Dermatology News

Chronic pruritus is a common problem among older individuals. During a session at the Dermatology Days of Paris 2024 conference dedicated to general practitioners, Juliette Delaunay, MD, a dermatologist and venereologist at Angers University Hospital Center in Angers, France, and Gabrielle Lisembard, MD, a general practitioner in the French town Grand-Fort-Philippe, discussed diagnostic approaches and key principles for the therapeutic management of pruritus.

Identifying Causes

“Pruritus in older people is most often linked to physiological changes in the skin caused by aging, leading to significant xerosis. However, before attributing it to aging, we need to rule out several causes,” Delaunay noted.

Beyond simple aging, one must consider autoimmune bullous dermatoses (bullous pemphigoid), drug-related causes, metabolic disorders (can occur at any age), cutaneous T-cell lymphomas, scabies, lice, and HIV infection.

 

Senile Pruritus

Aging-related xerosis can cause senile pruritus, often presenting as itching with scratch marks and dry skin. “This is a diagnosis of exclusion,” Delaunay insisted.

In older individuals with pruritus, initial examinations should include complete blood cell count (CBC), liver function tests, and thyroid-stimulating hormone levels. Syphilis serology, HIV testing, and beta-2 microglobulin levels are secondary evaluations. Renal function analysis may also be performed, and imaging may be required to investigate neoplasia.

“Annual etiological reassessment is essential if the initial evaluation is negative, as patients may later develop or report a neoplasia or hematological disorder,” Delaunay emphasized.

Paraneoplastic pruritus can occur, particularly those linked to hematological disorders (lymphomas, polycythemia, or myeloma).

 

Bullous Pemphigoid

Bullous pemphigoid often begins with pruritus, which can be severe and lead to insomnia. General practitioners should consider bullous pemphigoids when there is a bullous rash (tense blisters with citrine content) or an urticarial or chronic eczematous rash that does not heal spontaneously within a few days. The first-line biologic test to confirm the diagnosis is the CBC, which may reveal significant hypereosinophilia.

The diagnosis is confirmed by a skin biopsy showing a subepidermal blister with a preserved roof, unlike intraepidermal dermatoses, where the roof ruptures.

Direct immunofluorescence revealed deposits of immunoglobulin G antibodies along the dermoepidermal junction.

Approximately 40% of cases of bullous pemphigoid are associated with neurodegenerative diseases, such as stroke, parkinsonism, or dementia syndromes — occurring at a rate two to three times higher than in the general population.

It’s important to identify drugs that induce bullous pemphigoid, such as gliptins, anti-programmed cell death protein 1-programmed death-ligand 1 agents, loop diuretics (furosemide and bumetanide), anti-aldosterones (spironolactone), antiarrhythmics (amiodarone), and neuroleptics (phenothiazines).

“Stopping the medication is not mandatory if the bullous pemphigoid is well controlled by local or systemic treatments and the medication is essential. The decision to stop should be made on a case-by-case basis in consultation with the treating specialist,” Delaunay emphasized.

Treatment consists of very strong local corticosteroid therapy as the first-line treatment. If ineffective, systemic treatments based on methotrexate, oral corticosteroids, or immunomodulatory agents may be considered. Hospitalization is sometimes required.

 

Drug-Induced Pruritus

Drug-induced pruritus is common because older individuals often take multiple medications (antihypertensives, statins, oral hypoglycemics, psychotropic drugs, antiarrhythmics, etc.). “Sometimes, drug-induced pruritus can occur even if the medication was started several months or years ago,” Delaunay emphasized.

The lesions are generally nonspecific and scratching.

“This is a diagnosis of exclusion for other causes of pruritus. In the absence of specific lesions pointing to a dermatosis, eviction/reintroduction tests with treatments should be conducted one by one, which can be quite lengthy,” she explained.

 

Awareness for Scabies

Delaunay reminded attendees to consider scabies in older individuals when classic signs of pruritus flare up at night, with a rash affecting the face, scabs, or vesicles in the interdigital spaces of the hands, wrists, scrotal area, or the peri-mammary region.

“The incidence is increasing, particularly in nursing homes, where outbreaks pose a significant risk of rapid spread. Treatment involves three courses of topical and oral treatments administered on days 0, 7, and 14. All contact cases must also be treated. Sometimes, these thick lesions are stripped with 10% salicylated petroleum jelly. Environmental treatment with acaricides is essential, along with strict isolation measures,” Delaunay emphasized.

Adherent nits on the scalp or other hairy areas should raise suspicion of pediculosis.

 

Neurogenic and Psychogenic Origins

Neurogenic pruritus can occur during a stroke, presenting as contralateral pruritus, or in the presence of a brain tumor or following neurosurgery. Opioid-containing medications may also induce neurogenic pruritus.

The presence of unilateral painful or itchy sensations should prompt the investigation of shingles in older individuals.

Psychogenic pruritus is also common and can arise in the context of psychosis with parasitophobia or as part of anxiety-depression syndromes.

 

Supportive Measures

For managing pruritus, it is essential to:

• Keep nails trimmed short
• Wash with cold or lukewarm water
• Use lipid-rice soaps and syndets
• Avoid irritants, including antiseptics, cologne, no-rinse cleansers, and steroidal or nonsteroidal anti-inflammatory drugs
• Limit bathing frequency
• Avoid wearing nylon, wool, or tight clothing
• Minimize exposure to heat and excessive heating

“Alternatives to scratching, such as applying a moisturizing emollient, can be beneficial and may have a placebo effect,” explained the dermatologist. She further emphasized that local corticosteroids are effective only in the presence of inflammatory dermatosis and should not be applied to healthy skin. Similarly, antihistamines should only be prescribed if the pruritus is histamine-mediated.

Capsaicin may be useful in the treatment of localized neuropathic pruritus.

In cases of neurogenic pruritus, gabapentin and pregabalin may be prescribed, but tolerance can be problematic at this age. Other measures include acupuncture, cryotherapy, relaxation, hypnosis, psychotherapy, and music therapy. In cases of repeated therapeutic failure, patients may be treated with biotherapy (dupilumab) by a dermatologist.

 

This story was translated from Medscape’s 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.

Chronic pruritus is a common problem among older individuals. During a session at the Dermatology Days of Paris 2024 conference dedicated to general practitioners, Juliette Delaunay, MD, a dermatologist and venereologist at Angers University Hospital Center in Angers, France, and Gabrielle Lisembard, MD, a general practitioner in the French town Grand-Fort-Philippe, discussed diagnostic approaches and key principles for the therapeutic management of pruritus.

Identifying Causes

“Pruritus in older people is most often linked to physiological changes in the skin caused by aging, leading to significant xerosis. However, before attributing it to aging, we need to rule out several causes,” Delaunay noted.

Beyond simple aging, one must consider autoimmune bullous dermatoses (bullous pemphigoid), drug-related causes, metabolic disorders (can occur at any age), cutaneous T-cell lymphomas, scabies, lice, and HIV infection.

 

Senile Pruritus

Aging-related xerosis can cause senile pruritus, often presenting as itching with scratch marks and dry skin. “This is a diagnosis of exclusion,” Delaunay insisted.

In older individuals with pruritus, initial examinations should include complete blood cell count (CBC), liver function tests, and thyroid-stimulating hormone levels. Syphilis serology, HIV testing, and beta-2 microglobulin levels are secondary evaluations. Renal function analysis may also be performed, and imaging may be required to investigate neoplasia.

“Annual etiological reassessment is essential if the initial evaluation is negative, as patients may later develop or report a neoplasia or hematological disorder,” Delaunay emphasized.

Paraneoplastic pruritus can occur, particularly those linked to hematological disorders (lymphomas, polycythemia, or myeloma).

 

Bullous Pemphigoid

Bullous pemphigoid often begins with pruritus, which can be severe and lead to insomnia. General practitioners should consider bullous pemphigoids when there is a bullous rash (tense blisters with citrine content) or an urticarial or chronic eczematous rash that does not heal spontaneously within a few days. The first-line biologic test to confirm the diagnosis is the CBC, which may reveal significant hypereosinophilia.

The diagnosis is confirmed by a skin biopsy showing a subepidermal blister with a preserved roof, unlike intraepidermal dermatoses, where the roof ruptures.

Direct immunofluorescence revealed deposits of immunoglobulin G antibodies along the dermoepidermal junction.

Approximately 40% of cases of bullous pemphigoid are associated with neurodegenerative diseases, such as stroke, parkinsonism, or dementia syndromes — occurring at a rate two to three times higher than in the general population.

It’s important to identify drugs that induce bullous pemphigoid, such as gliptins, anti-programmed cell death protein 1-programmed death-ligand 1 agents, loop diuretics (furosemide and bumetanide), anti-aldosterones (spironolactone), antiarrhythmics (amiodarone), and neuroleptics (phenothiazines).

“Stopping the medication is not mandatory if the bullous pemphigoid is well controlled by local or systemic treatments and the medication is essential. The decision to stop should be made on a case-by-case basis in consultation with the treating specialist,” Delaunay emphasized.

Treatment consists of very strong local corticosteroid therapy as the first-line treatment. If ineffective, systemic treatments based on methotrexate, oral corticosteroids, or immunomodulatory agents may be considered. Hospitalization is sometimes required.

 

Drug-Induced Pruritus

Drug-induced pruritus is common because older individuals often take multiple medications (antihypertensives, statins, oral hypoglycemics, psychotropic drugs, antiarrhythmics, etc.). “Sometimes, drug-induced pruritus can occur even if the medication was started several months or years ago,” Delaunay emphasized.

The lesions are generally nonspecific and scratching.

“This is a diagnosis of exclusion for other causes of pruritus. In the absence of specific lesions pointing to a dermatosis, eviction/reintroduction tests with treatments should be conducted one by one, which can be quite lengthy,” she explained.

 

Awareness for Scabies

Delaunay reminded attendees to consider scabies in older individuals when classic signs of pruritus flare up at night, with a rash affecting the face, scabs, or vesicles in the interdigital spaces of the hands, wrists, scrotal area, or the peri-mammary region.

“The incidence is increasing, particularly in nursing homes, where outbreaks pose a significant risk of rapid spread. Treatment involves three courses of topical and oral treatments administered on days 0, 7, and 14. All contact cases must also be treated. Sometimes, these thick lesions are stripped with 10% salicylated petroleum jelly. Environmental treatment with acaricides is essential, along with strict isolation measures,” Delaunay emphasized.

Adherent nits on the scalp or other hairy areas should raise suspicion of pediculosis.

 

Neurogenic and Psychogenic Origins

Neurogenic pruritus can occur during a stroke, presenting as contralateral pruritus, or in the presence of a brain tumor or following neurosurgery. Opioid-containing medications may also induce neurogenic pruritus.

The presence of unilateral painful or itchy sensations should prompt the investigation of shingles in older individuals.

Psychogenic pruritus is also common and can arise in the context of psychosis with parasitophobia or as part of anxiety-depression syndromes.

 

Supportive Measures

For managing pruritus, it is essential to:

• Keep nails trimmed short
• Wash with cold or lukewarm water
• Use lipid-rice soaps and syndets
• Avoid irritants, including antiseptics, cologne, no-rinse cleansers, and steroidal or nonsteroidal anti-inflammatory drugs
• Limit bathing frequency
• Avoid wearing nylon, wool, or tight clothing
• Minimize exposure to heat and excessive heating

“Alternatives to scratching, such as applying a moisturizing emollient, can be beneficial and may have a placebo effect,” explained the dermatologist. She further emphasized that local corticosteroids are effective only in the presence of inflammatory dermatosis and should not be applied to healthy skin. Similarly, antihistamines should only be prescribed if the pruritus is histamine-mediated.

Capsaicin may be useful in the treatment of localized neuropathic pruritus.

In cases of neurogenic pruritus, gabapentin and pregabalin may be prescribed, but tolerance can be problematic at this age. Other measures include acupuncture, cryotherapy, relaxation, hypnosis, psychotherapy, and music therapy. In cases of repeated therapeutic failure, patients may be treated with biotherapy (dupilumab) by a dermatologist.

 

This story was translated from Medscape’s 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.

Chronic pruritus is a common problem among older individuals. During a session at the Dermatology Days of Paris 2024 conference dedicated to general practitioners, Juliette Delaunay, MD, a dermatologist and venereologist at Angers University Hospital Center in Angers, France, and Gabrielle Lisembard, MD, a general practitioner in the French town Grand-Fort-Philippe, discussed diagnostic approaches and key principles for the therapeutic management of pruritus.

Identifying Causes

“Pruritus in older people is most often linked to physiological changes in the skin caused by aging, leading to significant xerosis. However, before attributing it to aging, we need to rule out several causes,” Delaunay noted.

Beyond simple aging, one must consider autoimmune bullous dermatoses (bullous pemphigoid), drug-related causes, metabolic disorders (can occur at any age), cutaneous T-cell lymphomas, scabies, lice, and HIV infection.

 

Senile Pruritus

Aging-related xerosis can cause senile pruritus, often presenting as itching with scratch marks and dry skin. “This is a diagnosis of exclusion,” Delaunay insisted.

In older individuals with pruritus, initial examinations should include complete blood cell count (CBC), liver function tests, and thyroid-stimulating hormone levels. Syphilis serology, HIV testing, and beta-2 microglobulin levels are secondary evaluations. Renal function analysis may also be performed, and imaging may be required to investigate neoplasia.

“Annual etiological reassessment is essential if the initial evaluation is negative, as patients may later develop or report a neoplasia or hematological disorder,” Delaunay emphasized.

Paraneoplastic pruritus can occur, particularly those linked to hematological disorders (lymphomas, polycythemia, or myeloma).

 

Bullous Pemphigoid

Bullous pemphigoid often begins with pruritus, which can be severe and lead to insomnia. General practitioners should consider bullous pemphigoids when there is a bullous rash (tense blisters with citrine content) or an urticarial or chronic eczematous rash that does not heal spontaneously within a few days. The first-line biologic test to confirm the diagnosis is the CBC, which may reveal significant hypereosinophilia.

The diagnosis is confirmed by a skin biopsy showing a subepidermal blister with a preserved roof, unlike intraepidermal dermatoses, where the roof ruptures.

Direct immunofluorescence revealed deposits of immunoglobulin G antibodies along the dermoepidermal junction.

Approximately 40% of cases of bullous pemphigoid are associated with neurodegenerative diseases, such as stroke, parkinsonism, or dementia syndromes — occurring at a rate two to three times higher than in the general population.

It’s important to identify drugs that induce bullous pemphigoid, such as gliptins, anti-programmed cell death protein 1-programmed death-ligand 1 agents, loop diuretics (furosemide and bumetanide), anti-aldosterones (spironolactone), antiarrhythmics (amiodarone), and neuroleptics (phenothiazines).

“Stopping the medication is not mandatory if the bullous pemphigoid is well controlled by local or systemic treatments and the medication is essential. The decision to stop should be made on a case-by-case basis in consultation with the treating specialist,” Delaunay emphasized.

Treatment consists of very strong local corticosteroid therapy as the first-line treatment. If ineffective, systemic treatments based on methotrexate, oral corticosteroids, or immunomodulatory agents may be considered. Hospitalization is sometimes required.

 

Drug-Induced Pruritus

Drug-induced pruritus is common because older individuals often take multiple medications (antihypertensives, statins, oral hypoglycemics, psychotropic drugs, antiarrhythmics, etc.). “Sometimes, drug-induced pruritus can occur even if the medication was started several months or years ago,” Delaunay emphasized.

The lesions are generally nonspecific and scratching.

“This is a diagnosis of exclusion for other causes of pruritus. In the absence of specific lesions pointing to a dermatosis, eviction/reintroduction tests with treatments should be conducted one by one, which can be quite lengthy,” she explained.

 

Awareness for Scabies

Delaunay reminded attendees to consider scabies in older individuals when classic signs of pruritus flare up at night, with a rash affecting the face, scabs, or vesicles in the interdigital spaces of the hands, wrists, scrotal area, or the peri-mammary region.

“The incidence is increasing, particularly in nursing homes, where outbreaks pose a significant risk of rapid spread. Treatment involves three courses of topical and oral treatments administered on days 0, 7, and 14. All contact cases must also be treated. Sometimes, these thick lesions are stripped with 10% salicylated petroleum jelly. Environmental treatment with acaricides is essential, along with strict isolation measures,” Delaunay emphasized.

Adherent nits on the scalp or other hairy areas should raise suspicion of pediculosis.

 

Neurogenic and Psychogenic Origins

Neurogenic pruritus can occur during a stroke, presenting as contralateral pruritus, or in the presence of a brain tumor or following neurosurgery. Opioid-containing medications may also induce neurogenic pruritus.

The presence of unilateral painful or itchy sensations should prompt the investigation of shingles in older individuals.

Psychogenic pruritus is also common and can arise in the context of psychosis with parasitophobia or as part of anxiety-depression syndromes.

 

Supportive Measures

For managing pruritus, it is essential to:

• Keep nails trimmed short
• Wash with cold or lukewarm water
• Use lipid-rice soaps and syndets
• Avoid irritants, including antiseptics, cologne, no-rinse cleansers, and steroidal or nonsteroidal anti-inflammatory drugs
• Limit bathing frequency
• Avoid wearing nylon, wool, or tight clothing
• Minimize exposure to heat and excessive heating

“Alternatives to scratching, such as applying a moisturizing emollient, can be beneficial and may have a placebo effect,” explained the dermatologist. She further emphasized that local corticosteroids are effective only in the presence of inflammatory dermatosis and should not be applied to healthy skin. Similarly, antihistamines should only be prescribed if the pruritus is histamine-mediated.

Capsaicin may be useful in the treatment of localized neuropathic pruritus.

In cases of neurogenic pruritus, gabapentin and pregabalin may be prescribed, but tolerance can be problematic at this age. Other measures include acupuncture, cryotherapy, relaxation, hypnosis, psychotherapy, and music therapy. In cases of repeated therapeutic failure, patients may be treated with biotherapy (dupilumab) by a dermatologist.

 

This story was translated from Medscape’s 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.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany 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.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany 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.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany 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.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

NEW YORK — Over the past year, new evidence has emerged in support of the idea that psoriatic arthritis (PsA) is neither exclusively immune mediated nor a classic autoimmune disease, but that both mechanisms may be essential in disease pathogenesis, and that innate immune cells may possess adaptive properties that may lead to worsening of inflammation of the skin and joints.

Recent findings help dermatologists and rheumatologists to better understand the pathogenesis of PsA and may lead to more targeted and personalized therapies, Christopher Ritchlin, MD, MPH, who’s led research into the pathogenesis of inflammatory diseases, reported at the NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis.

Psoriasis and PsA, along with ankylosing spondylitis and Crohn’s disease, have been thought to be either immune mediated or a classic autoimmune disorder, Ritchlin, a rheumatologist and internist and director of the Clinical Immunology Research Unit at the University of Rochester in New York, said in an interview. “But emerging data reveal that these disorders might be triggered and sustained by both autoimmune and immune-mediated events,” he said.

 

Autoimmunity vs Immune Mediated

Autoimmune diseases are characterized by a specific autoantigen and antibody, such as the anti–cyclic citrullinated peptide antibody seen in rheumatoid arthritis, Ritchlin said. He cited a 2023 literature review from Italy that identified five autoantibodies and polymorphisms in PsA.

“In an immune-mediated disease, we demonstrate profound dysregulation of immune cells that promote inflammation, but we have not identified a specific autoantigen,” he said. “There’s an inflammatory response, which can be very severe, but we don’t know if it’s responding to an autoantigen or it’s just dysregulation of the T cells or the B cells or both.”

In a humanized mouse model developed by Maria Garcia-Hernandez, PhD, in Ritchlin’s lab, researchers found that both immunoglobulins and immune cells are required to recapitulate the skin and joint phenotypes. Ritchlin said that further analyses identified a putative autoantigen, which current experiments now underway are looking to confirm and should help discern distinctions in pathogenesis between a response to an autoantigen or cell dysregulation.

“There may be more than one type of immune inflammatory reaction that’s ongoing in individual tissue, and it may be different from one tissue to another,” Ritchlin said in an interview.

The immune-mediated and autoimmune properties of PsA are important to investigate, Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City, said in an interview.

“Classically considered an autoimmune disease, [PsA] may be better classified as an immune-mediated inflammatory disease,” Scher said. He noted one feature that makes PsA differ from classic autoimmunity is that it does not affect women predominantly.

“The fundamental question is whether there are elements of classic autoimmunity such as B cells that should be integrated into the research for future identification of novel therapeutics,” Scher said.

 

The ‘Additional Mechanism’

The additional mechanism Ritchlin referred to is “this idea of trained immunity,” he said, “where innate immune cells — fibroblasts, monocytes, keratinocytes — that are not considered to have [the] adaptive memory characteristic of T cells and B cells but act in an environment of inflammation and can actually develop sustained altered phenotypes in response to inflammation.”

A 2024 report from Europe outlined four characteristics of trained immunity, Ritchlin said, including that it is “antigen agnostic” and results from long-term reprogramming of cells through epigenetic and metabolic mechanisms. The effects of trained immunity are shorter in duration than that of classical adaptive immunity, he said.

These reprogrammed innate immune cells “retain a form of ‘memory’ after an initial stimulus, which can lead to enhanced or altered responses upon subsequent challenges,” Scher said.

In the context of PsA, Scher said, monocytes that express heightened inflammatory responses driven by metabolic and epigenetic reprogramming can become “trained” by triggers such as infections, cytokines (such as interleukin [IL]–1 beta and IL-17), or damage-associated molecular patterns that have been epigenetically modified to respond at higher rates in a future encounter with exacerbated production of proinflammatory cytokines, persistent inflammation, and flares.

Ritchlin explained how this emerging understanding of the mechanisms driving psoriasis and PsA is driving research into treatments.

“If you know that monocytes are undergoing change — these are innate cells, they’re not antigen driven — but that change is based on some type of pathway that makes the cell more inflammatory, then you can think about trying to block that pathway,” he said.

The goal would be to normalize the cellular environment that’s otherwise becoming activated to create the signs and symptoms of psoriasis and PsA, he said.

The other potential therapeutic target would be T cells, Ritchlin said. “There now are T cells that have been identified that have very specific alpha-beta receptors that are expanded in the peripheral blood, uveal fluid, and joints of HLAB27-positive patients with ankylosing spondylitis and anterior uveitis, which is thought to be immune mediated, not autoimmune.” 

Those HLAB27-positive patients “have expansion of a certain subtype of T cells, they have a specific receptor, and specific autoantigens have been identified pointing to a potential autoimmune response,” Ritchlin added.

An antibody that binds and removes specific T-cell receptor subsets may be an effective strategy without being immunosuppressive, Ritchlin said. “That’s real exciting, and we’re all hoping that is going to be a therapeutic approach that could be successful.”

Ritchlin disclosed financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

A version of this article appeared on Medscape.com.

NEW YORK — Over the past year, new evidence has emerged in support of the idea that psoriatic arthritis (PsA) is neither exclusively immune mediated nor a classic autoimmune disease, but that both mechanisms may be essential in disease pathogenesis, and that innate immune cells may possess adaptive properties that may lead to worsening of inflammation of the skin and joints.

Recent findings help dermatologists and rheumatologists to better understand the pathogenesis of PsA and may lead to more targeted and personalized therapies, Christopher Ritchlin, MD, MPH, who’s led research into the pathogenesis of inflammatory diseases, reported at the NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis.

Psoriasis and PsA, along with ankylosing spondylitis and Crohn’s disease, have been thought to be either immune mediated or a classic autoimmune disorder, Ritchlin, a rheumatologist and internist and director of the Clinical Immunology Research Unit at the University of Rochester in New York, said in an interview. “But emerging data reveal that these disorders might be triggered and sustained by both autoimmune and immune-mediated events,” he said.

 

Autoimmunity vs Immune Mediated

Autoimmune diseases are characterized by a specific autoantigen and antibody, such as the anti–cyclic citrullinated peptide antibody seen in rheumatoid arthritis, Ritchlin said. He cited a 2023 literature review from Italy that identified five autoantibodies and polymorphisms in PsA.

“In an immune-mediated disease, we demonstrate profound dysregulation of immune cells that promote inflammation, but we have not identified a specific autoantigen,” he said. “There’s an inflammatory response, which can be very severe, but we don’t know if it’s responding to an autoantigen or it’s just dysregulation of the T cells or the B cells or both.”

In a humanized mouse model developed by Maria Garcia-Hernandez, PhD, in Ritchlin’s lab, researchers found that both immunoglobulins and immune cells are required to recapitulate the skin and joint phenotypes. Ritchlin said that further analyses identified a putative autoantigen, which current experiments now underway are looking to confirm and should help discern distinctions in pathogenesis between a response to an autoantigen or cell dysregulation.

“There may be more than one type of immune inflammatory reaction that’s ongoing in individual tissue, and it may be different from one tissue to another,” Ritchlin said in an interview.

The immune-mediated and autoimmune properties of PsA are important to investigate, Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City, said in an interview.

“Classically considered an autoimmune disease, [PsA] may be better classified as an immune-mediated inflammatory disease,” Scher said. He noted one feature that makes PsA differ from classic autoimmunity is that it does not affect women predominantly.

“The fundamental question is whether there are elements of classic autoimmunity such as B cells that should be integrated into the research for future identification of novel therapeutics,” Scher said.

 

The ‘Additional Mechanism’

The additional mechanism Ritchlin referred to is “this idea of trained immunity,” he said, “where innate immune cells — fibroblasts, monocytes, keratinocytes — that are not considered to have [the] adaptive memory characteristic of T cells and B cells but act in an environment of inflammation and can actually develop sustained altered phenotypes in response to inflammation.”

A 2024 report from Europe outlined four characteristics of trained immunity, Ritchlin said, including that it is “antigen agnostic” and results from long-term reprogramming of cells through epigenetic and metabolic mechanisms. The effects of trained immunity are shorter in duration than that of classical adaptive immunity, he said.

These reprogrammed innate immune cells “retain a form of ‘memory’ after an initial stimulus, which can lead to enhanced or altered responses upon subsequent challenges,” Scher said.

In the context of PsA, Scher said, monocytes that express heightened inflammatory responses driven by metabolic and epigenetic reprogramming can become “trained” by triggers such as infections, cytokines (such as interleukin [IL]–1 beta and IL-17), or damage-associated molecular patterns that have been epigenetically modified to respond at higher rates in a future encounter with exacerbated production of proinflammatory cytokines, persistent inflammation, and flares.

Ritchlin explained how this emerging understanding of the mechanisms driving psoriasis and PsA is driving research into treatments.

“If you know that monocytes are undergoing change — these are innate cells, they’re not antigen driven — but that change is based on some type of pathway that makes the cell more inflammatory, then you can think about trying to block that pathway,” he said.

The goal would be to normalize the cellular environment that’s otherwise becoming activated to create the signs and symptoms of psoriasis and PsA, he said.

The other potential therapeutic target would be T cells, Ritchlin said. “There now are T cells that have been identified that have very specific alpha-beta receptors that are expanded in the peripheral blood, uveal fluid, and joints of HLAB27-positive patients with ankylosing spondylitis and anterior uveitis, which is thought to be immune mediated, not autoimmune.” 

Those HLAB27-positive patients “have expansion of a certain subtype of T cells, they have a specific receptor, and specific autoantigens have been identified pointing to a potential autoimmune response,” Ritchlin added.

An antibody that binds and removes specific T-cell receptor subsets may be an effective strategy without being immunosuppressive, Ritchlin said. “That’s real exciting, and we’re all hoping that is going to be a therapeutic approach that could be successful.”

Ritchlin disclosed financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

A version of this article appeared on Medscape.com.

NEW YORK — Over the past year, new evidence has emerged in support of the idea that psoriatic arthritis (PsA) is neither exclusively immune mediated nor a classic autoimmune disease, but that both mechanisms may be essential in disease pathogenesis, and that innate immune cells may possess adaptive properties that may lead to worsening of inflammation of the skin and joints.

Recent findings help dermatologists and rheumatologists to better understand the pathogenesis of PsA and may lead to more targeted and personalized therapies, Christopher Ritchlin, MD, MPH, who’s led research into the pathogenesis of inflammatory diseases, reported at the NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis.

Psoriasis and PsA, along with ankylosing spondylitis and Crohn’s disease, have been thought to be either immune mediated or a classic autoimmune disorder, Ritchlin, a rheumatologist and internist and director of the Clinical Immunology Research Unit at the University of Rochester in New York, said in an interview. “But emerging data reveal that these disorders might be triggered and sustained by both autoimmune and immune-mediated events,” he said.

 

Autoimmunity vs Immune Mediated

Autoimmune diseases are characterized by a specific autoantigen and antibody, such as the anti–cyclic citrullinated peptide antibody seen in rheumatoid arthritis, Ritchlin said. He cited a 2023 literature review from Italy that identified five autoantibodies and polymorphisms in PsA.

“In an immune-mediated disease, we demonstrate profound dysregulation of immune cells that promote inflammation, but we have not identified a specific autoantigen,” he said. “There’s an inflammatory response, which can be very severe, but we don’t know if it’s responding to an autoantigen or it’s just dysregulation of the T cells or the B cells or both.”

In a humanized mouse model developed by Maria Garcia-Hernandez, PhD, in Ritchlin’s lab, researchers found that both immunoglobulins and immune cells are required to recapitulate the skin and joint phenotypes. Ritchlin said that further analyses identified a putative autoantigen, which current experiments now underway are looking to confirm and should help discern distinctions in pathogenesis between a response to an autoantigen or cell dysregulation.

“There may be more than one type of immune inflammatory reaction that’s ongoing in individual tissue, and it may be different from one tissue to another,” Ritchlin said in an interview.

The immune-mediated and autoimmune properties of PsA are important to investigate, Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City, said in an interview.

“Classically considered an autoimmune disease, [PsA] may be better classified as an immune-mediated inflammatory disease,” Scher said. He noted one feature that makes PsA differ from classic autoimmunity is that it does not affect women predominantly.

“The fundamental question is whether there are elements of classic autoimmunity such as B cells that should be integrated into the research for future identification of novel therapeutics,” Scher said.

 

The ‘Additional Mechanism’

The additional mechanism Ritchlin referred to is “this idea of trained immunity,” he said, “where innate immune cells — fibroblasts, monocytes, keratinocytes — that are not considered to have [the] adaptive memory characteristic of T cells and B cells but act in an environment of inflammation and can actually develop sustained altered phenotypes in response to inflammation.”

A 2024 report from Europe outlined four characteristics of trained immunity, Ritchlin said, including that it is “antigen agnostic” and results from long-term reprogramming of cells through epigenetic and metabolic mechanisms. The effects of trained immunity are shorter in duration than that of classical adaptive immunity, he said.

These reprogrammed innate immune cells “retain a form of ‘memory’ after an initial stimulus, which can lead to enhanced or altered responses upon subsequent challenges,” Scher said.

In the context of PsA, Scher said, monocytes that express heightened inflammatory responses driven by metabolic and epigenetic reprogramming can become “trained” by triggers such as infections, cytokines (such as interleukin [IL]–1 beta and IL-17), or damage-associated molecular patterns that have been epigenetically modified to respond at higher rates in a future encounter with exacerbated production of proinflammatory cytokines, persistent inflammation, and flares.

Ritchlin explained how this emerging understanding of the mechanisms driving psoriasis and PsA is driving research into treatments.

“If you know that monocytes are undergoing change — these are innate cells, they’re not antigen driven — but that change is based on some type of pathway that makes the cell more inflammatory, then you can think about trying to block that pathway,” he said.

The goal would be to normalize the cellular environment that’s otherwise becoming activated to create the signs and symptoms of psoriasis and PsA, he said.

The other potential therapeutic target would be T cells, Ritchlin said. “There now are T cells that have been identified that have very specific alpha-beta receptors that are expanded in the peripheral blood, uveal fluid, and joints of HLAB27-positive patients with ankylosing spondylitis and anterior uveitis, which is thought to be immune mediated, not autoimmune.” 

Those HLAB27-positive patients “have expansion of a certain subtype of T cells, they have a specific receptor, and specific autoantigens have been identified pointing to a potential autoimmune response,” Ritchlin added.

An antibody that binds and removes specific T-cell receptor subsets may be an effective strategy without being immunosuppressive, Ritchlin said. “That’s real exciting, and we’re all hoping that is going to be a therapeutic approach that could be successful.”

Ritchlin disclosed financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

The newer biologics — interleukin (IL)–17, IL-12/23, and IL-23 inhibitors — demonstrate comparable cardiovascular safety profiles to tumor necrosis factor (TNF) inhibitors in biologic-naive patients with psoriasis or psoriatic arthritis (PsA).

METHODOLOGY:

• In a retrospective cohort study, researchers conducted an emulated target trial analysis using data of 32,098 biologic-naive patients with psoriasis or PsA who were treated with one of the newer biologics (infliximab, adalimumab, etanercept, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, and tildrakizumab) from the TriNetX Research Network between 2014 and 2022.
• Patients received TNF inhibitors (n = 20,314), IL-17 inhibitors (n = 5073), IL-12/23 inhibitors (n = 3573), or IL-23 inhibitors (n = 3138).
• A propensity-matched analysis compared each class of newer biologics with TNF inhibitors, adjusting for demographics, comorbidities, and medication use.
• The primary outcomes were major adverse cardiovascular events (MACE; myocardial infarction and stroke) or venous thromboembolic events (VTE).

TAKEAWAY:

• Compared with patients who received TNF inhibitors, the risk for MACE was not significantly different between patients who received IL-17 inhibitors (incidence rate ratio [IRR], 1.14; 95% CI, 0.86-1.52), IL-12/23 inhibitors (IRR, 1.24; 95% CI, 0.84-1.78), or IL-23 inhibitors (IRR, 0.93; 95% CI, 0.61-1.38)
• The VTE risk was also not significantly different between patients who received IL-17 inhibitors (IRR, 1.12; 95% CI, 0.63-2.08), IL-12/23 inhibitors (IRR, 1.51; 95% CI, 0.73-3.19), or IL-23 inhibitors (IRR, 1.42; 95% CI, 0.64-3.25) compared with those who received TNF inhibitors.
• Subgroup analyses for psoriasis or psoriatic arthritis alone confirmed consistent findings.
• Patients with preexisting hyperlipidemia and diabetes mellitus showed lower risks for MACE and VTE with newer biologics compared with TNF inhibitors. 

IN PRACTICE:

“No significant MACE and VTE risk differences were detected in patients with psoriasis or PsA between those receiving IL-17, IL-12/23, and IL-23 inhibitors and those with TNF inhibitors,” the authors concluded. These findings, they added “can be considered by physicians and patients when making treatment decisions” and also provide “evidence for future pharmacovigilance studies.”

SOURCE:

The study was led by Tai-Li Chen, MD, of the Department of Dermatology, Taipei Veterans General Hospital in Taipei, Taiwan. It was published online on December 27, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included potential residual confounding factors, lack of information on disease severity, and inclusion of predominantly White individuals.

DISCLOSURES:

The study received support from Taipei Veterans General Hospital and Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

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

TOPLINE:

The newer biologics — interleukin (IL)–17, IL-12/23, and IL-23 inhibitors — demonstrate comparable cardiovascular safety profiles to tumor necrosis factor (TNF) inhibitors in biologic-naive patients with psoriasis or psoriatic arthritis (PsA).

METHODOLOGY:

• In a retrospective cohort study, researchers conducted an emulated target trial analysis using data of 32,098 biologic-naive patients with psoriasis or PsA who were treated with one of the newer biologics (infliximab, adalimumab, etanercept, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, and tildrakizumab) from the TriNetX Research Network between 2014 and 2022.
• Patients received TNF inhibitors (n = 20,314), IL-17 inhibitors (n = 5073), IL-12/23 inhibitors (n = 3573), or IL-23 inhibitors (n = 3138).
• A propensity-matched analysis compared each class of newer biologics with TNF inhibitors, adjusting for demographics, comorbidities, and medication use.
• The primary outcomes were major adverse cardiovascular events (MACE; myocardial infarction and stroke) or venous thromboembolic events (VTE).

TAKEAWAY:

• Compared with patients who received TNF inhibitors, the risk for MACE was not significantly different between patients who received IL-17 inhibitors (incidence rate ratio [IRR], 1.14; 95% CI, 0.86-1.52), IL-12/23 inhibitors (IRR, 1.24; 95% CI, 0.84-1.78), or IL-23 inhibitors (IRR, 0.93; 95% CI, 0.61-1.38)
• The VTE risk was also not significantly different between patients who received IL-17 inhibitors (IRR, 1.12; 95% CI, 0.63-2.08), IL-12/23 inhibitors (IRR, 1.51; 95% CI, 0.73-3.19), or IL-23 inhibitors (IRR, 1.42; 95% CI, 0.64-3.25) compared with those who received TNF inhibitors.
• Subgroup analyses for psoriasis or psoriatic arthritis alone confirmed consistent findings.
• Patients with preexisting hyperlipidemia and diabetes mellitus showed lower risks for MACE and VTE with newer biologics compared with TNF inhibitors. 

IN PRACTICE:

“No significant MACE and VTE risk differences were detected in patients with psoriasis or PsA between those receiving IL-17, IL-12/23, and IL-23 inhibitors and those with TNF inhibitors,” the authors concluded. These findings, they added “can be considered by physicians and patients when making treatment decisions” and also provide “evidence for future pharmacovigilance studies.”

SOURCE:

The study was led by Tai-Li Chen, MD, of the Department of Dermatology, Taipei Veterans General Hospital in Taipei, Taiwan. It was published online on December 27, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included potential residual confounding factors, lack of information on disease severity, and inclusion of predominantly White individuals.

DISCLOSURES:

The study received support from Taipei Veterans General Hospital and Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

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

TOPLINE:

The newer biologics — interleukin (IL)–17, IL-12/23, and IL-23 inhibitors — demonstrate comparable cardiovascular safety profiles to tumor necrosis factor (TNF) inhibitors in biologic-naive patients with psoriasis or psoriatic arthritis (PsA).

METHODOLOGY:

• In a retrospective cohort study, researchers conducted an emulated target trial analysis using data of 32,098 biologic-naive patients with psoriasis or PsA who were treated with one of the newer biologics (infliximab, adalimumab, etanercept, certolizumab pegol, secukinumab, ixekizumab, brodalumab, ustekinumab, risankizumab, guselkumab, and tildrakizumab) from the TriNetX Research Network between 2014 and 2022.
• Patients received TNF inhibitors (n = 20,314), IL-17 inhibitors (n = 5073), IL-12/23 inhibitors (n = 3573), or IL-23 inhibitors (n = 3138).
• A propensity-matched analysis compared each class of newer biologics with TNF inhibitors, adjusting for demographics, comorbidities, and medication use.
• The primary outcomes were major adverse cardiovascular events (MACE; myocardial infarction and stroke) or venous thromboembolic events (VTE).

TAKEAWAY:

• Compared with patients who received TNF inhibitors, the risk for MACE was not significantly different between patients who received IL-17 inhibitors (incidence rate ratio [IRR], 1.14; 95% CI, 0.86-1.52), IL-12/23 inhibitors (IRR, 1.24; 95% CI, 0.84-1.78), or IL-23 inhibitors (IRR, 0.93; 95% CI, 0.61-1.38)
• The VTE risk was also not significantly different between patients who received IL-17 inhibitors (IRR, 1.12; 95% CI, 0.63-2.08), IL-12/23 inhibitors (IRR, 1.51; 95% CI, 0.73-3.19), or IL-23 inhibitors (IRR, 1.42; 95% CI, 0.64-3.25) compared with those who received TNF inhibitors.
• Subgroup analyses for psoriasis or psoriatic arthritis alone confirmed consistent findings.
• Patients with preexisting hyperlipidemia and diabetes mellitus showed lower risks for MACE and VTE with newer biologics compared with TNF inhibitors. 

IN PRACTICE:

“No significant MACE and VTE risk differences were detected in patients with psoriasis or PsA between those receiving IL-17, IL-12/23, and IL-23 inhibitors and those with TNF inhibitors,” the authors concluded. These findings, they added “can be considered by physicians and patients when making treatment decisions” and also provide “evidence for future pharmacovigilance studies.”

SOURCE:

The study was led by Tai-Li Chen, MD, of the Department of Dermatology, Taipei Veterans General Hospital in Taipei, Taiwan. It was published online on December 27, 2024, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

Study limitations included potential residual confounding factors, lack of information on disease severity, and inclusion of predominantly White individuals.

DISCLOSURES:

The study received support from Taipei Veterans General Hospital and Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

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

The cutting edge of treating solid tumors with cell therapies got notably sharper in 2024.

First came the US Food and Drug Administration (FDA) approval in February 2024 of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel in unresectable or metastatic melanoma that had progressed on prior immunotherapy, the first cellular therapy for any solid tumor. Then came the August FDA approval of afamitresgene autoleucel in unresectable or metastatic synovial sarcoma with failed chemotherapy, the first engineered T-cell therapy for cancers in soft tissue. 

“This was a pipe dream just a decade ago,” Alison Betof Warner, MD, PhD, lead author of a lifileucel study (NCT05640193), said in an interview with Medscape Medical News. “At the start of 2024, we had no approvals of these kinds of products in solid cancers. Now we have two.”

As the director of Solid Tumor Cell Therapy and leader of Stanford Medicine’s Melanoma and Cutaneous Oncology Clinical Research Group, Betof Warner has been at the forefront of developing commercial cell therapy using tumor-infiltrating lymphocytes (TILs). 

“The approval of lifileucel increases confidence that we can get these therapies across the regulatory finish line and to patients,” Betof Warner said during the interview. She was not involved in the development of afamitresgene autoleucel.

 

‘Reverse Engineering’

In addition to her contributions to the work that led to lifileucel’s approval, Betof Warner was the lead author on the first consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy. 

Betof Warner began studying TILs after doing research with her mentors in immuno-oncology, Jedd D. Wolchok and Michael A. Postow. Their investigations — including one that Betof Warner coauthored — into how monoclonal antibodies and checkpoint inhibitors, such as ipilimumab or nivolumab, might extend the lives of people with advanced unresectable or metastatic melanoma inspired her to push further to find ways to minimize treatment while maximizing outcomes for patients. Betof Warner’s interest overall, she said in the interview, is in capitalizing on what can be learned about how the immune system controls cancer.

“What we know is that the immune system has the ability to kill cancer,” Betof Warner said. “Therefore we need to be thinking about how we can increase immune surveillance. How can we enhance that before a patient develops advanced cancer? 

Betof Warner said that although TILs are now standard treatment in melanoma, there is about a 30% response rate compared with about a 50% response rate in immunotherapy, and the latter is easier for the patient to withstand. 

“Antibodies on the frontline are better than going through a surgery and then waiting weeks to get your therapy,” Betof Warner said in the interview. “You can come into my clinic and get an antibody therapy in 30 minutes and go straight to work. TILs require patients to be in the hospital for weeks at a time and out of work for months at a time.”

In an effort to combine therapies to maximize best outcomes, a phase 3 trial (NCT05727904) is currently recruiting. The TILVANCE-301 trial will compare immunotherapy plus adoptive cell therapy vs immunotherapy alone in untreated unresectable or metastatic melanoma. Betof Warner is not a part of this study.

 

Cell Therapies Include CAR T Cells and TCRT

In general, adoptive T-cell therapies such as TILs involve the isolation of autologous immune cells that are removed from the body and either expanded or modified to optimize their efficacy in fighting antigens, before their transfer to the patient as a living drug by infusion.

In addition to TILs, adoptive cell therapies for antitumor therapeutics include chimeric antigen receptor (CAR) T cells and engineered T-cell receptor therapy (TCRT).

In CAR T-cell therapy and TCRT, naive T cells are harvested from the patient’s blood then engineered to target a tumor. In TIL therapy, tumor-specific T cells are taken from the patient’s tumor. Once extracted, the respective cells are expanded billions of times and then delivered back to the patient’s body, said Betof Warner. 

“The main promise of this approach is to generate responses in what we know as ‘cold’ tumors, or tumors that do not have a lot of endogenous T-cell infiltration or where the T cells are not working well, to bring in tumor targeting T cells and then trigger an immune response,” Betof Warner told an audience at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.

TIL patients also receive interleukin (IL)-2 infusions to further stimulate the cells. In patients being treated with TCRT, they either receive low or no IL-2, Betof Warner said in her ASCO presentation, “Adopting Cutting-Edge Cell Therapies in Melanoma,” part of the session Beyond the Tip of the Iceberg: Next-Generation Cell-Based Therapies. 

Betof Warner takes Medscape Medical News through the history and ongoing investigations of cellular therapies for solid tumors, including her own research on these treatments. 

 

Decades in the Making

The National Cancer Institute began investigating TILs in the late 1980s, with the current National Cancer Institute (NCI) surgery chief, Steven Rosenberg, MD, PhD, leading the first-ever trials that showed TILs could shrink tumors in people with advanced melanoma.

Since then, NCI staff and others have also investigated TILs beyond melanoma and additional cell therapies based on CAR T cells and TCRT for antitumor therapeutics. 

“TCRs are different from CAR Ts because they go after intracellular antigens instead of extracellular antigens,” said Betof Warner. “That has appeal because many of the tumor antigens we’re looking for will be intracellular.” 

Because CAR T cells only target extracellular antigens, their utility is somewhat limited. Although several CAR T-cell therapies exist for blood cancers, there currently are no approved CAR T-cell therapies for solid tumors. However, several trials of CAR T cells in gastrointestinal cancers and melanoma are ongoing, said Betof Warner, who is not a part of these studies.

“We are starting to see early-phase efficacy in pediatric gliomas,” Betof Warner said, mentioning a study conducted by colleagues at Stanford who demonstrated potential for anti-GD2 CAR T-cell therapy in deadly pediatric diffuse midline gliomas, tumors on the spine and brain.

In their study, nine out of 11 participants (median age, 15 years) showed benefit from the cell therapy, with one participant’s tumors resolving completely. The results paved the way for the FDA to grant a Regenerative Medicine Advanced Therapy designation for use of anti-GD2 CAR T cells in H3K27M-positive diffuse midline gliomas. 

The investigators are now recruiting for a phase 1 trial (NCT04196413). Results of the initial study were published in Nature last month.

Another lesser-known cell therapy expected to advance at some point in the future for solid tumors is use of the body’s natural killer (NK) cells. “They’ve been known about for a long time, but they are more difficult to regulate, which is one reason why it has taken longer to make NK cell therapies,” said Betof Warner, who is not involved in the study of NK cells. “One of their advantages is that, potentially, there could be an ‘off the shelf’ NK product. They don’t necessarily have to be made with autologous cells.”

 

Risk-Benefit Profiles Depend on Mechanism of Action

If the corresponding TCR sequence of a tumor antigen is known, said Betof Warner, it is possible to use leukapheresis to generate naive circulating lymphocytes. Once infused, the manufactured TCRTs will activate in the body the same as native cells because the signaling is the same.
An advantage to TCRT compared with CAR T-cell therapy is that it targets intracellular proteins, which are significantly present in the tumor, Betof Warner said in her presentation at ASCO 2024. She clarified that tumors will usually be screened for the presence of this antigen before a patient is selected for treatment with that particular therapy, because not all antigens are highly expressed in every tumor. 

“Furthermore, the tumor antigen has to be presented by a major histocompatibility complex, meaning there are human leukocyte antigen restrictions, which impacts patient selection,” she said.

A risk with both TCRT and CAR T-cell therapy, according to Betof Warner, is that because there are often shared antigens between tumor and normal tissues, on-target/off-tumor toxicity is a risk.

“TILs are different because they are nonengineered, at least not for antigen recognition. They are polyclonal and go after multiple targets,” Betof Warner said. “TCRs and CARs are engineered to go after one target. So, TILs have much lower rates of on-tumor/off-target effects, vs when you engineer a very high affinity receptor like a TCR or CAR.”

A good example of how this amplification of TCR affinity can lead to poor outcomes is in metastatic melanoma, said Betof Warner. 

In investigations (NCI-07-C-0174 and NCI-07-C-0175) of TCRT in metastatic melanoma, for example, the researchers were targeting MART-1 or gp100, which are expressed in melanocytes. 

“The problem was that these antigens are also expressed in the eyes and ears, so it caused eye inflammation and hearing loss in a number of patients because it wasn’t specific enough for the tumor,” said Betof Warner. “So, if that target is highly expressed on normal tissue, then you have a high risk.”

 

Promise of PRAME

Betof Warner said the most promising TCRT at present is the investigational autologous cell therapy IMA203 (NCT03688124), which targets the preferentially expressed antigen (PRAME). Although PRAME is found in many tumors, this testis antigen does not tend to express in normal, healthy adult tissues. Betof Warner is not affiliated with this study. 

“It’s maybe the most exciting TCRT cell in melanoma,” Betof Warner told her audience at the ASCO 2024 meeting. Because the expression rate of PRAME in cutaneous and uveal melanoma is at or above 95% and 90%, respectively, she said “it is a really good target in melanoma.”

Phase 1a results reported in late 2023 from a first-in-human trial of IMA203 involving 13 persons with highly advanced melanoma and a median of 5.5 previous treatments showed a 50% objective response rate in the 12 evaluable results. The duration of response ranged between 2.2 and 14.7 months (median follow-up, 14 months).

The safety profile of the treatment was favorable, with no grade 3 adverse events occurring in more than 10% of the cohort, and no grade 5 adverse events at all.

Phase 1b results published in October by maker Immatics showed that in 28 heavily pretreated metastatic melanoma patients, IMA203 had a confirmed objective response rate of 54% with a median duration of response of 12.1 months, while maintaining a favorable tolerability profile. 

 

Accelerated Approvals, Boxed Warnings

The FDA granted accelerated approvals for both lifileucel, the TIL therapy, and afamitresgene autoleucel, the TCRT. 

Both were approved with boxed warnings. Lifileucel’s warning is for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Afamitresgene autoleucel’s boxed warning is for serious or fatal cytokine release syndrome, which may be severe or life-threatening.

With these approvals, the bar is now raised on TILs and TCRTs, said Betof Warner.

The lifileucel trial studied 73 patients whose melanoma had continued to metastasize despite treatment with a programmed cell death protein (PD-1)/ programmed death-ligand (PD-L1)–targeted immune checkpoint inhibitor and a BRAF inhibitor (if appropriate based on tumor mutation status), and whose lifileucel dose was at least 7.5 billion cells (the approved dose). The cohort also received a median of six IL-2 (aldesleukin) doses. 

The objective response rate was 31.5% (95% CI, 21.1-43.4), and median duration of response was not reached (lower bound of 95% CI, 4.1).

In the afamitresgene autoleucel study, 44 of 52 patients with synovial sarcoma received leukapheresis and a single infusion of afamitresgene autoleucel. 

The overall response rate was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8), and the median duration of response was 6 months (lower bound of 95% CI, 4.6). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response of 6 months or longer and 12 months or longer, respectively.

 

New Hope for Patients

Betof Warner and her colleagues are now recruiting for an open-label, phase 1/2 investigation of the safety and efficacy of the TIL therapy OBX-115 in adult advanced solid tumors in melanoma or non–small cell lung cancer. The first-in-human results of a previous trial were presented at the ASCO 2024 meeting, and OBX-115 received FDA fast track designation in July.

“I think the results are really promising,” said Betof Warner. “This is an engineered TIL that does not require administering IL-2 to the patient. There were four out of the nine patients who responded to the treatment and there were no dose-limiting toxicities, no cytokine and no intracranial — all of which is excellent.”

For Betof Warner, the possibility that by using their own immune system, patients with advanced and refractory cancers could soon have a one-time treatment with a cell therapy rather than innumerable bouts of chemotherapy pushes her onward.

“The idea that we can treat cancer one time and have it not recur for years — that’s pushing the start of saying there’s a cure of cancer. That a person could move on from cancer like they move on from an infection. That is the potential of this work. We’re not there yet, but that’s where we need to think and dream big,” she said.

Betof Warner disclosed consulting/advisory roles with BluePath Solutions, Bristol-Myers Squibb/Medarex, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Merck, Novartis, and Pfizer and research funding and travel expenses from Iovance Biotherapeutics.

 

A version of this article appeared on Medscape.com.

The cutting edge of treating solid tumors with cell therapies got notably sharper in 2024.

First came the US Food and Drug Administration (FDA) approval in February 2024 of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel in unresectable or metastatic melanoma that had progressed on prior immunotherapy, the first cellular therapy for any solid tumor. Then came the August FDA approval of afamitresgene autoleucel in unresectable or metastatic synovial sarcoma with failed chemotherapy, the first engineered T-cell therapy for cancers in soft tissue. 

“This was a pipe dream just a decade ago,” Alison Betof Warner, MD, PhD, lead author of a lifileucel study (NCT05640193), said in an interview with Medscape Medical News. “At the start of 2024, we had no approvals of these kinds of products in solid cancers. Now we have two.”

As the director of Solid Tumor Cell Therapy and leader of Stanford Medicine’s Melanoma and Cutaneous Oncology Clinical Research Group, Betof Warner has been at the forefront of developing commercial cell therapy using tumor-infiltrating lymphocytes (TILs). 

“The approval of lifileucel increases confidence that we can get these therapies across the regulatory finish line and to patients,” Betof Warner said during the interview. She was not involved in the development of afamitresgene autoleucel.

 

‘Reverse Engineering’

In addition to her contributions to the work that led to lifileucel’s approval, Betof Warner was the lead author on the first consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy. 

Betof Warner began studying TILs after doing research with her mentors in immuno-oncology, Jedd D. Wolchok and Michael A. Postow. Their investigations — including one that Betof Warner coauthored — into how monoclonal antibodies and checkpoint inhibitors, such as ipilimumab or nivolumab, might extend the lives of people with advanced unresectable or metastatic melanoma inspired her to push further to find ways to minimize treatment while maximizing outcomes for patients. Betof Warner’s interest overall, she said in the interview, is in capitalizing on what can be learned about how the immune system controls cancer.

“What we know is that the immune system has the ability to kill cancer,” Betof Warner said. “Therefore we need to be thinking about how we can increase immune surveillance. How can we enhance that before a patient develops advanced cancer? 

Betof Warner said that although TILs are now standard treatment in melanoma, there is about a 30% response rate compared with about a 50% response rate in immunotherapy, and the latter is easier for the patient to withstand. 

“Antibodies on the frontline are better than going through a surgery and then waiting weeks to get your therapy,” Betof Warner said in the interview. “You can come into my clinic and get an antibody therapy in 30 minutes and go straight to work. TILs require patients to be in the hospital for weeks at a time and out of work for months at a time.”

In an effort to combine therapies to maximize best outcomes, a phase 3 trial (NCT05727904) is currently recruiting. The TILVANCE-301 trial will compare immunotherapy plus adoptive cell therapy vs immunotherapy alone in untreated unresectable or metastatic melanoma. Betof Warner is not a part of this study.

 

Cell Therapies Include CAR T Cells and TCRT

In general, adoptive T-cell therapies such as TILs involve the isolation of autologous immune cells that are removed from the body and either expanded or modified to optimize their efficacy in fighting antigens, before their transfer to the patient as a living drug by infusion.

In addition to TILs, adoptive cell therapies for antitumor therapeutics include chimeric antigen receptor (CAR) T cells and engineered T-cell receptor therapy (TCRT).

In CAR T-cell therapy and TCRT, naive T cells are harvested from the patient’s blood then engineered to target a tumor. In TIL therapy, tumor-specific T cells are taken from the patient’s tumor. Once extracted, the respective cells are expanded billions of times and then delivered back to the patient’s body, said Betof Warner. 

“The main promise of this approach is to generate responses in what we know as ‘cold’ tumors, or tumors that do not have a lot of endogenous T-cell infiltration or where the T cells are not working well, to bring in tumor targeting T cells and then trigger an immune response,” Betof Warner told an audience at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.

TIL patients also receive interleukin (IL)-2 infusions to further stimulate the cells. In patients being treated with TCRT, they either receive low or no IL-2, Betof Warner said in her ASCO presentation, “Adopting Cutting-Edge Cell Therapies in Melanoma,” part of the session Beyond the Tip of the Iceberg: Next-Generation Cell-Based Therapies. 

Betof Warner takes Medscape Medical News through the history and ongoing investigations of cellular therapies for solid tumors, including her own research on these treatments. 

 

Decades in the Making

The National Cancer Institute began investigating TILs in the late 1980s, with the current National Cancer Institute (NCI) surgery chief, Steven Rosenberg, MD, PhD, leading the first-ever trials that showed TILs could shrink tumors in people with advanced melanoma.

Since then, NCI staff and others have also investigated TILs beyond melanoma and additional cell therapies based on CAR T cells and TCRT for antitumor therapeutics. 

“TCRs are different from CAR Ts because they go after intracellular antigens instead of extracellular antigens,” said Betof Warner. “That has appeal because many of the tumor antigens we’re looking for will be intracellular.” 

Because CAR T cells only target extracellular antigens, their utility is somewhat limited. Although several CAR T-cell therapies exist for blood cancers, there currently are no approved CAR T-cell therapies for solid tumors. However, several trials of CAR T cells in gastrointestinal cancers and melanoma are ongoing, said Betof Warner, who is not a part of these studies.

“We are starting to see early-phase efficacy in pediatric gliomas,” Betof Warner said, mentioning a study conducted by colleagues at Stanford who demonstrated potential for anti-GD2 CAR T-cell therapy in deadly pediatric diffuse midline gliomas, tumors on the spine and brain.

In their study, nine out of 11 participants (median age, 15 years) showed benefit from the cell therapy, with one participant’s tumors resolving completely. The results paved the way for the FDA to grant a Regenerative Medicine Advanced Therapy designation for use of anti-GD2 CAR T cells in H3K27M-positive diffuse midline gliomas. 

The investigators are now recruiting for a phase 1 trial (NCT04196413). Results of the initial study were published in Nature last month.

Another lesser-known cell therapy expected to advance at some point in the future for solid tumors is use of the body’s natural killer (NK) cells. “They’ve been known about for a long time, but they are more difficult to regulate, which is one reason why it has taken longer to make NK cell therapies,” said Betof Warner, who is not involved in the study of NK cells. “One of their advantages is that, potentially, there could be an ‘off the shelf’ NK product. They don’t necessarily have to be made with autologous cells.”

 

Risk-Benefit Profiles Depend on Mechanism of Action

If the corresponding TCR sequence of a tumor antigen is known, said Betof Warner, it is possible to use leukapheresis to generate naive circulating lymphocytes. Once infused, the manufactured TCRTs will activate in the body the same as native cells because the signaling is the same.
An advantage to TCRT compared with CAR T-cell therapy is that it targets intracellular proteins, which are significantly present in the tumor, Betof Warner said in her presentation at ASCO 2024. She clarified that tumors will usually be screened for the presence of this antigen before a patient is selected for treatment with that particular therapy, because not all antigens are highly expressed in every tumor. 

“Furthermore, the tumor antigen has to be presented by a major histocompatibility complex, meaning there are human leukocyte antigen restrictions, which impacts patient selection,” she said.

A risk with both TCRT and CAR T-cell therapy, according to Betof Warner, is that because there are often shared antigens between tumor and normal tissues, on-target/off-tumor toxicity is a risk.

“TILs are different because they are nonengineered, at least not for antigen recognition. They are polyclonal and go after multiple targets,” Betof Warner said. “TCRs and CARs are engineered to go after one target. So, TILs have much lower rates of on-tumor/off-target effects, vs when you engineer a very high affinity receptor like a TCR or CAR.”

A good example of how this amplification of TCR affinity can lead to poor outcomes is in metastatic melanoma, said Betof Warner. 

In investigations (NCI-07-C-0174 and NCI-07-C-0175) of TCRT in metastatic melanoma, for example, the researchers were targeting MART-1 or gp100, which are expressed in melanocytes. 

“The problem was that these antigens are also expressed in the eyes and ears, so it caused eye inflammation and hearing loss in a number of patients because it wasn’t specific enough for the tumor,” said Betof Warner. “So, if that target is highly expressed on normal tissue, then you have a high risk.”

 

Promise of PRAME

Betof Warner said the most promising TCRT at present is the investigational autologous cell therapy IMA203 (NCT03688124), which targets the preferentially expressed antigen (PRAME). Although PRAME is found in many tumors, this testis antigen does not tend to express in normal, healthy adult tissues. Betof Warner is not affiliated with this study. 

“It’s maybe the most exciting TCRT cell in melanoma,” Betof Warner told her audience at the ASCO 2024 meeting. Because the expression rate of PRAME in cutaneous and uveal melanoma is at or above 95% and 90%, respectively, she said “it is a really good target in melanoma.”

Phase 1a results reported in late 2023 from a first-in-human trial of IMA203 involving 13 persons with highly advanced melanoma and a median of 5.5 previous treatments showed a 50% objective response rate in the 12 evaluable results. The duration of response ranged between 2.2 and 14.7 months (median follow-up, 14 months).

The safety profile of the treatment was favorable, with no grade 3 adverse events occurring in more than 10% of the cohort, and no grade 5 adverse events at all.

Phase 1b results published in October by maker Immatics showed that in 28 heavily pretreated metastatic melanoma patients, IMA203 had a confirmed objective response rate of 54% with a median duration of response of 12.1 months, while maintaining a favorable tolerability profile. 

 

Accelerated Approvals, Boxed Warnings

The FDA granted accelerated approvals for both lifileucel, the TIL therapy, and afamitresgene autoleucel, the TCRT. 

Both were approved with boxed warnings. Lifileucel’s warning is for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Afamitresgene autoleucel’s boxed warning is for serious or fatal cytokine release syndrome, which may be severe or life-threatening.

With these approvals, the bar is now raised on TILs and TCRTs, said Betof Warner.

The lifileucel trial studied 73 patients whose melanoma had continued to metastasize despite treatment with a programmed cell death protein (PD-1)/ programmed death-ligand (PD-L1)–targeted immune checkpoint inhibitor and a BRAF inhibitor (if appropriate based on tumor mutation status), and whose lifileucel dose was at least 7.5 billion cells (the approved dose). The cohort also received a median of six IL-2 (aldesleukin) doses. 

The objective response rate was 31.5% (95% CI, 21.1-43.4), and median duration of response was not reached (lower bound of 95% CI, 4.1).

In the afamitresgene autoleucel study, 44 of 52 patients with synovial sarcoma received leukapheresis and a single infusion of afamitresgene autoleucel. 

The overall response rate was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8), and the median duration of response was 6 months (lower bound of 95% CI, 4.6). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response of 6 months or longer and 12 months or longer, respectively.

 

New Hope for Patients

Betof Warner and her colleagues are now recruiting for an open-label, phase 1/2 investigation of the safety and efficacy of the TIL therapy OBX-115 in adult advanced solid tumors in melanoma or non–small cell lung cancer. The first-in-human results of a previous trial were presented at the ASCO 2024 meeting, and OBX-115 received FDA fast track designation in July.

“I think the results are really promising,” said Betof Warner. “This is an engineered TIL that does not require administering IL-2 to the patient. There were four out of the nine patients who responded to the treatment and there were no dose-limiting toxicities, no cytokine and no intracranial — all of which is excellent.”

For Betof Warner, the possibility that by using their own immune system, patients with advanced and refractory cancers could soon have a one-time treatment with a cell therapy rather than innumerable bouts of chemotherapy pushes her onward.

“The idea that we can treat cancer one time and have it not recur for years — that’s pushing the start of saying there’s a cure of cancer. That a person could move on from cancer like they move on from an infection. That is the potential of this work. We’re not there yet, but that’s where we need to think and dream big,” she said.

Betof Warner disclosed consulting/advisory roles with BluePath Solutions, Bristol-Myers Squibb/Medarex, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Merck, Novartis, and Pfizer and research funding and travel expenses from Iovance Biotherapeutics.

 

A version of this article appeared on Medscape.com.

The cutting edge of treating solid tumors with cell therapies got notably sharper in 2024.

First came the US Food and Drug Administration (FDA) approval in February 2024 of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel in unresectable or metastatic melanoma that had progressed on prior immunotherapy, the first cellular therapy for any solid tumor. Then came the August FDA approval of afamitresgene autoleucel in unresectable or metastatic synovial sarcoma with failed chemotherapy, the first engineered T-cell therapy for cancers in soft tissue. 

“This was a pipe dream just a decade ago,” Alison Betof Warner, MD, PhD, lead author of a lifileucel study (NCT05640193), said in an interview with Medscape Medical News. “At the start of 2024, we had no approvals of these kinds of products in solid cancers. Now we have two.”

As the director of Solid Tumor Cell Therapy and leader of Stanford Medicine’s Melanoma and Cutaneous Oncology Clinical Research Group, Betof Warner has been at the forefront of developing commercial cell therapy using tumor-infiltrating lymphocytes (TILs). 

“The approval of lifileucel increases confidence that we can get these therapies across the regulatory finish line and to patients,” Betof Warner said during the interview. She was not involved in the development of afamitresgene autoleucel.

 

‘Reverse Engineering’

In addition to her contributions to the work that led to lifileucel’s approval, Betof Warner was the lead author on the first consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy. 

Betof Warner began studying TILs after doing research with her mentors in immuno-oncology, Jedd D. Wolchok and Michael A. Postow. Their investigations — including one that Betof Warner coauthored — into how monoclonal antibodies and checkpoint inhibitors, such as ipilimumab or nivolumab, might extend the lives of people with advanced unresectable or metastatic melanoma inspired her to push further to find ways to minimize treatment while maximizing outcomes for patients. Betof Warner’s interest overall, she said in the interview, is in capitalizing on what can be learned about how the immune system controls cancer.

“What we know is that the immune system has the ability to kill cancer,” Betof Warner said. “Therefore we need to be thinking about how we can increase immune surveillance. How can we enhance that before a patient develops advanced cancer? 

Betof Warner said that although TILs are now standard treatment in melanoma, there is about a 30% response rate compared with about a 50% response rate in immunotherapy, and the latter is easier for the patient to withstand. 

“Antibodies on the frontline are better than going through a surgery and then waiting weeks to get your therapy,” Betof Warner said in the interview. “You can come into my clinic and get an antibody therapy in 30 minutes and go straight to work. TILs require patients to be in the hospital for weeks at a time and out of work for months at a time.”

In an effort to combine therapies to maximize best outcomes, a phase 3 trial (NCT05727904) is currently recruiting. The TILVANCE-301 trial will compare immunotherapy plus adoptive cell therapy vs immunotherapy alone in untreated unresectable or metastatic melanoma. Betof Warner is not a part of this study.

 

Cell Therapies Include CAR T Cells and TCRT

In general, adoptive T-cell therapies such as TILs involve the isolation of autologous immune cells that are removed from the body and either expanded or modified to optimize their efficacy in fighting antigens, before their transfer to the patient as a living drug by infusion.

In addition to TILs, adoptive cell therapies for antitumor therapeutics include chimeric antigen receptor (CAR) T cells and engineered T-cell receptor therapy (TCRT).

In CAR T-cell therapy and TCRT, naive T cells are harvested from the patient’s blood then engineered to target a tumor. In TIL therapy, tumor-specific T cells are taken from the patient’s tumor. Once extracted, the respective cells are expanded billions of times and then delivered back to the patient’s body, said Betof Warner. 

“The main promise of this approach is to generate responses in what we know as ‘cold’ tumors, or tumors that do not have a lot of endogenous T-cell infiltration or where the T cells are not working well, to bring in tumor targeting T cells and then trigger an immune response,” Betof Warner told an audience at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.

TIL patients also receive interleukin (IL)-2 infusions to further stimulate the cells. In patients being treated with TCRT, they either receive low or no IL-2, Betof Warner said in her ASCO presentation, “Adopting Cutting-Edge Cell Therapies in Melanoma,” part of the session Beyond the Tip of the Iceberg: Next-Generation Cell-Based Therapies. 

Betof Warner takes Medscape Medical News through the history and ongoing investigations of cellular therapies for solid tumors, including her own research on these treatments. 

 

Decades in the Making

The National Cancer Institute began investigating TILs in the late 1980s, with the current National Cancer Institute (NCI) surgery chief, Steven Rosenberg, MD, PhD, leading the first-ever trials that showed TILs could shrink tumors in people with advanced melanoma.

Since then, NCI staff and others have also investigated TILs beyond melanoma and additional cell therapies based on CAR T cells and TCRT for antitumor therapeutics. 

“TCRs are different from CAR Ts because they go after intracellular antigens instead of extracellular antigens,” said Betof Warner. “That has appeal because many of the tumor antigens we’re looking for will be intracellular.” 

Because CAR T cells only target extracellular antigens, their utility is somewhat limited. Although several CAR T-cell therapies exist for blood cancers, there currently are no approved CAR T-cell therapies for solid tumors. However, several trials of CAR T cells in gastrointestinal cancers and melanoma are ongoing, said Betof Warner, who is not a part of these studies.

“We are starting to see early-phase efficacy in pediatric gliomas,” Betof Warner said, mentioning a study conducted by colleagues at Stanford who demonstrated potential for anti-GD2 CAR T-cell therapy in deadly pediatric diffuse midline gliomas, tumors on the spine and brain.

In their study, nine out of 11 participants (median age, 15 years) showed benefit from the cell therapy, with one participant’s tumors resolving completely. The results paved the way for the FDA to grant a Regenerative Medicine Advanced Therapy designation for use of anti-GD2 CAR T cells in H3K27M-positive diffuse midline gliomas. 

The investigators are now recruiting for a phase 1 trial (NCT04196413). Results of the initial study were published in Nature last month.

Another lesser-known cell therapy expected to advance at some point in the future for solid tumors is use of the body’s natural killer (NK) cells. “They’ve been known about for a long time, but they are more difficult to regulate, which is one reason why it has taken longer to make NK cell therapies,” said Betof Warner, who is not involved in the study of NK cells. “One of their advantages is that, potentially, there could be an ‘off the shelf’ NK product. They don’t necessarily have to be made with autologous cells.”

 

Risk-Benefit Profiles Depend on Mechanism of Action

If the corresponding TCR sequence of a tumor antigen is known, said Betof Warner, it is possible to use leukapheresis to generate naive circulating lymphocytes. Once infused, the manufactured TCRTs will activate in the body the same as native cells because the signaling is the same.
An advantage to TCRT compared with CAR T-cell therapy is that it targets intracellular proteins, which are significantly present in the tumor, Betof Warner said in her presentation at ASCO 2024. She clarified that tumors will usually be screened for the presence of this antigen before a patient is selected for treatment with that particular therapy, because not all antigens are highly expressed in every tumor. 

“Furthermore, the tumor antigen has to be presented by a major histocompatibility complex, meaning there are human leukocyte antigen restrictions, which impacts patient selection,” she said.

A risk with both TCRT and CAR T-cell therapy, according to Betof Warner, is that because there are often shared antigens between tumor and normal tissues, on-target/off-tumor toxicity is a risk.

“TILs are different because they are nonengineered, at least not for antigen recognition. They are polyclonal and go after multiple targets,” Betof Warner said. “TCRs and CARs are engineered to go after one target. So, TILs have much lower rates of on-tumor/off-target effects, vs when you engineer a very high affinity receptor like a TCR or CAR.”

A good example of how this amplification of TCR affinity can lead to poor outcomes is in metastatic melanoma, said Betof Warner. 

In investigations (NCI-07-C-0174 and NCI-07-C-0175) of TCRT in metastatic melanoma, for example, the researchers were targeting MART-1 or gp100, which are expressed in melanocytes. 

“The problem was that these antigens are also expressed in the eyes and ears, so it caused eye inflammation and hearing loss in a number of patients because it wasn’t specific enough for the tumor,” said Betof Warner. “So, if that target is highly expressed on normal tissue, then you have a high risk.”

 

Promise of PRAME

Betof Warner said the most promising TCRT at present is the investigational autologous cell therapy IMA203 (NCT03688124), which targets the preferentially expressed antigen (PRAME). Although PRAME is found in many tumors, this testis antigen does not tend to express in normal, healthy adult tissues. Betof Warner is not affiliated with this study. 

“It’s maybe the most exciting TCRT cell in melanoma,” Betof Warner told her audience at the ASCO 2024 meeting. Because the expression rate of PRAME in cutaneous and uveal melanoma is at or above 95% and 90%, respectively, she said “it is a really good target in melanoma.”

Phase 1a results reported in late 2023 from a first-in-human trial of IMA203 involving 13 persons with highly advanced melanoma and a median of 5.5 previous treatments showed a 50% objective response rate in the 12 evaluable results. The duration of response ranged between 2.2 and 14.7 months (median follow-up, 14 months).

The safety profile of the treatment was favorable, with no grade 3 adverse events occurring in more than 10% of the cohort, and no grade 5 adverse events at all.

Phase 1b results published in October by maker Immatics showed that in 28 heavily pretreated metastatic melanoma patients, IMA203 had a confirmed objective response rate of 54% with a median duration of response of 12.1 months, while maintaining a favorable tolerability profile. 

 

Accelerated Approvals, Boxed Warnings

The FDA granted accelerated approvals for both lifileucel, the TIL therapy, and afamitresgene autoleucel, the TCRT. 

Both were approved with boxed warnings. Lifileucel’s warning is for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Afamitresgene autoleucel’s boxed warning is for serious or fatal cytokine release syndrome, which may be severe or life-threatening.

With these approvals, the bar is now raised on TILs and TCRTs, said Betof Warner.

The lifileucel trial studied 73 patients whose melanoma had continued to metastasize despite treatment with a programmed cell death protein (PD-1)/ programmed death-ligand (PD-L1)–targeted immune checkpoint inhibitor and a BRAF inhibitor (if appropriate based on tumor mutation status), and whose lifileucel dose was at least 7.5 billion cells (the approved dose). The cohort also received a median of six IL-2 (aldesleukin) doses. 

The objective response rate was 31.5% (95% CI, 21.1-43.4), and median duration of response was not reached (lower bound of 95% CI, 4.1).

In the afamitresgene autoleucel study, 44 of 52 patients with synovial sarcoma received leukapheresis and a single infusion of afamitresgene autoleucel. 

The overall response rate was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8), and the median duration of response was 6 months (lower bound of 95% CI, 4.6). Among patients who were responsive to the treatment, 45.6% and 39.0% had a duration of response of 6 months or longer and 12 months or longer, respectively.

 

New Hope for Patients

Betof Warner and her colleagues are now recruiting for an open-label, phase 1/2 investigation of the safety and efficacy of the TIL therapy OBX-115 in adult advanced solid tumors in melanoma or non–small cell lung cancer. The first-in-human results of a previous trial were presented at the ASCO 2024 meeting, and OBX-115 received FDA fast track designation in July.

“I think the results are really promising,” said Betof Warner. “This is an engineered TIL that does not require administering IL-2 to the patient. There were four out of the nine patients who responded to the treatment and there were no dose-limiting toxicities, no cytokine and no intracranial — all of which is excellent.”

For Betof Warner, the possibility that by using their own immune system, patients with advanced and refractory cancers could soon have a one-time treatment with a cell therapy rather than innumerable bouts of chemotherapy pushes her onward.

“The idea that we can treat cancer one time and have it not recur for years — that’s pushing the start of saying there’s a cure of cancer. That a person could move on from cancer like they move on from an infection. That is the potential of this work. We’re not there yet, but that’s where we need to think and dream big,” she said.

Betof Warner disclosed consulting/advisory roles with BluePath Solutions, Bristol-Myers Squibb/Medarex, Immatics, Instil Bio, Iovance Biotherapeutics, Lyell Immunopharma, Merck, Novartis, and Pfizer and research funding and travel expenses from Iovance Biotherapeutics.

 

A version of this article appeared on Medscape.com.

TOPLINE:

A brief self-guided online cognitive-behavioral therapy (CBT) intervention was noninferior to comprehensive clinician-guided CBT in reducing symptoms in patients with atopic dermatitis (AD), with both groups showing similar improvements on the Patient-Oriented Eczema Measure (POEM).

METHODOLOGY:

• Researchers conducted a single-blind randomized clinical noninferiority trial at Karolinska Institutet in Stockholm, Sweden, enrolling 168 adults with AD (mean age, 39 years; 84.5% women) from November 2022 to April 2023.
• Participants were randomly assigned to either a 12-week self-guided online CBT intervention (n = 86) without clinician support or a comprehensive 12-week clinician-guided online CBT program (n = 82).
• The primary outcome was the change in POEM score from baseline; reduction of 4 or more points was considered a response, and the predefined noninferiority margin was 3 points.

TAKEAWAY:

• The clinician-guided group improved by 4.20 points on POEM, while the self-guided group improved by 4.60 points, with an estimated mean difference in change of 0.36 points, which was below noninferiority margin.
• Clinicians spent a mean of 36 minutes on treatment guidance and an additional 14 minutes on assessments in the clinician-guided group, whereas they spent only 15.8 minutes on assessments in the self-guided group.
• Both groups demonstrated significant improvements in quality of life, sleep, depressive mood, pruritus, and stress, with no serious adverse events being reported.
• Completion rates were higher in the self-guided group with 81% of participants completing five or more modules, compared with 67% in the clinician-guided group.

IN PRACTICE:

“Overall, the findings support a self-guided intervention as a noninferior and cost-effective alternative to a previously evaluated clinician-guided treatment,” the authors wrote. “Because psychological interventions are rare in dermatological care, this study is an important step toward implementation of CBT for people with AD. The effectiveness of CBT interventions in primary and dermatological specialist care should be investigated.”

SOURCE:

The study was led by Dorian Kern, PhD, Division of Psychology, Karolinska Institutet, and was published online in JAMA Dermatology.

LIMITATIONS: 

High data loss for secondary measurements could affect interpretation of these results. The study relied solely on self-reported measures. The predominance of women participants and the Swedish-language requirement may have limited participation from migrant populations, which could hinder the broader implementation of the study’s findings.

DISCLOSURES:

The study was supported by the Swedish Ministry of Health and Social Affairs. Kern reported receiving grants from the Swedish Ministry of Health and Social Affairs during the conduct of the study. Other authors also reported authorships and royalties, personal fees, grants, or held stocks in DahliaQomit.

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

TOPLINE:

A brief self-guided online cognitive-behavioral therapy (CBT) intervention was noninferior to comprehensive clinician-guided CBT in reducing symptoms in patients with atopic dermatitis (AD), with both groups showing similar improvements on the Patient-Oriented Eczema Measure (POEM).

METHODOLOGY:

• Researchers conducted a single-blind randomized clinical noninferiority trial at Karolinska Institutet in Stockholm, Sweden, enrolling 168 adults with AD (mean age, 39 years; 84.5% women) from November 2022 to April 2023.
• Participants were randomly assigned to either a 12-week self-guided online CBT intervention (n = 86) without clinician support or a comprehensive 12-week clinician-guided online CBT program (n = 82).
• The primary outcome was the change in POEM score from baseline; reduction of 4 or more points was considered a response, and the predefined noninferiority margin was 3 points.

TAKEAWAY:

• The clinician-guided group improved by 4.20 points on POEM, while the self-guided group improved by 4.60 points, with an estimated mean difference in change of 0.36 points, which was below noninferiority margin.
• Clinicians spent a mean of 36 minutes on treatment guidance and an additional 14 minutes on assessments in the clinician-guided group, whereas they spent only 15.8 minutes on assessments in the self-guided group.
• Both groups demonstrated significant improvements in quality of life, sleep, depressive mood, pruritus, and stress, with no serious adverse events being reported.
• Completion rates were higher in the self-guided group with 81% of participants completing five or more modules, compared with 67% in the clinician-guided group.

IN PRACTICE:

“Overall, the findings support a self-guided intervention as a noninferior and cost-effective alternative to a previously evaluated clinician-guided treatment,” the authors wrote. “Because psychological interventions are rare in dermatological care, this study is an important step toward implementation of CBT for people with AD. The effectiveness of CBT interventions in primary and dermatological specialist care should be investigated.”

SOURCE:

The study was led by Dorian Kern, PhD, Division of Psychology, Karolinska Institutet, and was published online in JAMA Dermatology.

LIMITATIONS: 

High data loss for secondary measurements could affect interpretation of these results. The study relied solely on self-reported measures. The predominance of women participants and the Swedish-language requirement may have limited participation from migrant populations, which could hinder the broader implementation of the study’s findings.

DISCLOSURES:

The study was supported by the Swedish Ministry of Health and Social Affairs. Kern reported receiving grants from the Swedish Ministry of Health and Social Affairs during the conduct of the study. Other authors also reported authorships and royalties, personal fees, grants, or held stocks in DahliaQomit.

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

TOPLINE:

A brief self-guided online cognitive-behavioral therapy (CBT) intervention was noninferior to comprehensive clinician-guided CBT in reducing symptoms in patients with atopic dermatitis (AD), with both groups showing similar improvements on the Patient-Oriented Eczema Measure (POEM).

METHODOLOGY:

• Researchers conducted a single-blind randomized clinical noninferiority trial at Karolinska Institutet in Stockholm, Sweden, enrolling 168 adults with AD (mean age, 39 years; 84.5% women) from November 2022 to April 2023.
• Participants were randomly assigned to either a 12-week self-guided online CBT intervention (n = 86) without clinician support or a comprehensive 12-week clinician-guided online CBT program (n = 82).
• The primary outcome was the change in POEM score from baseline; reduction of 4 or more points was considered a response, and the predefined noninferiority margin was 3 points.

TAKEAWAY:

• The clinician-guided group improved by 4.20 points on POEM, while the self-guided group improved by 4.60 points, with an estimated mean difference in change of 0.36 points, which was below noninferiority margin.
• Clinicians spent a mean of 36 minutes on treatment guidance and an additional 14 minutes on assessments in the clinician-guided group, whereas they spent only 15.8 minutes on assessments in the self-guided group.
• Both groups demonstrated significant improvements in quality of life, sleep, depressive mood, pruritus, and stress, with no serious adverse events being reported.
• Completion rates were higher in the self-guided group with 81% of participants completing five or more modules, compared with 67% in the clinician-guided group.

IN PRACTICE:

“Overall, the findings support a self-guided intervention as a noninferior and cost-effective alternative to a previously evaluated clinician-guided treatment,” the authors wrote. “Because psychological interventions are rare in dermatological care, this study is an important step toward implementation of CBT for people with AD. The effectiveness of CBT interventions in primary and dermatological specialist care should be investigated.”

SOURCE:

The study was led by Dorian Kern, PhD, Division of Psychology, Karolinska Institutet, and was published online in JAMA Dermatology.

LIMITATIONS: 

High data loss for secondary measurements could affect interpretation of these results. The study relied solely on self-reported measures. The predominance of women participants and the Swedish-language requirement may have limited participation from migrant populations, which could hinder the broader implementation of the study’s findings.

DISCLOSURES:

The study was supported by the Swedish Ministry of Health and Social Affairs. Kern reported receiving grants from the Swedish Ministry of Health and Social Affairs during the conduct of the study. Other authors also reported authorships and royalties, personal fees, grants, or held stocks in DahliaQomit.

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

TOPLINE:

A survey of dermatologists found that although all respondents receive inpatient central line dressing (CLD)-related consults, most lack standardized protocols for managing adverse skin reactions and reported varying management approaches.

METHODOLOGY:

• Researchers developed and administered a 14-item Qualtrics survey to 107 dermatologists providing pediatric inpatient care through the Society for Pediatric Dermatology’s Inpatient Dermatology Section and Section Chief email lists.
• A total of 35 dermatologists (33%) from multiple institutions responded to the survey; most respondents (94%) specialized in pediatric dermatology.
• Researchers assessed management of CLD-associated adverse skin reactions.

TAKEAWAY:

• All respondents reported receiving CLD-related consults, but 66% indicated there was no personal or institutional standardized approach for managing CLD-associated skin reactions.
• Respondents said most reactions were in children aged 1-12 years (19 or 76% of 25 respondents) compared with those aged < 1 year (3 or 12% of 25 respondents).
• Management strategies included switching to alternative products, applying topical corticosteroids, and performing patch testing for allergies. 

IN PRACTICE:

“Insights derived from this study, including variation in clinician familiarity with reaction patterns, underscore the necessity of a standardized protocol for classifying and managing cutaneous CLD reactions in pediatric patients,” the authors wrote. “Further investigation is needed to better characterize CLD-associated allergic CD [contact dermatitis], irritant CD, and skin infections, as well as at-risk populations, to better inform clinical approaches,” they added.

SOURCE:

The study was led by Carly Mulinda, Columbia University College of Physicians and Surgeons, New York, and was published online on December 16 in Pediatric Dermatology.

LIMITATIONS:

The authors noted variable respondent awareness of institutional CLD and potential recency bias as key limitations of the study.

DISCLOSURES:

Study funding source was not declared. The authors reported no conflicts of interest.
 

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

TOPLINE:

A survey of dermatologists found that although all respondents receive inpatient central line dressing (CLD)-related consults, most lack standardized protocols for managing adverse skin reactions and reported varying management approaches.

METHODOLOGY:

• Researchers developed and administered a 14-item Qualtrics survey to 107 dermatologists providing pediatric inpatient care through the Society for Pediatric Dermatology’s Inpatient Dermatology Section and Section Chief email lists.
• A total of 35 dermatologists (33%) from multiple institutions responded to the survey; most respondents (94%) specialized in pediatric dermatology.
• Researchers assessed management of CLD-associated adverse skin reactions.

TAKEAWAY:

• All respondents reported receiving CLD-related consults, but 66% indicated there was no personal or institutional standardized approach for managing CLD-associated skin reactions.
• Respondents said most reactions were in children aged 1-12 years (19 or 76% of 25 respondents) compared with those aged < 1 year (3 or 12% of 25 respondents).
• Management strategies included switching to alternative products, applying topical corticosteroids, and performing patch testing for allergies. 

IN PRACTICE:

“Insights derived from this study, including variation in clinician familiarity with reaction patterns, underscore the necessity of a standardized protocol for classifying and managing cutaneous CLD reactions in pediatric patients,” the authors wrote. “Further investigation is needed to better characterize CLD-associated allergic CD [contact dermatitis], irritant CD, and skin infections, as well as at-risk populations, to better inform clinical approaches,” they added.

SOURCE:

The study was led by Carly Mulinda, Columbia University College of Physicians and Surgeons, New York, and was published online on December 16 in Pediatric Dermatology.

LIMITATIONS:

The authors noted variable respondent awareness of institutional CLD and potential recency bias as key limitations of the study.

DISCLOSURES:

Study funding source was not declared. The authors reported no conflicts of interest.
 

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

TOPLINE:

A survey of dermatologists found that although all respondents receive inpatient central line dressing (CLD)-related consults, most lack standardized protocols for managing adverse skin reactions and reported varying management approaches.

METHODOLOGY:

• Researchers developed and administered a 14-item Qualtrics survey to 107 dermatologists providing pediatric inpatient care through the Society for Pediatric Dermatology’s Inpatient Dermatology Section and Section Chief email lists.
• A total of 35 dermatologists (33%) from multiple institutions responded to the survey; most respondents (94%) specialized in pediatric dermatology.
• Researchers assessed management of CLD-associated adverse skin reactions.

TAKEAWAY:

• All respondents reported receiving CLD-related consults, but 66% indicated there was no personal or institutional standardized approach for managing CLD-associated skin reactions.
• Respondents said most reactions were in children aged 1-12 years (19 or 76% of 25 respondents) compared with those aged < 1 year (3 or 12% of 25 respondents).
• Management strategies included switching to alternative products, applying topical corticosteroids, and performing patch testing for allergies. 

IN PRACTICE:

“Insights derived from this study, including variation in clinician familiarity with reaction patterns, underscore the necessity of a standardized protocol for classifying and managing cutaneous CLD reactions in pediatric patients,” the authors wrote. “Further investigation is needed to better characterize CLD-associated allergic CD [contact dermatitis], irritant CD, and skin infections, as well as at-risk populations, to better inform clinical approaches,” they added.

SOURCE:

The study was led by Carly Mulinda, Columbia University College of Physicians and Surgeons, New York, and was published online on December 16 in Pediatric Dermatology.

LIMITATIONS:

The authors noted variable respondent awareness of institutional CLD and potential recency bias as key limitations of the study.

DISCLOSURES:

Study funding source was not declared. The authors reported no conflicts of interest.
 

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

NEW YORK CITY — Rheumatologists, dermatologists, drug manufacturers, and researchers do not pay enough attention to the role sex and gender play in the pathogenesis and presentation of psoriatic arthritis (PsA), Lihi Eder, MD, PhD, said at the Tenth Annual NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Being mindful that the disease and treatments affect men and women differently makes patient management more personalized and effective, she noted.

“We tend to ignore sex and gender when we manage our patients in our approach to psoriatic arthritis as well as other rheumatic diseases,” Eder said. “We have to start thinking about sex of the patient as a biomarker that can potentially help us personalize care and move from a gender-blinded to a gender-specific approach.”

Eder, the Canada Research Chair in Inflammatory Rheumatic Diseases at the Women’s College Hospital of the University of Toronto, in Ontario, Canada, said much of the obfuscation of the role gender plays in PsA begins with research. “There’s very little research into sex differences in PsA,” she said. A meta-analysis published last year by her group found that while 51% of participants in 54 PsA trials were women, only nine (17%) reported baseline characteristics by sex, 18 (33%) reported efficacy by sex, and two (4%) reported safety endpoints by sex.

Eder said sex is a biological factor, whereas gender is a “more complex” factor based on social and cultural aspects of men and women.

 

PsA Differences in Women vs Men

Although the prevalence of PsA in men and women is similar, sex affects the risk of developing rheumatic disease. For example, Eder cited a host of studies that showed Sjögren’s syndrome and systemic lupus erythematosus have a 9:1 and 7:1 prevalence in women vs men, whereas gout has a 1:4 prevalence.

Her group’s 2013 study, along with a 2023 study from Italy, found significant differences in how PsA disease activity and quality of life differ between the two sexes.

“Females tend to have a higher tender joint count and more clinical entheses,” Eder said. “They also have worse patient-reported outcomes when it comes to pain, fatigue, and physical dysfunction, and these are things that would influence quality of life.

“On the other hand, when we look at male patients, they tend to have higher CRP [C-reactive protein] levels, they tend to have more severe restriction in the spine, and they also tend to have more severe psoriasis.”

She added that women are less likely than men to develop joint damage that’s picked up on x-rays.

 

Questioning Drug Development 

A gender gap exists across four phases of drug development, Eder said. Preclinical studies tend to rely on single-sex models, phase 1 clinical trials target a standard 70-kg healthy male, and phase 2 and 3 trials as well as postmarketing surveillance do not consider gender in study design and have limited reporting of sex-specific endpoints, she said.

“So, it’s very hard to pick up these signals, and this may explain why most of the drugs that are withdrawn from the market pose a greater risk for women than for men,” she said, citing a 2001 Government Accountability Office report that found that 80% of prescription drugs withdrawn from the market pose a greater risk for women.

That gender bias also carries over to drug commercialization, she said. The sleeping pill zolpidem remains one of the few drugs for which the Food and Drug Administration has approved sex-specific dosing, Eder noted.

Her group’s 2023 meta-analysis showed that men and women respond differently to approved biological disease-modifying antirheumatic drugs. That research, which included a subanalysis of 18 trials and 6821 patients, found that men had a better American College of Rheumatology 20 response to tumor necrosis factor (TNF), interleukin-17 (IL-17), and IL-23 inhibitors, but there was no difference between the sexes in response to Janus-activated kinase (JAK) and tyrosine kinase 2 inhibitors. The same subanalysis also found no difference in the placebo response between men and women in those trials.

“So this raises the question: Should we consider the sex of the patient when we select treatments?” Eder said.

A French study last year reported that men had higher rates of persistence after 1 year: 62% vs 52% for women for TNF inhibitor, IL-17 inhibitor, and IL-23 inhibitor agents, but persistence rates for JAK inhibitors were similar between sexes.

“People ask me should we start favoring JAK inhibitors for females,” Eder said. “I think it’s premature. We need to do more research, but it does raise the question.”

A study by Eder and her group reported that women were more likely than men to discontinue their medications because their symptoms did not improve or the side effects were intolerable.

Another sex-differentiating factor of PsA that clinicians should take into account, Eder said, is the way men and women experience pain. “Women tend to report higher levels of pain across different rheumatic conditions,” she said, citing her own group’s 2022 study and a 2020 Dutch study. Cultural differences in how the sexes approach pain may also come into play, with men expected to be more tolerant and women more susceptible to it, Eder added. 

 

Evidence Is Mounting, but More Is Needed

The evidence that explains why these apparent differences exist between men and women with PsA is still lacking, Eder said in an interview with Medscape Medical News. “It’s very hard now because we don’t know the differences,” she said. “It’s very hard to know the solutions when you don’t know why things are happening.”

Nonetheless, she said, in her own practice she tries to be attuned to pain in women and is trying to stay unbiased when her patients talk about pain.

“I’ve also started asking females as they go into menopause or around the age of the mid-40s — those that complain about pain — about other menopausal-related symptoms, which I didn’t do before,” Eder said. She said she counsels patients whose pain might be driven by potentially menopausal transition, especially if they’re taking hormone-replacement therapy. She added that she is also using objective measures to differentiate PsA-related pain from other causes, such as fibromyalgia or depression.

Asked to comment on this topic, Iannis Adamopoulos, PhD, associate professor of medicine and director of the Arthritis Program and Head of the Osteoimmunology Laboratory at Beth Israel Deaconess Medical Center, Boston, told Medscape Medical News, “the science is now building” to better understand how sex and gender influence PsA. He noted that the National Institutes of Health already mandates sex-specific mouse studies in any research it funds.

Human studies, however, must take into account a host of variables, Adamopoulos said. “You have more variation within the groups because you don’t control 100% of people; you don’t put them in cages,” he said.

In her presentation, Eder noted that her group’s research into sex dimorphisms in the proteomic profile in PsA found that men have 20 times more sex-specific differentially expressed proteins than women. But Adamopoulos said that “there are no male and female proteins at all. There could be different levels but not different proteins.”

The research into sex differences in PsA is nascent, he said, adding, “There’s still a lot to uncover.” 

Eder disclosed financial relationships with AbbVie, Eli Lilly, Pfizer, Novartis, Johnson & Johnson, Bristol Myers Squibb, UCB, Fresenius Kabi, and Sandoz. Adamopoulos had no relevant financial disclosures.

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

NEW YORK CITY — Rheumatologists, dermatologists, drug manufacturers, and researchers do not pay enough attention to the role sex and gender play in the pathogenesis and presentation of psoriatic arthritis (PsA), Lihi Eder, MD, PhD, said at the Tenth Annual NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Being mindful that the disease and treatments affect men and women differently makes patient management more personalized and effective, she noted.

“We tend to ignore sex and gender when we manage our patients in our approach to psoriatic arthritis as well as other rheumatic diseases,” Eder said. “We have to start thinking about sex of the patient as a biomarker that can potentially help us personalize care and move from a gender-blinded to a gender-specific approach.”

Eder, the Canada Research Chair in Inflammatory Rheumatic Diseases at the Women’s College Hospital of the University of Toronto, in Ontario, Canada, said much of the obfuscation of the role gender plays in PsA begins with research. “There’s very little research into sex differences in PsA,” she said. A meta-analysis published last year by her group found that while 51% of participants in 54 PsA trials were women, only nine (17%) reported baseline characteristics by sex, 18 (33%) reported efficacy by sex, and two (4%) reported safety endpoints by sex.

Eder said sex is a biological factor, whereas gender is a “more complex” factor based on social and cultural aspects of men and women.

 

PsA Differences in Women vs Men

Although the prevalence of PsA in men and women is similar, sex affects the risk of developing rheumatic disease. For example, Eder cited a host of studies that showed Sjögren’s syndrome and systemic lupus erythematosus have a 9:1 and 7:1 prevalence in women vs men, whereas gout has a 1:4 prevalence.

Her group’s 2013 study, along with a 2023 study from Italy, found significant differences in how PsA disease activity and quality of life differ between the two sexes.

“Females tend to have a higher tender joint count and more clinical entheses,” Eder said. “They also have worse patient-reported outcomes when it comes to pain, fatigue, and physical dysfunction, and these are things that would influence quality of life.

“On the other hand, when we look at male patients, they tend to have higher CRP [C-reactive protein] levels, they tend to have more severe restriction in the spine, and they also tend to have more severe psoriasis.”

She added that women are less likely than men to develop joint damage that’s picked up on x-rays.

 

Questioning Drug Development 

A gender gap exists across four phases of drug development, Eder said. Preclinical studies tend to rely on single-sex models, phase 1 clinical trials target a standard 70-kg healthy male, and phase 2 and 3 trials as well as postmarketing surveillance do not consider gender in study design and have limited reporting of sex-specific endpoints, she said.

“So, it’s very hard to pick up these signals, and this may explain why most of the drugs that are withdrawn from the market pose a greater risk for women than for men,” she said, citing a 2001 Government Accountability Office report that found that 80% of prescription drugs withdrawn from the market pose a greater risk for women.

That gender bias also carries over to drug commercialization, she said. The sleeping pill zolpidem remains one of the few drugs for which the Food and Drug Administration has approved sex-specific dosing, Eder noted.

Her group’s 2023 meta-analysis showed that men and women respond differently to approved biological disease-modifying antirheumatic drugs. That research, which included a subanalysis of 18 trials and 6821 patients, found that men had a better American College of Rheumatology 20 response to tumor necrosis factor (TNF), interleukin-17 (IL-17), and IL-23 inhibitors, but there was no difference between the sexes in response to Janus-activated kinase (JAK) and tyrosine kinase 2 inhibitors. The same subanalysis also found no difference in the placebo response between men and women in those trials.

“So this raises the question: Should we consider the sex of the patient when we select treatments?” Eder said.

A French study last year reported that men had higher rates of persistence after 1 year: 62% vs 52% for women for TNF inhibitor, IL-17 inhibitor, and IL-23 inhibitor agents, but persistence rates for JAK inhibitors were similar between sexes.

“People ask me should we start favoring JAK inhibitors for females,” Eder said. “I think it’s premature. We need to do more research, but it does raise the question.”

A study by Eder and her group reported that women were more likely than men to discontinue their medications because their symptoms did not improve or the side effects were intolerable.

Another sex-differentiating factor of PsA that clinicians should take into account, Eder said, is the way men and women experience pain. “Women tend to report higher levels of pain across different rheumatic conditions,” she said, citing her own group’s 2022 study and a 2020 Dutch study. Cultural differences in how the sexes approach pain may also come into play, with men expected to be more tolerant and women more susceptible to it, Eder added. 

 

Evidence Is Mounting, but More Is Needed

The evidence that explains why these apparent differences exist between men and women with PsA is still lacking, Eder said in an interview with Medscape Medical News. “It’s very hard now because we don’t know the differences,” she said. “It’s very hard to know the solutions when you don’t know why things are happening.”

Nonetheless, she said, in her own practice she tries to be attuned to pain in women and is trying to stay unbiased when her patients talk about pain.

“I’ve also started asking females as they go into menopause or around the age of the mid-40s — those that complain about pain — about other menopausal-related symptoms, which I didn’t do before,” Eder said. She said she counsels patients whose pain might be driven by potentially menopausal transition, especially if they’re taking hormone-replacement therapy. She added that she is also using objective measures to differentiate PsA-related pain from other causes, such as fibromyalgia or depression.

Asked to comment on this topic, Iannis Adamopoulos, PhD, associate professor of medicine and director of the Arthritis Program and Head of the Osteoimmunology Laboratory at Beth Israel Deaconess Medical Center, Boston, told Medscape Medical News, “the science is now building” to better understand how sex and gender influence PsA. He noted that the National Institutes of Health already mandates sex-specific mouse studies in any research it funds.

Human studies, however, must take into account a host of variables, Adamopoulos said. “You have more variation within the groups because you don’t control 100% of people; you don’t put them in cages,” he said.

In her presentation, Eder noted that her group’s research into sex dimorphisms in the proteomic profile in PsA found that men have 20 times more sex-specific differentially expressed proteins than women. But Adamopoulos said that “there are no male and female proteins at all. There could be different levels but not different proteins.”

The research into sex differences in PsA is nascent, he said, adding, “There’s still a lot to uncover.” 

Eder disclosed financial relationships with AbbVie, Eli Lilly, Pfizer, Novartis, Johnson & Johnson, Bristol Myers Squibb, UCB, Fresenius Kabi, and Sandoz. Adamopoulos had no relevant financial disclosures.

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

NEW YORK CITY — Rheumatologists, dermatologists, drug manufacturers, and researchers do not pay enough attention to the role sex and gender play in the pathogenesis and presentation of psoriatic arthritis (PsA), Lihi Eder, MD, PhD, said at the Tenth Annual NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Being mindful that the disease and treatments affect men and women differently makes patient management more personalized and effective, she noted.

“We tend to ignore sex and gender when we manage our patients in our approach to psoriatic arthritis as well as other rheumatic diseases,” Eder said. “We have to start thinking about sex of the patient as a biomarker that can potentially help us personalize care and move from a gender-blinded to a gender-specific approach.”

Eder, the Canada Research Chair in Inflammatory Rheumatic Diseases at the Women’s College Hospital of the University of Toronto, in Ontario, Canada, said much of the obfuscation of the role gender plays in PsA begins with research. “There’s very little research into sex differences in PsA,” she said. A meta-analysis published last year by her group found that while 51% of participants in 54 PsA trials were women, only nine (17%) reported baseline characteristics by sex, 18 (33%) reported efficacy by sex, and two (4%) reported safety endpoints by sex.

Eder said sex is a biological factor, whereas gender is a “more complex” factor based on social and cultural aspects of men and women.

 

PsA Differences in Women vs Men

Although the prevalence of PsA in men and women is similar, sex affects the risk of developing rheumatic disease. For example, Eder cited a host of studies that showed Sjögren’s syndrome and systemic lupus erythematosus have a 9:1 and 7:1 prevalence in women vs men, whereas gout has a 1:4 prevalence.

Her group’s 2013 study, along with a 2023 study from Italy, found significant differences in how PsA disease activity and quality of life differ between the two sexes.

“Females tend to have a higher tender joint count and more clinical entheses,” Eder said. “They also have worse patient-reported outcomes when it comes to pain, fatigue, and physical dysfunction, and these are things that would influence quality of life.

“On the other hand, when we look at male patients, they tend to have higher CRP [C-reactive protein] levels, they tend to have more severe restriction in the spine, and they also tend to have more severe psoriasis.”

She added that women are less likely than men to develop joint damage that’s picked up on x-rays.

 

Questioning Drug Development 

A gender gap exists across four phases of drug development, Eder said. Preclinical studies tend to rely on single-sex models, phase 1 clinical trials target a standard 70-kg healthy male, and phase 2 and 3 trials as well as postmarketing surveillance do not consider gender in study design and have limited reporting of sex-specific endpoints, she said.

“So, it’s very hard to pick up these signals, and this may explain why most of the drugs that are withdrawn from the market pose a greater risk for women than for men,” she said, citing a 2001 Government Accountability Office report that found that 80% of prescription drugs withdrawn from the market pose a greater risk for women.

That gender bias also carries over to drug commercialization, she said. The sleeping pill zolpidem remains one of the few drugs for which the Food and Drug Administration has approved sex-specific dosing, Eder noted.

Her group’s 2023 meta-analysis showed that men and women respond differently to approved biological disease-modifying antirheumatic drugs. That research, which included a subanalysis of 18 trials and 6821 patients, found that men had a better American College of Rheumatology 20 response to tumor necrosis factor (TNF), interleukin-17 (IL-17), and IL-23 inhibitors, but there was no difference between the sexes in response to Janus-activated kinase (JAK) and tyrosine kinase 2 inhibitors. The same subanalysis also found no difference in the placebo response between men and women in those trials.

“So this raises the question: Should we consider the sex of the patient when we select treatments?” Eder said.

A French study last year reported that men had higher rates of persistence after 1 year: 62% vs 52% for women for TNF inhibitor, IL-17 inhibitor, and IL-23 inhibitor agents, but persistence rates for JAK inhibitors were similar between sexes.

“People ask me should we start favoring JAK inhibitors for females,” Eder said. “I think it’s premature. We need to do more research, but it does raise the question.”

A study by Eder and her group reported that women were more likely than men to discontinue their medications because their symptoms did not improve or the side effects were intolerable.

Another sex-differentiating factor of PsA that clinicians should take into account, Eder said, is the way men and women experience pain. “Women tend to report higher levels of pain across different rheumatic conditions,” she said, citing her own group’s 2022 study and a 2020 Dutch study. Cultural differences in how the sexes approach pain may also come into play, with men expected to be more tolerant and women more susceptible to it, Eder added. 

 

Evidence Is Mounting, but More Is Needed

The evidence that explains why these apparent differences exist between men and women with PsA is still lacking, Eder said in an interview with Medscape Medical News. “It’s very hard now because we don’t know the differences,” she said. “It’s very hard to know the solutions when you don’t know why things are happening.”

Nonetheless, she said, in her own practice she tries to be attuned to pain in women and is trying to stay unbiased when her patients talk about pain.

“I’ve also started asking females as they go into menopause or around the age of the mid-40s — those that complain about pain — about other menopausal-related symptoms, which I didn’t do before,” Eder said. She said she counsels patients whose pain might be driven by potentially menopausal transition, especially if they’re taking hormone-replacement therapy. She added that she is also using objective measures to differentiate PsA-related pain from other causes, such as fibromyalgia or depression.

Asked to comment on this topic, Iannis Adamopoulos, PhD, associate professor of medicine and director of the Arthritis Program and Head of the Osteoimmunology Laboratory at Beth Israel Deaconess Medical Center, Boston, told Medscape Medical News, “the science is now building” to better understand how sex and gender influence PsA. He noted that the National Institutes of Health already mandates sex-specific mouse studies in any research it funds.

Human studies, however, must take into account a host of variables, Adamopoulos said. “You have more variation within the groups because you don’t control 100% of people; you don’t put them in cages,” he said.

In her presentation, Eder noted that her group’s research into sex dimorphisms in the proteomic profile in PsA found that men have 20 times more sex-specific differentially expressed proteins than women. But Adamopoulos said that “there are no male and female proteins at all. There could be different levels but not different proteins.”

The research into sex differences in PsA is nascent, he said, adding, “There’s still a lot to uncover.” 

Eder disclosed financial relationships with AbbVie, Eli Lilly, Pfizer, Novartis, Johnson & Johnson, Bristol Myers Squibb, UCB, Fresenius Kabi, and Sandoz. Adamopoulos had no relevant financial disclosures.

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

NEW YORK CITY — The idea of having dermatologists and rheumatologists under one roof to see patients with psoriasis prone to psoriatic arthritis (PsA) — a concept known as combined clinics — has been around for more than a decade, and the idea of personalized medicine for these patients even longer than that, yet both approaches to care have encountered a host of obstacles, a longtime research rheumatologist said.

“It’s important that we work together, but there is a problem in terms of staffing — managing the meetings with patients together — and in the states in particular it’s a matter of who’s charging for what,” Dafna Gladman, MD, a rheumatologist at the University of Toronto, in Ontario, Canada, told attendees at the annual New York University (NYU) Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Her institution has one of the 44 worldwide combined clinics registered in the Psoriasis & Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), of which Gladman is an advisory board member.

 

Barriers to Combined Clinics

“Some of the barriers are physical in the sense that, for the dermatologists and rheumatologists to work at the same time, you need the right space, and in many places, you just don’t have the space to have the two specialists sitting at the same time,” Gladman told Medscape Medical News.

Some centers get around this by having the dermatology and rheumatology clinics next to or near each other. “So these two specialists are close enough to be able to go from room to room,” she added.

Another challenge facing combined clinics lies in the nature of how dermatologists and rheumatologists see patients. “The dermatologist sees patients a lot faster than the rheumatologist, so if the dermatologist and rheumatologist are sitting together, the dermatologist may not see as many patients as they would otherwise and therefore may not get reimbursed properly,” Gladman said.

To overcome these challenges, different models have emerged, Gladman said. If space allows, the ideal model is to have both specialties in one clinic, she said, while compensating for the different pace at which dermatologists and rheumatologists see patients.

The other model is to locate the two clinics close enough so that a person with suspected PsA can get to the rheumatology clinic soon after their dermatologic consult, or the rheumatologist can go to the dermatology clinic, Gladman said. Or the situation may be reversed when the rheumatologist needs a dermatology consult, she added.

When that’s not possible, a virtual visit may be the solution, Gladman said. She noted that PPACMAN offers ways to overcome the challenges of running a combined clinic.

Whatever combined clinic model a center chooses, clinicians must be mindful of preventing patients from falling through the cracks, Gladman said.

“When you treat patients separately, the patient sees the rheumatologist, and the rheumatologist wants to do one thing; then they go to the dermatologist and the dermatologist wants to do another thing, and the patient doesn’t do anything because they don’t know what to choose,” she said.

The combined clinic allows the patient to get the opinions of both specialists and avoid the uncertainty about the course of treatment, Gladman added.

Some combined clinics may also house other specialists, such as gastroenterologists, cardiologists, and nurse practitioners, noted Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City. Such centers are typically in academic centers “given challenges with space, scheduling, and reimbursement,” he told Medscape Medical News. NYU has a PPACMAN-registered combined clinic.

Regardless of how combined clinics are organized, Scher said, “We have found that the most important aspect of combined clinics is the open communication and integration of care between and amongst specialists and patients.”

 

The Potential of Personalized Medicine

“Personalized medicine is where we need to get to,” Gladman told seminar attendees. She said she had hoped it would be further along by now and be more integrated into the care of patients with psoriasis and PsA. “The idea is to identify psoriasis patients that are destined to develop psoriatic arthritis,” she said.

Besides that, identifying biomarkers is key to advancing personalized medicine for psoriasis, Gladman noted.

“In the skin, it’s easy; even the patient can assess their psoriasis,” she said. “But in the joints, it’s very difficult, so it would be nice to have some kind of biomarker, whether it’s the blood or an imaging modality. We want to identify the biomarkers for drug response or lack thereof so we know what drugs would be appropriate for the individual patient, and therefore, we can provide the right drug for the right person and fortunately at the right time.”

In explaining why personalized medicine isn’t further along in dermatology and rheumatology, Gladman told Medscape Medical News, “It’s a matter of finding the right things; we haven’t solved the mystery.” She cited a previous discussion at the seminar about the pathogenesis of PsA. “One person thinks it’s the bone marrow and another thinks it’s the T cells, so we haven’t quite put it all together to have a definitive answer.”

Personalized medicine in psoriasis and PsA is a “key unmet need,” Scher said. “Multiomics” — a biological analysis approach that uses multiple “omes,” such as the genome and microbiome — digital features, and wearables “can unlock novel diagnostic and therapeutic pathways that are desperately needed to enhance clinical response in PsA,” he said.

Also emerging are humanized animal models for laboratory research, which Scher called “potentially very useful tools to personalize approaches to PsA pathogenesis and treatment.”

Gladman disclosed financial relationships with AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

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

NEW YORK CITY — The idea of having dermatologists and rheumatologists under one roof to see patients with psoriasis prone to psoriatic arthritis (PsA) — a concept known as combined clinics — has been around for more than a decade, and the idea of personalized medicine for these patients even longer than that, yet both approaches to care have encountered a host of obstacles, a longtime research rheumatologist said.

“It’s important that we work together, but there is a problem in terms of staffing — managing the meetings with patients together — and in the states in particular it’s a matter of who’s charging for what,” Dafna Gladman, MD, a rheumatologist at the University of Toronto, in Ontario, Canada, told attendees at the annual New York University (NYU) Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Her institution has one of the 44 worldwide combined clinics registered in the Psoriasis & Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), of which Gladman is an advisory board member.

 

Barriers to Combined Clinics

“Some of the barriers are physical in the sense that, for the dermatologists and rheumatologists to work at the same time, you need the right space, and in many places, you just don’t have the space to have the two specialists sitting at the same time,” Gladman told Medscape Medical News.

Some centers get around this by having the dermatology and rheumatology clinics next to or near each other. “So these two specialists are close enough to be able to go from room to room,” she added.

Another challenge facing combined clinics lies in the nature of how dermatologists and rheumatologists see patients. “The dermatologist sees patients a lot faster than the rheumatologist, so if the dermatologist and rheumatologist are sitting together, the dermatologist may not see as many patients as they would otherwise and therefore may not get reimbursed properly,” Gladman said.

To overcome these challenges, different models have emerged, Gladman said. If space allows, the ideal model is to have both specialties in one clinic, she said, while compensating for the different pace at which dermatologists and rheumatologists see patients.

The other model is to locate the two clinics close enough so that a person with suspected PsA can get to the rheumatology clinic soon after their dermatologic consult, or the rheumatologist can go to the dermatology clinic, Gladman said. Or the situation may be reversed when the rheumatologist needs a dermatology consult, she added.

When that’s not possible, a virtual visit may be the solution, Gladman said. She noted that PPACMAN offers ways to overcome the challenges of running a combined clinic.

Whatever combined clinic model a center chooses, clinicians must be mindful of preventing patients from falling through the cracks, Gladman said.

“When you treat patients separately, the patient sees the rheumatologist, and the rheumatologist wants to do one thing; then they go to the dermatologist and the dermatologist wants to do another thing, and the patient doesn’t do anything because they don’t know what to choose,” she said.

The combined clinic allows the patient to get the opinions of both specialists and avoid the uncertainty about the course of treatment, Gladman added.

Some combined clinics may also house other specialists, such as gastroenterologists, cardiologists, and nurse practitioners, noted Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City. Such centers are typically in academic centers “given challenges with space, scheduling, and reimbursement,” he told Medscape Medical News. NYU has a PPACMAN-registered combined clinic.

Regardless of how combined clinics are organized, Scher said, “We have found that the most important aspect of combined clinics is the open communication and integration of care between and amongst specialists and patients.”

 

The Potential of Personalized Medicine

“Personalized medicine is where we need to get to,” Gladman told seminar attendees. She said she had hoped it would be further along by now and be more integrated into the care of patients with psoriasis and PsA. “The idea is to identify psoriasis patients that are destined to develop psoriatic arthritis,” she said.

Besides that, identifying biomarkers is key to advancing personalized medicine for psoriasis, Gladman noted.

“In the skin, it’s easy; even the patient can assess their psoriasis,” she said. “But in the joints, it’s very difficult, so it would be nice to have some kind of biomarker, whether it’s the blood or an imaging modality. We want to identify the biomarkers for drug response or lack thereof so we know what drugs would be appropriate for the individual patient, and therefore, we can provide the right drug for the right person and fortunately at the right time.”

In explaining why personalized medicine isn’t further along in dermatology and rheumatology, Gladman told Medscape Medical News, “It’s a matter of finding the right things; we haven’t solved the mystery.” She cited a previous discussion at the seminar about the pathogenesis of PsA. “One person thinks it’s the bone marrow and another thinks it’s the T cells, so we haven’t quite put it all together to have a definitive answer.”

Personalized medicine in psoriasis and PsA is a “key unmet need,” Scher said. “Multiomics” — a biological analysis approach that uses multiple “omes,” such as the genome and microbiome — digital features, and wearables “can unlock novel diagnostic and therapeutic pathways that are desperately needed to enhance clinical response in PsA,” he said.

Also emerging are humanized animal models for laboratory research, which Scher called “potentially very useful tools to personalize approaches to PsA pathogenesis and treatment.”

Gladman disclosed financial relationships with AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

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

NEW YORK CITY — The idea of having dermatologists and rheumatologists under one roof to see patients with psoriasis prone to psoriatic arthritis (PsA) — a concept known as combined clinics — has been around for more than a decade, and the idea of personalized medicine for these patients even longer than that, yet both approaches to care have encountered a host of obstacles, a longtime research rheumatologist said.

“It’s important that we work together, but there is a problem in terms of staffing — managing the meetings with patients together — and in the states in particular it’s a matter of who’s charging for what,” Dafna Gladman, MD, a rheumatologist at the University of Toronto, in Ontario, Canada, told attendees at the annual New York University (NYU) Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis. Her institution has one of the 44 worldwide combined clinics registered in the Psoriasis & Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), of which Gladman is an advisory board member.

 

Barriers to Combined Clinics

“Some of the barriers are physical in the sense that, for the dermatologists and rheumatologists to work at the same time, you need the right space, and in many places, you just don’t have the space to have the two specialists sitting at the same time,” Gladman told Medscape Medical News.

Some centers get around this by having the dermatology and rheumatology clinics next to or near each other. “So these two specialists are close enough to be able to go from room to room,” she added.

Another challenge facing combined clinics lies in the nature of how dermatologists and rheumatologists see patients. “The dermatologist sees patients a lot faster than the rheumatologist, so if the dermatologist and rheumatologist are sitting together, the dermatologist may not see as many patients as they would otherwise and therefore may not get reimbursed properly,” Gladman said.

To overcome these challenges, different models have emerged, Gladman said. If space allows, the ideal model is to have both specialties in one clinic, she said, while compensating for the different pace at which dermatologists and rheumatologists see patients.

The other model is to locate the two clinics close enough so that a person with suspected PsA can get to the rheumatology clinic soon after their dermatologic consult, or the rheumatologist can go to the dermatology clinic, Gladman said. Or the situation may be reversed when the rheumatologist needs a dermatology consult, she added.

When that’s not possible, a virtual visit may be the solution, Gladman said. She noted that PPACMAN offers ways to overcome the challenges of running a combined clinic.

Whatever combined clinic model a center chooses, clinicians must be mindful of preventing patients from falling through the cracks, Gladman said.

“When you treat patients separately, the patient sees the rheumatologist, and the rheumatologist wants to do one thing; then they go to the dermatologist and the dermatologist wants to do another thing, and the patient doesn’t do anything because they don’t know what to choose,” she said.

The combined clinic allows the patient to get the opinions of both specialists and avoid the uncertainty about the course of treatment, Gladman added.

Some combined clinics may also house other specialists, such as gastroenterologists, cardiologists, and nurse practitioners, noted Jose U. Scher, MD, director of the Arthritis Clinic and Psoriatic Arthritis Center at NYU Langone Health in New York City. Such centers are typically in academic centers “given challenges with space, scheduling, and reimbursement,” he told Medscape Medical News. NYU has a PPACMAN-registered combined clinic.

Regardless of how combined clinics are organized, Scher said, “We have found that the most important aspect of combined clinics is the open communication and integration of care between and amongst specialists and patients.”

 

The Potential of Personalized Medicine

“Personalized medicine is where we need to get to,” Gladman told seminar attendees. She said she had hoped it would be further along by now and be more integrated into the care of patients with psoriasis and PsA. “The idea is to identify psoriasis patients that are destined to develop psoriatic arthritis,” she said.

Besides that, identifying biomarkers is key to advancing personalized medicine for psoriasis, Gladman noted.

“In the skin, it’s easy; even the patient can assess their psoriasis,” she said. “But in the joints, it’s very difficult, so it would be nice to have some kind of biomarker, whether it’s the blood or an imaging modality. We want to identify the biomarkers for drug response or lack thereof so we know what drugs would be appropriate for the individual patient, and therefore, we can provide the right drug for the right person and fortunately at the right time.”

In explaining why personalized medicine isn’t further along in dermatology and rheumatology, Gladman told Medscape Medical News, “It’s a matter of finding the right things; we haven’t solved the mystery.” She cited a previous discussion at the seminar about the pathogenesis of PsA. “One person thinks it’s the bone marrow and another thinks it’s the T cells, so we haven’t quite put it all together to have a definitive answer.”

Personalized medicine in psoriasis and PsA is a “key unmet need,” Scher said. “Multiomics” — a biological analysis approach that uses multiple “omes,” such as the genome and microbiome — digital features, and wearables “can unlock novel diagnostic and therapeutic pathways that are desperately needed to enhance clinical response in PsA,” he said.

Also emerging are humanized animal models for laboratory research, which Scher called “potentially very useful tools to personalize approaches to PsA pathogenesis and treatment.”

Gladman disclosed financial relationships with AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. Scher had no relevant financial relationships.

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