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Meta-analysis generally supports LI-RADS classification accuracy
Higher (more severe) Liver Imaging Reporting and Data System (LI-RADS) categories contained increasing proportions of hepatocellular carcinomas and overall malignancies, supporting the general reliability of the system, according to a systematic review and meta-analysis of 17 retrospective studies.
But 13% of LR-2 (“probably benign”) observations were actually hepatocellular carcinomas, as were 38% of LR-3 (“intermediate probability of malignancy”) observations, reported Christian B. van der Pol, MD, of McMaster University, Hamilton, Ont., and Christopher S. Lim, BBS, of Harvard Medical School, Boston, and their associates. Thus, clinicians should consider biopsy of many LR-3s, and LR-2s might need “more active management” than the currently recommended “return to surveillance,” including consideration for biopsy of solid LR-2 nodules measuring 1 cm or more, they wrote in Gastroenterology.
Histopathology confirmed that 93% of CT and MRI observations designated as LR-M (“definite or probable malignancy”) were indeed malignancies and that 36% were hepatocellular carcinomas,
The LI-RADS system, like its counterparts in breast and prostate imaging (BI-RADS and PI-RADS), classifies CT and MRI findings based on level of suspicion for malignancy. These categories include LR-M, LR-3, LR-2, LR-1 (“definitely benign”), LR-TIV (“definitely tumor in vein”), and LR-4 and LR-5 (“probably” and “definitely” hepatocellular carcinoma). However, CT and MRI interpretation is only as useful as it is accurate. To calculate actual percentages of hepatocellular carcinomas and overall malignancies within each LI-RADS category, the investigators analyzed aggregate data from studies found by searching MEDLINE, Embase, Cochrane CENTRAL, and Scopus during 2014-2018.
These 17 studies included 2,760 patients and 3,556 imaging observations. Pathology was the reference standard for LR-M, but for other LI-RADS categories, the researchers accepted strong clinical indicators of hepatocellular carcinoma, such as a 50% increase in lesion size within 6 months, or posttreatment recurrence of a previously confirmed malignancy. They classified observations as negative if they stayed stable in size for at least 12 months, spontaneously diminished in size, or disappeared without treatment.
In all, 94% and 97% of LR-5 observations were (respectively) hepatocellular carcinomas and other malignancies, as were 79% and 92% of LR-TIVs, 36% and 93% of LR-Ms, 74% and 80% of LR-4s, 38% and 40% of LR-3s, and 13% and 14% of LR-2s. No LR-1s were confirmed as malignant.
“Our data suggest biopsy of LI-RADS 3 observations should be considered in many patients, as a risk of 38% of HCC would usually provoke biopsy of a lesion elsewhere in the body,” the researchers wrote. They suggested consideration for biopsy of certain LR-2 lesions, but added that many “are small, perfusional alterations caused by arterioportal shunts, which are often not reported” and would be difficult or impossible to biopsy.
The study did not cover the most recent (2018) LI-RADS system, which featured several changes to simplify and better align it with American Association for the Study of Liver Diseases criteria, the researchers noted. They called for prospective studies to help confirm the accuracy of the LI-RADS system, particularly with regard to intermediate categories, such as LR-2.
The researchers disclosed no funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.
SOURCE: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.
Higher (more severe) Liver Imaging Reporting and Data System (LI-RADS) categories contained increasing proportions of hepatocellular carcinomas and overall malignancies, supporting the general reliability of the system, according to a systematic review and meta-analysis of 17 retrospective studies.
But 13% of LR-2 (“probably benign”) observations were actually hepatocellular carcinomas, as were 38% of LR-3 (“intermediate probability of malignancy”) observations, reported Christian B. van der Pol, MD, of McMaster University, Hamilton, Ont., and Christopher S. Lim, BBS, of Harvard Medical School, Boston, and their associates. Thus, clinicians should consider biopsy of many LR-3s, and LR-2s might need “more active management” than the currently recommended “return to surveillance,” including consideration for biopsy of solid LR-2 nodules measuring 1 cm or more, they wrote in Gastroenterology.
Histopathology confirmed that 93% of CT and MRI observations designated as LR-M (“definite or probable malignancy”) were indeed malignancies and that 36% were hepatocellular carcinomas,
The LI-RADS system, like its counterparts in breast and prostate imaging (BI-RADS and PI-RADS), classifies CT and MRI findings based on level of suspicion for malignancy. These categories include LR-M, LR-3, LR-2, LR-1 (“definitely benign”), LR-TIV (“definitely tumor in vein”), and LR-4 and LR-5 (“probably” and “definitely” hepatocellular carcinoma). However, CT and MRI interpretation is only as useful as it is accurate. To calculate actual percentages of hepatocellular carcinomas and overall malignancies within each LI-RADS category, the investigators analyzed aggregate data from studies found by searching MEDLINE, Embase, Cochrane CENTRAL, and Scopus during 2014-2018.
These 17 studies included 2,760 patients and 3,556 imaging observations. Pathology was the reference standard for LR-M, but for other LI-RADS categories, the researchers accepted strong clinical indicators of hepatocellular carcinoma, such as a 50% increase in lesion size within 6 months, or posttreatment recurrence of a previously confirmed malignancy. They classified observations as negative if they stayed stable in size for at least 12 months, spontaneously diminished in size, or disappeared without treatment.
In all, 94% and 97% of LR-5 observations were (respectively) hepatocellular carcinomas and other malignancies, as were 79% and 92% of LR-TIVs, 36% and 93% of LR-Ms, 74% and 80% of LR-4s, 38% and 40% of LR-3s, and 13% and 14% of LR-2s. No LR-1s were confirmed as malignant.
“Our data suggest biopsy of LI-RADS 3 observations should be considered in many patients, as a risk of 38% of HCC would usually provoke biopsy of a lesion elsewhere in the body,” the researchers wrote. They suggested consideration for biopsy of certain LR-2 lesions, but added that many “are small, perfusional alterations caused by arterioportal shunts, which are often not reported” and would be difficult or impossible to biopsy.
The study did not cover the most recent (2018) LI-RADS system, which featured several changes to simplify and better align it with American Association for the Study of Liver Diseases criteria, the researchers noted. They called for prospective studies to help confirm the accuracy of the LI-RADS system, particularly with regard to intermediate categories, such as LR-2.
The researchers disclosed no funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.
SOURCE: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.
Higher (more severe) Liver Imaging Reporting and Data System (LI-RADS) categories contained increasing proportions of hepatocellular carcinomas and overall malignancies, supporting the general reliability of the system, according to a systematic review and meta-analysis of 17 retrospective studies.
But 13% of LR-2 (“probably benign”) observations were actually hepatocellular carcinomas, as were 38% of LR-3 (“intermediate probability of malignancy”) observations, reported Christian B. van der Pol, MD, of McMaster University, Hamilton, Ont., and Christopher S. Lim, BBS, of Harvard Medical School, Boston, and their associates. Thus, clinicians should consider biopsy of many LR-3s, and LR-2s might need “more active management” than the currently recommended “return to surveillance,” including consideration for biopsy of solid LR-2 nodules measuring 1 cm or more, they wrote in Gastroenterology.
Histopathology confirmed that 93% of CT and MRI observations designated as LR-M (“definite or probable malignancy”) were indeed malignancies and that 36% were hepatocellular carcinomas,
The LI-RADS system, like its counterparts in breast and prostate imaging (BI-RADS and PI-RADS), classifies CT and MRI findings based on level of suspicion for malignancy. These categories include LR-M, LR-3, LR-2, LR-1 (“definitely benign”), LR-TIV (“definitely tumor in vein”), and LR-4 and LR-5 (“probably” and “definitely” hepatocellular carcinoma). However, CT and MRI interpretation is only as useful as it is accurate. To calculate actual percentages of hepatocellular carcinomas and overall malignancies within each LI-RADS category, the investigators analyzed aggregate data from studies found by searching MEDLINE, Embase, Cochrane CENTRAL, and Scopus during 2014-2018.
These 17 studies included 2,760 patients and 3,556 imaging observations. Pathology was the reference standard for LR-M, but for other LI-RADS categories, the researchers accepted strong clinical indicators of hepatocellular carcinoma, such as a 50% increase in lesion size within 6 months, or posttreatment recurrence of a previously confirmed malignancy. They classified observations as negative if they stayed stable in size for at least 12 months, spontaneously diminished in size, or disappeared without treatment.
In all, 94% and 97% of LR-5 observations were (respectively) hepatocellular carcinomas and other malignancies, as were 79% and 92% of LR-TIVs, 36% and 93% of LR-Ms, 74% and 80% of LR-4s, 38% and 40% of LR-3s, and 13% and 14% of LR-2s. No LR-1s were confirmed as malignant.
“Our data suggest biopsy of LI-RADS 3 observations should be considered in many patients, as a risk of 38% of HCC would usually provoke biopsy of a lesion elsewhere in the body,” the researchers wrote. They suggested consideration for biopsy of certain LR-2 lesions, but added that many “are small, perfusional alterations caused by arterioportal shunts, which are often not reported” and would be difficult or impossible to biopsy.
The study did not cover the most recent (2018) LI-RADS system, which featured several changes to simplify and better align it with American Association for the Study of Liver Diseases criteria, the researchers noted. They called for prospective studies to help confirm the accuracy of the LI-RADS system, particularly with regard to intermediate categories, such as LR-2.
The researchers disclosed no funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.
SOURCE: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.
FROM GASTROENTEROLOGY
Key clinical point: Consider biopsy of CT/MRI observations classified as LI-RADS 3 (intermediate probability of malignancy), as well as LI-RADS 2 (probably benign) observations that are solid nodules measuring at least 1 cm.
Major finding: In all, 13% of LR-2 observations were confirmed to be hepatocellular carcinomas, as were 38% of LR-3 observations.
Study details: Systematic review and meta-analysis of 17 retrospective studies.
Disclosures: The researchers disclosed no external funding sources. Dr. van der Pol, Dr. Lim, and three other investigators reported having no conflicts of interest. Five researchers reported that they are members of the LI-RADS Steering Committee and four disclosed ties to pharmaceutical companies.
Source: Van der Pol CB et al. Gastroenterology. 2018 Nov 13. doi: 10.1053/j.gastro.2018.11.020.
TNF inhibitors improve BMD in ankylosing spondylitis
Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.
The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.
K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.
After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.
In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.
Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.
“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.
They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.
“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.
No information on study funding or disclosures was available.
SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.
The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.
K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.
After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.
In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.
Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.
“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.
They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.
“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.
No information on study funding or disclosures was available.
SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
Long-term tumor necrosis factor inhibitor therapy improved bone mineral density but did not reduce vertebral fractures or radiographic progression in patients with ankylosing spondylitis, according to results from a prospective cohort study.
The study, published in the Journal of Bone and Mineral Research, not only confirms previous reports showing an improvement of the bone mineral density (BMD) during tumor necrosis factor inhibitor (TNFi) treatment in patients with ankylosing spondylitis but also an increase in the number and severity of vertebral fractures despite TNFi treatment.
K.J. Beek, of the Amsterdam Rheumatology and Immunology Centre in Amsterdam, and colleagues followed 135 patients with ankylosing spondylitis from the Amsterdam Spondyloarthritis cohort who were started on TNFi therapy after treatment failure of a minimum of two NSAIDs. Only study participants who were naive to TNFi therapy were enrolled in the study. The patients had a mean disease duration of nearly 12 years; 70% were men.
After 4 years of anti-TNF therapy, the proportion of patients with a low BMD of the hip on dual-energy x-ray absorptiometry significantly decreased from 40.1% to 31.8% (P = .03) and at the lumbar spine from 40.2% to 25.3% (P less than .001), respectively.
In addition, outcomes related to vertebral fractures, including incidence, prevalence, and severity, did not improve following 4 years of anti-TNF therapy. Vertebral fracture prevalence increased from 11.1% with at least one fracture to 19.3% with at least one fracture at the 4-year follow-up. Most of the vertebral fractures occurred in the thoracic rather than lumbar spine.
Radiographic progression significantly increased over the course of treatment, based on a rise in median modified Stoke Ankylosing Spondylitis Spinal Score from 4.0 at baseline to 6.5 at 4-year follow-up. Patients with vertebral fractures had significantly worse radiographic progression.
“These findings show a contradiction, with improvement of bone mineral density on the one hand but a worsening of the bone processes on the other hand, indicated by the increase of fractures and radiographic progression,” the investigators wrote.
They acknowledged a key limitation of the study was the observational design, which did not include a matched control group.
“A recommendation for future studies would be to replicate our results in larger groups of ankylosing spondylitis patients,” they concluded.
No information on study funding or disclosures was available.
SOURCE: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
FROM THE JOURNAL OF BONE AND MINERAL RESEARCH
Key clinical point: Long-term therapy with tumor necrosis factor inhibitors was shown to benefit bone mineral density in ankylosing spondylitis patients, but not vertebral fracture outcomes or radiographic progression.
Major finding: The proportion of patients with a low bone mineral density of the hip decreased from 40.1% to 31.8% (P = .03) after 4 years of tumor necrosis factor inhibitor treatment.
Study details: A prospective cohort study of 135 patients with ankylosing spondylitis treated with a tumor necrosis factor inhibitor for up to 4 years.
Disclosures: No information on study funding or disclosures was available.
Source: Beek KJ et al. J Bone Miner Res. 2019 Jan 28. doi: 10.1002/jbmr.3684.
Frailty, diabetes increase fragility fracture risk
increasing their risk of fragility fracture, according to findings from a prospective cohort study.
A total of 3,149 participants (70% women) were included in the study, 138 (60% women) of whom had type 2 diabetes. The mean age was 65 years and mean follow-up was 9.2 years. Over the study period, 611 fragility fractures were reported, of which 35 were in patients with diabetes and 576 in patients without diabetes. Overall, 25.4% of patients with diabetes experienced a fragility fracture, compared with 19.1% of control patients. Diabetes was associated with a significantly increased risk of all fragility fractures (hazard ratio, 1.54). It was also significantly associated with risk of hip fracture (HR, 2.60) but not clinical spine fracture.
In a Cox model incorporating the interaction between frailty index (FI) scores and diabetes, there was a significant association between FI and overall fracture risk per 0.01-point FI increase (HR, 1.02; 95% confidence interval, 1.01-1.03) and per 0.10-point FI increase (HR, 1.19; 95% CI, 1.10-1.33). However, no interaction between frailty and diabetes was observed for hip or clinical spine fractures.
“Frailty status may aid in the understanding of the paradox and thus enhance the quality of assessment and care for diabetes,” wrote Guowei Li, MBBS, PhD, of McMaster University, Hamilton, Ont., and his colleagues, adding that “particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.”
Four study authors reported conflicts of interest with some pharmaceutical companies that manufacture therapies for osteoporosis.
SOURCE: Li G et al. Diabetes Care. 2019 Jan 28. doi: 10.2337/dc18-1965.
increasing their risk of fragility fracture, according to findings from a prospective cohort study.
A total of 3,149 participants (70% women) were included in the study, 138 (60% women) of whom had type 2 diabetes. The mean age was 65 years and mean follow-up was 9.2 years. Over the study period, 611 fragility fractures were reported, of which 35 were in patients with diabetes and 576 in patients without diabetes. Overall, 25.4% of patients with diabetes experienced a fragility fracture, compared with 19.1% of control patients. Diabetes was associated with a significantly increased risk of all fragility fractures (hazard ratio, 1.54). It was also significantly associated with risk of hip fracture (HR, 2.60) but not clinical spine fracture.
In a Cox model incorporating the interaction between frailty index (FI) scores and diabetes, there was a significant association between FI and overall fracture risk per 0.01-point FI increase (HR, 1.02; 95% confidence interval, 1.01-1.03) and per 0.10-point FI increase (HR, 1.19; 95% CI, 1.10-1.33). However, no interaction between frailty and diabetes was observed for hip or clinical spine fractures.
“Frailty status may aid in the understanding of the paradox and thus enhance the quality of assessment and care for diabetes,” wrote Guowei Li, MBBS, PhD, of McMaster University, Hamilton, Ont., and his colleagues, adding that “particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.”
Four study authors reported conflicts of interest with some pharmaceutical companies that manufacture therapies for osteoporosis.
SOURCE: Li G et al. Diabetes Care. 2019 Jan 28. doi: 10.2337/dc18-1965.
increasing their risk of fragility fracture, according to findings from a prospective cohort study.
A total of 3,149 participants (70% women) were included in the study, 138 (60% women) of whom had type 2 diabetes. The mean age was 65 years and mean follow-up was 9.2 years. Over the study period, 611 fragility fractures were reported, of which 35 were in patients with diabetes and 576 in patients without diabetes. Overall, 25.4% of patients with diabetes experienced a fragility fracture, compared with 19.1% of control patients. Diabetes was associated with a significantly increased risk of all fragility fractures (hazard ratio, 1.54). It was also significantly associated with risk of hip fracture (HR, 2.60) but not clinical spine fracture.
In a Cox model incorporating the interaction between frailty index (FI) scores and diabetes, there was a significant association between FI and overall fracture risk per 0.01-point FI increase (HR, 1.02; 95% confidence interval, 1.01-1.03) and per 0.10-point FI increase (HR, 1.19; 95% CI, 1.10-1.33). However, no interaction between frailty and diabetes was observed for hip or clinical spine fractures.
“Frailty status may aid in the understanding of the paradox and thus enhance the quality of assessment and care for diabetes,” wrote Guowei Li, MBBS, PhD, of McMaster University, Hamilton, Ont., and his colleagues, adding that “particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.”
Four study authors reported conflicts of interest with some pharmaceutical companies that manufacture therapies for osteoporosis.
SOURCE: Li G et al. Diabetes Care. 2019 Jan 28. doi: 10.2337/dc18-1965.
FROM DIABETES CARE
Meet Dr. Vincent DeLeo at AAD
The new MDedge Dermatology podcast will feature Dr. Vincent A. DeLeo talking with colleagues about all things dermatology. The podcast will also feature news highlights.
Stop by our booth at AAD to chat with Dr. DeLeo!
Friday, March 1, 2019
2 pm to 3 pm
Booths 1721 and 1723
The new MDedge Dermatology podcast will feature Dr. Vincent A. DeLeo talking with colleagues about all things dermatology. The podcast will also feature news highlights.
Stop by our booth at AAD to chat with Dr. DeLeo!
Friday, March 1, 2019
2 pm to 3 pm
Booths 1721 and 1723
The new MDedge Dermatology podcast will feature Dr. Vincent A. DeLeo talking with colleagues about all things dermatology. The podcast will also feature news highlights.
Stop by our booth at AAD to chat with Dr. DeLeo!
Friday, March 1, 2019
2 pm to 3 pm
Booths 1721 and 1723
Biomarkers predict VTE risk with menopausal oral hormone therapy
CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.
She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.
“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.
The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.
In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.
Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).
Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.
In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.
In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.
“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.
Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.
The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.
The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.
And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).
At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.
Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.
CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.
She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.
“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.
The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.
In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.
Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).
Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.
In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.
In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.
“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.
Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.
The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.
The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.
And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).
At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.
Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.
CHICAGO – An elevated baseline D-dimer level is helpful to women and their physicians in clarifying decision making about oral hormone therapy for troublesome menopausal symptoms, Mary Cushman, MD, said at the American Heart Association scientific sessions.
She was lead investigator in a nested case-control study embedded in the landmark Women’s Health Initiative (WHI), which showed that participants who had a baseline D-dimer greater than 0.54 mg/L – putting them in the top 25% – and were randomized to oral menopausal hormone therapy had a 5-year incidence of venous thromboembolism (VTE) of 6%. That’s 500% higher than in women with a lower D-dimer randomized to placebo.
“The number needed to test for D-dimer in advance of prescribing in order to prevent one VTE over 5 years of hormone therapy was only 33. So this is potentially something in the toolbox you can use in counseling women about oral hormone therapy,” said Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont, Burlington.
The biomarker study included 1,082 WHI participants aged 50-79 years randomized to oral conjugated equine estrogen with or without medroxyprogesterone acetate or to placebo, 215 of whom experienced VTE during a mean 4.1 years of follow-up. Levels of a variety of biomarkers obtained at baseline were assessed in terms of their associated risk of future VTE. The biomarkers included C-reactive protein and procoagulant, anticoagulant, and fibrinolytic factors.
In a logistic regression analysis adjusted for age, race, body mass index, and hysterectomy, the strongest association with VTE was a high D-dimer. That 500% increased risk of VTE with hormone therapy in women with a D-dimer greater than 0.54 mg/L was comparable in magnitude with the risk Dr. Cushman and her coinvestigators previously reported for the combination of factor V Leiden and hormone therapy.
Dr. Cushman and her associates also took a first step towards developing a multibiomarker risk score. They found that WHI participants randomized to hormone therapy who had abnormal baseline values for any three or more of eight biomarkers had a 1,450% greater risk of future VTE than women with zero or one abnormal biomarker who were assigned to placebo. The eight-biomarker panel described in the recently published study comprised D-dimer, factor V Leiden, protein C, total protein S, free protein S, antithrombin, plasmin-antiplasmin complex, and fragment 1.2. However, the investigators indicated the risk score needs further study before it’s ready for adoption in clinical practice (Res Pract Thromb Haemost. 2018 Apr 17;2[2]:310-9).
Dr. Cushman noted that, although the main findings of the WHI have largely resulted in abandonment of menopausal hormone therapy for disease prevention, many women still want to take oral hormone therapy for relief of bothersome menopausal symptoms. She tries to steer them instead to safer nonoral formulations. Transdermal estrogen replacement has no associated risk of VTE and doesn’t activate anticoagulation. Neither does vaginal estradiol.
In offering what she called “the 30,000-foot view of the impact of venous thrombosis on women’s health,” Dr. Cushman noted that VTE is the third-most common vascular disease in the United States, with up to 900,000 cases per year. The lifetime risk in women after age 45 is 8.4%. Half of VTEs are provoked and therefore potentially preventable, with common triggers being surgery, cancer, pregnancy, trauma, and immobilization, especially during travel.
In addition, a retrospective study conducted in the Worcester, Mass., area showed that 1-month mortality after VTE remained static in the 5%-10% range during 1999-2009.
“This is a fatal disease, even though we treat it as an outpatient quite a lot,” Dr. Cushman observed.
Common nonfatal complications of VTE include major bleeding in 5%-10% of cases, a recurrence rate of 5%-10% annually, a 20%-40% of the burdensome and not infrequently disabling condition known as postthrombotic syndrome, and a 3%-4% incidence of chronic thromboembolic pulmonary hypertension. Yet despite the seriousness of VTE, awareness about VTE is poor among both patients and physicians, and appropriate prophylaxis is underutilized, she said.
The key to improved primary prevention of VTE, Dr. Cushman continued, is greater attention to modifiable behavioral risk factors, along with more use of prophylactic medication when needed.
The traditional cardiovascular risk factors, like hypertension, smoking, and hyperlipidemia, aren’t relevant to VTE risk. But obesity and sedentary lifestyle have come to be recognized as important modifiable risk factors. In one study of more than 30,000 Americans, the risk of VTE was shown to be reduced by 40% in individuals who exercised at least four times per week, compared with the physically inactive.
And in an analysis led by Dr. Cushman of nearly 21,000 participants over age 45 years with 12.6 years of follow-up in the Longitudinal Investigation of Thromboembolism Etiology (LITE), the investigators found that greater levels of all body size measures – not just body mass index, but calf circumference, waist-hip ratio, hip circumference, and others – were associated with increased VTE risk. These associations weren’t affected by levels of circulating biomarkers for inflammation or hypercoagulability, suggesting that it’s obesity per se, with its associated adverse impact on blood flow caused by physical factors, that explains the mechanism underlying obesity as a risk factor for VTE (Thromb Res. 2016 Aug;144:127-32).
At the meeting’s opening ceremonies, AHA President Ivor Benjamin, MD, of the Medical College of Wisconsin, Milwaukee, presented Dr. Cushman with the AHA Population Research Prize. She was honored for her “critically acclaimed research utilizing biomarker assessments in population studies to elucidate pathways of disease etiology for the three most common vascular diseases – coronary heart disease, stroke, and venous thromboembolism – as well as their risk factors,” said Dr. Benjamin.
Dr. Cushman reported having no financial conflicts regarding her D-dimer study, which was funded by the National Institutes of Health.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Women in the top 25% for D-dimer level before going on menopausal hormone therapy had a 6% incidence of venous thromboembolism over 5 years.
Study details: This was a nested case-control study focused on identifying biomarkers for venous thromboembolism risk which included 1,082 participants in the Women’s Health Initiative randomized to menopausal hormone therapy or placebo.
Disclosures: The presenter reported having no financial conflicts regarding the study, which was funded by the National Institutes of Health.
Cerdulatinib yields ‘encouraging’ results in CTCL, PTCL
LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).
The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).
The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.
“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.
Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.
Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.
PTCL cohort
The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.
The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.
Responses according to subtype were as follows:
- 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
- 2 CRs in PTCL not otherwise specified.
- 1 CR in gamma-delta T-cell lymphoma.
- 1 PR in ALK-negative anaplastic large-cell lymphoma.
- 1 CR and 1 PR in adult T-cell leukemia/lymphoma.
Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.
The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).
There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
CTCL cohort
The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.
The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.
Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.
“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.
The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).
“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”
She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.
“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.
She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).
The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).
The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.
“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.
Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.
Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.
PTCL cohort
The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.
The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.
Responses according to subtype were as follows:
- 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
- 2 CRs in PTCL not otherwise specified.
- 1 CR in gamma-delta T-cell lymphoma.
- 1 PR in ALK-negative anaplastic large-cell lymphoma.
- 1 CR and 1 PR in adult T-cell leukemia/lymphoma.
Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.
The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).
There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
CTCL cohort
The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.
The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.
Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.
“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.
The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).
“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”
She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.
“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.
She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).
The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).
The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.
“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.
Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.
Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.
PTCL cohort
The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.
The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.
Responses according to subtype were as follows:
- 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
- 2 CRs in PTCL not otherwise specified.
- 1 CR in gamma-delta T-cell lymphoma.
- 1 PR in ALK-negative anaplastic large-cell lymphoma.
- 1 CR and 1 PR in adult T-cell leukemia/lymphoma.
Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.
The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).
There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
CTCL cohort
The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.
The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.
The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.
Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.
“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.
The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).
“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”
She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.
“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.
She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: The overall response rate was 34% in patients with peripheral T-cell lymphoma (PTCL) and 26% in patients with cutaneous T-cell lymphoma (CTCL).
Study details: Expansion cohorts of a phase 2 trial including 45 PTCL patients and 29 CTCL patients
Disclosures: The study was funded by Portola Pharmaceuticals. The investigator reported having no relevant conflicts.
President Trump calls for end to HIV/AIDS, pediatric cancer
HIV/AIDS, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights of President Donald Trump’s second State of the Union address Feb. 5.
Mr. Trump promised to push for funds to end HIV/AIDS and childhood cancer within in 10 years. “In recent years, we have made remarkable progress in the fight against HIV and AIDS. Scientific breakthroughs have brought a once-distant dream within reach,” he said to assembled members of Congress and leaders of the executive and judicial branches of government. “My budget will ask Democrats and Republicans to make the needed commitment to eliminate the HIV epidemic in the United States within 10 years.”
Following the speech, Alex Azar, secretary of the Department of Health and Human Services, offered more details in a blog post on the agency’s website.
Funding for the initiative, dubbed “Ending the HIV Epidemic: A Plan for America,” will have three components.
The first involves increasing investments in “geographic hotspots” though existing programs like the Ryan White HIV/AIDS Program and a new community health center–based program to provide antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) to those at the highest risk of contracting the disease.
Second is the use of data to track where the disease is spreading most rapidly to help target prevention, care, and treatment at the local level. The third will provide funds for the creation of a local HIV HealthForce in these targeted areas to expand HIV prevention and treatment efforts.
A fact sheet on this initiative called for a 75% reduction in new cases of HIV infection in 5 years and at least a 90% reduction within 10 years.
President Trump called for similar efforts to address pediatric cancer.
“Tonight I am also asking you to join me in another fight that all American can get behind – the fight against childhood cancer,” he said, adding that his budget request will come with a line item of $500 million over 10 years to fund research. “Many childhood cancers have not seen new therapies in decades.”
President Trump also asked Congress to legislate a prohibition of late-term abortion.
“There could be no greater contrast to the beautiful image of a mother holding her infant child than the chilling displays our nation saw in recent days,” he said. “Lawmakers in New York cheered with delight upon the passage of legislation that would allow a baby to be ripped from the mother’s womb moments from birth. These are living, feeling beautiful babies who will never get the chance to share their love and their dreams with the world. ... Let us work together to build a culture that cherishes innocent life.”
He also touched on the recurring themes regarding lowering the cost of health care and prescription drugs, as well as protecting those with preexisting conditions, something he called a major priority.
“It’s unacceptable that Americans pay vastly more than people in other countries for the exact same drugs, often made in the exact same place. This is wrong. This is unfair and together we will stop it, and we will stop it fast,” he said.
He did not offer any specific policy recommendation on how to address prescription drug costs, other than a comment on the need for greater price transparency.
“I am asking Congress to pass legislation that finally takes on the problem of global freeloading and delivers fairness and price transparency for American patients,” he said.
“We should also require drug companies, insurance companies, and hospitals to disclose real prices to foster competition and bring costs way down.”
SOURCE: Trump D. State of the Union Address, Feb. 5, 2019.
HIV/AIDS, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights of President Donald Trump’s second State of the Union address Feb. 5.
Mr. Trump promised to push for funds to end HIV/AIDS and childhood cancer within in 10 years. “In recent years, we have made remarkable progress in the fight against HIV and AIDS. Scientific breakthroughs have brought a once-distant dream within reach,” he said to assembled members of Congress and leaders of the executive and judicial branches of government. “My budget will ask Democrats and Republicans to make the needed commitment to eliminate the HIV epidemic in the United States within 10 years.”
Following the speech, Alex Azar, secretary of the Department of Health and Human Services, offered more details in a blog post on the agency’s website.
Funding for the initiative, dubbed “Ending the HIV Epidemic: A Plan for America,” will have three components.
The first involves increasing investments in “geographic hotspots” though existing programs like the Ryan White HIV/AIDS Program and a new community health center–based program to provide antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) to those at the highest risk of contracting the disease.
Second is the use of data to track where the disease is spreading most rapidly to help target prevention, care, and treatment at the local level. The third will provide funds for the creation of a local HIV HealthForce in these targeted areas to expand HIV prevention and treatment efforts.
A fact sheet on this initiative called for a 75% reduction in new cases of HIV infection in 5 years and at least a 90% reduction within 10 years.
President Trump called for similar efforts to address pediatric cancer.
“Tonight I am also asking you to join me in another fight that all American can get behind – the fight against childhood cancer,” he said, adding that his budget request will come with a line item of $500 million over 10 years to fund research. “Many childhood cancers have not seen new therapies in decades.”
President Trump also asked Congress to legislate a prohibition of late-term abortion.
“There could be no greater contrast to the beautiful image of a mother holding her infant child than the chilling displays our nation saw in recent days,” he said. “Lawmakers in New York cheered with delight upon the passage of legislation that would allow a baby to be ripped from the mother’s womb moments from birth. These are living, feeling beautiful babies who will never get the chance to share their love and their dreams with the world. ... Let us work together to build a culture that cherishes innocent life.”
He also touched on the recurring themes regarding lowering the cost of health care and prescription drugs, as well as protecting those with preexisting conditions, something he called a major priority.
“It’s unacceptable that Americans pay vastly more than people in other countries for the exact same drugs, often made in the exact same place. This is wrong. This is unfair and together we will stop it, and we will stop it fast,” he said.
He did not offer any specific policy recommendation on how to address prescription drug costs, other than a comment on the need for greater price transparency.
“I am asking Congress to pass legislation that finally takes on the problem of global freeloading and delivers fairness and price transparency for American patients,” he said.
“We should also require drug companies, insurance companies, and hospitals to disclose real prices to foster competition and bring costs way down.”
SOURCE: Trump D. State of the Union Address, Feb. 5, 2019.
HIV/AIDS, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights of President Donald Trump’s second State of the Union address Feb. 5.
Mr. Trump promised to push for funds to end HIV/AIDS and childhood cancer within in 10 years. “In recent years, we have made remarkable progress in the fight against HIV and AIDS. Scientific breakthroughs have brought a once-distant dream within reach,” he said to assembled members of Congress and leaders of the executive and judicial branches of government. “My budget will ask Democrats and Republicans to make the needed commitment to eliminate the HIV epidemic in the United States within 10 years.”
Following the speech, Alex Azar, secretary of the Department of Health and Human Services, offered more details in a blog post on the agency’s website.
Funding for the initiative, dubbed “Ending the HIV Epidemic: A Plan for America,” will have three components.
The first involves increasing investments in “geographic hotspots” though existing programs like the Ryan White HIV/AIDS Program and a new community health center–based program to provide antiretroviral therapy (ART) and preexposure prophylaxis (PrEP) to those at the highest risk of contracting the disease.
Second is the use of data to track where the disease is spreading most rapidly to help target prevention, care, and treatment at the local level. The third will provide funds for the creation of a local HIV HealthForce in these targeted areas to expand HIV prevention and treatment efforts.
A fact sheet on this initiative called for a 75% reduction in new cases of HIV infection in 5 years and at least a 90% reduction within 10 years.
President Trump called for similar efforts to address pediatric cancer.
“Tonight I am also asking you to join me in another fight that all American can get behind – the fight against childhood cancer,” he said, adding that his budget request will come with a line item of $500 million over 10 years to fund research. “Many childhood cancers have not seen new therapies in decades.”
President Trump also asked Congress to legislate a prohibition of late-term abortion.
“There could be no greater contrast to the beautiful image of a mother holding her infant child than the chilling displays our nation saw in recent days,” he said. “Lawmakers in New York cheered with delight upon the passage of legislation that would allow a baby to be ripped from the mother’s womb moments from birth. These are living, feeling beautiful babies who will never get the chance to share their love and their dreams with the world. ... Let us work together to build a culture that cherishes innocent life.”
He also touched on the recurring themes regarding lowering the cost of health care and prescription drugs, as well as protecting those with preexisting conditions, something he called a major priority.
“It’s unacceptable that Americans pay vastly more than people in other countries for the exact same drugs, often made in the exact same place. This is wrong. This is unfair and together we will stop it, and we will stop it fast,” he said.
He did not offer any specific policy recommendation on how to address prescription drug costs, other than a comment on the need for greater price transparency.
“I am asking Congress to pass legislation that finally takes on the problem of global freeloading and delivers fairness and price transparency for American patients,” he said.
“We should also require drug companies, insurance companies, and hospitals to disclose real prices to foster competition and bring costs way down.”
SOURCE: Trump D. State of the Union Address, Feb. 5, 2019.
Key clinical point: President Trump calls for an end to HIV/AIDS and pediatric cancer in 10 years.
Major finding: His budget will request $500 million for cancer research and as yet undisclosed amount for HIV/AIDS research.
Study details: More specific details on the proposals will likely come when the president makes his budget submission to Congress in the coming weeks.
Disclosures: There are no disclosures.
Source: Trump D. State of the Union Address, Feb. 5, 2019.
Psoriatic arthritis eludes early diagnosis
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Most patients with psoriatic arthritis first present with psoriasis only. Their skin disorder precedes any joint involvement, often by several years. That suggests targeting interventions to patients with psoriasis to prevent or slow their progression to psoriatic arthritis, as well as following psoriatic patients closely to diagnose psoriatic arthritis quickly when it first appears. It’s a simple and attractive management premise that’s been challenging to apply in practice.
It’s not that clinicians aren’t motivated to diagnose psoriatic arthritis (PsA) in patients early, hopefully as soon as it appears. The susceptibility of patients with psoriasis to develop PsA is well described, with an annual progression rate of about 3%, and adverse consequences result from even a 6-month delay in diagnosis.
“Some physicians still don’t ask psoriasis patients about joint pain, or their symptoms are misinterpreted as something else,” said Lihi Eder, MD, a rheumatologist at Women’s College Research Institute, Toronto, and the University of Toronto. “Although there is increased awareness about PsA, there are still delays in diagnosis,” she said in an interview.
“Often there is a massive delay in diagnosis, and we know from a number of studies that longer duration of symptoms before diagnosis is associated with poorer outcomes,” said Laura C. Coates, MBChB, PhD, a rheumatologist at the University of Oxford (England). The delay to PsA diagnosis is generally “longer than for equivalent rheumatoid arthritis patients. PsA patients take longer to ask a primary care physician for help, longer to get a referral to a rheumatologist, and longer to get a diagnosis” from a rheumatologist. “We need to educate patients with psoriasis about their risk so that they seek help, educate GPs about whom to refer, and educate rheumatologists about diagnosis,” Dr. Coates said.
“It is very important to diagnose PsA as early as possible. We know that a delay in diagnosis and treatment can lead to worse outcomes and joint damage,” said Soumya M. Reddy, MD, codirector of the Psoriasis and Psoriatic Arthritis Center at New York University Langone Health in New York. “The heterogeneity of clinical manifestations of PsA can make it difficult to diagnose, and in some cases this leads to delayed diagnosis.”
“We are increasingly interested in the concept of preventing PsA. Psoriasis is a unique disease state in which we have an at-risk population where 30% will develop an inflammatory and potentially damaging arthritis. This may become important as our skin treatments may also treat musculoskeletal components of the disease,” said Joseph F. Merola, MD, director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital in Boston and double board certified in dermatology and rheumatology.
Focusing on patients with psoriasis
Treatment of psoriasis makes sense to address several quality-of-life issues, but controlling the severity of psoriatic skin manifestations gives patients no guarantees about their possible progression to PsA.
“So many people have mild psoriasis that, although they are less likely, proportionately, to get PsA, we still see many in the clinic,” said Dr. Coates. “Patients with severe skin involvement have a good reason to get treatment, which could help test whether a drug slows progression to arthritis. But it’s unethical to not treat severe psoriasis just to have a comparison group.” Aside from skin psoriasis, “we don’t have any other good markers,” Dr. Coates noted.
PsA can develop in patients who had psoriasis in the past but without currently active disease. “At the level of individual patients you can’t say someone is protected from developing PsA because their psoriasis is inactive,” Dr. Eder said. “No study has looked at whether treatment of psoriasis reduces the risk for progression to PsA. We don’t know whether any treatments that reduce inflammation in psoriasis also reduce progression to PsA.” Regardless, treating psoriasis is important because it improves quality of life and may have a beneficial, long-term effects on possible cardiovascular disease effects from psoriasis, Dr. Eder said.
Her research group is now studying the associations among different biological drugs taken by patients with psoriasis and their subsequent incidence of PsA with use of medical records from about 4 million Israeli residents. Other studies are also looking at this, but they are all observational and therefore are subject to unidentified confounders, she noted. A more definitive demonstration of PsA protection would need a randomized trial.
“The idea of preventing the transition from psoriasis to PsA is an exciting concept. But currently, there are no established treatments for preventing transition of psoriasis to PsA. It’s an area of active research, and the holy grail of psoriatic disease research. We do not yet know whether successful treatment of skin psoriasis delays the onset of arthritis,” Dr. Reddy said in an interview.
“The risk of developing PsA increases as the severity of skin psoriasis increases, measured by percentage of body surface area affected. However, there is only a weak correlation between the severity of skin disease and the severity of PsA,” said Joel M. Gelfand, MD, professor of dermatology at the University of Pennsylvania in Philadelphia.
Widening the PsA diagnostic net
What’s elusive is some other parameter to identify the 3% of psoriasis patients who will develop PsA during the next year – or at least a better way to find patients as soon as they have what is identifiably PsA.
The diagnostic definition for PsA that many experts now accept is actually a set of classification criteria, CASPAR (Classification Criteria for Psoriatic Arthritis) (Arthritis Rheum. 2006 Aug;54[8]:2665-73). But in actual practice, diagnosing PsA relies heavily on clinical skill, case recognition, and ruling out mimickers.
“The CASPAR criteria were developed as classification criteria to use in studies, but they are also quite helpful in diagnosing PsA. It is the agreed on definition of PsA at the moment,” said Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania.
“CASPAR fills the role at present for clinical trials, but the diagnosis remains clinical, based on history, physical findings, and supported by lab and radiology findings,” Dr. Merola said. “A clinical prediction tool and a proper biomarker would be of great value.”
“We certainly use CASPAR criteria in the clinic, but they do not include all PsA patients; sometimes we diagnose PsA in patients who don’t meet the CASPAR criteria,” Dr. Coates said.
“In practice, rheumatologists mostly use their clinical judgment: a patient with history and findings typical of PsA after ruling out other causes. But distinguishing inflammatory from noninflammatory arthritis – like osteoarthritis or fibromyalgia – can be quite difficult; that’s the main challenge,” Dr. Eder said. “Rheumatologists rely on their clinical skill and experience. PsA can be difficult to diagnose. There is no biomarker for it. PsA is complex [to diagnose], and that’s why it’s diagnosed later. A primary care physician might get a negative result on a rheumatoid factor test and think that rules out PsA, but it doesn’t.”
Dr. Eder and others suggest that ultrasound may be a useful tool for earlier diagnosis of PsA. Ultrasound is more sensitive than a physical examination and can detect inflammation in joints and entheses, she noted. Another effective method may be more systematic use of screening questionnaires, Dr. Coates said, or simply more systematic questioning of patients.
“Questionnaires are not a high priority for a primary care physician who may have only a few patients with psoriasis. Even some dermatologists may not use the questionnaires because they take time to administer and assess. But just asking a psoriasis patient whether they have joint symptoms is enough,” Dr. Eder said. All clinicians who encounter patients with psoriasis should ask about musculoskeletal symptoms and refer when appropriate to a rheumatologist, Dr. Reddy said.
The earliest indicators of PsA
Evidence supporting ultrasound’s value for early PsA diagnosis came in a report at the most recent annual meeting of the American College of Rheumatology in Chicago in October 2018. Researchers from the University of Rochester (New York) used ultrasound to examine 78 patients with psoriasis but without PsA or musculoskeletal symptoms and 25 healthy controls. They found ultrasound abnormalities in almost half of the patients with psoriasis, significantly more than in the controls (Thiele R et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 2904).
Another report at the ACR annual meeting last October looked at the incidence of physician visits for nonspecific musculoskeletal symptoms during each of the 5 years preceding diagnosis of PsA. A prior report from Dr. Eder and her associates had documented in an observational cohort of 410 patients with psoriasis that, prior to development of PsA, patients often had nonspecific musculoskeletal symptoms of joint pain, fatigue, and stiffness that constituted a “preclinical” phase (Arthritis Rheumatol. 2017 March;69[3]:622-9).
In October, Dr. Eder reported how the appearance of musculoskeletal symptoms played out in terms of physician visits. She and her associates analyzed data from an Ontario health insurance database that included about 430,000 Ontario patients seen by 466 primary care physicians, which included 462 patients with a new diagnosis of PsA and 2,310 matched controls. The results showed that, in every year during the 5 years preceding diagnosis of PsA, the patients who would wind up getting diagnosed had roughly twice the number of visits to a primary care physician each year for nonspecific musculoskeletal issues. A similar pattern of doubled visits occurred for people prior to their PsA diagnosis going to physicians who specialize in musculoskeletal conditions, and when the analysis focused on visits to rheumatologists, patients who went on to get diagnosed with PsA had a nearly sevenfold increased rate of these visits, compared with controls, for each of the 5 years preceding their PsA diagnosis (Eder L et al. Arthritis Rheumatol. 2018;70[suppl 10]: Abstract 967).
These results “highlight that in many patients PsA is not an acute disease that starts suddenly. In many patients, there is a period when the patient experiences musculoskeletal symptoms and sees a primary care physician or rheumatologist and may be diagnosed with something that is not PsA. That means that the delay in diagnosis [of PsA] may have happened because the patients were misdiagnosed. It reinforces the need for better diagnostic tools,” Dr. Eder said. “We have focused on getting these patients to see a rheumatologist earlier, but that may not be enough. These patients may not receive routine follow-up; we need to do more follow-up on patients like these.” Diagnosing PsA early means earlier treatment, a better chance of reaching remission, less chance of permanent joint damage, and better quality of life.
The challenges of making an early diagnosis were also documented in a study reported by Dr. Ogdie during the June 2018 annual congress of the European League Against Rheumatism. Dr. Ogdie reported on the survey responses of 203 patients who said they had been diagnosed with PsA whose index diagnosis was a median of 6 years before they completed the survey. A total of 195 of these patients, or 96%, said that they had received at least one misdiagnosis prior to their PsA diagnosis (Odgie A et al. Ann Rheum Dis. 2018;77[Suppl 2]:163. Abstract THU0292). The most common misdiagnoses were psychosomatic disease, reported by 27% of the patients; osteoarthritis in 22%; anxiety or depression in 18%; and an orthopedic problem in 18%. (Patients could report more than one type of misdiagnosis.)
The results “showed that patients often had substantial delays and misdiagnoses before they received a PsA diagnosis,” Dr. Ogdie and her associates concluded. Although the CASPAR classification criteria may be the agreed on PsA definition, recent findings suggest a pre-PsA stage exists with musculoskeletal and other abnormalities. “How may we diagnose ‘pre-PsA’? How might we capture this transition phase from psoriasis to PsA before the CASPAR criteria are fulfilled,” she wondered in an interview. “If we could stop PsA before it is clinically relevant, that could dramatically change the course of the disease. This is a big need in the field right now.”
Weight loss and other interventions
Aside from treating psoriasis and perhaps putting a patient with psoriasis in a PsA-prevention trial, one of the best ways to prevent PsA may be weight loss.
Results from “some studies suggest that being overweight increases the risk for developing PsA. Obesity also exacerbates skin psoriasis, makes treatment less effective, and further increases the risk of cardiometabolic diseases associated with psoriasis,” Dr. Gelfand said. “All patients with psoriatic disease should be educated about the importance of maintaining a healthy body weight.”
“Several studies suggest that obesity is a risk factor for developing PsA. Obesity likely plays a role in driving or contributing to inflammation in psoriatic disease,” said Dr. Reddy, who noted that other PsA risk factors include nail psoriasis and first-degree relatives with PsA. Dr. Ogdie also cited uveitis and prior joint trauma as other risk factors.
“Strong observational data link obesity and PsA incidence. I talk to psoriasis patients about weight control, and selected patients could even consider bariatric surgery,” Dr. Eder said. Losing at least 5% of body mass index can make a difference, she added.
At the 2018 annual meeting of the American College of Rheumatology, researchers from the University of Bath (England) reported results from a retrospective, observational study of more than 90,000 people with recent-onset psoriasis; they found that people with an obese BMI had twice the rate of progression to PsA when compared with people with a normal BMI. Overweight people had a nearly 80% higher rate of incident PsA (Green A et al. Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2134).
Hints have also emerged that new approaches to treating psoriasis also could help to keep PsA precursors at bay. One recent example from researchers at the University of Leeds (England) was a phase 2 study of 73 patients with moderate to severe psoriasis but no PsA who underwent ultrasound screening of their entheses for signs of inflammatory changes. The 23 patients underwent 52 weeks of treatment with the drug ustekinumab (Stelara), an antagonist of interleukin-12 and -23 that is approved for U.S. marketing to treat both psoriasis and PsA. After 24 weeks on treatment, their mean inflammation scores had dropped by more than 40%, and the effect persisted through 52 weeks of treatment (Arthritis Rheum. 2018 Nov 22. doi: 10.1002/art.40778).
Despite this promise, the researchers “haven’t looked long enough or in enough people to see whether this actually stops patients from developing PsA,” Dr. Coates commented. It also remains unclear whether this or another ultrasound abnormality detectable in joints or entheses is a reliable predictor of PsA, she noted.
“We still have a lot to learn about how to classify patients as high risk” for PsA, Dr. Ogdie concluded.
Dr. Eder has received research and educational grants from AbbVie, Amgen, Celgene, Lilly, Novartis, and UCB. Dr. Coates has received honoraria, research funding, or both from more than a dozen companies. Dr. Reddy has been a consultant to AbbVie, Novartis, Pfizer, and UCB. Dr. Merola has been a consultant to AbbVie, Celgene, GlaxoSmithKline, Janssen, Lilly, Novartis, Samumed, Sanofi, and UCB and has received research grants from Aclaris, Biogen, Incyte, Novartis, Pfizer, and Sanofi. Dr. Gelfand has been a consultant, adviser, or both to more than a dozen companies. Dr. Ogdie has been a consultant to AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Lilly, Novartis, Pfizer, and Takeda.
Arterial stiffness index may be potent tool for PAD risk stratification
An increased peripheral arterial stiffness index was associated with an increased rate of major adverse cardiac events (MACEs), independent of age, coronary artery disease, and Rutherford category, according to the results of a study of patients with peripheral arterial disease (PAD) presenting to the vascular surgery outpatient clinic at the San Francisco Veterans Affairs Medical Center.
Seventy-two patients with PAD were recruited during 2011-2016 and each had baseline radial artery applanation tonometry performed at a baseline visit. Their central radial artery augmentation index (AIX), normalized to 75 beats/min, and the peripheral AIX were calculated using pulse wave analysis. Subsequent MACEs were identified by chart review in the Journal of Surgical Research.
The cohort was predominately male (96%) and white (69%), with an average age of 69.4 years.
During a median follow-up period of 34 months, 14 patients experienced a MACE (19%). These events included eight myocardial infarctions or coronary revascularizations, four deaths from a cardiac cause, one stroke, and one transient ischemic attack. Unadjusted Cox proportional hazards models identified a significant association between the peripheral AIX and rate of MACE (hazard ratio, 1.54; 95% confidence interval, 1.06-2.22; P less than .02).
the researchers concluded.
The study was funded by public institutions including the National Institutes of Heath, the University of California, San Francisco, and a Society for Vascular Surgery Seed Grant and Career Development Award. The authors reported that they had no disclosures.
SOURCE: Ramirez JL et al. J Surg Res 2019;235:250-7.
An increased peripheral arterial stiffness index was associated with an increased rate of major adverse cardiac events (MACEs), independent of age, coronary artery disease, and Rutherford category, according to the results of a study of patients with peripheral arterial disease (PAD) presenting to the vascular surgery outpatient clinic at the San Francisco Veterans Affairs Medical Center.
Seventy-two patients with PAD were recruited during 2011-2016 and each had baseline radial artery applanation tonometry performed at a baseline visit. Their central radial artery augmentation index (AIX), normalized to 75 beats/min, and the peripheral AIX were calculated using pulse wave analysis. Subsequent MACEs were identified by chart review in the Journal of Surgical Research.
The cohort was predominately male (96%) and white (69%), with an average age of 69.4 years.
During a median follow-up period of 34 months, 14 patients experienced a MACE (19%). These events included eight myocardial infarctions or coronary revascularizations, four deaths from a cardiac cause, one stroke, and one transient ischemic attack. Unadjusted Cox proportional hazards models identified a significant association between the peripheral AIX and rate of MACE (hazard ratio, 1.54; 95% confidence interval, 1.06-2.22; P less than .02).
the researchers concluded.
The study was funded by public institutions including the National Institutes of Heath, the University of California, San Francisco, and a Society for Vascular Surgery Seed Grant and Career Development Award. The authors reported that they had no disclosures.
SOURCE: Ramirez JL et al. J Surg Res 2019;235:250-7.
An increased peripheral arterial stiffness index was associated with an increased rate of major adverse cardiac events (MACEs), independent of age, coronary artery disease, and Rutherford category, according to the results of a study of patients with peripheral arterial disease (PAD) presenting to the vascular surgery outpatient clinic at the San Francisco Veterans Affairs Medical Center.
Seventy-two patients with PAD were recruited during 2011-2016 and each had baseline radial artery applanation tonometry performed at a baseline visit. Their central radial artery augmentation index (AIX), normalized to 75 beats/min, and the peripheral AIX were calculated using pulse wave analysis. Subsequent MACEs were identified by chart review in the Journal of Surgical Research.
The cohort was predominately male (96%) and white (69%), with an average age of 69.4 years.
During a median follow-up period of 34 months, 14 patients experienced a MACE (19%). These events included eight myocardial infarctions or coronary revascularizations, four deaths from a cardiac cause, one stroke, and one transient ischemic attack. Unadjusted Cox proportional hazards models identified a significant association between the peripheral AIX and rate of MACE (hazard ratio, 1.54; 95% confidence interval, 1.06-2.22; P less than .02).
the researchers concluded.
The study was funded by public institutions including the National Institutes of Heath, the University of California, San Francisco, and a Society for Vascular Surgery Seed Grant and Career Development Award. The authors reported that they had no disclosures.
SOURCE: Ramirez JL et al. J Surg Res 2019;235:250-7.
FROM THE JOURNAL OF SURGICAL RESEARCH
Key clinical point: An increased peripheral arterial stiffness index was associated with an increased rate of MACEs.
Major finding: There was significant association between peripheral arterial stiffness and the rate of MACE (P less than .02).
Study details: Chart review study of 72 patients with PAD over time.
Disclosures: The study was funded by various public institutions. The authors reported that they had no disclosures.
Source: Ramirez JL et al. J Surg Res 2019 Mar;235:250-7.
PTSD and Emotional Eating
Nearly 80% of veterans are overweight or obese. According to researchers from Walter Reed National Military Medical Center in Maryland and Yale School of Medicine in Connecticut, obesity is more common among veterans with posttraumatic stress disorder (PTSD) compared with that in other veterans in the VHA (47% vs 41%). Moreover, they say, veterans with PTSD lose less weight during weight-loss treatment than do those without comorbid mental health conditions. PTSD also has been associated with night eating, food addiction, binge eating, and eating as a coping strategy. In a national survey, veterans who self-reported a diagnosis of PTSD were more likely to endorse eating because of emotions or stress.
The researchers conducted a study of 126 veterans referred to the MOVE! Weight Management Program at VA Connecticut Healthcare System. Although it replicates and extends findings from other studies, they believe theirs is the first study examining emotional eating among veterans seeking obesity treatment.
The veterans were given the Yale Emotional Overeating Questionnaire (YEOQ), which assesses how often the respondent has eaten an unusually large amount of food in response to anxiety, sadness, loneliness, tiredness, anger, happiness, boredom, guilt, and physical pain. The researchers also used the Primary Care PTSD Screen to test for PTSD.
A positive PTSD screen was associated with significantly higher scores on the YEOQ overall as well as higher scores on each individual item. Higher scores on the PTSD screen also were associated with more frequent emotional eating for all emotions.
The researchers note that findings about the predictive validity of emotional eating questionnaires have been mixed. Although emotions may influence eating patterns, other mechanisms could be at work, such as general concern about, or lack of control over, eating.
However, the researchers suggest that veterans with PTSD may need specific attention given to alternative coping strategies when facing difficult emotions as part of weight loss treatment.
Nearly 80% of veterans are overweight or obese. According to researchers from Walter Reed National Military Medical Center in Maryland and Yale School of Medicine in Connecticut, obesity is more common among veterans with posttraumatic stress disorder (PTSD) compared with that in other veterans in the VHA (47% vs 41%). Moreover, they say, veterans with PTSD lose less weight during weight-loss treatment than do those without comorbid mental health conditions. PTSD also has been associated with night eating, food addiction, binge eating, and eating as a coping strategy. In a national survey, veterans who self-reported a diagnosis of PTSD were more likely to endorse eating because of emotions or stress.
The researchers conducted a study of 126 veterans referred to the MOVE! Weight Management Program at VA Connecticut Healthcare System. Although it replicates and extends findings from other studies, they believe theirs is the first study examining emotional eating among veterans seeking obesity treatment.
The veterans were given the Yale Emotional Overeating Questionnaire (YEOQ), which assesses how often the respondent has eaten an unusually large amount of food in response to anxiety, sadness, loneliness, tiredness, anger, happiness, boredom, guilt, and physical pain. The researchers also used the Primary Care PTSD Screen to test for PTSD.
A positive PTSD screen was associated with significantly higher scores on the YEOQ overall as well as higher scores on each individual item. Higher scores on the PTSD screen also were associated with more frequent emotional eating for all emotions.
The researchers note that findings about the predictive validity of emotional eating questionnaires have been mixed. Although emotions may influence eating patterns, other mechanisms could be at work, such as general concern about, or lack of control over, eating.
However, the researchers suggest that veterans with PTSD may need specific attention given to alternative coping strategies when facing difficult emotions as part of weight loss treatment.
Nearly 80% of veterans are overweight or obese. According to researchers from Walter Reed National Military Medical Center in Maryland and Yale School of Medicine in Connecticut, obesity is more common among veterans with posttraumatic stress disorder (PTSD) compared with that in other veterans in the VHA (47% vs 41%). Moreover, they say, veterans with PTSD lose less weight during weight-loss treatment than do those without comorbid mental health conditions. PTSD also has been associated with night eating, food addiction, binge eating, and eating as a coping strategy. In a national survey, veterans who self-reported a diagnosis of PTSD were more likely to endorse eating because of emotions or stress.
The researchers conducted a study of 126 veterans referred to the MOVE! Weight Management Program at VA Connecticut Healthcare System. Although it replicates and extends findings from other studies, they believe theirs is the first study examining emotional eating among veterans seeking obesity treatment.
The veterans were given the Yale Emotional Overeating Questionnaire (YEOQ), which assesses how often the respondent has eaten an unusually large amount of food in response to anxiety, sadness, loneliness, tiredness, anger, happiness, boredom, guilt, and physical pain. The researchers also used the Primary Care PTSD Screen to test for PTSD.
A positive PTSD screen was associated with significantly higher scores on the YEOQ overall as well as higher scores on each individual item. Higher scores on the PTSD screen also were associated with more frequent emotional eating for all emotions.
The researchers note that findings about the predictive validity of emotional eating questionnaires have been mixed. Although emotions may influence eating patterns, other mechanisms could be at work, such as general concern about, or lack of control over, eating.
However, the researchers suggest that veterans with PTSD may need specific attention given to alternative coping strategies when facing difficult emotions as part of weight loss treatment.