Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Moderna and Merck have presented promising results from their phase 2b clinical trial that investigated a combination of a messenger RNA (mRNA) vaccine and a cancer drug for the treatment of melanoma.

Is mRNA set to shake up the world of cancer treatment? This is certainly what Moderna seems to think; the pharmaceutical company has published the results of a phase 2b trial combining its mRNA vaccine (mRNA-4157 [V940]) with Merck’s cancer drug KEYTRUDA. While these are not the final results but rather mid-term data from the 3-year follow-up, they are somewhat promising. The randomized KEYNOTE-942/mRNA-4157-P201 clinical trial involves patients with high-risk (stage III/IV) melanoma following complete resection.

Relapse Risk Halved

Treatment with mRNA-4157 (V940) in combination with pembrolizumab led to a clinically meaningful improvement in recurrence-free survival, reducing the risk for recurrence or death by 49%, compared with pembrolizumab alone. The combination of mRNA-4157 (V940) with pembrolizumab also continued to demonstrate a meaningful improvement in distant metastasis-free survival compared with pembrolizumab alone, reducing the risk of developing distant metastasis or death by 62%. “The KEYNOTE-942/mRNA-4157-P201 study was the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and the first combination therapy to show a significant benefit over pembrolizumab alone in adjuvant melanoma,” said Kyle Holen, MD, Moderna’s senior vice president, after presenting these results. 

Side Effects

The combined treatment also did not demonstrate more significant side effects than pembrolizumab alone. The number of patients reporting treatment-related adverse events of grade 3 or greater was similar between the arms (25% for mRNA-4157 [V940] with pembrolizumab vs 20% for KEYTRUDA alone). The most common adverse events of any grade attributed to mRNA-4157 (V940) were fatigue (60.6%), injection site pain (56.7%), and chills (49%). Based on data from the phase 2b KEYNOTE-942/mRNA-4157-P201 study, the US Food and Drug Administration and European Medicines Agency granted breakthrough therapy designation and recognition under the the Priority Medicines scheme, respectively, for mRNA-4157 (V940) in combination with KEYTRUDA for the adjuvant treatment of patients with high-risk melanoma.

Phase 3 Trial

In July, Moderna and Merck announced the launch of a phase 3 trial, assessing “mRNA-4157 [V940] in combination with pembrolizumab as adjuvant treatment in patients with high-risk resected melanoma [stages IIB-IV].” Stéphane Bancel, Moderna’s director general, believes that an mRNA vaccine for melanoma could be available in 2025.

Other Cancer Vaccines

Moderna is not the only laboratory to set its sights on developing a vaccine for cancer. In May, BioNTech, in partnership with Roche, proposed a phase 1 clinical trial of a vaccine targeting pancreatic cancer in Nature. In June, at the American Society of Clinical Oncology›s conference, Transgene presented its conclusions concerning its viral vector vaccines against ENT and papillomavirus-linked cancers. And in September, Ose Immunotherapeutics made headlines with its vaccine for advanced lung cancer.

This article was translated from Univadis France, which is part of the Medscape Professional Network.

Moderna and Merck have presented promising results from their phase 2b clinical trial that investigated a combination of a messenger RNA (mRNA) vaccine and a cancer drug for the treatment of melanoma.

Is mRNA set to shake up the world of cancer treatment? This is certainly what Moderna seems to think; the pharmaceutical company has published the results of a phase 2b trial combining its mRNA vaccine (mRNA-4157 [V940]) with Merck’s cancer drug KEYTRUDA. While these are not the final results but rather mid-term data from the 3-year follow-up, they are somewhat promising. The randomized KEYNOTE-942/mRNA-4157-P201 clinical trial involves patients with high-risk (stage III/IV) melanoma following complete resection.

Relapse Risk Halved

Treatment with mRNA-4157 (V940) in combination with pembrolizumab led to a clinically meaningful improvement in recurrence-free survival, reducing the risk for recurrence or death by 49%, compared with pembrolizumab alone. The combination of mRNA-4157 (V940) with pembrolizumab also continued to demonstrate a meaningful improvement in distant metastasis-free survival compared with pembrolizumab alone, reducing the risk of developing distant metastasis or death by 62%. “The KEYNOTE-942/mRNA-4157-P201 study was the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and the first combination therapy to show a significant benefit over pembrolizumab alone in adjuvant melanoma,” said Kyle Holen, MD, Moderna’s senior vice president, after presenting these results. 

Side Effects

The combined treatment also did not demonstrate more significant side effects than pembrolizumab alone. The number of patients reporting treatment-related adverse events of grade 3 or greater was similar between the arms (25% for mRNA-4157 [V940] with pembrolizumab vs 20% for KEYTRUDA alone). The most common adverse events of any grade attributed to mRNA-4157 (V940) were fatigue (60.6%), injection site pain (56.7%), and chills (49%). Based on data from the phase 2b KEYNOTE-942/mRNA-4157-P201 study, the US Food and Drug Administration and European Medicines Agency granted breakthrough therapy designation and recognition under the the Priority Medicines scheme, respectively, for mRNA-4157 (V940) in combination with KEYTRUDA for the adjuvant treatment of patients with high-risk melanoma.

Phase 3 Trial

In July, Moderna and Merck announced the launch of a phase 3 trial, assessing “mRNA-4157 [V940] in combination with pembrolizumab as adjuvant treatment in patients with high-risk resected melanoma [stages IIB-IV].” Stéphane Bancel, Moderna’s director general, believes that an mRNA vaccine for melanoma could be available in 2025.

Other Cancer Vaccines

Moderna is not the only laboratory to set its sights on developing a vaccine for cancer. In May, BioNTech, in partnership with Roche, proposed a phase 1 clinical trial of a vaccine targeting pancreatic cancer in Nature. In June, at the American Society of Clinical Oncology›s conference, Transgene presented its conclusions concerning its viral vector vaccines against ENT and papillomavirus-linked cancers. And in September, Ose Immunotherapeutics made headlines with its vaccine for advanced lung cancer.

This article was translated from Univadis France, which is part of the Medscape Professional Network.

Moderna and Merck have presented promising results from their phase 2b clinical trial that investigated a combination of a messenger RNA (mRNA) vaccine and a cancer drug for the treatment of melanoma.

Is mRNA set to shake up the world of cancer treatment? This is certainly what Moderna seems to think; the pharmaceutical company has published the results of a phase 2b trial combining its mRNA vaccine (mRNA-4157 [V940]) with Merck’s cancer drug KEYTRUDA. While these are not the final results but rather mid-term data from the 3-year follow-up, they are somewhat promising. The randomized KEYNOTE-942/mRNA-4157-P201 clinical trial involves patients with high-risk (stage III/IV) melanoma following complete resection.

Relapse Risk Halved

Treatment with mRNA-4157 (V940) in combination with pembrolizumab led to a clinically meaningful improvement in recurrence-free survival, reducing the risk for recurrence or death by 49%, compared with pembrolizumab alone. The combination of mRNA-4157 (V940) with pembrolizumab also continued to demonstrate a meaningful improvement in distant metastasis-free survival compared with pembrolizumab alone, reducing the risk of developing distant metastasis or death by 62%. “The KEYNOTE-942/mRNA-4157-P201 study was the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and the first combination therapy to show a significant benefit over pembrolizumab alone in adjuvant melanoma,” said Kyle Holen, MD, Moderna’s senior vice president, after presenting these results. 

Side Effects

The combined treatment also did not demonstrate more significant side effects than pembrolizumab alone. The number of patients reporting treatment-related adverse events of grade 3 or greater was similar between the arms (25% for mRNA-4157 [V940] with pembrolizumab vs 20% for KEYTRUDA alone). The most common adverse events of any grade attributed to mRNA-4157 (V940) were fatigue (60.6%), injection site pain (56.7%), and chills (49%). Based on data from the phase 2b KEYNOTE-942/mRNA-4157-P201 study, the US Food and Drug Administration and European Medicines Agency granted breakthrough therapy designation and recognition under the the Priority Medicines scheme, respectively, for mRNA-4157 (V940) in combination with KEYTRUDA for the adjuvant treatment of patients with high-risk melanoma.

Phase 3 Trial

In July, Moderna and Merck announced the launch of a phase 3 trial, assessing “mRNA-4157 [V940] in combination with pembrolizumab as adjuvant treatment in patients with high-risk resected melanoma [stages IIB-IV].” Stéphane Bancel, Moderna’s director general, believes that an mRNA vaccine for melanoma could be available in 2025.

Other Cancer Vaccines

Moderna is not the only laboratory to set its sights on developing a vaccine for cancer. In May, BioNTech, in partnership with Roche, proposed a phase 1 clinical trial of a vaccine targeting pancreatic cancer in Nature. In June, at the American Society of Clinical Oncology›s conference, Transgene presented its conclusions concerning its viral vector vaccines against ENT and papillomavirus-linked cancers. And in September, Ose Immunotherapeutics made headlines with its vaccine for advanced lung cancer.

This article was translated from Univadis France, which is part of the Medscape Professional Network.

TOPLINE:

The efficacy of clascoterone cream 1% for treating acne vulgaris appears to increase over time after 12 weeks of use and up to 1 year.

METHODOLOGY:

• A 1% cream formulation of clascoterone, a topical androgen receptor inhibitor, is approved for the treatment of acne vulgaris in patients aged 12 years and older based on results from two identical phase 3 12-week trials, NCT02608450 and NCT02608476, and a long-term extension (LTE) study.
• The purpose of the current study was to evaluate the integrated efficacy of clascoterone cream 1% (Winlevi) in the intention-to-treat population of patients from all three trials.
• In the pivotal trials, investigators randomized patients with acne 1:1 to receive clascoterone cream 1% or vehicle twice daily for 12 weeks. Participants were eligible to enter the LTE study, in which patients applied clascoterone to the face, and if they wanted to, the trunk for up to 9 more months.
• To assess combined efficacy, researchers evaluated the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of 0 or 1.

TAKEAWAY:

• Of the 1143 patients from the pivotal trials who completed 12 weeks of treatment, 576 were in the clascoterone group and 567 were in the vehicle group. Of the 600 patients who entered the LTE study, 311 were in the clascoterone group and 289 were in the vehicle group. Of these, 343 completed the LTE study.
• At week 12, the proportion of patients who achieved treatment success was higher in the clascoterone group than in the vehicle group (19.9% vs 7.7%, respectively; P < .0001).
• In the LTE study, the proportion of patients previously treated with clascoterone who achieved a facial IGA of 0/1 increased from 13.5% at extension day 0 to 29.9% at extension day 274, while the proportion of patients previously treated with vehicle and switched to clascoterone who achieved a facial IGA of 0/1 increased from 6.2% at extension day 0 to 30.4% at extension day 274.
• Similarly, the proportion of patients in the LTE study with a truncal IGA of 0/1 increased from 4.9% at extension day 0 to 31.7% on extension day 274.

IN PRACTICE:

“Clinicians may consider counseling patients that treatment persistence is required to maximize the efficacy of clascoterone treatment,” the authors concluded.

SOURCE:

Lawrence F. Eichenfield, MD, of the departments of dermatology and pediatrics at the University of California and Rady Children’s Hospital, San Diego, California, led the research. The study was published in the January 2024 issue of the Journal of Drugs in Dermatology.

LIMITATIONS:

There was a high patient discontinuation rate before and during the LET study. Also, no assessment was made as to how clascoterone affected patients’ quality of life.

DISCLOSURES:

Clascoterone manufacturer Cassiopea funded the studies. Dr. Eichenfield and fellow investigators Adelaide A. Hebert, MD, and Linda Stein Gold, MD, received compensation from Cassiopea as advisers and disclosed ties to many other pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The efficacy of clascoterone cream 1% for treating acne vulgaris appears to increase over time after 12 weeks of use and up to 1 year.

METHODOLOGY:

• A 1% cream formulation of clascoterone, a topical androgen receptor inhibitor, is approved for the treatment of acne vulgaris in patients aged 12 years and older based on results from two identical phase 3 12-week trials, NCT02608450 and NCT02608476, and a long-term extension (LTE) study.
• The purpose of the current study was to evaluate the integrated efficacy of clascoterone cream 1% (Winlevi) in the intention-to-treat population of patients from all three trials.
• In the pivotal trials, investigators randomized patients with acne 1:1 to receive clascoterone cream 1% or vehicle twice daily for 12 weeks. Participants were eligible to enter the LTE study, in which patients applied clascoterone to the face, and if they wanted to, the trunk for up to 9 more months.
• To assess combined efficacy, researchers evaluated the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of 0 or 1.

TAKEAWAY:

• Of the 1143 patients from the pivotal trials who completed 12 weeks of treatment, 576 were in the clascoterone group and 567 were in the vehicle group. Of the 600 patients who entered the LTE study, 311 were in the clascoterone group and 289 were in the vehicle group. Of these, 343 completed the LTE study.
• At week 12, the proportion of patients who achieved treatment success was higher in the clascoterone group than in the vehicle group (19.9% vs 7.7%, respectively; P < .0001).
• In the LTE study, the proportion of patients previously treated with clascoterone who achieved a facial IGA of 0/1 increased from 13.5% at extension day 0 to 29.9% at extension day 274, while the proportion of patients previously treated with vehicle and switched to clascoterone who achieved a facial IGA of 0/1 increased from 6.2% at extension day 0 to 30.4% at extension day 274.
• Similarly, the proportion of patients in the LTE study with a truncal IGA of 0/1 increased from 4.9% at extension day 0 to 31.7% on extension day 274.

IN PRACTICE:

“Clinicians may consider counseling patients that treatment persistence is required to maximize the efficacy of clascoterone treatment,” the authors concluded.

SOURCE:

Lawrence F. Eichenfield, MD, of the departments of dermatology and pediatrics at the University of California and Rady Children’s Hospital, San Diego, California, led the research. The study was published in the January 2024 issue of the Journal of Drugs in Dermatology.

LIMITATIONS:

There was a high patient discontinuation rate before and during the LET study. Also, no assessment was made as to how clascoterone affected patients’ quality of life.

DISCLOSURES:

Clascoterone manufacturer Cassiopea funded the studies. Dr. Eichenfield and fellow investigators Adelaide A. Hebert, MD, and Linda Stein Gold, MD, received compensation from Cassiopea as advisers and disclosed ties to many other pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The efficacy of clascoterone cream 1% for treating acne vulgaris appears to increase over time after 12 weeks of use and up to 1 year.

METHODOLOGY:

• A 1% cream formulation of clascoterone, a topical androgen receptor inhibitor, is approved for the treatment of acne vulgaris in patients aged 12 years and older based on results from two identical phase 3 12-week trials, NCT02608450 and NCT02608476, and a long-term extension (LTE) study.
• The purpose of the current study was to evaluate the integrated efficacy of clascoterone cream 1% (Winlevi) in the intention-to-treat population of patients from all three trials.
• In the pivotal trials, investigators randomized patients with acne 1:1 to receive clascoterone cream 1% or vehicle twice daily for 12 weeks. Participants were eligible to enter the LTE study, in which patients applied clascoterone to the face, and if they wanted to, the trunk for up to 9 more months.
• To assess combined efficacy, researchers evaluated the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of 0 or 1.

TAKEAWAY:

• Of the 1143 patients from the pivotal trials who completed 12 weeks of treatment, 576 were in the clascoterone group and 567 were in the vehicle group. Of the 600 patients who entered the LTE study, 311 were in the clascoterone group and 289 were in the vehicle group. Of these, 343 completed the LTE study.
• At week 12, the proportion of patients who achieved treatment success was higher in the clascoterone group than in the vehicle group (19.9% vs 7.7%, respectively; P < .0001).
• In the LTE study, the proportion of patients previously treated with clascoterone who achieved a facial IGA of 0/1 increased from 13.5% at extension day 0 to 29.9% at extension day 274, while the proportion of patients previously treated with vehicle and switched to clascoterone who achieved a facial IGA of 0/1 increased from 6.2% at extension day 0 to 30.4% at extension day 274.
• Similarly, the proportion of patients in the LTE study with a truncal IGA of 0/1 increased from 4.9% at extension day 0 to 31.7% on extension day 274.

IN PRACTICE:

“Clinicians may consider counseling patients that treatment persistence is required to maximize the efficacy of clascoterone treatment,” the authors concluded.

SOURCE:

Lawrence F. Eichenfield, MD, of the departments of dermatology and pediatrics at the University of California and Rady Children’s Hospital, San Diego, California, led the research. The study was published in the January 2024 issue of the Journal of Drugs in Dermatology.

LIMITATIONS:

There was a high patient discontinuation rate before and during the LET study. Also, no assessment was made as to how clascoterone affected patients’ quality of life.

DISCLOSURES:

Clascoterone manufacturer Cassiopea funded the studies. Dr. Eichenfield and fellow investigators Adelaide A. Hebert, MD, and Linda Stein Gold, MD, received compensation from Cassiopea as advisers and disclosed ties to many other pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Previous gestational diabetes mellitus (GDM) nearly doubles future chronic kidney disease (CKD) risk, irrespective of subsequent diabetes and hypertension, a study showed.

METHODOLOGY:

• A nationwide, cohort study was based on data from the Danish Medical Birth Register and included 697,622 women who gave birth between 1997 and 2018.
• Of all study participants, 3.4% reported GDM in at least one pregnancy, and 12.8% of women with GDM received insulin, a proxy for a more severe metabolic dysfunction.
• The women were followed up for a median of 11.9 years.
• Researchers studied CKD and acute kidney disease as the outcomes of interest, the mediating effects of subsequent diabetes and hypertension on future CKD, and how GDM severity affected later risk for kidney disease.

TAKEAWAY:

• Women with GDM showed significantly higher CKD risk than those without GDM (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.67-2.21).
• Women who received insulin during pregnancy due to severe metabolic dysfunction but did not develop subsequent diabetes had a proportionally higher risk for CKD (aHR, 2.35; 95% CI, 1.39-3.97).
• Women with GDM who went on to develop diabetes or hypertension faced even higher risks for CKD, suggesting that preventing diabetes and hypertension after GDM may reduce the development of CKD.
• GDM did not affect the risk for acute kidney disease (aHR, 1.08; 95% CI, 0.90-1.29).

IN PRACTICE:

“Women with severe metabolic dysfunction during pregnancy constitute a high-risk group regarding future CKD,” the authors wrote. “The significantly elevated CKD risk was observed from 2 years after pregnancy and beyond.”

SOURCE:

The study, with first author Maria Hornstrup Christensen, of Odense University Hospital, Odense, Denmark, was published online on December 15 in Diabetes Care.

LIMITATIONS:

GDM may be underdiagnosed, and undiagnosed diabetes may be misclassified as GDM. The proxies of GDM and insulin treatment may not have captured the increasing severity of metabolic dysfunction. The prevalence of insulin treatment was lower than expected, perhaps due to the practice of providing a patient’s first insulin pen without a prescription and perhaps not recording it in a patient’s health record.

DISCLOSURES:

This work received financial support from the University of Southern Denmark, the Region of Southern Denmark, and the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Previous gestational diabetes mellitus (GDM) nearly doubles future chronic kidney disease (CKD) risk, irrespective of subsequent diabetes and hypertension, a study showed.

METHODOLOGY:

• A nationwide, cohort study was based on data from the Danish Medical Birth Register and included 697,622 women who gave birth between 1997 and 2018.
• Of all study participants, 3.4% reported GDM in at least one pregnancy, and 12.8% of women with GDM received insulin, a proxy for a more severe metabolic dysfunction.
• The women were followed up for a median of 11.9 years.
• Researchers studied CKD and acute kidney disease as the outcomes of interest, the mediating effects of subsequent diabetes and hypertension on future CKD, and how GDM severity affected later risk for kidney disease.

TAKEAWAY:

• Women with GDM showed significantly higher CKD risk than those without GDM (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.67-2.21).
• Women who received insulin during pregnancy due to severe metabolic dysfunction but did not develop subsequent diabetes had a proportionally higher risk for CKD (aHR, 2.35; 95% CI, 1.39-3.97).
• Women with GDM who went on to develop diabetes or hypertension faced even higher risks for CKD, suggesting that preventing diabetes and hypertension after GDM may reduce the development of CKD.
• GDM did not affect the risk for acute kidney disease (aHR, 1.08; 95% CI, 0.90-1.29).

IN PRACTICE:

“Women with severe metabolic dysfunction during pregnancy constitute a high-risk group regarding future CKD,” the authors wrote. “The significantly elevated CKD risk was observed from 2 years after pregnancy and beyond.”

SOURCE:

The study, with first author Maria Hornstrup Christensen, of Odense University Hospital, Odense, Denmark, was published online on December 15 in Diabetes Care.

LIMITATIONS:

GDM may be underdiagnosed, and undiagnosed diabetes may be misclassified as GDM. The proxies of GDM and insulin treatment may not have captured the increasing severity of metabolic dysfunction. The prevalence of insulin treatment was lower than expected, perhaps due to the practice of providing a patient’s first insulin pen without a prescription and perhaps not recording it in a patient’s health record.

DISCLOSURES:

This work received financial support from the University of Southern Denmark, the Region of Southern Denmark, and the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Previous gestational diabetes mellitus (GDM) nearly doubles future chronic kidney disease (CKD) risk, irrespective of subsequent diabetes and hypertension, a study showed.

METHODOLOGY:

• A nationwide, cohort study was based on data from the Danish Medical Birth Register and included 697,622 women who gave birth between 1997 and 2018.
• Of all study participants, 3.4% reported GDM in at least one pregnancy, and 12.8% of women with GDM received insulin, a proxy for a more severe metabolic dysfunction.
• The women were followed up for a median of 11.9 years.
• Researchers studied CKD and acute kidney disease as the outcomes of interest, the mediating effects of subsequent diabetes and hypertension on future CKD, and how GDM severity affected later risk for kidney disease.

TAKEAWAY:

• Women with GDM showed significantly higher CKD risk than those without GDM (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.67-2.21).
• Women who received insulin during pregnancy due to severe metabolic dysfunction but did not develop subsequent diabetes had a proportionally higher risk for CKD (aHR, 2.35; 95% CI, 1.39-3.97).
• Women with GDM who went on to develop diabetes or hypertension faced even higher risks for CKD, suggesting that preventing diabetes and hypertension after GDM may reduce the development of CKD.
• GDM did not affect the risk for acute kidney disease (aHR, 1.08; 95% CI, 0.90-1.29).

IN PRACTICE:

“Women with severe metabolic dysfunction during pregnancy constitute a high-risk group regarding future CKD,” the authors wrote. “The significantly elevated CKD risk was observed from 2 years after pregnancy and beyond.”

SOURCE:

The study, with first author Maria Hornstrup Christensen, of Odense University Hospital, Odense, Denmark, was published online on December 15 in Diabetes Care.

LIMITATIONS:

GDM may be underdiagnosed, and undiagnosed diabetes may be misclassified as GDM. The proxies of GDM and insulin treatment may not have captured the increasing severity of metabolic dysfunction. The prevalence of insulin treatment was lower than expected, perhaps due to the practice of providing a patient’s first insulin pen without a prescription and perhaps not recording it in a patient’s health record.

DISCLOSURES:

This work received financial support from the University of Southern Denmark, the Region of Southern Denmark, and the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation. The authors declared no conflicts of interest.
 

A version of this article appeared on Medscape.com.

Patients may be familiar with several myths and have misconceptions about headaches and migraine, which often arise due to a combination of factors, including limited understanding of the conditions, cultural beliefs, misinformation, and the complex nature of headaches. Being aware of these myths and seeking accurate information help patients to better understand and manage their headaches.

Myth: Migraine Is the Most Common Type of Headache

This is not true. The most common type of headache is tension-type headache, and it's the kind of headache that almost everyone has from time to time. Between 40% and 80% of the US population have had some form of tension-type headache, but only about 13% of the adult population have migraine. Stress can make muscles in the head and neck tense and knotted, and these muscles can be the source of a tension-type headache. Sometimes these headaches are not at all related to muscles or stress. Neck position may also be a factor. Pain from this type of headache is usually felt on both sides of the head and presents more often as steady, dull pressure or pain that’s usually mild to moderate in intensity. The pain can be in the forehead and eyes or further back in the head. Tension-type headaches are not usually associated with nausea, vomiting, or light and sound sensitivity.

When a tension-type headache is really severe, patients could consider this headache a migraine. Clinicians can easily distinguish tension-type headache from migraine, which often presents on one side of the head, with moderate or severe intensity, is throbbing, and is associated with nausea, vomiting, and light and sound sensitivity.

Myth: Only Adults Get Headaches

False. Headaches aren’t experienced just by adults. However, unlike adults, children find it harder to explain their headaches. It is true that adults have more migraines than children; children’s migraines are often hard for doctors to recognize. A 6- to 9-year-old child is 50% less likely than an adult to have migraine, and their attacks are more often bilateral, are shorter, and respond to sleep quickly.

Myth: Migraines Are Just Really Bad Headaches

False. They are bad, but that is only a small part of the story. A migraine attack is different from other headaches; they actually are 1 of the 3 primary headache disorders, along with tension-type headache and cluster headache. A moderate or severe headache is one of the many characteristics of migraine, and some patients do not even have a headache during a migraine attack. Migraine is an inherited disease of the brain and other parts of the nervous system and can feel much worse than a normal headache. During a migraine attack, the brain does not process sensory data, such as lights, sound, or touch, properly. Patients might even experience visual, sensory, or speech problems (ie, auras) and sometime see flashing lights or zigzag lines that blink on and off or blind spots in their vision. Patients with migraine are often nauseated and severely bothered by light, sound, and even smells. Migraine headaches can last between 4 and 72 hours on average, causing disability, tiredness, and inability to think clearly or work productively, which adds to the burden of the disease. So, migraine is not just a headache. 

Myth: More Women Than Men Experience Migraine 

This is true. Epidemiologic data show a 3-fold higher incidence of migraine in women than men, starting from puberty and throughout life. From about 6 to 12 years, boys have a slightly higher incidence than girls, but then migraine occurrence levels off and becomes a disease primarily of women. The modulation of neuronal and vascular reactivity by hormones (namely estrogens and progesterone) is a crucial aspect of migraine in some women only. These hormones exert influence on a spectrum of neuromediators and neurotransmitters, potentially leading to functional and structural variations in specific brain regions associated with migraine pathogenesis. Beyond their central effects, sex hormones also modulate vascular tone. Therefore, migraine follows a pattern throughout a woman’s life corresponding to the fluctuation of estrogen. Within a year of their first menstrual period, many girls with migraine have their first attack. They are more likely to have a migraine attack just before and at the start of menses, and at other times of the month as well. They feel better when pregnant and worse after they stop breastfeeding, and they start to feel worse prior to menopause. Then they improve a few years after menopause.

While men are less at risk of having migraine, they’re more likely to have cluster headache than women (although this type of headache is rare compared with other headaches like migraine). Only about 0.1% or less of the population of adults in the US experience this type of headache. Cluster headache gets its name from the clustering of attacks occurring 2 to 6 times per day for 4 to 10 weeks and disappearing as quickly as they came. This headache pain is felt exclusively in or behind 1 eye and rarely elsewhere, on the same side of the head. There is also a clustering of other symptoms called autonomic findings, such as tearing and redness of 1 eye, stuffiness and running in 1 nostril, sweating over 1 eyebrow, drooping of 1 eyelid, and a small pupil—all on the same side of the head the pain is radiating from. Most patients have only some of these findings. Cluster headaches tend to occur every year around the same time (circannual). When a patient is in a cycle of cluster headaches, they often occur at the same time each day (circadian). These set times of the year and of the day are caused by the biological clock deep down under the brain in the hypothalamus.

Myth: All Headaches Are Psychological

This is not true. Usually the underlying cause of migraine is genetically-inherited, but each attack may be triggered by an underlying cause (eg, drop in barometric pressure, menses, certain food/drinks, lack of sleep, stress, etc). Even tension-type headaches can be triggered by muscles in the head and neck becoming tense, stressful events, or jaw issues, which in turn send out pain signals that are felt on both sides of the head.

Many years ago (ie, 1950s-1960s), it was thought that the underlying cause of migraine in women was psychological issues; that has been disproven many times. Both men and women have migraine, and they both can have coexisting psychological issues (ie, depression, anxiety, and other psychiatric problems). 

Myth: Migraines Aren’t Serious

Most types of migraine in and of themselves are not serious; however, chronic migraine can continue for years and is debilitating and disabling—becoming a serious issue for patients. These patients usually take many medications, are obese, can have big changes in weight and severe insomnia, don’t exercise enough, and develop other illnesses. Migraine can severely impact quality of life; many people living with migraine have reported reduced productivity while at work, lack of promotion, loss of jobs, and a disruption in their family, social, and leisure activities.

Migraine attacks vary from one person to another and can be quite different from one attack to another in the same person. Hemiplegic migraine, a rare and distinct subtype that is sometimes inherited, is characterized by neurologic symptoms (multiple auras, including a significant weakness or paralysis on 1 side of the body). Although these patients seem much sicker and have multiple types of auras and 1-sided weakness with a prolonged headache, most recover without serious consequences. 

Myth: Lack of Sleep Causes Migraine 

Yes, lack of sleep is a known trigger for migraine in many people, but lack of sleep is not the cause of migraine. Sleep deprivation and irregular sleep patterns can disrupt the delicate balance of neurotransmitters and hormones in the brain, potentially triggering migraine in susceptible individuals. Additionally, inadequate sleep may contribute to increased stress and tension, which are also common triggers for migraine. In fact, many people with migraine do have sleep issues, which can range from trouble falling asleep to early morning awakening without being able to get back to sleep or frequently interrupted sleep each night. Correcting the sleep problem is part of the migraine therapy. Patients should be checked for sleep apnea if they wake with headache in the morning. Medication overuse headache should also be considered.

Establishing a regular sleep routine and ensuring an adequate amount of sleep can be important components of managing migraine symptoms, particularly for those who find a connection between their sleep patterns and the onset of a migraine attack. However, the relationship between sleep and migraine can vary widely among individuals, and other factors may also contribute to migraine triggers.

Myth: Caffeine Causes Migraine

This is a myth; caffeine does not cause migraine but definitely can be a trigger for some people. Coffee and caffeine and migraine have a complex relationship: excessive caffeine consumption or withdrawal can trigger migraine attacks, but caffeine can also help alleviate headaches (including migraine) due to its analgesic properties. Caffeine is a major component of many over-the-counter medicines for migraine. Some people find drinking coffee or a soda or taking a caffeine tablet at the onset of a migraine attack lowers the intensity of a migraine headache. Regular use of caffeine, either as “treatment” or for pleasure, is not advised in patients with migraine. Most doctors limit caffeine to a regular cup of coffee or tea per day, with no caffeine-containing sodas or chocolate in their patients with migraine; caffeine withdrawal is also a frequent migraine trigger. Patients can notice withdrawal headaches when they stop coffee, even if they are only consuming 1 cup per day. Most people drink a lot more.

Myth: Headache Medicine Will Cure Migraine

False. There currently is no “cure” for migraine. There are several medicines available that certainly can help prevent, abort, or control symptoms of migraine. Some of these medications include over-the-counter analgesics; triptans (like sumatriptan or rizatriptan); gepants, which are small molecule CGRP (calcitonin gene-related peptide) antagonists; CGRP antibodies given by injection; antidepressants; antiseizure medicines; and beta-blockers. 

Myth: You Cannot Take Any Migraine Medications During Pregnancy

Migraine medications, such as triptans, are relatively safe during pregnancy, particularly after the first trimester. Acetaminophen in low doses is safe as well, but some of the preventive antiseizure medications should be avoided due to the risk of halting the pregnancy or producing a congenital malformation. Noninvasive wearable devices (such as Nerivio), biofeedback training, mindfulness, and relaxation techniques are particularly appealing to pregnant women as they have high efficacy with virtually no lasting side effects. 

Although patients who are pregnant might have an increased flurry of migraine headaches in the first trimester of their pregnancy, they will most likely have a decreased number of attacks in the next 2 trimesters of their pregnancy, making them feel really well. The first trimester is a dangerous time for fetuses to be exposed to certain medicines that are foreign to them, as their organs are still being formed. There are medicines that doctors feel are less problematic both for acute care and prevention of migraine during pregnancy; therefore, patients with a history of migraine should always consult with their obstetrician-gynecologist and a neurologist (or other doctor they usually see for their migraine care) before taking any medication if they are planning a pregnancy or are pregnant. 

Effective nonpharmaceutical options are available for all patients with migraine, whether pregnant or not. Maintaining a healthy lifestyle, which includes getting 7 to 10 hours of sleep each night, drinking plenty of water each day, getting ample nutrition from healthy foods, and eliminating as many sources of extra stress as possible can help reduce the risk of a migraine, even when exposed to a known trigger.

Medications may also lead to headaches by a phenomenon called medication overuse headache, if the rescue medication is taken too often. Clinicians recommend no more than 2 days per week of any acute care medication and taking a good preventive medication if needed.

Myth: “Migraine Diets” Cure Migraine

This is false. Avoiding known food triggers can reduce the risk of a migraine attack, but a diet regimen is not a cure. Although eating healthy foods and avoiding certain kinds of food that trigger migraine can eliminate triggering the episodes, there are other factors to take into account. For instance, the migraine diet cannot address a lack of sleep, stress, or hormonal changes a person experiences. Only very few patients with migraine can say their medication has cured their migraine, but it could happen.

Myth: Dietary Supplements Can Cure Migraine

This myth is not true. Supplements can help migraine headache or prevent triggering it, but they won’t cure it. Supplements, such as magnesium, vitamin D3, coenzyme Q10, vitamin B2 (riboflavin), feverfew, melatonin, and vitamin B2 are important additions to the migraine treatment armamentarium, but no one specific vitamin/mineral or supplement has been proven to help prevent or relieve migraine for everyone. They help some people immensely and do little for others, just as with any pharmacologic agent.

Myth: It’s Not a Migraine Unless You Experience Aura

This is not true, as most migraines present without aura. Migraine with typical aura affects 30% of patients with migraine.

Myth: Researchers No Longer Investigate Migraine

False; there are several ongoing studies working to address the pathophysiology of migraine and find new treatment options. Recently, neuromodulation devices have entered the market. One such device from Theranica (called Nerivio) now has clearance from the US Food and Drug Administration for acute and preventive migraine treatment from age 12 and up. One phase 4 study by Theranica shows that Nerivio appears to be safe during pregnancy.                                                                                                                                                         

Several migraine studies of note include the following:

• OnabotulinumtoxinA as a treatment for hemiplegic migraine: This project aims to evaluate the response to onabotulinumtoxinA treatments in patients with hemiplegic migraine evaluated at Mayo Clinic.

• Occipital nerve stimulation for migraine: OPTIMISE. This study is evaluating the safety and efficacy of occipital nerve stimulation (ONS) using the Boston Scientific Corporation (BSC) Precision™ System in the management of intractable chronic migraine, when used in conjunction with antimigraine medications.

• The Medication Overuse Treatment Strategy trial: This study is comparing the outcomes among patients randomized to 1 of the 2 treatment strategies for treating patients who have chronic migraine with medication overuse.

• Metformin is being investigated as a treatment for the prevention of episodic migraine.

Myth: Migraine Cannot Be Diagnosed Without an Imaging Exam

This is false. Migraine is a clinical diagnosis and does not need any imaging to confirm. Imaging is indicated only if the symptoms are not clear or if there are neurologic symptoms or warning signs accompanying the migraine. In such cases, imaging would be warranted to rule out other pathologies. A magnetic resonance imaging scan is performed to rule out other pathology, not to diagnose migraine. A clinician must identify a pattern in the patient’s history according to the diagnostic criteria of the International Headache Society to diagnose migraine, which include that the patient had 5 previous attacks without aura or 2 attacks with aura.

Summary

Headaches, especially migraine, can be unpleasant and disabling and can significantly affect a patient’s quality of life. However, pharmaceutical and nonpharmaceutical interventions that can help are available. Lifestyle changes, including diet, sleep, and stress reduction can ease symptoms and reduce the frequency of migraine attacks. As researchers continue to investigate the pathophysiology of migraine, they are sure to identify better treatments and, perhaps one day—a cure.

Patients may be familiar with several myths and have misconceptions about headaches and migraine, which often arise due to a combination of factors, including limited understanding of the conditions, cultural beliefs, misinformation, and the complex nature of headaches. Being aware of these myths and seeking accurate information help patients to better understand and manage their headaches.

Myth: Migraine Is the Most Common Type of Headache

This is not true. The most common type of headache is tension-type headache, and it's the kind of headache that almost everyone has from time to time. Between 40% and 80% of the US population have had some form of tension-type headache, but only about 13% of the adult population have migraine. Stress can make muscles in the head and neck tense and knotted, and these muscles can be the source of a tension-type headache. Sometimes these headaches are not at all related to muscles or stress. Neck position may also be a factor. Pain from this type of headache is usually felt on both sides of the head and presents more often as steady, dull pressure or pain that’s usually mild to moderate in intensity. The pain can be in the forehead and eyes or further back in the head. Tension-type headaches are not usually associated with nausea, vomiting, or light and sound sensitivity.

When a tension-type headache is really severe, patients could consider this headache a migraine. Clinicians can easily distinguish tension-type headache from migraine, which often presents on one side of the head, with moderate or severe intensity, is throbbing, and is associated with nausea, vomiting, and light and sound sensitivity.

Myth: Only Adults Get Headaches

False. Headaches aren’t experienced just by adults. However, unlike adults, children find it harder to explain their headaches. It is true that adults have more migraines than children; children’s migraines are often hard for doctors to recognize. A 6- to 9-year-old child is 50% less likely than an adult to have migraine, and their attacks are more often bilateral, are shorter, and respond to sleep quickly.

Myth: Migraines Are Just Really Bad Headaches

False. They are bad, but that is only a small part of the story. A migraine attack is different from other headaches; they actually are 1 of the 3 primary headache disorders, along with tension-type headache and cluster headache. A moderate or severe headache is one of the many characteristics of migraine, and some patients do not even have a headache during a migraine attack. Migraine is an inherited disease of the brain and other parts of the nervous system and can feel much worse than a normal headache. During a migraine attack, the brain does not process sensory data, such as lights, sound, or touch, properly. Patients might even experience visual, sensory, or speech problems (ie, auras) and sometime see flashing lights or zigzag lines that blink on and off or blind spots in their vision. Patients with migraine are often nauseated and severely bothered by light, sound, and even smells. Migraine headaches can last between 4 and 72 hours on average, causing disability, tiredness, and inability to think clearly or work productively, which adds to the burden of the disease. So, migraine is not just a headache. 

Myth: More Women Than Men Experience Migraine 

This is true. Epidemiologic data show a 3-fold higher incidence of migraine in women than men, starting from puberty and throughout life. From about 6 to 12 years, boys have a slightly higher incidence than girls, but then migraine occurrence levels off and becomes a disease primarily of women. The modulation of neuronal and vascular reactivity by hormones (namely estrogens and progesterone) is a crucial aspect of migraine in some women only. These hormones exert influence on a spectrum of neuromediators and neurotransmitters, potentially leading to functional and structural variations in specific brain regions associated with migraine pathogenesis. Beyond their central effects, sex hormones also modulate vascular tone. Therefore, migraine follows a pattern throughout a woman’s life corresponding to the fluctuation of estrogen. Within a year of their first menstrual period, many girls with migraine have their first attack. They are more likely to have a migraine attack just before and at the start of menses, and at other times of the month as well. They feel better when pregnant and worse after they stop breastfeeding, and they start to feel worse prior to menopause. Then they improve a few years after menopause.

While men are less at risk of having migraine, they’re more likely to have cluster headache than women (although this type of headache is rare compared with other headaches like migraine). Only about 0.1% or less of the population of adults in the US experience this type of headache. Cluster headache gets its name from the clustering of attacks occurring 2 to 6 times per day for 4 to 10 weeks and disappearing as quickly as they came. This headache pain is felt exclusively in or behind 1 eye and rarely elsewhere, on the same side of the head. There is also a clustering of other symptoms called autonomic findings, such as tearing and redness of 1 eye, stuffiness and running in 1 nostril, sweating over 1 eyebrow, drooping of 1 eyelid, and a small pupil—all on the same side of the head the pain is radiating from. Most patients have only some of these findings. Cluster headaches tend to occur every year around the same time (circannual). When a patient is in a cycle of cluster headaches, they often occur at the same time each day (circadian). These set times of the year and of the day are caused by the biological clock deep down under the brain in the hypothalamus.

Myth: All Headaches Are Psychological

This is not true. Usually the underlying cause of migraine is genetically-inherited, but each attack may be triggered by an underlying cause (eg, drop in barometric pressure, menses, certain food/drinks, lack of sleep, stress, etc). Even tension-type headaches can be triggered by muscles in the head and neck becoming tense, stressful events, or jaw issues, which in turn send out pain signals that are felt on both sides of the head.

Many years ago (ie, 1950s-1960s), it was thought that the underlying cause of migraine in women was psychological issues; that has been disproven many times. Both men and women have migraine, and they both can have coexisting psychological issues (ie, depression, anxiety, and other psychiatric problems). 

Myth: Migraines Aren’t Serious

Most types of migraine in and of themselves are not serious; however, chronic migraine can continue for years and is debilitating and disabling—becoming a serious issue for patients. These patients usually take many medications, are obese, can have big changes in weight and severe insomnia, don’t exercise enough, and develop other illnesses. Migraine can severely impact quality of life; many people living with migraine have reported reduced productivity while at work, lack of promotion, loss of jobs, and a disruption in their family, social, and leisure activities.

Migraine attacks vary from one person to another and can be quite different from one attack to another in the same person. Hemiplegic migraine, a rare and distinct subtype that is sometimes inherited, is characterized by neurologic symptoms (multiple auras, including a significant weakness or paralysis on 1 side of the body). Although these patients seem much sicker and have multiple types of auras and 1-sided weakness with a prolonged headache, most recover without serious consequences. 

Myth: Lack of Sleep Causes Migraine 

Yes, lack of sleep is a known trigger for migraine in many people, but lack of sleep is not the cause of migraine. Sleep deprivation and irregular sleep patterns can disrupt the delicate balance of neurotransmitters and hormones in the brain, potentially triggering migraine in susceptible individuals. Additionally, inadequate sleep may contribute to increased stress and tension, which are also common triggers for migraine. In fact, many people with migraine do have sleep issues, which can range from trouble falling asleep to early morning awakening without being able to get back to sleep or frequently interrupted sleep each night. Correcting the sleep problem is part of the migraine therapy. Patients should be checked for sleep apnea if they wake with headache in the morning. Medication overuse headache should also be considered.

Establishing a regular sleep routine and ensuring an adequate amount of sleep can be important components of managing migraine symptoms, particularly for those who find a connection between their sleep patterns and the onset of a migraine attack. However, the relationship between sleep and migraine can vary widely among individuals, and other factors may also contribute to migraine triggers.

Myth: Caffeine Causes Migraine

This is a myth; caffeine does not cause migraine but definitely can be a trigger for some people. Coffee and caffeine and migraine have a complex relationship: excessive caffeine consumption or withdrawal can trigger migraine attacks, but caffeine can also help alleviate headaches (including migraine) due to its analgesic properties. Caffeine is a major component of many over-the-counter medicines for migraine. Some people find drinking coffee or a soda or taking a caffeine tablet at the onset of a migraine attack lowers the intensity of a migraine headache. Regular use of caffeine, either as “treatment” or for pleasure, is not advised in patients with migraine. Most doctors limit caffeine to a regular cup of coffee or tea per day, with no caffeine-containing sodas or chocolate in their patients with migraine; caffeine withdrawal is also a frequent migraine trigger. Patients can notice withdrawal headaches when they stop coffee, even if they are only consuming 1 cup per day. Most people drink a lot more.

Myth: Headache Medicine Will Cure Migraine

False. There currently is no “cure” for migraine. There are several medicines available that certainly can help prevent, abort, or control symptoms of migraine. Some of these medications include over-the-counter analgesics; triptans (like sumatriptan or rizatriptan); gepants, which are small molecule CGRP (calcitonin gene-related peptide) antagonists; CGRP antibodies given by injection; antidepressants; antiseizure medicines; and beta-blockers. 

Myth: You Cannot Take Any Migraine Medications During Pregnancy

Migraine medications, such as triptans, are relatively safe during pregnancy, particularly after the first trimester. Acetaminophen in low doses is safe as well, but some of the preventive antiseizure medications should be avoided due to the risk of halting the pregnancy or producing a congenital malformation. Noninvasive wearable devices (such as Nerivio), biofeedback training, mindfulness, and relaxation techniques are particularly appealing to pregnant women as they have high efficacy with virtually no lasting side effects. 

Although patients who are pregnant might have an increased flurry of migraine headaches in the first trimester of their pregnancy, they will most likely have a decreased number of attacks in the next 2 trimesters of their pregnancy, making them feel really well. The first trimester is a dangerous time for fetuses to be exposed to certain medicines that are foreign to them, as their organs are still being formed. There are medicines that doctors feel are less problematic both for acute care and prevention of migraine during pregnancy; therefore, patients with a history of migraine should always consult with their obstetrician-gynecologist and a neurologist (or other doctor they usually see for their migraine care) before taking any medication if they are planning a pregnancy or are pregnant. 

Effective nonpharmaceutical options are available for all patients with migraine, whether pregnant or not. Maintaining a healthy lifestyle, which includes getting 7 to 10 hours of sleep each night, drinking plenty of water each day, getting ample nutrition from healthy foods, and eliminating as many sources of extra stress as possible can help reduce the risk of a migraine, even when exposed to a known trigger.

Medications may also lead to headaches by a phenomenon called medication overuse headache, if the rescue medication is taken too often. Clinicians recommend no more than 2 days per week of any acute care medication and taking a good preventive medication if needed.

Myth: “Migraine Diets” Cure Migraine

This is false. Avoiding known food triggers can reduce the risk of a migraine attack, but a diet regimen is not a cure. Although eating healthy foods and avoiding certain kinds of food that trigger migraine can eliminate triggering the episodes, there are other factors to take into account. For instance, the migraine diet cannot address a lack of sleep, stress, or hormonal changes a person experiences. Only very few patients with migraine can say their medication has cured their migraine, but it could happen.

Myth: Dietary Supplements Can Cure Migraine

This myth is not true. Supplements can help migraine headache or prevent triggering it, but they won’t cure it. Supplements, such as magnesium, vitamin D3, coenzyme Q10, vitamin B2 (riboflavin), feverfew, melatonin, and vitamin B2 are important additions to the migraine treatment armamentarium, but no one specific vitamin/mineral or supplement has been proven to help prevent or relieve migraine for everyone. They help some people immensely and do little for others, just as with any pharmacologic agent.

Myth: It’s Not a Migraine Unless You Experience Aura

This is not true, as most migraines present without aura. Migraine with typical aura affects 30% of patients with migraine.

Myth: Researchers No Longer Investigate Migraine

False; there are several ongoing studies working to address the pathophysiology of migraine and find new treatment options. Recently, neuromodulation devices have entered the market. One such device from Theranica (called Nerivio) now has clearance from the US Food and Drug Administration for acute and preventive migraine treatment from age 12 and up. One phase 4 study by Theranica shows that Nerivio appears to be safe during pregnancy.                                                                                                                                                         

Several migraine studies of note include the following:

• OnabotulinumtoxinA as a treatment for hemiplegic migraine: This project aims to evaluate the response to onabotulinumtoxinA treatments in patients with hemiplegic migraine evaluated at Mayo Clinic.

• Occipital nerve stimulation for migraine: OPTIMISE. This study is evaluating the safety and efficacy of occipital nerve stimulation (ONS) using the Boston Scientific Corporation (BSC) Precision™ System in the management of intractable chronic migraine, when used in conjunction with antimigraine medications.

• The Medication Overuse Treatment Strategy trial: This study is comparing the outcomes among patients randomized to 1 of the 2 treatment strategies for treating patients who have chronic migraine with medication overuse.

• Metformin is being investigated as a treatment for the prevention of episodic migraine.

Myth: Migraine Cannot Be Diagnosed Without an Imaging Exam

This is false. Migraine is a clinical diagnosis and does not need any imaging to confirm. Imaging is indicated only if the symptoms are not clear or if there are neurologic symptoms or warning signs accompanying the migraine. In such cases, imaging would be warranted to rule out other pathologies. A magnetic resonance imaging scan is performed to rule out other pathology, not to diagnose migraine. A clinician must identify a pattern in the patient’s history according to the diagnostic criteria of the International Headache Society to diagnose migraine, which include that the patient had 5 previous attacks without aura or 2 attacks with aura.

Summary

Headaches, especially migraine, can be unpleasant and disabling and can significantly affect a patient’s quality of life. However, pharmaceutical and nonpharmaceutical interventions that can help are available. Lifestyle changes, including diet, sleep, and stress reduction can ease symptoms and reduce the frequency of migraine attacks. As researchers continue to investigate the pathophysiology of migraine, they are sure to identify better treatments and, perhaps one day—a cure.

Patients may be familiar with several myths and have misconceptions about headaches and migraine, which often arise due to a combination of factors, including limited understanding of the conditions, cultural beliefs, misinformation, and the complex nature of headaches. Being aware of these myths and seeking accurate information help patients to better understand and manage their headaches.

Myth: Migraine Is the Most Common Type of Headache

This is not true. The most common type of headache is tension-type headache, and it's the kind of headache that almost everyone has from time to time. Between 40% and 80% of the US population have had some form of tension-type headache, but only about 13% of the adult population have migraine. Stress can make muscles in the head and neck tense and knotted, and these muscles can be the source of a tension-type headache. Sometimes these headaches are not at all related to muscles or stress. Neck position may also be a factor. Pain from this type of headache is usually felt on both sides of the head and presents more often as steady, dull pressure or pain that’s usually mild to moderate in intensity. The pain can be in the forehead and eyes or further back in the head. Tension-type headaches are not usually associated with nausea, vomiting, or light and sound sensitivity.

When a tension-type headache is really severe, patients could consider this headache a migraine. Clinicians can easily distinguish tension-type headache from migraine, which often presents on one side of the head, with moderate or severe intensity, is throbbing, and is associated with nausea, vomiting, and light and sound sensitivity.

Myth: Only Adults Get Headaches

False. Headaches aren’t experienced just by adults. However, unlike adults, children find it harder to explain their headaches. It is true that adults have more migraines than children; children’s migraines are often hard for doctors to recognize. A 6- to 9-year-old child is 50% less likely than an adult to have migraine, and their attacks are more often bilateral, are shorter, and respond to sleep quickly.

Myth: Migraines Are Just Really Bad Headaches

False. They are bad, but that is only a small part of the story. A migraine attack is different from other headaches; they actually are 1 of the 3 primary headache disorders, along with tension-type headache and cluster headache. A moderate or severe headache is one of the many characteristics of migraine, and some patients do not even have a headache during a migraine attack. Migraine is an inherited disease of the brain and other parts of the nervous system and can feel much worse than a normal headache. During a migraine attack, the brain does not process sensory data, such as lights, sound, or touch, properly. Patients might even experience visual, sensory, or speech problems (ie, auras) and sometime see flashing lights or zigzag lines that blink on and off or blind spots in their vision. Patients with migraine are often nauseated and severely bothered by light, sound, and even smells. Migraine headaches can last between 4 and 72 hours on average, causing disability, tiredness, and inability to think clearly or work productively, which adds to the burden of the disease. So, migraine is not just a headache. 

Myth: More Women Than Men Experience Migraine 

This is true. Epidemiologic data show a 3-fold higher incidence of migraine in women than men, starting from puberty and throughout life. From about 6 to 12 years, boys have a slightly higher incidence than girls, but then migraine occurrence levels off and becomes a disease primarily of women. The modulation of neuronal and vascular reactivity by hormones (namely estrogens and progesterone) is a crucial aspect of migraine in some women only. These hormones exert influence on a spectrum of neuromediators and neurotransmitters, potentially leading to functional and structural variations in specific brain regions associated with migraine pathogenesis. Beyond their central effects, sex hormones also modulate vascular tone. Therefore, migraine follows a pattern throughout a woman’s life corresponding to the fluctuation of estrogen. Within a year of their first menstrual period, many girls with migraine have their first attack. They are more likely to have a migraine attack just before and at the start of menses, and at other times of the month as well. They feel better when pregnant and worse after they stop breastfeeding, and they start to feel worse prior to menopause. Then they improve a few years after menopause.

While men are less at risk of having migraine, they’re more likely to have cluster headache than women (although this type of headache is rare compared with other headaches like migraine). Only about 0.1% or less of the population of adults in the US experience this type of headache. Cluster headache gets its name from the clustering of attacks occurring 2 to 6 times per day for 4 to 10 weeks and disappearing as quickly as they came. This headache pain is felt exclusively in or behind 1 eye and rarely elsewhere, on the same side of the head. There is also a clustering of other symptoms called autonomic findings, such as tearing and redness of 1 eye, stuffiness and running in 1 nostril, sweating over 1 eyebrow, drooping of 1 eyelid, and a small pupil—all on the same side of the head the pain is radiating from. Most patients have only some of these findings. Cluster headaches tend to occur every year around the same time (circannual). When a patient is in a cycle of cluster headaches, they often occur at the same time each day (circadian). These set times of the year and of the day are caused by the biological clock deep down under the brain in the hypothalamus.

Myth: All Headaches Are Psychological

This is not true. Usually the underlying cause of migraine is genetically-inherited, but each attack may be triggered by an underlying cause (eg, drop in barometric pressure, menses, certain food/drinks, lack of sleep, stress, etc). Even tension-type headaches can be triggered by muscles in the head and neck becoming tense, stressful events, or jaw issues, which in turn send out pain signals that are felt on both sides of the head.

Many years ago (ie, 1950s-1960s), it was thought that the underlying cause of migraine in women was psychological issues; that has been disproven many times. Both men and women have migraine, and they both can have coexisting psychological issues (ie, depression, anxiety, and other psychiatric problems). 

Myth: Migraines Aren’t Serious

Most types of migraine in and of themselves are not serious; however, chronic migraine can continue for years and is debilitating and disabling—becoming a serious issue for patients. These patients usually take many medications, are obese, can have big changes in weight and severe insomnia, don’t exercise enough, and develop other illnesses. Migraine can severely impact quality of life; many people living with migraine have reported reduced productivity while at work, lack of promotion, loss of jobs, and a disruption in their family, social, and leisure activities.

Migraine attacks vary from one person to another and can be quite different from one attack to another in the same person. Hemiplegic migraine, a rare and distinct subtype that is sometimes inherited, is characterized by neurologic symptoms (multiple auras, including a significant weakness or paralysis on 1 side of the body). Although these patients seem much sicker and have multiple types of auras and 1-sided weakness with a prolonged headache, most recover without serious consequences. 

Myth: Lack of Sleep Causes Migraine 

Yes, lack of sleep is a known trigger for migraine in many people, but lack of sleep is not the cause of migraine. Sleep deprivation and irregular sleep patterns can disrupt the delicate balance of neurotransmitters and hormones in the brain, potentially triggering migraine in susceptible individuals. Additionally, inadequate sleep may contribute to increased stress and tension, which are also common triggers for migraine. In fact, many people with migraine do have sleep issues, which can range from trouble falling asleep to early morning awakening without being able to get back to sleep or frequently interrupted sleep each night. Correcting the sleep problem is part of the migraine therapy. Patients should be checked for sleep apnea if they wake with headache in the morning. Medication overuse headache should also be considered.

Establishing a regular sleep routine and ensuring an adequate amount of sleep can be important components of managing migraine symptoms, particularly for those who find a connection between their sleep patterns and the onset of a migraine attack. However, the relationship between sleep and migraine can vary widely among individuals, and other factors may also contribute to migraine triggers.

Myth: Caffeine Causes Migraine

This is a myth; caffeine does not cause migraine but definitely can be a trigger for some people. Coffee and caffeine and migraine have a complex relationship: excessive caffeine consumption or withdrawal can trigger migraine attacks, but caffeine can also help alleviate headaches (including migraine) due to its analgesic properties. Caffeine is a major component of many over-the-counter medicines for migraine. Some people find drinking coffee or a soda or taking a caffeine tablet at the onset of a migraine attack lowers the intensity of a migraine headache. Regular use of caffeine, either as “treatment” or for pleasure, is not advised in patients with migraine. Most doctors limit caffeine to a regular cup of coffee or tea per day, with no caffeine-containing sodas or chocolate in their patients with migraine; caffeine withdrawal is also a frequent migraine trigger. Patients can notice withdrawal headaches when they stop coffee, even if they are only consuming 1 cup per day. Most people drink a lot more.

Myth: Headache Medicine Will Cure Migraine

False. There currently is no “cure” for migraine. There are several medicines available that certainly can help prevent, abort, or control symptoms of migraine. Some of these medications include over-the-counter analgesics; triptans (like sumatriptan or rizatriptan); gepants, which are small molecule CGRP (calcitonin gene-related peptide) antagonists; CGRP antibodies given by injection; antidepressants; antiseizure medicines; and beta-blockers. 

Myth: You Cannot Take Any Migraine Medications During Pregnancy

Migraine medications, such as triptans, are relatively safe during pregnancy, particularly after the first trimester. Acetaminophen in low doses is safe as well, but some of the preventive antiseizure medications should be avoided due to the risk of halting the pregnancy or producing a congenital malformation. Noninvasive wearable devices (such as Nerivio), biofeedback training, mindfulness, and relaxation techniques are particularly appealing to pregnant women as they have high efficacy with virtually no lasting side effects. 

Although patients who are pregnant might have an increased flurry of migraine headaches in the first trimester of their pregnancy, they will most likely have a decreased number of attacks in the next 2 trimesters of their pregnancy, making them feel really well. The first trimester is a dangerous time for fetuses to be exposed to certain medicines that are foreign to them, as their organs are still being formed. There are medicines that doctors feel are less problematic both for acute care and prevention of migraine during pregnancy; therefore, patients with a history of migraine should always consult with their obstetrician-gynecologist and a neurologist (or other doctor they usually see for their migraine care) before taking any medication if they are planning a pregnancy or are pregnant. 

Effective nonpharmaceutical options are available for all patients with migraine, whether pregnant or not. Maintaining a healthy lifestyle, which includes getting 7 to 10 hours of sleep each night, drinking plenty of water each day, getting ample nutrition from healthy foods, and eliminating as many sources of extra stress as possible can help reduce the risk of a migraine, even when exposed to a known trigger.

Medications may also lead to headaches by a phenomenon called medication overuse headache, if the rescue medication is taken too often. Clinicians recommend no more than 2 days per week of any acute care medication and taking a good preventive medication if needed.

Myth: “Migraine Diets” Cure Migraine

This is false. Avoiding known food triggers can reduce the risk of a migraine attack, but a diet regimen is not a cure. Although eating healthy foods and avoiding certain kinds of food that trigger migraine can eliminate triggering the episodes, there are other factors to take into account. For instance, the migraine diet cannot address a lack of sleep, stress, or hormonal changes a person experiences. Only very few patients with migraine can say their medication has cured their migraine, but it could happen.

Myth: Dietary Supplements Can Cure Migraine

This myth is not true. Supplements can help migraine headache or prevent triggering it, but they won’t cure it. Supplements, such as magnesium, vitamin D3, coenzyme Q10, vitamin B2 (riboflavin), feverfew, melatonin, and vitamin B2 are important additions to the migraine treatment armamentarium, but no one specific vitamin/mineral or supplement has been proven to help prevent or relieve migraine for everyone. They help some people immensely and do little for others, just as with any pharmacologic agent.

Myth: It’s Not a Migraine Unless You Experience Aura

This is not true, as most migraines present without aura. Migraine with typical aura affects 30% of patients with migraine.

Myth: Researchers No Longer Investigate Migraine

False; there are several ongoing studies working to address the pathophysiology of migraine and find new treatment options. Recently, neuromodulation devices have entered the market. One such device from Theranica (called Nerivio) now has clearance from the US Food and Drug Administration for acute and preventive migraine treatment from age 12 and up. One phase 4 study by Theranica shows that Nerivio appears to be safe during pregnancy.                                                                                                                                                         

Several migraine studies of note include the following:

• OnabotulinumtoxinA as a treatment for hemiplegic migraine: This project aims to evaluate the response to onabotulinumtoxinA treatments in patients with hemiplegic migraine evaluated at Mayo Clinic.

• Occipital nerve stimulation for migraine: OPTIMISE. This study is evaluating the safety and efficacy of occipital nerve stimulation (ONS) using the Boston Scientific Corporation (BSC) Precision™ System in the management of intractable chronic migraine, when used in conjunction with antimigraine medications.

• The Medication Overuse Treatment Strategy trial: This study is comparing the outcomes among patients randomized to 1 of the 2 treatment strategies for treating patients who have chronic migraine with medication overuse.

• Metformin is being investigated as a treatment for the prevention of episodic migraine.

Myth: Migraine Cannot Be Diagnosed Without an Imaging Exam

This is false. Migraine is a clinical diagnosis and does not need any imaging to confirm. Imaging is indicated only if the symptoms are not clear or if there are neurologic symptoms or warning signs accompanying the migraine. In such cases, imaging would be warranted to rule out other pathologies. A magnetic resonance imaging scan is performed to rule out other pathology, not to diagnose migraine. A clinician must identify a pattern in the patient’s history according to the diagnostic criteria of the International Headache Society to diagnose migraine, which include that the patient had 5 previous attacks without aura or 2 attacks with aura.

Summary

Headaches, especially migraine, can be unpleasant and disabling and can significantly affect a patient’s quality of life. However, pharmaceutical and nonpharmaceutical interventions that can help are available. Lifestyle changes, including diet, sleep, and stress reduction can ease symptoms and reduce the frequency of migraine attacks. As researchers continue to investigate the pathophysiology of migraine, they are sure to identify better treatments and, perhaps one day—a cure.

Follow your own path to better outcomes for patients with GI diseases at Digestive Disease Week^® (DDW) 2024, the world’s largest and most comprehensive gathering of gastroenterology clinicians, researchers and industry. Registration and housing are now open, and AGA members can save up to $380 on registration fees. Discounted registration rates are also available through the March 13 early bird deadline. AGA member trainees, students, residents and postdoctoral fellows can register for free through this date. Visit ddw.org/register to join us.

This year, DDW takes place May 18-21, in Washington, D.C., and online. Whether you work in patient care, research, training or academia, you’ll find content tailored to your essential role at every step.

Add on to your DDW experience with AGA’s one-day Postgraduate Course. Join us on May 18, from D.C. or online, to explore challenging patient cases, high-impact papers, and important practice updates that you can use immediately upon your return to the clinic. Learn more at pgcourse.gastro.org.

Follow your own path to better outcomes for patients with GI diseases at Digestive Disease Week^® (DDW) 2024, the world’s largest and most comprehensive gathering of gastroenterology clinicians, researchers and industry. Registration and housing are now open, and AGA members can save up to $380 on registration fees. Discounted registration rates are also available through the March 13 early bird deadline. AGA member trainees, students, residents and postdoctoral fellows can register for free through this date. Visit ddw.org/register to join us.

This year, DDW takes place May 18-21, in Washington, D.C., and online. Whether you work in patient care, research, training or academia, you’ll find content tailored to your essential role at every step.

Add on to your DDW experience with AGA’s one-day Postgraduate Course. Join us on May 18, from D.C. or online, to explore challenging patient cases, high-impact papers, and important practice updates that you can use immediately upon your return to the clinic. Learn more at pgcourse.gastro.org.

Follow your own path to better outcomes for patients with GI diseases at Digestive Disease Week^® (DDW) 2024, the world’s largest and most comprehensive gathering of gastroenterology clinicians, researchers and industry. Registration and housing are now open, and AGA members can save up to $380 on registration fees. Discounted registration rates are also available through the March 13 early bird deadline. AGA member trainees, students, residents and postdoctoral fellows can register for free through this date. Visit ddw.org/register to join us.

This year, DDW takes place May 18-21, in Washington, D.C., and online. Whether you work in patient care, research, training or academia, you’ll find content tailored to your essential role at every step.

Add on to your DDW experience with AGA’s one-day Postgraduate Course. Join us on May 18, from D.C. or online, to explore challenging patient cases, high-impact papers, and important practice updates that you can use immediately upon your return to the clinic. Learn more at pgcourse.gastro.org.

TOPLINE:

Exercise with weight machines or elastic resistance bands yielded similar improvements in strength and function in adults with psoriatic arthritis (PsA) after 12 weeks.

METHODOLOGY:

• Researchers recruited 41 adults aged 18-65 years with PsA who were then randomized to a functional training group (FT) or a resistance exercise group (RE) for 12 weeks of twice-weekly, 55-minute sessions under the supervision of a physical trainer.
• Functional training involved the use of elastic bands to work upper body, lower body, and trunk muscles including the biceps, triceps, back quadriceps, glutes, and hips; the RE used weight machines instead of bands.
• Participants were evaluated at baseline and after 6 and 12 weeks of training sessions; the primary outcome was functional status based on the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
• Secondary outcomes included the Bath Ankylosing Spondylitis Functional Index (BASFI) to assess functional capacity, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Score in 28 joints (DAS28) to assess disease activity, and the Short Form 36 (SF-36) to measure quality of life.

TAKEAWAY:

• Participants in both groups showed significant improvement from baseline on the primary outcome measure, with no significant differences between the groups on the primary outcome of function or secondary measures of function and disease activity after 12 weeks.
• Significant intragroup changes occurred between times for both groups on the HAQ-S, BASFI, BASDAI, and DAS28 (P = .001, .007, .001, and .001, respectively).
• Improvement in quality of life was significant from baseline and similar between the FT and RE, with the exception of the “social aspects” domain, for which only the FT showed significant improvement.
• No intervention-related adverse events were reported in either group.

IN PRACTICE:

Despite the absence of consensus guidelines on the use and effectiveness of FT and RE, “we can conclude that both FT and RE have similar effectiveness in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis,” the researchers wrote.

SOURCE:

The study was led by Diego Roger Silva, MD, of the Universidade Federal de São Paulo, Brazil, and published online in Advances in Rheumatology.

LIMITATIONS:

The study population was recruited from outpatient clinics, and the mean age of 52 years was higher than in previous studies; the study also lacked long-term follow-up data.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Exercise with weight machines or elastic resistance bands yielded similar improvements in strength and function in adults with psoriatic arthritis (PsA) after 12 weeks.

METHODOLOGY:

• Researchers recruited 41 adults aged 18-65 years with PsA who were then randomized to a functional training group (FT) or a resistance exercise group (RE) for 12 weeks of twice-weekly, 55-minute sessions under the supervision of a physical trainer.
• Functional training involved the use of elastic bands to work upper body, lower body, and trunk muscles including the biceps, triceps, back quadriceps, glutes, and hips; the RE used weight machines instead of bands.
• Participants were evaluated at baseline and after 6 and 12 weeks of training sessions; the primary outcome was functional status based on the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
• Secondary outcomes included the Bath Ankylosing Spondylitis Functional Index (BASFI) to assess functional capacity, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Score in 28 joints (DAS28) to assess disease activity, and the Short Form 36 (SF-36) to measure quality of life.

TAKEAWAY:

• Participants in both groups showed significant improvement from baseline on the primary outcome measure, with no significant differences between the groups on the primary outcome of function or secondary measures of function and disease activity after 12 weeks.
• Significant intragroup changes occurred between times for both groups on the HAQ-S, BASFI, BASDAI, and DAS28 (P = .001, .007, .001, and .001, respectively).
• Improvement in quality of life was significant from baseline and similar between the FT and RE, with the exception of the “social aspects” domain, for which only the FT showed significant improvement.
• No intervention-related adverse events were reported in either group.

IN PRACTICE:

Despite the absence of consensus guidelines on the use and effectiveness of FT and RE, “we can conclude that both FT and RE have similar effectiveness in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis,” the researchers wrote.

SOURCE:

The study was led by Diego Roger Silva, MD, of the Universidade Federal de São Paulo, Brazil, and published online in Advances in Rheumatology.

LIMITATIONS:

The study population was recruited from outpatient clinics, and the mean age of 52 years was higher than in previous studies; the study also lacked long-term follow-up data.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Exercise with weight machines or elastic resistance bands yielded similar improvements in strength and function in adults with psoriatic arthritis (PsA) after 12 weeks.

METHODOLOGY:

• Researchers recruited 41 adults aged 18-65 years with PsA who were then randomized to a functional training group (FT) or a resistance exercise group (RE) for 12 weeks of twice-weekly, 55-minute sessions under the supervision of a physical trainer.
• Functional training involved the use of elastic bands to work upper body, lower body, and trunk muscles including the biceps, triceps, back quadriceps, glutes, and hips; the RE used weight machines instead of bands.
• Participants were evaluated at baseline and after 6 and 12 weeks of training sessions; the primary outcome was functional status based on the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
• Secondary outcomes included the Bath Ankylosing Spondylitis Functional Index (BASFI) to assess functional capacity, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Score in 28 joints (DAS28) to assess disease activity, and the Short Form 36 (SF-36) to measure quality of life.

TAKEAWAY:

• Participants in both groups showed significant improvement from baseline on the primary outcome measure, with no significant differences between the groups on the primary outcome of function or secondary measures of function and disease activity after 12 weeks.
• Significant intragroup changes occurred between times for both groups on the HAQ-S, BASFI, BASDAI, and DAS28 (P = .001, .007, .001, and .001, respectively).
• Improvement in quality of life was significant from baseline and similar between the FT and RE, with the exception of the “social aspects” domain, for which only the FT showed significant improvement.
• No intervention-related adverse events were reported in either group.

IN PRACTICE:

Despite the absence of consensus guidelines on the use and effectiveness of FT and RE, “we can conclude that both FT and RE have similar effectiveness in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis,” the researchers wrote.

SOURCE:

The study was led by Diego Roger Silva, MD, of the Universidade Federal de São Paulo, Brazil, and published online in Advances in Rheumatology.

LIMITATIONS:

The study population was recruited from outpatient clinics, and the mean age of 52 years was higher than in previous studies; the study also lacked long-term follow-up data.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults whose rheumatoid arthritis caused them severe functional limitations showed significant improvement in measures of function and quality of life following at least 1 year of a personalized, supervised exercise program than those who received usual care.

METHODOLOGY:

• Researchers randomized 217 adults with rheumatoid arthritis and severe functional limitations to an active exercise intervention delivered by a physical therapist (PT) or usual care; the mean age of the participants was approximately 59 years, and approximately 90% were female.
• The intervention consisted of individualized goal setting, active exercises adapted to functional limitations, and education about self-management of physical activity in two sessions per week for the first 12 weeks, followed by once weekly sessions with the option for additional sessions if needed. The primary care PTs in the Netherlands who treated the patients were primarily recruited through a national network of PTs with specific expertise regarding rheumatic diseases.
• In considering each participant’s three most limited activities, the study’s primary outcome at 52 weeks measured the change from the one ranked highest at baseline on the Patient-Specific Complaints Numeric Rating Scale (PSC1 NRS); secondary outcomes included changes in the NRS for participants’ second and third most difficult activities, as well as the Patient Reported Outcome Measurement Information System Physical Function-10, the Health Assessment Questionnaire-Disability Index, the Rheumatoid Arthritis Quality of Life Questionnaire, the 36-Item Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scales (PCS and MCS), and the 6-minute walk test.

TAKEAWAY:

• At 52 weeks, the change in PSC1 NRS was significantly greater in the intervention group than in the usual care group, with a mean difference of −1.7 and a between-group effect size from baseline of 0.7.
• Improvements in secondary outcome measures at 52 weeks also were significantly greater in the intervention group than in the usual care group, with the exception of the SF-36 MCS, which showed no difference between the groups.
• A total of 89 participants in the intervention group and 45 participants in the usual care group responded to questions about muscle soreness and fatigue; 70% and 60%, and 71% and 64%, of each group reported these conditions, respectively.

IN PRACTICE:

“The completion of the trial substantiates the feasibility of recruiting and training primary care [physical therapists] to deliver a complex intervention,” although more research is needed to explore long-term outcomes and cost-effectiveness, the researchers wrote.

SOURCE:

The lead author on the study was Max M.H. Teuwen, MSc, a PhD candidate at Leiden University Medical Center, Leiden, the Netherlands. The study was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The participants were not blinded to their group, and blinded assessors became aware of the allocations, which might have impacted measurements; other limitations included lack of data on medication changes and the exclusion of physical activity amount as an outcome measure.

DISCLOSURES:

The study was supported by the Netherlands Organization for Health Research and Development; the Ministry of Health, Welfare and Sport; the Royal Dutch Society for Physical Therapy; and the Dutch Arthritis Society. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults whose rheumatoid arthritis caused them severe functional limitations showed significant improvement in measures of function and quality of life following at least 1 year of a personalized, supervised exercise program than those who received usual care.

METHODOLOGY:

• Researchers randomized 217 adults with rheumatoid arthritis and severe functional limitations to an active exercise intervention delivered by a physical therapist (PT) or usual care; the mean age of the participants was approximately 59 years, and approximately 90% were female.
• The intervention consisted of individualized goal setting, active exercises adapted to functional limitations, and education about self-management of physical activity in two sessions per week for the first 12 weeks, followed by once weekly sessions with the option for additional sessions if needed. The primary care PTs in the Netherlands who treated the patients were primarily recruited through a national network of PTs with specific expertise regarding rheumatic diseases.
• In considering each participant’s three most limited activities, the study’s primary outcome at 52 weeks measured the change from the one ranked highest at baseline on the Patient-Specific Complaints Numeric Rating Scale (PSC1 NRS); secondary outcomes included changes in the NRS for participants’ second and third most difficult activities, as well as the Patient Reported Outcome Measurement Information System Physical Function-10, the Health Assessment Questionnaire-Disability Index, the Rheumatoid Arthritis Quality of Life Questionnaire, the 36-Item Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scales (PCS and MCS), and the 6-minute walk test.

TAKEAWAY:

• At 52 weeks, the change in PSC1 NRS was significantly greater in the intervention group than in the usual care group, with a mean difference of −1.7 and a between-group effect size from baseline of 0.7.
• Improvements in secondary outcome measures at 52 weeks also were significantly greater in the intervention group than in the usual care group, with the exception of the SF-36 MCS, which showed no difference between the groups.
• A total of 89 participants in the intervention group and 45 participants in the usual care group responded to questions about muscle soreness and fatigue; 70% and 60%, and 71% and 64%, of each group reported these conditions, respectively.

IN PRACTICE:

“The completion of the trial substantiates the feasibility of recruiting and training primary care [physical therapists] to deliver a complex intervention,” although more research is needed to explore long-term outcomes and cost-effectiveness, the researchers wrote.

SOURCE:

The lead author on the study was Max M.H. Teuwen, MSc, a PhD candidate at Leiden University Medical Center, Leiden, the Netherlands. The study was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The participants were not blinded to their group, and blinded assessors became aware of the allocations, which might have impacted measurements; other limitations included lack of data on medication changes and the exclusion of physical activity amount as an outcome measure.

DISCLOSURES:

The study was supported by the Netherlands Organization for Health Research and Development; the Ministry of Health, Welfare and Sport; the Royal Dutch Society for Physical Therapy; and the Dutch Arthritis Society. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults whose rheumatoid arthritis caused them severe functional limitations showed significant improvement in measures of function and quality of life following at least 1 year of a personalized, supervised exercise program than those who received usual care.

METHODOLOGY:

• Researchers randomized 217 adults with rheumatoid arthritis and severe functional limitations to an active exercise intervention delivered by a physical therapist (PT) or usual care; the mean age of the participants was approximately 59 years, and approximately 90% were female.
• The intervention consisted of individualized goal setting, active exercises adapted to functional limitations, and education about self-management of physical activity in two sessions per week for the first 12 weeks, followed by once weekly sessions with the option for additional sessions if needed. The primary care PTs in the Netherlands who treated the patients were primarily recruited through a national network of PTs with specific expertise regarding rheumatic diseases.
• In considering each participant’s three most limited activities, the study’s primary outcome at 52 weeks measured the change from the one ranked highest at baseline on the Patient-Specific Complaints Numeric Rating Scale (PSC1 NRS); secondary outcomes included changes in the NRS for participants’ second and third most difficult activities, as well as the Patient Reported Outcome Measurement Information System Physical Function-10, the Health Assessment Questionnaire-Disability Index, the Rheumatoid Arthritis Quality of Life Questionnaire, the 36-Item Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scales (PCS and MCS), and the 6-minute walk test.

TAKEAWAY:

• At 52 weeks, the change in PSC1 NRS was significantly greater in the intervention group than in the usual care group, with a mean difference of −1.7 and a between-group effect size from baseline of 0.7.
• Improvements in secondary outcome measures at 52 weeks also were significantly greater in the intervention group than in the usual care group, with the exception of the SF-36 MCS, which showed no difference between the groups.
• A total of 89 participants in the intervention group and 45 participants in the usual care group responded to questions about muscle soreness and fatigue; 70% and 60%, and 71% and 64%, of each group reported these conditions, respectively.

IN PRACTICE:

“The completion of the trial substantiates the feasibility of recruiting and training primary care [physical therapists] to deliver a complex intervention,” although more research is needed to explore long-term outcomes and cost-effectiveness, the researchers wrote.

SOURCE:

The lead author on the study was Max M.H. Teuwen, MSc, a PhD candidate at Leiden University Medical Center, Leiden, the Netherlands. The study was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The participants were not blinded to their group, and blinded assessors became aware of the allocations, which might have impacted measurements; other limitations included lack of data on medication changes and the exclusion of physical activity amount as an outcome measure.

DISCLOSURES:

The study was supported by the Netherlands Organization for Health Research and Development; the Ministry of Health, Welfare and Sport; the Royal Dutch Society for Physical Therapy; and the Dutch Arthritis Society. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Women with autoimmune disease are more likely to have perinatal depression (PND), according to findings from a new study that also suggested the reverse relationship is true: Women with a history of PND have a higher risk of developing autoimmune disease.

The research, published online on January 9, 2024, in Molecular Psychiatry, was led by Emma Bränn, PhD, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the group of approximately 815,000 women and 1.3 million pregnancies, just more than 55,000 women had been diagnosed with depression during their pregnancy or within a year after delivery.

The researchers then compared the incidence of 41 autoimmune diseases in women who had and did not have PND. They controlled for factors including genetic makeup and childhood environment.

Results indicated that women with autoimmune disease were 30% more likely to have PND (odds ratio, 1.30; 95% CI, 1.25-1.35). Conversely, women with PND were 30% more likely than women with no PND to develop an autoimmune disease (hazard ratio, 1.30; 95% CI, 1.25-1.36).

A sibling comparison helped confirm the results by controlling for some shared genetic and early life environmental factors related to the household in which sisters grew up.
 

Potential Shared Biological Mechanisms

The association was independent of psychiatric comorbidities, suggesting there may be shared biological mechanisms.

Dr. Bränn told this news organization that the research team wanted to do the study because previous research has shown involvement of the immune system in depression, with similarities in both the symptoms of immune system–activated diseases and depression and the molecular pathways activated by the immune system.

“Adding on top of the tremendous changes in the immune system that we see in the body of the woman during the perinatal period, we hypothesized that autoimmune diseases could be associated to perinatal depression,” she said. “This had also been shown in some previous literature but not to the extent as what we have investigated in this paper.”

She said their results help make a case for counseling women at several points in healthcare interactions — before and after conception and childbirth — and in rheumatology visits to inform women with autoimmune diseases who are contemplating motherhood of the association with developing PND. The results may also demonstrate a need for monitoring women in these groups for depression or autoimmune disease.

Fred Miller, MD, PhD, retired Scientist Emeritus of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, who was not part of the study, said the results seem plausible as they build on early work that demonstrated selected associations between autoimmune conditions and mental illness.

“These associations may be the result of shared genetic and environmental risk factors, including stress, hormonal changes, medications, and the proinflammatory states that can lead to both,” he said.

The novelty, he said, is in the relatively strong associations of PND with autoimmune disease overall and with specific autoimmune diseases.
 

Strong Link Found With Multiple Sclerosis (MS)

According to the paper, a significant positive bidirectional link was found for autoimmune thyroid disease, psoriasis, MS, ulcerative colitis, and celiac disease.

Researchers found a particularly strong association — double the risk in both directions — between PND and MS.

Dr. Miller said though it is unclear from this study why the association of PND with MS was stronger than with other autoimmune diseases, people with MS are known to be at a high risk for depression in general. That may come from greater shared genetic and environmental risk factors, he added.

Additionally, MS is one of the more common autoimmune diseases, he noted, so the population is larger for study.

He said he was surprised the researchers didn’t investigate medication use because medications used in depression have immunologic effects and medications used in autoimmune diseases could have effects on mental conditions.

The study has implications for clinicians in a wide variety of specialties, Dr. Miller noted.

“It suggests that caregivers be more alert to the signs of developing autoimmune disease in women with perinatal depression and to the signs of developing perinatal depression in those with autoimmune disease,” Dr. Miller said, “so that appropriate screening, diagnostics, and interventions may be undertaken.”

The researchers say they will continue to examine the long-term effects of depression during pregnancy and in the year after childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” Dr. Bränn said. “We hope that our results will help decision-makers to steer funding toward maternal healthcare so that more women can get help and support in time.”

The study was financed by Karolinska Institute, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Council, and the Icelandic Research Fund.

The researchers and Dr. Miller reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women with autoimmune disease are more likely to have perinatal depression (PND), according to findings from a new study that also suggested the reverse relationship is true: Women with a history of PND have a higher risk of developing autoimmune disease.

The research, published online on January 9, 2024, in Molecular Psychiatry, was led by Emma Bränn, PhD, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the group of approximately 815,000 women and 1.3 million pregnancies, just more than 55,000 women had been diagnosed with depression during their pregnancy or within a year after delivery.

The researchers then compared the incidence of 41 autoimmune diseases in women who had and did not have PND. They controlled for factors including genetic makeup and childhood environment.

Results indicated that women with autoimmune disease were 30% more likely to have PND (odds ratio, 1.30; 95% CI, 1.25-1.35). Conversely, women with PND were 30% more likely than women with no PND to develop an autoimmune disease (hazard ratio, 1.30; 95% CI, 1.25-1.36).

A sibling comparison helped confirm the results by controlling for some shared genetic and early life environmental factors related to the household in which sisters grew up.
 

Potential Shared Biological Mechanisms

The association was independent of psychiatric comorbidities, suggesting there may be shared biological mechanisms.

Dr. Bränn told this news organization that the research team wanted to do the study because previous research has shown involvement of the immune system in depression, with similarities in both the symptoms of immune system–activated diseases and depression and the molecular pathways activated by the immune system.

“Adding on top of the tremendous changes in the immune system that we see in the body of the woman during the perinatal period, we hypothesized that autoimmune diseases could be associated to perinatal depression,” she said. “This had also been shown in some previous literature but not to the extent as what we have investigated in this paper.”

She said their results help make a case for counseling women at several points in healthcare interactions — before and after conception and childbirth — and in rheumatology visits to inform women with autoimmune diseases who are contemplating motherhood of the association with developing PND. The results may also demonstrate a need for monitoring women in these groups for depression or autoimmune disease.

Fred Miller, MD, PhD, retired Scientist Emeritus of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, who was not part of the study, said the results seem plausible as they build on early work that demonstrated selected associations between autoimmune conditions and mental illness.

“These associations may be the result of shared genetic and environmental risk factors, including stress, hormonal changes, medications, and the proinflammatory states that can lead to both,” he said.

The novelty, he said, is in the relatively strong associations of PND with autoimmune disease overall and with specific autoimmune diseases.
 

Strong Link Found With Multiple Sclerosis (MS)

According to the paper, a significant positive bidirectional link was found for autoimmune thyroid disease, psoriasis, MS, ulcerative colitis, and celiac disease.

Researchers found a particularly strong association — double the risk in both directions — between PND and MS.

Dr. Miller said though it is unclear from this study why the association of PND with MS was stronger than with other autoimmune diseases, people with MS are known to be at a high risk for depression in general. That may come from greater shared genetic and environmental risk factors, he added.

Additionally, MS is one of the more common autoimmune diseases, he noted, so the population is larger for study.

He said he was surprised the researchers didn’t investigate medication use because medications used in depression have immunologic effects and medications used in autoimmune diseases could have effects on mental conditions.

The study has implications for clinicians in a wide variety of specialties, Dr. Miller noted.

“It suggests that caregivers be more alert to the signs of developing autoimmune disease in women with perinatal depression and to the signs of developing perinatal depression in those with autoimmune disease,” Dr. Miller said, “so that appropriate screening, diagnostics, and interventions may be undertaken.”

The researchers say they will continue to examine the long-term effects of depression during pregnancy and in the year after childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” Dr. Bränn said. “We hope that our results will help decision-makers to steer funding toward maternal healthcare so that more women can get help and support in time.”

The study was financed by Karolinska Institute, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Council, and the Icelandic Research Fund.

The researchers and Dr. Miller reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women with autoimmune disease are more likely to have perinatal depression (PND), according to findings from a new study that also suggested the reverse relationship is true: Women with a history of PND have a higher risk of developing autoimmune disease.

The research, published online on January 9, 2024, in Molecular Psychiatry, was led by Emma Bränn, PhD, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the group of approximately 815,000 women and 1.3 million pregnancies, just more than 55,000 women had been diagnosed with depression during their pregnancy or within a year after delivery.

The researchers then compared the incidence of 41 autoimmune diseases in women who had and did not have PND. They controlled for factors including genetic makeup and childhood environment.

Results indicated that women with autoimmune disease were 30% more likely to have PND (odds ratio, 1.30; 95% CI, 1.25-1.35). Conversely, women with PND were 30% more likely than women with no PND to develop an autoimmune disease (hazard ratio, 1.30; 95% CI, 1.25-1.36).

A sibling comparison helped confirm the results by controlling for some shared genetic and early life environmental factors related to the household in which sisters grew up.
 

Potential Shared Biological Mechanisms

The association was independent of psychiatric comorbidities, suggesting there may be shared biological mechanisms.

Dr. Bränn told this news organization that the research team wanted to do the study because previous research has shown involvement of the immune system in depression, with similarities in both the symptoms of immune system–activated diseases and depression and the molecular pathways activated by the immune system.

“Adding on top of the tremendous changes in the immune system that we see in the body of the woman during the perinatal period, we hypothesized that autoimmune diseases could be associated to perinatal depression,” she said. “This had also been shown in some previous literature but not to the extent as what we have investigated in this paper.”

She said their results help make a case for counseling women at several points in healthcare interactions — before and after conception and childbirth — and in rheumatology visits to inform women with autoimmune diseases who are contemplating motherhood of the association with developing PND. The results may also demonstrate a need for monitoring women in these groups for depression or autoimmune disease.

Fred Miller, MD, PhD, retired Scientist Emeritus of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, who was not part of the study, said the results seem plausible as they build on early work that demonstrated selected associations between autoimmune conditions and mental illness.

“These associations may be the result of shared genetic and environmental risk factors, including stress, hormonal changes, medications, and the proinflammatory states that can lead to both,” he said.

The novelty, he said, is in the relatively strong associations of PND with autoimmune disease overall and with specific autoimmune diseases.
 

Strong Link Found With Multiple Sclerosis (MS)

According to the paper, a significant positive bidirectional link was found for autoimmune thyroid disease, psoriasis, MS, ulcerative colitis, and celiac disease.

Researchers found a particularly strong association — double the risk in both directions — between PND and MS.

Dr. Miller said though it is unclear from this study why the association of PND with MS was stronger than with other autoimmune diseases, people with MS are known to be at a high risk for depression in general. That may come from greater shared genetic and environmental risk factors, he added.

Additionally, MS is one of the more common autoimmune diseases, he noted, so the population is larger for study.

He said he was surprised the researchers didn’t investigate medication use because medications used in depression have immunologic effects and medications used in autoimmune diseases could have effects on mental conditions.

The study has implications for clinicians in a wide variety of specialties, Dr. Miller noted.

“It suggests that caregivers be more alert to the signs of developing autoimmune disease in women with perinatal depression and to the signs of developing perinatal depression in those with autoimmune disease,” Dr. Miller said, “so that appropriate screening, diagnostics, and interventions may be undertaken.”

The researchers say they will continue to examine the long-term effects of depression during pregnancy and in the year after childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” Dr. Bränn said. “We hope that our results will help decision-makers to steer funding toward maternal healthcare so that more women can get help and support in time.”

The study was financed by Karolinska Institute, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Council, and the Icelandic Research Fund.

The researchers and Dr. Miller reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.