Dually active antiretroviral therapy (DAART) for HIV-infected patients may be the best treatment option to also protect these individuals against hepatitis B virus (HBV) infection, according to results of a study in the Journal of Infectious Diseases.

“Vaccination against HBV remains the mainstay of preventing HBV acquisition both in HIV-infected and uninfected individuals,” states the study, led by Roger Kouyos, Ph.D., of University Hospital Zürich. “However, owing to HIV’s effect on the immune system, mounting and maintaining a protective immune response against HBV is sometimes unattainable, with a success rate between 18% and 71%.”

©vchal/Thinkstock

Dr. Kouyos and his colleagues collected CD4, CD8, and HIV-1 viral load data for 1,716 patients in the Swiss HIV Cohort Study – an ongoing, prospective cohort study that began in 1988 – and updated the data continuously during follow-up visits every 3 months, on average. Subjects were enrolled if they had negative baseline HBV serology and at least one additional HBV test after the initial one, and were either a man who had sex with men, a heterosexual, or an intravenous drug user – the three major groups examined by the study (J Infect Dis. 2016 May 18. doi:10.1093/infdis/jiw195).

DAART treatment consisted of tenofovir, lamivudine, and emtricitabine. Antiretroviral treatment history was also collected, and at follow-up examinations every 6 months, subjects were asked about occasional sex partners and frequency of condom use during the preceding 6 months. All were tested for at least one HBV marker: surface antigen (HBsAg), anti–hepatitis B core antibodies (AntiHBc), or hepatitis B virus DNA.

Of the 1,716 subjects enrolled, 177 had HBV. Of these, 86 (49%) were men who had sex with men. Most subjects underwent at least two HBV tests, with the median time between tests being 29 months (range of 12-58 months). In the transmission group, the overall incidence rate of HBV was 16 (95% confidence interval, 14-19), while it was 25 (21-31) for men who had sex with men, 9 (6-11) for heterosexuals, and 28 (21-38) for intravenous drug users.

DAART, however, was shown to significantly reduce HBV-infection risk. Univariate analysis yielded a hazard ratio of 0.4 (95% CI, 0.2-0.6), and multivariate analysis showed even more significant effects for intravenous drug users (3.8, 2.4-6.1), men who had sex with men (2.7, 1.7-4.2), and those who had unprotected sex (1.9, 1.4-2.6).

“Our study confirms the importance of viral suppression (and the implicit adherence) in reaching the protective effect of DAART,” the authors concluded, noting that “Our study adds to the growing body of evidence that early antiretroviral therapy initiation, regardless of CD4 counts, has a strong beneficial public health impact, including preexposure prophylaxis of HBV coinfections.”

The study was supported by the Swiss HIV Cohort Study, the Swiss National Science Foundation, the European Community’s Seventh Framework Program, and the Union Bank of Switzerland. Dr. Kouyos reported travel grants from Gilead. Other coauthors reported research, educational, and travel grants from Roche, Abbott, Bristol-Myers Squibb, Gilead, Astra-Zeneca, GlaxoSmithKline, Pfizer, and Astellas.

[email protected]

Dually active antiretroviral therapy (DAART) for HIV-infected patients may be the best treatment option to also protect these individuals against hepatitis B virus (HBV) infection, according to results of a study in the Journal of Infectious Diseases.

“Vaccination against HBV remains the mainstay of preventing HBV acquisition both in HIV-infected and uninfected individuals,” states the study, led by Roger Kouyos, Ph.D., of University Hospital Zürich. “However, owing to HIV’s effect on the immune system, mounting and maintaining a protective immune response against HBV is sometimes unattainable, with a success rate between 18% and 71%.”

©vchal/Thinkstock

Dr. Kouyos and his colleagues collected CD4, CD8, and HIV-1 viral load data for 1,716 patients in the Swiss HIV Cohort Study – an ongoing, prospective cohort study that began in 1988 – and updated the data continuously during follow-up visits every 3 months, on average. Subjects were enrolled if they had negative baseline HBV serology and at least one additional HBV test after the initial one, and were either a man who had sex with men, a heterosexual, or an intravenous drug user – the three major groups examined by the study (J Infect Dis. 2016 May 18. doi:10.1093/infdis/jiw195).

DAART treatment consisted of tenofovir, lamivudine, and emtricitabine. Antiretroviral treatment history was also collected, and at follow-up examinations every 6 months, subjects were asked about occasional sex partners and frequency of condom use during the preceding 6 months. All were tested for at least one HBV marker: surface antigen (HBsAg), anti–hepatitis B core antibodies (AntiHBc), or hepatitis B virus DNA.

Of the 1,716 subjects enrolled, 177 had HBV. Of these, 86 (49%) were men who had sex with men. Most subjects underwent at least two HBV tests, with the median time between tests being 29 months (range of 12-58 months). In the transmission group, the overall incidence rate of HBV was 16 (95% confidence interval, 14-19), while it was 25 (21-31) for men who had sex with men, 9 (6-11) for heterosexuals, and 28 (21-38) for intravenous drug users.

DAART, however, was shown to significantly reduce HBV-infection risk. Univariate analysis yielded a hazard ratio of 0.4 (95% CI, 0.2-0.6), and multivariate analysis showed even more significant effects for intravenous drug users (3.8, 2.4-6.1), men who had sex with men (2.7, 1.7-4.2), and those who had unprotected sex (1.9, 1.4-2.6).

“Our study confirms the importance of viral suppression (and the implicit adherence) in reaching the protective effect of DAART,” the authors concluded, noting that “Our study adds to the growing body of evidence that early antiretroviral therapy initiation, regardless of CD4 counts, has a strong beneficial public health impact, including preexposure prophylaxis of HBV coinfections.”

The study was supported by the Swiss HIV Cohort Study, the Swiss National Science Foundation, the European Community’s Seventh Framework Program, and the Union Bank of Switzerland. Dr. Kouyos reported travel grants from Gilead. Other coauthors reported research, educational, and travel grants from Roche, Abbott, Bristol-Myers Squibb, Gilead, Astra-Zeneca, GlaxoSmithKline, Pfizer, and Astellas.

[email protected]

Dually active antiretroviral therapy (DAART) for HIV-infected patients may be the best treatment option to also protect these individuals against hepatitis B virus (HBV) infection, according to results of a study in the Journal of Infectious Diseases.

“Vaccination against HBV remains the mainstay of preventing HBV acquisition both in HIV-infected and uninfected individuals,” states the study, led by Roger Kouyos, Ph.D., of University Hospital Zürich. “However, owing to HIV’s effect on the immune system, mounting and maintaining a protective immune response against HBV is sometimes unattainable, with a success rate between 18% and 71%.”

©vchal/Thinkstock

Dr. Kouyos and his colleagues collected CD4, CD8, and HIV-1 viral load data for 1,716 patients in the Swiss HIV Cohort Study – an ongoing, prospective cohort study that began in 1988 – and updated the data continuously during follow-up visits every 3 months, on average. Subjects were enrolled if they had negative baseline HBV serology and at least one additional HBV test after the initial one, and were either a man who had sex with men, a heterosexual, or an intravenous drug user – the three major groups examined by the study (J Infect Dis. 2016 May 18. doi:10.1093/infdis/jiw195).

DAART treatment consisted of tenofovir, lamivudine, and emtricitabine. Antiretroviral treatment history was also collected, and at follow-up examinations every 6 months, subjects were asked about occasional sex partners and frequency of condom use during the preceding 6 months. All were tested for at least one HBV marker: surface antigen (HBsAg), anti–hepatitis B core antibodies (AntiHBc), or hepatitis B virus DNA.

Of the 1,716 subjects enrolled, 177 had HBV. Of these, 86 (49%) were men who had sex with men. Most subjects underwent at least two HBV tests, with the median time between tests being 29 months (range of 12-58 months). In the transmission group, the overall incidence rate of HBV was 16 (95% confidence interval, 14-19), while it was 25 (21-31) for men who had sex with men, 9 (6-11) for heterosexuals, and 28 (21-38) for intravenous drug users.

DAART, however, was shown to significantly reduce HBV-infection risk. Univariate analysis yielded a hazard ratio of 0.4 (95% CI, 0.2-0.6), and multivariate analysis showed even more significant effects for intravenous drug users (3.8, 2.4-6.1), men who had sex with men (2.7, 1.7-4.2), and those who had unprotected sex (1.9, 1.4-2.6).

“Our study confirms the importance of viral suppression (and the implicit adherence) in reaching the protective effect of DAART,” the authors concluded, noting that “Our study adds to the growing body of evidence that early antiretroviral therapy initiation, regardless of CD4 counts, has a strong beneficial public health impact, including preexposure prophylaxis of HBV coinfections.”

The study was supported by the Swiss HIV Cohort Study, the Swiss National Science Foundation, the European Community’s Seventh Framework Program, and the Union Bank of Switzerland. Dr. Kouyos reported travel grants from Gilead. Other coauthors reported research, educational, and travel grants from Roche, Abbott, Bristol-Myers Squibb, Gilead, Astra-Zeneca, GlaxoSmithKline, Pfizer, and Astellas.

[email protected]

CHICAGO – Hormonal maintenance therapy after primary treatment was associated with significantly prolonged progression-free survival when compared with surveillance in a retrospective study of women with stage II-IV low-grade serous carcinoma of the ovary or peritoneum.

The findings are “potentially practice-changing,” Dr. David Marc Gershenson of the University of Texas MD Anderson Cancer Center, Houston, said at the annual meeting of the American Society of Clinical Oncology.

©moodboard/Thinkstock

Of 204 women with newly diagnosed low-grade serous carcinoma (LGSC) who underwent primary cytoreductive surgery followed by platinum-based chemotherapy, 70 received hormonal maintenance therapy after completion of primary chemotherapy and 134 underwent surveillance. Median progression-free survival (PFS) was 64.9 vs. 27.3 months, respectively (33 months overall), Dr. Gershenson said.

“To date, 40% of the hormone maintenance therapy group has not relapsed, compared [with] only 12% in the surveillance group,” he said.

Median overall survival was not statistically different, but there was a trend toward an overall survival benefit in the hormonal maintenance therapy group (115.7 vs. 98.8 months). In a subset analysis in women who were clinically disease free at the completion of primary chemotherapy, the median PFS was 29.9 months in 121 women undergoing surveillance, vs. 81.1 months in 27 receiving hormone maintenance therapy. The mean overall survival was also statistically different in the subset analysis (106.8 vs. 191.3 months).

On multivariable analysis, four factors reached significance: hormone maintenance therapy vs. surveillance (hazard ratio, 0.23), peritoneum vs. ovary as primary site (HR, 0.45), no gross residual disease vs. gross residual disease (HR, 0.49),and persistent disease at completion of chemotherapy, vs. no evidence of disease (HR, 0.42).

Patients included in the study presented between 1981 and 2013. They had a median age of 47.6 years, about 3/4 had primary ovarian LGSC, and about 1/4 had primary peritoneal LGSC.

Patients in the hormonal therapy group were treated with letrozole (54%), tamoxifen (29%), anastrozole (3%), leuprolide acetate (7%), depot medroxyprogesterone acetate (1%), and leuprolide acetate + tamoxifen or letrozole (3% each). Median duration of hormonal maintenance therapy was 33.3 months (range of 1-223), and follow-up was at least 2 years in those who had not recurred.

LGSC is a rare subtype that accounts for about 10% of serous carcinomas of the ovary or peritoneum. These cancers may arise de novo or after a diagnosis of serous borderline tumor. LGSC, relative to high-grade serous carcinoma (HGSC), is characterized by younger age at diagnosis, chemoresistance, prolonged overall survival, and aberrations within the MAP kinase signaling pathway, Dr. Gershenson said.

The findings are of interest as primary postoperative platinum-based chemotherapy remains the standard for women with newly diagnosed metastatic ovarian or peritoneal LGSC despite multiple reports indicating that this subtype is relatively chemoresistant. For example, in the AGO database of 5,114 patients accrued to four separate phase III trials, the response rate to chemotherapy in women with suboptimally debulked LGSC was significantly lower than in women with suboptimally debulked HGSC (23% vs. 90%), he said.

However, no prospective clinical trials have been conducted in the front line setting in women with LGSC, he noted.

Recent reports of promising activity of hormonal therapy in the recurrent setting have led to an increase in interest in integrating the modality into the primary treatment setting. One study showed a high frequency of ER and PR expression in LGSC, and another showed that hormonal therapy for recurrent LGSC was associated with an objective response rate of 9%, stable disease rate of 66% and median progression-free survival of 7.4 months.

“Some patients derived several years of benefit,” he said. “In addition, low-grade serous carcinoma bears a striking resemblance to luminal breast cancer in that women who are 35 years of age or younger appear to have a significantly worse prognosis.”

Some have concluded, based on these findings, that platinum-based chemotherapy is of no value in the frontline treatment of LGSC and should be abandoned, Dr. Gershenson said.

The current findings, though limited by factors such as their retrospective nature, missing data, a long study period, and possible referral bias suggest that hormonal maintenance therapy deserves a closer look, Dr. Gershenson said.

“The findings of this hypotheses-generating study are potentially practice changing and warrant further investigation using a prospective trial design,” he concluded.

Dr. Gershenson reported stock ownership in AbbVie, Biogen Idec, Celgene, GlaxoSmithKline, Johnson & Johnson, Merck, and Pfizer; consulting or advisory roles with Clovis Oncology, and patents with Elsevier and UpToDate.

[email protected]

CHICAGO – Hormonal maintenance therapy after primary treatment was associated with significantly prolonged progression-free survival when compared with surveillance in a retrospective study of women with stage II-IV low-grade serous carcinoma of the ovary or peritoneum.

The findings are “potentially practice-changing,” Dr. David Marc Gershenson of the University of Texas MD Anderson Cancer Center, Houston, said at the annual meeting of the American Society of Clinical Oncology.

©moodboard/Thinkstock

Of 204 women with newly diagnosed low-grade serous carcinoma (LGSC) who underwent primary cytoreductive surgery followed by platinum-based chemotherapy, 70 received hormonal maintenance therapy after completion of primary chemotherapy and 134 underwent surveillance. Median progression-free survival (PFS) was 64.9 vs. 27.3 months, respectively (33 months overall), Dr. Gershenson said.

“To date, 40% of the hormone maintenance therapy group has not relapsed, compared [with] only 12% in the surveillance group,” he said.

Median overall survival was not statistically different, but there was a trend toward an overall survival benefit in the hormonal maintenance therapy group (115.7 vs. 98.8 months). In a subset analysis in women who were clinically disease free at the completion of primary chemotherapy, the median PFS was 29.9 months in 121 women undergoing surveillance, vs. 81.1 months in 27 receiving hormone maintenance therapy. The mean overall survival was also statistically different in the subset analysis (106.8 vs. 191.3 months).

On multivariable analysis, four factors reached significance: hormone maintenance therapy vs. surveillance (hazard ratio, 0.23), peritoneum vs. ovary as primary site (HR, 0.45), no gross residual disease vs. gross residual disease (HR, 0.49),and persistent disease at completion of chemotherapy, vs. no evidence of disease (HR, 0.42).

Patients included in the study presented between 1981 and 2013. They had a median age of 47.6 years, about 3/4 had primary ovarian LGSC, and about 1/4 had primary peritoneal LGSC.

Patients in the hormonal therapy group were treated with letrozole (54%), tamoxifen (29%), anastrozole (3%), leuprolide acetate (7%), depot medroxyprogesterone acetate (1%), and leuprolide acetate + tamoxifen or letrozole (3% each). Median duration of hormonal maintenance therapy was 33.3 months (range of 1-223), and follow-up was at least 2 years in those who had not recurred.

LGSC is a rare subtype that accounts for about 10% of serous carcinomas of the ovary or peritoneum. These cancers may arise de novo or after a diagnosis of serous borderline tumor. LGSC, relative to high-grade serous carcinoma (HGSC), is characterized by younger age at diagnosis, chemoresistance, prolonged overall survival, and aberrations within the MAP kinase signaling pathway, Dr. Gershenson said.

The findings are of interest as primary postoperative platinum-based chemotherapy remains the standard for women with newly diagnosed metastatic ovarian or peritoneal LGSC despite multiple reports indicating that this subtype is relatively chemoresistant. For example, in the AGO database of 5,114 patients accrued to four separate phase III trials, the response rate to chemotherapy in women with suboptimally debulked LGSC was significantly lower than in women with suboptimally debulked HGSC (23% vs. 90%), he said.

However, no prospective clinical trials have been conducted in the front line setting in women with LGSC, he noted.

Recent reports of promising activity of hormonal therapy in the recurrent setting have led to an increase in interest in integrating the modality into the primary treatment setting. One study showed a high frequency of ER and PR expression in LGSC, and another showed that hormonal therapy for recurrent LGSC was associated with an objective response rate of 9%, stable disease rate of 66% and median progression-free survival of 7.4 months.

“Some patients derived several years of benefit,” he said. “In addition, low-grade serous carcinoma bears a striking resemblance to luminal breast cancer in that women who are 35 years of age or younger appear to have a significantly worse prognosis.”

Some have concluded, based on these findings, that platinum-based chemotherapy is of no value in the frontline treatment of LGSC and should be abandoned, Dr. Gershenson said.

The current findings, though limited by factors such as their retrospective nature, missing data, a long study period, and possible referral bias suggest that hormonal maintenance therapy deserves a closer look, Dr. Gershenson said.

“The findings of this hypotheses-generating study are potentially practice changing and warrant further investigation using a prospective trial design,” he concluded.

Dr. Gershenson reported stock ownership in AbbVie, Biogen Idec, Celgene, GlaxoSmithKline, Johnson & Johnson, Merck, and Pfizer; consulting or advisory roles with Clovis Oncology, and patents with Elsevier and UpToDate.

[email protected]

CHICAGO – Hormonal maintenance therapy after primary treatment was associated with significantly prolonged progression-free survival when compared with surveillance in a retrospective study of women with stage II-IV low-grade serous carcinoma of the ovary or peritoneum.

The findings are “potentially practice-changing,” Dr. David Marc Gershenson of the University of Texas MD Anderson Cancer Center, Houston, said at the annual meeting of the American Society of Clinical Oncology.

©moodboard/Thinkstock

Of 204 women with newly diagnosed low-grade serous carcinoma (LGSC) who underwent primary cytoreductive surgery followed by platinum-based chemotherapy, 70 received hormonal maintenance therapy after completion of primary chemotherapy and 134 underwent surveillance. Median progression-free survival (PFS) was 64.9 vs. 27.3 months, respectively (33 months overall), Dr. Gershenson said.

“To date, 40% of the hormone maintenance therapy group has not relapsed, compared [with] only 12% in the surveillance group,” he said.

Median overall survival was not statistically different, but there was a trend toward an overall survival benefit in the hormonal maintenance therapy group (115.7 vs. 98.8 months). In a subset analysis in women who were clinically disease free at the completion of primary chemotherapy, the median PFS was 29.9 months in 121 women undergoing surveillance, vs. 81.1 months in 27 receiving hormone maintenance therapy. The mean overall survival was also statistically different in the subset analysis (106.8 vs. 191.3 months).

On multivariable analysis, four factors reached significance: hormone maintenance therapy vs. surveillance (hazard ratio, 0.23), peritoneum vs. ovary as primary site (HR, 0.45), no gross residual disease vs. gross residual disease (HR, 0.49),and persistent disease at completion of chemotherapy, vs. no evidence of disease (HR, 0.42).

Patients included in the study presented between 1981 and 2013. They had a median age of 47.6 years, about 3/4 had primary ovarian LGSC, and about 1/4 had primary peritoneal LGSC.

Patients in the hormonal therapy group were treated with letrozole (54%), tamoxifen (29%), anastrozole (3%), leuprolide acetate (7%), depot medroxyprogesterone acetate (1%), and leuprolide acetate + tamoxifen or letrozole (3% each). Median duration of hormonal maintenance therapy was 33.3 months (range of 1-223), and follow-up was at least 2 years in those who had not recurred.

LGSC is a rare subtype that accounts for about 10% of serous carcinomas of the ovary or peritoneum. These cancers may arise de novo or after a diagnosis of serous borderline tumor. LGSC, relative to high-grade serous carcinoma (HGSC), is characterized by younger age at diagnosis, chemoresistance, prolonged overall survival, and aberrations within the MAP kinase signaling pathway, Dr. Gershenson said.

The findings are of interest as primary postoperative platinum-based chemotherapy remains the standard for women with newly diagnosed metastatic ovarian or peritoneal LGSC despite multiple reports indicating that this subtype is relatively chemoresistant. For example, in the AGO database of 5,114 patients accrued to four separate phase III trials, the response rate to chemotherapy in women with suboptimally debulked LGSC was significantly lower than in women with suboptimally debulked HGSC (23% vs. 90%), he said.

However, no prospective clinical trials have been conducted in the front line setting in women with LGSC, he noted.

Recent reports of promising activity of hormonal therapy in the recurrent setting have led to an increase in interest in integrating the modality into the primary treatment setting. One study showed a high frequency of ER and PR expression in LGSC, and another showed that hormonal therapy for recurrent LGSC was associated with an objective response rate of 9%, stable disease rate of 66% and median progression-free survival of 7.4 months.

“Some patients derived several years of benefit,” he said. “In addition, low-grade serous carcinoma bears a striking resemblance to luminal breast cancer in that women who are 35 years of age or younger appear to have a significantly worse prognosis.”

Some have concluded, based on these findings, that platinum-based chemotherapy is of no value in the frontline treatment of LGSC and should be abandoned, Dr. Gershenson said.

The current findings, though limited by factors such as their retrospective nature, missing data, a long study period, and possible referral bias suggest that hormonal maintenance therapy deserves a closer look, Dr. Gershenson said.

“The findings of this hypotheses-generating study are potentially practice changing and warrant further investigation using a prospective trial design,” he concluded.

Dr. Gershenson reported stock ownership in AbbVie, Biogen Idec, Celgene, GlaxoSmithKline, Johnson & Johnson, Merck, and Pfizer; consulting or advisory roles with Clovis Oncology, and patents with Elsevier and UpToDate.

[email protected]

SAN DIEGO – It takes more than the usual 5 mg/kg of infliximab to heal perianal fistulas in some Crohn’s disease patients, according to a multicenter review of 117 cases.

The investigators aimed for trough levels of at least 10-20 mcg/mL, higher than the usual target of perhaps 7 mcg/mL or less. Doing so generally required 10 mg/kg every 8 weeks, but a few patients needed 10 mg/kg or even 15 mg/kg every 4 weeks. Fistulas healed in 63 (54%) patients and closed in 36 (31%).

Troughs of at least 10 mcg/mL and a history of dose escalation were both independent predictors of fistula healing, defined as the absence of drainage. Patients with fistula healing had significantly higher infliximab levels compared to those with active fistulas (18.5 vs. 6.5 mcg/mL; P less than .0001), and there was an incremental gain in healing with higher infliximab levels up to 50 mcg/mL. The association between infliximab levels and fistula healing had an area under the curve of 0.82 (P less than .0001) and the association with fistula closure was 0.69 (P = .014).

“Infliximab levels needed to achieve fistula healing were higher than what [has] been described for mucosal healing. Achieving higher infliximab levels in patients with Crohn’s disease and perianal fistulas may improve outcomes and should be considered in a treat-to-target strategy. At least 10-20 mcg/mL may be needed to achieve fistula healing in some patients,” concluded investigator Dr. Andres J. Yarur, a gastroenterologist at the Medical College of Wisconsin, Milwaukee.

“Obviously, in somebody with active perianal fistulas” at a trough of 30 mcg/mL, “it’s time to try something else, but I don’t give up on infliximab at a level of 7 mcg/mL, like a lot of people do. I’m kind of aggressive with these patients.” There wasn’t a formal assessment of adverse events, but “we have not really seen any side effects,” he said at the annual Digestive Disease Week meeting. One audience member remarked that the findings will likely change how he treats Crohn’s fistulas.

Dr. Yarur said he wasn’t surprised by the findings, “but I have more reassurance now” that aggressive dosing is the way to go for aggressive Crohn’s.

The patients were an average of 39 years old, with a mean disease duration of 12 years; about half were women. They were on infliximab for a median of 19 months. Infliximab antibodies dropped the likelihood of healing (odds ratio, 0.04; 95% confidence interval, 0.005-0.3; P less than .001) and closure (OR 0.038; 95% CI, 0.005-0.3; P less than .0001). About two-thirds of the patients were on concomitant immunomodulators, but they did not increase the odds of healing (OR 1.7; 95% CI, 0.8-3.7; P = .157).

“We usually start at a standard dose of 5 mg/kg, and then start checking troughs at week 14, before the first maintenance dose, and adjust” upward to hit the trough target. However, dosing also depends on “how much I think the patient needs. I don’t think we should standardize trough levels,” Dr. Yarur said. The team checks levels with the homogeneous mobility-shift assay from Prometheus Laboratories. “The type of assay you use is very important,” because interpretation of the results varies from one to the next.

De-escalation is on a case-by-case basis. “I would be very careful de-escalating somebody [who] has very aggressive disease. Many times patients don’t want to go down. They say ‘I feel good doc. I have no side effects. Leave me on my dose,’ ” he said.

There was a lack of cross-sectional imaging in the study; the investigators couldn’t distinguish simple fistulas from complex ones in their review.

Dr. Yarur had no disclosures. There was no industry funding for the work.

[email protected]

SAN DIEGO – It takes more than the usual 5 mg/kg of infliximab to heal perianal fistulas in some Crohn’s disease patients, according to a multicenter review of 117 cases.

The investigators aimed for trough levels of at least 10-20 mcg/mL, higher than the usual target of perhaps 7 mcg/mL or less. Doing so generally required 10 mg/kg every 8 weeks, but a few patients needed 10 mg/kg or even 15 mg/kg every 4 weeks. Fistulas healed in 63 (54%) patients and closed in 36 (31%).

Troughs of at least 10 mcg/mL and a history of dose escalation were both independent predictors of fistula healing, defined as the absence of drainage. Patients with fistula healing had significantly higher infliximab levels compared to those with active fistulas (18.5 vs. 6.5 mcg/mL; P less than .0001), and there was an incremental gain in healing with higher infliximab levels up to 50 mcg/mL. The association between infliximab levels and fistula healing had an area under the curve of 0.82 (P less than .0001) and the association with fistula closure was 0.69 (P = .014).

“Infliximab levels needed to achieve fistula healing were higher than what [has] been described for mucosal healing. Achieving higher infliximab levels in patients with Crohn’s disease and perianal fistulas may improve outcomes and should be considered in a treat-to-target strategy. At least 10-20 mcg/mL may be needed to achieve fistula healing in some patients,” concluded investigator Dr. Andres J. Yarur, a gastroenterologist at the Medical College of Wisconsin, Milwaukee.

“Obviously, in somebody with active perianal fistulas” at a trough of 30 mcg/mL, “it’s time to try something else, but I don’t give up on infliximab at a level of 7 mcg/mL, like a lot of people do. I’m kind of aggressive with these patients.” There wasn’t a formal assessment of adverse events, but “we have not really seen any side effects,” he said at the annual Digestive Disease Week meeting. One audience member remarked that the findings will likely change how he treats Crohn’s fistulas.

Dr. Yarur said he wasn’t surprised by the findings, “but I have more reassurance now” that aggressive dosing is the way to go for aggressive Crohn’s.

The patients were an average of 39 years old, with a mean disease duration of 12 years; about half were women. They were on infliximab for a median of 19 months. Infliximab antibodies dropped the likelihood of healing (odds ratio, 0.04; 95% confidence interval, 0.005-0.3; P less than .001) and closure (OR 0.038; 95% CI, 0.005-0.3; P less than .0001). About two-thirds of the patients were on concomitant immunomodulators, but they did not increase the odds of healing (OR 1.7; 95% CI, 0.8-3.7; P = .157).

“We usually start at a standard dose of 5 mg/kg, and then start checking troughs at week 14, before the first maintenance dose, and adjust” upward to hit the trough target. However, dosing also depends on “how much I think the patient needs. I don’t think we should standardize trough levels,” Dr. Yarur said. The team checks levels with the homogeneous mobility-shift assay from Prometheus Laboratories. “The type of assay you use is very important,” because interpretation of the results varies from one to the next.

De-escalation is on a case-by-case basis. “I would be very careful de-escalating somebody [who] has very aggressive disease. Many times patients don’t want to go down. They say ‘I feel good doc. I have no side effects. Leave me on my dose,’ ” he said.

There was a lack of cross-sectional imaging in the study; the investigators couldn’t distinguish simple fistulas from complex ones in their review.

Dr. Yarur had no disclosures. There was no industry funding for the work.

[email protected]

SAN DIEGO – It takes more than the usual 5 mg/kg of infliximab to heal perianal fistulas in some Crohn’s disease patients, according to a multicenter review of 117 cases.

The investigators aimed for trough levels of at least 10-20 mcg/mL, higher than the usual target of perhaps 7 mcg/mL or less. Doing so generally required 10 mg/kg every 8 weeks, but a few patients needed 10 mg/kg or even 15 mg/kg every 4 weeks. Fistulas healed in 63 (54%) patients and closed in 36 (31%).

Troughs of at least 10 mcg/mL and a history of dose escalation were both independent predictors of fistula healing, defined as the absence of drainage. Patients with fistula healing had significantly higher infliximab levels compared to those with active fistulas (18.5 vs. 6.5 mcg/mL; P less than .0001), and there was an incremental gain in healing with higher infliximab levels up to 50 mcg/mL. The association between infliximab levels and fistula healing had an area under the curve of 0.82 (P less than .0001) and the association with fistula closure was 0.69 (P = .014).

“Infliximab levels needed to achieve fistula healing were higher than what [has] been described for mucosal healing. Achieving higher infliximab levels in patients with Crohn’s disease and perianal fistulas may improve outcomes and should be considered in a treat-to-target strategy. At least 10-20 mcg/mL may be needed to achieve fistula healing in some patients,” concluded investigator Dr. Andres J. Yarur, a gastroenterologist at the Medical College of Wisconsin, Milwaukee.

“Obviously, in somebody with active perianal fistulas” at a trough of 30 mcg/mL, “it’s time to try something else, but I don’t give up on infliximab at a level of 7 mcg/mL, like a lot of people do. I’m kind of aggressive with these patients.” There wasn’t a formal assessment of adverse events, but “we have not really seen any side effects,” he said at the annual Digestive Disease Week meeting. One audience member remarked that the findings will likely change how he treats Crohn’s fistulas.

Dr. Yarur said he wasn’t surprised by the findings, “but I have more reassurance now” that aggressive dosing is the way to go for aggressive Crohn’s.

The patients were an average of 39 years old, with a mean disease duration of 12 years; about half were women. They were on infliximab for a median of 19 months. Infliximab antibodies dropped the likelihood of healing (odds ratio, 0.04; 95% confidence interval, 0.005-0.3; P less than .001) and closure (OR 0.038; 95% CI, 0.005-0.3; P less than .0001). About two-thirds of the patients were on concomitant immunomodulators, but they did not increase the odds of healing (OR 1.7; 95% CI, 0.8-3.7; P = .157).

“We usually start at a standard dose of 5 mg/kg, and then start checking troughs at week 14, before the first maintenance dose, and adjust” upward to hit the trough target. However, dosing also depends on “how much I think the patient needs. I don’t think we should standardize trough levels,” Dr. Yarur said. The team checks levels with the homogeneous mobility-shift assay from Prometheus Laboratories. “The type of assay you use is very important,” because interpretation of the results varies from one to the next.

De-escalation is on a case-by-case basis. “I would be very careful de-escalating somebody [who] has very aggressive disease. Many times patients don’t want to go down. They say ‘I feel good doc. I have no side effects. Leave me on my dose,’ ” he said.

There was a lack of cross-sectional imaging in the study; the investigators couldn’t distinguish simple fistulas from complex ones in their review.

Dr. Yarur had no disclosures. There was no industry funding for the work.

[email protected]

Dr. Catalina Matiz and David Ginsberg discuss the diagnosis and treatment of phytophotodermatitis. 

Phytophotodermatitis

The term phytophotodermatitis was first used in 1942 by Robert Klaber, but knowledge of this condition dates back as far as 1500 BC.^1,2 It is a nonimmune reaction caused by exposure to chemicals called furocoumarins and psoralens, found in a variety of plants and fruits such as lemons, limes, celery, parsnips, figs, carrots, dill, mustard, and rindweed.^1,2

When these chemicals get in contact with the skin and are then exposed to UV light from the sun, a phototoxic reaction occurs. This reaction leads to cell membrane damage and cell death, which after the acute insult has resolved results in postinflammatory hyperpigmentation that may last months and is not responsive to bleaching skin treatments.^1,2

Studies have shown that long-wave length UV radiation is the best trigger to induce this irritating reaction.² There have been rare reports of photosensitivity reactions due to ingestion of large quantities of plants containing furocoumarins and psoralens.³ Plants known to cause phytophotodermatitis are found in almost every country across the globe, and exposure does not have to just be to the fruit, but contact with the leaves or sap also can induce the reaction.^2-4 Typically after contact with the plant, followed by sun exposure, erythema will begin within 1 to 2 days, followed by bullae and vesicles, which tend to coalesce and burst over the following days. The patient is left with hyperpigmentation.^2-4

Differential diagnosis

This condition can be difficult to diagnose and is often confused with type IV hypersensitivity reaction, eczema, herpes simplex virus (HSV), and burns, potentially leading to suspicion of child abuse.^4,5 A thorough and detailed history is essential to correctly making the diagnosis and ruling out other potential causes.

Because the cause in children is often due to exposure to certain plants, unsupervised time outdoors leading to a rash may lead parents to think of poison ivy or poison oak, which are type IV hypersensitivity reactions.^4,5 Although the rash may appear in a similar time course, the evolution to hyperpigmented patches is a distinguishing feature that helps to make the diagnosis of phytophotodermatitis.⁴ The postinflammatory hyperpigmentation, along with the clinical course, also can help differentiate it from burns and HSV infections, which it sometimes is mistaken for due to the bullous and vesicular lesions.^4,5

Treatment

Counseling for avoidance of the exposure in the future is the most important aspect of treatment in order to prevent recurrences. Depending on the extent of the inflammatory reaction prior to the hyperpigmentation, no treatment may be needed for mild cases, but for more extreme bullous reactions, systemic steroids may be used.⁴

Topical corticosteroids and sun avoidance are the mainstays for treating mild to moderate cases. UV avoidance can be difficult because the long wave-length UV radiation that causes this reaction is not blocked by windows, and therefore it is important to keep affected areas covered even while indoors during daylight hours.⁴

There is no effective treatment for the hyperpigmented lesions. Patients need to be informed that this may resolve in months.

References

1. Br J Dermatol. 1942;54(7):193-211.
2. Clin Dermatol. 1986 Apr-Jun;4(2):102-21.
3. Arch Dermatol. 1990 Oct;126(10):1334-6.
4. J Am Acad Dermatol. 2007 Nov;57(5 Suppl):S88-91.
5. Arch Fam Med. 2000 Jan;9(1):88.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego, and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

Dr. Catalina Matiz and David Ginsberg discuss the diagnosis and treatment of phytophotodermatitis. 

Phytophotodermatitis

The term phytophotodermatitis was first used in 1942 by Robert Klaber, but knowledge of this condition dates back as far as 1500 BC.^1,2 It is a nonimmune reaction caused by exposure to chemicals called furocoumarins and psoralens, found in a variety of plants and fruits such as lemons, limes, celery, parsnips, figs, carrots, dill, mustard, and rindweed.^1,2

When these chemicals get in contact with the skin and are then exposed to UV light from the sun, a phototoxic reaction occurs. This reaction leads to cell membrane damage and cell death, which after the acute insult has resolved results in postinflammatory hyperpigmentation that may last months and is not responsive to bleaching skin treatments.^1,2

Studies have shown that long-wave length UV radiation is the best trigger to induce this irritating reaction.² There have been rare reports of photosensitivity reactions due to ingestion of large quantities of plants containing furocoumarins and psoralens.³ Plants known to cause phytophotodermatitis are found in almost every country across the globe, and exposure does not have to just be to the fruit, but contact with the leaves or sap also can induce the reaction.^2-4 Typically after contact with the plant, followed by sun exposure, erythema will begin within 1 to 2 days, followed by bullae and vesicles, which tend to coalesce and burst over the following days. The patient is left with hyperpigmentation.^2-4

Differential diagnosis

This condition can be difficult to diagnose and is often confused with type IV hypersensitivity reaction, eczema, herpes simplex virus (HSV), and burns, potentially leading to suspicion of child abuse.^4,5 A thorough and detailed history is essential to correctly making the diagnosis and ruling out other potential causes.

Because the cause in children is often due to exposure to certain plants, unsupervised time outdoors leading to a rash may lead parents to think of poison ivy or poison oak, which are type IV hypersensitivity reactions.^4,5 Although the rash may appear in a similar time course, the evolution to hyperpigmented patches is a distinguishing feature that helps to make the diagnosis of phytophotodermatitis.⁴ The postinflammatory hyperpigmentation, along with the clinical course, also can help differentiate it from burns and HSV infections, which it sometimes is mistaken for due to the bullous and vesicular lesions.^4,5

Treatment

Counseling for avoidance of the exposure in the future is the most important aspect of treatment in order to prevent recurrences. Depending on the extent of the inflammatory reaction prior to the hyperpigmentation, no treatment may be needed for mild cases, but for more extreme bullous reactions, systemic steroids may be used.⁴

Topical corticosteroids and sun avoidance are the mainstays for treating mild to moderate cases. UV avoidance can be difficult because the long wave-length UV radiation that causes this reaction is not blocked by windows, and therefore it is important to keep affected areas covered even while indoors during daylight hours.⁴

There is no effective treatment for the hyperpigmented lesions. Patients need to be informed that this may resolve in months.

References

1. Br J Dermatol. 1942;54(7):193-211.
2. Clin Dermatol. 1986 Apr-Jun;4(2):102-21.
3. Arch Dermatol. 1990 Oct;126(10):1334-6.
4. J Am Acad Dermatol. 2007 Nov;57(5 Suppl):S88-91.
5. Arch Fam Med. 2000 Jan;9(1):88.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego, and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

Dr. Catalina Matiz and David Ginsberg discuss the diagnosis and treatment of phytophotodermatitis. 

Phytophotodermatitis

The term phytophotodermatitis was first used in 1942 by Robert Klaber, but knowledge of this condition dates back as far as 1500 BC.^1,2 It is a nonimmune reaction caused by exposure to chemicals called furocoumarins and psoralens, found in a variety of plants and fruits such as lemons, limes, celery, parsnips, figs, carrots, dill, mustard, and rindweed.^1,2

When these chemicals get in contact with the skin and are then exposed to UV light from the sun, a phototoxic reaction occurs. This reaction leads to cell membrane damage and cell death, which after the acute insult has resolved results in postinflammatory hyperpigmentation that may last months and is not responsive to bleaching skin treatments.^1,2

Studies have shown that long-wave length UV radiation is the best trigger to induce this irritating reaction.² There have been rare reports of photosensitivity reactions due to ingestion of large quantities of plants containing furocoumarins and psoralens.³ Plants known to cause phytophotodermatitis are found in almost every country across the globe, and exposure does not have to just be to the fruit, but contact with the leaves or sap also can induce the reaction.^2-4 Typically after contact with the plant, followed by sun exposure, erythema will begin within 1 to 2 days, followed by bullae and vesicles, which tend to coalesce and burst over the following days. The patient is left with hyperpigmentation.^2-4

Differential diagnosis

This condition can be difficult to diagnose and is often confused with type IV hypersensitivity reaction, eczema, herpes simplex virus (HSV), and burns, potentially leading to suspicion of child abuse.^4,5 A thorough and detailed history is essential to correctly making the diagnosis and ruling out other potential causes.

Because the cause in children is often due to exposure to certain plants, unsupervised time outdoors leading to a rash may lead parents to think of poison ivy or poison oak, which are type IV hypersensitivity reactions.^4,5 Although the rash may appear in a similar time course, the evolution to hyperpigmented patches is a distinguishing feature that helps to make the diagnosis of phytophotodermatitis.⁴ The postinflammatory hyperpigmentation, along with the clinical course, also can help differentiate it from burns and HSV infections, which it sometimes is mistaken for due to the bullous and vesicular lesions.^4,5

Treatment

Counseling for avoidance of the exposure in the future is the most important aspect of treatment in order to prevent recurrences. Depending on the extent of the inflammatory reaction prior to the hyperpigmentation, no treatment may be needed for mild cases, but for more extreme bullous reactions, systemic steroids may be used.⁴

Topical corticosteroids and sun avoidance are the mainstays for treating mild to moderate cases. UV avoidance can be difficult because the long wave-length UV radiation that causes this reaction is not blocked by windows, and therefore it is important to keep affected areas covered even while indoors during daylight hours.⁴

There is no effective treatment for the hyperpigmented lesions. Patients need to be informed that this may resolve in months.

References

1. Br J Dermatol. 1942;54(7):193-211.
2. Clin Dermatol. 1986 Apr-Jun;4(2):102-21.
3. Arch Dermatol. 1990 Oct;126(10):1334-6.
4. J Am Acad Dermatol. 2007 Nov;57(5 Suppl):S88-91.
5. Arch Fam Med. 2000 Jan;9(1):88.

Dr. Matiz is assistant professor of dermatology at Rady Children’s Hospital San Diego–University of California, San Diego, and Mr. Ginsberg is a research associate at the hospital. Dr. Matiz and Mr. Ginsberg said they have no relevant financial disclosures.

NEW ORLEANS – Fewer than one-third of patients with diabetes being cared for by a public hospital system underwent screening for retinopathy within the past year, judging from the results from a survey of administrative data.

“Diabetic retinopathy is a major cause of vision loss in the United States,” researchers led by Dr. David C. Ziemer wrote in an abstract presented during a poster session at the annual scientific sessions of the American Diabetes Association.

“In 2011, the age-adjusted percentage of adults with diagnosed diabetes reporting visual impairment was 17.6%. This is a pressing issue as the number of Americans with diabetic retinopathy is expected to double from 7.7 million in 2010 to 15.6 million in 2050.”

In an effort to plan for better diabetic retinopathy screening, Dr. Ziemer and his associates analyzed 2014 administrative data from 19,361 patients with diabetes who attended one of several clinics operated by the Atlanta-based Grady Health System. Diabetic retinopathy was considered complete if ophthalmology clinic, optometry, or retinal photograph visit was attended. The researchers also surveyed a convenience sample of 80 patients about their diabetic retinopathy screening in the past year.

The mean age of patients was 57 years, their mean hemoglobin A_1c level was 7.8%, 59% were female, and 83% were African-American. Of the 19,361 patients, 5,595 (29%) underwent diabetic retinopathy screening and 13,766 (71%) did not. The unscreened had a mean of 1 clinic visit for diabetes care, compared with a mean of 3.1 for those who underwent screening (P less than .0005). In the analysis of administrative data, Dr. Ziemer, of the division of endocrinology at Emory University, Atlanta, reported that 29% of patients underwent diabetic retinopathy screening in the past year, with variation by care site that ranged from 5% to 66%, and 5,000 had no diabetes continuity care visit.

Factors associated with increased diabetic retinopathy screening were treatment in a diabetes clinic (odds ratio, 2.8), treatment in a primary care clinic (OR, 2.1), and being older (OR, 1.03/year; P less than .001 for all associations), according to a multivariable analysis. Factors associated with decreased diabetic retinopathy screening were Hispanic ethnicity (OR, 0.7) and having a mental health diagnosis (OR, .8; P less than .001 for both associations). The researchers also found that having an in-clinic eye screening doubled the proportion of diabetic retinopathy screenings (48% vs. 22%) and decreased the number of screenings done in an outside clinic (45% vs. 95%).

Of the 80 patients who completed the survey, 68% reported that they underwent diabetic retinopathy screening within the past year, which was in contrast to the 29% reported by administrative data. In addition, 50% of survey respondents who did not undergo diabetic retinopathy screening reported that they received a referral, yet more than 40% failed to honor eye appointments. “The first barrier to address is people who don’t keep appointments,” Dr. Ziemer said in an interview. “Getting people in care is one issue. Having the capacity is another. That’s a real problem.”

The study was supported by the American Diabetes Association. Dr. Ziemer reported having no financial disclosures.

[email protected]

NEW ORLEANS – Fewer than one-third of patients with diabetes being cared for by a public hospital system underwent screening for retinopathy within the past year, judging from the results from a survey of administrative data.

“Diabetic retinopathy is a major cause of vision loss in the United States,” researchers led by Dr. David C. Ziemer wrote in an abstract presented during a poster session at the annual scientific sessions of the American Diabetes Association.

“In 2011, the age-adjusted percentage of adults with diagnosed diabetes reporting visual impairment was 17.6%. This is a pressing issue as the number of Americans with diabetic retinopathy is expected to double from 7.7 million in 2010 to 15.6 million in 2050.”

In an effort to plan for better diabetic retinopathy screening, Dr. Ziemer and his associates analyzed 2014 administrative data from 19,361 patients with diabetes who attended one of several clinics operated by the Atlanta-based Grady Health System. Diabetic retinopathy was considered complete if ophthalmology clinic, optometry, or retinal photograph visit was attended. The researchers also surveyed a convenience sample of 80 patients about their diabetic retinopathy screening in the past year.

The mean age of patients was 57 years, their mean hemoglobin A_1c level was 7.8%, 59% were female, and 83% were African-American. Of the 19,361 patients, 5,595 (29%) underwent diabetic retinopathy screening and 13,766 (71%) did not. The unscreened had a mean of 1 clinic visit for diabetes care, compared with a mean of 3.1 for those who underwent screening (P less than .0005). In the analysis of administrative data, Dr. Ziemer, of the division of endocrinology at Emory University, Atlanta, reported that 29% of patients underwent diabetic retinopathy screening in the past year, with variation by care site that ranged from 5% to 66%, and 5,000 had no diabetes continuity care visit.

Factors associated with increased diabetic retinopathy screening were treatment in a diabetes clinic (odds ratio, 2.8), treatment in a primary care clinic (OR, 2.1), and being older (OR, 1.03/year; P less than .001 for all associations), according to a multivariable analysis. Factors associated with decreased diabetic retinopathy screening were Hispanic ethnicity (OR, 0.7) and having a mental health diagnosis (OR, .8; P less than .001 for both associations). The researchers also found that having an in-clinic eye screening doubled the proportion of diabetic retinopathy screenings (48% vs. 22%) and decreased the number of screenings done in an outside clinic (45% vs. 95%).

Of the 80 patients who completed the survey, 68% reported that they underwent diabetic retinopathy screening within the past year, which was in contrast to the 29% reported by administrative data. In addition, 50% of survey respondents who did not undergo diabetic retinopathy screening reported that they received a referral, yet more than 40% failed to honor eye appointments. “The first barrier to address is people who don’t keep appointments,” Dr. Ziemer said in an interview. “Getting people in care is one issue. Having the capacity is another. That’s a real problem.”

The study was supported by the American Diabetes Association. Dr. Ziemer reported having no financial disclosures.

[email protected]

NEW ORLEANS – Fewer than one-third of patients with diabetes being cared for by a public hospital system underwent screening for retinopathy within the past year, judging from the results from a survey of administrative data.

“Diabetic retinopathy is a major cause of vision loss in the United States,” researchers led by Dr. David C. Ziemer wrote in an abstract presented during a poster session at the annual scientific sessions of the American Diabetes Association.

“In 2011, the age-adjusted percentage of adults with diagnosed diabetes reporting visual impairment was 17.6%. This is a pressing issue as the number of Americans with diabetic retinopathy is expected to double from 7.7 million in 2010 to 15.6 million in 2050.”

In an effort to plan for better diabetic retinopathy screening, Dr. Ziemer and his associates analyzed 2014 administrative data from 19,361 patients with diabetes who attended one of several clinics operated by the Atlanta-based Grady Health System. Diabetic retinopathy was considered complete if ophthalmology clinic, optometry, or retinal photograph visit was attended. The researchers also surveyed a convenience sample of 80 patients about their diabetic retinopathy screening in the past year.

The mean age of patients was 57 years, their mean hemoglobin A_1c level was 7.8%, 59% were female, and 83% were African-American. Of the 19,361 patients, 5,595 (29%) underwent diabetic retinopathy screening and 13,766 (71%) did not. The unscreened had a mean of 1 clinic visit for diabetes care, compared with a mean of 3.1 for those who underwent screening (P less than .0005). In the analysis of administrative data, Dr. Ziemer, of the division of endocrinology at Emory University, Atlanta, reported that 29% of patients underwent diabetic retinopathy screening in the past year, with variation by care site that ranged from 5% to 66%, and 5,000 had no diabetes continuity care visit.

Factors associated with increased diabetic retinopathy screening were treatment in a diabetes clinic (odds ratio, 2.8), treatment in a primary care clinic (OR, 2.1), and being older (OR, 1.03/year; P less than .001 for all associations), according to a multivariable analysis. Factors associated with decreased diabetic retinopathy screening were Hispanic ethnicity (OR, 0.7) and having a mental health diagnosis (OR, .8; P less than .001 for both associations). The researchers also found that having an in-clinic eye screening doubled the proportion of diabetic retinopathy screenings (48% vs. 22%) and decreased the number of screenings done in an outside clinic (45% vs. 95%).

Of the 80 patients who completed the survey, 68% reported that they underwent diabetic retinopathy screening within the past year, which was in contrast to the 29% reported by administrative data. In addition, 50% of survey respondents who did not undergo diabetic retinopathy screening reported that they received a referral, yet more than 40% failed to honor eye appointments. “The first barrier to address is people who don’t keep appointments,” Dr. Ziemer said in an interview. “Getting people in care is one issue. Having the capacity is another. That’s a real problem.”

The study was supported by the American Diabetes Association. Dr. Ziemer reported having no financial disclosures.

[email protected]

VANCOUVER – The antioxidant edaravone was associated with less deterioration in functional rating and quality of life scales when started early in the course of amyotrophic lateral sclerosis (ALS), based on results from a set of trials conducted in Japan and reported at the annual meeting of the American Academy of Neurology.

Edaravone is thought to confer neuroprotection in part through its free radical–scavenging activity and first garnered interest for the treatment of acute ischemic stroke, according to presenting author Dr. Joseph M. Palumbo, vice president and head of Clinical Research at Mitsubishi Tanabe Pharma Development America, the maker of edaravone. It is now approved in several countries for that indication.

Susan London/Frontline Medical News

In a pivotal randomized phase III trial, Dr. Palumbo and his colleagues studied 137 patients who had definite or probable ALS, were less than 2 years out from symptom onset, had normal respiratory function, and were able to perform most activities of daily living. All patients received standard of care, usually including riluzole (Rilutek), plus either edaravone (MCI-186) or placebo.

After 24 weeks of treatment, compared with placebo, edaravone was associated with a smaller decline in scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) (–5.01 vs. –7.50; difference between groups, 2.49; P = .0013), according to data reported in a poster session at the meeting.

Significant benefit was seen on the limb and bulbar subscales, and there was a trend favoring edaravone on the respiratory subscale. Additionally, patients given edaravone had comparatively less deterioration in quality of life as assessed with the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) (P = .03). Grip strength did not differ between groups, and there were no deaths in either group.

“We are not aware of any other positive phase III study in maybe a generation, since riluzole, in ALS. So we are showing this data and we are hopeful that people are as excited as we are,” Dr. Palumbo said in an interview.

In the area of safety, edaravone and placebo did not differ significantly with respect to the rate of adverse events, with contusion, dysphagia, and constipation predominating. The most common serious adverse event was dysphagia, seen in 12% of each group.

The trial’s findings led to approval of edaravone for treatment of ALS in Japan, where it is marketed as Radicut. Additionally, the U.S. Food and Drug Administration (FDA) granted edaravone orphan drug designation for ALS but has not approved it for this indication.

An additional 24-week open-label extension study among 123 patients from the trial, in which all received the drug regardless of their initially assigned treatment, showed that the benefit of edaravone was durable. Patients who continued treatment with the drug had less of a decline from baseline in ALSFRS-R score than did peers switched to the drug from placebo (difference between groups, 4.17; P = .004), according to data reported in another poster. Also, the former had a lower risk of death (P = .019) and less decline in lung function. Meanwhile, the drug’s safety profile remained good.

The researchers are preparing their findings for journal submission and are revisiting the drug’s regulatory status in the United States, according to Dr. Palumbo. “We’re talking to the FDA now. We’ve got our fingers crossed.”

There is no compelling reason to think that the drug’s efficacy in the U.S. population would differ from that in the Japanese population, but that will ultimately be an issue for regulators to decide, he said.

It is difficult to compare edaravone with other ALS treatment options, as all patients in the trial concomitantly received standard of care, Dr. Palumbo explained. “We can only speak about standard of care, and we think that we’ve improved on standard of care here,” he maintained.

The initial phase III trial of edaravone in ALS, which enrolled a population having a wider range of disease severity, failed to meet its primary endpoint of improvement in ALSFRS-R score (Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:610-7). An extension study in 181 patients, also reported in a poster at the meeting, supported post hoc findings hinting that the timing of drug initiation was important.

“We learned a tremendous amount in that study about who the patients were who would ultimately benefit,” Dr. Palumbo commented. “We had a number of hypotheses. One hypothesis was that if we found patients who in fact were still functional at baseline and who really had the diagnosis – they had either definite or probable ALS – and still had very good respiratory function, that we would likely find a signal there.”

Rounding out the set of trials was a small randomized placebo-controlled trial among 25 patients with more advanced ALS, done at the request of Japanese health authorities. Results showed that edaravone was safe in this population but had no clear benefit.

Dr. Palumbo disclosed that he is an employee of Mitsubishi Tanabe Pharma Development America, Inc. The trials were sponsored by Mitsubishi Tanabe Pharma Corporation.

VANCOUVER – The antioxidant edaravone was associated with less deterioration in functional rating and quality of life scales when started early in the course of amyotrophic lateral sclerosis (ALS), based on results from a set of trials conducted in Japan and reported at the annual meeting of the American Academy of Neurology.

Edaravone is thought to confer neuroprotection in part through its free radical–scavenging activity and first garnered interest for the treatment of acute ischemic stroke, according to presenting author Dr. Joseph M. Palumbo, vice president and head of Clinical Research at Mitsubishi Tanabe Pharma Development America, the maker of edaravone. It is now approved in several countries for that indication.

Susan London/Frontline Medical News

In a pivotal randomized phase III trial, Dr. Palumbo and his colleagues studied 137 patients who had definite or probable ALS, were less than 2 years out from symptom onset, had normal respiratory function, and were able to perform most activities of daily living. All patients received standard of care, usually including riluzole (Rilutek), plus either edaravone (MCI-186) or placebo.

After 24 weeks of treatment, compared with placebo, edaravone was associated with a smaller decline in scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) (–5.01 vs. –7.50; difference between groups, 2.49; P = .0013), according to data reported in a poster session at the meeting.

Significant benefit was seen on the limb and bulbar subscales, and there was a trend favoring edaravone on the respiratory subscale. Additionally, patients given edaravone had comparatively less deterioration in quality of life as assessed with the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) (P = .03). Grip strength did not differ between groups, and there were no deaths in either group.

“We are not aware of any other positive phase III study in maybe a generation, since riluzole, in ALS. So we are showing this data and we are hopeful that people are as excited as we are,” Dr. Palumbo said in an interview.

In the area of safety, edaravone and placebo did not differ significantly with respect to the rate of adverse events, with contusion, dysphagia, and constipation predominating. The most common serious adverse event was dysphagia, seen in 12% of each group.

The trial’s findings led to approval of edaravone for treatment of ALS in Japan, where it is marketed as Radicut. Additionally, the U.S. Food and Drug Administration (FDA) granted edaravone orphan drug designation for ALS but has not approved it for this indication.

An additional 24-week open-label extension study among 123 patients from the trial, in which all received the drug regardless of their initially assigned treatment, showed that the benefit of edaravone was durable. Patients who continued treatment with the drug had less of a decline from baseline in ALSFRS-R score than did peers switched to the drug from placebo (difference between groups, 4.17; P = .004), according to data reported in another poster. Also, the former had a lower risk of death (P = .019) and less decline in lung function. Meanwhile, the drug’s safety profile remained good.

The researchers are preparing their findings for journal submission and are revisiting the drug’s regulatory status in the United States, according to Dr. Palumbo. “We’re talking to the FDA now. We’ve got our fingers crossed.”

There is no compelling reason to think that the drug’s efficacy in the U.S. population would differ from that in the Japanese population, but that will ultimately be an issue for regulators to decide, he said.

It is difficult to compare edaravone with other ALS treatment options, as all patients in the trial concomitantly received standard of care, Dr. Palumbo explained. “We can only speak about standard of care, and we think that we’ve improved on standard of care here,” he maintained.

The initial phase III trial of edaravone in ALS, which enrolled a population having a wider range of disease severity, failed to meet its primary endpoint of improvement in ALSFRS-R score (Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:610-7). An extension study in 181 patients, also reported in a poster at the meeting, supported post hoc findings hinting that the timing of drug initiation was important.

“We learned a tremendous amount in that study about who the patients were who would ultimately benefit,” Dr. Palumbo commented. “We had a number of hypotheses. One hypothesis was that if we found patients who in fact were still functional at baseline and who really had the diagnosis – they had either definite or probable ALS – and still had very good respiratory function, that we would likely find a signal there.”

Rounding out the set of trials was a small randomized placebo-controlled trial among 25 patients with more advanced ALS, done at the request of Japanese health authorities. Results showed that edaravone was safe in this population but had no clear benefit.

Dr. Palumbo disclosed that he is an employee of Mitsubishi Tanabe Pharma Development America, Inc. The trials were sponsored by Mitsubishi Tanabe Pharma Corporation.

VANCOUVER – The antioxidant edaravone was associated with less deterioration in functional rating and quality of life scales when started early in the course of amyotrophic lateral sclerosis (ALS), based on results from a set of trials conducted in Japan and reported at the annual meeting of the American Academy of Neurology.

Edaravone is thought to confer neuroprotection in part through its free radical–scavenging activity and first garnered interest for the treatment of acute ischemic stroke, according to presenting author Dr. Joseph M. Palumbo, vice president and head of Clinical Research at Mitsubishi Tanabe Pharma Development America, the maker of edaravone. It is now approved in several countries for that indication.

Susan London/Frontline Medical News

In a pivotal randomized phase III trial, Dr. Palumbo and his colleagues studied 137 patients who had definite or probable ALS, were less than 2 years out from symptom onset, had normal respiratory function, and were able to perform most activities of daily living. All patients received standard of care, usually including riluzole (Rilutek), plus either edaravone (MCI-186) or placebo.

After 24 weeks of treatment, compared with placebo, edaravone was associated with a smaller decline in scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) (–5.01 vs. –7.50; difference between groups, 2.49; P = .0013), according to data reported in a poster session at the meeting.

Significant benefit was seen on the limb and bulbar subscales, and there was a trend favoring edaravone on the respiratory subscale. Additionally, patients given edaravone had comparatively less deterioration in quality of life as assessed with the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) (P = .03). Grip strength did not differ between groups, and there were no deaths in either group.

“We are not aware of any other positive phase III study in maybe a generation, since riluzole, in ALS. So we are showing this data and we are hopeful that people are as excited as we are,” Dr. Palumbo said in an interview.

In the area of safety, edaravone and placebo did not differ significantly with respect to the rate of adverse events, with contusion, dysphagia, and constipation predominating. The most common serious adverse event was dysphagia, seen in 12% of each group.

The trial’s findings led to approval of edaravone for treatment of ALS in Japan, where it is marketed as Radicut. Additionally, the U.S. Food and Drug Administration (FDA) granted edaravone orphan drug designation for ALS but has not approved it for this indication.

An additional 24-week open-label extension study among 123 patients from the trial, in which all received the drug regardless of their initially assigned treatment, showed that the benefit of edaravone was durable. Patients who continued treatment with the drug had less of a decline from baseline in ALSFRS-R score than did peers switched to the drug from placebo (difference between groups, 4.17; P = .004), according to data reported in another poster. Also, the former had a lower risk of death (P = .019) and less decline in lung function. Meanwhile, the drug’s safety profile remained good.

The researchers are preparing their findings for journal submission and are revisiting the drug’s regulatory status in the United States, according to Dr. Palumbo. “We’re talking to the FDA now. We’ve got our fingers crossed.”

There is no compelling reason to think that the drug’s efficacy in the U.S. population would differ from that in the Japanese population, but that will ultimately be an issue for regulators to decide, he said.

It is difficult to compare edaravone with other ALS treatment options, as all patients in the trial concomitantly received standard of care, Dr. Palumbo explained. “We can only speak about standard of care, and we think that we’ve improved on standard of care here,” he maintained.

The initial phase III trial of edaravone in ALS, which enrolled a population having a wider range of disease severity, failed to meet its primary endpoint of improvement in ALSFRS-R score (Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:610-7). An extension study in 181 patients, also reported in a poster at the meeting, supported post hoc findings hinting that the timing of drug initiation was important.

“We learned a tremendous amount in that study about who the patients were who would ultimately benefit,” Dr. Palumbo commented. “We had a number of hypotheses. One hypothesis was that if we found patients who in fact were still functional at baseline and who really had the diagnosis – they had either definite or probable ALS – and still had very good respiratory function, that we would likely find a signal there.”

Rounding out the set of trials was a small randomized placebo-controlled trial among 25 patients with more advanced ALS, done at the request of Japanese health authorities. Results showed that edaravone was safe in this population but had no clear benefit.

Dr. Palumbo disclosed that he is an employee of Mitsubishi Tanabe Pharma Development America, Inc. The trials were sponsored by Mitsubishi Tanabe Pharma Corporation.

VANCOUVER – Dimethyl fumarate and fingolimod appear to have an edge over other disease-modifying therapies for multiple sclerosis (MS) in real-world practice, according to a comparative effectiveness study reported at the annual meeting of the American Academy of Neurology.

Dr. Jacqueline A. Nicholas, a neuroimmunologist and MS specialist with the OhioHealth Multiple Sclerosis Center, Riverside Methodist Hospital, Columbus, and her colleagues analyzed claims data from 5,004 commercially insured adults with MS in the United States who started treatment with any of five oral and injectable disease-modifying therapies.

Susan London/Frontline Medical News

Findings reported at the meeting showed that dimethyl fumarate netted the greatest reduction in annualized relapse rate, at one-third, followed by fingolimod, at about one-fourth. The adjusted risk of relapse in the year after drug initiation was significantly higher for interferon-beta, glatiramer acetate, and teriflunomide, compared with dimethyl fumarate.

“Right now, a lot of the data that we have to use in the clinic is based on clinical trials data. That’s often not what we see in the real world, the MS centers, and even the outpatient neurology setting,” Dr. Nicholas said in an interview. “This study is nice just because it points out that when you look at real-world data, it shows, yes, that these drugs work, and that some of the initial benefit for the oral disease-modifying therapies is what we thought. Obviously, we don’t have cross-trial comparisons to make from the clinical trials, so this is real data that we can actually use in our clinic setting.”

The findings are also helpful given changing health care models and ongoing issues with reimbursement and obtaining insurance approval to use various drugs, she added. “These are things that we can show to those payers as to why it’s important that we have these therapies and that we be able to decide as MS specialists what’s going to be best for the patient.

“Right now, the biggest challenge in the MS world is that obviously, as an MS specialist, you have a lot of experience and knowledge. And based on poor prognostic factors, when somebody comes in, you may not want to go with an escalation model [of treatment], where you are starting with something that a payer may think we should start with, an injectable,” Dr. Nicholas added. “Somebody may have more aggressive disease, and maybe you are going to want to start with an oral or an IV drug. But the payers are the ones right now who have the say. So it’s a lot of time and a lot of work [getting insurance approval], and while you are fighting to get what you know your patient needs, your patient’s suffering, accumulating disability, and possibly having more relapses.”

For the study, the investigators analyzed administrative data from the Truven MarketScan Commercial Claims Databases for 2012 through 2014.

Analyses were based on 2,564 patients treated with dimethyl fumarate (brand name Tecfidera), 735 with interferon-beta (Rebif, Avonex, Betaseron, and Extavia), 827 with glatiramer acetate (Copaxone), 417 with teriflunomide (Aubagio), and 461 with fingolimod (Gilenya).

Comparing the year before and the year after drug initiation, only dimethyl fumarate and fingolimod were associated with significant reductions in the annualized relapse rate, according to findings reported in a poster session. The reductions were 33% and 27%, respectively.

In the postinitiation year and with dimethyl fumarate as the comparator, the adjusted incidence rate ratio for relapse was similar for fingolimod but significantly higher for glatiramer acetate (1.28), interferon-beta (1.25), and teriflunomide (1.28).

“I don’t think that these findings are surprising,” Dr. Nicholas said. “I work in a large MS center and I would say this is generally what I see clinically in terms of the effectiveness. So it’s more reassuring to me than anything.”

She acknowledged that safety and tolerability will also come into play when selecting among disease-modifying therapies. “Those data are incredibly important, and we certainly balance that. With a health care claims database, that’s hard data to pull unless you are looking at one specific [adverse effect], but that’s something that needs to be very carefully weighed with the efficacy data for the patient,” she said.

In a companion study also reported in the poster session, the investigators compared the impact of starting the same five drugs on health care costs and utilization.

Results of that study showed that total health care costs rose in the postinitiation year for all five drugs, with the increase ranging from $38,801 for dimethyl fumarate to $52,352 for fingolimod.

However, total nonprescription medical costs decreased across the board, apparently driven by both less use of outpatient services and fewer inpatient hospital stays, with the greatest reduction seen for dimethyl fumarate.

Dr. Nicholas disclosed that she has received research funding from Genzyme, Novartis, Teva, Biogen, and Alexion, and has received consulting and speaking honoraria from Genzyme, Novartis, Teva, Biogen, and Medtronic. The study was supported by Biogen.

VANCOUVER – Dimethyl fumarate and fingolimod appear to have an edge over other disease-modifying therapies for multiple sclerosis (MS) in real-world practice, according to a comparative effectiveness study reported at the annual meeting of the American Academy of Neurology.

Dr. Jacqueline A. Nicholas, a neuroimmunologist and MS specialist with the OhioHealth Multiple Sclerosis Center, Riverside Methodist Hospital, Columbus, and her colleagues analyzed claims data from 5,004 commercially insured adults with MS in the United States who started treatment with any of five oral and injectable disease-modifying therapies.

Susan London/Frontline Medical News

Findings reported at the meeting showed that dimethyl fumarate netted the greatest reduction in annualized relapse rate, at one-third, followed by fingolimod, at about one-fourth. The adjusted risk of relapse in the year after drug initiation was significantly higher for interferon-beta, glatiramer acetate, and teriflunomide, compared with dimethyl fumarate.

“Right now, a lot of the data that we have to use in the clinic is based on clinical trials data. That’s often not what we see in the real world, the MS centers, and even the outpatient neurology setting,” Dr. Nicholas said in an interview. “This study is nice just because it points out that when you look at real-world data, it shows, yes, that these drugs work, and that some of the initial benefit for the oral disease-modifying therapies is what we thought. Obviously, we don’t have cross-trial comparisons to make from the clinical trials, so this is real data that we can actually use in our clinic setting.”

The findings are also helpful given changing health care models and ongoing issues with reimbursement and obtaining insurance approval to use various drugs, she added. “These are things that we can show to those payers as to why it’s important that we have these therapies and that we be able to decide as MS specialists what’s going to be best for the patient.

“Right now, the biggest challenge in the MS world is that obviously, as an MS specialist, you have a lot of experience and knowledge. And based on poor prognostic factors, when somebody comes in, you may not want to go with an escalation model [of treatment], where you are starting with something that a payer may think we should start with, an injectable,” Dr. Nicholas added. “Somebody may have more aggressive disease, and maybe you are going to want to start with an oral or an IV drug. But the payers are the ones right now who have the say. So it’s a lot of time and a lot of work [getting insurance approval], and while you are fighting to get what you know your patient needs, your patient’s suffering, accumulating disability, and possibly having more relapses.”

For the study, the investigators analyzed administrative data from the Truven MarketScan Commercial Claims Databases for 2012 through 2014.

Analyses were based on 2,564 patients treated with dimethyl fumarate (brand name Tecfidera), 735 with interferon-beta (Rebif, Avonex, Betaseron, and Extavia), 827 with glatiramer acetate (Copaxone), 417 with teriflunomide (Aubagio), and 461 with fingolimod (Gilenya).

Comparing the year before and the year after drug initiation, only dimethyl fumarate and fingolimod were associated with significant reductions in the annualized relapse rate, according to findings reported in a poster session. The reductions were 33% and 27%, respectively.

In the postinitiation year and with dimethyl fumarate as the comparator, the adjusted incidence rate ratio for relapse was similar for fingolimod but significantly higher for glatiramer acetate (1.28), interferon-beta (1.25), and teriflunomide (1.28).

“I don’t think that these findings are surprising,” Dr. Nicholas said. “I work in a large MS center and I would say this is generally what I see clinically in terms of the effectiveness. So it’s more reassuring to me than anything.”

She acknowledged that safety and tolerability will also come into play when selecting among disease-modifying therapies. “Those data are incredibly important, and we certainly balance that. With a health care claims database, that’s hard data to pull unless you are looking at one specific [adverse effect], but that’s something that needs to be very carefully weighed with the efficacy data for the patient,” she said.

In a companion study also reported in the poster session, the investigators compared the impact of starting the same five drugs on health care costs and utilization.

Results of that study showed that total health care costs rose in the postinitiation year for all five drugs, with the increase ranging from $38,801 for dimethyl fumarate to $52,352 for fingolimod.

However, total nonprescription medical costs decreased across the board, apparently driven by both less use of outpatient services and fewer inpatient hospital stays, with the greatest reduction seen for dimethyl fumarate.

Dr. Nicholas disclosed that she has received research funding from Genzyme, Novartis, Teva, Biogen, and Alexion, and has received consulting and speaking honoraria from Genzyme, Novartis, Teva, Biogen, and Medtronic. The study was supported by Biogen.

VANCOUVER – Dimethyl fumarate and fingolimod appear to have an edge over other disease-modifying therapies for multiple sclerosis (MS) in real-world practice, according to a comparative effectiveness study reported at the annual meeting of the American Academy of Neurology.

Dr. Jacqueline A. Nicholas, a neuroimmunologist and MS specialist with the OhioHealth Multiple Sclerosis Center, Riverside Methodist Hospital, Columbus, and her colleagues analyzed claims data from 5,004 commercially insured adults with MS in the United States who started treatment with any of five oral and injectable disease-modifying therapies.

Susan London/Frontline Medical News

Findings reported at the meeting showed that dimethyl fumarate netted the greatest reduction in annualized relapse rate, at one-third, followed by fingolimod, at about one-fourth. The adjusted risk of relapse in the year after drug initiation was significantly higher for interferon-beta, glatiramer acetate, and teriflunomide, compared with dimethyl fumarate.

“Right now, a lot of the data that we have to use in the clinic is based on clinical trials data. That’s often not what we see in the real world, the MS centers, and even the outpatient neurology setting,” Dr. Nicholas said in an interview. “This study is nice just because it points out that when you look at real-world data, it shows, yes, that these drugs work, and that some of the initial benefit for the oral disease-modifying therapies is what we thought. Obviously, we don’t have cross-trial comparisons to make from the clinical trials, so this is real data that we can actually use in our clinic setting.”

The findings are also helpful given changing health care models and ongoing issues with reimbursement and obtaining insurance approval to use various drugs, she added. “These are things that we can show to those payers as to why it’s important that we have these therapies and that we be able to decide as MS specialists what’s going to be best for the patient.

“Right now, the biggest challenge in the MS world is that obviously, as an MS specialist, you have a lot of experience and knowledge. And based on poor prognostic factors, when somebody comes in, you may not want to go with an escalation model [of treatment], where you are starting with something that a payer may think we should start with, an injectable,” Dr. Nicholas added. “Somebody may have more aggressive disease, and maybe you are going to want to start with an oral or an IV drug. But the payers are the ones right now who have the say. So it’s a lot of time and a lot of work [getting insurance approval], and while you are fighting to get what you know your patient needs, your patient’s suffering, accumulating disability, and possibly having more relapses.”

For the study, the investigators analyzed administrative data from the Truven MarketScan Commercial Claims Databases for 2012 through 2014.

Analyses were based on 2,564 patients treated with dimethyl fumarate (brand name Tecfidera), 735 with interferon-beta (Rebif, Avonex, Betaseron, and Extavia), 827 with glatiramer acetate (Copaxone), 417 with teriflunomide (Aubagio), and 461 with fingolimod (Gilenya).

Comparing the year before and the year after drug initiation, only dimethyl fumarate and fingolimod were associated with significant reductions in the annualized relapse rate, according to findings reported in a poster session. The reductions were 33% and 27%, respectively.

In the postinitiation year and with dimethyl fumarate as the comparator, the adjusted incidence rate ratio for relapse was similar for fingolimod but significantly higher for glatiramer acetate (1.28), interferon-beta (1.25), and teriflunomide (1.28).

“I don’t think that these findings are surprising,” Dr. Nicholas said. “I work in a large MS center and I would say this is generally what I see clinically in terms of the effectiveness. So it’s more reassuring to me than anything.”

She acknowledged that safety and tolerability will also come into play when selecting among disease-modifying therapies. “Those data are incredibly important, and we certainly balance that. With a health care claims database, that’s hard data to pull unless you are looking at one specific [adverse effect], but that’s something that needs to be very carefully weighed with the efficacy data for the patient,” she said.

In a companion study also reported in the poster session, the investigators compared the impact of starting the same five drugs on health care costs and utilization.

Results of that study showed that total health care costs rose in the postinitiation year for all five drugs, with the increase ranging from $38,801 for dimethyl fumarate to $52,352 for fingolimod.

However, total nonprescription medical costs decreased across the board, apparently driven by both less use of outpatient services and fewer inpatient hospital stays, with the greatest reduction seen for dimethyl fumarate.

Dr. Nicholas disclosed that she has received research funding from Genzyme, Novartis, Teva, Biogen, and Alexion, and has received consulting and speaking honoraria from Genzyme, Novartis, Teva, Biogen, and Medtronic. The study was supported by Biogen.

Rheumatoid arthritis patients on anti–tumor necrosis factor medications had approximately twice the rate of serious adverse events as did psoriasis patients on the same medications, based on data from a pair of prospective studies of about 4,000 adults.

The findings were published online in the British Journal of Dermatology.

“Current trends are to extrapolate the abundant literature existing on the safety of TNF antagonists in RA to define safety management for psoriasis,” wrote Dr. Ignacio García-Doval of the Fundación Academia Española de Dermatología y Venereología, Madrid, and colleagues. However, data on the similarity of risk associated with anti-TNF medications in RA and psoriasis are limited, the investigators said (BJD. 2016. doi: 10.1111/bjd.14776).

The researchers compared data from two similarly designed, overlapping prospective safety registry studies of anti-TNF medications in RA patients (the BIOBADASER study) and psoriasis patients (the BIOBADADERM study).

In the cohort of 3,171 RA patients, the researchers identified 1,248 serious or fatal adverse events during 16,230 person-years of follow-up; in the cohort of 946 psoriasis patients, they identified 124 serious or fatal adverse events during 2,760 person-years of follow-up. The resulting incidence rate ratio of psoriasis to RA was 0.6. The increased risk of serious adverse events for RA patients compared with psoriasis patients remained after the investigators controlled for confounding factors including age, sex, treatments, and comorbid conditions including hypertension, diabetes, hypercholesterolemia, and methotrexate therapy, for a hazard ratio of 0.54.

Moreover, the types of serious adverse events were different between the RA and psoriasis groups. Among those with RA, the rates of serious infections, cardiac disorders, respiratory disorders, and infusion reactions were significantly greater among those with RA, while psoriatic patients “had more skin and subcutaneous tissue disorders and hepatobiliary disorders,” the researchers noted.

By contrast, “rates of nonserious adverse events cannot be compared between the two cohorts,” because of differences in definitions, they pointed out. These differences resulted in a nonserious adverse event rate that was more than twice as high in the psoriasis group as in the RA group (582.2 events per 1,000 patient-years vs. 242.8 events per 1,000 patient-years).

Based on the findings, “published safety results of TNF-antagonists in RA cannot be fully extrapolated to psoriasis, as patients with RA have a higher risk and a different pattern of serious adverse events,” they concluded.

The BIOBADADERM project is promoted by the Fundación Academia Española de Dermatología y Venereología, which is supported by the Spanish Medicines and Health Products Agency and by multiple pharmaceutical companies. BIOBADASER received funding from Fundacion Española de Reumatología and the Spanish Medicines and Health Products Agency and grants from numerous pharmaceutical companies. Lead author Dr. Garcia-Doval disclosed travel grants for congresses from Merck/Schering-Plough Pharmaceuticals, Pfizer, and Janssen; the remaining two authors disclosed being a speaker and/or a consultant for several companies, including AbbVie.

Rheumatoid arthritis patients on anti–tumor necrosis factor medications had approximately twice the rate of serious adverse events as did psoriasis patients on the same medications, based on data from a pair of prospective studies of about 4,000 adults.

The findings were published online in the British Journal of Dermatology.

“Current trends are to extrapolate the abundant literature existing on the safety of TNF antagonists in RA to define safety management for psoriasis,” wrote Dr. Ignacio García-Doval of the Fundación Academia Española de Dermatología y Venereología, Madrid, and colleagues. However, data on the similarity of risk associated with anti-TNF medications in RA and psoriasis are limited, the investigators said (BJD. 2016. doi: 10.1111/bjd.14776).

The researchers compared data from two similarly designed, overlapping prospective safety registry studies of anti-TNF medications in RA patients (the BIOBADASER study) and psoriasis patients (the BIOBADADERM study).

In the cohort of 3,171 RA patients, the researchers identified 1,248 serious or fatal adverse events during 16,230 person-years of follow-up; in the cohort of 946 psoriasis patients, they identified 124 serious or fatal adverse events during 2,760 person-years of follow-up. The resulting incidence rate ratio of psoriasis to RA was 0.6. The increased risk of serious adverse events for RA patients compared with psoriasis patients remained after the investigators controlled for confounding factors including age, sex, treatments, and comorbid conditions including hypertension, diabetes, hypercholesterolemia, and methotrexate therapy, for a hazard ratio of 0.54.

Moreover, the types of serious adverse events were different between the RA and psoriasis groups. Among those with RA, the rates of serious infections, cardiac disorders, respiratory disorders, and infusion reactions were significantly greater among those with RA, while psoriatic patients “had more skin and subcutaneous tissue disorders and hepatobiliary disorders,” the researchers noted.

By contrast, “rates of nonserious adverse events cannot be compared between the two cohorts,” because of differences in definitions, they pointed out. These differences resulted in a nonserious adverse event rate that was more than twice as high in the psoriasis group as in the RA group (582.2 events per 1,000 patient-years vs. 242.8 events per 1,000 patient-years).

Based on the findings, “published safety results of TNF-antagonists in RA cannot be fully extrapolated to psoriasis, as patients with RA have a higher risk and a different pattern of serious adverse events,” they concluded.

The BIOBADADERM project is promoted by the Fundación Academia Española de Dermatología y Venereología, which is supported by the Spanish Medicines and Health Products Agency and by multiple pharmaceutical companies. BIOBADASER received funding from Fundacion Española de Reumatología and the Spanish Medicines and Health Products Agency and grants from numerous pharmaceutical companies. Lead author Dr. Garcia-Doval disclosed travel grants for congresses from Merck/Schering-Plough Pharmaceuticals, Pfizer, and Janssen; the remaining two authors disclosed being a speaker and/or a consultant for several companies, including AbbVie.

Rheumatoid arthritis patients on anti–tumor necrosis factor medications had approximately twice the rate of serious adverse events as did psoriasis patients on the same medications, based on data from a pair of prospective studies of about 4,000 adults.

The findings were published online in the British Journal of Dermatology.

“Current trends are to extrapolate the abundant literature existing on the safety of TNF antagonists in RA to define safety management for psoriasis,” wrote Dr. Ignacio García-Doval of the Fundación Academia Española de Dermatología y Venereología, Madrid, and colleagues. However, data on the similarity of risk associated with anti-TNF medications in RA and psoriasis are limited, the investigators said (BJD. 2016. doi: 10.1111/bjd.14776).

The researchers compared data from two similarly designed, overlapping prospective safety registry studies of anti-TNF medications in RA patients (the BIOBADASER study) and psoriasis patients (the BIOBADADERM study).

In the cohort of 3,171 RA patients, the researchers identified 1,248 serious or fatal adverse events during 16,230 person-years of follow-up; in the cohort of 946 psoriasis patients, they identified 124 serious or fatal adverse events during 2,760 person-years of follow-up. The resulting incidence rate ratio of psoriasis to RA was 0.6. The increased risk of serious adverse events for RA patients compared with psoriasis patients remained after the investigators controlled for confounding factors including age, sex, treatments, and comorbid conditions including hypertension, diabetes, hypercholesterolemia, and methotrexate therapy, for a hazard ratio of 0.54.

Moreover, the types of serious adverse events were different between the RA and psoriasis groups. Among those with RA, the rates of serious infections, cardiac disorders, respiratory disorders, and infusion reactions were significantly greater among those with RA, while psoriatic patients “had more skin and subcutaneous tissue disorders and hepatobiliary disorders,” the researchers noted.

By contrast, “rates of nonserious adverse events cannot be compared between the two cohorts,” because of differences in definitions, they pointed out. These differences resulted in a nonserious adverse event rate that was more than twice as high in the psoriasis group as in the RA group (582.2 events per 1,000 patient-years vs. 242.8 events per 1,000 patient-years).

Based on the findings, “published safety results of TNF-antagonists in RA cannot be fully extrapolated to psoriasis, as patients with RA have a higher risk and a different pattern of serious adverse events,” they concluded.

The BIOBADADERM project is promoted by the Fundación Academia Española de Dermatología y Venereología, which is supported by the Spanish Medicines and Health Products Agency and by multiple pharmaceutical companies. BIOBADASER received funding from Fundacion Española de Reumatología and the Spanish Medicines and Health Products Agency and grants from numerous pharmaceutical companies. Lead author Dr. Garcia-Doval disclosed travel grants for congresses from Merck/Schering-Plough Pharmaceuticals, Pfizer, and Janssen; the remaining two authors disclosed being a speaker and/or a consultant for several companies, including AbbVie.

As lawmakers grapple with how best to combat the nation’s prescription painkiller abuse crisis, a recent survey is shedding light on how patients who get these medications  — drugs such as OxyContin, methadone or Vicodin — sometimes share or mishandle them.

According to findings detailed in a research letter published Monday in JAMA Internal Medicine, about one in five people who were prescribed the highly addictive drugs reported having shared their meds with a friend, often to help the other person manage pain. Most people with a prescription either had or expected to have extra pills left after finishing treatment. And almost 50 percent didn’t know how to safely get rid of the drugs left over after their treatment was complete, or how to store them while going through treatment.

The study’s authors suggested that the results point to changes doctors could make in prescribing practices and counseling to help alleviate the problems.

“We’ve all been saying leftover medications are an issue,” said Wilson Compton, deputy director of the federal National Institute on Drug Abuse, who wasn’t involved with the study. “Now I have a number that is concerning.”

The survey was sent to a random sample of almost 5,000 people in 2015. Of the recipients, about 1,000 had used prescription painkillers in the past year. Almost all of the people in this group responded to the survey.

Public concerns about painkiller abuse are growing louder. About 2 million people were addicted to prescription opioids in 2014, the most recent year for which data is available, according to the Centers for Disease Control and Prevention. Overdoses kill 44 people per day, the U.S. Department of Health and Human Services estimates. Researchers say deaths in 2014 were almost four times as common as they were in 2000.

“There’s a growing awareness among medical advisers, policymakers and even members of the general public that these are medications that can do serious harm,” said Colleen Barry, one of the study’s authors. She is a professor of health policy at Johns Hopkins University and co-director of the university’s Center for Mental Health and Addiction Policy Research.

And it is not news that most people who use prescription painkillers for nonmedical reasons often get them through social channels rather than a physician. In 2013 — the most recent year for which this data is available — the National Survey on Drug Use and Health estimated that number to be more than 80 percent.

But this paper’s findings illustrate some of the forces behind drug-sharing, Barry said, and in turn indicate how to stop it. For instance, the authors recommend that doctors prescribe smaller amounts of drugs, to minimize leftovers that could be shared or stolen. That tracks with new opioid prescribing guidelines issued by the Centers for Disease Control and Prevention.

“We probably prescribe a little bit more than we need to, and it’s not like people throw these away afterward. The leftovers are something we’re not thinking about,” said Jonathan Chen, an instructor at Stanford University School of Medicine, who has researched opioid abuse. Chen, who was not involved in the study, is also a practicing physician.

Meanwhile, it’s still tough for people to get rid of the drugs when they finish with them, and few say they know about safe storage practices. That’s another avenue for prevention.

Most respondents, for instance, didn’t lock up the pills when storing them. That makes it easier for someone else to take them.

And the prevalence of sharing medications suggests consumers need to be better educated about how addictive prescription opioids are, Barry said.

Doctors, added NIDA’s Compton, also need to understand the risk that, when they prescribe pills, they could end up used by someone else.

“One out of five people that I write a prescription to for opioids may share those with someone else. That’s a lot of people,” he said.

Physicians, meanwhile, haven’t historically been trained to counsel patients on safe drug disposal, meaning patients are often left unaware. Just under a quarter of respondents reported they remembered learning from the doctor or nurse about how to get rid of their meds safely. Chen said he couldn’t recall ever going over disposal practices with a patient. Even if he did, he said, it’s hard to know if patients would remember that information.

And when they are informed, it’s still difficult for consumers to easily get rid of pills they no longer need. The federal Drug Enforcement Administration sponsors “drug take-back days” twice a year. Some local law enforcement agencies hold similar events. But such events are often sporadic enough that it’s hard to make them a real habit, Barry noted.

Making those practices easier is essential, Barry said. And changing the culture around those drugs is key, so people understand the risk.

“Just the realization on the part of the public as well as physicians that these medications are not like Tylenol — these are highly addictive meds,” she said. “That message is starting to get out there.”

This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation.

As lawmakers grapple with how best to combat the nation’s prescription painkiller abuse crisis, a recent survey is shedding light on how patients who get these medications  — drugs such as OxyContin, methadone or Vicodin — sometimes share or mishandle them.

According to findings detailed in a research letter published Monday in JAMA Internal Medicine, about one in five people who were prescribed the highly addictive drugs reported having shared their meds with a friend, often to help the other person manage pain. Most people with a prescription either had or expected to have extra pills left after finishing treatment. And almost 50 percent didn’t know how to safely get rid of the drugs left over after their treatment was complete, or how to store them while going through treatment.

The study’s authors suggested that the results point to changes doctors could make in prescribing practices and counseling to help alleviate the problems.

“We’ve all been saying leftover medications are an issue,” said Wilson Compton, deputy director of the federal National Institute on Drug Abuse, who wasn’t involved with the study. “Now I have a number that is concerning.”

The survey was sent to a random sample of almost 5,000 people in 2015. Of the recipients, about 1,000 had used prescription painkillers in the past year. Almost all of the people in this group responded to the survey.

Public concerns about painkiller abuse are growing louder. About 2 million people were addicted to prescription opioids in 2014, the most recent year for which data is available, according to the Centers for Disease Control and Prevention. Overdoses kill 44 people per day, the U.S. Department of Health and Human Services estimates. Researchers say deaths in 2014 were almost four times as common as they were in 2000.

“There’s a growing awareness among medical advisers, policymakers and even members of the general public that these are medications that can do serious harm,” said Colleen Barry, one of the study’s authors. She is a professor of health policy at Johns Hopkins University and co-director of the university’s Center for Mental Health and Addiction Policy Research.

And it is not news that most people who use prescription painkillers for nonmedical reasons often get them through social channels rather than a physician. In 2013 — the most recent year for which this data is available — the National Survey on Drug Use and Health estimated that number to be more than 80 percent.

But this paper’s findings illustrate some of the forces behind drug-sharing, Barry said, and in turn indicate how to stop it. For instance, the authors recommend that doctors prescribe smaller amounts of drugs, to minimize leftovers that could be shared or stolen. That tracks with new opioid prescribing guidelines issued by the Centers for Disease Control and Prevention.

“We probably prescribe a little bit more than we need to, and it’s not like people throw these away afterward. The leftovers are something we’re not thinking about,” said Jonathan Chen, an instructor at Stanford University School of Medicine, who has researched opioid abuse. Chen, who was not involved in the study, is also a practicing physician.

Meanwhile, it’s still tough for people to get rid of the drugs when they finish with them, and few say they know about safe storage practices. That’s another avenue for prevention.

Most respondents, for instance, didn’t lock up the pills when storing them. That makes it easier for someone else to take them.

And the prevalence of sharing medications suggests consumers need to be better educated about how addictive prescription opioids are, Barry said.

Doctors, added NIDA’s Compton, also need to understand the risk that, when they prescribe pills, they could end up used by someone else.

“One out of five people that I write a prescription to for opioids may share those with someone else. That’s a lot of people,” he said.

Physicians, meanwhile, haven’t historically been trained to counsel patients on safe drug disposal, meaning patients are often left unaware. Just under a quarter of respondents reported they remembered learning from the doctor or nurse about how to get rid of their meds safely. Chen said he couldn’t recall ever going over disposal practices with a patient. Even if he did, he said, it’s hard to know if patients would remember that information.

And when they are informed, it’s still difficult for consumers to easily get rid of pills they no longer need. The federal Drug Enforcement Administration sponsors “drug take-back days” twice a year. Some local law enforcement agencies hold similar events. But such events are often sporadic enough that it’s hard to make them a real habit, Barry noted.

Making those practices easier is essential, Barry said. And changing the culture around those drugs is key, so people understand the risk.

“Just the realization on the part of the public as well as physicians that these medications are not like Tylenol — these are highly addictive meds,” she said. “That message is starting to get out there.”

This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation.

As lawmakers grapple with how best to combat the nation’s prescription painkiller abuse crisis, a recent survey is shedding light on how patients who get these medications  — drugs such as OxyContin, methadone or Vicodin — sometimes share or mishandle them.

According to findings detailed in a research letter published Monday in JAMA Internal Medicine, about one in five people who were prescribed the highly addictive drugs reported having shared their meds with a friend, often to help the other person manage pain. Most people with a prescription either had or expected to have extra pills left after finishing treatment. And almost 50 percent didn’t know how to safely get rid of the drugs left over after their treatment was complete, or how to store them while going through treatment.

The study’s authors suggested that the results point to changes doctors could make in prescribing practices and counseling to help alleviate the problems.

“We’ve all been saying leftover medications are an issue,” said Wilson Compton, deputy director of the federal National Institute on Drug Abuse, who wasn’t involved with the study. “Now I have a number that is concerning.”

The survey was sent to a random sample of almost 5,000 people in 2015. Of the recipients, about 1,000 had used prescription painkillers in the past year. Almost all of the people in this group responded to the survey.

Public concerns about painkiller abuse are growing louder. About 2 million people were addicted to prescription opioids in 2014, the most recent year for which data is available, according to the Centers for Disease Control and Prevention. Overdoses kill 44 people per day, the U.S. Department of Health and Human Services estimates. Researchers say deaths in 2014 were almost four times as common as they were in 2000.

“There’s a growing awareness among medical advisers, policymakers and even members of the general public that these are medications that can do serious harm,” said Colleen Barry, one of the study’s authors. She is a professor of health policy at Johns Hopkins University and co-director of the university’s Center for Mental Health and Addiction Policy Research.

And it is not news that most people who use prescription painkillers for nonmedical reasons often get them through social channels rather than a physician. In 2013 — the most recent year for which this data is available — the National Survey on Drug Use and Health estimated that number to be more than 80 percent.

But this paper’s findings illustrate some of the forces behind drug-sharing, Barry said, and in turn indicate how to stop it. For instance, the authors recommend that doctors prescribe smaller amounts of drugs, to minimize leftovers that could be shared or stolen. That tracks with new opioid prescribing guidelines issued by the Centers for Disease Control and Prevention.

“We probably prescribe a little bit more than we need to, and it’s not like people throw these away afterward. The leftovers are something we’re not thinking about,” said Jonathan Chen, an instructor at Stanford University School of Medicine, who has researched opioid abuse. Chen, who was not involved in the study, is also a practicing physician.

Meanwhile, it’s still tough for people to get rid of the drugs when they finish with them, and few say they know about safe storage practices. That’s another avenue for prevention.

Most respondents, for instance, didn’t lock up the pills when storing them. That makes it easier for someone else to take them.

And the prevalence of sharing medications suggests consumers need to be better educated about how addictive prescription opioids are, Barry said.

Doctors, added NIDA’s Compton, also need to understand the risk that, when they prescribe pills, they could end up used by someone else.

“One out of five people that I write a prescription to for opioids may share those with someone else. That’s a lot of people,” he said.

Physicians, meanwhile, haven’t historically been trained to counsel patients on safe drug disposal, meaning patients are often left unaware. Just under a quarter of respondents reported they remembered learning from the doctor or nurse about how to get rid of their meds safely. Chen said he couldn’t recall ever going over disposal practices with a patient. Even if he did, he said, it’s hard to know if patients would remember that information.

And when they are informed, it’s still difficult for consumers to easily get rid of pills they no longer need. The federal Drug Enforcement Administration sponsors “drug take-back days” twice a year. Some local law enforcement agencies hold similar events. But such events are often sporadic enough that it’s hard to make them a real habit, Barry noted.

Making those practices easier is essential, Barry said. And changing the culture around those drugs is key, so people understand the risk.

“Just the realization on the part of the public as well as physicians that these medications are not like Tylenol — these are highly addictive meds,” she said. “That message is starting to get out there.”

This story was produced by Kaiser Health News, which publishes California Healthline, a service of the California Health Care Foundation.

CHICAGO – Long-term maintenance monotherapy with olaparib following a response to platinum therapy in patients with recurrent high-grade serous ovarian cancer was associated with continued benefit vs. placebo in an updated analysis of the randomized phase II Study 19.

The new survival analysis supports prior Study 19 data showing a significant progression-free survival (PFS) advantage and a delay in time to first and second subsequent therapy in the 136 patients in the study with a BRCA 1/2 mutation who were treated with the approved PARP inhibitor, Dr. Jonathan A. Ledermann reported at the annual meeting of the American Society of Clinical Oncology.

©thegoodphoto/Thinkstock

The PFS in the overall study population of 265 patients in that prior analysis was 8.4 months in the olaparib group vs. 4.8 months in the placebo group (hazard ratio, 0.35). The PFS in the BRCA mutation subpopulation was 11.2 and 4.3 months in the groups, respectively (HR, 0.18), reported Dr. Ledermann of University College London.

“Time to first subsequent therapy or death was significantly improved with olaparib. This represents the time that women are free from the next line of chemotherapy,” he said, adding that time to second subsequent therapy or death was also significantly improved with olaparib.

“[These measures] can demonstrate the benefit beyond the next line of chemotherapy, and also help to address the confounding impact of crossover that occurs in many trials,” he explained.

Neither of two prior data analyses, the first with data maturity of 38% and the second with maturity of 58%, showed an improvement in overall survival in Study 19 participants.

In the current analysis, with a data cut-off of Sept. 31, 2015 (an additional 3 years of follow-up since the last analysis), and data maturity of 77%, overall survival was 29.8 and 27.8 months in 136 treatment group patients and 129 placebo group patients, respectively (HR, 0.73). In the BRCA mutation subgroup, the median overall survival was 34.9 months with treatment, vs. 30.2 months with placebo (HR, 0.62). For 118 patients with BRCA wild type, the hazard ratio was 0.83.

The differences did not meet the criteria for statistical significance, as the study was not powered to show a difference in overall survival, but a restricted means analysis to compare mean survival – a “useful additional way of looking at the data, rather than the point-estimated median PFS, particularly as the data mature” – showed a mean overall survival of 40.1 and 34.9 months in the olaparib and placebo patients, respectively (difference of 5.2 months), and 44.3 and 36.9 months in the BRCA mutation subgroup (difference of 7.4 months).

As for the median time to first subsequent therapy in BRCA mutation patients in the current analysis, the benefit of olaparib is maintained, with a 9.4-month difference between the treatment and placebo groups (15.6 vs. 6.2), and this was highly statistically significant (HR, 0.32; data maturity, 82%). For wild-type patients, the difference in the median was 6 months (12.9 vs. 6.9 months; HR, 0.45; maturity, 91%).

The same was true for the time to second subsequent treatment in BRCA mutation patients (22 vs. 15.3 months; HR, 0.41; data maturity, 79%), he said, noting that 23% of placebo patients crossed over to a PARP inhibitor at some point in their treatment.

A separation between the groups was also seen in BRCA wild-type patients (median of 17 vs. 14.7 months; HR, 0.63; data maturity, 90%), “perhaps maintained by those patients taking the drug for a long time,” Dr. Ledermann said.

At a median follow-up of 5.9 years, 15 patients were still receiving olaparib (11%), including 8 BRCA mutation patients and 7 BRCA wild-type patients. One patient was still receiving placebo.

“So 13% were on the drug for at least 5 years, 15% in the BRCA mutation subgroup were on it for at least 5 years, and 12% of patients with the BRCA wild type were on the drug for at least 5 years,” Dr. Ledermann said, noting that this represents “unprecedented long-term exposure to olaparib.”

Olaparib is a potent oral PARP inhibitor that traps PARP at sites of DNA damage, which blocks base-excision repair and leads to the collapse of DNA replication forks and the accumulation of DNA double-strand breaks, Dr. Ledermann explained, noting that the agent induces synthetic lethality in tumors with deficient hemologous recombination repair, which is most often seen with BRCA 1/2 mutations.

In Study 19, patients received 400 mg of olaparib twice daily or placebo after response to platinum-based therapy. BRCA mutation status was known for 254/265 patients (96%) from germline or tumor tests.

No new safety signals were observed with the longer follow-up, and the frequency of common adverse events, including nausea, fatigue, vomiting, and anemia was consistent with that seen in the overall population, with most adverse events initially reported during the first 2 years, he said.

The greatest benefits, in terms of overall survival and time to first and second subsequent treatment, were seen in patients with BRCA mutation, he concluded.

This study was sponsored by AstraZeneca. Dr. Ledermann reported that he has participated in advisory boards and lecture symposia and received institutional and personal fees from AstraZeneca, personal fees from Roche and Pfizer, and institutional fees from Clovis Oncology and Merck.

[email protected]

CHICAGO – Long-term maintenance monotherapy with olaparib following a response to platinum therapy in patients with recurrent high-grade serous ovarian cancer was associated with continued benefit vs. placebo in an updated analysis of the randomized phase II Study 19.

The new survival analysis supports prior Study 19 data showing a significant progression-free survival (PFS) advantage and a delay in time to first and second subsequent therapy in the 136 patients in the study with a BRCA 1/2 mutation who were treated with the approved PARP inhibitor, Dr. Jonathan A. Ledermann reported at the annual meeting of the American Society of Clinical Oncology.

©thegoodphoto/Thinkstock

The PFS in the overall study population of 265 patients in that prior analysis was 8.4 months in the olaparib group vs. 4.8 months in the placebo group (hazard ratio, 0.35). The PFS in the BRCA mutation subpopulation was 11.2 and 4.3 months in the groups, respectively (HR, 0.18), reported Dr. Ledermann of University College London.

“Time to first subsequent therapy or death was significantly improved with olaparib. This represents the time that women are free from the next line of chemotherapy,” he said, adding that time to second subsequent therapy or death was also significantly improved with olaparib.

“[These measures] can demonstrate the benefit beyond the next line of chemotherapy, and also help to address the confounding impact of crossover that occurs in many trials,” he explained.

Neither of two prior data analyses, the first with data maturity of 38% and the second with maturity of 58%, showed an improvement in overall survival in Study 19 participants.

In the current analysis, with a data cut-off of Sept. 31, 2015 (an additional 3 years of follow-up since the last analysis), and data maturity of 77%, overall survival was 29.8 and 27.8 months in 136 treatment group patients and 129 placebo group patients, respectively (HR, 0.73). In the BRCA mutation subgroup, the median overall survival was 34.9 months with treatment, vs. 30.2 months with placebo (HR, 0.62). For 118 patients with BRCA wild type, the hazard ratio was 0.83.

The differences did not meet the criteria for statistical significance, as the study was not powered to show a difference in overall survival, but a restricted means analysis to compare mean survival – a “useful additional way of looking at the data, rather than the point-estimated median PFS, particularly as the data mature” – showed a mean overall survival of 40.1 and 34.9 months in the olaparib and placebo patients, respectively (difference of 5.2 months), and 44.3 and 36.9 months in the BRCA mutation subgroup (difference of 7.4 months).

As for the median time to first subsequent therapy in BRCA mutation patients in the current analysis, the benefit of olaparib is maintained, with a 9.4-month difference between the treatment and placebo groups (15.6 vs. 6.2), and this was highly statistically significant (HR, 0.32; data maturity, 82%). For wild-type patients, the difference in the median was 6 months (12.9 vs. 6.9 months; HR, 0.45; maturity, 91%).

The same was true for the time to second subsequent treatment in BRCA mutation patients (22 vs. 15.3 months; HR, 0.41; data maturity, 79%), he said, noting that 23% of placebo patients crossed over to a PARP inhibitor at some point in their treatment.

A separation between the groups was also seen in BRCA wild-type patients (median of 17 vs. 14.7 months; HR, 0.63; data maturity, 90%), “perhaps maintained by those patients taking the drug for a long time,” Dr. Ledermann said.

At a median follow-up of 5.9 years, 15 patients were still receiving olaparib (11%), including 8 BRCA mutation patients and 7 BRCA wild-type patients. One patient was still receiving placebo.

“So 13% were on the drug for at least 5 years, 15% in the BRCA mutation subgroup were on it for at least 5 years, and 12% of patients with the BRCA wild type were on the drug for at least 5 years,” Dr. Ledermann said, noting that this represents “unprecedented long-term exposure to olaparib.”

Olaparib is a potent oral PARP inhibitor that traps PARP at sites of DNA damage, which blocks base-excision repair and leads to the collapse of DNA replication forks and the accumulation of DNA double-strand breaks, Dr. Ledermann explained, noting that the agent induces synthetic lethality in tumors with deficient hemologous recombination repair, which is most often seen with BRCA 1/2 mutations.

In Study 19, patients received 400 mg of olaparib twice daily or placebo after response to platinum-based therapy. BRCA mutation status was known for 254/265 patients (96%) from germline or tumor tests.

No new safety signals were observed with the longer follow-up, and the frequency of common adverse events, including nausea, fatigue, vomiting, and anemia was consistent with that seen in the overall population, with most adverse events initially reported during the first 2 years, he said.

The greatest benefits, in terms of overall survival and time to first and second subsequent treatment, were seen in patients with BRCA mutation, he concluded.

This study was sponsored by AstraZeneca. Dr. Ledermann reported that he has participated in advisory boards and lecture symposia and received institutional and personal fees from AstraZeneca, personal fees from Roche and Pfizer, and institutional fees from Clovis Oncology and Merck.

[email protected]

CHICAGO – Long-term maintenance monotherapy with olaparib following a response to platinum therapy in patients with recurrent high-grade serous ovarian cancer was associated with continued benefit vs. placebo in an updated analysis of the randomized phase II Study 19.

The new survival analysis supports prior Study 19 data showing a significant progression-free survival (PFS) advantage and a delay in time to first and second subsequent therapy in the 136 patients in the study with a BRCA 1/2 mutation who were treated with the approved PARP inhibitor, Dr. Jonathan A. Ledermann reported at the annual meeting of the American Society of Clinical Oncology.

©thegoodphoto/Thinkstock

The PFS in the overall study population of 265 patients in that prior analysis was 8.4 months in the olaparib group vs. 4.8 months in the placebo group (hazard ratio, 0.35). The PFS in the BRCA mutation subpopulation was 11.2 and 4.3 months in the groups, respectively (HR, 0.18), reported Dr. Ledermann of University College London.

“Time to first subsequent therapy or death was significantly improved with olaparib. This represents the time that women are free from the next line of chemotherapy,” he said, adding that time to second subsequent therapy or death was also significantly improved with olaparib.

“[These measures] can demonstrate the benefit beyond the next line of chemotherapy, and also help to address the confounding impact of crossover that occurs in many trials,” he explained.

Neither of two prior data analyses, the first with data maturity of 38% and the second with maturity of 58%, showed an improvement in overall survival in Study 19 participants.

In the current analysis, with a data cut-off of Sept. 31, 2015 (an additional 3 years of follow-up since the last analysis), and data maturity of 77%, overall survival was 29.8 and 27.8 months in 136 treatment group patients and 129 placebo group patients, respectively (HR, 0.73). In the BRCA mutation subgroup, the median overall survival was 34.9 months with treatment, vs. 30.2 months with placebo (HR, 0.62). For 118 patients with BRCA wild type, the hazard ratio was 0.83.

The differences did not meet the criteria for statistical significance, as the study was not powered to show a difference in overall survival, but a restricted means analysis to compare mean survival – a “useful additional way of looking at the data, rather than the point-estimated median PFS, particularly as the data mature” – showed a mean overall survival of 40.1 and 34.9 months in the olaparib and placebo patients, respectively (difference of 5.2 months), and 44.3 and 36.9 months in the BRCA mutation subgroup (difference of 7.4 months).

As for the median time to first subsequent therapy in BRCA mutation patients in the current analysis, the benefit of olaparib is maintained, with a 9.4-month difference between the treatment and placebo groups (15.6 vs. 6.2), and this was highly statistically significant (HR, 0.32; data maturity, 82%). For wild-type patients, the difference in the median was 6 months (12.9 vs. 6.9 months; HR, 0.45; maturity, 91%).

The same was true for the time to second subsequent treatment in BRCA mutation patients (22 vs. 15.3 months; HR, 0.41; data maturity, 79%), he said, noting that 23% of placebo patients crossed over to a PARP inhibitor at some point in their treatment.

A separation between the groups was also seen in BRCA wild-type patients (median of 17 vs. 14.7 months; HR, 0.63; data maturity, 90%), “perhaps maintained by those patients taking the drug for a long time,” Dr. Ledermann said.

At a median follow-up of 5.9 years, 15 patients were still receiving olaparib (11%), including 8 BRCA mutation patients and 7 BRCA wild-type patients. One patient was still receiving placebo.

“So 13% were on the drug for at least 5 years, 15% in the BRCA mutation subgroup were on it for at least 5 years, and 12% of patients with the BRCA wild type were on the drug for at least 5 years,” Dr. Ledermann said, noting that this represents “unprecedented long-term exposure to olaparib.”

Olaparib is a potent oral PARP inhibitor that traps PARP at sites of DNA damage, which blocks base-excision repair and leads to the collapse of DNA replication forks and the accumulation of DNA double-strand breaks, Dr. Ledermann explained, noting that the agent induces synthetic lethality in tumors with deficient hemologous recombination repair, which is most often seen with BRCA 1/2 mutations.

In Study 19, patients received 400 mg of olaparib twice daily or placebo after response to platinum-based therapy. BRCA mutation status was known for 254/265 patients (96%) from germline or tumor tests.

No new safety signals were observed with the longer follow-up, and the frequency of common adverse events, including nausea, fatigue, vomiting, and anemia was consistent with that seen in the overall population, with most adverse events initially reported during the first 2 years, he said.

The greatest benefits, in terms of overall survival and time to first and second subsequent treatment, were seen in patients with BRCA mutation, he concluded.

This study was sponsored by AstraZeneca. Dr. Ledermann reported that he has participated in advisory boards and lecture symposia and received institutional and personal fees from AstraZeneca, personal fees from Roche and Pfizer, and institutional fees from Clovis Oncology and Merck.

[email protected]