice self-regulation. Here, the goal is to delay the time between being triggered by the patient who gets under your skin and your response to that person, such as saying you received “a page or an important text before you walk out of the exam room,” he said. This principle also applies to messages that unreasonable individuals send by e-mail or through messages on their patient portal. “Probably the biggest mistakes I’ve seen from physicians is when they get really angry and they write an angry portal message or e-mail and send it out,” Dr. Reichenberg said. “If I feel triggered, I wait to respond. I’ll sometimes forward [the response] it to my nurse and request that person to send it out the next morning, so the reply reads, ‘Dr. Reichenberg said…’ That gives me the chance to calm down. It also gives the patient a chance to calm down.”

Never worry alone. When struggling to communicate effectively with a difficult patient, he recommends seeking input from a trusted physician colleague. “Better yet, pick up the phone and call the patient’s primary care doctor or another specialist who takes care of that person, and talk about it,” he said. “Figure out if this is your problem or the patient’s problem. They may offer advice on how to handle that person.”

Know when the conflict is untenable. Sometimes it’s best to resign from providing care to difficult patients. “I might write or say something like, ‘I resign from your care. I do not have any expertise to help you with your problem,’ ” Dr. Reichenberg said. “Or, ‘I don’t know that I have the infrastructure to handle the kind of problems you have. I’m not sure we’re the best fit.’ I would suggest that you not give every single detail about why you’re firing them, because the patients could write a step-by-step response, arguing against that.” If you decide to terminate the relationship with a patient, make sure that he or she is not in an acute phase of their illness. “You do not want to get sued for patient abandonment,” he said. “Know your state laws. In general, you’re going to give them a statement of intent to terminate — usually in 30 days — but you have to agree to treat them emergently.” Dr. Reichenberg also provides them with a referral source so they can find a new physician and waives the fee for sending medical records to the new provider. “Also, though it’s not required, I’ll include a statement about the consequences of not receiving care, if I think that they’re [neglecting] their own care,” he said.

Dr. Reichenberg reported having no financial disclosures.

SAN DIEGO — In his role as chief medical officer for Ascension Medical Group–Texas, which employs about 1,000 physicians across every medical specialty, dermatologist Jason S. Reichenberg, MD, MBA, has heard his share of stories about patients who treat medical staff aggressively, incessantly complain, or threaten to file lawsuits for the care or treatment they’ve received.

At the annual meeting of the American Academy of Dermatology, Dr. Reichenberg, professor of dermatology at the University of Texas at Austin, shared several tips for managing such difficult patients:

Look for ‘red flags’ that raise concerns. This may include patients’ unrealistic expectations for a cure, “which could be because of their cultural or educational background,” he said. Difficult patients also may view physicians as enemies.

Dr. Reichenberg

“They may quote legal jargon or threaten consequences if there is a bad outcome,” he explained. “They may say, ‘I’m a great reviewer on Yelp and I look forward to giving you a great Yelp review when we finish today.’ They may also have previously sued physicians, or they may tell you that their last physician was horrible.”

Shift into robot mode. In other words, don’t stray from your practice’s protocol by offering special treatment to difficult patients. For example, if a difficult patient shows up 15 minutes late and the office has a policy that patients should be rescheduled if they arrive 10 minutes late, “do not break that policy no matter what, because that’s your protocol,” he advised. “You also do not promise anything you don’t know or that nobody could know. If a difficult patient asks, ‘what is the statistical chance that I’ll get better with this treatment,’ you either say, ‘studies have shown that this is the exact percentage,’ or ‘I don’t know. We’re going to do our best.’”

Set expectations at the outset. “If I walk into the room and the nurse has been in there for 25 minutes doing the intake and I know it’s going to be a long visit, I’ll start by saying, ‘I have 8 minutes to see you today,’ ” Dr. Reichenberg said. “ ‘Whatever we don’t finish today we’ll have to do during a follow-up visit, so let’s please prioritize what we need to do.’ ” Sometimes he sets his smartphone alarm to 8 minutes and when the timer goes off, he’ll say, “I’m so sorry, but I have to go.” For talkative patients, he continued, “I’ll ask, ‘is it okay if I interrupt you if I have a clarifying question?’ That gives you permission to interrupt.”

Blame a third “party” or policy. When patients express anger, find an “enemy” that you can be angry at together. “You might say something like, ‘I’m as frustrated as you are; I can’t believe how broken our health care system is that I have only 8 minutes with you today,’ ” he advised. “Show that you’re on the same side as them.” You could also blame a policy by saying something like, “I’m sorry; I can’t do that for you. My practice has strict rules about that. I’m as frustrated as you are.”

Practice self-regulation. Here, the goal is to delay the time between being triggered by the patient who gets under your skin and your response to that person, such as saying you received “a page or an important text before you walk out of the exam room,” he said. This principle also applies to messages that unreasonable individuals send by e-mail or through messages on their patient portal. “Probably the biggest mistakes I’ve seen from physicians is when they get really angry and they write an angry portal message or e-mail and send it out,” Dr. Reichenberg said. “If I feel triggered, I wait to respond. I’ll sometimes forward [the response] it to my nurse and request that person to send it out the next morning, so the reply reads, ‘Dr. Reichenberg said…’ That gives me the chance to calm down. It also gives the patient a chance to calm down.”

Never worry alone. When struggling to communicate effectively with a difficult patient, he recommends seeking input from a trusted physician colleague. “Better yet, pick up the phone and call the patient’s primary care doctor or another specialist who takes care of that person, and talk about it,” he said. “Figure out if this is your problem or the patient’s problem. They may offer advice on how to handle that person.”

Know when the conflict is untenable. Sometimes it’s best to resign from providing care to difficult patients. “I might write or say something like, ‘I resign from your care. I do not have any expertise to help you with your problem,’ ” Dr. Reichenberg said. “Or, ‘I don’t know that I have the infrastructure to handle the kind of problems you have. I’m not sure we’re the best fit.’ I would suggest that you not give every single detail about why you’re firing them, because the patients could write a step-by-step response, arguing against that.” If you decide to terminate the relationship with a patient, make sure that he or she is not in an acute phase of their illness. “You do not want to get sued for patient abandonment,” he said. “Know your state laws. In general, you’re going to give them a statement of intent to terminate — usually in 30 days — but you have to agree to treat them emergently.” Dr. Reichenberg also provides them with a referral source so they can find a new physician and waives the fee for sending medical records to the new provider. “Also, though it’s not required, I’ll include a statement about the consequences of not receiving care, if I think that they’re [neglecting] their own care,” he said.

Dr. Reichenberg reported having no financial disclosures.

SAN DIEGO — In his role as chief medical officer for Ascension Medical Group–Texas, which employs about 1,000 physicians across every medical specialty, dermatologist Jason S. Reichenberg, MD, MBA, has heard his share of stories about patients who treat medical staff aggressively, incessantly complain, or threaten to file lawsuits for the care or treatment they’ve received.

At the annual meeting of the American Academy of Dermatology, Dr. Reichenberg, professor of dermatology at the University of Texas at Austin, shared several tips for managing such difficult patients:

Look for ‘red flags’ that raise concerns. This may include patients’ unrealistic expectations for a cure, “which could be because of their cultural or educational background,” he said. Difficult patients also may view physicians as enemies.

Dr. Reichenberg

“They may quote legal jargon or threaten consequences if there is a bad outcome,” he explained. “They may say, ‘I’m a great reviewer on Yelp and I look forward to giving you a great Yelp review when we finish today.’ They may also have previously sued physicians, or they may tell you that their last physician was horrible.”

Shift into robot mode. In other words, don’t stray from your practice’s protocol by offering special treatment to difficult patients. For example, if a difficult patient shows up 15 minutes late and the office has a policy that patients should be rescheduled if they arrive 10 minutes late, “do not break that policy no matter what, because that’s your protocol,” he advised. “You also do not promise anything you don’t know or that nobody could know. If a difficult patient asks, ‘what is the statistical chance that I’ll get better with this treatment,’ you either say, ‘studies have shown that this is the exact percentage,’ or ‘I don’t know. We’re going to do our best.’”

Set expectations at the outset. “If I walk into the room and the nurse has been in there for 25 minutes doing the intake and I know it’s going to be a long visit, I’ll start by saying, ‘I have 8 minutes to see you today,’ ” Dr. Reichenberg said. “ ‘Whatever we don’t finish today we’ll have to do during a follow-up visit, so let’s please prioritize what we need to do.’ ” Sometimes he sets his smartphone alarm to 8 minutes and when the timer goes off, he’ll say, “I’m so sorry, but I have to go.” For talkative patients, he continued, “I’ll ask, ‘is it okay if I interrupt you if I have a clarifying question?’ That gives you permission to interrupt.”

Blame a third “party” or policy. When patients express anger, find an “enemy” that you can be angry at together. “You might say something like, ‘I’m as frustrated as you are; I can’t believe how broken our health care system is that I have only 8 minutes with you today,’ ” he advised. “Show that you’re on the same side as them.” You could also blame a policy by saying something like, “I’m sorry; I can’t do that for you. My practice has strict rules about that. I’m as frustrated as you are.”

Practice self-regulation. Here, the goal is to delay the time between being triggered by the patient who gets under your skin and your response to that person, such as saying you received “a page or an important text before you walk out of the exam room,” he said. This principle also applies to messages that unreasonable individuals send by e-mail or through messages on their patient portal. “Probably the biggest mistakes I’ve seen from physicians is when they get really angry and they write an angry portal message or e-mail and send it out,” Dr. Reichenberg said. “If I feel triggered, I wait to respond. I’ll sometimes forward [the response] it to my nurse and request that person to send it out the next morning, so the reply reads, ‘Dr. Reichenberg said…’ That gives me the chance to calm down. It also gives the patient a chance to calm down.”

Never worry alone. When struggling to communicate effectively with a difficult patient, he recommends seeking input from a trusted physician colleague. “Better yet, pick up the phone and call the patient’s primary care doctor or another specialist who takes care of that person, and talk about it,” he said. “Figure out if this is your problem or the patient’s problem. They may offer advice on how to handle that person.”

Know when the conflict is untenable. Sometimes it’s best to resign from providing care to difficult patients. “I might write or say something like, ‘I resign from your care. I do not have any expertise to help you with your problem,’ ” Dr. Reichenberg said. “Or, ‘I don’t know that I have the infrastructure to handle the kind of problems you have. I’m not sure we’re the best fit.’ I would suggest that you not give every single detail about why you’re firing them, because the patients could write a step-by-step response, arguing against that.” If you decide to terminate the relationship with a patient, make sure that he or she is not in an acute phase of their illness. “You do not want to get sued for patient abandonment,” he said. “Know your state laws. In general, you’re going to give them a statement of intent to terminate — usually in 30 days — but you have to agree to treat them emergently.” Dr. Reichenberg also provides them with a referral source so they can find a new physician and waives the fee for sending medical records to the new provider. “Also, though it’s not required, I’ll include a statement about the consequences of not receiving care, if I think that they’re [neglecting] their own care,” he said.

Dr. Reichenberg reported having no financial disclosures.

SAN DIEGO — In the next few years, expect intradermal injections of botulinum toxin A for the improvement in the appearance of pores, sebum, skin texture, and rosacea to gain a foothold in dermatology practices, Jeremy B. Green, MD, predicts.

“This technique is more popular in Asia than it is here in the US,” Dr. Green, who practices dermatology in Coral Gables, Florida, said at the annual meeting of the American Academy of Dermatology. As opposed to intramuscular injections, “it’s an intradermal delivery, so you use numbing cream prior, and you’re injecting botulinum toxin A nearly parallel to the skin surface with the bevel of the needle up,” he said. “You want to use a precise product. It’s uncomfortable delivering volume so superficially due to the tissue distention, so I also use a massager. I inject approximately 0.05 mL to 0.1 mL per point. This does really work.”

This mode of delivery was evaluated in a prospective, double-blind, split-face study in South Korea, which enrolled 18 volunteers who received an intradermal injection of botulinum toxin A into one cheek and normal saline into the contralateral side as a control. Participants were between 30 and 54 years of age and were seen at the clinic 2, 4, 8, and 12 weeks after the injection. At each visit, investigators took photographs, used a facial analyzer to evaluate the pores and wrinkles of the infraorbital area, and used a Sebumeter to evaluate sebum secretions from both cheeks. Improvement or aggravation in skin texture was evaluated by both volunteers and clinicians on a numeric scale from –4 (severe aggravation) to +4 (marked improvement) at each visit, and following photographic review, the wrinkle score of the nasolabial fold was graded on a 5-point scale.

The researchers observed no significant effects on the wrinkles of the infraorbital area and on sebum secretion. However, on the side where botulinum toxin A was injected, there were significant improvements in the wrinkles of the nasolabial fold and skin texture, they reported. The effects on nasolabial fold wrinkles lasted 12 weeks, effects on skin texture lasted 8 weeks, and improvement in pore size was only observed at week 2, they wrote. One serious adverse event occurred: a case of facial palsy after the injection of 30 units of botulinum toxin A in one cheek. However, injection of 20 units of botulinum toxin A in one cheek was not associated with any adverse events.

“The duration of these treatments is yet to be determined, but I think this is definitely going to gain popularity in the US,” said Dr. Green, clinical assistant professor of dermatology at the University of Miami Department of Dermatology and Cutaneous Surgery.
 

Recently Approved Neurotoxin

He also discussed letibotulinumtoxinA-wlbg (Letybo), an injectable neurotoxin long used in South Korea, which the US Food and Drug Administration (FDA) approved for the temporary improvement in the appearance of moderate to severe glabellar (frown) lines in adults on March 4, 2024. Approval was based on positive results from three phase 3 trials of letibotulinumtoxinA-wlbg that enrolled more than 1,000 individuals in the United States and Europe.

“This is the sixth approved neurotoxin in the US,” Dr. Green said. “It is derived from the CBFC26 strain of Clostridium botulinum, and it’s a purified 900 kDa type A toxin complex with human serum albumin and sodium chloride as its excipients.” It comes in a 50-unit or 100-unit vial and requires refrigeration. “To me, the most fascinating thing about this product is that it has been the number-one selling botulinum toxin on the South Korea market for the last 5 years,” he said. “But what do we know about its characteristics?”

In a non-inferiority trial, Chinese researchers enrolled 500 patients with moderate to severe glabellar wrinkles to investigate the efficacy and safety of letibotulinumtoxinA-wlbg and onabotulinumtoxinA. Participants were randomized 3:1 to receive 20 U of letibotulinumtoxinA-wlbg or onabotulinumtoxinA and then observed them for 16 weeks. The primary endpoint was noninferiority in the proportion of study participants who received a score of 0 or 1 for glabellar wrinkles on a four-point photographic evaluation scale, as assessed by an evaluator at maximum frown at 4 weeks.

At week 4, 88.49% of participants in the letibotulinumtoxinA-wlbg arm achieved a score of 0 or 1 for glabellar wrinkles, compared with 87.39% of those in the onabotulinumtoxinA arm (P = .7469). No significant differences were observed for secondary efficacy or safety endpoints between the two treatments. “It will be interesting to see how this product does when it’s available to us,” Dr. Green said.

Another potential newcomer is ready-to-use liquid botulinum neurotoxin. RelabotulinumtoxinA is a complex, protein-free, ready-to-use liquid botulinum toxin A designed to avoid the traditional requirement to reconstitute it from powder, according to Galderma. It features a saline phosphate buffer solution, so it contains no human or animal-derived excipients, Dr. Green pointed out, and it eliminates the variability, errors, and risks associated with reconstitution.

“There was a report in the neurology literature of botulinum toxin being reconstituted with sterile water for cervical dystonia,” he noted. “When this was injected, it was excruciatingly painful, because it created an osmotic gradient within the muscle. So, if we can take a step away from human error, that would be a good thing.”

To date, Dr. Green said, four phase 3 trials of relabotulinumtoxinA involving more than 1,900 patients have been conducted in the United States and Canada evaluating its use for glabellar frown lines and lateral canthal lines, “and the data is impressive,” he said. This product is still investigational, said Dr. Green, who has not had experience injecting it in the clinical trial program.

The idea of a rapid onset botulinum toxin is also emerging. TrenibotulinumtoxinE, which is being developed by Allergan, “is similar to a type A neurotoxin,” Dr. Green said. “It inhibits neuromuscular transmission via presynaptic vesicular protein synaptosomal-associated protein (SNAP)-25 but at a different cleavage site. It has a faster onset — within one day — but a shorter duration — 3-4 weeks.”

In a dose escalation study of its use for glabellar frown lines, 80% of participants achieved a two-grade investigator-rated improvement in glabellar frown line severity at maximum frown at the highest dose. The maximum clinical effect of trenibotulinumtoxinE was seen within 24 hours and lasted between 14 and 30 days.

“The question is, if it is approved by the FDA, where would this product fit in our practices?” Dr. Green asked. “The effect is gone in 3 weeks as opposed to 4 months,” so this may be an option to recommend for someone who is reticent to try neurotoxins, he said, “or a patient who comes to you on a Friday and says, ‘I have a gala tomorrow night.’ ”

Dr. Green disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for many pharmaceutical companies, including Allergan and Galderma.

SAN DIEGO — In the next few years, expect intradermal injections of botulinum toxin A for the improvement in the appearance of pores, sebum, skin texture, and rosacea to gain a foothold in dermatology practices, Jeremy B. Green, MD, predicts.

“This technique is more popular in Asia than it is here in the US,” Dr. Green, who practices dermatology in Coral Gables, Florida, said at the annual meeting of the American Academy of Dermatology. As opposed to intramuscular injections, “it’s an intradermal delivery, so you use numbing cream prior, and you’re injecting botulinum toxin A nearly parallel to the skin surface with the bevel of the needle up,” he said. “You want to use a precise product. It’s uncomfortable delivering volume so superficially due to the tissue distention, so I also use a massager. I inject approximately 0.05 mL to 0.1 mL per point. This does really work.”

This mode of delivery was evaluated in a prospective, double-blind, split-face study in South Korea, which enrolled 18 volunteers who received an intradermal injection of botulinum toxin A into one cheek and normal saline into the contralateral side as a control. Participants were between 30 and 54 years of age and were seen at the clinic 2, 4, 8, and 12 weeks after the injection. At each visit, investigators took photographs, used a facial analyzer to evaluate the pores and wrinkles of the infraorbital area, and used a Sebumeter to evaluate sebum secretions from both cheeks. Improvement or aggravation in skin texture was evaluated by both volunteers and clinicians on a numeric scale from –4 (severe aggravation) to +4 (marked improvement) at each visit, and following photographic review, the wrinkle score of the nasolabial fold was graded on a 5-point scale.

The researchers observed no significant effects on the wrinkles of the infraorbital area and on sebum secretion. However, on the side where botulinum toxin A was injected, there were significant improvements in the wrinkles of the nasolabial fold and skin texture, they reported. The effects on nasolabial fold wrinkles lasted 12 weeks, effects on skin texture lasted 8 weeks, and improvement in pore size was only observed at week 2, they wrote. One serious adverse event occurred: a case of facial palsy after the injection of 30 units of botulinum toxin A in one cheek. However, injection of 20 units of botulinum toxin A in one cheek was not associated with any adverse events.

“The duration of these treatments is yet to be determined, but I think this is definitely going to gain popularity in the US,” said Dr. Green, clinical assistant professor of dermatology at the University of Miami Department of Dermatology and Cutaneous Surgery.
 

Recently Approved Neurotoxin

He also discussed letibotulinumtoxinA-wlbg (Letybo), an injectable neurotoxin long used in South Korea, which the US Food and Drug Administration (FDA) approved for the temporary improvement in the appearance of moderate to severe glabellar (frown) lines in adults on March 4, 2024. Approval was based on positive results from three phase 3 trials of letibotulinumtoxinA-wlbg that enrolled more than 1,000 individuals in the United States and Europe.

“This is the sixth approved neurotoxin in the US,” Dr. Green said. “It is derived from the CBFC26 strain of Clostridium botulinum, and it’s a purified 900 kDa type A toxin complex with human serum albumin and sodium chloride as its excipients.” It comes in a 50-unit or 100-unit vial and requires refrigeration. “To me, the most fascinating thing about this product is that it has been the number-one selling botulinum toxin on the South Korea market for the last 5 years,” he said. “But what do we know about its characteristics?”

In a non-inferiority trial, Chinese researchers enrolled 500 patients with moderate to severe glabellar wrinkles to investigate the efficacy and safety of letibotulinumtoxinA-wlbg and onabotulinumtoxinA. Participants were randomized 3:1 to receive 20 U of letibotulinumtoxinA-wlbg or onabotulinumtoxinA and then observed them for 16 weeks. The primary endpoint was noninferiority in the proportion of study participants who received a score of 0 or 1 for glabellar wrinkles on a four-point photographic evaluation scale, as assessed by an evaluator at maximum frown at 4 weeks.

At week 4, 88.49% of participants in the letibotulinumtoxinA-wlbg arm achieved a score of 0 or 1 for glabellar wrinkles, compared with 87.39% of those in the onabotulinumtoxinA arm (P = .7469). No significant differences were observed for secondary efficacy or safety endpoints between the two treatments. “It will be interesting to see how this product does when it’s available to us,” Dr. Green said.

Another potential newcomer is ready-to-use liquid botulinum neurotoxin. RelabotulinumtoxinA is a complex, protein-free, ready-to-use liquid botulinum toxin A designed to avoid the traditional requirement to reconstitute it from powder, according to Galderma. It features a saline phosphate buffer solution, so it contains no human or animal-derived excipients, Dr. Green pointed out, and it eliminates the variability, errors, and risks associated with reconstitution.

“There was a report in the neurology literature of botulinum toxin being reconstituted with sterile water for cervical dystonia,” he noted. “When this was injected, it was excruciatingly painful, because it created an osmotic gradient within the muscle. So, if we can take a step away from human error, that would be a good thing.”

To date, Dr. Green said, four phase 3 trials of relabotulinumtoxinA involving more than 1,900 patients have been conducted in the United States and Canada evaluating its use for glabellar frown lines and lateral canthal lines, “and the data is impressive,” he said. This product is still investigational, said Dr. Green, who has not had experience injecting it in the clinical trial program.

The idea of a rapid onset botulinum toxin is also emerging. TrenibotulinumtoxinE, which is being developed by Allergan, “is similar to a type A neurotoxin,” Dr. Green said. “It inhibits neuromuscular transmission via presynaptic vesicular protein synaptosomal-associated protein (SNAP)-25 but at a different cleavage site. It has a faster onset — within one day — but a shorter duration — 3-4 weeks.”

In a dose escalation study of its use for glabellar frown lines, 80% of participants achieved a two-grade investigator-rated improvement in glabellar frown line severity at maximum frown at the highest dose. The maximum clinical effect of trenibotulinumtoxinE was seen within 24 hours and lasted between 14 and 30 days.

“The question is, if it is approved by the FDA, where would this product fit in our practices?” Dr. Green asked. “The effect is gone in 3 weeks as opposed to 4 months,” so this may be an option to recommend for someone who is reticent to try neurotoxins, he said, “or a patient who comes to you on a Friday and says, ‘I have a gala tomorrow night.’ ”

Dr. Green disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for many pharmaceutical companies, including Allergan and Galderma.

SAN DIEGO — In the next few years, expect intradermal injections of botulinum toxin A for the improvement in the appearance of pores, sebum, skin texture, and rosacea to gain a foothold in dermatology practices, Jeremy B. Green, MD, predicts.

“This technique is more popular in Asia than it is here in the US,” Dr. Green, who practices dermatology in Coral Gables, Florida, said at the annual meeting of the American Academy of Dermatology. As opposed to intramuscular injections, “it’s an intradermal delivery, so you use numbing cream prior, and you’re injecting botulinum toxin A nearly parallel to the skin surface with the bevel of the needle up,” he said. “You want to use a precise product. It’s uncomfortable delivering volume so superficially due to the tissue distention, so I also use a massager. I inject approximately 0.05 mL to 0.1 mL per point. This does really work.”

This mode of delivery was evaluated in a prospective, double-blind, split-face study in South Korea, which enrolled 18 volunteers who received an intradermal injection of botulinum toxin A into one cheek and normal saline into the contralateral side as a control. Participants were between 30 and 54 years of age and were seen at the clinic 2, 4, 8, and 12 weeks after the injection. At each visit, investigators took photographs, used a facial analyzer to evaluate the pores and wrinkles of the infraorbital area, and used a Sebumeter to evaluate sebum secretions from both cheeks. Improvement or aggravation in skin texture was evaluated by both volunteers and clinicians on a numeric scale from –4 (severe aggravation) to +4 (marked improvement) at each visit, and following photographic review, the wrinkle score of the nasolabial fold was graded on a 5-point scale.

The researchers observed no significant effects on the wrinkles of the infraorbital area and on sebum secretion. However, on the side where botulinum toxin A was injected, there were significant improvements in the wrinkles of the nasolabial fold and skin texture, they reported. The effects on nasolabial fold wrinkles lasted 12 weeks, effects on skin texture lasted 8 weeks, and improvement in pore size was only observed at week 2, they wrote. One serious adverse event occurred: a case of facial palsy after the injection of 30 units of botulinum toxin A in one cheek. However, injection of 20 units of botulinum toxin A in one cheek was not associated with any adverse events.

“The duration of these treatments is yet to be determined, but I think this is definitely going to gain popularity in the US,” said Dr. Green, clinical assistant professor of dermatology at the University of Miami Department of Dermatology and Cutaneous Surgery.
 

Recently Approved Neurotoxin

He also discussed letibotulinumtoxinA-wlbg (Letybo), an injectable neurotoxin long used in South Korea, which the US Food and Drug Administration (FDA) approved for the temporary improvement in the appearance of moderate to severe glabellar (frown) lines in adults on March 4, 2024. Approval was based on positive results from three phase 3 trials of letibotulinumtoxinA-wlbg that enrolled more than 1,000 individuals in the United States and Europe.

“This is the sixth approved neurotoxin in the US,” Dr. Green said. “It is derived from the CBFC26 strain of Clostridium botulinum, and it’s a purified 900 kDa type A toxin complex with human serum albumin and sodium chloride as its excipients.” It comes in a 50-unit or 100-unit vial and requires refrigeration. “To me, the most fascinating thing about this product is that it has been the number-one selling botulinum toxin on the South Korea market for the last 5 years,” he said. “But what do we know about its characteristics?”

In a non-inferiority trial, Chinese researchers enrolled 500 patients with moderate to severe glabellar wrinkles to investigate the efficacy and safety of letibotulinumtoxinA-wlbg and onabotulinumtoxinA. Participants were randomized 3:1 to receive 20 U of letibotulinumtoxinA-wlbg or onabotulinumtoxinA and then observed them for 16 weeks. The primary endpoint was noninferiority in the proportion of study participants who received a score of 0 or 1 for glabellar wrinkles on a four-point photographic evaluation scale, as assessed by an evaluator at maximum frown at 4 weeks.

At week 4, 88.49% of participants in the letibotulinumtoxinA-wlbg arm achieved a score of 0 or 1 for glabellar wrinkles, compared with 87.39% of those in the onabotulinumtoxinA arm (P = .7469). No significant differences were observed for secondary efficacy or safety endpoints between the two treatments. “It will be interesting to see how this product does when it’s available to us,” Dr. Green said.

Another potential newcomer is ready-to-use liquid botulinum neurotoxin. RelabotulinumtoxinA is a complex, protein-free, ready-to-use liquid botulinum toxin A designed to avoid the traditional requirement to reconstitute it from powder, according to Galderma. It features a saline phosphate buffer solution, so it contains no human or animal-derived excipients, Dr. Green pointed out, and it eliminates the variability, errors, and risks associated with reconstitution.

“There was a report in the neurology literature of botulinum toxin being reconstituted with sterile water for cervical dystonia,” he noted. “When this was injected, it was excruciatingly painful, because it created an osmotic gradient within the muscle. So, if we can take a step away from human error, that would be a good thing.”

To date, Dr. Green said, four phase 3 trials of relabotulinumtoxinA involving more than 1,900 patients have been conducted in the United States and Canada evaluating its use for glabellar frown lines and lateral canthal lines, “and the data is impressive,” he said. This product is still investigational, said Dr. Green, who has not had experience injecting it in the clinical trial program.

The idea of a rapid onset botulinum toxin is also emerging. TrenibotulinumtoxinE, which is being developed by Allergan, “is similar to a type A neurotoxin,” Dr. Green said. “It inhibits neuromuscular transmission via presynaptic vesicular protein synaptosomal-associated protein (SNAP)-25 but at a different cleavage site. It has a faster onset — within one day — but a shorter duration — 3-4 weeks.”

In a dose escalation study of its use for glabellar frown lines, 80% of participants achieved a two-grade investigator-rated improvement in glabellar frown line severity at maximum frown at the highest dose. The maximum clinical effect of trenibotulinumtoxinE was seen within 24 hours and lasted between 14 and 30 days.

“The question is, if it is approved by the FDA, where would this product fit in our practices?” Dr. Green asked. “The effect is gone in 3 weeks as opposed to 4 months,” so this may be an option to recommend for someone who is reticent to try neurotoxins, he said, “or a patient who comes to you on a Friday and says, ‘I have a gala tomorrow night.’ ”

Dr. Green disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for many pharmaceutical companies, including Allergan and Galderma.

SAN DIEGO — In two different phase 2b trial extensions, oral treatment with Janus kinase (JAK) inhibitors showed improved skin clearance in patients with vitiligo, according to presentations at a late-breaking session at the annual meeting of the American Academy of Dermatology (AAD).

In one, the addition of narrow-band ultraviolet-B (NB-UVB) light therapy to ritlecitinib appears more effective than ritlecitinib alone. In the other study, the effectiveness of upadacitinib appears to improve over time.

Based on the ritlecitinib data, “if you have phototherapy in your office, it might be good to couple it with ritlecitinib for vitiligo patients,” said Emma Guttman-Yassky, MD, PhD, chair of the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, who presented the findings.

However, because of the relatively small numbers in the extension study, Dr. Guttman-Yassky characterized the evidence as preliminary and in need of further investigation.

For vitiligo, the only approved JAK inhibitor is ruxolitinib, 1.5%, in a cream formulation. In June, ritlecitinib (Litfulo) was approved by the Food and Drug Administration (FDA) for alopecia areata. Phototherapy, which has been used for decades in the treatment of vitiligo, has an established efficacy and safety profile as a stand-alone vitiligo treatment. Upadacitinib has numerous indications for inflammatory diseases, such as rheumatoid arthritis, and was granted FDA approval for atopic dermatitis in 2022.
 

NB-UVB Arm Added in Ritlecitinib Extension

The ritlecitinib study population was drawn from patients with non-segmental vitiligo who initially participated in a 24-week dose-ranging period of a phase 2b trial published last year. In that study, 364 patients were randomized to doses of once-daily ritlecitinib ranging from 10 to 50 mg with or without a 4-week loading regimen. Higher doses were generally associated with greater efficacy on the primary endpoint of facial vitiligo area scoring index (F-VASI) but not with a greater risk for adverse events.

In the 24-week extension study, 187 patients received a 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib for the remaining 20 weeks. Another 43 patients were randomized to one of two arms: The same 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib or to 50-mg daily ritlecitinib without a loading dose but combined with NB-UVB delivered twice per week.

Important to interpretation of results, there was an additional twist. Patients in the randomized arm who had < 10% improvement in the total vitiligo area severity index (T-VASI) at week 12 of the extension were discontinued from the study.

The endpoints considered when comparing ritlecitinib with or without NB-UVB at the end of the extension study were F-VASI, T-VASI, patient global impression of change, and adverse events. Responses were assessed on the basis of both observed and last observation carried forward (LOCF).

Of the 43 people, who were randomized in the extension study, nine (21%) had < 10% improvement in T-VASI and were therefore discontinued from the study.

At the end of 24 weeks, both groups had a substantial response to their assigned therapy, but the addition of NB-UVB increased rates of response, although not always at a level of statistical significance, according to Dr. Guttman-Yassky.

For the percent improvement in F-VASI, specifically, the increase did not reach significance on the basis of LOCF (57.9% vs 51.5%; P = .158) but was highly significant on the basis of observed responses (69.6% vs 55.1%; P = .009). For T-VASI, differences for adjunctive NB-UVB over monotherapy did not reach significance for either observed or LOCF responses, but it was significant for observed responses in a patient global impression of change.
 

Small Numbers Limit Strength of Ritlecitinib, NB-UVB Evidence

However, Dr. Guttman-Yassky said it is important “to pay attention to the sample sizes” when noting the lack of significance.

The combination appeared safe, and there were no side effects associated with the addition of twice-weekly NB-UVB to ritlecitinib.

She acknowledged that the design of this analysis was “complicated” and that the number of randomized patients was small. She suggested the findings support the potential for benefit from the combination of a JAK inhibitor and NB-UVB, both of which have shown efficacy as monotherapy in previous studies. She indicated that a trial of this combination is reasonable while awaiting a more definitive study.

One of the questions that might be posed in a larger study is the timing of NB-UVB, such as whether it is best reserved for those with inadequate early response to a JAK inhibitor or if optimal results are achieved when a JAK inhibitor and NB-UVB are initiated simultaneously.

Upadacitinib Monotherapy Results

One rationale for initiating therapy with the combination of a JAK inhibitor and NB-UVB is the potential for a more rapid response, but extended results from a second phase 2b study with a different oral JAK inhibitor, upadacitinib, suggested responses on JAK inhibitor monotherapy improve steadily over time.

“The overall efficacy continued to improve without reaching a plateau at 1 year,” reported Thierry Passeron, MD, PhD, professor and chair, Department of Dermatology, Université Côte d’Azur, Nice, France. He spoke at the same AAD late-breaking session as Dr. Guttman-Yassky.

The 24-week dose-ranging data from the upadacitinib trial were previously reported at the 2023 annual meeting of the European Association of Dermatology and Venereology. In the placebo-controlled portion, which randomized 185 patients with extensive non-segmental vitiligo to 6 mg, 11 mg, or 22 mg, the two higher doses were significantly more effective than placebo.

In the extension, patients in the placebo group were randomized to 11 mg or 22 mg, while those in the higher dose groups remained on their assigned therapies.
 

F-VASI Almost Doubled in Extension Trial

From week 24 to week 52, there was nearly a doubling of the percent F-VASI reduction, climbing from 32% to 60.8% in the 11-mg group and from 38.7% to 64.9% in the 22-mg group, Dr. Passeron said. Placebo groups who were switched to active therapy at 24 weeks rapidly approached the rates of F-VASI response of those initiated on upadacitinib.

The percent reductions in T-VASI, although lower, followed the same pattern. For the 11-mg group, the reduction climbed from 16% at 24 weeks to 44.7% at 52 weeks. For the 22-mg group, the reduction climbed from 22.9% to 44.4%. Patients who were switched from placebo to 11 mg or to 22 mg also experienced improvements in T-VASI up to 52 weeks, although the level of improvement was lower than that in patients initially randomized to the higher doses of upadacitinib.

There were “no new safety signals” for upadacitinib, which is FDA-approved for multiple indications, according to Dr. Passeron. He said acne-like lesions were the most bothersome adverse event, and cases of herpes zoster were “rare.”

A version of these data was published in a British Journal of Dermatology supplement just prior to the AAD meeting.

Phase 3 vitiligo trials are planned for both ritlecitinib and upadacitinib.

Dr. Guttman-Yassky reported financial relationships with approximately 45 pharmaceutical companies, including Pfizer, which makes ritlecitinib and provided funding for the study she discussed. Dr. Passeron reported financial relationships with approximately 40 pharmaceutical companies, including AbbVie, which makes upadacitinib and provided funding for the study he discussed.

A version of this article appeared on Medscape.com.

SAN DIEGO — In two different phase 2b trial extensions, oral treatment with Janus kinase (JAK) inhibitors showed improved skin clearance in patients with vitiligo, according to presentations at a late-breaking session at the annual meeting of the American Academy of Dermatology (AAD).

In one, the addition of narrow-band ultraviolet-B (NB-UVB) light therapy to ritlecitinib appears more effective than ritlecitinib alone. In the other study, the effectiveness of upadacitinib appears to improve over time.

Based on the ritlecitinib data, “if you have phototherapy in your office, it might be good to couple it with ritlecitinib for vitiligo patients,” said Emma Guttman-Yassky, MD, PhD, chair of the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, who presented the findings.

However, because of the relatively small numbers in the extension study, Dr. Guttman-Yassky characterized the evidence as preliminary and in need of further investigation.

For vitiligo, the only approved JAK inhibitor is ruxolitinib, 1.5%, in a cream formulation. In June, ritlecitinib (Litfulo) was approved by the Food and Drug Administration (FDA) for alopecia areata. Phototherapy, which has been used for decades in the treatment of vitiligo, has an established efficacy and safety profile as a stand-alone vitiligo treatment. Upadacitinib has numerous indications for inflammatory diseases, such as rheumatoid arthritis, and was granted FDA approval for atopic dermatitis in 2022.
 

NB-UVB Arm Added in Ritlecitinib Extension

The ritlecitinib study population was drawn from patients with non-segmental vitiligo who initially participated in a 24-week dose-ranging period of a phase 2b trial published last year. In that study, 364 patients were randomized to doses of once-daily ritlecitinib ranging from 10 to 50 mg with or without a 4-week loading regimen. Higher doses were generally associated with greater efficacy on the primary endpoint of facial vitiligo area scoring index (F-VASI) but not with a greater risk for adverse events.

In the 24-week extension study, 187 patients received a 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib for the remaining 20 weeks. Another 43 patients were randomized to one of two arms: The same 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib or to 50-mg daily ritlecitinib without a loading dose but combined with NB-UVB delivered twice per week.

Important to interpretation of results, there was an additional twist. Patients in the randomized arm who had < 10% improvement in the total vitiligo area severity index (T-VASI) at week 12 of the extension were discontinued from the study.

The endpoints considered when comparing ritlecitinib with or without NB-UVB at the end of the extension study were F-VASI, T-VASI, patient global impression of change, and adverse events. Responses were assessed on the basis of both observed and last observation carried forward (LOCF).

Of the 43 people, who were randomized in the extension study, nine (21%) had < 10% improvement in T-VASI and were therefore discontinued from the study.

At the end of 24 weeks, both groups had a substantial response to their assigned therapy, but the addition of NB-UVB increased rates of response, although not always at a level of statistical significance, according to Dr. Guttman-Yassky.

For the percent improvement in F-VASI, specifically, the increase did not reach significance on the basis of LOCF (57.9% vs 51.5%; P = .158) but was highly significant on the basis of observed responses (69.6% vs 55.1%; P = .009). For T-VASI, differences for adjunctive NB-UVB over monotherapy did not reach significance for either observed or LOCF responses, but it was significant for observed responses in a patient global impression of change.
 

Small Numbers Limit Strength of Ritlecitinib, NB-UVB Evidence

However, Dr. Guttman-Yassky said it is important “to pay attention to the sample sizes” when noting the lack of significance.

The combination appeared safe, and there were no side effects associated with the addition of twice-weekly NB-UVB to ritlecitinib.

She acknowledged that the design of this analysis was “complicated” and that the number of randomized patients was small. She suggested the findings support the potential for benefit from the combination of a JAK inhibitor and NB-UVB, both of which have shown efficacy as monotherapy in previous studies. She indicated that a trial of this combination is reasonable while awaiting a more definitive study.

One of the questions that might be posed in a larger study is the timing of NB-UVB, such as whether it is best reserved for those with inadequate early response to a JAK inhibitor or if optimal results are achieved when a JAK inhibitor and NB-UVB are initiated simultaneously.

Upadacitinib Monotherapy Results

One rationale for initiating therapy with the combination of a JAK inhibitor and NB-UVB is the potential for a more rapid response, but extended results from a second phase 2b study with a different oral JAK inhibitor, upadacitinib, suggested responses on JAK inhibitor monotherapy improve steadily over time.

“The overall efficacy continued to improve without reaching a plateau at 1 year,” reported Thierry Passeron, MD, PhD, professor and chair, Department of Dermatology, Université Côte d’Azur, Nice, France. He spoke at the same AAD late-breaking session as Dr. Guttman-Yassky.

The 24-week dose-ranging data from the upadacitinib trial were previously reported at the 2023 annual meeting of the European Association of Dermatology and Venereology. In the placebo-controlled portion, which randomized 185 patients with extensive non-segmental vitiligo to 6 mg, 11 mg, or 22 mg, the two higher doses were significantly more effective than placebo.

In the extension, patients in the placebo group were randomized to 11 mg or 22 mg, while those in the higher dose groups remained on their assigned therapies.
 

F-VASI Almost Doubled in Extension Trial

From week 24 to week 52, there was nearly a doubling of the percent F-VASI reduction, climbing from 32% to 60.8% in the 11-mg group and from 38.7% to 64.9% in the 22-mg group, Dr. Passeron said. Placebo groups who were switched to active therapy at 24 weeks rapidly approached the rates of F-VASI response of those initiated on upadacitinib.

The percent reductions in T-VASI, although lower, followed the same pattern. For the 11-mg group, the reduction climbed from 16% at 24 weeks to 44.7% at 52 weeks. For the 22-mg group, the reduction climbed from 22.9% to 44.4%. Patients who were switched from placebo to 11 mg or to 22 mg also experienced improvements in T-VASI up to 52 weeks, although the level of improvement was lower than that in patients initially randomized to the higher doses of upadacitinib.

There were “no new safety signals” for upadacitinib, which is FDA-approved for multiple indications, according to Dr. Passeron. He said acne-like lesions were the most bothersome adverse event, and cases of herpes zoster were “rare.”

A version of these data was published in a British Journal of Dermatology supplement just prior to the AAD meeting.

Phase 3 vitiligo trials are planned for both ritlecitinib and upadacitinib.

Dr. Guttman-Yassky reported financial relationships with approximately 45 pharmaceutical companies, including Pfizer, which makes ritlecitinib and provided funding for the study she discussed. Dr. Passeron reported financial relationships with approximately 40 pharmaceutical companies, including AbbVie, which makes upadacitinib and provided funding for the study he discussed.

A version of this article appeared on Medscape.com.

SAN DIEGO — In two different phase 2b trial extensions, oral treatment with Janus kinase (JAK) inhibitors showed improved skin clearance in patients with vitiligo, according to presentations at a late-breaking session at the annual meeting of the American Academy of Dermatology (AAD).

In one, the addition of narrow-band ultraviolet-B (NB-UVB) light therapy to ritlecitinib appears more effective than ritlecitinib alone. In the other study, the effectiveness of upadacitinib appears to improve over time.

Based on the ritlecitinib data, “if you have phototherapy in your office, it might be good to couple it with ritlecitinib for vitiligo patients,” said Emma Guttman-Yassky, MD, PhD, chair of the Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, who presented the findings.

However, because of the relatively small numbers in the extension study, Dr. Guttman-Yassky characterized the evidence as preliminary and in need of further investigation.

For vitiligo, the only approved JAK inhibitor is ruxolitinib, 1.5%, in a cream formulation. In June, ritlecitinib (Litfulo) was approved by the Food and Drug Administration (FDA) for alopecia areata. Phototherapy, which has been used for decades in the treatment of vitiligo, has an established efficacy and safety profile as a stand-alone vitiligo treatment. Upadacitinib has numerous indications for inflammatory diseases, such as rheumatoid arthritis, and was granted FDA approval for atopic dermatitis in 2022.
 

NB-UVB Arm Added in Ritlecitinib Extension

The ritlecitinib study population was drawn from patients with non-segmental vitiligo who initially participated in a 24-week dose-ranging period of a phase 2b trial published last year. In that study, 364 patients were randomized to doses of once-daily ritlecitinib ranging from 10 to 50 mg with or without a 4-week loading regimen. Higher doses were generally associated with greater efficacy on the primary endpoint of facial vitiligo area scoring index (F-VASI) but not with a greater risk for adverse events.

In the 24-week extension study, 187 patients received a 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib for the remaining 20 weeks. Another 43 patients were randomized to one of two arms: The same 4-week loading regimen of 200-mg ritlecitinib daily followed by 50 mg of daily ritlecitinib or to 50-mg daily ritlecitinib without a loading dose but combined with NB-UVB delivered twice per week.

Important to interpretation of results, there was an additional twist. Patients in the randomized arm who had < 10% improvement in the total vitiligo area severity index (T-VASI) at week 12 of the extension were discontinued from the study.

The endpoints considered when comparing ritlecitinib with or without NB-UVB at the end of the extension study were F-VASI, T-VASI, patient global impression of change, and adverse events. Responses were assessed on the basis of both observed and last observation carried forward (LOCF).

Of the 43 people, who were randomized in the extension study, nine (21%) had < 10% improvement in T-VASI and were therefore discontinued from the study.

At the end of 24 weeks, both groups had a substantial response to their assigned therapy, but the addition of NB-UVB increased rates of response, although not always at a level of statistical significance, according to Dr. Guttman-Yassky.

For the percent improvement in F-VASI, specifically, the increase did not reach significance on the basis of LOCF (57.9% vs 51.5%; P = .158) but was highly significant on the basis of observed responses (69.6% vs 55.1%; P = .009). For T-VASI, differences for adjunctive NB-UVB over monotherapy did not reach significance for either observed or LOCF responses, but it was significant for observed responses in a patient global impression of change.
 

Small Numbers Limit Strength of Ritlecitinib, NB-UVB Evidence

However, Dr. Guttman-Yassky said it is important “to pay attention to the sample sizes” when noting the lack of significance.

The combination appeared safe, and there were no side effects associated with the addition of twice-weekly NB-UVB to ritlecitinib.

She acknowledged that the design of this analysis was “complicated” and that the number of randomized patients was small. She suggested the findings support the potential for benefit from the combination of a JAK inhibitor and NB-UVB, both of which have shown efficacy as monotherapy in previous studies. She indicated that a trial of this combination is reasonable while awaiting a more definitive study.

One of the questions that might be posed in a larger study is the timing of NB-UVB, such as whether it is best reserved for those with inadequate early response to a JAK inhibitor or if optimal results are achieved when a JAK inhibitor and NB-UVB are initiated simultaneously.

Upadacitinib Monotherapy Results

One rationale for initiating therapy with the combination of a JAK inhibitor and NB-UVB is the potential for a more rapid response, but extended results from a second phase 2b study with a different oral JAK inhibitor, upadacitinib, suggested responses on JAK inhibitor monotherapy improve steadily over time.

“The overall efficacy continued to improve without reaching a plateau at 1 year,” reported Thierry Passeron, MD, PhD, professor and chair, Department of Dermatology, Université Côte d’Azur, Nice, France. He spoke at the same AAD late-breaking session as Dr. Guttman-Yassky.

The 24-week dose-ranging data from the upadacitinib trial were previously reported at the 2023 annual meeting of the European Association of Dermatology and Venereology. In the placebo-controlled portion, which randomized 185 patients with extensive non-segmental vitiligo to 6 mg, 11 mg, or 22 mg, the two higher doses were significantly more effective than placebo.

In the extension, patients in the placebo group were randomized to 11 mg or 22 mg, while those in the higher dose groups remained on their assigned therapies.
 

F-VASI Almost Doubled in Extension Trial

From week 24 to week 52, there was nearly a doubling of the percent F-VASI reduction, climbing from 32% to 60.8% in the 11-mg group and from 38.7% to 64.9% in the 22-mg group, Dr. Passeron said. Placebo groups who were switched to active therapy at 24 weeks rapidly approached the rates of F-VASI response of those initiated on upadacitinib.

The percent reductions in T-VASI, although lower, followed the same pattern. For the 11-mg group, the reduction climbed from 16% at 24 weeks to 44.7% at 52 weeks. For the 22-mg group, the reduction climbed from 22.9% to 44.4%. Patients who were switched from placebo to 11 mg or to 22 mg also experienced improvements in T-VASI up to 52 weeks, although the level of improvement was lower than that in patients initially randomized to the higher doses of upadacitinib.

There were “no new safety signals” for upadacitinib, which is FDA-approved for multiple indications, according to Dr. Passeron. He said acne-like lesions were the most bothersome adverse event, and cases of herpes zoster were “rare.”

A version of these data was published in a British Journal of Dermatology supplement just prior to the AAD meeting.

Phase 3 vitiligo trials are planned for both ritlecitinib and upadacitinib.

Dr. Guttman-Yassky reported financial relationships with approximately 45 pharmaceutical companies, including Pfizer, which makes ritlecitinib and provided funding for the study she discussed. Dr. Passeron reported financial relationships with approximately 40 pharmaceutical companies, including AbbVie, which makes upadacitinib and provided funding for the study he discussed.

A version of this article appeared on Medscape.com.

An “inevitable” global surge in prostate cancer is coming, with a worldwide doubling of cases to 2.9 million and an 85% increase in deaths to nearly 700,000 by the year 2040, the Lancet Commission on Prostate Cancer warned this week.

At a meeting of urologists in Paris, the commission said that the acceleration is already underway in high-income countries such as the United States and the United Kingdom but will gain momentum in low- and medium-income countries.

Nick James, MD, lead author of The Lancet report and professor of prostate and bladder cancer research at The Institute of Cancer Research in London, said that the surge, in part, is a medical success story.

“Prostate cancer paradoxically is a problem baked into the biology. Men get prostate cancer as they age,” Dr. James told this news organization. 

“There is a big rise in the high-income countries. But we’re going to see a big rise in the number of 50-, 60-, 70-year-olds in the coming decades in the poorer countries, and with that comes more prostate cancer. High-income countries such as the UK and USA will also see smaller increases for the same reason.”

According to the report, to be presented April 6 at the 2024 European Association of Urology Congress in Paris, “The case for prostate cancer screening for all men aged 50-70 years (and all men of African origin aged 45–70 years) in high-income countries is strengthening with improved use of technologies such as MRI and growing evidence for the safety of active surveillance.”

Andrew Vickers, PhD, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City, said that the Lancet Commission came to similar conclusions as he and an international group of researchers did in a 2023 policy paper in The BMJ. A major gap, Dr. Vickers said, is misuse of prostate-specific antigen (PSA) screening. 

“We found that the ubiquitous policy compromise of letting patients decide for themselves about PSA has led to the worst possible outcomes of overuse in men unlikely to benefit, high rates of overdiagnosis and overtreatment, and economic and racial inequity,” Dr. Vickers said. “Our view is that PSA screening should be done well — by implementing straightforward harm-reduction strategies like restricting screening in older men and use of secondary tests before biopsy — or not at all.”

Dr. James said that undertreatment of advanced disease is widespread; only about 30%-40% of men in the United States receive combination hormone therapy for metastatic disease, for example. “Simply doing what we know works would improve outcomes,” he said.

Dr. James said that men of African ancestry are twice as likely to develop prostate cancer, but whether treatment should follow a different approach in these men is unclear. The new report stressed the need to include more men of African ancestry in research.

Brandon Mahal, MD, vice chair of research in radiation oncology the University of Miami Sylvester Comprehensive Cancer Center and a coauthor of the report, said that new approaches are needed to enable earlier diagnosis of prostate cancer in men in low- to middle-income countries, where most patients present with metastatic disease and are less likely to survive for long periods.

Dr. James recommended pop-up clinics and mobile testing to encourage men who are at high risk for prostate cancer but feel well to detect lethal cancers early.

In England, for example, Dr. James helped introduce an outreach program called The Man Van which provided free health checks, including PSA tests, to high-risk men in London. 

“By bringing a van with quick and easy testing straight to men at work and in the community, and targeting those who have a higher risk of prostate cancer, we provided thousands of health checks which resulted in almost 100 cancer diagnoses in men who might otherwise have only seen a doctor once their cancer has progressed to a more advanced stage,” he said.

He noted that the medical community worldwide is ill-prepared for the onslaught of prostate cancer cases.

“The solution cannot be training more urologists, radiation oncologists, pathologists, and radiologists because it simply takes too long,” Dr. James said. However, increased use of nurses and artificial intelligence may help. “In my own hospital, biopsies are a nurse-led and -delivered service. AI is extraordinarily good at diagnosis already and will only get better,” he said.

In poorer countries, smartphones could fill gaps too. “The same technology that does face recognition already can say that’s a Gleason 7 prostate cancer,” Dr. James said. “It’s not being rolled out in countries like America of course because pathologists’ income is at risk.”

Dr. James, Dr. Vickers, and Dr. Mahal reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

An “inevitable” global surge in prostate cancer is coming, with a worldwide doubling of cases to 2.9 million and an 85% increase in deaths to nearly 700,000 by the year 2040, the Lancet Commission on Prostate Cancer warned this week.

At a meeting of urologists in Paris, the commission said that the acceleration is already underway in high-income countries such as the United States and the United Kingdom but will gain momentum in low- and medium-income countries.

Nick James, MD, lead author of The Lancet report and professor of prostate and bladder cancer research at The Institute of Cancer Research in London, said that the surge, in part, is a medical success story.

“Prostate cancer paradoxically is a problem baked into the biology. Men get prostate cancer as they age,” Dr. James told this news organization. 

“There is a big rise in the high-income countries. But we’re going to see a big rise in the number of 50-, 60-, 70-year-olds in the coming decades in the poorer countries, and with that comes more prostate cancer. High-income countries such as the UK and USA will also see smaller increases for the same reason.”

According to the report, to be presented April 6 at the 2024 European Association of Urology Congress in Paris, “The case for prostate cancer screening for all men aged 50-70 years (and all men of African origin aged 45–70 years) in high-income countries is strengthening with improved use of technologies such as MRI and growing evidence for the safety of active surveillance.”

Andrew Vickers, PhD, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City, said that the Lancet Commission came to similar conclusions as he and an international group of researchers did in a 2023 policy paper in The BMJ. A major gap, Dr. Vickers said, is misuse of prostate-specific antigen (PSA) screening. 

“We found that the ubiquitous policy compromise of letting patients decide for themselves about PSA has led to the worst possible outcomes of overuse in men unlikely to benefit, high rates of overdiagnosis and overtreatment, and economic and racial inequity,” Dr. Vickers said. “Our view is that PSA screening should be done well — by implementing straightforward harm-reduction strategies like restricting screening in older men and use of secondary tests before biopsy — or not at all.”

Dr. James said that undertreatment of advanced disease is widespread; only about 30%-40% of men in the United States receive combination hormone therapy for metastatic disease, for example. “Simply doing what we know works would improve outcomes,” he said.

Dr. James said that men of African ancestry are twice as likely to develop prostate cancer, but whether treatment should follow a different approach in these men is unclear. The new report stressed the need to include more men of African ancestry in research.

Brandon Mahal, MD, vice chair of research in radiation oncology the University of Miami Sylvester Comprehensive Cancer Center and a coauthor of the report, said that new approaches are needed to enable earlier diagnosis of prostate cancer in men in low- to middle-income countries, where most patients present with metastatic disease and are less likely to survive for long periods.

Dr. James recommended pop-up clinics and mobile testing to encourage men who are at high risk for prostate cancer but feel well to detect lethal cancers early.

In England, for example, Dr. James helped introduce an outreach program called The Man Van which provided free health checks, including PSA tests, to high-risk men in London. 

“By bringing a van with quick and easy testing straight to men at work and in the community, and targeting those who have a higher risk of prostate cancer, we provided thousands of health checks which resulted in almost 100 cancer diagnoses in men who might otherwise have only seen a doctor once their cancer has progressed to a more advanced stage,” he said.

He noted that the medical community worldwide is ill-prepared for the onslaught of prostate cancer cases.

“The solution cannot be training more urologists, radiation oncologists, pathologists, and radiologists because it simply takes too long,” Dr. James said. However, increased use of nurses and artificial intelligence may help. “In my own hospital, biopsies are a nurse-led and -delivered service. AI is extraordinarily good at diagnosis already and will only get better,” he said.

In poorer countries, smartphones could fill gaps too. “The same technology that does face recognition already can say that’s a Gleason 7 prostate cancer,” Dr. James said. “It’s not being rolled out in countries like America of course because pathologists’ income is at risk.”

Dr. James, Dr. Vickers, and Dr. Mahal reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

An “inevitable” global surge in prostate cancer is coming, with a worldwide doubling of cases to 2.9 million and an 85% increase in deaths to nearly 700,000 by the year 2040, the Lancet Commission on Prostate Cancer warned this week.

At a meeting of urologists in Paris, the commission said that the acceleration is already underway in high-income countries such as the United States and the United Kingdom but will gain momentum in low- and medium-income countries.

Nick James, MD, lead author of The Lancet report and professor of prostate and bladder cancer research at The Institute of Cancer Research in London, said that the surge, in part, is a medical success story.

“Prostate cancer paradoxically is a problem baked into the biology. Men get prostate cancer as they age,” Dr. James told this news organization. 

“There is a big rise in the high-income countries. But we’re going to see a big rise in the number of 50-, 60-, 70-year-olds in the coming decades in the poorer countries, and with that comes more prostate cancer. High-income countries such as the UK and USA will also see smaller increases for the same reason.”

According to the report, to be presented April 6 at the 2024 European Association of Urology Congress in Paris, “The case for prostate cancer screening for all men aged 50-70 years (and all men of African origin aged 45–70 years) in high-income countries is strengthening with improved use of technologies such as MRI and growing evidence for the safety of active surveillance.”

Andrew Vickers, PhD, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City, said that the Lancet Commission came to similar conclusions as he and an international group of researchers did in a 2023 policy paper in The BMJ. A major gap, Dr. Vickers said, is misuse of prostate-specific antigen (PSA) screening. 

“We found that the ubiquitous policy compromise of letting patients decide for themselves about PSA has led to the worst possible outcomes of overuse in men unlikely to benefit, high rates of overdiagnosis and overtreatment, and economic and racial inequity,” Dr. Vickers said. “Our view is that PSA screening should be done well — by implementing straightforward harm-reduction strategies like restricting screening in older men and use of secondary tests before biopsy — or not at all.”

Dr. James said that undertreatment of advanced disease is widespread; only about 30%-40% of men in the United States receive combination hormone therapy for metastatic disease, for example. “Simply doing what we know works would improve outcomes,” he said.

Dr. James said that men of African ancestry are twice as likely to develop prostate cancer, but whether treatment should follow a different approach in these men is unclear. The new report stressed the need to include more men of African ancestry in research.

Brandon Mahal, MD, vice chair of research in radiation oncology the University of Miami Sylvester Comprehensive Cancer Center and a coauthor of the report, said that new approaches are needed to enable earlier diagnosis of prostate cancer in men in low- to middle-income countries, where most patients present with metastatic disease and are less likely to survive for long periods.

Dr. James recommended pop-up clinics and mobile testing to encourage men who are at high risk for prostate cancer but feel well to detect lethal cancers early.

In England, for example, Dr. James helped introduce an outreach program called The Man Van which provided free health checks, including PSA tests, to high-risk men in London. 

“By bringing a van with quick and easy testing straight to men at work and in the community, and targeting those who have a higher risk of prostate cancer, we provided thousands of health checks which resulted in almost 100 cancer diagnoses in men who might otherwise have only seen a doctor once their cancer has progressed to a more advanced stage,” he said.

He noted that the medical community worldwide is ill-prepared for the onslaught of prostate cancer cases.

“The solution cannot be training more urologists, radiation oncologists, pathologists, and radiologists because it simply takes too long,” Dr. James said. However, increased use of nurses and artificial intelligence may help. “In my own hospital, biopsies are a nurse-led and -delivered service. AI is extraordinarily good at diagnosis already and will only get better,” he said.

In poorer countries, smartphones could fill gaps too. “The same technology that does face recognition already can say that’s a Gleason 7 prostate cancer,” Dr. James said. “It’s not being rolled out in countries like America of course because pathologists’ income is at risk.”

Dr. James, Dr. Vickers, and Dr. Mahal reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — In the clinical opinion of Jenny E. Murase, MD, caring for patients with delusional infestation — the conviction that one is infested by animate or inanimate pathogens without medical or microbiological evidence of a true infestation — puts a dermatologist’s communication skills to the ultimate test.

“The fact that delusional infestation is a fixed, false belief [means] we will never agree with patients on the etiology by definition,” Dr. Murase, a dermatologist with the Palo Alto Foundation Medical Group, Mountain View, California, said at the annual meeting of the American Academy of Dermatology. “But somehow, we must come to some kind of an agreement on how to approach this therapeutically.”

Patients with delusional infestation (DI) often describe a cutaneous sensation of itching or crawling, biting, stinging — a pins and needles sensation. “Formication is when there’s a crawling sensation on the surface of the skin,” she said. “That’s something we can agree on — the fact that there is a shared understanding that they’re experiencing some kind of sensation in their skin.”

First described in 1894, several different terms have been used to describe DI in the past, including acarophobia, delusions of parasitosis, Ekbom syndrome, and Morgellons disease. The current term used for DI includes other animate or inanimate pathogens besides parasites.

The average dermatologist manages two to three patients with DI every 5 years, “so it’s not uncommon,” said Dr. Murase, who also holds a faculty position in the department of dermatology at the University of California, San Francisco. Females are about 2.5 times more likely to be affected compared with males, she said, and 8%-12% of patients with DI have a friend or relative who shares the symptom, and they often accompany them to the office visit. “Initially, you’re trying to determine if this a primary condition where it’s only the cutaneous condition the patient is experiencing, or if there is a secondary condition like an underlying psychiatric disorder or medical condition or drug use that contributes to the sensation,” she said.

According to a descriptive study of 115 patients with DI, 50% had at least one drug detected in hair samples, and nearly 60% had evidence of some cognitive impairment that could not be explained by deficits in IQ. Another study of 147 patients with DI seen at the Mayo Clinic between 2001 and 2007 found that 81% had a prior psychiatric condition and 26% had a shared psychotic disorder.
 

Phased Approach to Treatment

Dr. Murase discussed her phased approach to caring for patients with DI, based on a review article that she and colleagues published in the International Journal of Dermatology. Phase 1 involves preparing for the visit by asking staff to refer to patients with DI as VIPs and allowing them to talk freely about the sensation they’re experiencing. “The goal is to improve the patient’s condition, not to convince the patient that he or she is delusional,” Dr. Murase explained. “Many patients can’t distinguish between when they’re talking to the doctor and when they’re talking to a nurse or a nurse practitioner; they like to feel that they’re being heard and listened to.”

She also recommends scheduling patients with DI for the end of the day and arranging frequent follow-up visits. “Making them feel valued is the bottom line,” she emphasized. “Remember: They’re less likely to respect socially defined boundaries like time constraints, so you do have to set boundaries, and don’t take what they may say to you personally. You’re not going to be able to care for that individual unless you do that. They may appear defiant, frustrated, and angry, but the fact that they showed up in your office means that you can help that person.”

Phase 2 of care for these patients consists of building a therapeutic rapport by greeting them with a smile and positive attitude and using welcoming body language such as sitting side-by-side during the office visit as opposed to face-to-face, “so it’s a less aggressive approach,” she said. Next, ask about their goal with a question such as, “Is it more important for you to find the bug/virus or to improve your condition?”

During the visit, “you’re continually shifting from etiology — which they are desperate to understand — to a shared desire for treatment,” Dr. Murase said. “No one knows what causes DI and remember, in medicine we treat patients when the exact etiology is unknown. So, we’re not doing anything that differently. Focus on the effect that the symptoms are having on their life. Say something like, ‘it must be so miserable to be living this way. I really want to help you.’ ”

Phase 3 of care for patients with DI involves performing a thorough history and physical exam. The initial office visit should include a full body exam to rule out any underlying dermatologic condition that may be causing the sensation they’re complaining about. She cited a retrospective study of 108 patients who presented to the Mayo Clinic with DI as the main reason for their office visit. Of the 80 patients who had a biopsy, 61% had chronic dermatitis; 48% had excoriation, ulceration, or erosion; and 31% had nonspecific dermal inflammation.

Whether to perform a biopsy or not is controversial, Dr. Murase added, because it’s probably not going to change the clinical impression or diagnosis. “If you agree to do the biopsy, get a verbal contract with the patient,” she advised. “You might say, ‘We’re going to do this. You’re going to choose the site, we’re going to do a biopsy, but we are going to be in agreement here that, if we can’t find the etiology, that you will still be open to going on therapy.’ This is important because it establishes a therapeutic alliance.”

Since patients with DI often bring in their own specimens, she also recommends providing them with microscope glass slides without cover slips and asking them to use clear tape, not tape that is opaque or matted, to cover the specimen.

To rule out other illnesses and conditions that could be triggering the perceived DI, she said lab tests to consider include a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, calcium, hemoglobin A1c, vitamin B12, urinalysis, toxicology screen, HIV/hepatitis C, and rapid plasma reagin.
 

Starting Treatment

Phase 4 of care for patients with DI involves initiating therapy, which includes demonstrating empathy by reflecting on the detrimental effects of the patient’s reported sensations on their quality of life. “Emphasize that you are not questioning their experience, and that you don’t doubt that they feel things on their skin,” Dr. Murase said. “Recommend medications on an empirical or ‘trial and error’ pragmatic basis. I often tell patients, ‘I will never give up on you if you will never give up on me.’”

For treating patients with DI, her first-generation antipsychotic of choice is pimozide. She starts at a dose of 0.5 mg, building up to 2-3 mg once a day. Haloperidol is another option: 0.5 mg to start, building up to 1-5 mg every night at bedtime. “This requires monitoring for bone suppression via CBC and hypermetabolic complications via fasting lipids and HbA1c,” she said. “There is also an increased risk of prolonged QT with pimozide and risk of extrapyramidal symptoms and tardive dyskinesia.”

Second-generation antipsychotics to consider include risperidone (0.5 mg to start, building up to 102 mg at bedtime); olanzapine (2.5 mg to start, building up to 5-10 mg at bedtime); aripiprazole (2-5 mg to start, building up to 10-15 mg a day), and quetiapine (12.5 mg to start, building up to 200 mg at bedtime).

For all medical therapy she recommends starting patients with a low dose, increasing by 0.5 mg every 2-3 weeks, and let them be “stable and comfortable” for 3-4 months, and then taper down the dose by 0.5 mg every 2-4 weeks or more slowly. In the medical chart, Dr. Murase recommends avoiding use of the terms “psychosis” and “delusions.” Instead, “formication” (tactile hallucination of insects crawling on or within the skin) or “cutaneous dysesthesia” are better terms if patients access their records, she said.

Dr. Murase reported having no relevant disclosures.

SAN DIEGO — In the clinical opinion of Jenny E. Murase, MD, caring for patients with delusional infestation — the conviction that one is infested by animate or inanimate pathogens without medical or microbiological evidence of a true infestation — puts a dermatologist’s communication skills to the ultimate test.

“The fact that delusional infestation is a fixed, false belief [means] we will never agree with patients on the etiology by definition,” Dr. Murase, a dermatologist with the Palo Alto Foundation Medical Group, Mountain View, California, said at the annual meeting of the American Academy of Dermatology. “But somehow, we must come to some kind of an agreement on how to approach this therapeutically.”

Patients with delusional infestation (DI) often describe a cutaneous sensation of itching or crawling, biting, stinging — a pins and needles sensation. “Formication is when there’s a crawling sensation on the surface of the skin,” she said. “That’s something we can agree on — the fact that there is a shared understanding that they’re experiencing some kind of sensation in their skin.”

First described in 1894, several different terms have been used to describe DI in the past, including acarophobia, delusions of parasitosis, Ekbom syndrome, and Morgellons disease. The current term used for DI includes other animate or inanimate pathogens besides parasites.

The average dermatologist manages two to three patients with DI every 5 years, “so it’s not uncommon,” said Dr. Murase, who also holds a faculty position in the department of dermatology at the University of California, San Francisco. Females are about 2.5 times more likely to be affected compared with males, she said, and 8%-12% of patients with DI have a friend or relative who shares the symptom, and they often accompany them to the office visit. “Initially, you’re trying to determine if this a primary condition where it’s only the cutaneous condition the patient is experiencing, or if there is a secondary condition like an underlying psychiatric disorder or medical condition or drug use that contributes to the sensation,” she said.

According to a descriptive study of 115 patients with DI, 50% had at least one drug detected in hair samples, and nearly 60% had evidence of some cognitive impairment that could not be explained by deficits in IQ. Another study of 147 patients with DI seen at the Mayo Clinic between 2001 and 2007 found that 81% had a prior psychiatric condition and 26% had a shared psychotic disorder.
 

Phased Approach to Treatment

Dr. Murase discussed her phased approach to caring for patients with DI, based on a review article that she and colleagues published in the International Journal of Dermatology. Phase 1 involves preparing for the visit by asking staff to refer to patients with DI as VIPs and allowing them to talk freely about the sensation they’re experiencing. “The goal is to improve the patient’s condition, not to convince the patient that he or she is delusional,” Dr. Murase explained. “Many patients can’t distinguish between when they’re talking to the doctor and when they’re talking to a nurse or a nurse practitioner; they like to feel that they’re being heard and listened to.”

She also recommends scheduling patients with DI for the end of the day and arranging frequent follow-up visits. “Making them feel valued is the bottom line,” she emphasized. “Remember: They’re less likely to respect socially defined boundaries like time constraints, so you do have to set boundaries, and don’t take what they may say to you personally. You’re not going to be able to care for that individual unless you do that. They may appear defiant, frustrated, and angry, but the fact that they showed up in your office means that you can help that person.”

Phase 2 of care for these patients consists of building a therapeutic rapport by greeting them with a smile and positive attitude and using welcoming body language such as sitting side-by-side during the office visit as opposed to face-to-face, “so it’s a less aggressive approach,” she said. Next, ask about their goal with a question such as, “Is it more important for you to find the bug/virus or to improve your condition?”

During the visit, “you’re continually shifting from etiology — which they are desperate to understand — to a shared desire for treatment,” Dr. Murase said. “No one knows what causes DI and remember, in medicine we treat patients when the exact etiology is unknown. So, we’re not doing anything that differently. Focus on the effect that the symptoms are having on their life. Say something like, ‘it must be so miserable to be living this way. I really want to help you.’ ”

Phase 3 of care for patients with DI involves performing a thorough history and physical exam. The initial office visit should include a full body exam to rule out any underlying dermatologic condition that may be causing the sensation they’re complaining about. She cited a retrospective study of 108 patients who presented to the Mayo Clinic with DI as the main reason for their office visit. Of the 80 patients who had a biopsy, 61% had chronic dermatitis; 48% had excoriation, ulceration, or erosion; and 31% had nonspecific dermal inflammation.

Whether to perform a biopsy or not is controversial, Dr. Murase added, because it’s probably not going to change the clinical impression or diagnosis. “If you agree to do the biopsy, get a verbal contract with the patient,” she advised. “You might say, ‘We’re going to do this. You’re going to choose the site, we’re going to do a biopsy, but we are going to be in agreement here that, if we can’t find the etiology, that you will still be open to going on therapy.’ This is important because it establishes a therapeutic alliance.”

Since patients with DI often bring in their own specimens, she also recommends providing them with microscope glass slides without cover slips and asking them to use clear tape, not tape that is opaque or matted, to cover the specimen.

To rule out other illnesses and conditions that could be triggering the perceived DI, she said lab tests to consider include a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, calcium, hemoglobin A1c, vitamin B12, urinalysis, toxicology screen, HIV/hepatitis C, and rapid plasma reagin.
 

Starting Treatment

Phase 4 of care for patients with DI involves initiating therapy, which includes demonstrating empathy by reflecting on the detrimental effects of the patient’s reported sensations on their quality of life. “Emphasize that you are not questioning their experience, and that you don’t doubt that they feel things on their skin,” Dr. Murase said. “Recommend medications on an empirical or ‘trial and error’ pragmatic basis. I often tell patients, ‘I will never give up on you if you will never give up on me.’”

For treating patients with DI, her first-generation antipsychotic of choice is pimozide. She starts at a dose of 0.5 mg, building up to 2-3 mg once a day. Haloperidol is another option: 0.5 mg to start, building up to 1-5 mg every night at bedtime. “This requires monitoring for bone suppression via CBC and hypermetabolic complications via fasting lipids and HbA1c,” she said. “There is also an increased risk of prolonged QT with pimozide and risk of extrapyramidal symptoms and tardive dyskinesia.”

Second-generation antipsychotics to consider include risperidone (0.5 mg to start, building up to 102 mg at bedtime); olanzapine (2.5 mg to start, building up to 5-10 mg at bedtime); aripiprazole (2-5 mg to start, building up to 10-15 mg a day), and quetiapine (12.5 mg to start, building up to 200 mg at bedtime).

For all medical therapy she recommends starting patients with a low dose, increasing by 0.5 mg every 2-3 weeks, and let them be “stable and comfortable” for 3-4 months, and then taper down the dose by 0.5 mg every 2-4 weeks or more slowly. In the medical chart, Dr. Murase recommends avoiding use of the terms “psychosis” and “delusions.” Instead, “formication” (tactile hallucination of insects crawling on or within the skin) or “cutaneous dysesthesia” are better terms if patients access their records, she said.

Dr. Murase reported having no relevant disclosures.

SAN DIEGO — In the clinical opinion of Jenny E. Murase, MD, caring for patients with delusional infestation — the conviction that one is infested by animate or inanimate pathogens without medical or microbiological evidence of a true infestation — puts a dermatologist’s communication skills to the ultimate test.

“The fact that delusional infestation is a fixed, false belief [means] we will never agree with patients on the etiology by definition,” Dr. Murase, a dermatologist with the Palo Alto Foundation Medical Group, Mountain View, California, said at the annual meeting of the American Academy of Dermatology. “But somehow, we must come to some kind of an agreement on how to approach this therapeutically.”

Patients with delusional infestation (DI) often describe a cutaneous sensation of itching or crawling, biting, stinging — a pins and needles sensation. “Formication is when there’s a crawling sensation on the surface of the skin,” she said. “That’s something we can agree on — the fact that there is a shared understanding that they’re experiencing some kind of sensation in their skin.”

First described in 1894, several different terms have been used to describe DI in the past, including acarophobia, delusions of parasitosis, Ekbom syndrome, and Morgellons disease. The current term used for DI includes other animate or inanimate pathogens besides parasites.

The average dermatologist manages two to three patients with DI every 5 years, “so it’s not uncommon,” said Dr. Murase, who also holds a faculty position in the department of dermatology at the University of California, San Francisco. Females are about 2.5 times more likely to be affected compared with males, she said, and 8%-12% of patients with DI have a friend or relative who shares the symptom, and they often accompany them to the office visit. “Initially, you’re trying to determine if this a primary condition where it’s only the cutaneous condition the patient is experiencing, or if there is a secondary condition like an underlying psychiatric disorder or medical condition or drug use that contributes to the sensation,” she said.

According to a descriptive study of 115 patients with DI, 50% had at least one drug detected in hair samples, and nearly 60% had evidence of some cognitive impairment that could not be explained by deficits in IQ. Another study of 147 patients with DI seen at the Mayo Clinic between 2001 and 2007 found that 81% had a prior psychiatric condition and 26% had a shared psychotic disorder.
 

Phased Approach to Treatment

Dr. Murase discussed her phased approach to caring for patients with DI, based on a review article that she and colleagues published in the International Journal of Dermatology. Phase 1 involves preparing for the visit by asking staff to refer to patients with DI as VIPs and allowing them to talk freely about the sensation they’re experiencing. “The goal is to improve the patient’s condition, not to convince the patient that he or she is delusional,” Dr. Murase explained. “Many patients can’t distinguish between when they’re talking to the doctor and when they’re talking to a nurse or a nurse practitioner; they like to feel that they’re being heard and listened to.”

She also recommends scheduling patients with DI for the end of the day and arranging frequent follow-up visits. “Making them feel valued is the bottom line,” she emphasized. “Remember: They’re less likely to respect socially defined boundaries like time constraints, so you do have to set boundaries, and don’t take what they may say to you personally. You’re not going to be able to care for that individual unless you do that. They may appear defiant, frustrated, and angry, but the fact that they showed up in your office means that you can help that person.”

Phase 2 of care for these patients consists of building a therapeutic rapport by greeting them with a smile and positive attitude and using welcoming body language such as sitting side-by-side during the office visit as opposed to face-to-face, “so it’s a less aggressive approach,” she said. Next, ask about their goal with a question such as, “Is it more important for you to find the bug/virus or to improve your condition?”

During the visit, “you’re continually shifting from etiology — which they are desperate to understand — to a shared desire for treatment,” Dr. Murase said. “No one knows what causes DI and remember, in medicine we treat patients when the exact etiology is unknown. So, we’re not doing anything that differently. Focus on the effect that the symptoms are having on their life. Say something like, ‘it must be so miserable to be living this way. I really want to help you.’ ”

Phase 3 of care for patients with DI involves performing a thorough history and physical exam. The initial office visit should include a full body exam to rule out any underlying dermatologic condition that may be causing the sensation they’re complaining about. She cited a retrospective study of 108 patients who presented to the Mayo Clinic with DI as the main reason for their office visit. Of the 80 patients who had a biopsy, 61% had chronic dermatitis; 48% had excoriation, ulceration, or erosion; and 31% had nonspecific dermal inflammation.

Whether to perform a biopsy or not is controversial, Dr. Murase added, because it’s probably not going to change the clinical impression or diagnosis. “If you agree to do the biopsy, get a verbal contract with the patient,” she advised. “You might say, ‘We’re going to do this. You’re going to choose the site, we’re going to do a biopsy, but we are going to be in agreement here that, if we can’t find the etiology, that you will still be open to going on therapy.’ This is important because it establishes a therapeutic alliance.”

Since patients with DI often bring in their own specimens, she also recommends providing them with microscope glass slides without cover slips and asking them to use clear tape, not tape that is opaque or matted, to cover the specimen.

To rule out other illnesses and conditions that could be triggering the perceived DI, she said lab tests to consider include a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, calcium, hemoglobin A1c, vitamin B12, urinalysis, toxicology screen, HIV/hepatitis C, and rapid plasma reagin.
 

Starting Treatment

Phase 4 of care for patients with DI involves initiating therapy, which includes demonstrating empathy by reflecting on the detrimental effects of the patient’s reported sensations on their quality of life. “Emphasize that you are not questioning their experience, and that you don’t doubt that they feel things on their skin,” Dr. Murase said. “Recommend medications on an empirical or ‘trial and error’ pragmatic basis. I often tell patients, ‘I will never give up on you if you will never give up on me.’”

For treating patients with DI, her first-generation antipsychotic of choice is pimozide. She starts at a dose of 0.5 mg, building up to 2-3 mg once a day. Haloperidol is another option: 0.5 mg to start, building up to 1-5 mg every night at bedtime. “This requires monitoring for bone suppression via CBC and hypermetabolic complications via fasting lipids and HbA1c,” she said. “There is also an increased risk of prolonged QT with pimozide and risk of extrapyramidal symptoms and tardive dyskinesia.”

Second-generation antipsychotics to consider include risperidone (0.5 mg to start, building up to 102 mg at bedtime); olanzapine (2.5 mg to start, building up to 5-10 mg at bedtime); aripiprazole (2-5 mg to start, building up to 10-15 mg a day), and quetiapine (12.5 mg to start, building up to 200 mg at bedtime).

For all medical therapy she recommends starting patients with a low dose, increasing by 0.5 mg every 2-3 weeks, and let them be “stable and comfortable” for 3-4 months, and then taper down the dose by 0.5 mg every 2-4 weeks or more slowly. In the medical chart, Dr. Murase recommends avoiding use of the terms “psychosis” and “delusions.” Instead, “formication” (tactile hallucination of insects crawling on or within the skin) or “cutaneous dysesthesia” are better terms if patients access their records, she said.

Dr. Murase reported having no relevant disclosures.

SAN DIEGO — In the opinion of Patricia A. Treadwell, MD, providing health equity in dermatology means providing support for everyone, regardless of their financial circumstances or their skin color.

It also means embracing diversity, which she defined as diversity of thinking. “If you look at the literature, diversity in higher education and health profession training settings is associated with better educational outcomes for all students,” Dr. Treadwell, professor emeritus of dermatology and pediatrics at Indiana University School of Medicine, Indianapolis, said in a presentation on health equity during the plenary session at the annual meeting of the American Academy of Dermatology. “Each person brings a variety of experiences and perspectives. This provides a wide range of opinions and different ways to look at things. Racial and ethnic minority providers can help health organization reduce cultural and linguistic barriers and improve cultural competence.”

Dr. Treadwell

Such efforts matter, she continued, because according to the United States Census, Black individuals make up 13.6% of the population, while Latinx individuals represent 19.1% of the population. “So, melanin matters,” she said. “If you look at a dermatology textbook, a high percentage [of cases] are identified as Caucasian individuals, which results in an overrepresentation of Caucasians in photographs. That can result in delayed or missed diagnoses [in different skin types]. If you are contributing to cases in textbooks, make sure you have a variety of different skin types so that individuals who are referring to the textbooks will be more equipped.”

Practicing dermatologists can support diversity by offering opportunities to underrepresented in medicine (URM) students, “African-American students, Hispanic students, and Native American students,” said Dr. Treadwell, who was chief of pediatric dermatology at Riley Hospital for Children in Indianapolis from 1987 to 2004. “You also want to be encouraging,” she said.

Dermatologists can also support diversity by providing precepting opportunities, “because many [medical] students may not have connections and networks. Providing those opportunities is important,” she said. Another way to help is to be a mentor to young dermatologists. “I certainly have had mentors in my career who have been very helpful,” she said. “They’ve given me advice about things I was not familiar with.”

Dr. Treadwell suggested the Skin of Color Society as an organization that can assist with networking, mentoring, and research efforts. She also cited the Society for Pediatric Dermatology’s Equity, Diversity, and Inclusion Committee, formed in 2020. One of its initiatives was assembling a special issue of Pediatric Dermatology dedicated to DEI issues, which was published in November 2021.

Dr. Treadwell concluded her presentation by encouraging dermatologists to find ways to care for uninsured or underinsured patients, particularly those with skin of color. This might involve work at a county hospital “to provide access, to serve the patients ... and helping to decrease some the issues in terms of health equity,” she said.

Dr. Treadwell reported having no relevant disclosures. At the plenary session, she presented the John Kenney Jr., MD Lifetime Achievement Award and Lectureship.

SAN DIEGO — In the opinion of Patricia A. Treadwell, MD, providing health equity in dermatology means providing support for everyone, regardless of their financial circumstances or their skin color.

It also means embracing diversity, which she defined as diversity of thinking. “If you look at the literature, diversity in higher education and health profession training settings is associated with better educational outcomes for all students,” Dr. Treadwell, professor emeritus of dermatology and pediatrics at Indiana University School of Medicine, Indianapolis, said in a presentation on health equity during the plenary session at the annual meeting of the American Academy of Dermatology. “Each person brings a variety of experiences and perspectives. This provides a wide range of opinions and different ways to look at things. Racial and ethnic minority providers can help health organization reduce cultural and linguistic barriers and improve cultural competence.”

Dr. Treadwell

Such efforts matter, she continued, because according to the United States Census, Black individuals make up 13.6% of the population, while Latinx individuals represent 19.1% of the population. “So, melanin matters,” she said. “If you look at a dermatology textbook, a high percentage [of cases] are identified as Caucasian individuals, which results in an overrepresentation of Caucasians in photographs. That can result in delayed or missed diagnoses [in different skin types]. If you are contributing to cases in textbooks, make sure you have a variety of different skin types so that individuals who are referring to the textbooks will be more equipped.”

Practicing dermatologists can support diversity by offering opportunities to underrepresented in medicine (URM) students, “African-American students, Hispanic students, and Native American students,” said Dr. Treadwell, who was chief of pediatric dermatology at Riley Hospital for Children in Indianapolis from 1987 to 2004. “You also want to be encouraging,” she said.

Dermatologists can also support diversity by providing precepting opportunities, “because many [medical] students may not have connections and networks. Providing those opportunities is important,” she said. Another way to help is to be a mentor to young dermatologists. “I certainly have had mentors in my career who have been very helpful,” she said. “They’ve given me advice about things I was not familiar with.”

Dr. Treadwell suggested the Skin of Color Society as an organization that can assist with networking, mentoring, and research efforts. She also cited the Society for Pediatric Dermatology’s Equity, Diversity, and Inclusion Committee, formed in 2020. One of its initiatives was assembling a special issue of Pediatric Dermatology dedicated to DEI issues, which was published in November 2021.

Dr. Treadwell concluded her presentation by encouraging dermatologists to find ways to care for uninsured or underinsured patients, particularly those with skin of color. This might involve work at a county hospital “to provide access, to serve the patients ... and helping to decrease some the issues in terms of health equity,” she said.

Dr. Treadwell reported having no relevant disclosures. At the plenary session, she presented the John Kenney Jr., MD Lifetime Achievement Award and Lectureship.

SAN DIEGO — In the opinion of Patricia A. Treadwell, MD, providing health equity in dermatology means providing support for everyone, regardless of their financial circumstances or their skin color.

It also means embracing diversity, which she defined as diversity of thinking. “If you look at the literature, diversity in higher education and health profession training settings is associated with better educational outcomes for all students,” Dr. Treadwell, professor emeritus of dermatology and pediatrics at Indiana University School of Medicine, Indianapolis, said in a presentation on health equity during the plenary session at the annual meeting of the American Academy of Dermatology. “Each person brings a variety of experiences and perspectives. This provides a wide range of opinions and different ways to look at things. Racial and ethnic minority providers can help health organization reduce cultural and linguistic barriers and improve cultural competence.”

Dr. Treadwell

Such efforts matter, she continued, because according to the United States Census, Black individuals make up 13.6% of the population, while Latinx individuals represent 19.1% of the population. “So, melanin matters,” she said. “If you look at a dermatology textbook, a high percentage [of cases] are identified as Caucasian individuals, which results in an overrepresentation of Caucasians in photographs. That can result in delayed or missed diagnoses [in different skin types]. If you are contributing to cases in textbooks, make sure you have a variety of different skin types so that individuals who are referring to the textbooks will be more equipped.”

Practicing dermatologists can support diversity by offering opportunities to underrepresented in medicine (URM) students, “African-American students, Hispanic students, and Native American students,” said Dr. Treadwell, who was chief of pediatric dermatology at Riley Hospital for Children in Indianapolis from 1987 to 2004. “You also want to be encouraging,” she said.

Dermatologists can also support diversity by providing precepting opportunities, “because many [medical] students may not have connections and networks. Providing those opportunities is important,” she said. Another way to help is to be a mentor to young dermatologists. “I certainly have had mentors in my career who have been very helpful,” she said. “They’ve given me advice about things I was not familiar with.”

Dr. Treadwell suggested the Skin of Color Society as an organization that can assist with networking, mentoring, and research efforts. She also cited the Society for Pediatric Dermatology’s Equity, Diversity, and Inclusion Committee, formed in 2020. One of its initiatives was assembling a special issue of Pediatric Dermatology dedicated to DEI issues, which was published in November 2021.

Dr. Treadwell concluded her presentation by encouraging dermatologists to find ways to care for uninsured or underinsured patients, particularly those with skin of color. This might involve work at a county hospital “to provide access, to serve the patients ... and helping to decrease some the issues in terms of health equity,” she said.

Dr. Treadwell reported having no relevant disclosures. At the plenary session, she presented the John Kenney Jr., MD Lifetime Achievement Award and Lectureship.

Exposure to pesticides is associated with an increased risk for pancreatic adenocarcinoma, according to two French studies presented at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology. One of them, a case-control study, showed an elevated risk in individuals whose adipose tissue contained substances that are now banned.

“The association between pesticides and pancreatic cancer exists. It is of low magnitude but robust, concerning cumulative pesticides and three substances: Mancozeb, glyphosate, and sulfur in spray form,” said Mathias Brugel, MD, hospital practitioner at Basque Coast Hospital Center in Bayonne, France, during his presentation.

Regarding the four other liposoluble substances associated with an increased risk for pancreatic cancer in the second study, “their use has been banned since the 1990s, but they are still present in soils and in the air,” Dr. Brugel told this news organization.

For example, in Reims, France, the assessment of air quality by ATMO Grand Est revealed the presence of banned pesticides in the air, he added. However, Dr. Brugel stressed that a cause-effect relationship between pesticide exposure and the risk for pancreatic cancer cannot be established with these studies.
 

Incidence Rising Constantly

The incidence of pancreatic adenocarcinoma has been increasing steadily for more than 30 years. In France, nearly 16,000 new cases were reported in 2023, which represented an annual increase of about 2%. According to the National Cancer Institute, “pancreatic adenocarcinoma could become the second leading cause of cancer mortality by 2030.”

“This increase in incidence is particularly strong in France compared with other Western countries. The causes are still poorly understood. One might wonder whether environmental factors like pesticides are involved,” said Dr. Brugel.

Known to have a mechanism of action favoring oncogenesis, pesticides are suspected of being responsible for the rise in certain cancers, especially given their extensive use in France. In total, around 300 substances are authorized, and 65,000 tons are applied each year, making France the largest consumer of pesticides in Europe.

“Contamination is ubiquitous, meaning they are found in soil, water, air, and in individuals,” said Dr. Brugel. According to a study by the Institute for Scientific Expertise Research, pesticide residues were detected in 64% of hair samples taken from French volunteers.

The literature increasingly reported data suggesting a link between pesticide exposure and the development of certain diseases like cancer. A 2021 document by Inserm notably confirmed the strong presumption of a link between occupational pesticide exposure and pathologies such as non-Hodgkin’s lymphoma and prostate cancer.
 

High-Incidence Zones

To explore the link between pesticide exposure and pancreatic cancer, Dr. Brugel and his colleagues conducted the EcoPESTIPAC and PESTIPAC studies, the results of which were presented at this year’s conference.

In EcoPESTIPAC, researchers conducted a national ecological regression by dividing the entire French territory into 5529 spatial units. The number of pancreatic cancer cases per spatial unit per year (disease-mapping) was determined using the National Health Data System.

Nine chemicals, including glyphosate, were included, thus covering half of pesticide purchases in France. The cumulative quantity of pesticides, regardless of molecule, was also examined. Pesticide exposure was estimated by the median ratio between pesticide purchase and agricultural area per spatial unit over an 11-year period from early 2011 to the end of 2021.

Mor than 134,000 cases of pancreatic cancer were reported during this period. The analysis revealed three high-incidence zones located around Paris, in central France, and in the Mediterranean basin, while spatial units in the western region showed the lowest incidences.

The heterogeneous distribution of the disease suggests the involvement of risk factors, said Dr. Brugel. After adjusting for confounding factors such as smoking, the study showed an increased risk for pancreatic cancer associated with the cumulative quantity of pesticides and three specific substances: Sulfur in spray form, mancozeb, and glyphosate.
 

Risk Increases

A dose-response relationship was evident. For an increase in pesticide use of 2.5 kg/hectare over 11 years, the risk for pancreatic adenocarcinoma increased from 0.9% to 1.4%. “The increase is relatively small, but one must not forget that this risk applies to all of France,” said Dr. Brugel. Indeed, the risk appeared homogeneous across the entire territory.

This was the first study to explore this link at the national level. Although the association between the four identified factors and pancreatic risk was robust, the study had some limitations. It relied on the quantities of pesticides purchased to estimate the quantities used, Dr. Brugel pointed out.

The second study, PESTIPAC, was a case-control study conducted at the Reims University Hospital to explore the association between pancreatic adenocarcinoma and concentrations of organochlorine pesticides in fat and urine.

The study included 26 patients with pancreatic cancer who had abdominal surgery that allowed for adipose tissue sampling (minimum 10 g). Urine was collected in the morning on an empty stomach.

A control group was formed by including 26 other patients who underwent surgery for a benign abdominal condition such as gallstones or hernia, thus allowing for the same sampling. Individuals in both groups were matched for age and body mass index, two risk factors for pancreatic cancer.
 

Banned Substances

In total, 345 substances were searched for using chromatography and mass spectrometry. Analyses revealed the presence of five banned substances in all patients, while nine substances were found in half of the samples.

“Contamination is very widespread, both in patients with pancreatic cancer and in the controls,” said Dr. Brugel. Consequently, for this study, between-group comparisons of substances present in all individuals could not be performed.

After adjustment, an association with an increased risk for pancreatic cancer was nonetheless observed with four liposoluble substances: 4,4-DDE, mirex or perchlordecone, trans-nonachlor, and cis-nonachlor. All four substances are herbicides that have been banned for at least 30 years.

The study also aimed to assess the effect of pesticide presence in the body on survival after pancreatic cancer. The results showed no significant difference for overall survival or progression-free survival.

“Pesticides are a credible candidate to explain the increase in the incidence of pancreatic adenocarcinoma,” said Dr. Brugel. However, “if associations between pancreatic cancer and pesticides exist, they remain poorly understood, and it is difficult to establish clear causality.”

Further large-scale studies will be needed to confirm these associations. An evaluation of the general population’s exposure to banned substances also appears justified, according to the researchers.

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

Exposure to pesticides is associated with an increased risk for pancreatic adenocarcinoma, according to two French studies presented at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology. One of them, a case-control study, showed an elevated risk in individuals whose adipose tissue contained substances that are now banned.

“The association between pesticides and pancreatic cancer exists. It is of low magnitude but robust, concerning cumulative pesticides and three substances: Mancozeb, glyphosate, and sulfur in spray form,” said Mathias Brugel, MD, hospital practitioner at Basque Coast Hospital Center in Bayonne, France, during his presentation.

Regarding the four other liposoluble substances associated with an increased risk for pancreatic cancer in the second study, “their use has been banned since the 1990s, but they are still present in soils and in the air,” Dr. Brugel told this news organization.

For example, in Reims, France, the assessment of air quality by ATMO Grand Est revealed the presence of banned pesticides in the air, he added. However, Dr. Brugel stressed that a cause-effect relationship between pesticide exposure and the risk for pancreatic cancer cannot be established with these studies.
 

Incidence Rising Constantly

The incidence of pancreatic adenocarcinoma has been increasing steadily for more than 30 years. In France, nearly 16,000 new cases were reported in 2023, which represented an annual increase of about 2%. According to the National Cancer Institute, “pancreatic adenocarcinoma could become the second leading cause of cancer mortality by 2030.”

“This increase in incidence is particularly strong in France compared with other Western countries. The causes are still poorly understood. One might wonder whether environmental factors like pesticides are involved,” said Dr. Brugel.

Known to have a mechanism of action favoring oncogenesis, pesticides are suspected of being responsible for the rise in certain cancers, especially given their extensive use in France. In total, around 300 substances are authorized, and 65,000 tons are applied each year, making France the largest consumer of pesticides in Europe.

“Contamination is ubiquitous, meaning they are found in soil, water, air, and in individuals,” said Dr. Brugel. According to a study by the Institute for Scientific Expertise Research, pesticide residues were detected in 64% of hair samples taken from French volunteers.

The literature increasingly reported data suggesting a link between pesticide exposure and the development of certain diseases like cancer. A 2021 document by Inserm notably confirmed the strong presumption of a link between occupational pesticide exposure and pathologies such as non-Hodgkin’s lymphoma and prostate cancer.
 

High-Incidence Zones

To explore the link between pesticide exposure and pancreatic cancer, Dr. Brugel and his colleagues conducted the EcoPESTIPAC and PESTIPAC studies, the results of which were presented at this year’s conference.

In EcoPESTIPAC, researchers conducted a national ecological regression by dividing the entire French territory into 5529 spatial units. The number of pancreatic cancer cases per spatial unit per year (disease-mapping) was determined using the National Health Data System.

Nine chemicals, including glyphosate, were included, thus covering half of pesticide purchases in France. The cumulative quantity of pesticides, regardless of molecule, was also examined. Pesticide exposure was estimated by the median ratio between pesticide purchase and agricultural area per spatial unit over an 11-year period from early 2011 to the end of 2021.

Mor than 134,000 cases of pancreatic cancer were reported during this period. The analysis revealed three high-incidence zones located around Paris, in central France, and in the Mediterranean basin, while spatial units in the western region showed the lowest incidences.

The heterogeneous distribution of the disease suggests the involvement of risk factors, said Dr. Brugel. After adjusting for confounding factors such as smoking, the study showed an increased risk for pancreatic cancer associated with the cumulative quantity of pesticides and three specific substances: Sulfur in spray form, mancozeb, and glyphosate.
 

Risk Increases

A dose-response relationship was evident. For an increase in pesticide use of 2.5 kg/hectare over 11 years, the risk for pancreatic adenocarcinoma increased from 0.9% to 1.4%. “The increase is relatively small, but one must not forget that this risk applies to all of France,” said Dr. Brugel. Indeed, the risk appeared homogeneous across the entire territory.

This was the first study to explore this link at the national level. Although the association between the four identified factors and pancreatic risk was robust, the study had some limitations. It relied on the quantities of pesticides purchased to estimate the quantities used, Dr. Brugel pointed out.

The second study, PESTIPAC, was a case-control study conducted at the Reims University Hospital to explore the association between pancreatic adenocarcinoma and concentrations of organochlorine pesticides in fat and urine.

The study included 26 patients with pancreatic cancer who had abdominal surgery that allowed for adipose tissue sampling (minimum 10 g). Urine was collected in the morning on an empty stomach.

A control group was formed by including 26 other patients who underwent surgery for a benign abdominal condition such as gallstones or hernia, thus allowing for the same sampling. Individuals in both groups were matched for age and body mass index, two risk factors for pancreatic cancer.
 

Banned Substances

In total, 345 substances were searched for using chromatography and mass spectrometry. Analyses revealed the presence of five banned substances in all patients, while nine substances were found in half of the samples.

“Contamination is very widespread, both in patients with pancreatic cancer and in the controls,” said Dr. Brugel. Consequently, for this study, between-group comparisons of substances present in all individuals could not be performed.

After adjustment, an association with an increased risk for pancreatic cancer was nonetheless observed with four liposoluble substances: 4,4-DDE, mirex or perchlordecone, trans-nonachlor, and cis-nonachlor. All four substances are herbicides that have been banned for at least 30 years.

The study also aimed to assess the effect of pesticide presence in the body on survival after pancreatic cancer. The results showed no significant difference for overall survival or progression-free survival.

“Pesticides are a credible candidate to explain the increase in the incidence of pancreatic adenocarcinoma,” said Dr. Brugel. However, “if associations between pancreatic cancer and pesticides exist, they remain poorly understood, and it is difficult to establish clear causality.”

Further large-scale studies will be needed to confirm these associations. An evaluation of the general population’s exposure to banned substances also appears justified, according to the researchers.

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

Exposure to pesticides is associated with an increased risk for pancreatic adenocarcinoma, according to two French studies presented at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology. One of them, a case-control study, showed an elevated risk in individuals whose adipose tissue contained substances that are now banned.

“The association between pesticides and pancreatic cancer exists. It is of low magnitude but robust, concerning cumulative pesticides and three substances: Mancozeb, glyphosate, and sulfur in spray form,” said Mathias Brugel, MD, hospital practitioner at Basque Coast Hospital Center in Bayonne, France, during his presentation.

Regarding the four other liposoluble substances associated with an increased risk for pancreatic cancer in the second study, “their use has been banned since the 1990s, but they are still present in soils and in the air,” Dr. Brugel told this news organization.

For example, in Reims, France, the assessment of air quality by ATMO Grand Est revealed the presence of banned pesticides in the air, he added. However, Dr. Brugel stressed that a cause-effect relationship between pesticide exposure and the risk for pancreatic cancer cannot be established with these studies.
 

Incidence Rising Constantly

The incidence of pancreatic adenocarcinoma has been increasing steadily for more than 30 years. In France, nearly 16,000 new cases were reported in 2023, which represented an annual increase of about 2%. According to the National Cancer Institute, “pancreatic adenocarcinoma could become the second leading cause of cancer mortality by 2030.”

“This increase in incidence is particularly strong in France compared with other Western countries. The causes are still poorly understood. One might wonder whether environmental factors like pesticides are involved,” said Dr. Brugel.

Known to have a mechanism of action favoring oncogenesis, pesticides are suspected of being responsible for the rise in certain cancers, especially given their extensive use in France. In total, around 300 substances are authorized, and 65,000 tons are applied each year, making France the largest consumer of pesticides in Europe.

“Contamination is ubiquitous, meaning they are found in soil, water, air, and in individuals,” said Dr. Brugel. According to a study by the Institute for Scientific Expertise Research, pesticide residues were detected in 64% of hair samples taken from French volunteers.

The literature increasingly reported data suggesting a link between pesticide exposure and the development of certain diseases like cancer. A 2021 document by Inserm notably confirmed the strong presumption of a link between occupational pesticide exposure and pathologies such as non-Hodgkin’s lymphoma and prostate cancer.
 

High-Incidence Zones

To explore the link between pesticide exposure and pancreatic cancer, Dr. Brugel and his colleagues conducted the EcoPESTIPAC and PESTIPAC studies, the results of which were presented at this year’s conference.

In EcoPESTIPAC, researchers conducted a national ecological regression by dividing the entire French territory into 5529 spatial units. The number of pancreatic cancer cases per spatial unit per year (disease-mapping) was determined using the National Health Data System.

Nine chemicals, including glyphosate, were included, thus covering half of pesticide purchases in France. The cumulative quantity of pesticides, regardless of molecule, was also examined. Pesticide exposure was estimated by the median ratio between pesticide purchase and agricultural area per spatial unit over an 11-year period from early 2011 to the end of 2021.

Mor than 134,000 cases of pancreatic cancer were reported during this period. The analysis revealed three high-incidence zones located around Paris, in central France, and in the Mediterranean basin, while spatial units in the western region showed the lowest incidences.

The heterogeneous distribution of the disease suggests the involvement of risk factors, said Dr. Brugel. After adjusting for confounding factors such as smoking, the study showed an increased risk for pancreatic cancer associated with the cumulative quantity of pesticides and three specific substances: Sulfur in spray form, mancozeb, and glyphosate.
 

Risk Increases

A dose-response relationship was evident. For an increase in pesticide use of 2.5 kg/hectare over 11 years, the risk for pancreatic adenocarcinoma increased from 0.9% to 1.4%. “The increase is relatively small, but one must not forget that this risk applies to all of France,” said Dr. Brugel. Indeed, the risk appeared homogeneous across the entire territory.

This was the first study to explore this link at the national level. Although the association between the four identified factors and pancreatic risk was robust, the study had some limitations. It relied on the quantities of pesticides purchased to estimate the quantities used, Dr. Brugel pointed out.

The second study, PESTIPAC, was a case-control study conducted at the Reims University Hospital to explore the association between pancreatic adenocarcinoma and concentrations of organochlorine pesticides in fat and urine.

The study included 26 patients with pancreatic cancer who had abdominal surgery that allowed for adipose tissue sampling (minimum 10 g). Urine was collected in the morning on an empty stomach.

A control group was formed by including 26 other patients who underwent surgery for a benign abdominal condition such as gallstones or hernia, thus allowing for the same sampling. Individuals in both groups were matched for age and body mass index, two risk factors for pancreatic cancer.
 

Banned Substances

In total, 345 substances were searched for using chromatography and mass spectrometry. Analyses revealed the presence of five banned substances in all patients, while nine substances were found in half of the samples.

“Contamination is very widespread, both in patients with pancreatic cancer and in the controls,” said Dr. Brugel. Consequently, for this study, between-group comparisons of substances present in all individuals could not be performed.

After adjustment, an association with an increased risk for pancreatic cancer was nonetheless observed with four liposoluble substances: 4,4-DDE, mirex or perchlordecone, trans-nonachlor, and cis-nonachlor. All four substances are herbicides that have been banned for at least 30 years.

The study also aimed to assess the effect of pesticide presence in the body on survival after pancreatic cancer. The results showed no significant difference for overall survival or progression-free survival.

“Pesticides are a credible candidate to explain the increase in the incidence of pancreatic adenocarcinoma,” said Dr. Brugel. However, “if associations between pancreatic cancer and pesticides exist, they remain poorly understood, and it is difficult to establish clear causality.”

Further large-scale studies will be needed to confirm these associations. An evaluation of the general population’s exposure to banned substances also appears justified, according to the researchers.

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

CORRECTED April 7, 2024 // An earlier version of this article misstated the clinical factors of children with CNO that were significantly associated with the need for second-line treatment, as well as the scope of assessments of aspects of disease involvement and their relationship to total number of days on NSAID monotherapy and the odds of needing a second-line treatment.

Children with chronic nonbacterial osteomyelitis (CNO) who had symmetric bone lesions or multiple affected body regions were more likely to need second-line treatment than were patients without these features, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

CNO is an auto-inflammatory condition that results in sterile inflammatory bone lesions and most commonly affects the long bones of people who are skeletally immature. After a first-line treatment of nonsteroidal anti-inflammatory drugs (NSAIDs), second-line treatments per CARRA guidelines typically include methotrexate or sulfasalazine, tumor necrosis factor (TNF)–alpha inhibitors, and bisphosphonates.

“Since it’s common for there to be long delays before diagnosis of CNO, it is important to start an effective treatment promptly,” Katherine D. Nowicki, MD, of Children’s Hospital Colorado, Aurora, told attendees. “While we have guidance on which treatments to use, it remains unclear which patients are most likely to respond to NSAIDs and which patients will require a second-line treatment.”
 

Findings Helpful for Counseling

Melissa S. Oliver, MD, MS, assistant professor of clinical pediatrics in rheumatology at Riley Children’s Health at Indiana University Health, Indianapolis, who was not involved in the research, said the findings of this study are helpful in “counseling families and patients at that initial visit and having a lower threshold to start a second-line agent if NSAID monotherapy is not working well.”

There are no clinical trials on patients with CNO, Dr. Oliver said, so very little data exist for guiding clinicians on the best therapy to use and how long to keep patients on therapy while minimizing risk for flare when coming off therapy.

A key clinical takeaway for clinicians is being able to tell patients with unifocal disease that they may not need to be on NSAIDs for a long period and can still do well, Dr. Oliver said. For patients with multifocal disease with symmetric bone lesions or multiple regions involved with CNO, “pediatric rheumatologists should have a lower threshold to start a second-line therapy for these patients,” she said.

Findings From Largest Single-Center Cohort in North America

Their topline findings revealed that patients with unifocal disease at diagnosis required 47% fewer total days of NSAID monotherapy treatment than those with multifocal disease at diagnosis, Dr. Nowicki told attendees. Having symmetric bone lesions increased the likelihood of needing a second-line therapy by 6.86 times compared with those without symmetric bone lesions, and for each additional region affected by CNO, the odds of needing a second-line therapy increased by a factor of 1.94, she said.

There were no significant differences in patient ages or sex or in mean interval from symptom onset to treatment onset across treatment groups. However, patients who received second-line treatment did have a significantly longer average time from symptom onset to diagnosis (324 days) than those who had a short course (119 days) or long course (270 days) of NSAIDs (P = .023). Mean follow-up was also significantly longer for patients with second-line treatment (3.8 years) or long-course NSAIDs (2.7 years) than for those with short-course NSAIDs (1.2 years; P < .001).

Mean erythrocyte sedimentation rate or C-reactive protein did not differ across treatment groups nor did presence of a CNO lesion on x-rays at presentation. But significantly more patients in the second-line group had a biopsy (94%) than in the long-course (74%) or short-course (69%) NSAID groups (P = .0025). They were also more likely to have one or more whole-body MRIs. Most of the patients on short-course (88%) and long-course (82%) NSAIDs did not undergo a whole-body MRI, whereas most patients (59%) on a second-line treatment underwent at least one and 24% underwent three or more MRIs (P < .001).

More patients on short-course NSAIDs had unifocal disease at diagnosis (72%) than those on long-course NSAIDs (47%) or a second-line treatment (41%; P = .015). Patients on a second-line treatment were also more likely to have symmetric involvement in the same bone (73% vs 16% short-course and 23% long-course NSAIDs) and to have more regions of the body affected (P < .001).

There were significant differences in mean days on NSAID monotherapy and number of NSAIDs trialed. Patients on a second-line treatment had a mean 441 days of NSAID monotherapy compared with 175 days for patients on short-course NSAIDs and 725 for patients on long-course NSAIDs (P < .001). Nearly all the short-course patients (94%) trialed a single NSAID, while more than half the long-course and second-line patients trialed two or more (P < .001).

None of the patients on short-course NSAIDs had complications. More patients on second-line treatments had vertebral height loss (20%) or amplified pain (14%) than long-course patients (13% and 5%, respectively; P = .02).

At the study’s end date, nearly all the patients on short-course NSAIDs were in remission (94%) compared with 71% of patients on long-course NSAIDs and only half of patients (51%) on the second-line treatment (P < .001). None of the patients on short-course NSAIDs had active disease compared with 11% of patients on long-course NSAIDs and 20% of patients on second-line treatments (P = .02).

This study included the largest single-center cohort of patients with CNO in North America, all treated at a multidisciplinary clinic with a protocolized treatment approach, but it remains limited by its retrospective nature and the missing data for 70 patients, Dr. Nowicki said. She noted that whole-body MRI was not systematically performed on all patients, so it was possible patients without a whole-body MRI had undetected asymptomatic lesions.

Despite these limitations, Dr. Oliver said retrospective studies like these can help pediatric rheumatologists get an idea of reasonable therapies to start, how long to keep patients on them, and when to escalate to the next step.

“I hope one day our CNO research will be able to tell us about which is the optimal second-line therapy for patients, such as bisphosphonates vs TNF inhibitors vs DMARDs [disease-modifying antirheumatic drugs],” Dr. Oliver said.

Dr. Nowicki and Dr. Oliver reported no disclosures. Information on study funding was not provided.

A version of this article appeared on Medscape.com .

CORRECTED April 7, 2024 // An earlier version of this article misstated the clinical factors of children with CNO that were significantly associated with the need for second-line treatment, as well as the scope of assessments of aspects of disease involvement and their relationship to total number of days on NSAID monotherapy and the odds of needing a second-line treatment.

Children with chronic nonbacterial osteomyelitis (CNO) who had symmetric bone lesions or multiple affected body regions were more likely to need second-line treatment than were patients without these features, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

CNO is an auto-inflammatory condition that results in sterile inflammatory bone lesions and most commonly affects the long bones of people who are skeletally immature. After a first-line treatment of nonsteroidal anti-inflammatory drugs (NSAIDs), second-line treatments per CARRA guidelines typically include methotrexate or sulfasalazine, tumor necrosis factor (TNF)–alpha inhibitors, and bisphosphonates.

“Since it’s common for there to be long delays before diagnosis of CNO, it is important to start an effective treatment promptly,” Katherine D. Nowicki, MD, of Children’s Hospital Colorado, Aurora, told attendees. “While we have guidance on which treatments to use, it remains unclear which patients are most likely to respond to NSAIDs and which patients will require a second-line treatment.”
 

Findings Helpful for Counseling

Melissa S. Oliver, MD, MS, assistant professor of clinical pediatrics in rheumatology at Riley Children’s Health at Indiana University Health, Indianapolis, who was not involved in the research, said the findings of this study are helpful in “counseling families and patients at that initial visit and having a lower threshold to start a second-line agent if NSAID monotherapy is not working well.”

There are no clinical trials on patients with CNO, Dr. Oliver said, so very little data exist for guiding clinicians on the best therapy to use and how long to keep patients on therapy while minimizing risk for flare when coming off therapy.

A key clinical takeaway for clinicians is being able to tell patients with unifocal disease that they may not need to be on NSAIDs for a long period and can still do well, Dr. Oliver said. For patients with multifocal disease with symmetric bone lesions or multiple regions involved with CNO, “pediatric rheumatologists should have a lower threshold to start a second-line therapy for these patients,” she said.

Findings From Largest Single-Center Cohort in North America

Their topline findings revealed that patients with unifocal disease at diagnosis required 47% fewer total days of NSAID monotherapy treatment than those with multifocal disease at diagnosis, Dr. Nowicki told attendees. Having symmetric bone lesions increased the likelihood of needing a second-line therapy by 6.86 times compared with those without symmetric bone lesions, and for each additional region affected by CNO, the odds of needing a second-line therapy increased by a factor of 1.94, she said.

There were no significant differences in patient ages or sex or in mean interval from symptom onset to treatment onset across treatment groups. However, patients who received second-line treatment did have a significantly longer average time from symptom onset to diagnosis (324 days) than those who had a short course (119 days) or long course (270 days) of NSAIDs (P = .023). Mean follow-up was also significantly longer for patients with second-line treatment (3.8 years) or long-course NSAIDs (2.7 years) than for those with short-course NSAIDs (1.2 years; P < .001).

Mean erythrocyte sedimentation rate or C-reactive protein did not differ across treatment groups nor did presence of a CNO lesion on x-rays at presentation. But significantly more patients in the second-line group had a biopsy (94%) than in the long-course (74%) or short-course (69%) NSAID groups (P = .0025). They were also more likely to have one or more whole-body MRIs. Most of the patients on short-course (88%) and long-course (82%) NSAIDs did not undergo a whole-body MRI, whereas most patients (59%) on a second-line treatment underwent at least one and 24% underwent three or more MRIs (P < .001).

More patients on short-course NSAIDs had unifocal disease at diagnosis (72%) than those on long-course NSAIDs (47%) or a second-line treatment (41%; P = .015). Patients on a second-line treatment were also more likely to have symmetric involvement in the same bone (73% vs 16% short-course and 23% long-course NSAIDs) and to have more regions of the body affected (P < .001).

There were significant differences in mean days on NSAID monotherapy and number of NSAIDs trialed. Patients on a second-line treatment had a mean 441 days of NSAID monotherapy compared with 175 days for patients on short-course NSAIDs and 725 for patients on long-course NSAIDs (P < .001). Nearly all the short-course patients (94%) trialed a single NSAID, while more than half the long-course and second-line patients trialed two or more (P < .001).

None of the patients on short-course NSAIDs had complications. More patients on second-line treatments had vertebral height loss (20%) or amplified pain (14%) than long-course patients (13% and 5%, respectively; P = .02).

At the study’s end date, nearly all the patients on short-course NSAIDs were in remission (94%) compared with 71% of patients on long-course NSAIDs and only half of patients (51%) on the second-line treatment (P < .001). None of the patients on short-course NSAIDs had active disease compared with 11% of patients on long-course NSAIDs and 20% of patients on second-line treatments (P = .02).

This study included the largest single-center cohort of patients with CNO in North America, all treated at a multidisciplinary clinic with a protocolized treatment approach, but it remains limited by its retrospective nature and the missing data for 70 patients, Dr. Nowicki said. She noted that whole-body MRI was not systematically performed on all patients, so it was possible patients without a whole-body MRI had undetected asymptomatic lesions.

Despite these limitations, Dr. Oliver said retrospective studies like these can help pediatric rheumatologists get an idea of reasonable therapies to start, how long to keep patients on them, and when to escalate to the next step.

“I hope one day our CNO research will be able to tell us about which is the optimal second-line therapy for patients, such as bisphosphonates vs TNF inhibitors vs DMARDs [disease-modifying antirheumatic drugs],” Dr. Oliver said.

Dr. Nowicki and Dr. Oliver reported no disclosures. Information on study funding was not provided.

A version of this article appeared on Medscape.com .

CORRECTED April 7, 2024 // An earlier version of this article misstated the clinical factors of children with CNO that were significantly associated with the need for second-line treatment, as well as the scope of assessments of aspects of disease involvement and their relationship to total number of days on NSAID monotherapy and the odds of needing a second-line treatment.

Children with chronic nonbacterial osteomyelitis (CNO) who had symmetric bone lesions or multiple affected body regions were more likely to need second-line treatment than were patients without these features, according to findings presented at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

CNO is an auto-inflammatory condition that results in sterile inflammatory bone lesions and most commonly affects the long bones of people who are skeletally immature. After a first-line treatment of nonsteroidal anti-inflammatory drugs (NSAIDs), second-line treatments per CARRA guidelines typically include methotrexate or sulfasalazine, tumor necrosis factor (TNF)–alpha inhibitors, and bisphosphonates.

“Since it’s common for there to be long delays before diagnosis of CNO, it is important to start an effective treatment promptly,” Katherine D. Nowicki, MD, of Children’s Hospital Colorado, Aurora, told attendees. “While we have guidance on which treatments to use, it remains unclear which patients are most likely to respond to NSAIDs and which patients will require a second-line treatment.”
 

Findings Helpful for Counseling

Melissa S. Oliver, MD, MS, assistant professor of clinical pediatrics in rheumatology at Riley Children’s Health at Indiana University Health, Indianapolis, who was not involved in the research, said the findings of this study are helpful in “counseling families and patients at that initial visit and having a lower threshold to start a second-line agent if NSAID monotherapy is not working well.”

There are no clinical trials on patients with CNO, Dr. Oliver said, so very little data exist for guiding clinicians on the best therapy to use and how long to keep patients on therapy while minimizing risk for flare when coming off therapy.

A key clinical takeaway for clinicians is being able to tell patients with unifocal disease that they may not need to be on NSAIDs for a long period and can still do well, Dr. Oliver said. For patients with multifocal disease with symmetric bone lesions or multiple regions involved with CNO, “pediatric rheumatologists should have a lower threshold to start a second-line therapy for these patients,” she said.

Findings From Largest Single-Center Cohort in North America

Their topline findings revealed that patients with unifocal disease at diagnosis required 47% fewer total days of NSAID monotherapy treatment than those with multifocal disease at diagnosis, Dr. Nowicki told attendees. Having symmetric bone lesions increased the likelihood of needing a second-line therapy by 6.86 times compared with those without symmetric bone lesions, and for each additional region affected by CNO, the odds of needing a second-line therapy increased by a factor of 1.94, she said.

There were no significant differences in patient ages or sex or in mean interval from symptom onset to treatment onset across treatment groups. However, patients who received second-line treatment did have a significantly longer average time from symptom onset to diagnosis (324 days) than those who had a short course (119 days) or long course (270 days) of NSAIDs (P = .023). Mean follow-up was also significantly longer for patients with second-line treatment (3.8 years) or long-course NSAIDs (2.7 years) than for those with short-course NSAIDs (1.2 years; P < .001).

Mean erythrocyte sedimentation rate or C-reactive protein did not differ across treatment groups nor did presence of a CNO lesion on x-rays at presentation. But significantly more patients in the second-line group had a biopsy (94%) than in the long-course (74%) or short-course (69%) NSAID groups (P = .0025). They were also more likely to have one or more whole-body MRIs. Most of the patients on short-course (88%) and long-course (82%) NSAIDs did not undergo a whole-body MRI, whereas most patients (59%) on a second-line treatment underwent at least one and 24% underwent three or more MRIs (P < .001).

More patients on short-course NSAIDs had unifocal disease at diagnosis (72%) than those on long-course NSAIDs (47%) or a second-line treatment (41%; P = .015). Patients on a second-line treatment were also more likely to have symmetric involvement in the same bone (73% vs 16% short-course and 23% long-course NSAIDs) and to have more regions of the body affected (P < .001).

There were significant differences in mean days on NSAID monotherapy and number of NSAIDs trialed. Patients on a second-line treatment had a mean 441 days of NSAID monotherapy compared with 175 days for patients on short-course NSAIDs and 725 for patients on long-course NSAIDs (P < .001). Nearly all the short-course patients (94%) trialed a single NSAID, while more than half the long-course and second-line patients trialed two or more (P < .001).

None of the patients on short-course NSAIDs had complications. More patients on second-line treatments had vertebral height loss (20%) or amplified pain (14%) than long-course patients (13% and 5%, respectively; P = .02).

At the study’s end date, nearly all the patients on short-course NSAIDs were in remission (94%) compared with 71% of patients on long-course NSAIDs and only half of patients (51%) on the second-line treatment (P < .001). None of the patients on short-course NSAIDs had active disease compared with 11% of patients on long-course NSAIDs and 20% of patients on second-line treatments (P = .02).

This study included the largest single-center cohort of patients with CNO in North America, all treated at a multidisciplinary clinic with a protocolized treatment approach, but it remains limited by its retrospective nature and the missing data for 70 patients, Dr. Nowicki said. She noted that whole-body MRI was not systematically performed on all patients, so it was possible patients without a whole-body MRI had undetected asymptomatic lesions.

Despite these limitations, Dr. Oliver said retrospective studies like these can help pediatric rheumatologists get an idea of reasonable therapies to start, how long to keep patients on them, and when to escalate to the next step.

“I hope one day our CNO research will be able to tell us about which is the optimal second-line therapy for patients, such as bisphosphonates vs TNF inhibitors vs DMARDs [disease-modifying antirheumatic drugs],” Dr. Oliver said.

Dr. Nowicki and Dr. Oliver reported no disclosures. Information on study funding was not provided.

A version of this article appeared on Medscape.com .