Factoring hyponatremic status into liver graft allocations led to significant reductions in wait-list mortality, researchers reported in the November issue of Gastroenterology.

©Eraxion/thinkstockphotos.com

Hyponatremic patients with low MELD scores benefited significantly from allocation based on the end-stage liver disease–sodium (MELD-Na) score, while its survival benefit was less evident among patients with higher scores, said Shunji Nagai, MD, PhD, of Henry Ford Hospital, Detroit, and his associates. “Therefore, liver allocation rules such as Share 15 and Share 35 need to be revised to fulfill the Final Rule under the MELD-Na based allocation,” they wrote.

The Share 35 rule offers liver grafts locally and regionally to wait-listed patients with MELD-Na scores of at least 35. Under the Share 15 rule, livers are offered regionally or nationally before considering local candidates with MELD scores under 15. The traditional MELD scoring system excluded hyponatremia, which has since been found to independently predict death from cirrhosis. Therefore, in January 2016, a modified MELD-Na score was implemented for patients with traditional MELD scores of at least 12. The MELD-Na score assigns patients between 1 and 11 additional points, and patients with low MELD scores and severe hyponatremia receive the most points. To assess the impact of this change, Dr. Nagai and his associates compared wait-list and posttransplantation outcomes during the pre and post–MELD-Na eras and the survival benefit of liver transplantation during the MELD-Na period. The study included all adults wait-listed for livers from June 2013, when Share 35 was implemented, through September 2017.

Mortality within 90 days on the wait list fell significantly during the MELD-Na era (hazard ratio, 0.74; P less than .001). Transplantation conferred a “definitive” survival benefit when MELD-Na scores were 21-23 (HR versus wait list, 0.34; P less than .001). During the traditional MELD period, the equivalent cutoff was 15-17 (HR, 0.36; P less than .001). “As such, the current rules for liver allocation may be suboptimal under the MELD-Na–based allocation and the criteria for Share 15 may need to be revisited,” the researchers wrote. They recommended raising the cutoff to 21.

The study also confirmed mild hyponatremia (130-134 mmol/L), moderate hyponatremia (125-129 mmol/L), and severe hyponatremia (less than 125 mmol/L) as independent predictors of wait-list mortality during the traditional MELD era. Hazard ratios were 1.4, 1.8, and 1.7, respectively (all P less than .001). The implementation of MELD-Na significantly weakened these associations, with HRs of 1.1 (P = .3), 1.3 (P = .02), and 1.4 (P = .04), respectively).

The probability of transplantation also rose significantly during the MELD-Na era (HR, 1.2; P less than .001), possibly because of the opioid epidemic, the researchers said. Although greater availability of liver grafts might have improved wait-list outcomes, all score categories would have shown a positive impact if this was the only reason, they added. Instead, MELD-Na most benefited patients with lower scores.

Finally, posttransplantation outcomes worsened during the MELD-Na era, perhaps because of transplant population aging. However, the survival benefit of transplant shifted to higher score ranges during the MELD-Na era even after the researchers controlled for this effect. “According to this analysis,” they wrote, “the survival benefit of liver transplant was definitive in patients with score category of 21-23, which could further validate our proposal to revise Share 15 rule to ‘Share 21.’ ”

The investigators reported having no external funding sources or conflicts of interest.

SOURCE: Nagai S et al. Gastroenterology. 2018 Jul 26. doi: 10.1053/j.gastro.2018.07.025.

Factoring hyponatremic status into liver graft allocations led to significant reductions in wait-list mortality, researchers reported in the November issue of Gastroenterology.

©Eraxion/thinkstockphotos.com

Hyponatremic patients with low MELD scores benefited significantly from allocation based on the end-stage liver disease–sodium (MELD-Na) score, while its survival benefit was less evident among patients with higher scores, said Shunji Nagai, MD, PhD, of Henry Ford Hospital, Detroit, and his associates. “Therefore, liver allocation rules such as Share 15 and Share 35 need to be revised to fulfill the Final Rule under the MELD-Na based allocation,” they wrote.

The Share 35 rule offers liver grafts locally and regionally to wait-listed patients with MELD-Na scores of at least 35. Under the Share 15 rule, livers are offered regionally or nationally before considering local candidates with MELD scores under 15. The traditional MELD scoring system excluded hyponatremia, which has since been found to independently predict death from cirrhosis. Therefore, in January 2016, a modified MELD-Na score was implemented for patients with traditional MELD scores of at least 12. The MELD-Na score assigns patients between 1 and 11 additional points, and patients with low MELD scores and severe hyponatremia receive the most points. To assess the impact of this change, Dr. Nagai and his associates compared wait-list and posttransplantation outcomes during the pre and post–MELD-Na eras and the survival benefit of liver transplantation during the MELD-Na period. The study included all adults wait-listed for livers from June 2013, when Share 35 was implemented, through September 2017.

Mortality within 90 days on the wait list fell significantly during the MELD-Na era (hazard ratio, 0.74; P less than .001). Transplantation conferred a “definitive” survival benefit when MELD-Na scores were 21-23 (HR versus wait list, 0.34; P less than .001). During the traditional MELD period, the equivalent cutoff was 15-17 (HR, 0.36; P less than .001). “As such, the current rules for liver allocation may be suboptimal under the MELD-Na–based allocation and the criteria for Share 15 may need to be revisited,” the researchers wrote. They recommended raising the cutoff to 21.

The study also confirmed mild hyponatremia (130-134 mmol/L), moderate hyponatremia (125-129 mmol/L), and severe hyponatremia (less than 125 mmol/L) as independent predictors of wait-list mortality during the traditional MELD era. Hazard ratios were 1.4, 1.8, and 1.7, respectively (all P less than .001). The implementation of MELD-Na significantly weakened these associations, with HRs of 1.1 (P = .3), 1.3 (P = .02), and 1.4 (P = .04), respectively).

The probability of transplantation also rose significantly during the MELD-Na era (HR, 1.2; P less than .001), possibly because of the opioid epidemic, the researchers said. Although greater availability of liver grafts might have improved wait-list outcomes, all score categories would have shown a positive impact if this was the only reason, they added. Instead, MELD-Na most benefited patients with lower scores.

Finally, posttransplantation outcomes worsened during the MELD-Na era, perhaps because of transplant population aging. However, the survival benefit of transplant shifted to higher score ranges during the MELD-Na era even after the researchers controlled for this effect. “According to this analysis,” they wrote, “the survival benefit of liver transplant was definitive in patients with score category of 21-23, which could further validate our proposal to revise Share 15 rule to ‘Share 21.’ ”

The investigators reported having no external funding sources or conflicts of interest.

SOURCE: Nagai S et al. Gastroenterology. 2018 Jul 26. doi: 10.1053/j.gastro.2018.07.025.

Factoring hyponatremic status into liver graft allocations led to significant reductions in wait-list mortality, researchers reported in the November issue of Gastroenterology.

©Eraxion/thinkstockphotos.com

Hyponatremic patients with low MELD scores benefited significantly from allocation based on the end-stage liver disease–sodium (MELD-Na) score, while its survival benefit was less evident among patients with higher scores, said Shunji Nagai, MD, PhD, of Henry Ford Hospital, Detroit, and his associates. “Therefore, liver allocation rules such as Share 15 and Share 35 need to be revised to fulfill the Final Rule under the MELD-Na based allocation,” they wrote.

The Share 35 rule offers liver grafts locally and regionally to wait-listed patients with MELD-Na scores of at least 35. Under the Share 15 rule, livers are offered regionally or nationally before considering local candidates with MELD scores under 15. The traditional MELD scoring system excluded hyponatremia, which has since been found to independently predict death from cirrhosis. Therefore, in January 2016, a modified MELD-Na score was implemented for patients with traditional MELD scores of at least 12. The MELD-Na score assigns patients between 1 and 11 additional points, and patients with low MELD scores and severe hyponatremia receive the most points. To assess the impact of this change, Dr. Nagai and his associates compared wait-list and posttransplantation outcomes during the pre and post–MELD-Na eras and the survival benefit of liver transplantation during the MELD-Na period. The study included all adults wait-listed for livers from June 2013, when Share 35 was implemented, through September 2017.

Mortality within 90 days on the wait list fell significantly during the MELD-Na era (hazard ratio, 0.74; P less than .001). Transplantation conferred a “definitive” survival benefit when MELD-Na scores were 21-23 (HR versus wait list, 0.34; P less than .001). During the traditional MELD period, the equivalent cutoff was 15-17 (HR, 0.36; P less than .001). “As such, the current rules for liver allocation may be suboptimal under the MELD-Na–based allocation and the criteria for Share 15 may need to be revisited,” the researchers wrote. They recommended raising the cutoff to 21.

The study also confirmed mild hyponatremia (130-134 mmol/L), moderate hyponatremia (125-129 mmol/L), and severe hyponatremia (less than 125 mmol/L) as independent predictors of wait-list mortality during the traditional MELD era. Hazard ratios were 1.4, 1.8, and 1.7, respectively (all P less than .001). The implementation of MELD-Na significantly weakened these associations, with HRs of 1.1 (P = .3), 1.3 (P = .02), and 1.4 (P = .04), respectively).

The probability of transplantation also rose significantly during the MELD-Na era (HR, 1.2; P less than .001), possibly because of the opioid epidemic, the researchers said. Although greater availability of liver grafts might have improved wait-list outcomes, all score categories would have shown a positive impact if this was the only reason, they added. Instead, MELD-Na most benefited patients with lower scores.

Finally, posttransplantation outcomes worsened during the MELD-Na era, perhaps because of transplant population aging. However, the survival benefit of transplant shifted to higher score ranges during the MELD-Na era even after the researchers controlled for this effect. “According to this analysis,” they wrote, “the survival benefit of liver transplant was definitive in patients with score category of 21-23, which could further validate our proposal to revise Share 15 rule to ‘Share 21.’ ”

The investigators reported having no external funding sources or conflicts of interest.

SOURCE: Nagai S et al. Gastroenterology. 2018 Jul 26. doi: 10.1053/j.gastro.2018.07.025.

The Food and Drug Administration has expanded the indication for the fat-removing CoolSculpting procedure to include treatment of the submandibular area.

FDA clearance of the expanded indication was based on results of a 22-week study in which patients achieved a mean 33% reduction in fat layer thickness after two treatments. In addition, 85% of patients reported satisfaction with their treatment in that and two other studies. The data were provided in Allergan’s press release announcing the clearance for the cryolipolysis device.

Adverse events associated with the CoolSculpting treatment include temporary redness, swelling, blanching, bruising, firmness, tingling, stinging, tenderness, cramping, aching, itching, and skin sensitivity. People with cryoglobulinemia, cold agglutinin disease, or paroxysmal cold hemoglobinuria should not receive CoolSculpting treatments, according to the company.

The FDA also expanded the CoolSculpting indication to people with a body mass index up to 46.2 kg/m² when treating the submental and submandibular areas.

[email protected]

The Food and Drug Administration has expanded the indication for the fat-removing CoolSculpting procedure to include treatment of the submandibular area.

FDA clearance of the expanded indication was based on results of a 22-week study in which patients achieved a mean 33% reduction in fat layer thickness after two treatments. In addition, 85% of patients reported satisfaction with their treatment in that and two other studies. The data were provided in Allergan’s press release announcing the clearance for the cryolipolysis device.

Adverse events associated with the CoolSculpting treatment include temporary redness, swelling, blanching, bruising, firmness, tingling, stinging, tenderness, cramping, aching, itching, and skin sensitivity. People with cryoglobulinemia, cold agglutinin disease, or paroxysmal cold hemoglobinuria should not receive CoolSculpting treatments, according to the company.

The FDA also expanded the CoolSculpting indication to people with a body mass index up to 46.2 kg/m² when treating the submental and submandibular areas.

[email protected]

The Food and Drug Administration has expanded the indication for the fat-removing CoolSculpting procedure to include treatment of the submandibular area.

FDA clearance of the expanded indication was based on results of a 22-week study in which patients achieved a mean 33% reduction in fat layer thickness after two treatments. In addition, 85% of patients reported satisfaction with their treatment in that and two other studies. The data were provided in Allergan’s press release announcing the clearance for the cryolipolysis device.

Adverse events associated with the CoolSculpting treatment include temporary redness, swelling, blanching, bruising, firmness, tingling, stinging, tenderness, cramping, aching, itching, and skin sensitivity. People with cryoglobulinemia, cold agglutinin disease, or paroxysmal cold hemoglobinuria should not receive CoolSculpting treatments, according to the company.

The FDA also expanded the CoolSculpting indication to people with a body mass index up to 46.2 kg/m² when treating the submental and submandibular areas.

[email protected]

Advanced indolent lymphoma patients can be treated with a rituximab-containing regimen as first-line therapy and, in some cases, skip chemotherapy altogether, a study with 10 years of follow-up data suggests.

Patho/Wikimedia Commons/CC BY-SA 3.0

After a median of 10.6 years’ follow-up, almost three-quarters of patients (73%) in the study were alive, and 36% never required chemotherapy.

“This [overall survival] is at least as good as that observed in modern immunochemotherapy trials,” Sandra Lockmer, MD, of Karolinska University Hospital in Stockholm and her colleagues reported in the Journal of Clinical Oncology.

The study included 321 patients who were previously untreated and had been enrolled in two randomized clinical trials performed by the Nordic Lymphoma Group. The trials randomized patients to receive either rituximab monotherapy or rituximab combined with interferon alfa-2a. Neither trial used up-front chemotherapy.

Patients included in the follow-up analysis had follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, or indolent lymphoma not otherwise specified.

The overall survival rate at 10 years after trial assignment was 75% and 66% after 15 years. Similarly, the lymphoma-specific survival rate was 81% at 10 years after trial assignment and 77% at 15 years, the researchers reported.

Overall, 117 patients did not require treatment with chemotherapy, but 24 patients were further treated with antibodies and/or radiation. Of the 93 patients who received no additional therapies after frontline treatment, 9 patients died from causes unrelated to their lymphoma.

Among the 237 patients who failed initial treatment, the median time to treatment failure was 1.5 years.

In terms of transformation to aggressive lymphoma, the rate was 2.4%/person-year overall. The cumulative risk of transformation was 20% at 10 years after trial assignment and 24% at 15 years.

The study was funded in part by the Stockholm County Council and by the Nordic Lymphoma Group. The trials analyzed in the study were supported by Roche. Dr. Lockmer reported having no financial disclosures. Her coauthors reported relationships with Novartis, Gilead, Roche, and Takeda, among others.

[email protected]

SOURCE: Lockmer S et al. J Clin Oncol. 2018 Oct 4:JCO1800262. doi: 10.1200/JCO.18.00262.

Advanced indolent lymphoma patients can be treated with a rituximab-containing regimen as first-line therapy and, in some cases, skip chemotherapy altogether, a study with 10 years of follow-up data suggests.

Patho/Wikimedia Commons/CC BY-SA 3.0

After a median of 10.6 years’ follow-up, almost three-quarters of patients (73%) in the study were alive, and 36% never required chemotherapy.

“This [overall survival] is at least as good as that observed in modern immunochemotherapy trials,” Sandra Lockmer, MD, of Karolinska University Hospital in Stockholm and her colleagues reported in the Journal of Clinical Oncology.

The study included 321 patients who were previously untreated and had been enrolled in two randomized clinical trials performed by the Nordic Lymphoma Group. The trials randomized patients to receive either rituximab monotherapy or rituximab combined with interferon alfa-2a. Neither trial used up-front chemotherapy.

Patients included in the follow-up analysis had follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, or indolent lymphoma not otherwise specified.

The overall survival rate at 10 years after trial assignment was 75% and 66% after 15 years. Similarly, the lymphoma-specific survival rate was 81% at 10 years after trial assignment and 77% at 15 years, the researchers reported.

Overall, 117 patients did not require treatment with chemotherapy, but 24 patients were further treated with antibodies and/or radiation. Of the 93 patients who received no additional therapies after frontline treatment, 9 patients died from causes unrelated to their lymphoma.

Among the 237 patients who failed initial treatment, the median time to treatment failure was 1.5 years.

In terms of transformation to aggressive lymphoma, the rate was 2.4%/person-year overall. The cumulative risk of transformation was 20% at 10 years after trial assignment and 24% at 15 years.

The study was funded in part by the Stockholm County Council and by the Nordic Lymphoma Group. The trials analyzed in the study were supported by Roche. Dr. Lockmer reported having no financial disclosures. Her coauthors reported relationships with Novartis, Gilead, Roche, and Takeda, among others.

[email protected]

SOURCE: Lockmer S et al. J Clin Oncol. 2018 Oct 4:JCO1800262. doi: 10.1200/JCO.18.00262.

Advanced indolent lymphoma patients can be treated with a rituximab-containing regimen as first-line therapy and, in some cases, skip chemotherapy altogether, a study with 10 years of follow-up data suggests.

Patho/Wikimedia Commons/CC BY-SA 3.0

After a median of 10.6 years’ follow-up, almost three-quarters of patients (73%) in the study were alive, and 36% never required chemotherapy.

“This [overall survival] is at least as good as that observed in modern immunochemotherapy trials,” Sandra Lockmer, MD, of Karolinska University Hospital in Stockholm and her colleagues reported in the Journal of Clinical Oncology.

The study included 321 patients who were previously untreated and had been enrolled in two randomized clinical trials performed by the Nordic Lymphoma Group. The trials randomized patients to receive either rituximab monotherapy or rituximab combined with interferon alfa-2a. Neither trial used up-front chemotherapy.

Patients included in the follow-up analysis had follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, or indolent lymphoma not otherwise specified.

The overall survival rate at 10 years after trial assignment was 75% and 66% after 15 years. Similarly, the lymphoma-specific survival rate was 81% at 10 years after trial assignment and 77% at 15 years, the researchers reported.

Overall, 117 patients did not require treatment with chemotherapy, but 24 patients were further treated with antibodies and/or radiation. Of the 93 patients who received no additional therapies after frontline treatment, 9 patients died from causes unrelated to their lymphoma.

Among the 237 patients who failed initial treatment, the median time to treatment failure was 1.5 years.

In terms of transformation to aggressive lymphoma, the rate was 2.4%/person-year overall. The cumulative risk of transformation was 20% at 10 years after trial assignment and 24% at 15 years.

The study was funded in part by the Stockholm County Council and by the Nordic Lymphoma Group. The trials analyzed in the study were supported by Roche. Dr. Lockmer reported having no financial disclosures. Her coauthors reported relationships with Novartis, Gilead, Roche, and Takeda, among others.

[email protected]

SOURCE: Lockmer S et al. J Clin Oncol. 2018 Oct 4:JCO1800262. doi: 10.1200/JCO.18.00262.

New evidence provides estimates of the pregnancy rates for American women with multiple sclerosis (MS), their complication rates, and the rates of relapse and disease-modifying drug treatment during different phases before and after pregnancy.

The two new studies, conducted by Maria K. Houtchens, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues involved retrospective mining of U.S. commercial health plan data in the IQVIA Real-World Data Adjudicated Claims–U.S. database between Jan. 1, 2006, and June 30, 2015.

The mean age of pregnant women in the nine annual cohorts during that period was just over 32 years for those with MS and just over 29 years for those without. The percentage of women without MS who had a pregnancy-related claim in the database declined from 8.83% in 2006 to 7.75% in 2014 after adjusting for age, region, payer, and Charlson Comorbidity Index score, whereas the percentage increased in women with MS during the same period, from 7.91% to 9.47%. The investigators matched 2,115 women with MS and 2,115 without MS who had live births for a variety of variables and found that women with MS had higher rates of premature labor (31.4% vs. 27.4%; P = .005), infection in pregnancy (13.3% vs. 10.9%; P = .016), maternal cardiovascular disease (3.0% vs. 1.9%; P = .028), anemia or acquired coagulation disorder (2.5% vs. 1.3%; P = .007), neurologic complications in pregnancy (1.6% vs. 0.6%; P = .005), and sexually transmitted diseases in pregnancy (0.4% vs. 0%; P = .045). During labor and delivery, women with MS who had a live birth more often had a claim for acquired damage to the fetus (27.8% vs. 23.5%; P = .002) and congenital fetal malformations (13.2% vs. 10.3%; P = .004) than did women without MS.

In the second study, Dr. Houtchens and two coauthors from the first study of the database reported on a set of 2,158 women who had a live birth during the study period and had 1 year of continuous insurance eligibility before and after pregnancy. The odds for having an MS relapse declined during pregnancy (odds ratio, 0.623; 95% confidence interval, 0.521-0.744), rose during the 6-week postpartum puerperium (OR, 1.710; 95% CI, 1.358-2.152), and leveled off during the last three postpartum quarters to remain at a higher level than before pregnancy (OR, 1.216; 95% CI, 1.052-1.406). Disease-modifying drug treatment followed the same pattern with 20% using it before pregnancy, dropping to about 2% in the second trimester, and peaking in about a quarter of all patients 9-12 months post partum.

[email protected]

SOURCES: Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006382; Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006384.

New evidence provides estimates of the pregnancy rates for American women with multiple sclerosis (MS), their complication rates, and the rates of relapse and disease-modifying drug treatment during different phases before and after pregnancy.

The two new studies, conducted by Maria K. Houtchens, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues involved retrospective mining of U.S. commercial health plan data in the IQVIA Real-World Data Adjudicated Claims–U.S. database between Jan. 1, 2006, and June 30, 2015.

The mean age of pregnant women in the nine annual cohorts during that period was just over 32 years for those with MS and just over 29 years for those without. The percentage of women without MS who had a pregnancy-related claim in the database declined from 8.83% in 2006 to 7.75% in 2014 after adjusting for age, region, payer, and Charlson Comorbidity Index score, whereas the percentage increased in women with MS during the same period, from 7.91% to 9.47%. The investigators matched 2,115 women with MS and 2,115 without MS who had live births for a variety of variables and found that women with MS had higher rates of premature labor (31.4% vs. 27.4%; P = .005), infection in pregnancy (13.3% vs. 10.9%; P = .016), maternal cardiovascular disease (3.0% vs. 1.9%; P = .028), anemia or acquired coagulation disorder (2.5% vs. 1.3%; P = .007), neurologic complications in pregnancy (1.6% vs. 0.6%; P = .005), and sexually transmitted diseases in pregnancy (0.4% vs. 0%; P = .045). During labor and delivery, women with MS who had a live birth more often had a claim for acquired damage to the fetus (27.8% vs. 23.5%; P = .002) and congenital fetal malformations (13.2% vs. 10.3%; P = .004) than did women without MS.

In the second study, Dr. Houtchens and two coauthors from the first study of the database reported on a set of 2,158 women who had a live birth during the study period and had 1 year of continuous insurance eligibility before and after pregnancy. The odds for having an MS relapse declined during pregnancy (odds ratio, 0.623; 95% confidence interval, 0.521-0.744), rose during the 6-week postpartum puerperium (OR, 1.710; 95% CI, 1.358-2.152), and leveled off during the last three postpartum quarters to remain at a higher level than before pregnancy (OR, 1.216; 95% CI, 1.052-1.406). Disease-modifying drug treatment followed the same pattern with 20% using it before pregnancy, dropping to about 2% in the second trimester, and peaking in about a quarter of all patients 9-12 months post partum.

[email protected]

SOURCES: Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006382; Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006384.

New evidence provides estimates of the pregnancy rates for American women with multiple sclerosis (MS), their complication rates, and the rates of relapse and disease-modifying drug treatment during different phases before and after pregnancy.

The two new studies, conducted by Maria K. Houtchens, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues involved retrospective mining of U.S. commercial health plan data in the IQVIA Real-World Data Adjudicated Claims–U.S. database between Jan. 1, 2006, and June 30, 2015.

The mean age of pregnant women in the nine annual cohorts during that period was just over 32 years for those with MS and just over 29 years for those without. The percentage of women without MS who had a pregnancy-related claim in the database declined from 8.83% in 2006 to 7.75% in 2014 after adjusting for age, region, payer, and Charlson Comorbidity Index score, whereas the percentage increased in women with MS during the same period, from 7.91% to 9.47%. The investigators matched 2,115 women with MS and 2,115 without MS who had live births for a variety of variables and found that women with MS had higher rates of premature labor (31.4% vs. 27.4%; P = .005), infection in pregnancy (13.3% vs. 10.9%; P = .016), maternal cardiovascular disease (3.0% vs. 1.9%; P = .028), anemia or acquired coagulation disorder (2.5% vs. 1.3%; P = .007), neurologic complications in pregnancy (1.6% vs. 0.6%; P = .005), and sexually transmitted diseases in pregnancy (0.4% vs. 0%; P = .045). During labor and delivery, women with MS who had a live birth more often had a claim for acquired damage to the fetus (27.8% vs. 23.5%; P = .002) and congenital fetal malformations (13.2% vs. 10.3%; P = .004) than did women without MS.

In the second study, Dr. Houtchens and two coauthors from the first study of the database reported on a set of 2,158 women who had a live birth during the study period and had 1 year of continuous insurance eligibility before and after pregnancy. The odds for having an MS relapse declined during pregnancy (odds ratio, 0.623; 95% confidence interval, 0.521-0.744), rose during the 6-week postpartum puerperium (OR, 1.710; 95% CI, 1.358-2.152), and leveled off during the last three postpartum quarters to remain at a higher level than before pregnancy (OR, 1.216; 95% CI, 1.052-1.406). Disease-modifying drug treatment followed the same pattern with 20% using it before pregnancy, dropping to about 2% in the second trimester, and peaking in about a quarter of all patients 9-12 months post partum.

[email protected]

SOURCES: Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006382; Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006384.

Endometriosis patients experiencing infertility can benefit from assisted reproductive technology (ART) at a young age, but non-ART infertility treatment is less likely to succeed in the endometriosis population, according to data from approximately 1,800 women with infertility.

©ktsimage/iStockphoto.com

Moderate to severe endometriosis had a negative impact on the outcome of ART, but “the efficacy of non-ART treatment in patients with endometriosis remains elusive” wrote Wataru Isono of the University of Tokyo, and colleagues.

In a study published in the Journal of Obstetrics & Gynaecology Research, the investigators sought to determine the impact of endometriosis severity on the effectiveness of non-ART treatment. They calculated the cumulative live birth rates for women treated with ART and non-ART.

Overall, 49% of the 894 ART patients and 22% of the 1,358 non-ART patients gave birth after treatment. The birth rate remained more than twice as high among ART patients across all age groups, but declined among ART patients starting at 35 years of age and declined sharply as patients reached 40 years of age.

“The most important aspect of this study was that we determined the limitations of non-ART and sought to identify optimal management methods, as non-ART can be a more cost-effective treatment than ART in certain circumstances,” the researchers noted.

They then focused on 288 patients with advanced endometriosis, defined as stage III or IV according to the revised American Society for Reproductive Medicine score. Notably, the presence of moderate to severe endometriosis had a significant effect on the outcomes of non-ART patients in their 30s, but ART was effective in this age group in a multivariate analysis. The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%). However, cumulative live birth rates after ART were not significantly different among advanced endometriosis patients, compared with patients without advanced endometriosis (45% vs. 51%).

The study was limited by several factors including the inability to analyze the varied types of infertility treatment, Dr. Isono and associates noted. However, “our results may provide infertility patients with accurate information regarding their expected probabilities of achieving a live birth and may help them select the optimal treatment based on their classification according to various risk factors,” they said.

The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.

SOURCE: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.

Endometriosis patients experiencing infertility can benefit from assisted reproductive technology (ART) at a young age, but non-ART infertility treatment is less likely to succeed in the endometriosis population, according to data from approximately 1,800 women with infertility.

©ktsimage/iStockphoto.com

Moderate to severe endometriosis had a negative impact on the outcome of ART, but “the efficacy of non-ART treatment in patients with endometriosis remains elusive” wrote Wataru Isono of the University of Tokyo, and colleagues.

In a study published in the Journal of Obstetrics & Gynaecology Research, the investigators sought to determine the impact of endometriosis severity on the effectiveness of non-ART treatment. They calculated the cumulative live birth rates for women treated with ART and non-ART.

Overall, 49% of the 894 ART patients and 22% of the 1,358 non-ART patients gave birth after treatment. The birth rate remained more than twice as high among ART patients across all age groups, but declined among ART patients starting at 35 years of age and declined sharply as patients reached 40 years of age.

“The most important aspect of this study was that we determined the limitations of non-ART and sought to identify optimal management methods, as non-ART can be a more cost-effective treatment than ART in certain circumstances,” the researchers noted.

They then focused on 288 patients with advanced endometriosis, defined as stage III or IV according to the revised American Society for Reproductive Medicine score. Notably, the presence of moderate to severe endometriosis had a significant effect on the outcomes of non-ART patients in their 30s, but ART was effective in this age group in a multivariate analysis. The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%). However, cumulative live birth rates after ART were not significantly different among advanced endometriosis patients, compared with patients without advanced endometriosis (45% vs. 51%).

The study was limited by several factors including the inability to analyze the varied types of infertility treatment, Dr. Isono and associates noted. However, “our results may provide infertility patients with accurate information regarding their expected probabilities of achieving a live birth and may help them select the optimal treatment based on their classification according to various risk factors,” they said.

The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.

SOURCE: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.

Endometriosis patients experiencing infertility can benefit from assisted reproductive technology (ART) at a young age, but non-ART infertility treatment is less likely to succeed in the endometriosis population, according to data from approximately 1,800 women with infertility.

©ktsimage/iStockphoto.com

Moderate to severe endometriosis had a negative impact on the outcome of ART, but “the efficacy of non-ART treatment in patients with endometriosis remains elusive” wrote Wataru Isono of the University of Tokyo, and colleagues.

In a study published in the Journal of Obstetrics & Gynaecology Research, the investigators sought to determine the impact of endometriosis severity on the effectiveness of non-ART treatment. They calculated the cumulative live birth rates for women treated with ART and non-ART.

Overall, 49% of the 894 ART patients and 22% of the 1,358 non-ART patients gave birth after treatment. The birth rate remained more than twice as high among ART patients across all age groups, but declined among ART patients starting at 35 years of age and declined sharply as patients reached 40 years of age.

“The most important aspect of this study was that we determined the limitations of non-ART and sought to identify optimal management methods, as non-ART can be a more cost-effective treatment than ART in certain circumstances,” the researchers noted.

They then focused on 288 patients with advanced endometriosis, defined as stage III or IV according to the revised American Society for Reproductive Medicine score. Notably, the presence of moderate to severe endometriosis had a significant effect on the outcomes of non-ART patients in their 30s, but ART was effective in this age group in a multivariate analysis. The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%). However, cumulative live birth rates after ART were not significantly different among advanced endometriosis patients, compared with patients without advanced endometriosis (45% vs. 51%).

The study was limited by several factors including the inability to analyze the varied types of infertility treatment, Dr. Isono and associates noted. However, “our results may provide infertility patients with accurate information regarding their expected probabilities of achieving a live birth and may help them select the optimal treatment based on their classification according to various risk factors,” they said.

The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.

SOURCE: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.

MONTEREY, CALIF. – It’s only found in 2%-3% of allergy cases. So why was propylene glycol (PG) declared the Allergen of the Year for 2018 by the North American Contact Dermatitis Society? Because, a dermatologist told colleagues, it’s so common.

“If you’re allergic to it, it’s tough to stay away from it,” said Joseph F. Fowler Jr., MD, clinical professor of dermatology at the University of Louisville (Ky.) in a presentation about contact dermatitis at the annual Coastal Dermatology Symposium.

Indeed, the synthetic compound PG is found in skin care products and cosmetics, coated pills, topical medications such as corticosteroids, foods (including bread, food coloring, and such flavorings as vanilla extracts). “It’s in every topical acne product I know of,” and is even in brake fluid and so-called nontoxic antifreeze, he said. (Propylene glycol shouldn’t be confused with the poisonous toxin ethylene glycol, which also is found in antifreeze.)

Patients can be tested for allergy to PG, Dr. Fowler pointed out, but it’s important to understand that it can trigger an irritation reaction that can be mistaken for an allergic reaction.

Dr. Fowler offered the following tips related to contact dermatitis and allergens. Be aware that metals, topical antibiotics, fragrances, and preservatives are most likely to cause allergic contact dermatitis. According to 2016 figures on allergen prevalence from the North American Contact Dermatitis Group (NACDG), allergy to the metal nickel is the most common (16%); followed by neomycin (9%); fragrance mix I, a mixture of fragrances used in allergen testing (9%); bacitracin (8%); and myroxylon, also known as balsam of Peru, which is used for a variety of purposes in food, medicines, and fragrances (7%).

These are followed by the metal cobalt (6%); the preservatives quaternium 15 and formaldehyde (both 6%); para-phenylenediamine, also known as PPD, which is used in hair dye (5%); and the fragrance mix II (5%), another mix of fragrances used in allergen testing.

Dr. Fowler cautioned that nickel can trigger an intense body-wide allergic reaction in children with atopic dermatitis. “In this situation, it’s really good to be compulsive and tell parents to absolutely keep that person away from nickel as much as humanly possible,” he said.

Keep an eye out for allergens that aren’t on the NACDG list, which includes 70 items. According to Dr. Fowler, more than 20% of his patients were positive to allergens not on the NACDG list.

Contact dermatitis is as common in children as in adults and can even be more common in children. An Italian study published in 2012 found that 70% of children aged 1-15 years tested via patch test were allergic to at least one allergen, a number that’s similar in adults (Dermatitis. 2012 Nov-Dec;23[6]:275-80). There are wide disparities in reported levels of children who are allergic to nickel, cobalt, and myroxylon, Dr. Fowler said.

The T.R.U.E. Test patch test system has value, compared with standard patch tests, but beware of its limitations, he advised. T.R.U.E. is easy to use and requires no prep time, he said, but the number of allergens is limited. By contrast, his clinic mostly uses the Finn Chambers on Scanpor tape system, which can test for many more allergens and is cheaper if used at least 5-10 times a month.

He cautioned that T.R.U.E. could miss the cause of contact dermatitis as often as 39% of the time, as demonstrated in one study of children undergoing patch testing (Arch Dermatol. 2008 Oct;144[10]:1329-36). However, he said, the T.R.U.E test has value in detecting allergies to nickel, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and neomycin (J Am Acad Dermatol. 2001 Dec;45[6]:836-9).

Consider patch testing in a child with eczema if the eczema is not in normal atopic areas, it spreads beyond normal areas, it doesn’t respond to usual treatments, or it begins later than 5 years of age.

And, Dr. Fowler added, it’s fine to perform patch testing on patients who are taking antihistamines, tumor necrosis factor–alpha inhibitors, NSAIDs, or methotrexate.

Dr. Fowler disclosed consulting for IntraDerm, serving on speakers bureaus for SmartPractice and Regeneron/Sanofi, and serving as an investigator for companies that include AbbVie, Allergan, Bayer, Dow, Galderma, Johnson & Johnson, Eli Lilly, Merck, Regeneron, SmartPractice, and Valeant (now Bausch).

The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

 

MONTEREY, CALIF. – It’s only found in 2%-3% of allergy cases. So why was propylene glycol (PG) declared the Allergen of the Year for 2018 by the North American Contact Dermatitis Society? Because, a dermatologist told colleagues, it’s so common.

“If you’re allergic to it, it’s tough to stay away from it,” said Joseph F. Fowler Jr., MD, clinical professor of dermatology at the University of Louisville (Ky.) in a presentation about contact dermatitis at the annual Coastal Dermatology Symposium.

Indeed, the synthetic compound PG is found in skin care products and cosmetics, coated pills, topical medications such as corticosteroids, foods (including bread, food coloring, and such flavorings as vanilla extracts). “It’s in every topical acne product I know of,” and is even in brake fluid and so-called nontoxic antifreeze, he said. (Propylene glycol shouldn’t be confused with the poisonous toxin ethylene glycol, which also is found in antifreeze.)

Patients can be tested for allergy to PG, Dr. Fowler pointed out, but it’s important to understand that it can trigger an irritation reaction that can be mistaken for an allergic reaction.

Dr. Fowler offered the following tips related to contact dermatitis and allergens. Be aware that metals, topical antibiotics, fragrances, and preservatives are most likely to cause allergic contact dermatitis. According to 2016 figures on allergen prevalence from the North American Contact Dermatitis Group (NACDG), allergy to the metal nickel is the most common (16%); followed by neomycin (9%); fragrance mix I, a mixture of fragrances used in allergen testing (9%); bacitracin (8%); and myroxylon, also known as balsam of Peru, which is used for a variety of purposes in food, medicines, and fragrances (7%).

These are followed by the metal cobalt (6%); the preservatives quaternium 15 and formaldehyde (both 6%); para-phenylenediamine, also known as PPD, which is used in hair dye (5%); and the fragrance mix II (5%), another mix of fragrances used in allergen testing.

Dr. Fowler cautioned that nickel can trigger an intense body-wide allergic reaction in children with atopic dermatitis. “In this situation, it’s really good to be compulsive and tell parents to absolutely keep that person away from nickel as much as humanly possible,” he said.

Keep an eye out for allergens that aren’t on the NACDG list, which includes 70 items. According to Dr. Fowler, more than 20% of his patients were positive to allergens not on the NACDG list.

Contact dermatitis is as common in children as in adults and can even be more common in children. An Italian study published in 2012 found that 70% of children aged 1-15 years tested via patch test were allergic to at least one allergen, a number that’s similar in adults (Dermatitis. 2012 Nov-Dec;23[6]:275-80). There are wide disparities in reported levels of children who are allergic to nickel, cobalt, and myroxylon, Dr. Fowler said.

The T.R.U.E. Test patch test system has value, compared with standard patch tests, but beware of its limitations, he advised. T.R.U.E. is easy to use and requires no prep time, he said, but the number of allergens is limited. By contrast, his clinic mostly uses the Finn Chambers on Scanpor tape system, which can test for many more allergens and is cheaper if used at least 5-10 times a month.

He cautioned that T.R.U.E. could miss the cause of contact dermatitis as often as 39% of the time, as demonstrated in one study of children undergoing patch testing (Arch Dermatol. 2008 Oct;144[10]:1329-36). However, he said, the T.R.U.E test has value in detecting allergies to nickel, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and neomycin (J Am Acad Dermatol. 2001 Dec;45[6]:836-9).

Consider patch testing in a child with eczema if the eczema is not in normal atopic areas, it spreads beyond normal areas, it doesn’t respond to usual treatments, or it begins later than 5 years of age.

And, Dr. Fowler added, it’s fine to perform patch testing on patients who are taking antihistamines, tumor necrosis factor–alpha inhibitors, NSAIDs, or methotrexate.

Dr. Fowler disclosed consulting for IntraDerm, serving on speakers bureaus for SmartPractice and Regeneron/Sanofi, and serving as an investigator for companies that include AbbVie, Allergan, Bayer, Dow, Galderma, Johnson & Johnson, Eli Lilly, Merck, Regeneron, SmartPractice, and Valeant (now Bausch).

The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

 

MONTEREY, CALIF. – It’s only found in 2%-3% of allergy cases. So why was propylene glycol (PG) declared the Allergen of the Year for 2018 by the North American Contact Dermatitis Society? Because, a dermatologist told colleagues, it’s so common.

“If you’re allergic to it, it’s tough to stay away from it,” said Joseph F. Fowler Jr., MD, clinical professor of dermatology at the University of Louisville (Ky.) in a presentation about contact dermatitis at the annual Coastal Dermatology Symposium.

Indeed, the synthetic compound PG is found in skin care products and cosmetics, coated pills, topical medications such as corticosteroids, foods (including bread, food coloring, and such flavorings as vanilla extracts). “It’s in every topical acne product I know of,” and is even in brake fluid and so-called nontoxic antifreeze, he said. (Propylene glycol shouldn’t be confused with the poisonous toxin ethylene glycol, which also is found in antifreeze.)

Patients can be tested for allergy to PG, Dr. Fowler pointed out, but it’s important to understand that it can trigger an irritation reaction that can be mistaken for an allergic reaction.

Dr. Fowler offered the following tips related to contact dermatitis and allergens. Be aware that metals, topical antibiotics, fragrances, and preservatives are most likely to cause allergic contact dermatitis. According to 2016 figures on allergen prevalence from the North American Contact Dermatitis Group (NACDG), allergy to the metal nickel is the most common (16%); followed by neomycin (9%); fragrance mix I, a mixture of fragrances used in allergen testing (9%); bacitracin (8%); and myroxylon, also known as balsam of Peru, which is used for a variety of purposes in food, medicines, and fragrances (7%).

These are followed by the metal cobalt (6%); the preservatives quaternium 15 and formaldehyde (both 6%); para-phenylenediamine, also known as PPD, which is used in hair dye (5%); and the fragrance mix II (5%), another mix of fragrances used in allergen testing.

Dr. Fowler cautioned that nickel can trigger an intense body-wide allergic reaction in children with atopic dermatitis. “In this situation, it’s really good to be compulsive and tell parents to absolutely keep that person away from nickel as much as humanly possible,” he said.

Keep an eye out for allergens that aren’t on the NACDG list, which includes 70 items. According to Dr. Fowler, more than 20% of his patients were positive to allergens not on the NACDG list.

Contact dermatitis is as common in children as in adults and can even be more common in children. An Italian study published in 2012 found that 70% of children aged 1-15 years tested via patch test were allergic to at least one allergen, a number that’s similar in adults (Dermatitis. 2012 Nov-Dec;23[6]:275-80). There are wide disparities in reported levels of children who are allergic to nickel, cobalt, and myroxylon, Dr. Fowler said.

The T.R.U.E. Test patch test system has value, compared with standard patch tests, but beware of its limitations, he advised. T.R.U.E. is easy to use and requires no prep time, he said, but the number of allergens is limited. By contrast, his clinic mostly uses the Finn Chambers on Scanpor tape system, which can test for many more allergens and is cheaper if used at least 5-10 times a month.

He cautioned that T.R.U.E. could miss the cause of contact dermatitis as often as 39% of the time, as demonstrated in one study of children undergoing patch testing (Arch Dermatol. 2008 Oct;144[10]:1329-36). However, he said, the T.R.U.E test has value in detecting allergies to nickel, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and neomycin (J Am Acad Dermatol. 2001 Dec;45[6]:836-9).

Consider patch testing in a child with eczema if the eczema is not in normal atopic areas, it spreads beyond normal areas, it doesn’t respond to usual treatments, or it begins later than 5 years of age.

And, Dr. Fowler added, it’s fine to perform patch testing on patients who are taking antihistamines, tumor necrosis factor–alpha inhibitors, NSAIDs, or methotrexate.

Dr. Fowler disclosed consulting for IntraDerm, serving on speakers bureaus for SmartPractice and Regeneron/Sanofi, and serving as an investigator for companies that include AbbVie, Allergan, Bayer, Dow, Galderma, Johnson & Johnson, Eli Lilly, Merck, Regeneron, SmartPractice, and Valeant (now Bausch).

The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

 

Neither age nor previous hormone therapy had statistically significant associations with the effect of intravaginal prasterone on dyspareunia severity, according to a new subgroup analysis of clinical trial data. In a trend that did not reach statistical significance, though, women who were further away from menopause reported numerically smaller improvements in dyspareunia, compared with baseline values, said David F. Archer, MD.

“This was an unexpected finding,” he said in an interview.

In a subgroup analysis of data from two clinical trials of intravaginal prasterone (Intrarosa), Dr. Archer and his colleagues sought to investigate whether age, time since menopause, or any previous use of hormone replacement therapy influenced prasterone’s efficacy in treating dyspareunia.

Dr. Archer and his collaborators pooled data from two prospective, randomized, double-blind, placebo-controlled trials (NCT02013544 and NCT01256684) of intravaginal prasterone dosed at 0.50%, 6.5 mg once daily for 12 weeks; he presented the subgroup analyses at the annual meeting of the North American Menopause Society in San Diego.

For each subgroup, Dr. Archer, a professor of obstetrics and gynecology at Eastern Virginia Medical School, Norfolk, and his coinvestigators compared the mean differences in dyspareunia severity score of women who received prasterone and those who received placebo.

All subgroup analyses used the endpoint of improvement in moderate to severe dyspareunia or whether dyspareunia was the most bothersome symptoms for the women participating in the study. The investigators began by looking at the subgroup of 460 women who were 56 years and older at baseline and compared them with the 180 younger participants.

The 283 older participants who received prasterone saw a decrease of 0.36 points in a dyspareunia severity score versus a 0.44 point decrease for the 123 women aged 55 and younger who received prasterone, a nonsignificant difference between subgroups. The decrease compared with placebo-takers was significant in both cases, however (P = .0003 and P =.0031, respectively).

Looking at time since menopause, Dr. Archer and his collaborators divided participants into 33 individuals who were 1 or 2 years post menopause, 86 women who were 3-5 years post menopause, and 521 women who had experienced menopause at least 6 years before study baseline.

In this analysis, 22 of the earliest postmenopause women received prasterone, seeing a 1.59 point drop in dyspareunia severity. For the 59 women in the prasterone study arms who were 3-5 year past menopause, the decrease from baseline was 0.59 points. Finally, among the 325 women who received prasterone and experienced menopause 6 or more years ago, the decrease was 0.27 points.

Although there was a numeric difference in the change in dyspareunia score severity among these groups, the differences were not statistically significant, said Dr. Archer. Again, though, those who took prasterone had a significant reduction in dyspareunia severity scores when compared with those taking placebo (P less than .0001, P = .0136, and P = .0024, respectively).

In the prasterone study arms, 184 had previously used hormone therapy, and 222 had not. After 12 weeks of intravaginal prasterone, there was no statistically significant difference between the two subgroups, with a decreases in dyspareunia severity scores of 0.45 and 0.32, respectively. The decreases in severity scores when compared with those among women who took placebo were again statistically significant for both subgroups, however (P = .0002 and P = .0057, respectively).

Prasterone is a steroid that is also known as dehydroepiandrosterone (DHEA) and is an endogenous hormone that is a precursor for estrogens and androgens. Prasterone’s mechanism of action to reduce vulvar and vaginal atrophy is not completely understood, according to the Food and Drug Administration.

“The nonstatistically significant smaller effect on dyspareunia observed when treatment is initiated after a longer period after menopause suggests that a longer treatment period could be needed to achieve optimal benefit and that treatment of dyspareunia should be initiated as early as possible after menopause,” said Dr. Archer.

Dr. Archer reported grant support from and consulting relationships with several pharmaceutical companies, including Endoceutics, the producer of Intrarosa intravaginal prasterone.

[email protected]

Neither age nor previous hormone therapy had statistically significant associations with the effect of intravaginal prasterone on dyspareunia severity, according to a new subgroup analysis of clinical trial data. In a trend that did not reach statistical significance, though, women who were further away from menopause reported numerically smaller improvements in dyspareunia, compared with baseline values, said David F. Archer, MD.

“This was an unexpected finding,” he said in an interview.

In a subgroup analysis of data from two clinical trials of intravaginal prasterone (Intrarosa), Dr. Archer and his colleagues sought to investigate whether age, time since menopause, or any previous use of hormone replacement therapy influenced prasterone’s efficacy in treating dyspareunia.

Dr. Archer and his collaborators pooled data from two prospective, randomized, double-blind, placebo-controlled trials (NCT02013544 and NCT01256684) of intravaginal prasterone dosed at 0.50%, 6.5 mg once daily for 12 weeks; he presented the subgroup analyses at the annual meeting of the North American Menopause Society in San Diego.

For each subgroup, Dr. Archer, a professor of obstetrics and gynecology at Eastern Virginia Medical School, Norfolk, and his coinvestigators compared the mean differences in dyspareunia severity score of women who received prasterone and those who received placebo.

All subgroup analyses used the endpoint of improvement in moderate to severe dyspareunia or whether dyspareunia was the most bothersome symptoms for the women participating in the study. The investigators began by looking at the subgroup of 460 women who were 56 years and older at baseline and compared them with the 180 younger participants.

The 283 older participants who received prasterone saw a decrease of 0.36 points in a dyspareunia severity score versus a 0.44 point decrease for the 123 women aged 55 and younger who received prasterone, a nonsignificant difference between subgroups. The decrease compared with placebo-takers was significant in both cases, however (P = .0003 and P =.0031, respectively).

Looking at time since menopause, Dr. Archer and his collaborators divided participants into 33 individuals who were 1 or 2 years post menopause, 86 women who were 3-5 years post menopause, and 521 women who had experienced menopause at least 6 years before study baseline.

In this analysis, 22 of the earliest postmenopause women received prasterone, seeing a 1.59 point drop in dyspareunia severity. For the 59 women in the prasterone study arms who were 3-5 year past menopause, the decrease from baseline was 0.59 points. Finally, among the 325 women who received prasterone and experienced menopause 6 or more years ago, the decrease was 0.27 points.

Although there was a numeric difference in the change in dyspareunia score severity among these groups, the differences were not statistically significant, said Dr. Archer. Again, though, those who took prasterone had a significant reduction in dyspareunia severity scores when compared with those taking placebo (P less than .0001, P = .0136, and P = .0024, respectively).

In the prasterone study arms, 184 had previously used hormone therapy, and 222 had not. After 12 weeks of intravaginal prasterone, there was no statistically significant difference between the two subgroups, with a decreases in dyspareunia severity scores of 0.45 and 0.32, respectively. The decreases in severity scores when compared with those among women who took placebo were again statistically significant for both subgroups, however (P = .0002 and P = .0057, respectively).

Prasterone is a steroid that is also known as dehydroepiandrosterone (DHEA) and is an endogenous hormone that is a precursor for estrogens and androgens. Prasterone’s mechanism of action to reduce vulvar and vaginal atrophy is not completely understood, according to the Food and Drug Administration.

“The nonstatistically significant smaller effect on dyspareunia observed when treatment is initiated after a longer period after menopause suggests that a longer treatment period could be needed to achieve optimal benefit and that treatment of dyspareunia should be initiated as early as possible after menopause,” said Dr. Archer.

Dr. Archer reported grant support from and consulting relationships with several pharmaceutical companies, including Endoceutics, the producer of Intrarosa intravaginal prasterone.

[email protected]

Neither age nor previous hormone therapy had statistically significant associations with the effect of intravaginal prasterone on dyspareunia severity, according to a new subgroup analysis of clinical trial data. In a trend that did not reach statistical significance, though, women who were further away from menopause reported numerically smaller improvements in dyspareunia, compared with baseline values, said David F. Archer, MD.

“This was an unexpected finding,” he said in an interview.

In a subgroup analysis of data from two clinical trials of intravaginal prasterone (Intrarosa), Dr. Archer and his colleagues sought to investigate whether age, time since menopause, or any previous use of hormone replacement therapy influenced prasterone’s efficacy in treating dyspareunia.

Dr. Archer and his collaborators pooled data from two prospective, randomized, double-blind, placebo-controlled trials (NCT02013544 and NCT01256684) of intravaginal prasterone dosed at 0.50%, 6.5 mg once daily for 12 weeks; he presented the subgroup analyses at the annual meeting of the North American Menopause Society in San Diego.

For each subgroup, Dr. Archer, a professor of obstetrics and gynecology at Eastern Virginia Medical School, Norfolk, and his coinvestigators compared the mean differences in dyspareunia severity score of women who received prasterone and those who received placebo.

All subgroup analyses used the endpoint of improvement in moderate to severe dyspareunia or whether dyspareunia was the most bothersome symptoms for the women participating in the study. The investigators began by looking at the subgroup of 460 women who were 56 years and older at baseline and compared them with the 180 younger participants.

The 283 older participants who received prasterone saw a decrease of 0.36 points in a dyspareunia severity score versus a 0.44 point decrease for the 123 women aged 55 and younger who received prasterone, a nonsignificant difference between subgroups. The decrease compared with placebo-takers was significant in both cases, however (P = .0003 and P =.0031, respectively).

Looking at time since menopause, Dr. Archer and his collaborators divided participants into 33 individuals who were 1 or 2 years post menopause, 86 women who were 3-5 years post menopause, and 521 women who had experienced menopause at least 6 years before study baseline.

In this analysis, 22 of the earliest postmenopause women received prasterone, seeing a 1.59 point drop in dyspareunia severity. For the 59 women in the prasterone study arms who were 3-5 year past menopause, the decrease from baseline was 0.59 points. Finally, among the 325 women who received prasterone and experienced menopause 6 or more years ago, the decrease was 0.27 points.

Although there was a numeric difference in the change in dyspareunia score severity among these groups, the differences were not statistically significant, said Dr. Archer. Again, though, those who took prasterone had a significant reduction in dyspareunia severity scores when compared with those taking placebo (P less than .0001, P = .0136, and P = .0024, respectively).

In the prasterone study arms, 184 had previously used hormone therapy, and 222 had not. After 12 weeks of intravaginal prasterone, there was no statistically significant difference between the two subgroups, with a decreases in dyspareunia severity scores of 0.45 and 0.32, respectively. The decreases in severity scores when compared with those among women who took placebo were again statistically significant for both subgroups, however (P = .0002 and P = .0057, respectively).

Prasterone is a steroid that is also known as dehydroepiandrosterone (DHEA) and is an endogenous hormone that is a precursor for estrogens and androgens. Prasterone’s mechanism of action to reduce vulvar and vaginal atrophy is not completely understood, according to the Food and Drug Administration.

“The nonstatistically significant smaller effect on dyspareunia observed when treatment is initiated after a longer period after menopause suggests that a longer treatment period could be needed to achieve optimal benefit and that treatment of dyspareunia should be initiated as early as possible after menopause,” said Dr. Archer.

Dr. Archer reported grant support from and consulting relationships with several pharmaceutical companies, including Endoceutics, the producer of Intrarosa intravaginal prasterone.

[email protected]

Recent research has pointed to a role for measuring neurofilament light (Nf-L) chain levels to predict disease severity in multiple sclerosis (MS). Several papers presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin will describe new developments on the topic.

A highlighted session on the congress’s last day explores recent development in progressive MS. While much of the research on using Nf-L as a biomarker focuses on relapsing remitting MS, researchers from University Hospital, Basel, Switzerland, and Novartis used data from placebo-controlled, phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND) to learn how to use biomarkers to track brain atrophy in patients with primary and secondary progressive MS. Hear the results from lead researcher Jens Kuhle, MD, in Hall A at 10:30 a.m. (local time) on Friday, Oct. 12.

Nf-L also is being looked at as a way to suss out treatment failure. Researchers with the Swiss MS Cohort Study will present their study of Nf-L as a biomarker of suboptimal treatment response in patients with relapsing remitting MS on established disease-modifying therapy. Their findings will be presented by Özguer Yaldizli, MD, also of University Hospital, also in Hall A, at 8:30 a.m. (local time) on Friday, Oct. 12.

Follow #ECTRIMS2018 on Twitter to see live highlights and perspective from researchers and meeting attendees.

[email protected]

Recent research has pointed to a role for measuring neurofilament light (Nf-L) chain levels to predict disease severity in multiple sclerosis (MS). Several papers presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin will describe new developments on the topic.

A highlighted session on the congress’s last day explores recent development in progressive MS. While much of the research on using Nf-L as a biomarker focuses on relapsing remitting MS, researchers from University Hospital, Basel, Switzerland, and Novartis used data from placebo-controlled, phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND) to learn how to use biomarkers to track brain atrophy in patients with primary and secondary progressive MS. Hear the results from lead researcher Jens Kuhle, MD, in Hall A at 10:30 a.m. (local time) on Friday, Oct. 12.

Nf-L also is being looked at as a way to suss out treatment failure. Researchers with the Swiss MS Cohort Study will present their study of Nf-L as a biomarker of suboptimal treatment response in patients with relapsing remitting MS on established disease-modifying therapy. Their findings will be presented by Özguer Yaldizli, MD, also of University Hospital, also in Hall A, at 8:30 a.m. (local time) on Friday, Oct. 12.

Follow #ECTRIMS2018 on Twitter to see live highlights and perspective from researchers and meeting attendees.

[email protected]

Recent research has pointed to a role for measuring neurofilament light (Nf-L) chain levels to predict disease severity in multiple sclerosis (MS). Several papers presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin will describe new developments on the topic.

A highlighted session on the congress’s last day explores recent development in progressive MS. While much of the research on using Nf-L as a biomarker focuses on relapsing remitting MS, researchers from University Hospital, Basel, Switzerland, and Novartis used data from placebo-controlled, phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND) to learn how to use biomarkers to track brain atrophy in patients with primary and secondary progressive MS. Hear the results from lead researcher Jens Kuhle, MD, in Hall A at 10:30 a.m. (local time) on Friday, Oct. 12.

Nf-L also is being looked at as a way to suss out treatment failure. Researchers with the Swiss MS Cohort Study will present their study of Nf-L as a biomarker of suboptimal treatment response in patients with relapsing remitting MS on established disease-modifying therapy. Their findings will be presented by Özguer Yaldizli, MD, also of University Hospital, also in Hall A, at 8:30 a.m. (local time) on Friday, Oct. 12.

Follow #ECTRIMS2018 on Twitter to see live highlights and perspective from researchers and meeting attendees.

[email protected]

In the drug-pricing battle, progressive lawmakers such as Sen. Bernie Sanders (I-Vt.) and patients’ rights activists rarely find themselves in step with the health industry’s big players.

But in a twist, these usually at-odds actors are championing similar tactics to tame prescription drug prices.

The strategies involve repurposing two obscure and rarely deployed workarounds in patent law that, in different ways, empower the federal government to take back patents and license them to other companies. The first is known as “march-in rights.” The second is generally referred to as Section 1498 because of its location in the U.S. Code.

Sanders has in recent years pointed to these steps as useful tools in the drug-pricing debate.

As an indicator of how high the stakes have become, these ideas also are finding traction among some major health industry players – most notably, two large trade groups that represent health plans and the “middlemen” companies that negotiate drug coverage.

“It used to be the case that everyone played nicely with one another, and now as prices have gone up, the knives have come out,” said Jacob S. Sherkow, a law professor at New York University who focuses on intellectual property and the pharmaceutical industry.

The push for march-in rights gained momentum this past summer, when activists launched a campaign challenging the patent for Truvada (emtricitabine/tenofovir), the HIV treatment by Gilead Sciences that has been shown to reduce the risks of contracting HIV when taken daily as a preventive.

Initially, patient advocates focused mainly on shaming insurance companies into providing better coverage of that pill, also known as pre-exposure prophylaxis, or PrEP, because it is taken before someone is exposed to the virus. But they soon found themselves targeting a frustration that insurance companies happened to share: the drug’s list price.

James Krellenstein, cofounder of the PrEP4All Collaboration, an advocacy group, was part of that campaign. Health plans had put barriers in place to limit access to the drug, he said. But they, too, were worried about Truvada’s escalating price.

“You can’t scale up to a level you need to unless we deal with the pricing problem,” he said.

Now, as insurers signal they might adopt an approach similar to that of the campaign, he voiced skepticism. On the one hand, the support could benefit their cause. At the same time, “they have their interests, and that’s not the interests of public health,” Mr. Krellenstein said.

Still, in Washington, the influence of groups like America’s Health Insurance Plans (AHIP), which is the largest trade association for health insurers, and the Pharmaceutical Care Management Association (PCMA), which represents those middlemen companies known as pharmacy benefit managers (PBMs), could add political credibility to these long-shot ideas.

President Trump has said curbing prescription drug costs is a high priority. But, as congressional action seems increasingly unlikely, these two approaches offer another possible path forward.

They are “already part of a law that is intact. ... An option the administration can take now,” said Walid Gellad, MD, MPH, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

AHIP says the Department of Health & Human Services should lean on a federal statute that lets the government take over drug patents and grant them to other manufacturers, as long as it adequately compensates the original patent holder.

Meanwhile, PCMA is pressing the administration to use the march-in rights championed by HIV activists. Provided under the 1980 Bayh-Dole Act, they empower the government to rescind a drug’s patent and let other companies develop versions of it. This applies only if government funding helped develop the drug, and it can be invoked only in specific circumstances, including a threat to public health or safety.

“Everybody is feeling the heat, and I think that is the reason you’re seeing this interest in using the tools that exist,” said Amy Kapczynski, a professor at Yale Law School who has written extensively about drug patents.

But opposition is strong among drugmakers.

“Policies should spur competition and new innovations to meet patient needs not disincentivize them such as the use of 1498 and march-in could do,” said Priscilla VanderVeer, a spokeswoman for the Pharmaceutical Researchers and Manufacturers of America, or PhRMA, a trade and lobbying group.

Gilead, which manufactures Truvada, has a similar stance.

“We believe that there is no rationale or precedent for the government to exercise march-in or other [intellectual property] rights related to Truvada for PrEP,” said Ryan McKeel, a spokesman for Gilead. The company’s other efforts to make the drug “available for health and safety needs,” he added, “clearly satisfy” the company’s legal requirements.

And the potential for march-in authority is still theoretical. It has never been used, despite at least five petitions to the National Institutes of Health, three of which cited high drug prices.

Section 1498 was used to negotiate lower drug prices in the 1960s and 1970s, but has since faded. In 2001, during the nation’s anthrax scare, HHS threatened to invoke it to procure more of the antibiotic used to treat the deadly bacterial disease, according to contemporaneous reports. Last year, Louisiana’s health secretary unsuccessfully tried to use it to ease the toll pricey hepatitis C medications exerted on the state’s Medicaid program.

NIH Director Francis Collins, MD, PhD, remains skeptical, repeatedly saying that a drug’s price doesn’t constitute a health or safety concern within the agency’s jurisdiction.

HHS Secretary Alex M. Azar II, speaking at a June Senate hearing, described march-in, also known as “compulsory licensing,” as a “socialist” approach.

But health plans and other payers, increasingly squeezed by fast-climbing prices, are undeterred – touting this kind of intervention as a “market-based solution.”

“The trends of drug prices in this country suggest that we all collectively need to find new approaches – including new approaches that are available under existing law – to try to change this trend,” said Mark Hamelburg, AHIP’s senior vice president of federal programs.

Kaiser Permanente, the health system and insurance provider, called for leveraging Section 1498 in a public comment submitted to HHS about its strategy to bring down drug prices. In a similar filing, Humana, a major insurer, pointed to “existing law [that] allows for actions around patents,” singling out march-in rights.

Humana did not respond to requests for comment. Both PCMA and Kaiser Permanente declined to comment beyond their statements. (Kaiser Health News is not affiliated with Kaiser Permanente.)

Nonetheless, experts say there are serious sticking points.

Neither of these legal provisions would be a sweeping solution. And both require administration buy-in.

“They’re only as effective as the government’s willingness to pursue them,” said Robin Feldman, a law professor at the University of California-Hastings.

Simply taking a patent doesn’t bring down prices, either. There are other ways manufacturers gain favorable market positioning for specific drugs, said Rachel Sachs, an associate law professor at Washington University in St. Louis who tracks drug-pricing laws.

And creating an opening for generics is only one step. Another drugmaker would still need to create a competing product, gain approval, and make it available. Then, theoretically, market competition can kick in.

Finally, there’s no guarantee such savings would benefit consumers, argued Nicholson Price, an assistant professor at the University of Michigan Law School. Insurance plans or PBMs could simply bargain greater discounts on drugs and pocket the money. (AHIP says any savings should be passed on.)

That’s the fundamental question, Mr. Krellenstein said.

“Is this going to be more armor in the fighting [between payers and drug companies]?” he said. “Or is it actually going to be a dramatic reform that actually results in real changes, that actually makes it easier for Americans to access the medications they need?”
 

KHN’s coverage of prescription drug development, costs, and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

In the drug-pricing battle, progressive lawmakers such as Sen. Bernie Sanders (I-Vt.) and patients’ rights activists rarely find themselves in step with the health industry’s big players.

But in a twist, these usually at-odds actors are championing similar tactics to tame prescription drug prices.

The strategies involve repurposing two obscure and rarely deployed workarounds in patent law that, in different ways, empower the federal government to take back patents and license them to other companies. The first is known as “march-in rights.” The second is generally referred to as Section 1498 because of its location in the U.S. Code.

Sanders has in recent years pointed to these steps as useful tools in the drug-pricing debate.

As an indicator of how high the stakes have become, these ideas also are finding traction among some major health industry players – most notably, two large trade groups that represent health plans and the “middlemen” companies that negotiate drug coverage.

“It used to be the case that everyone played nicely with one another, and now as prices have gone up, the knives have come out,” said Jacob S. Sherkow, a law professor at New York University who focuses on intellectual property and the pharmaceutical industry.

The push for march-in rights gained momentum this past summer, when activists launched a campaign challenging the patent for Truvada (emtricitabine/tenofovir), the HIV treatment by Gilead Sciences that has been shown to reduce the risks of contracting HIV when taken daily as a preventive.

Initially, patient advocates focused mainly on shaming insurance companies into providing better coverage of that pill, also known as pre-exposure prophylaxis, or PrEP, because it is taken before someone is exposed to the virus. But they soon found themselves targeting a frustration that insurance companies happened to share: the drug’s list price.

James Krellenstein, cofounder of the PrEP4All Collaboration, an advocacy group, was part of that campaign. Health plans had put barriers in place to limit access to the drug, he said. But they, too, were worried about Truvada’s escalating price.

“You can’t scale up to a level you need to unless we deal with the pricing problem,” he said.

Now, as insurers signal they might adopt an approach similar to that of the campaign, he voiced skepticism. On the one hand, the support could benefit their cause. At the same time, “they have their interests, and that’s not the interests of public health,” Mr. Krellenstein said.

Still, in Washington, the influence of groups like America’s Health Insurance Plans (AHIP), which is the largest trade association for health insurers, and the Pharmaceutical Care Management Association (PCMA), which represents those middlemen companies known as pharmacy benefit managers (PBMs), could add political credibility to these long-shot ideas.

President Trump has said curbing prescription drug costs is a high priority. But, as congressional action seems increasingly unlikely, these two approaches offer another possible path forward.

They are “already part of a law that is intact. ... An option the administration can take now,” said Walid Gellad, MD, MPH, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

AHIP says the Department of Health & Human Services should lean on a federal statute that lets the government take over drug patents and grant them to other manufacturers, as long as it adequately compensates the original patent holder.

Meanwhile, PCMA is pressing the administration to use the march-in rights championed by HIV activists. Provided under the 1980 Bayh-Dole Act, they empower the government to rescind a drug’s patent and let other companies develop versions of it. This applies only if government funding helped develop the drug, and it can be invoked only in specific circumstances, including a threat to public health or safety.

“Everybody is feeling the heat, and I think that is the reason you’re seeing this interest in using the tools that exist,” said Amy Kapczynski, a professor at Yale Law School who has written extensively about drug patents.

But opposition is strong among drugmakers.

“Policies should spur competition and new innovations to meet patient needs not disincentivize them such as the use of 1498 and march-in could do,” said Priscilla VanderVeer, a spokeswoman for the Pharmaceutical Researchers and Manufacturers of America, or PhRMA, a trade and lobbying group.

Gilead, which manufactures Truvada, has a similar stance.

“We believe that there is no rationale or precedent for the government to exercise march-in or other [intellectual property] rights related to Truvada for PrEP,” said Ryan McKeel, a spokesman for Gilead. The company’s other efforts to make the drug “available for health and safety needs,” he added, “clearly satisfy” the company’s legal requirements.

And the potential for march-in authority is still theoretical. It has never been used, despite at least five petitions to the National Institutes of Health, three of which cited high drug prices.

Section 1498 was used to negotiate lower drug prices in the 1960s and 1970s, but has since faded. In 2001, during the nation’s anthrax scare, HHS threatened to invoke it to procure more of the antibiotic used to treat the deadly bacterial disease, according to contemporaneous reports. Last year, Louisiana’s health secretary unsuccessfully tried to use it to ease the toll pricey hepatitis C medications exerted on the state’s Medicaid program.

NIH Director Francis Collins, MD, PhD, remains skeptical, repeatedly saying that a drug’s price doesn’t constitute a health or safety concern within the agency’s jurisdiction.

HHS Secretary Alex M. Azar II, speaking at a June Senate hearing, described march-in, also known as “compulsory licensing,” as a “socialist” approach.

But health plans and other payers, increasingly squeezed by fast-climbing prices, are undeterred – touting this kind of intervention as a “market-based solution.”

“The trends of drug prices in this country suggest that we all collectively need to find new approaches – including new approaches that are available under existing law – to try to change this trend,” said Mark Hamelburg, AHIP’s senior vice president of federal programs.

Kaiser Permanente, the health system and insurance provider, called for leveraging Section 1498 in a public comment submitted to HHS about its strategy to bring down drug prices. In a similar filing, Humana, a major insurer, pointed to “existing law [that] allows for actions around patents,” singling out march-in rights.

Humana did not respond to requests for comment. Both PCMA and Kaiser Permanente declined to comment beyond their statements. (Kaiser Health News is not affiliated with Kaiser Permanente.)

Nonetheless, experts say there are serious sticking points.

Neither of these legal provisions would be a sweeping solution. And both require administration buy-in.

“They’re only as effective as the government’s willingness to pursue them,” said Robin Feldman, a law professor at the University of California-Hastings.

Simply taking a patent doesn’t bring down prices, either. There are other ways manufacturers gain favorable market positioning for specific drugs, said Rachel Sachs, an associate law professor at Washington University in St. Louis who tracks drug-pricing laws.

And creating an opening for generics is only one step. Another drugmaker would still need to create a competing product, gain approval, and make it available. Then, theoretically, market competition can kick in.

Finally, there’s no guarantee such savings would benefit consumers, argued Nicholson Price, an assistant professor at the University of Michigan Law School. Insurance plans or PBMs could simply bargain greater discounts on drugs and pocket the money. (AHIP says any savings should be passed on.)

That’s the fundamental question, Mr. Krellenstein said.

“Is this going to be more armor in the fighting [between payers and drug companies]?” he said. “Or is it actually going to be a dramatic reform that actually results in real changes, that actually makes it easier for Americans to access the medications they need?”
 

KHN’s coverage of prescription drug development, costs, and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

In the drug-pricing battle, progressive lawmakers such as Sen. Bernie Sanders (I-Vt.) and patients’ rights activists rarely find themselves in step with the health industry’s big players.

But in a twist, these usually at-odds actors are championing similar tactics to tame prescription drug prices.

The strategies involve repurposing two obscure and rarely deployed workarounds in patent law that, in different ways, empower the federal government to take back patents and license them to other companies. The first is known as “march-in rights.” The second is generally referred to as Section 1498 because of its location in the U.S. Code.

Sanders has in recent years pointed to these steps as useful tools in the drug-pricing debate.

As an indicator of how high the stakes have become, these ideas also are finding traction among some major health industry players – most notably, two large trade groups that represent health plans and the “middlemen” companies that negotiate drug coverage.

“It used to be the case that everyone played nicely with one another, and now as prices have gone up, the knives have come out,” said Jacob S. Sherkow, a law professor at New York University who focuses on intellectual property and the pharmaceutical industry.

The push for march-in rights gained momentum this past summer, when activists launched a campaign challenging the patent for Truvada (emtricitabine/tenofovir), the HIV treatment by Gilead Sciences that has been shown to reduce the risks of contracting HIV when taken daily as a preventive.

Initially, patient advocates focused mainly on shaming insurance companies into providing better coverage of that pill, also known as pre-exposure prophylaxis, or PrEP, because it is taken before someone is exposed to the virus. But they soon found themselves targeting a frustration that insurance companies happened to share: the drug’s list price.

James Krellenstein, cofounder of the PrEP4All Collaboration, an advocacy group, was part of that campaign. Health plans had put barriers in place to limit access to the drug, he said. But they, too, were worried about Truvada’s escalating price.

“You can’t scale up to a level you need to unless we deal with the pricing problem,” he said.

Now, as insurers signal they might adopt an approach similar to that of the campaign, he voiced skepticism. On the one hand, the support could benefit their cause. At the same time, “they have their interests, and that’s not the interests of public health,” Mr. Krellenstein said.

Still, in Washington, the influence of groups like America’s Health Insurance Plans (AHIP), which is the largest trade association for health insurers, and the Pharmaceutical Care Management Association (PCMA), which represents those middlemen companies known as pharmacy benefit managers (PBMs), could add political credibility to these long-shot ideas.

President Trump has said curbing prescription drug costs is a high priority. But, as congressional action seems increasingly unlikely, these two approaches offer another possible path forward.

They are “already part of a law that is intact. ... An option the administration can take now,” said Walid Gellad, MD, MPH, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

AHIP says the Department of Health & Human Services should lean on a federal statute that lets the government take over drug patents and grant them to other manufacturers, as long as it adequately compensates the original patent holder.

Meanwhile, PCMA is pressing the administration to use the march-in rights championed by HIV activists. Provided under the 1980 Bayh-Dole Act, they empower the government to rescind a drug’s patent and let other companies develop versions of it. This applies only if government funding helped develop the drug, and it can be invoked only in specific circumstances, including a threat to public health or safety.

“Everybody is feeling the heat, and I think that is the reason you’re seeing this interest in using the tools that exist,” said Amy Kapczynski, a professor at Yale Law School who has written extensively about drug patents.

But opposition is strong among drugmakers.

“Policies should spur competition and new innovations to meet patient needs not disincentivize them such as the use of 1498 and march-in could do,” said Priscilla VanderVeer, a spokeswoman for the Pharmaceutical Researchers and Manufacturers of America, or PhRMA, a trade and lobbying group.

Gilead, which manufactures Truvada, has a similar stance.

“We believe that there is no rationale or precedent for the government to exercise march-in or other [intellectual property] rights related to Truvada for PrEP,” said Ryan McKeel, a spokesman for Gilead. The company’s other efforts to make the drug “available for health and safety needs,” he added, “clearly satisfy” the company’s legal requirements.

And the potential for march-in authority is still theoretical. It has never been used, despite at least five petitions to the National Institutes of Health, three of which cited high drug prices.

Section 1498 was used to negotiate lower drug prices in the 1960s and 1970s, but has since faded. In 2001, during the nation’s anthrax scare, HHS threatened to invoke it to procure more of the antibiotic used to treat the deadly bacterial disease, according to contemporaneous reports. Last year, Louisiana’s health secretary unsuccessfully tried to use it to ease the toll pricey hepatitis C medications exerted on the state’s Medicaid program.

NIH Director Francis Collins, MD, PhD, remains skeptical, repeatedly saying that a drug’s price doesn’t constitute a health or safety concern within the agency’s jurisdiction.

HHS Secretary Alex M. Azar II, speaking at a June Senate hearing, described march-in, also known as “compulsory licensing,” as a “socialist” approach.

But health plans and other payers, increasingly squeezed by fast-climbing prices, are undeterred – touting this kind of intervention as a “market-based solution.”

“The trends of drug prices in this country suggest that we all collectively need to find new approaches – including new approaches that are available under existing law – to try to change this trend,” said Mark Hamelburg, AHIP’s senior vice president of federal programs.

Kaiser Permanente, the health system and insurance provider, called for leveraging Section 1498 in a public comment submitted to HHS about its strategy to bring down drug prices. In a similar filing, Humana, a major insurer, pointed to “existing law [that] allows for actions around patents,” singling out march-in rights.

Humana did not respond to requests for comment. Both PCMA and Kaiser Permanente declined to comment beyond their statements. (Kaiser Health News is not affiliated with Kaiser Permanente.)

Nonetheless, experts say there are serious sticking points.

Neither of these legal provisions would be a sweeping solution. And both require administration buy-in.

“They’re only as effective as the government’s willingness to pursue them,” said Robin Feldman, a law professor at the University of California-Hastings.

Simply taking a patent doesn’t bring down prices, either. There are other ways manufacturers gain favorable market positioning for specific drugs, said Rachel Sachs, an associate law professor at Washington University in St. Louis who tracks drug-pricing laws.

And creating an opening for generics is only one step. Another drugmaker would still need to create a competing product, gain approval, and make it available. Then, theoretically, market competition can kick in.

Finally, there’s no guarantee such savings would benefit consumers, argued Nicholson Price, an assistant professor at the University of Michigan Law School. Insurance plans or PBMs could simply bargain greater discounts on drugs and pocket the money. (AHIP says any savings should be passed on.)

That’s the fundamental question, Mr. Krellenstein said.

“Is this going to be more armor in the fighting [between payers and drug companies]?” he said. “Or is it actually going to be a dramatic reform that actually results in real changes, that actually makes it easier for Americans to access the medications they need?”
 

KHN’s coverage of prescription drug development, costs, and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

PHOENIX – Opioid use in urologic oncology patients dropped by 46% after one high-volume surgical center introduced changes to order sets and adopted new patient communication strategies, a researcher has reported.

The changes, which promoted opioid-sparing pain regimens, led to a substantial drop in postoperative opioid use with no compromise in pain control, according to Kerri Stevenson, a nurse practitioner with Stanford Health Care.

“Patients can be successfully managed with minimal opioid medication,” Ms. Stevenson said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

However, “it takes a multidisciplinary team for effective change to occur – this cannot be done in silos,” she told attendees at the meeting.

Seeking to reduce their reliance on opioids to manage postoperative pain, Ms. Stevenson and her colleagues set out to reduce opioid use by 50%, from a baseline morphine equivalent daily dose (MEDD) of 95.1 in June to September 2017 to a target of 47.5 by March 2018.

The actual MEDD at the end of the quality improvement project was 51.5, a 46% reduction that was just shy of that goal, she reported.

Factors fueling opioid use included patient expectations that they would be used and the belief that adjunct medications were not as effective as opioids, Dr. Stevenson found in a team survey.

“We decided to target those,” she said. “Our key drivers were really focused on appropriate prescriptions, increasing patient and provider awareness, standardizing our pathways, and setting expectations.”

To tackle the problem, they revised EMR order sets to default to selection of adjunct medications, educated providers, and introduced new patient communication strategies.

Instead of asking “Would you like me to bring you some oxycodone?” providers would instead start by asking about the patient’s current pain control medications and whether they were working well. When prescribed, opioids should be started at lower doses and escalated only if needed.

“Once we started our interventions, we noticed an immediate effect,” Ms. Stevenson.

The decreases were consistent across a range of surgery types. For example, the MEDD dropped to 55.1 with robotic prostatectomy, a procedure with a 1-day admission and very small incisions, and to 50.6 for open radical cystectomy, which involves a large incision and a stay of approximately 4 days, she said.

To address concerns that they might just be undertreating patients, investigators looked retrospectively at pain scores. They saw no differences pre- and post intervention in pain or anxiety scores within the first 24-48 hours post procedure, Ms. Stevenson reported.

Ms. Stevenson had no disclosures related to the presentation. Coauthor Jay Bakul Shah, MD of Stanford Health Care reported a consulting or advisory role with Pacira Pharmaceuticals.

SOURCE: Stevenson K et al. Quality Care Symposium, Abstract 269.

PHOENIX – Opioid use in urologic oncology patients dropped by 46% after one high-volume surgical center introduced changes to order sets and adopted new patient communication strategies, a researcher has reported.

The changes, which promoted opioid-sparing pain regimens, led to a substantial drop in postoperative opioid use with no compromise in pain control, according to Kerri Stevenson, a nurse practitioner with Stanford Health Care.

“Patients can be successfully managed with minimal opioid medication,” Ms. Stevenson said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

However, “it takes a multidisciplinary team for effective change to occur – this cannot be done in silos,” she told attendees at the meeting.

Seeking to reduce their reliance on opioids to manage postoperative pain, Ms. Stevenson and her colleagues set out to reduce opioid use by 50%, from a baseline morphine equivalent daily dose (MEDD) of 95.1 in June to September 2017 to a target of 47.5 by March 2018.

The actual MEDD at the end of the quality improvement project was 51.5, a 46% reduction that was just shy of that goal, she reported.

Factors fueling opioid use included patient expectations that they would be used and the belief that adjunct medications were not as effective as opioids, Dr. Stevenson found in a team survey.

“We decided to target those,” she said. “Our key drivers were really focused on appropriate prescriptions, increasing patient and provider awareness, standardizing our pathways, and setting expectations.”

To tackle the problem, they revised EMR order sets to default to selection of adjunct medications, educated providers, and introduced new patient communication strategies.

Instead of asking “Would you like me to bring you some oxycodone?” providers would instead start by asking about the patient’s current pain control medications and whether they were working well. When prescribed, opioids should be started at lower doses and escalated only if needed.

“Once we started our interventions, we noticed an immediate effect,” Ms. Stevenson.

The decreases were consistent across a range of surgery types. For example, the MEDD dropped to 55.1 with robotic prostatectomy, a procedure with a 1-day admission and very small incisions, and to 50.6 for open radical cystectomy, which involves a large incision and a stay of approximately 4 days, she said.

To address concerns that they might just be undertreating patients, investigators looked retrospectively at pain scores. They saw no differences pre- and post intervention in pain or anxiety scores within the first 24-48 hours post procedure, Ms. Stevenson reported.

Ms. Stevenson had no disclosures related to the presentation. Coauthor Jay Bakul Shah, MD of Stanford Health Care reported a consulting or advisory role with Pacira Pharmaceuticals.

SOURCE: Stevenson K et al. Quality Care Symposium, Abstract 269.

PHOENIX – Opioid use in urologic oncology patients dropped by 46% after one high-volume surgical center introduced changes to order sets and adopted new patient communication strategies, a researcher has reported.

The changes, which promoted opioid-sparing pain regimens, led to a substantial drop in postoperative opioid use with no compromise in pain control, according to Kerri Stevenson, a nurse practitioner with Stanford Health Care.

“Patients can be successfully managed with minimal opioid medication,” Ms. Stevenson said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

However, “it takes a multidisciplinary team for effective change to occur – this cannot be done in silos,” she told attendees at the meeting.

Seeking to reduce their reliance on opioids to manage postoperative pain, Ms. Stevenson and her colleagues set out to reduce opioid use by 50%, from a baseline morphine equivalent daily dose (MEDD) of 95.1 in June to September 2017 to a target of 47.5 by March 2018.

The actual MEDD at the end of the quality improvement project was 51.5, a 46% reduction that was just shy of that goal, she reported.

Factors fueling opioid use included patient expectations that they would be used and the belief that adjunct medications were not as effective as opioids, Dr. Stevenson found in a team survey.

“We decided to target those,” she said. “Our key drivers were really focused on appropriate prescriptions, increasing patient and provider awareness, standardizing our pathways, and setting expectations.”

To tackle the problem, they revised EMR order sets to default to selection of adjunct medications, educated providers, and introduced new patient communication strategies.

Instead of asking “Would you like me to bring you some oxycodone?” providers would instead start by asking about the patient’s current pain control medications and whether they were working well. When prescribed, opioids should be started at lower doses and escalated only if needed.

“Once we started our interventions, we noticed an immediate effect,” Ms. Stevenson.

The decreases were consistent across a range of surgery types. For example, the MEDD dropped to 55.1 with robotic prostatectomy, a procedure with a 1-day admission and very small incisions, and to 50.6 for open radical cystectomy, which involves a large incision and a stay of approximately 4 days, she said.

To address concerns that they might just be undertreating patients, investigators looked retrospectively at pain scores. They saw no differences pre- and post intervention in pain or anxiety scores within the first 24-48 hours post procedure, Ms. Stevenson reported.

Ms. Stevenson had no disclosures related to the presentation. Coauthor Jay Bakul Shah, MD of Stanford Health Care reported a consulting or advisory role with Pacira Pharmaceuticals.

SOURCE: Stevenson K et al. Quality Care Symposium, Abstract 269.