Though survival rates of patients with metastatic breast cancer (MBC) have increased over the last 2 decades, a new study has indicated disparities exist across regions and by variables like age and race.

“It appears from these results that we may be at a crossroads for MBC treatment and survival,” wrote Judith A. Malmgren, PhD, of the University of Washington and her coauthors. The study was published in Cancer. “Access to appropriate, timely, and up‐to‐date diagnosis, care, treatment, and surveillance could turn this fatal disease into a chronic and treatable phenomenon, depending on patient factors, molecular subtype, and insurance capacity to pay for treatment,” they said.

To determine how breast cancer outcomes might vary across regions, the researchers compared breast cancer–specific survival rates (BCSS) from Surveillance, Epidemiology, and End Results-9 (SEER-9) registry data minus a regional subset from the Seattle-Puget Sound (S-PS) region (n = 12,121) to patients from that S-PS region (n = 1,931) and to an individual cohort in that area (n = 261). Five-year BCSS rates were calculated for three time periods: 1990‐1998, 1999‐2004, and 2005‐2011.

All analyzed patients were diagnosed with a first primary, de novo, stage IV breast cancer between the ages of 25 and 84 years from 1990 to 2011. Patients in the SEER-9 group and the S-PS region had a mean age of 61 years, compared with the individual cohort’s mean age of 55 years. Patients in the individual cohort were more likely to reside in a major metropolitan area of over 1 million people, compared with the SEER group and the S-PS region (86% versus 61% and 58%, respectively).

Patients in the SEER-9 group had improved BCSS rates over the study period, from 19% in 1990-1998 (95% confidence interval, 18%-21%; P less than .001) to 26% in 2005-2011 (95% CI, 24%-27%; P less than .001). Patients in the S-PS region saw even greater improvements in BCSS rates, from 21% in 1990-1998 (95% CI, 18%-24%; P less than .001) to 35% in 2005-2011 (95% CI, 32%-39%; P less than .001). But the largest improvement in survival rates came from patients in the individual cohort, who went from 29% in 1990-1998 (95% CI, 18%-37%; P less than .001) to 56% in 2005-2011 (95% CI, 45%-65%; P = .004).

In a proportional hazards model for breast cancer–specific death, reduced hazard in the SEER-9 group was associated with surgery (hazard ratio, 0.58; 95% CI, 0.55-0.61; P less than .001), an age less than 70 (HR, 0.77; 95% CI, 0.73-0.82; P less than .001) and white race (HR, 0.84; 95% CI, 0.79-0.89; P less than .001). Similar associations were seen in the S-PS region with surgery (HR, 0.57; 95% CI, 0.50-0.66; P less than .001) and an age less than 70 (HR, 0.72; 95% CI, 0.62-0.84; P less than .001), but not white race.

The study results “indicate that the stage IV population that is living longer may be benefiting from many of the same therapies used to treat early breast cancer, especially for patients who are able to handle adjuvant chemotherapy treatment and are HR‐positive,” the researchers said. “However, the lag in survival improvement across different population‐based, geographic regions suggests that some groups and regions may benefit unequally from treatment advances as well as timely diagnosis.”

The study was funded by the Kaplan Cancer Research Fund, the Metastatic Breast Cancer Alliance, and the Surveillance, Epidemiology, and End Results Cancer Surveillance System program of the National Cancer Institute. The authors reported no conflicts of interest.

SOURCE: Malmgren JA et al. Cancer. 2019 Oct 22. doi: 10.1002/cncr.32531.

Though survival rates of patients with metastatic breast cancer (MBC) have increased over the last 2 decades, a new study has indicated disparities exist across regions and by variables like age and race.

“It appears from these results that we may be at a crossroads for MBC treatment and survival,” wrote Judith A. Malmgren, PhD, of the University of Washington and her coauthors. The study was published in Cancer. “Access to appropriate, timely, and up‐to‐date diagnosis, care, treatment, and surveillance could turn this fatal disease into a chronic and treatable phenomenon, depending on patient factors, molecular subtype, and insurance capacity to pay for treatment,” they said.

To determine how breast cancer outcomes might vary across regions, the researchers compared breast cancer–specific survival rates (BCSS) from Surveillance, Epidemiology, and End Results-9 (SEER-9) registry data minus a regional subset from the Seattle-Puget Sound (S-PS) region (n = 12,121) to patients from that S-PS region (n = 1,931) and to an individual cohort in that area (n = 261). Five-year BCSS rates were calculated for three time periods: 1990‐1998, 1999‐2004, and 2005‐2011.

All analyzed patients were diagnosed with a first primary, de novo, stage IV breast cancer between the ages of 25 and 84 years from 1990 to 2011. Patients in the SEER-9 group and the S-PS region had a mean age of 61 years, compared with the individual cohort’s mean age of 55 years. Patients in the individual cohort were more likely to reside in a major metropolitan area of over 1 million people, compared with the SEER group and the S-PS region (86% versus 61% and 58%, respectively).

Patients in the SEER-9 group had improved BCSS rates over the study period, from 19% in 1990-1998 (95% confidence interval, 18%-21%; P less than .001) to 26% in 2005-2011 (95% CI, 24%-27%; P less than .001). Patients in the S-PS region saw even greater improvements in BCSS rates, from 21% in 1990-1998 (95% CI, 18%-24%; P less than .001) to 35% in 2005-2011 (95% CI, 32%-39%; P less than .001). But the largest improvement in survival rates came from patients in the individual cohort, who went from 29% in 1990-1998 (95% CI, 18%-37%; P less than .001) to 56% in 2005-2011 (95% CI, 45%-65%; P = .004).

In a proportional hazards model for breast cancer–specific death, reduced hazard in the SEER-9 group was associated with surgery (hazard ratio, 0.58; 95% CI, 0.55-0.61; P less than .001), an age less than 70 (HR, 0.77; 95% CI, 0.73-0.82; P less than .001) and white race (HR, 0.84; 95% CI, 0.79-0.89; P less than .001). Similar associations were seen in the S-PS region with surgery (HR, 0.57; 95% CI, 0.50-0.66; P less than .001) and an age less than 70 (HR, 0.72; 95% CI, 0.62-0.84; P less than .001), but not white race.

The study results “indicate that the stage IV population that is living longer may be benefiting from many of the same therapies used to treat early breast cancer, especially for patients who are able to handle adjuvant chemotherapy treatment and are HR‐positive,” the researchers said. “However, the lag in survival improvement across different population‐based, geographic regions suggests that some groups and regions may benefit unequally from treatment advances as well as timely diagnosis.”

The study was funded by the Kaplan Cancer Research Fund, the Metastatic Breast Cancer Alliance, and the Surveillance, Epidemiology, and End Results Cancer Surveillance System program of the National Cancer Institute. The authors reported no conflicts of interest.

SOURCE: Malmgren JA et al. Cancer. 2019 Oct 22. doi: 10.1002/cncr.32531.

Though survival rates of patients with metastatic breast cancer (MBC) have increased over the last 2 decades, a new study has indicated disparities exist across regions and by variables like age and race.

“It appears from these results that we may be at a crossroads for MBC treatment and survival,” wrote Judith A. Malmgren, PhD, of the University of Washington and her coauthors. The study was published in Cancer. “Access to appropriate, timely, and up‐to‐date diagnosis, care, treatment, and surveillance could turn this fatal disease into a chronic and treatable phenomenon, depending on patient factors, molecular subtype, and insurance capacity to pay for treatment,” they said.

To determine how breast cancer outcomes might vary across regions, the researchers compared breast cancer–specific survival rates (BCSS) from Surveillance, Epidemiology, and End Results-9 (SEER-9) registry data minus a regional subset from the Seattle-Puget Sound (S-PS) region (n = 12,121) to patients from that S-PS region (n = 1,931) and to an individual cohort in that area (n = 261). Five-year BCSS rates were calculated for three time periods: 1990‐1998, 1999‐2004, and 2005‐2011.

All analyzed patients were diagnosed with a first primary, de novo, stage IV breast cancer between the ages of 25 and 84 years from 1990 to 2011. Patients in the SEER-9 group and the S-PS region had a mean age of 61 years, compared with the individual cohort’s mean age of 55 years. Patients in the individual cohort were more likely to reside in a major metropolitan area of over 1 million people, compared with the SEER group and the S-PS region (86% versus 61% and 58%, respectively).

Patients in the SEER-9 group had improved BCSS rates over the study period, from 19% in 1990-1998 (95% confidence interval, 18%-21%; P less than .001) to 26% in 2005-2011 (95% CI, 24%-27%; P less than .001). Patients in the S-PS region saw even greater improvements in BCSS rates, from 21% in 1990-1998 (95% CI, 18%-24%; P less than .001) to 35% in 2005-2011 (95% CI, 32%-39%; P less than .001). But the largest improvement in survival rates came from patients in the individual cohort, who went from 29% in 1990-1998 (95% CI, 18%-37%; P less than .001) to 56% in 2005-2011 (95% CI, 45%-65%; P = .004).

In a proportional hazards model for breast cancer–specific death, reduced hazard in the SEER-9 group was associated with surgery (hazard ratio, 0.58; 95% CI, 0.55-0.61; P less than .001), an age less than 70 (HR, 0.77; 95% CI, 0.73-0.82; P less than .001) and white race (HR, 0.84; 95% CI, 0.79-0.89; P less than .001). Similar associations were seen in the S-PS region with surgery (HR, 0.57; 95% CI, 0.50-0.66; P less than .001) and an age less than 70 (HR, 0.72; 95% CI, 0.62-0.84; P less than .001), but not white race.

The study results “indicate that the stage IV population that is living longer may be benefiting from many of the same therapies used to treat early breast cancer, especially for patients who are able to handle adjuvant chemotherapy treatment and are HR‐positive,” the researchers said. “However, the lag in survival improvement across different population‐based, geographic regions suggests that some groups and regions may benefit unequally from treatment advances as well as timely diagnosis.”

The study was funded by the Kaplan Cancer Research Fund, the Metastatic Breast Cancer Alliance, and the Surveillance, Epidemiology, and End Results Cancer Surveillance System program of the National Cancer Institute. The authors reported no conflicts of interest.

SOURCE: Malmgren JA et al. Cancer. 2019 Oct 22. doi: 10.1002/cncr.32531.

BARCELONA – Nivolumab, compared with docetaxel chemotherapy, led to a fivefold improvement in 5-year overall survival among previously treated patients with non–small cell lung cancer (NSCLC), according to a pooled analysis of data from the phase 3 CheckMate 017 and 057 trials.

Sharon Worcester/MDedge News

The 5-year overall survival (OS) rates from the two randomized registrational trials, which established the programmed death-1 (PD-1) inhibitor nivolumab as the standard salvage therapy for NSCLC, were 13.4% vs. 2.6% (median, 11.1 vs. 8.1 months) with nivolumab and docetaxel, respectively, Scott Gettinger, MD, reported at the World Conference on Lung Cancer.

“These are the first randomized trials to report 5-year outcomes for a PD-1 axis inhibitor in patients with previously treated advanced non–small lung cancer,” said Dr. Gettinger, a professor at the Yale Comprehensive Cancer Center, New Haven, Conn. “This is really unprecedented; we wouldn’t expect many patients to be out 5 years in this scenario.”

Notably, the 5-year OS benefit was seen in both trials, he said, explaining that each compared nivolumab and docetaxel, but CheckMate 017 included patients with only squamous NSCLC, and CheckMate 057 included only non–squamous NSCLC patients.

The trials randomized 272 and 582 patients, respectively, and both demonstrated significantly improved 12-month OS with nivolumab – regardless of programmed death-ligand 1 (PD-L1) expression levels. Common eligibility criteria included stage IIIb/IV disease, good performance status (ECOG performance score of 0-1), and 1 prior platinum-based chemotherapy; CheckMate 057 further allowed prior tyrosine kinase inhibitor treatment for known anaplastic lymphoma kinase (ALK) translocation or epidermal growth factor receptor (EGFR) mutation, and allowed prior maintenance therapy. Doses in both trials were 3 mg/kg of nivolumab every 2 weeks or 75 mg/m² of intravenous docetaxel every 3 weeks until disease progression or unacceptable toxicity.

The pooled data also showed an improvement in progression-free survival (PFS) at 5 years (8% vs. 0%) with nivolumab vs. docetaxel groups.

“Again, we don’t see this in trials – more commonly we see zero patients without progression, and that’s what we saw with the docetaxel arm,” said Dr. Gettinger, who also is the Disease Aligned Research Team Leader, Thoracic Oncology Program, at the cancer center.

The median duration of responses with nivolumab was 19.9 months vs. 5.6 months with docetaxel, and 32.2% of nivolumab responders were still without progression at 5 years, he noted.

A common question in the clinic relates to the prognosis in patients who do well with PD-1 axis inhibitors, which prompted an additional analysis across the two trials, he said, noting that 60%, 78%, and 88% of patients who had not progressed at 2, 3, or 4 years, respectively, also had not progressed at 5 years, and 80%, 93%, and 100%, of patients in those groups were alive at 5 years. In the docetaxel arm, only 4, 1, and 0 patients had PFS at 2, 3, and 4, years, respectively, and none of those patients survived to 5 years, he said.

No new safety signals were seen with long-term follow-up, he added.

“In fact there was only one grade 3 or higher toxicity that was related to treatment in the nivolumab arm, and this was a grade 3 lipase elevation. There was one patient who discontinued nivolumab after 3 years, and this was for a grade 2 rash and eczema that had waxed and waned since starting nivolumab,” he said.

Also of note, 10% of nivolumab-treated patients who were off treatment at 5 years – for variable periods of time – had not progressed and had not received subsequent therapy.

“So we clearly see benefit in our patients long after they finish a course or stop for some reason,” he said.

CheckMate 017 and 057 were funded by Bristol-Myers Squibb. Dr. Gettinger reported advisory board and/or consulting work for, and/or research funding from Bristol-Myers Squibb, Nektar Therapeutics, Genentech/Roche, Iovance, and Takeda/Ariad.

SOURCE: Gettinger S et al. WCLC 2019, Abstract PR04.03.

BARCELONA – Nivolumab, compared with docetaxel chemotherapy, led to a fivefold improvement in 5-year overall survival among previously treated patients with non–small cell lung cancer (NSCLC), according to a pooled analysis of data from the phase 3 CheckMate 017 and 057 trials.

Sharon Worcester/MDedge News

The 5-year overall survival (OS) rates from the two randomized registrational trials, which established the programmed death-1 (PD-1) inhibitor nivolumab as the standard salvage therapy for NSCLC, were 13.4% vs. 2.6% (median, 11.1 vs. 8.1 months) with nivolumab and docetaxel, respectively, Scott Gettinger, MD, reported at the World Conference on Lung Cancer.

“These are the first randomized trials to report 5-year outcomes for a PD-1 axis inhibitor in patients with previously treated advanced non–small lung cancer,” said Dr. Gettinger, a professor at the Yale Comprehensive Cancer Center, New Haven, Conn. “This is really unprecedented; we wouldn’t expect many patients to be out 5 years in this scenario.”

Notably, the 5-year OS benefit was seen in both trials, he said, explaining that each compared nivolumab and docetaxel, but CheckMate 017 included patients with only squamous NSCLC, and CheckMate 057 included only non–squamous NSCLC patients.

The trials randomized 272 and 582 patients, respectively, and both demonstrated significantly improved 12-month OS with nivolumab – regardless of programmed death-ligand 1 (PD-L1) expression levels. Common eligibility criteria included stage IIIb/IV disease, good performance status (ECOG performance score of 0-1), and 1 prior platinum-based chemotherapy; CheckMate 057 further allowed prior tyrosine kinase inhibitor treatment for known anaplastic lymphoma kinase (ALK) translocation or epidermal growth factor receptor (EGFR) mutation, and allowed prior maintenance therapy. Doses in both trials were 3 mg/kg of nivolumab every 2 weeks or 75 mg/m² of intravenous docetaxel every 3 weeks until disease progression or unacceptable toxicity.

The pooled data also showed an improvement in progression-free survival (PFS) at 5 years (8% vs. 0%) with nivolumab vs. docetaxel groups.

“Again, we don’t see this in trials – more commonly we see zero patients without progression, and that’s what we saw with the docetaxel arm,” said Dr. Gettinger, who also is the Disease Aligned Research Team Leader, Thoracic Oncology Program, at the cancer center.

The median duration of responses with nivolumab was 19.9 months vs. 5.6 months with docetaxel, and 32.2% of nivolumab responders were still without progression at 5 years, he noted.

A common question in the clinic relates to the prognosis in patients who do well with PD-1 axis inhibitors, which prompted an additional analysis across the two trials, he said, noting that 60%, 78%, and 88% of patients who had not progressed at 2, 3, or 4 years, respectively, also had not progressed at 5 years, and 80%, 93%, and 100%, of patients in those groups were alive at 5 years. In the docetaxel arm, only 4, 1, and 0 patients had PFS at 2, 3, and 4, years, respectively, and none of those patients survived to 5 years, he said.

No new safety signals were seen with long-term follow-up, he added.

“In fact there was only one grade 3 or higher toxicity that was related to treatment in the nivolumab arm, and this was a grade 3 lipase elevation. There was one patient who discontinued nivolumab after 3 years, and this was for a grade 2 rash and eczema that had waxed and waned since starting nivolumab,” he said.

Also of note, 10% of nivolumab-treated patients who were off treatment at 5 years – for variable periods of time – had not progressed and had not received subsequent therapy.

“So we clearly see benefit in our patients long after they finish a course or stop for some reason,” he said.

CheckMate 017 and 057 were funded by Bristol-Myers Squibb. Dr. Gettinger reported advisory board and/or consulting work for, and/or research funding from Bristol-Myers Squibb, Nektar Therapeutics, Genentech/Roche, Iovance, and Takeda/Ariad.

SOURCE: Gettinger S et al. WCLC 2019, Abstract PR04.03.

BARCELONA – Nivolumab, compared with docetaxel chemotherapy, led to a fivefold improvement in 5-year overall survival among previously treated patients with non–small cell lung cancer (NSCLC), according to a pooled analysis of data from the phase 3 CheckMate 017 and 057 trials.

Sharon Worcester/MDedge News

The 5-year overall survival (OS) rates from the two randomized registrational trials, which established the programmed death-1 (PD-1) inhibitor nivolumab as the standard salvage therapy for NSCLC, were 13.4% vs. 2.6% (median, 11.1 vs. 8.1 months) with nivolumab and docetaxel, respectively, Scott Gettinger, MD, reported at the World Conference on Lung Cancer.

“These are the first randomized trials to report 5-year outcomes for a PD-1 axis inhibitor in patients with previously treated advanced non–small lung cancer,” said Dr. Gettinger, a professor at the Yale Comprehensive Cancer Center, New Haven, Conn. “This is really unprecedented; we wouldn’t expect many patients to be out 5 years in this scenario.”

Notably, the 5-year OS benefit was seen in both trials, he said, explaining that each compared nivolumab and docetaxel, but CheckMate 017 included patients with only squamous NSCLC, and CheckMate 057 included only non–squamous NSCLC patients.

The trials randomized 272 and 582 patients, respectively, and both demonstrated significantly improved 12-month OS with nivolumab – regardless of programmed death-ligand 1 (PD-L1) expression levels. Common eligibility criteria included stage IIIb/IV disease, good performance status (ECOG performance score of 0-1), and 1 prior platinum-based chemotherapy; CheckMate 057 further allowed prior tyrosine kinase inhibitor treatment for known anaplastic lymphoma kinase (ALK) translocation or epidermal growth factor receptor (EGFR) mutation, and allowed prior maintenance therapy. Doses in both trials were 3 mg/kg of nivolumab every 2 weeks or 75 mg/m² of intravenous docetaxel every 3 weeks until disease progression or unacceptable toxicity.

The pooled data also showed an improvement in progression-free survival (PFS) at 5 years (8% vs. 0%) with nivolumab vs. docetaxel groups.

“Again, we don’t see this in trials – more commonly we see zero patients without progression, and that’s what we saw with the docetaxel arm,” said Dr. Gettinger, who also is the Disease Aligned Research Team Leader, Thoracic Oncology Program, at the cancer center.

The median duration of responses with nivolumab was 19.9 months vs. 5.6 months with docetaxel, and 32.2% of nivolumab responders were still without progression at 5 years, he noted.

A common question in the clinic relates to the prognosis in patients who do well with PD-1 axis inhibitors, which prompted an additional analysis across the two trials, he said, noting that 60%, 78%, and 88% of patients who had not progressed at 2, 3, or 4 years, respectively, also had not progressed at 5 years, and 80%, 93%, and 100%, of patients in those groups were alive at 5 years. In the docetaxel arm, only 4, 1, and 0 patients had PFS at 2, 3, and 4, years, respectively, and none of those patients survived to 5 years, he said.

No new safety signals were seen with long-term follow-up, he added.

“In fact there was only one grade 3 or higher toxicity that was related to treatment in the nivolumab arm, and this was a grade 3 lipase elevation. There was one patient who discontinued nivolumab after 3 years, and this was for a grade 2 rash and eczema that had waxed and waned since starting nivolumab,” he said.

Also of note, 10% of nivolumab-treated patients who were off treatment at 5 years – for variable periods of time – had not progressed and had not received subsequent therapy.

“So we clearly see benefit in our patients long after they finish a course or stop for some reason,” he said.

CheckMate 017 and 057 were funded by Bristol-Myers Squibb. Dr. Gettinger reported advisory board and/or consulting work for, and/or research funding from Bristol-Myers Squibb, Nektar Therapeutics, Genentech/Roche, Iovance, and Takeda/Ariad.

SOURCE: Gettinger S et al. WCLC 2019, Abstract PR04.03.

Certain myeloablative conditioning regimens are among several novel risk factors for melanoma after allogeneic hematopoietic stem cell transplantation (HCT), according to findings from a nested case-control study.

The study included 140 cases of melanoma and 557 controls matched by age at HCT, sex, primary disease, and survival time. The results showed a significantly increased melanoma risk in HCT survivors who received total body irradiation–based myeloablative conditioning, reduced-intensity conditioning with melphalan, or reduced-intensity conditioning with fludarabine, compared with those who received busulfan-based myeloablative conditioning (odds ratios, 1.77, 2.60, and 2.72, respectively), Megan M. Herr, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, and the Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues reported in the Journal of the American Academy of Dermatology.

Melanoma risk also was increased in patients who experienced acute graft-versus-host disease (GVHD) with stage 2 or greater skin involvement (OR, 1.92 vs. those with no acute GVHD), chronic GVHD without skin involvement (OR, 1.91 vs. those with no chronic GVHD), or keratinocytic carcinoma (OR, 2.37), and in those who resided in areas with higher ambient ultraviolet radiation (OR for the highest vs. lowest tertile, 1.64).

The UV radiation finding was more pronounced for melanomas occurring 6 or more years after transplant (OR, 3.04 for highest vs. lowest tertile), whereas ambient UV radiation was not associated with melanomas occurring earlier (ORs, 1.37 for less than 3 years and 0.98 at 3-6 years), the investigators noted.

The findings, based on large-scale and detailed clinical data from the Center for International Blood and Marrow Transplant Research for HCT performed during 1985-2012, show that melanoma after HCT has a multifactorial etiology that includes patient-, transplant-, and posttransplant-related factors, they said, noting that the findings also underscore the importance of “prioritization of high-risk survivors for adherence to prevention and screening recommendations.”

Those recommendations call for routine skin examination and photoprotective precautions – particularly in HCT survivors at the highest risk – but studies of screening behaviors suggest that fewer than two-thirds of HCT survivors adhere to these recommendations, they said, concluding that further research on the cost-effectiveness of melanoma screening is warranted, as is investigation into whether current approaches are associated with melanoma risk.

This work was supported by the intramural research program of the National Cancer Institute, the National Institutes of Health, and the Department of Health & Human Services. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Herr MM et al. J Am Acad Dermatol. 2019 Oct 22. doi: 10.1016/j.jaad.2019.10.034.




 

Certain myeloablative conditioning regimens are among several novel risk factors for melanoma after allogeneic hematopoietic stem cell transplantation (HCT), according to findings from a nested case-control study.

The study included 140 cases of melanoma and 557 controls matched by age at HCT, sex, primary disease, and survival time. The results showed a significantly increased melanoma risk in HCT survivors who received total body irradiation–based myeloablative conditioning, reduced-intensity conditioning with melphalan, or reduced-intensity conditioning with fludarabine, compared with those who received busulfan-based myeloablative conditioning (odds ratios, 1.77, 2.60, and 2.72, respectively), Megan M. Herr, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, and the Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues reported in the Journal of the American Academy of Dermatology.

Melanoma risk also was increased in patients who experienced acute graft-versus-host disease (GVHD) with stage 2 or greater skin involvement (OR, 1.92 vs. those with no acute GVHD), chronic GVHD without skin involvement (OR, 1.91 vs. those with no chronic GVHD), or keratinocytic carcinoma (OR, 2.37), and in those who resided in areas with higher ambient ultraviolet radiation (OR for the highest vs. lowest tertile, 1.64).

The UV radiation finding was more pronounced for melanomas occurring 6 or more years after transplant (OR, 3.04 for highest vs. lowest tertile), whereas ambient UV radiation was not associated with melanomas occurring earlier (ORs, 1.37 for less than 3 years and 0.98 at 3-6 years), the investigators noted.

The findings, based on large-scale and detailed clinical data from the Center for International Blood and Marrow Transplant Research for HCT performed during 1985-2012, show that melanoma after HCT has a multifactorial etiology that includes patient-, transplant-, and posttransplant-related factors, they said, noting that the findings also underscore the importance of “prioritization of high-risk survivors for adherence to prevention and screening recommendations.”

Those recommendations call for routine skin examination and photoprotective precautions – particularly in HCT survivors at the highest risk – but studies of screening behaviors suggest that fewer than two-thirds of HCT survivors adhere to these recommendations, they said, concluding that further research on the cost-effectiveness of melanoma screening is warranted, as is investigation into whether current approaches are associated with melanoma risk.

This work was supported by the intramural research program of the National Cancer Institute, the National Institutes of Health, and the Department of Health & Human Services. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Herr MM et al. J Am Acad Dermatol. 2019 Oct 22. doi: 10.1016/j.jaad.2019.10.034.




 

Certain myeloablative conditioning regimens are among several novel risk factors for melanoma after allogeneic hematopoietic stem cell transplantation (HCT), according to findings from a nested case-control study.

The study included 140 cases of melanoma and 557 controls matched by age at HCT, sex, primary disease, and survival time. The results showed a significantly increased melanoma risk in HCT survivors who received total body irradiation–based myeloablative conditioning, reduced-intensity conditioning with melphalan, or reduced-intensity conditioning with fludarabine, compared with those who received busulfan-based myeloablative conditioning (odds ratios, 1.77, 2.60, and 2.72, respectively), Megan M. Herr, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, and the Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues reported in the Journal of the American Academy of Dermatology.

Melanoma risk also was increased in patients who experienced acute graft-versus-host disease (GVHD) with stage 2 or greater skin involvement (OR, 1.92 vs. those with no acute GVHD), chronic GVHD without skin involvement (OR, 1.91 vs. those with no chronic GVHD), or keratinocytic carcinoma (OR, 2.37), and in those who resided in areas with higher ambient ultraviolet radiation (OR for the highest vs. lowest tertile, 1.64).

The UV radiation finding was more pronounced for melanomas occurring 6 or more years after transplant (OR, 3.04 for highest vs. lowest tertile), whereas ambient UV radiation was not associated with melanomas occurring earlier (ORs, 1.37 for less than 3 years and 0.98 at 3-6 years), the investigators noted.

The findings, based on large-scale and detailed clinical data from the Center for International Blood and Marrow Transplant Research for HCT performed during 1985-2012, show that melanoma after HCT has a multifactorial etiology that includes patient-, transplant-, and posttransplant-related factors, they said, noting that the findings also underscore the importance of “prioritization of high-risk survivors for adherence to prevention and screening recommendations.”

Those recommendations call for routine skin examination and photoprotective precautions – particularly in HCT survivors at the highest risk – but studies of screening behaviors suggest that fewer than two-thirds of HCT survivors adhere to these recommendations, they said, concluding that further research on the cost-effectiveness of melanoma screening is warranted, as is investigation into whether current approaches are associated with melanoma risk.

This work was supported by the intramural research program of the National Cancer Institute, the National Institutes of Health, and the Department of Health & Human Services. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Herr MM et al. J Am Acad Dermatol. 2019 Oct 22. doi: 10.1016/j.jaad.2019.10.034.




 

The presence of insomnia symptoms increases the likelihood of cardiovascular or cerebrovascular disease during approximately 10 years of follow-up, according to a large cohort study of adults in China. A greater number of insomnia symptoms is associated with increased risk, and this relationship is more evident in younger adults and in adults without hypertension at baseline, researchers reported Nov. 6 in Neurology.

Karen Winton/iStockphoto

“These results suggest that, if we can target people who are having trouble sleeping with behavioral therapies, it’s possible that we could reduce the number of cases of stroke, heart attack, and other diseases later down the line,” study author Liming Li, MD, professor of epidemiology at Peking University, Beijing, said in a news release.

To clarify the relationships between individual insomnia symptoms, cardiocerebral vascular diseases, and potential effect modifiers, Dr. Li and colleagues analyzed data from the China Kadoorie Biobank Study. For this study, more than 500,000 adults in China aged 30-79 years completed a baseline survey during 2004-2008. The present analysis included data from 487,200 participants who did not have a history of stroke, coronary heart disease, or cancer at baseline.

For the baseline survey, participants answered questions about whether specific insomnia symptoms occurred at least 3 days per week during the past month. The symptoms included difficulty initiating or maintaining sleep (that is, sleep onset latency of 30 minutes or more after going to bed or waking up in the middle of the night); waking too early and being unable to fall back asleep; and trouble functioning during the day because of bad sleep.

The researchers assessed the incidence of cardiocerebral vascular diseases through 2016 by examining disease registries, national health insurance claims databases, and local records. Investigators identified participants with any cardiocerebral vascular disease and assessed the incidence of ischemic heart disease, acute myocardial infarction, hemorrhagic stroke, and ischemic stroke. The researchers followed each participant until the diagnosis of a cardiocerebral vascular disease outcome, death from any cause, loss to follow-up, or Dec. 31, 2016. The researchers used Cox proportional hazard models to estimate hazard ratios for the association between each insomnia symptom and cardiocerebral vascular disease outcomes. They adjusted the models for established and potential confounding factors, including age, income, smoking status, diet, and physical activity.

More than 16% had any insomnia symptom

Of the 487,200 participants, 11.3% had difficulty initiating or maintaining sleep, 10.4% had early morning awakening, and 2.2% had daytime dysfunction attributed to poor sleep. Compared with participants without insomnia symptoms, participants with insomnia symptoms tended to be older and were more likely to be female, not married, and from a rural area. In addition, those with insomnia symptoms were more likely have depression or anxiety symptoms, lower education level, lower household income, and lower body mass index. They also were more likely to have a history of diabetes mellitus. During a median follow-up of 9.6 years, 130,032 cases of cardiocerebral vascular disease occurred, including 40,348 cases of ischemic heart disease and 45,316 cases of stroke.

After adjustment for potential confounders, each insomnia symptom was associated with greater risk of cardiocerebral vascular disease. For difficulty initiating or maintaining sleep, the hazard ratio was 1.09. For early-morning awakening, the HR was 1.07. For daytime dysfunction, the HR was 1.13. Each insomnia symptom was associated with increased risk of ischemic heart disease and ischemic stroke, whereas only difficulty initiating or maintaining sleep was associated with increased risk of acute MI.

In all, 16.4% of participants reported any insomnia symptom; 10% had one symptom, 5.2% had two symptoms, and 1.2% had three symptoms. “Compared with those without any insomnia symptoms, participants with one, two, or three symptoms had a 7%, 10%, or 18% higher risk of total [cardiocerebral vascular disease] incidence, respectively,” the authors wrote. “Our study is the first large-scale cohort study that identified positive dose-response relationships between the number of insomnia symptoms and risks of [cardiocerebral vascular diseases, ischemic heart disease] and stroke incidence.”

Opportunity for intervention

Compared with clinical diagnostic criteria for insomnia, “individual insomnia symptoms are better defined and more feasible to assess with questionnaires in large-scale population studies and clinical practice,” Dr. Li and colleagues wrote. “Moreover, it is reasonable that insomnia symptoms are more modifiable and precisely targetable through behavioral therapies before developing into clinically significant insomnia disorder. Therefore, future clinical trials or community-based intervention studies should be conducted to test whether lifestyle or sleep hygiene interventions for insomnia symptoms can reduce subsequent [cardiocerebral vascular disease] risks.”

The results suggest that efforts aimed at early detection and intervention should include a focus on younger adults and people who do not have high blood pressure, Dr. Li said.

The self-reported insomnia symptoms used in this study have not been fully validated, the investigators noted. The researchers also lacked information about potential confounders, such as shift work and obstructive sleep apnea, that are risk factors for coronary heart disease or stroke and may interfere with insomnia symptoms. In addition, the study did not capture changes in insomnia symptoms over time.

This study was supported by the National Key Research and Development Program of China, the Chinese Ministry of Science and Technology, and the National Natural Science Foundation of China. The China Kadoorie Biobank surveys were supported by grants from the Kadoorie Charitable Foundation and the U.K. Wellcome Trust. The authors had no relevant disclosures.

[email protected]

SOURCE: Zheng B et al. Neurology. 2019 Nov 6. doi: 10.1212/WNL.0000000000008581.

The presence of insomnia symptoms increases the likelihood of cardiovascular or cerebrovascular disease during approximately 10 years of follow-up, according to a large cohort study of adults in China. A greater number of insomnia symptoms is associated with increased risk, and this relationship is more evident in younger adults and in adults without hypertension at baseline, researchers reported Nov. 6 in Neurology.

Karen Winton/iStockphoto

“These results suggest that, if we can target people who are having trouble sleeping with behavioral therapies, it’s possible that we could reduce the number of cases of stroke, heart attack, and other diseases later down the line,” study author Liming Li, MD, professor of epidemiology at Peking University, Beijing, said in a news release.

To clarify the relationships between individual insomnia symptoms, cardiocerebral vascular diseases, and potential effect modifiers, Dr. Li and colleagues analyzed data from the China Kadoorie Biobank Study. For this study, more than 500,000 adults in China aged 30-79 years completed a baseline survey during 2004-2008. The present analysis included data from 487,200 participants who did not have a history of stroke, coronary heart disease, or cancer at baseline.

For the baseline survey, participants answered questions about whether specific insomnia symptoms occurred at least 3 days per week during the past month. The symptoms included difficulty initiating or maintaining sleep (that is, sleep onset latency of 30 minutes or more after going to bed or waking up in the middle of the night); waking too early and being unable to fall back asleep; and trouble functioning during the day because of bad sleep.

The researchers assessed the incidence of cardiocerebral vascular diseases through 2016 by examining disease registries, national health insurance claims databases, and local records. Investigators identified participants with any cardiocerebral vascular disease and assessed the incidence of ischemic heart disease, acute myocardial infarction, hemorrhagic stroke, and ischemic stroke. The researchers followed each participant until the diagnosis of a cardiocerebral vascular disease outcome, death from any cause, loss to follow-up, or Dec. 31, 2016. The researchers used Cox proportional hazard models to estimate hazard ratios for the association between each insomnia symptom and cardiocerebral vascular disease outcomes. They adjusted the models for established and potential confounding factors, including age, income, smoking status, diet, and physical activity.

More than 16% had any insomnia symptom

Of the 487,200 participants, 11.3% had difficulty initiating or maintaining sleep, 10.4% had early morning awakening, and 2.2% had daytime dysfunction attributed to poor sleep. Compared with participants without insomnia symptoms, participants with insomnia symptoms tended to be older and were more likely to be female, not married, and from a rural area. In addition, those with insomnia symptoms were more likely have depression or anxiety symptoms, lower education level, lower household income, and lower body mass index. They also were more likely to have a history of diabetes mellitus. During a median follow-up of 9.6 years, 130,032 cases of cardiocerebral vascular disease occurred, including 40,348 cases of ischemic heart disease and 45,316 cases of stroke.

After adjustment for potential confounders, each insomnia symptom was associated with greater risk of cardiocerebral vascular disease. For difficulty initiating or maintaining sleep, the hazard ratio was 1.09. For early-morning awakening, the HR was 1.07. For daytime dysfunction, the HR was 1.13. Each insomnia symptom was associated with increased risk of ischemic heart disease and ischemic stroke, whereas only difficulty initiating or maintaining sleep was associated with increased risk of acute MI.

In all, 16.4% of participants reported any insomnia symptom; 10% had one symptom, 5.2% had two symptoms, and 1.2% had three symptoms. “Compared with those without any insomnia symptoms, participants with one, two, or three symptoms had a 7%, 10%, or 18% higher risk of total [cardiocerebral vascular disease] incidence, respectively,” the authors wrote. “Our study is the first large-scale cohort study that identified positive dose-response relationships between the number of insomnia symptoms and risks of [cardiocerebral vascular diseases, ischemic heart disease] and stroke incidence.”

Opportunity for intervention

Compared with clinical diagnostic criteria for insomnia, “individual insomnia symptoms are better defined and more feasible to assess with questionnaires in large-scale population studies and clinical practice,” Dr. Li and colleagues wrote. “Moreover, it is reasonable that insomnia symptoms are more modifiable and precisely targetable through behavioral therapies before developing into clinically significant insomnia disorder. Therefore, future clinical trials or community-based intervention studies should be conducted to test whether lifestyle or sleep hygiene interventions for insomnia symptoms can reduce subsequent [cardiocerebral vascular disease] risks.”

The results suggest that efforts aimed at early detection and intervention should include a focus on younger adults and people who do not have high blood pressure, Dr. Li said.

The self-reported insomnia symptoms used in this study have not been fully validated, the investigators noted. The researchers also lacked information about potential confounders, such as shift work and obstructive sleep apnea, that are risk factors for coronary heart disease or stroke and may interfere with insomnia symptoms. In addition, the study did not capture changes in insomnia symptoms over time.

This study was supported by the National Key Research and Development Program of China, the Chinese Ministry of Science and Technology, and the National Natural Science Foundation of China. The China Kadoorie Biobank surveys were supported by grants from the Kadoorie Charitable Foundation and the U.K. Wellcome Trust. The authors had no relevant disclosures.

[email protected]

SOURCE: Zheng B et al. Neurology. 2019 Nov 6. doi: 10.1212/WNL.0000000000008581.

The presence of insomnia symptoms increases the likelihood of cardiovascular or cerebrovascular disease during approximately 10 years of follow-up, according to a large cohort study of adults in China. A greater number of insomnia symptoms is associated with increased risk, and this relationship is more evident in younger adults and in adults without hypertension at baseline, researchers reported Nov. 6 in Neurology.

Karen Winton/iStockphoto

“These results suggest that, if we can target people who are having trouble sleeping with behavioral therapies, it’s possible that we could reduce the number of cases of stroke, heart attack, and other diseases later down the line,” study author Liming Li, MD, professor of epidemiology at Peking University, Beijing, said in a news release.

To clarify the relationships between individual insomnia symptoms, cardiocerebral vascular diseases, and potential effect modifiers, Dr. Li and colleagues analyzed data from the China Kadoorie Biobank Study. For this study, more than 500,000 adults in China aged 30-79 years completed a baseline survey during 2004-2008. The present analysis included data from 487,200 participants who did not have a history of stroke, coronary heart disease, or cancer at baseline.

For the baseline survey, participants answered questions about whether specific insomnia symptoms occurred at least 3 days per week during the past month. The symptoms included difficulty initiating or maintaining sleep (that is, sleep onset latency of 30 minutes or more after going to bed or waking up in the middle of the night); waking too early and being unable to fall back asleep; and trouble functioning during the day because of bad sleep.

The researchers assessed the incidence of cardiocerebral vascular diseases through 2016 by examining disease registries, national health insurance claims databases, and local records. Investigators identified participants with any cardiocerebral vascular disease and assessed the incidence of ischemic heart disease, acute myocardial infarction, hemorrhagic stroke, and ischemic stroke. The researchers followed each participant until the diagnosis of a cardiocerebral vascular disease outcome, death from any cause, loss to follow-up, or Dec. 31, 2016. The researchers used Cox proportional hazard models to estimate hazard ratios for the association between each insomnia symptom and cardiocerebral vascular disease outcomes. They adjusted the models for established and potential confounding factors, including age, income, smoking status, diet, and physical activity.

More than 16% had any insomnia symptom

Of the 487,200 participants, 11.3% had difficulty initiating or maintaining sleep, 10.4% had early morning awakening, and 2.2% had daytime dysfunction attributed to poor sleep. Compared with participants without insomnia symptoms, participants with insomnia symptoms tended to be older and were more likely to be female, not married, and from a rural area. In addition, those with insomnia symptoms were more likely have depression or anxiety symptoms, lower education level, lower household income, and lower body mass index. They also were more likely to have a history of diabetes mellitus. During a median follow-up of 9.6 years, 130,032 cases of cardiocerebral vascular disease occurred, including 40,348 cases of ischemic heart disease and 45,316 cases of stroke.

After adjustment for potential confounders, each insomnia symptom was associated with greater risk of cardiocerebral vascular disease. For difficulty initiating or maintaining sleep, the hazard ratio was 1.09. For early-morning awakening, the HR was 1.07. For daytime dysfunction, the HR was 1.13. Each insomnia symptom was associated with increased risk of ischemic heart disease and ischemic stroke, whereas only difficulty initiating or maintaining sleep was associated with increased risk of acute MI.

In all, 16.4% of participants reported any insomnia symptom; 10% had one symptom, 5.2% had two symptoms, and 1.2% had three symptoms. “Compared with those without any insomnia symptoms, participants with one, two, or three symptoms had a 7%, 10%, or 18% higher risk of total [cardiocerebral vascular disease] incidence, respectively,” the authors wrote. “Our study is the first large-scale cohort study that identified positive dose-response relationships between the number of insomnia symptoms and risks of [cardiocerebral vascular diseases, ischemic heart disease] and stroke incidence.”

Opportunity for intervention

Compared with clinical diagnostic criteria for insomnia, “individual insomnia symptoms are better defined and more feasible to assess with questionnaires in large-scale population studies and clinical practice,” Dr. Li and colleagues wrote. “Moreover, it is reasonable that insomnia symptoms are more modifiable and precisely targetable through behavioral therapies before developing into clinically significant insomnia disorder. Therefore, future clinical trials or community-based intervention studies should be conducted to test whether lifestyle or sleep hygiene interventions for insomnia symptoms can reduce subsequent [cardiocerebral vascular disease] risks.”

The results suggest that efforts aimed at early detection and intervention should include a focus on younger adults and people who do not have high blood pressure, Dr. Li said.

The self-reported insomnia symptoms used in this study have not been fully validated, the investigators noted. The researchers also lacked information about potential confounders, such as shift work and obstructive sleep apnea, that are risk factors for coronary heart disease or stroke and may interfere with insomnia symptoms. In addition, the study did not capture changes in insomnia symptoms over time.

This study was supported by the National Key Research and Development Program of China, the Chinese Ministry of Science and Technology, and the National Natural Science Foundation of China. The China Kadoorie Biobank surveys were supported by grants from the Kadoorie Charitable Foundation and the U.K. Wellcome Trust. The authors had no relevant disclosures.

[email protected]

SOURCE: Zheng B et al. Neurology. 2019 Nov 6. doi: 10.1212/WNL.0000000000008581.

BARCELONA – People diagnosed with type 2 diabetes when they are 18-39 years old have significantly higher cardiometabolic risk burden, compared with older people, according to the results of a large study from the United Kingdom presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

Patients in that younger age group were found to have higher glycated hemoglobin (HbA_1c) levels, along with higher levels of low-density lipoprotein cholesterol and higher body weight.

“We wanted to evaluate the population-level trend in the incidence of young-onset type 2 diabetes in the United Kingdom, compared with later-onset diabetes,” said senior study author Sanjoy Paul, PhD, the director of the Melbourne EpiCentre at the University of Melbourne at a press briefing during the meeting.

Other aims of the study were to compare temporal trends in the incidence of atherosclerotic cardiovascular disease in younger and older patients with type 2 diabetes, and to see how being “high risk” at diagnosis affected patients’ risk of ASCVD and subsequent risk of death.

High-risk status was defined as having at least two of the risk factors for ASCVD – smoking, high systolic blood pressure, high low-density lipoprotein cholesterol, or chronic kidney disease.

The investigators searched a nationally representative sample of primary care electronic medical records from The Health Improvement Network (THIN) database to find incident cases of type 2 diabetes that occurred between 2000 and 2017, with a total of 370,854 cases identified.

At diagnosis of type 2 diabetes, 8% of the sample (n = 29,678) was aged 18-39 years; 15% (n = 56,798), 40-49 years; 25% (n = 93,698), 50-59 years; 29% (n = 107,261), 60-69 years; and 23% (n = 83,419), 70-79 years. Follow-up was just more than 6 years.

Baseline HbA_1c in the respective age groups was 8.6%, 8.4%, 8.1%, 7.8%, and 7.6%, with more than 55% of patients in the two youngest age groups having an HbA_1c of 7.5% or higher, compared with 34%-47% in the three oldest age groups.

The percentage of patients with a high LDL cholesterol value (2.6 mmol/L or higher in those without ASCVD, and 1.8 or higher in those with ASCVD) was 71%, 75%, 74%, 69%, and 65%, from the youngest to oldest age groups. A respective 71%, 70%, 66%, 57%, and 44% of the patients had a body mass index of 35 kg/m² or higher.

Few younger patients had ASCVD at diagnosis (2% of the 18-39 age group; 6% of the 40-49 group), with higher rates in the older age groups (13% of the 50-59 group; 23% of the 60-69 group; and 33% of the 70-79 group).

The percentage of patients considered to be at high risk of ASCVD at diagnosis was 23%, 37%, 45%, 50%, and 53%, respectively, across the five age groups.

Although high systolic blood pressure (SBP; 130 mmHg in those with ASCVD, 140 mmHg in those without) was more common in the older age groups (52% at 50-59 years; 60% at 60-69 years, and 64% at 70-79 years,) a substantial proportion of the younger patients also had a high SBP (27% at 18-39 years and 41% at 40-49 years).

Sara Freeman/MDedge News

SOURCE: Koye D et al. EASD 2019, Abstract 82.
 

BARCELONA – People diagnosed with type 2 diabetes when they are 18-39 years old have significantly higher cardiometabolic risk burden, compared with older people, according to the results of a large study from the United Kingdom presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

Patients in that younger age group were found to have higher glycated hemoglobin (HbA_1c) levels, along with higher levels of low-density lipoprotein cholesterol and higher body weight.

“We wanted to evaluate the population-level trend in the incidence of young-onset type 2 diabetes in the United Kingdom, compared with later-onset diabetes,” said senior study author Sanjoy Paul, PhD, the director of the Melbourne EpiCentre at the University of Melbourne at a press briefing during the meeting.

Other aims of the study were to compare temporal trends in the incidence of atherosclerotic cardiovascular disease in younger and older patients with type 2 diabetes, and to see how being “high risk” at diagnosis affected patients’ risk of ASCVD and subsequent risk of death.

High-risk status was defined as having at least two of the risk factors for ASCVD – smoking, high systolic blood pressure, high low-density lipoprotein cholesterol, or chronic kidney disease.

The investigators searched a nationally representative sample of primary care electronic medical records from The Health Improvement Network (THIN) database to find incident cases of type 2 diabetes that occurred between 2000 and 2017, with a total of 370,854 cases identified.

At diagnosis of type 2 diabetes, 8% of the sample (n = 29,678) was aged 18-39 years; 15% (n = 56,798), 40-49 years; 25% (n = 93,698), 50-59 years; 29% (n = 107,261), 60-69 years; and 23% (n = 83,419), 70-79 years. Follow-up was just more than 6 years.

Baseline HbA_1c in the respective age groups was 8.6%, 8.4%, 8.1%, 7.8%, and 7.6%, with more than 55% of patients in the two youngest age groups having an HbA_1c of 7.5% or higher, compared with 34%-47% in the three oldest age groups.

The percentage of patients with a high LDL cholesterol value (2.6 mmol/L or higher in those without ASCVD, and 1.8 or higher in those with ASCVD) was 71%, 75%, 74%, 69%, and 65%, from the youngest to oldest age groups. A respective 71%, 70%, 66%, 57%, and 44% of the patients had a body mass index of 35 kg/m² or higher.

Few younger patients had ASCVD at diagnosis (2% of the 18-39 age group; 6% of the 40-49 group), with higher rates in the older age groups (13% of the 50-59 group; 23% of the 60-69 group; and 33% of the 70-79 group).

The percentage of patients considered to be at high risk of ASCVD at diagnosis was 23%, 37%, 45%, 50%, and 53%, respectively, across the five age groups.

Although high systolic blood pressure (SBP; 130 mmHg in those with ASCVD, 140 mmHg in those without) was more common in the older age groups (52% at 50-59 years; 60% at 60-69 years, and 64% at 70-79 years,) a substantial proportion of the younger patients also had a high SBP (27% at 18-39 years and 41% at 40-49 years).

Sara Freeman/MDedge News

SOURCE: Koye D et al. EASD 2019, Abstract 82.
 

BARCELONA – People diagnosed with type 2 diabetes when they are 18-39 years old have significantly higher cardiometabolic risk burden, compared with older people, according to the results of a large study from the United Kingdom presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

Patients in that younger age group were found to have higher glycated hemoglobin (HbA_1c) levels, along with higher levels of low-density lipoprotein cholesterol and higher body weight.

“We wanted to evaluate the population-level trend in the incidence of young-onset type 2 diabetes in the United Kingdom, compared with later-onset diabetes,” said senior study author Sanjoy Paul, PhD, the director of the Melbourne EpiCentre at the University of Melbourne at a press briefing during the meeting.

Other aims of the study were to compare temporal trends in the incidence of atherosclerotic cardiovascular disease in younger and older patients with type 2 diabetes, and to see how being “high risk” at diagnosis affected patients’ risk of ASCVD and subsequent risk of death.

High-risk status was defined as having at least two of the risk factors for ASCVD – smoking, high systolic blood pressure, high low-density lipoprotein cholesterol, or chronic kidney disease.

The investigators searched a nationally representative sample of primary care electronic medical records from The Health Improvement Network (THIN) database to find incident cases of type 2 diabetes that occurred between 2000 and 2017, with a total of 370,854 cases identified.

At diagnosis of type 2 diabetes, 8% of the sample (n = 29,678) was aged 18-39 years; 15% (n = 56,798), 40-49 years; 25% (n = 93,698), 50-59 years; 29% (n = 107,261), 60-69 years; and 23% (n = 83,419), 70-79 years. Follow-up was just more than 6 years.

Baseline HbA_1c in the respective age groups was 8.6%, 8.4%, 8.1%, 7.8%, and 7.6%, with more than 55% of patients in the two youngest age groups having an HbA_1c of 7.5% or higher, compared with 34%-47% in the three oldest age groups.

The percentage of patients with a high LDL cholesterol value (2.6 mmol/L or higher in those without ASCVD, and 1.8 or higher in those with ASCVD) was 71%, 75%, 74%, 69%, and 65%, from the youngest to oldest age groups. A respective 71%, 70%, 66%, 57%, and 44% of the patients had a body mass index of 35 kg/m² or higher.

Few younger patients had ASCVD at diagnosis (2% of the 18-39 age group; 6% of the 40-49 group), with higher rates in the older age groups (13% of the 50-59 group; 23% of the 60-69 group; and 33% of the 70-79 group).

The percentage of patients considered to be at high risk of ASCVD at diagnosis was 23%, 37%, 45%, 50%, and 53%, respectively, across the five age groups.

Although high systolic blood pressure (SBP; 130 mmHg in those with ASCVD, 140 mmHg in those without) was more common in the older age groups (52% at 50-59 years; 60% at 60-69 years, and 64% at 70-79 years,) a substantial proportion of the younger patients also had a high SBP (27% at 18-39 years and 41% at 40-49 years).

Sara Freeman/MDedge News

SOURCE: Koye D et al. EASD 2019, Abstract 82.
 

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.

CDC/Molly Kurnit, M.P.H.

The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.

“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.

“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”

In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.

They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.

This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.

The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.

“These results suggest that, rather than a simple loss of total IgG, there is a restructuring of the antibody repertoire after measles,” Dr. Mina and associates wrote.

They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.

In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.

The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
 

SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.

CDC/Molly Kurnit, M.P.H.

The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.

“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.

“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”

In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.

They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.

This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.

The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.

“These results suggest that, rather than a simple loss of total IgG, there is a restructuring of the antibody repertoire after measles,” Dr. Mina and associates wrote.

They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.

In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.

The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
 

SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.

CDC/Molly Kurnit, M.P.H.

The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.

“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.

“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”

In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.

They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.

This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.

The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.

“These results suggest that, rather than a simple loss of total IgG, there is a restructuring of the antibody repertoire after measles,” Dr. Mina and associates wrote.

They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.

In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.

The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
 

SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

Dear Colleagues,

Forty years ago, dermatology practice was different. No patient came to the office for a “full-body check,” nor did anyone show up for hair removal or questions about cosmetic procedures or skin care advice.

Needle nippers were around, but no elaborate, molded-plastic contraptions like the sharps containers now in wide use. You sent pathology specimens in plastic cylinders by U.S. mail; then you called the lab 2 weeks later to ask, “Where’s the report on Jane Smith, with the rule out melanoma,” and the lab said, “Jane who?”

Of course, some things about practice have not changed. Patients with atopic dermatitis still ask why eczema comes back and why we can’t give them something to make it go away once and for all. Some referring physicians still treat scaly rashes with ketoconazole cream (and when that fails, oral fluconazole, which doesn’t work either).

Of course the biggest change between then and now, coincident with the rise of computers and technology, is the advent and ubiquity of that great swindle foisted upon the profession and the public – electronic health records – with their unfulfilled promises of cost-savings and efficiency and unconceded consequences: turning healers into harried data-entry drudges too busy clicking mice to make eye contact with humans. Yes, the Emperor has clothes. The Emperor is wearing Depends.

I wrote my first column for this periodical 22 years ago; this will be my last. My wonderful editor, Elizabeth Mechcatie, has agreed to take under advisement a proposal that I go on sending occasional dispatches under the heading “Pruritus Emeritus.” My family used to refer to those in the anomalous state of being emeritus – it means, roughly, “Forgotten, but not gone” – by rhyming emeritus with sinusitis.

There is no way to remember 40 years of patients. Many came just once, others several times. Some moved away, some passed away, changed primary doctors, changed insurances. Some grew too old to visit, sent regretful notes apologizing for finding the drive too long, the parking too hard. Some returned after an absence of a decade or 3, having forgotten that they had once come for the same problem, or come at all.

But there have been other patients who formed a real bond, whose names and faces still come readily to mind, who visited over long periods, sent their spouses, family members, even children and grandchildren. The stories of their lives became part of mine, and sometimes mine part of theirs.

Though hardly an old-movie buff, I know the famous scene in Casablanca in which a radiant Ingrid Bergman (that skin!) asks Dooley Wilson – the piano player, Sam – to play the song Humphrey Bogart does not want to hear:

“You must remember this

A kiss is just a kiss

A sigh is just a sigh

The fundamental things apply

As time goes by.”

Over the last 40 years there have been substantial advances in the way we treat patients, though perhaps not enough to justify the endless noisy hype about imminent breakthroughs and looming disruptions, therapies, and apps that are sure to change practice and civilization as we know them. Altogether too much noise, at least for my taste. But not inside the examining room.

Outside the room rages the din of demographic updates, of online checks of insurance eligibility, referral status, prior authorizations, the blare of marketing and promotion, the cacophony of metrics and algorithms.

Inside the room, however, quiet reigns. A patient presents with a symptom or a sign, or the fear of a symptom or anxiety over the meaning of a sign, filtered through a jumble of ideas – misremembered, half understood, at times mutually contradictory – that amplify fears common to anyone who visits a practitioner, however minor the presenting complaint: pain, debility, decline, isolation, solitude, death.

And the practitioner attends, considers, contextualizes, counsels, consoles, and conveys a response to the patient’s questions, whether in so many words or by body language or tone of voice, offers answers not just to what the patient has asked but the ones the patient meant to ask but did not know how.

“Yes, sir, death waits for all of us in the end, but for you, perhaps, not today.”

“Yes, madam, illness can be a frightening affair, but your case is not as bad as you think it is and won’t move as fast as you imagine. And as to your being limited and alone – well, not yet. There are those you can rely on, people with a bit of knowledge and a little experience, who are committed to doing what can be done to bend the arc of illness in your favor.”

That fundamental role will, it seems to me, always apply as long people practice medicine.

With all good wishes for personal happiness and professional success,

Alan Rockoff
 

Dear Colleagues,

Forty years ago, dermatology practice was different. No patient came to the office for a “full-body check,” nor did anyone show up for hair removal or questions about cosmetic procedures or skin care advice.

Needle nippers were around, but no elaborate, molded-plastic contraptions like the sharps containers now in wide use. You sent pathology specimens in plastic cylinders by U.S. mail; then you called the lab 2 weeks later to ask, “Where’s the report on Jane Smith, with the rule out melanoma,” and the lab said, “Jane who?”

Of course, some things about practice have not changed. Patients with atopic dermatitis still ask why eczema comes back and why we can’t give them something to make it go away once and for all. Some referring physicians still treat scaly rashes with ketoconazole cream (and when that fails, oral fluconazole, which doesn’t work either).

Of course the biggest change between then and now, coincident with the rise of computers and technology, is the advent and ubiquity of that great swindle foisted upon the profession and the public – electronic health records – with their unfulfilled promises of cost-savings and efficiency and unconceded consequences: turning healers into harried data-entry drudges too busy clicking mice to make eye contact with humans. Yes, the Emperor has clothes. The Emperor is wearing Depends.

I wrote my first column for this periodical 22 years ago; this will be my last. My wonderful editor, Elizabeth Mechcatie, has agreed to take under advisement a proposal that I go on sending occasional dispatches under the heading “Pruritus Emeritus.” My family used to refer to those in the anomalous state of being emeritus – it means, roughly, “Forgotten, but not gone” – by rhyming emeritus with sinusitis.

There is no way to remember 40 years of patients. Many came just once, others several times. Some moved away, some passed away, changed primary doctors, changed insurances. Some grew too old to visit, sent regretful notes apologizing for finding the drive too long, the parking too hard. Some returned after an absence of a decade or 3, having forgotten that they had once come for the same problem, or come at all.

But there have been other patients who formed a real bond, whose names and faces still come readily to mind, who visited over long periods, sent their spouses, family members, even children and grandchildren. The stories of their lives became part of mine, and sometimes mine part of theirs.

Though hardly an old-movie buff, I know the famous scene in Casablanca in which a radiant Ingrid Bergman (that skin!) asks Dooley Wilson – the piano player, Sam – to play the song Humphrey Bogart does not want to hear:

“You must remember this

A kiss is just a kiss

A sigh is just a sigh

The fundamental things apply

As time goes by.”

Over the last 40 years there have been substantial advances in the way we treat patients, though perhaps not enough to justify the endless noisy hype about imminent breakthroughs and looming disruptions, therapies, and apps that are sure to change practice and civilization as we know them. Altogether too much noise, at least for my taste. But not inside the examining room.

Outside the room rages the din of demographic updates, of online checks of insurance eligibility, referral status, prior authorizations, the blare of marketing and promotion, the cacophony of metrics and algorithms.

Inside the room, however, quiet reigns. A patient presents with a symptom or a sign, or the fear of a symptom or anxiety over the meaning of a sign, filtered through a jumble of ideas – misremembered, half understood, at times mutually contradictory – that amplify fears common to anyone who visits a practitioner, however minor the presenting complaint: pain, debility, decline, isolation, solitude, death.

And the practitioner attends, considers, contextualizes, counsels, consoles, and conveys a response to the patient’s questions, whether in so many words or by body language or tone of voice, offers answers not just to what the patient has asked but the ones the patient meant to ask but did not know how.

“Yes, sir, death waits for all of us in the end, but for you, perhaps, not today.”

“Yes, madam, illness can be a frightening affair, but your case is not as bad as you think it is and won’t move as fast as you imagine. And as to your being limited and alone – well, not yet. There are those you can rely on, people with a bit of knowledge and a little experience, who are committed to doing what can be done to bend the arc of illness in your favor.”

That fundamental role will, it seems to me, always apply as long people practice medicine.

With all good wishes for personal happiness and professional success,

Alan Rockoff
 

Dear Colleagues,

Forty years ago, dermatology practice was different. No patient came to the office for a “full-body check,” nor did anyone show up for hair removal or questions about cosmetic procedures or skin care advice.

Needle nippers were around, but no elaborate, molded-plastic contraptions like the sharps containers now in wide use. You sent pathology specimens in plastic cylinders by U.S. mail; then you called the lab 2 weeks later to ask, “Where’s the report on Jane Smith, with the rule out melanoma,” and the lab said, “Jane who?”

Of course, some things about practice have not changed. Patients with atopic dermatitis still ask why eczema comes back and why we can’t give them something to make it go away once and for all. Some referring physicians still treat scaly rashes with ketoconazole cream (and when that fails, oral fluconazole, which doesn’t work either).

Of course the biggest change between then and now, coincident with the rise of computers and technology, is the advent and ubiquity of that great swindle foisted upon the profession and the public – electronic health records – with their unfulfilled promises of cost-savings and efficiency and unconceded consequences: turning healers into harried data-entry drudges too busy clicking mice to make eye contact with humans. Yes, the Emperor has clothes. The Emperor is wearing Depends.

I wrote my first column for this periodical 22 years ago; this will be my last. My wonderful editor, Elizabeth Mechcatie, has agreed to take under advisement a proposal that I go on sending occasional dispatches under the heading “Pruritus Emeritus.” My family used to refer to those in the anomalous state of being emeritus – it means, roughly, “Forgotten, but not gone” – by rhyming emeritus with sinusitis.

There is no way to remember 40 years of patients. Many came just once, others several times. Some moved away, some passed away, changed primary doctors, changed insurances. Some grew too old to visit, sent regretful notes apologizing for finding the drive too long, the parking too hard. Some returned after an absence of a decade or 3, having forgotten that they had once come for the same problem, or come at all.

But there have been other patients who formed a real bond, whose names and faces still come readily to mind, who visited over long periods, sent their spouses, family members, even children and grandchildren. The stories of their lives became part of mine, and sometimes mine part of theirs.

Though hardly an old-movie buff, I know the famous scene in Casablanca in which a radiant Ingrid Bergman (that skin!) asks Dooley Wilson – the piano player, Sam – to play the song Humphrey Bogart does not want to hear:

“You must remember this

A kiss is just a kiss

A sigh is just a sigh

The fundamental things apply

As time goes by.”

Over the last 40 years there have been substantial advances in the way we treat patients, though perhaps not enough to justify the endless noisy hype about imminent breakthroughs and looming disruptions, therapies, and apps that are sure to change practice and civilization as we know them. Altogether too much noise, at least for my taste. But not inside the examining room.

Outside the room rages the din of demographic updates, of online checks of insurance eligibility, referral status, prior authorizations, the blare of marketing and promotion, the cacophony of metrics and algorithms.

Inside the room, however, quiet reigns. A patient presents with a symptom or a sign, or the fear of a symptom or anxiety over the meaning of a sign, filtered through a jumble of ideas – misremembered, half understood, at times mutually contradictory – that amplify fears common to anyone who visits a practitioner, however minor the presenting complaint: pain, debility, decline, isolation, solitude, death.

And the practitioner attends, considers, contextualizes, counsels, consoles, and conveys a response to the patient’s questions, whether in so many words or by body language or tone of voice, offers answers not just to what the patient has asked but the ones the patient meant to ask but did not know how.

“Yes, sir, death waits for all of us in the end, but for you, perhaps, not today.”

“Yes, madam, illness can be a frightening affair, but your case is not as bad as you think it is and won’t move as fast as you imagine. And as to your being limited and alone – well, not yet. There are those you can rely on, people with a bit of knowledge and a little experience, who are committed to doing what can be done to bend the arc of illness in your favor.”

That fundamental role will, it seems to me, always apply as long people practice medicine.

With all good wishes for personal happiness and professional success,

Alan Rockoff
 

When it comes to repairing knee cartilage, a new study found no significant differences between autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation with a collagen membrane (ACI-C) as treatment options.

“If the conclusion of the present study stands and is confirmed by further clinical trials, AMIC could be considered an equal alternative to techniques based on chondrocyte transplantation for treatment of cartilage defects of the knee,” wrote Vegard Fossum, MD, of University Hospital of North Norway, Tromsø, and coauthors, adding that cost and comparative ease might actually make AMIC the preferred choice. The study was published in the Orthopaedic Journal of Sports Medicine.

To evaluate outcomes of the two procedures, the researchers initiated a clinical trial of 41 patients with at least one chondral or osteochondral defect of the distal femur or patella. They were split into two groups: those treated with ACI-C (n = 21) and those treated with AMIC (n = 20). At 1- and 2-year follow-up, patients were assessed via improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), compared with baseline, along with Lysholm and visual analog scale (VAS) pain scores.

After 1 and 2 years, both groups saw improvements from baseline. At 2 years, the AMIC group had an 18.1 change in KOOS, compared with 10.3 in the ACI-C group (P = .17). Two-year improvements on the Lysholm score (19.7 in AMIC, compared with 17.0 in ACI-C, P = .66) and VAS pain score (30.6 in AMIC versus 19.6 in ACI-C, P = .19) were not significantly different. Two patients in the AMIC group had undergone total knee replacement after 2 years, compared with zero in the ACI-C group.

The authors noted their study’s potential limitations, including the small number of patients in each group – the initial plan was to include 80 total – and its broad inclusion criteria. However, since the aim was to compare treatment results and not evaluate effectiveness, they did not consider the broad criteria “a major limitation.”

The authors reported no conflicts of interest.

SOURCE: Fossum V et al. Orthop J Sports Med. 2019 Sept 17. doi: 10.1177/2325967119868212.

When it comes to repairing knee cartilage, a new study found no significant differences between autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation with a collagen membrane (ACI-C) as treatment options.

“If the conclusion of the present study stands and is confirmed by further clinical trials, AMIC could be considered an equal alternative to techniques based on chondrocyte transplantation for treatment of cartilage defects of the knee,” wrote Vegard Fossum, MD, of University Hospital of North Norway, Tromsø, and coauthors, adding that cost and comparative ease might actually make AMIC the preferred choice. The study was published in the Orthopaedic Journal of Sports Medicine.

To evaluate outcomes of the two procedures, the researchers initiated a clinical trial of 41 patients with at least one chondral or osteochondral defect of the distal femur or patella. They were split into two groups: those treated with ACI-C (n = 21) and those treated with AMIC (n = 20). At 1- and 2-year follow-up, patients were assessed via improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), compared with baseline, along with Lysholm and visual analog scale (VAS) pain scores.

After 1 and 2 years, both groups saw improvements from baseline. At 2 years, the AMIC group had an 18.1 change in KOOS, compared with 10.3 in the ACI-C group (P = .17). Two-year improvements on the Lysholm score (19.7 in AMIC, compared with 17.0 in ACI-C, P = .66) and VAS pain score (30.6 in AMIC versus 19.6 in ACI-C, P = .19) were not significantly different. Two patients in the AMIC group had undergone total knee replacement after 2 years, compared with zero in the ACI-C group.

The authors noted their study’s potential limitations, including the small number of patients in each group – the initial plan was to include 80 total – and its broad inclusion criteria. However, since the aim was to compare treatment results and not evaluate effectiveness, they did not consider the broad criteria “a major limitation.”

The authors reported no conflicts of interest.

SOURCE: Fossum V et al. Orthop J Sports Med. 2019 Sept 17. doi: 10.1177/2325967119868212.

When it comes to repairing knee cartilage, a new study found no significant differences between autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation with a collagen membrane (ACI-C) as treatment options.

“If the conclusion of the present study stands and is confirmed by further clinical trials, AMIC could be considered an equal alternative to techniques based on chondrocyte transplantation for treatment of cartilage defects of the knee,” wrote Vegard Fossum, MD, of University Hospital of North Norway, Tromsø, and coauthors, adding that cost and comparative ease might actually make AMIC the preferred choice. The study was published in the Orthopaedic Journal of Sports Medicine.

To evaluate outcomes of the two procedures, the researchers initiated a clinical trial of 41 patients with at least one chondral or osteochondral defect of the distal femur or patella. They were split into two groups: those treated with ACI-C (n = 21) and those treated with AMIC (n = 20). At 1- and 2-year follow-up, patients were assessed via improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), compared with baseline, along with Lysholm and visual analog scale (VAS) pain scores.

After 1 and 2 years, both groups saw improvements from baseline. At 2 years, the AMIC group had an 18.1 change in KOOS, compared with 10.3 in the ACI-C group (P = .17). Two-year improvements on the Lysholm score (19.7 in AMIC, compared with 17.0 in ACI-C, P = .66) and VAS pain score (30.6 in AMIC versus 19.6 in ACI-C, P = .19) were not significantly different. Two patients in the AMIC group had undergone total knee replacement after 2 years, compared with zero in the ACI-C group.

The authors noted their study’s potential limitations, including the small number of patients in each group – the initial plan was to include 80 total – and its broad inclusion criteria. However, since the aim was to compare treatment results and not evaluate effectiveness, they did not consider the broad criteria “a major limitation.”

The authors reported no conflicts of interest.

SOURCE: Fossum V et al. Orthop J Sports Med. 2019 Sept 17. doi: 10.1177/2325967119868212.

The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.

By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.

“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.

The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.

In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.

The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.

Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.

With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.

The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.

MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.

In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.

The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.

SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.

The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.

By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.

“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.

The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.

In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.

The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.

Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.

With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.

The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.

MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.

In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.

The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.

SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.

The combination of rituximab and bendamustine (RB) provided “excellent” survival with less toxicity, compared with a cytarabine-based induction regimen, in transplant-eligible patients with mantle cell lymphoma, according to a long-term follow-up report from randomized phase 2 trial.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The 5-year survival rates for RB were “provocatively similar” to what was achieved with the standard, intensive R-hyperCVAD regimen, investigators said in this update on the Southwest Oncology Group (SWOG) S1106 study.

By contrast, the R-hyperCVAD regimen was associated with more toxicity and higher failure rates for stem cell mobilization, according to the report’s lead author, Manali Kamdar, MD, of the University of Colorado, Denver, and coauthors.

“Overall, S1106 demonstrated that an outpatient-based, less intensive induction therapy of bendamustine plus rituximab is highly effective, safe, and durable in untreated transplant-eligible MCL patients,” Dr. Kamdar and her colleagues reported in Blood Advances.

The results have guided the design of an upcoming study, EA4181, in which patients with mantle cell lymphoma will be treated with an RB backbone plus cytarabine, the BTK inhibitor acalabrutinib, or both, according to the authors.

In the present study, S1106, patients with mantle cell lymphoma were randomized to receive RB or the R-hyperCVAD regimen, which consisted of rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with high-dose cytarabine and methotrexate. Both regimens were followed by autologous hematopoietic stem cell transplant.

The stem cell mobilization failure rate was 29% in the R-hyperCVAD arm in an interim analysis conducted after 53 of a planned 160 patients had been enrolled, including 35 in the RB arm and 17 in the R-hyperCVAD arm, according to a report published in the British Journal of Haematology (2016 Dec 19. doi: 10.1111/bjh.14480). That analysis triggered a shutdown of the study, based on a rule stating that either arm would be deemed “unacceptably toxic” if the mobilization rate exceeded 10%.

Accordingly, R-hyperCVAD is “not an ideal platform” for future trials, the investigators said. At that time, the estimated 2-year progression-free survival (PFS) was 81% versus 82% for RB and R-hyperCVAD, respectively, while overall survival (OS) was 87% versus 88%.

With additional follow-up, the 5-year PFS is 66% and 62% in the RB and R-hyperCVAD arms, respectively, while 5-year OS is 80% and 74%, according to the investigators.

The RB regimen also results in “excellent” minimal residual disease (MRD) negativity, they added.

MRD status was evaluated in 12 paired pre- and postinduction therapy specimens, of which 2 pairs were from patients in the R-hyperCVAD arm, and 10 pairs were from patients in the RB arm.

In the R-hyperCVAD arm, both patients were MRD positive at baseline, and MRD negative after induction, according to the investigators. Similarly, 9 of 10 patients in the RB arm were MRD positive at baseline, and of those, 7 converted to MRD negative following induction.

The research was supported by the National Cancer Institute, and in part by Sequenta (Adaptive Biotechnologies). Dr. Kamdar reported being on the speakers bureau of Seattle Genetics and receiving consultancy fees from AstraZeneca, Celgene, and Genentech. Co-authors of the study provided disclosures related to Millennium Pharmaceuticals, Affimed, Seattle Genetics, Pharmacyclics, and Merck, among others.

SOURCE: Kamdar M et al. Blood Adv. 2019 Oct 22;3(20):3132-5.

MADRID – Nemolizumab, an investigational humanized monoclonal antibody targeting the interleukin-31 receptor alpha subunit, achieved rapid and clinically meaningful improvement in both itch and skin lesions of severe prurigo nodularis in a phase 2b, randomized trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

“We saw onset of pruritus improvement in week 1 and onset of lesion healing at week 4,” reported Dr. Stander, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).

The study results confirm IL-31 signaling as an important therapeutic target in prurigo nodularis and herald the arrival of nemolizumab as a promising potential therapy for severely affected patients, she added.

Prurigo nodularis is a chronic, highly pruritic disease that is difficult to treat and carries a high disease burden. While the disease’s pathogenesis is not completely understood, IL-31 is up-regulated in affected patients. And IL-31, a proinflammatory and immunomodulatory cytokine, is known to have a broad range of actions, including serving as a link between the immune and neural systems, as well as induction of itch and skin lesions.

Dr. Stander presented the results of a 20-center, double-blind, phase 2b clinical trial in which 70 patients with prurigo nodularis were randomized to subcutaneous nemolizumab at 0.5 mg/kg or placebo at weeks 0, 4, and 8, then followed off therapy out to week 18. These were severely affected patients: their mean weekly peak pruritus score on a 0-10 numeric rating scale was 8.4, with 7 being the accepted threshold for severe itch. The group had a mean Dermatologic Life Quality Index score of 16.4; 40% of patients had more than 100 nodules on their body, and the rest had 20-100.

The primary endpoint was the percentage decrease in the peak pruritus score from baseline to week 4, at which point they had only received one dose. The nemolizumab group averaged a 53.4% reduction, compared with 15.3% in placebo-treated controls. At week 12, a full month after the final injection, the split was 63.2% versus 20.2%. And at week 18, the nemolizumab group maintained a mean 58.2% reduction from baseline versus 20.9% in controls.

“The effect starts at week 1, with a 26% reduction in itch intensity in the nemolizumab group, compared to 6.7% with placebo,” the dermatologist observed.

The absolute decrease in weekly peak pruritus score at week 12 was 5.2 points with nemolizumab and 1.7 points with placebo.

Among the secondary endpoints was achievement of an Investigator Global Assessment score of 0-1, meaning clear or almost clear of skin lesions. The rate in the nemolizumab group climbed steadily from week 4 on, reaching 38.2% and still rising without a plateau at week 18, versus 5.6% in controls.

Another secondary endpoint was 75% or greater healing on the 7-item Prurigo Activity Scale. By week 4 there was already a statistically significant between-group difference: 23.5% versus 11.2%. Once again, in the nemolizumab group, this rate climbed without a plateau through the study’s end at week 18, by which point it was 44.1%, compared with 8.4% among those on placebo.

Scores on the Dermatologic Life Quality Index improved by an average of 10.2 points at week 4 in patients on nemolizumab, compared with 6 points among controls.

Self-reported sleep disturbance scores improved by 56% at week 4 in the nemolizumab group and 22.9% with placebo.

The safety profile of nemolizumab was similar to that of placebo, with roughly 5.7% of patients in each study arm withdrawing because of treatment-emergent adverse events. Unlike in the positive studies of the IL-31 inhibitor in patients with atopic dermatitis – another potential indication under active investigation – there was no signal of an increased risk of staphylococcal skin infections, conjunctivitis, or head and neck dermatitis in patients on nemolizumab for prurigo nodularis. Patients with comorbid atopic dermatitis were excluded from the prurigo nodularis trial in order to get a clearer picture of the biologic’s efficacy and safety specifically for that condition.

Dr. Stander reported serving as a consultant to Galderma, the study sponsor, as well as numerous other pharmaceutical companies.

[email protected]

MADRID – Nemolizumab, an investigational humanized monoclonal antibody targeting the interleukin-31 receptor alpha subunit, achieved rapid and clinically meaningful improvement in both itch and skin lesions of severe prurigo nodularis in a phase 2b, randomized trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

“We saw onset of pruritus improvement in week 1 and onset of lesion healing at week 4,” reported Dr. Stander, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).

The study results confirm IL-31 signaling as an important therapeutic target in prurigo nodularis and herald the arrival of nemolizumab as a promising potential therapy for severely affected patients, she added.

Prurigo nodularis is a chronic, highly pruritic disease that is difficult to treat and carries a high disease burden. While the disease’s pathogenesis is not completely understood, IL-31 is up-regulated in affected patients. And IL-31, a proinflammatory and immunomodulatory cytokine, is known to have a broad range of actions, including serving as a link between the immune and neural systems, as well as induction of itch and skin lesions.

Dr. Stander presented the results of a 20-center, double-blind, phase 2b clinical trial in which 70 patients with prurigo nodularis were randomized to subcutaneous nemolizumab at 0.5 mg/kg or placebo at weeks 0, 4, and 8, then followed off therapy out to week 18. These were severely affected patients: their mean weekly peak pruritus score on a 0-10 numeric rating scale was 8.4, with 7 being the accepted threshold for severe itch. The group had a mean Dermatologic Life Quality Index score of 16.4; 40% of patients had more than 100 nodules on their body, and the rest had 20-100.

The primary endpoint was the percentage decrease in the peak pruritus score from baseline to week 4, at which point they had only received one dose. The nemolizumab group averaged a 53.4% reduction, compared with 15.3% in placebo-treated controls. At week 12, a full month after the final injection, the split was 63.2% versus 20.2%. And at week 18, the nemolizumab group maintained a mean 58.2% reduction from baseline versus 20.9% in controls.

“The effect starts at week 1, with a 26% reduction in itch intensity in the nemolizumab group, compared to 6.7% with placebo,” the dermatologist observed.

The absolute decrease in weekly peak pruritus score at week 12 was 5.2 points with nemolizumab and 1.7 points with placebo.

Among the secondary endpoints was achievement of an Investigator Global Assessment score of 0-1, meaning clear or almost clear of skin lesions. The rate in the nemolizumab group climbed steadily from week 4 on, reaching 38.2% and still rising without a plateau at week 18, versus 5.6% in controls.

Another secondary endpoint was 75% or greater healing on the 7-item Prurigo Activity Scale. By week 4 there was already a statistically significant between-group difference: 23.5% versus 11.2%. Once again, in the nemolizumab group, this rate climbed without a plateau through the study’s end at week 18, by which point it was 44.1%, compared with 8.4% among those on placebo.

Scores on the Dermatologic Life Quality Index improved by an average of 10.2 points at week 4 in patients on nemolizumab, compared with 6 points among controls.

Self-reported sleep disturbance scores improved by 56% at week 4 in the nemolizumab group and 22.9% with placebo.

The safety profile of nemolizumab was similar to that of placebo, with roughly 5.7% of patients in each study arm withdrawing because of treatment-emergent adverse events. Unlike in the positive studies of the IL-31 inhibitor in patients with atopic dermatitis – another potential indication under active investigation – there was no signal of an increased risk of staphylococcal skin infections, conjunctivitis, or head and neck dermatitis in patients on nemolizumab for prurigo nodularis. Patients with comorbid atopic dermatitis were excluded from the prurigo nodularis trial in order to get a clearer picture of the biologic’s efficacy and safety specifically for that condition.

Dr. Stander reported serving as a consultant to Galderma, the study sponsor, as well as numerous other pharmaceutical companies.

[email protected]

MADRID – Nemolizumab, an investigational humanized monoclonal antibody targeting the interleukin-31 receptor alpha subunit, achieved rapid and clinically meaningful improvement in both itch and skin lesions of severe prurigo nodularis in a phase 2b, randomized trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

“We saw onset of pruritus improvement in week 1 and onset of lesion healing at week 4,” reported Dr. Stander, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).

The study results confirm IL-31 signaling as an important therapeutic target in prurigo nodularis and herald the arrival of nemolizumab as a promising potential therapy for severely affected patients, she added.

Prurigo nodularis is a chronic, highly pruritic disease that is difficult to treat and carries a high disease burden. While the disease’s pathogenesis is not completely understood, IL-31 is up-regulated in affected patients. And IL-31, a proinflammatory and immunomodulatory cytokine, is known to have a broad range of actions, including serving as a link between the immune and neural systems, as well as induction of itch and skin lesions.

Dr. Stander presented the results of a 20-center, double-blind, phase 2b clinical trial in which 70 patients with prurigo nodularis were randomized to subcutaneous nemolizumab at 0.5 mg/kg or placebo at weeks 0, 4, and 8, then followed off therapy out to week 18. These were severely affected patients: their mean weekly peak pruritus score on a 0-10 numeric rating scale was 8.4, with 7 being the accepted threshold for severe itch. The group had a mean Dermatologic Life Quality Index score of 16.4; 40% of patients had more than 100 nodules on their body, and the rest had 20-100.

The primary endpoint was the percentage decrease in the peak pruritus score from baseline to week 4, at which point they had only received one dose. The nemolizumab group averaged a 53.4% reduction, compared with 15.3% in placebo-treated controls. At week 12, a full month after the final injection, the split was 63.2% versus 20.2%. And at week 18, the nemolizumab group maintained a mean 58.2% reduction from baseline versus 20.9% in controls.

“The effect starts at week 1, with a 26% reduction in itch intensity in the nemolizumab group, compared to 6.7% with placebo,” the dermatologist observed.

The absolute decrease in weekly peak pruritus score at week 12 was 5.2 points with nemolizumab and 1.7 points with placebo.

Among the secondary endpoints was achievement of an Investigator Global Assessment score of 0-1, meaning clear or almost clear of skin lesions. The rate in the nemolizumab group climbed steadily from week 4 on, reaching 38.2% and still rising without a plateau at week 18, versus 5.6% in controls.

Another secondary endpoint was 75% or greater healing on the 7-item Prurigo Activity Scale. By week 4 there was already a statistically significant between-group difference: 23.5% versus 11.2%. Once again, in the nemolizumab group, this rate climbed without a plateau through the study’s end at week 18, by which point it was 44.1%, compared with 8.4% among those on placebo.

Scores on the Dermatologic Life Quality Index improved by an average of 10.2 points at week 4 in patients on nemolizumab, compared with 6 points among controls.

Self-reported sleep disturbance scores improved by 56% at week 4 in the nemolizumab group and 22.9% with placebo.

The safety profile of nemolizumab was similar to that of placebo, with roughly 5.7% of patients in each study arm withdrawing because of treatment-emergent adverse events. Unlike in the positive studies of the IL-31 inhibitor in patients with atopic dermatitis – another potential indication under active investigation – there was no signal of an increased risk of staphylococcal skin infections, conjunctivitis, or head and neck dermatitis in patients on nemolizumab for prurigo nodularis. Patients with comorbid atopic dermatitis were excluded from the prurigo nodularis trial in order to get a clearer picture of the biologic’s efficacy and safety specifically for that condition.

Dr. Stander reported serving as a consultant to Galderma, the study sponsor, as well as numerous other pharmaceutical companies.

[email protected]