Amyloid PET may help facilitate diagnosis of inclusion body myositis

Amyloid PET imaging may help to accurately identify inclusion body myositis and distinguish it from polymyositis, which could potentially avoid misdiagnosis and unnecessary immunosuppressive medication, according to findings from a small prospective cohort study.

The study, which found significantly greater uptake of the imaging agent [18F]florbetapir (Amyvid) in muscle from patients with inclusion body myositis (IBM) than in those with polymyositis (PM), builds on previous research showing that the intramuscular beta-amyloid seen in histopathologic analysis of IBM can help distinguish it from PM, but this approach has a low sensitivity along with high diagnostic specificity. The latest diagnostic criteria for IBM have also shifted away from strict histopathologic analysis toward identifying its characteristic clinical pattern of muscle weakness, first author James B. Lilleker, PhD, of the Centre for Musculoskeletal Research at the University of Manchester (England) and his colleagues wrote in Annals of the Rheumatic Diseases.

“While this has improved sensitivity, clinically detectable weakness implies that significant and irreversible muscle damage has occurred, reducing the likelihood that novel treatments will be effective,” the researchers wrote.

Thomas E. Lloyd II, MD, PhD, codirector of the myositis center at Johns Hopkins University, Baltimore, said in an interview that IBM is difficult to diagnose because of a lack of awareness of the early clinical signs and symptoms of the disease among primary care physicians, neurologists, and rheumatologists.

“Typically, a myositis specialist can make the diagnosis based on a combination of history and exam [slowly progressive weakness affecting distal finger flexors and knee extensors] and muscle biopsy features [endomysial inflammation with rimmed vacuoles and protein aggregates],” said Dr. Lloyd, who was not involved in the current study. “However, early in the course of disease, some patients may be misdiagnosed with polymyositis due to having atypical clinical or pathological features, especially if the muscle biopsy lacks rimmed vacuoles or the patient lacks obvious finger flexor weakness.”

But amyloid PET is promising and needs further analysis comparing it with expert diagnosis, Dr. Lloyd said. “I think this imaging method has greatest potential utility to be helpful diagnostically early in the course of disease, when diagnosis of IBM can be most challenging. This approach may also have potential to identify presymptomatic patients, especially if amyloid imaging becomes used for screening for Alzheimer’s disease in the future.”

Dr. Lilleker and colleagues set out to determine whether amyloid PET with [18F]florbetapir could distinguish between IBM and PM. They identified 10 patients with IBM and 6 patients with PM and scanned each patient from shoulders to ankles with CT and PET, followed by a same-day, whole-body MRI scan. Overall, regions of interest included the left arm, right and left forearms, right and left thighs, and right and left calves. The researchers calculated the [18F]florbetapir standard uptake values (SUVs) for each region of interest while SUV ratios (SUVRs) were calculated using the lumbar fat pad reference region.

The IBM patients (9 men, 1 woman) had a mean age of 68.3 years at the time of the scan and a mean disease duration of 4 years, and they were not currently taking immunosuppressive treatments; however, patients had previously taken prednisolone (3 of 10 patients), azathioprine (1 of 10 patients), and mycophenolate (1 of 10 patients). In the PM group (4 men, 2 women), patients’ mean age was 59.7 years, with a mean disease duration of 1.5 years.

The researchers found significantly increased overall [18F]florbetapir SUVRs among all regions of interest for IBM patients (median total SUVR, 1.45; interquartile range, 1.28-2.05), compared with PM patients (total SUVR, 1.01; IQR, 0.80-1.22; P = .005). In addition, when total [18F]florbetapir SUVR was 1.28 or greater, the diagnostic sensitivity for IBM was 80% and specificity was 100%, with an area under the curve of 0.93. There were also no significant associations between total [18F]florbetapir SUVR and age at the time of the scan, disease duration, or clinical outcome measurements such as manual muscle testing of 26 muscles (MMT26), Health Assessment Questionnaire disability index, and IBM Functional Rating Scale.

Dr. Lilleker and his colleagues noted the small study size as a potential limitation, but said other factors such as age and disease severity, which differed between groups, were unlikely to affect the [18F]florbetapir SUVR.

The rarity of PM may make it difficult to determine amyloid PET imaging’s effectiveness in diagnosing IBM when compared with more traditional methods, Dr. Lloyd noted.

“Whether PET imaging is more sensitive than expert diagnosis using traditional methods [careful physical exam of individual distal interphalangeal finger flexor muscles, MRI imaging of thighs, detailed pathological analysis of muscle biopsy including immunostaining for p62/SQSTM1, detailed serum autoantibody testing, etc.] remains to be determined,” he said.

This study was supported by grants from the National Institute for Health Research Manchester Musculoskeletal Biomedical Research Centre, the Medical Research Council, and an award from the Centre for Imaging Sciences at the University of Manchester. The authors reported no conflicts of interest. Dr. Lloyd reported being a consultant for Acceleron and principal investigator for IBM clinical trials sponsored by Orphazyme and Regeneron.

SOURCE: Lilleker JB et al. Ann Rheum Dis. 2019 Feb 13. doi: 10.1136/annrheumdis-2018-214644.

Amyloid PET imaging may help to accurately identify inclusion body myositis and distinguish it from polymyositis, which could potentially avoid misdiagnosis and unnecessary immunosuppressive medication, according to findings from a small prospective cohort study.

The study, which found significantly greater uptake of the imaging agent [18F]florbetapir (Amyvid) in muscle from patients with inclusion body myositis (IBM) than in those with polymyositis (PM), builds on previous research showing that the intramuscular beta-amyloid seen in histopathologic analysis of IBM can help distinguish it from PM, but this approach has a low sensitivity along with high diagnostic specificity. The latest diagnostic criteria for IBM have also shifted away from strict histopathologic analysis toward identifying its characteristic clinical pattern of muscle weakness, first author James B. Lilleker, PhD, of the Centre for Musculoskeletal Research at the University of Manchester (England) and his colleagues wrote in Annals of the Rheumatic Diseases.

“While this has improved sensitivity, clinically detectable weakness implies that significant and irreversible muscle damage has occurred, reducing the likelihood that novel treatments will be effective,” the researchers wrote.

Thomas E. Lloyd II, MD, PhD, codirector of the myositis center at Johns Hopkins University, Baltimore, said in an interview that IBM is difficult to diagnose because of a lack of awareness of the early clinical signs and symptoms of the disease among primary care physicians, neurologists, and rheumatologists.

“Typically, a myositis specialist can make the diagnosis based on a combination of history and exam [slowly progressive weakness affecting distal finger flexors and knee extensors] and muscle biopsy features [endomysial inflammation with rimmed vacuoles and protein aggregates],” said Dr. Lloyd, who was not involved in the current study. “However, early in the course of disease, some patients may be misdiagnosed with polymyositis due to having atypical clinical or pathological features, especially if the muscle biopsy lacks rimmed vacuoles or the patient lacks obvious finger flexor weakness.”

But amyloid PET is promising and needs further analysis comparing it with expert diagnosis, Dr. Lloyd said. “I think this imaging method has greatest potential utility to be helpful diagnostically early in the course of disease, when diagnosis of IBM can be most challenging. This approach may also have potential to identify presymptomatic patients, especially if amyloid imaging becomes used for screening for Alzheimer’s disease in the future.”

Dr. Lilleker and colleagues set out to determine whether amyloid PET with [18F]florbetapir could distinguish between IBM and PM. They identified 10 patients with IBM and 6 patients with PM and scanned each patient from shoulders to ankles with CT and PET, followed by a same-day, whole-body MRI scan. Overall, regions of interest included the left arm, right and left forearms, right and left thighs, and right and left calves. The researchers calculated the [18F]florbetapir standard uptake values (SUVs) for each region of interest while SUV ratios (SUVRs) were calculated using the lumbar fat pad reference region.

The IBM patients (9 men, 1 woman) had a mean age of 68.3 years at the time of the scan and a mean disease duration of 4 years, and they were not currently taking immunosuppressive treatments; however, patients had previously taken prednisolone (3 of 10 patients), azathioprine (1 of 10 patients), and mycophenolate (1 of 10 patients). In the PM group (4 men, 2 women), patients’ mean age was 59.7 years, with a mean disease duration of 1.5 years.

The researchers found significantly increased overall [18F]florbetapir SUVRs among all regions of interest for IBM patients (median total SUVR, 1.45; interquartile range, 1.28-2.05), compared with PM patients (total SUVR, 1.01; IQR, 0.80-1.22; P = .005). In addition, when total [18F]florbetapir SUVR was 1.28 or greater, the diagnostic sensitivity for IBM was 80% and specificity was 100%, with an area under the curve of 0.93. There were also no significant associations between total [18F]florbetapir SUVR and age at the time of the scan, disease duration, or clinical outcome measurements such as manual muscle testing of 26 muscles (MMT26), Health Assessment Questionnaire disability index, and IBM Functional Rating Scale.

Dr. Lilleker and his colleagues noted the small study size as a potential limitation, but said other factors such as age and disease severity, which differed between groups, were unlikely to affect the [18F]florbetapir SUVR.

The rarity of PM may make it difficult to determine amyloid PET imaging’s effectiveness in diagnosing IBM when compared with more traditional methods, Dr. Lloyd noted.

“Whether PET imaging is more sensitive than expert diagnosis using traditional methods [careful physical exam of individual distal interphalangeal finger flexor muscles, MRI imaging of thighs, detailed pathological analysis of muscle biopsy including immunostaining for p62/SQSTM1, detailed serum autoantibody testing, etc.] remains to be determined,” he said.

This study was supported by grants from the National Institute for Health Research Manchester Musculoskeletal Biomedical Research Centre, the Medical Research Council, and an award from the Centre for Imaging Sciences at the University of Manchester. The authors reported no conflicts of interest. Dr. Lloyd reported being a consultant for Acceleron and principal investigator for IBM clinical trials sponsored by Orphazyme and Regeneron.

SOURCE: Lilleker JB et al. Ann Rheum Dis. 2019 Feb 13. doi: 10.1136/annrheumdis-2018-214644.

Amyloid PET imaging may help to accurately identify inclusion body myositis and distinguish it from polymyositis, which could potentially avoid misdiagnosis and unnecessary immunosuppressive medication, according to findings from a small prospective cohort study.

The study, which found significantly greater uptake of the imaging agent [18F]florbetapir (Amyvid) in muscle from patients with inclusion body myositis (IBM) than in those with polymyositis (PM), builds on previous research showing that the intramuscular beta-amyloid seen in histopathologic analysis of IBM can help distinguish it from PM, but this approach has a low sensitivity along with high diagnostic specificity. The latest diagnostic criteria for IBM have also shifted away from strict histopathologic analysis toward identifying its characteristic clinical pattern of muscle weakness, first author James B. Lilleker, PhD, of the Centre for Musculoskeletal Research at the University of Manchester (England) and his colleagues wrote in Annals of the Rheumatic Diseases.

“While this has improved sensitivity, clinically detectable weakness implies that significant and irreversible muscle damage has occurred, reducing the likelihood that novel treatments will be effective,” the researchers wrote.

Thomas E. Lloyd II, MD, PhD, codirector of the myositis center at Johns Hopkins University, Baltimore, said in an interview that IBM is difficult to diagnose because of a lack of awareness of the early clinical signs and symptoms of the disease among primary care physicians, neurologists, and rheumatologists.

“Typically, a myositis specialist can make the diagnosis based on a combination of history and exam [slowly progressive weakness affecting distal finger flexors and knee extensors] and muscle biopsy features [endomysial inflammation with rimmed vacuoles and protein aggregates],” said Dr. Lloyd, who was not involved in the current study. “However, early in the course of disease, some patients may be misdiagnosed with polymyositis due to having atypical clinical or pathological features, especially if the muscle biopsy lacks rimmed vacuoles or the patient lacks obvious finger flexor weakness.”

But amyloid PET is promising and needs further analysis comparing it with expert diagnosis, Dr. Lloyd said. “I think this imaging method has greatest potential utility to be helpful diagnostically early in the course of disease, when diagnosis of IBM can be most challenging. This approach may also have potential to identify presymptomatic patients, especially if amyloid imaging becomes used for screening for Alzheimer’s disease in the future.”

Dr. Lilleker and colleagues set out to determine whether amyloid PET with [18F]florbetapir could distinguish between IBM and PM. They identified 10 patients with IBM and 6 patients with PM and scanned each patient from shoulders to ankles with CT and PET, followed by a same-day, whole-body MRI scan. Overall, regions of interest included the left arm, right and left forearms, right and left thighs, and right and left calves. The researchers calculated the [18F]florbetapir standard uptake values (SUVs) for each region of interest while SUV ratios (SUVRs) were calculated using the lumbar fat pad reference region.

The IBM patients (9 men, 1 woman) had a mean age of 68.3 years at the time of the scan and a mean disease duration of 4 years, and they were not currently taking immunosuppressive treatments; however, patients had previously taken prednisolone (3 of 10 patients), azathioprine (1 of 10 patients), and mycophenolate (1 of 10 patients). In the PM group (4 men, 2 women), patients’ mean age was 59.7 years, with a mean disease duration of 1.5 years.

The researchers found significantly increased overall [18F]florbetapir SUVRs among all regions of interest for IBM patients (median total SUVR, 1.45; interquartile range, 1.28-2.05), compared with PM patients (total SUVR, 1.01; IQR, 0.80-1.22; P = .005). In addition, when total [18F]florbetapir SUVR was 1.28 or greater, the diagnostic sensitivity for IBM was 80% and specificity was 100%, with an area under the curve of 0.93. There were also no significant associations between total [18F]florbetapir SUVR and age at the time of the scan, disease duration, or clinical outcome measurements such as manual muscle testing of 26 muscles (MMT26), Health Assessment Questionnaire disability index, and IBM Functional Rating Scale.

Dr. Lilleker and his colleagues noted the small study size as a potential limitation, but said other factors such as age and disease severity, which differed between groups, were unlikely to affect the [18F]florbetapir SUVR.

The rarity of PM may make it difficult to determine amyloid PET imaging’s effectiveness in diagnosing IBM when compared with more traditional methods, Dr. Lloyd noted.

“Whether PET imaging is more sensitive than expert diagnosis using traditional methods [careful physical exam of individual distal interphalangeal finger flexor muscles, MRI imaging of thighs, detailed pathological analysis of muscle biopsy including immunostaining for p62/SQSTM1, detailed serum autoantibody testing, etc.] remains to be determined,” he said.

This study was supported by grants from the National Institute for Health Research Manchester Musculoskeletal Biomedical Research Centre, the Medical Research Council, and an award from the Centre for Imaging Sciences at the University of Manchester. The authors reported no conflicts of interest. Dr. Lloyd reported being a consultant for Acceleron and principal investigator for IBM clinical trials sponsored by Orphazyme and Regeneron.

SOURCE: Lilleker JB et al. Ann Rheum Dis. 2019 Feb 13. doi: 10.1136/annrheumdis-2018-214644.