The investigational interleukin-6 inhibitor sirukumab proved effective and safe for rheumatoid arthritis patients who failed to respond to or were intolerant of multiple previous therapies in a phase III trial reported online in The Lancet.

These patients are “exceptionally treatment-resistant” and have “substantial clinical needs with the lowest chance of treatment success,” said first author Daniel Aletaha, MD, of the division of rheumatology at the Medical University of Vienna, and his associates.

Two different doses of sirukumab provided rapid and sustained improvements in rheumatoid arthritis (RA) signs and symptoms, physical function, and health status. These were accompanied by improvements in physical and mental well-being, a result that is particularly relevant for RA patients, who have a high prevalence of mood disorders. It has been estimated that 39% of RA patients have moderate to severe depressive symptoms, the investigators noted.

They assessed sirukumab in the manufacturer-funded trial involving 878 adults treated and followed at 183 centers in 20 countries across North America, Europe, Latin America, and Asia. These patients included 59% who had failed to respond to or had been intolerant of two or more biologic disease-modifying antirheumatic drugs (39% to two or more tumor necrosis factor inhibitors) and numerous other RA treatments.

The patients in the study, called SIRROUND-T, were randomly assigned to receive 50 mg sirukumab every 4 weeks (292 patients in the low-dose group), 100 mg sirukumab every 2 weeks (292 in the high-dose group), or matching placebo (294 patients in the control group) via subcutaneous injections for 52 weeks. Patients receiving placebo whose condition worsened were allowed an “early escape,” a blinded switch to either dose of the active drug for the remainder of the trial. At week 24, patients remaining in the placebo groups also were randomly assigned in a blinded manner to switch to active treatment (Lancet. 2017 Feb 15. doi: 10.1016/S0140-6736[17]30401-4). All patients were allowed to continue using any concomitant disease-modifying antirheumatic drugs (DMARDs). At baseline, only 80% were using a conventional synthetic DMARD, and about 25% of patients in each group were not taking methotrexate.

The primary efficacy endpoint was the proportion of patients achieving an ACR20 response (a 20% or greater improvement in swollen joint count and tender joint count plus a 20% or greater improvement in at least three factors: pain, patient-assessed disease activity, physician-assessed disease activity, patient-assessed physical function, and C-reactive protein levels) at week 16. Sirukumab achieved higher levels of response in both the low-dose (40% of patients) and high-dose (45%) groups than did placebo (24%).

In addition, significantly higher proportions of patients receiving active treatment achieved the secondary endpoints of ACR20, ACR50, and ACR70 at week 24. Greater improvements, including remission, also were noted with sirukumab than with placebo according to the Simplified Disease Activity Index, ACR/EULAR criteria, and the Health Assessment Questionnaire–Disability Index. And significantly greater improvements also were seen in the Functional Assessment of Chronic Illness Therapy–Fatigue score, the 36-Item Short Form Health Survey, the Work Limitations Questionnaire, the EuroQol-5 Dimension questionnaire, and the EuroQol Health State Visual Analogue Scale.

In both active-treatment groups, all of these improvements were noted as early as within 2 weeks of starting treatment and persisted through follow-ups at week 24 and week 52.

Rates of adverse events, serious adverse events, and adverse events leading to treatment discontinuation were similar across the three study groups. Infections (primarily pneumonia) and infestations were the most frequent adverse events leading to discontinuation. No cases of tuberculosis or serious opportunistic infections were reported. Both doses of sirukumab induced declines in neutrophil, platelet, and white blood cell counts, as well as increases in alanine aminotransferase, aspartate aminotransferase, bilirubin, cholesterol, and triglycerides. Nine patients had hypersensitivity reactions, including one classified as serious dermatitis; all of these patients were taking the high dose of sirukumab. One of the five patient deaths that occurred, a fatal case of pneumonia, was considered possibly related to sirukumab.

This trial was funded by Janssen and GlaxoSmithKline, which also participated in the study design, data collection and analysis, and writing the results. Dr. Aletaha reported serving as a consultant for or receiving research support from AbbVie, Pfizer, Grünenthal, Merck, Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche. His associates reported ties to numerous industry sources.

The investigational interleukin-6 inhibitor sirukumab proved effective and safe for rheumatoid arthritis patients who failed to respond to or were intolerant of multiple previous therapies in a phase III trial reported online in The Lancet.

These patients are “exceptionally treatment-resistant” and have “substantial clinical needs with the lowest chance of treatment success,” said first author Daniel Aletaha, MD, of the division of rheumatology at the Medical University of Vienna, and his associates.

Two different doses of sirukumab provided rapid and sustained improvements in rheumatoid arthritis (RA) signs and symptoms, physical function, and health status. These were accompanied by improvements in physical and mental well-being, a result that is particularly relevant for RA patients, who have a high prevalence of mood disorders. It has been estimated that 39% of RA patients have moderate to severe depressive symptoms, the investigators noted.

They assessed sirukumab in the manufacturer-funded trial involving 878 adults treated and followed at 183 centers in 20 countries across North America, Europe, Latin America, and Asia. These patients included 59% who had failed to respond to or had been intolerant of two or more biologic disease-modifying antirheumatic drugs (39% to two or more tumor necrosis factor inhibitors) and numerous other RA treatments.

The patients in the study, called SIRROUND-T, were randomly assigned to receive 50 mg sirukumab every 4 weeks (292 patients in the low-dose group), 100 mg sirukumab every 2 weeks (292 in the high-dose group), or matching placebo (294 patients in the control group) via subcutaneous injections for 52 weeks. Patients receiving placebo whose condition worsened were allowed an “early escape,” a blinded switch to either dose of the active drug for the remainder of the trial. At week 24, patients remaining in the placebo groups also were randomly assigned in a blinded manner to switch to active treatment (Lancet. 2017 Feb 15. doi: 10.1016/S0140-6736[17]30401-4). All patients were allowed to continue using any concomitant disease-modifying antirheumatic drugs (DMARDs). At baseline, only 80% were using a conventional synthetic DMARD, and about 25% of patients in each group were not taking methotrexate.

The primary efficacy endpoint was the proportion of patients achieving an ACR20 response (a 20% or greater improvement in swollen joint count and tender joint count plus a 20% or greater improvement in at least three factors: pain, patient-assessed disease activity, physician-assessed disease activity, patient-assessed physical function, and C-reactive protein levels) at week 16. Sirukumab achieved higher levels of response in both the low-dose (40% of patients) and high-dose (45%) groups than did placebo (24%).

In addition, significantly higher proportions of patients receiving active treatment achieved the secondary endpoints of ACR20, ACR50, and ACR70 at week 24. Greater improvements, including remission, also were noted with sirukumab than with placebo according to the Simplified Disease Activity Index, ACR/EULAR criteria, and the Health Assessment Questionnaire–Disability Index. And significantly greater improvements also were seen in the Functional Assessment of Chronic Illness Therapy–Fatigue score, the 36-Item Short Form Health Survey, the Work Limitations Questionnaire, the EuroQol-5 Dimension questionnaire, and the EuroQol Health State Visual Analogue Scale.

In both active-treatment groups, all of these improvements were noted as early as within 2 weeks of starting treatment and persisted through follow-ups at week 24 and week 52.

Rates of adverse events, serious adverse events, and adverse events leading to treatment discontinuation were similar across the three study groups. Infections (primarily pneumonia) and infestations were the most frequent adverse events leading to discontinuation. No cases of tuberculosis or serious opportunistic infections were reported. Both doses of sirukumab induced declines in neutrophil, platelet, and white blood cell counts, as well as increases in alanine aminotransferase, aspartate aminotransferase, bilirubin, cholesterol, and triglycerides. Nine patients had hypersensitivity reactions, including one classified as serious dermatitis; all of these patients were taking the high dose of sirukumab. One of the five patient deaths that occurred, a fatal case of pneumonia, was considered possibly related to sirukumab.

This trial was funded by Janssen and GlaxoSmithKline, which also participated in the study design, data collection and analysis, and writing the results. Dr. Aletaha reported serving as a consultant for or receiving research support from AbbVie, Pfizer, Grünenthal, Merck, Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche. His associates reported ties to numerous industry sources.

The investigational interleukin-6 inhibitor sirukumab proved effective and safe for rheumatoid arthritis patients who failed to respond to or were intolerant of multiple previous therapies in a phase III trial reported online in The Lancet.

These patients are “exceptionally treatment-resistant” and have “substantial clinical needs with the lowest chance of treatment success,” said first author Daniel Aletaha, MD, of the division of rheumatology at the Medical University of Vienna, and his associates.

Two different doses of sirukumab provided rapid and sustained improvements in rheumatoid arthritis (RA) signs and symptoms, physical function, and health status. These were accompanied by improvements in physical and mental well-being, a result that is particularly relevant for RA patients, who have a high prevalence of mood disorders. It has been estimated that 39% of RA patients have moderate to severe depressive symptoms, the investigators noted.

They assessed sirukumab in the manufacturer-funded trial involving 878 adults treated and followed at 183 centers in 20 countries across North America, Europe, Latin America, and Asia. These patients included 59% who had failed to respond to or had been intolerant of two or more biologic disease-modifying antirheumatic drugs (39% to two or more tumor necrosis factor inhibitors) and numerous other RA treatments.

The patients in the study, called SIRROUND-T, were randomly assigned to receive 50 mg sirukumab every 4 weeks (292 patients in the low-dose group), 100 mg sirukumab every 2 weeks (292 in the high-dose group), or matching placebo (294 patients in the control group) via subcutaneous injections for 52 weeks. Patients receiving placebo whose condition worsened were allowed an “early escape,” a blinded switch to either dose of the active drug for the remainder of the trial. At week 24, patients remaining in the placebo groups also were randomly assigned in a blinded manner to switch to active treatment (Lancet. 2017 Feb 15. doi: 10.1016/S0140-6736[17]30401-4). All patients were allowed to continue using any concomitant disease-modifying antirheumatic drugs (DMARDs). At baseline, only 80% were using a conventional synthetic DMARD, and about 25% of patients in each group were not taking methotrexate.

The primary efficacy endpoint was the proportion of patients achieving an ACR20 response (a 20% or greater improvement in swollen joint count and tender joint count plus a 20% or greater improvement in at least three factors: pain, patient-assessed disease activity, physician-assessed disease activity, patient-assessed physical function, and C-reactive protein levels) at week 16. Sirukumab achieved higher levels of response in both the low-dose (40% of patients) and high-dose (45%) groups than did placebo (24%).

In addition, significantly higher proportions of patients receiving active treatment achieved the secondary endpoints of ACR20, ACR50, and ACR70 at week 24. Greater improvements, including remission, also were noted with sirukumab than with placebo according to the Simplified Disease Activity Index, ACR/EULAR criteria, and the Health Assessment Questionnaire–Disability Index. And significantly greater improvements also were seen in the Functional Assessment of Chronic Illness Therapy–Fatigue score, the 36-Item Short Form Health Survey, the Work Limitations Questionnaire, the EuroQol-5 Dimension questionnaire, and the EuroQol Health State Visual Analogue Scale.

In both active-treatment groups, all of these improvements were noted as early as within 2 weeks of starting treatment and persisted through follow-ups at week 24 and week 52.

Rates of adverse events, serious adverse events, and adverse events leading to treatment discontinuation were similar across the three study groups. Infections (primarily pneumonia) and infestations were the most frequent adverse events leading to discontinuation. No cases of tuberculosis or serious opportunistic infections were reported. Both doses of sirukumab induced declines in neutrophil, platelet, and white blood cell counts, as well as increases in alanine aminotransferase, aspartate aminotransferase, bilirubin, cholesterol, and triglycerides. Nine patients had hypersensitivity reactions, including one classified as serious dermatitis; all of these patients were taking the high dose of sirukumab. One of the five patient deaths that occurred, a fatal case of pneumonia, was considered possibly related to sirukumab.

This trial was funded by Janssen and GlaxoSmithKline, which also participated in the study design, data collection and analysis, and writing the results. Dr. Aletaha reported serving as a consultant for or receiving research support from AbbVie, Pfizer, Grünenthal, Merck, Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche. His associates reported ties to numerous industry sources.

The recognition that human papillomavirus (HPV) oncogenic viruses cause cervical carcinoma remains one of the most game-changing medical discoveries of the last century. Improvements in screening options for detecting cervical cancer precursors followed. We now have the ability to detect high-risk HPV subtypes in routine specimens. Finally, a highly effective vaccine was developed that targets HPV types 16 and 18, which are responsible for causing approximately 70% of all cases of cervical carcinoma.

In one of the original vaccines HPV types 6 and 11, responsible for 90% of all genital warts, were also targeted. In 2014, a 9-valent vaccine incorporating an additional 5 HPV strains (31, 33, 45, 52, and 58) was approved and is set to replace all previous vaccine versions. Together, these 7 oncogenic HPV types are responsible for approximately 90% of HPV-related cancers, including cervical, anal, oropharyngeal, vaginal, and vulvar cancer.

By vaccinating boys and girls between ages 9 and 21 (for males) and 9 and 26 (for females), we could effectively eliminate 90% of genital warts and 90% of all HPV-related cancers. So why have we not capitalized on this extraordinary discovery? In 2016, why were only 40% of teenage girls and less than 25% of teenage boys vaccinated against HPV when we are immunizing 80% to 90% of these populations with tetanus, diphtheria, and acellular pertusis (Tdap) and meningococcal vaccines?

Related article:
2016 Update on cervical disease

Barriers to HPV vaccination

When the first HPV vaccine was approved in 2006, cost was a significant factor. Many health insurance plans did not cover this “discretionary” vaccine, which was viewed as a prevention for sexually transmitted infections rather than as a valuable intervention for the prevention of cervical and other cancers. At well over $125 per dose with 3 doses required for a full series, ObGyns were reluctant to stock and provide these expensive vaccines without assurance of reimbursement. The logistics of recalling patients for their subsequent vaccine doses were challenging for offices that were not accustomed to seeing patients for preventive care activities more than once a year. In addition, the office infrastructure required to maintain the vaccine stock and manage the necessary paperwork could be daunting. Finally, the requirement that patients be observed for 15 to 30 minutes in the office after vaccine administration created efficiency and rooming problems in busy, active practices.

Over time, almost all payers covered the HPV vaccines, but the logistical issues in ObGyn practices remain. Pediatric practices, on the other hand, are ideally suited for vaccine administration. Unfortunately, our colleagues delivering preventive care to young teens have persisted in considering the HPV vaccine as an optional adjunct to routine vaccination despite the advice of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), which for many years has recommended the HPV vaccine for girls. In 2011, the ACIP extended the HPV vaccine recommendation to include boys beginning at ages 11 to 12.

New 2-dose HPV vaccine schedule for children <15 years

In October 2016, 10 years after the first HPV vaccine approval, the ACIP and the CDC approved a reduced, 2-dose schedule for those younger than 15.¹ The first dose can be administered simultaneously with other recommended vaccines for 11- to 12-year-olds (the meningococcal and Tdap vaccines) and the second dose, 6 or 12 months later.² The 12-month interval would allow administration, once again, of all required vaccines at the annual visit.

Pivotal immunogenicity study

The new recommendation is based on robust multinational data (52 sites in 15 countries, N = 1,518) from an open-label trial.³ Immunogenicity of 2 doses of the 9-valent HPV vaccine in girls and boys ages 9 to 14 was compared with that of a standard 3-dose regimen in adolescents and young women ages 16 to 26. Five cohorts were studied: boys 9 to 14 given 2 doses at 6-month intervals; girls 9 to 14 given 2 doses at 6-month intervals; boys and girls 9 to 14 given 2 doses at a 12-month interval; girls 9 to 14 given the standard 3-dose regimen; and girls and young women 16 to 26 receiving 3 doses over 6 months.

The authors assessed the antibody responses against each HPV subtype 1 month after the final vaccine dose. Data from 1,377 participants (90.7% of the original cohort) were analyzed. Prespecified antibody titers were set conservatively to ensure adequate immunogenicity. Noninferiority criteria had to be met for all 9 HPV types.

Trial results. The immune responses for the 9- to 14-year-olds were consistently higher than those for the 16- to 26-year-old age group regardless of the regimen—not a surprising finding since the initial trials for HPV vaccine demonstrated a greater response among younger vaccine recipients. In this trial, higher antibody responses were found for the 12-month dosing interval than for the 6-month interval, although both regimens produced an adequate response.

Immunogenicity remained at 6 months. Antibody levels were retested 6 months after the last dose of HPV vaccine in a post hoc analysis. In all groups the antibody titers declined; however, there was no difference between the 2- and 3-dose cohorts. All levels remained above a threshold required for immunogenicity.

Related article:
2015 Update on cervical disease: New ammo for HPV prevention and screening

Simplified dosing may help increase vaccination rates

What does this new dosing regimen mean for practice? It will be simpler to incorporate HPV vaccination routinely into the standard vaccine regimen for preadolescent boys and girls. In addition, counseling for HPV vaccine administration can be combined with counseling for the meningococcal vaccine and routine Tdap booster.

Notably, primary care physicians have reported perceiving HPV vaccine discussions with parents as burdensome, and they tend to discuss it last after conversations about Tdap and meningococcal vaccines.⁴ Brewer and colleagues⁵ documented a 5% increase in first HPV vaccine doses among patients in practices in which the providers were taught to “announce” the need for HPV vaccine along with other routine vaccines. There was no increase in HPV vaccine uptake among practices in which providers were taught to “discuss” HPV with parents and to address their concerns, or in control practices. Therefore, less conversation about HPV and the HPV vaccine, as distinct from any other recommended vaccines, is better.

With the new 2-dose regimen, it should be easier to convey that the HPV vaccine is another necessary, routine intervention for children’s health. We should be able to achieve 90% vaccination rates for HPV—similar to rates for Tdap.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The recognition that human papillomavirus (HPV) oncogenic viruses cause cervical carcinoma remains one of the most game-changing medical discoveries of the last century. Improvements in screening options for detecting cervical cancer precursors followed. We now have the ability to detect high-risk HPV subtypes in routine specimens. Finally, a highly effective vaccine was developed that targets HPV types 16 and 18, which are responsible for causing approximately 70% of all cases of cervical carcinoma.

In one of the original vaccines HPV types 6 and 11, responsible for 90% of all genital warts, were also targeted. In 2014, a 9-valent vaccine incorporating an additional 5 HPV strains (31, 33, 45, 52, and 58) was approved and is set to replace all previous vaccine versions. Together, these 7 oncogenic HPV types are responsible for approximately 90% of HPV-related cancers, including cervical, anal, oropharyngeal, vaginal, and vulvar cancer.

By vaccinating boys and girls between ages 9 and 21 (for males) and 9 and 26 (for females), we could effectively eliminate 90% of genital warts and 90% of all HPV-related cancers. So why have we not capitalized on this extraordinary discovery? In 2016, why were only 40% of teenage girls and less than 25% of teenage boys vaccinated against HPV when we are immunizing 80% to 90% of these populations with tetanus, diphtheria, and acellular pertusis (Tdap) and meningococcal vaccines?

Related article:
2016 Update on cervical disease

Barriers to HPV vaccination

When the first HPV vaccine was approved in 2006, cost was a significant factor. Many health insurance plans did not cover this “discretionary” vaccine, which was viewed as a prevention for sexually transmitted infections rather than as a valuable intervention for the prevention of cervical and other cancers. At well over $125 per dose with 3 doses required for a full series, ObGyns were reluctant to stock and provide these expensive vaccines without assurance of reimbursement. The logistics of recalling patients for their subsequent vaccine doses were challenging for offices that were not accustomed to seeing patients for preventive care activities more than once a year. In addition, the office infrastructure required to maintain the vaccine stock and manage the necessary paperwork could be daunting. Finally, the requirement that patients be observed for 15 to 30 minutes in the office after vaccine administration created efficiency and rooming problems in busy, active practices.

Over time, almost all payers covered the HPV vaccines, but the logistical issues in ObGyn practices remain. Pediatric practices, on the other hand, are ideally suited for vaccine administration. Unfortunately, our colleagues delivering preventive care to young teens have persisted in considering the HPV vaccine as an optional adjunct to routine vaccination despite the advice of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), which for many years has recommended the HPV vaccine for girls. In 2011, the ACIP extended the HPV vaccine recommendation to include boys beginning at ages 11 to 12.

New 2-dose HPV vaccine schedule for children <15 years

In October 2016, 10 years after the first HPV vaccine approval, the ACIP and the CDC approved a reduced, 2-dose schedule for those younger than 15.¹ The first dose can be administered simultaneously with other recommended vaccines for 11- to 12-year-olds (the meningococcal and Tdap vaccines) and the second dose, 6 or 12 months later.² The 12-month interval would allow administration, once again, of all required vaccines at the annual visit.

Pivotal immunogenicity study

The new recommendation is based on robust multinational data (52 sites in 15 countries, N = 1,518) from an open-label trial.³ Immunogenicity of 2 doses of the 9-valent HPV vaccine in girls and boys ages 9 to 14 was compared with that of a standard 3-dose regimen in adolescents and young women ages 16 to 26. Five cohorts were studied: boys 9 to 14 given 2 doses at 6-month intervals; girls 9 to 14 given 2 doses at 6-month intervals; boys and girls 9 to 14 given 2 doses at a 12-month interval; girls 9 to 14 given the standard 3-dose regimen; and girls and young women 16 to 26 receiving 3 doses over 6 months.

The authors assessed the antibody responses against each HPV subtype 1 month after the final vaccine dose. Data from 1,377 participants (90.7% of the original cohort) were analyzed. Prespecified antibody titers were set conservatively to ensure adequate immunogenicity. Noninferiority criteria had to be met for all 9 HPV types.

Trial results. The immune responses for the 9- to 14-year-olds were consistently higher than those for the 16- to 26-year-old age group regardless of the regimen—not a surprising finding since the initial trials for HPV vaccine demonstrated a greater response among younger vaccine recipients. In this trial, higher antibody responses were found for the 12-month dosing interval than for the 6-month interval, although both regimens produced an adequate response.

Immunogenicity remained at 6 months. Antibody levels were retested 6 months after the last dose of HPV vaccine in a post hoc analysis. In all groups the antibody titers declined; however, there was no difference between the 2- and 3-dose cohorts. All levels remained above a threshold required for immunogenicity.

Related article:
2015 Update on cervical disease: New ammo for HPV prevention and screening

Simplified dosing may help increase vaccination rates

What does this new dosing regimen mean for practice? It will be simpler to incorporate HPV vaccination routinely into the standard vaccine regimen for preadolescent boys and girls. In addition, counseling for HPV vaccine administration can be combined with counseling for the meningococcal vaccine and routine Tdap booster.

Notably, primary care physicians have reported perceiving HPV vaccine discussions with parents as burdensome, and they tend to discuss it last after conversations about Tdap and meningococcal vaccines.⁴ Brewer and colleagues⁵ documented a 5% increase in first HPV vaccine doses among patients in practices in which the providers were taught to “announce” the need for HPV vaccine along with other routine vaccines. There was no increase in HPV vaccine uptake among practices in which providers were taught to “discuss” HPV with parents and to address their concerns, or in control practices. Therefore, less conversation about HPV and the HPV vaccine, as distinct from any other recommended vaccines, is better.

With the new 2-dose regimen, it should be easier to convey that the HPV vaccine is another necessary, routine intervention for children’s health. We should be able to achieve 90% vaccination rates for HPV—similar to rates for Tdap.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The recognition that human papillomavirus (HPV) oncogenic viruses cause cervical carcinoma remains one of the most game-changing medical discoveries of the last century. Improvements in screening options for detecting cervical cancer precursors followed. We now have the ability to detect high-risk HPV subtypes in routine specimens. Finally, a highly effective vaccine was developed that targets HPV types 16 and 18, which are responsible for causing approximately 70% of all cases of cervical carcinoma.

In one of the original vaccines HPV types 6 and 11, responsible for 90% of all genital warts, were also targeted. In 2014, a 9-valent vaccine incorporating an additional 5 HPV strains (31, 33, 45, 52, and 58) was approved and is set to replace all previous vaccine versions. Together, these 7 oncogenic HPV types are responsible for approximately 90% of HPV-related cancers, including cervical, anal, oropharyngeal, vaginal, and vulvar cancer.

By vaccinating boys and girls between ages 9 and 21 (for males) and 9 and 26 (for females), we could effectively eliminate 90% of genital warts and 90% of all HPV-related cancers. So why have we not capitalized on this extraordinary discovery? In 2016, why were only 40% of teenage girls and less than 25% of teenage boys vaccinated against HPV when we are immunizing 80% to 90% of these populations with tetanus, diphtheria, and acellular pertusis (Tdap) and meningococcal vaccines?

Related article:
2016 Update on cervical disease

Barriers to HPV vaccination

When the first HPV vaccine was approved in 2006, cost was a significant factor. Many health insurance plans did not cover this “discretionary” vaccine, which was viewed as a prevention for sexually transmitted infections rather than as a valuable intervention for the prevention of cervical and other cancers. At well over $125 per dose with 3 doses required for a full series, ObGyns were reluctant to stock and provide these expensive vaccines without assurance of reimbursement. The logistics of recalling patients for their subsequent vaccine doses were challenging for offices that were not accustomed to seeing patients for preventive care activities more than once a year. In addition, the office infrastructure required to maintain the vaccine stock and manage the necessary paperwork could be daunting. Finally, the requirement that patients be observed for 15 to 30 minutes in the office after vaccine administration created efficiency and rooming problems in busy, active practices.

Over time, almost all payers covered the HPV vaccines, but the logistical issues in ObGyn practices remain. Pediatric practices, on the other hand, are ideally suited for vaccine administration. Unfortunately, our colleagues delivering preventive care to young teens have persisted in considering the HPV vaccine as an optional adjunct to routine vaccination despite the advice of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), which for many years has recommended the HPV vaccine for girls. In 2011, the ACIP extended the HPV vaccine recommendation to include boys beginning at ages 11 to 12.

New 2-dose HPV vaccine schedule for children <15 years

In October 2016, 10 years after the first HPV vaccine approval, the ACIP and the CDC approved a reduced, 2-dose schedule for those younger than 15.¹ The first dose can be administered simultaneously with other recommended vaccines for 11- to 12-year-olds (the meningococcal and Tdap vaccines) and the second dose, 6 or 12 months later.² The 12-month interval would allow administration, once again, of all required vaccines at the annual visit.

Pivotal immunogenicity study

The new recommendation is based on robust multinational data (52 sites in 15 countries, N = 1,518) from an open-label trial.³ Immunogenicity of 2 doses of the 9-valent HPV vaccine in girls and boys ages 9 to 14 was compared with that of a standard 3-dose regimen in adolescents and young women ages 16 to 26. Five cohorts were studied: boys 9 to 14 given 2 doses at 6-month intervals; girls 9 to 14 given 2 doses at 6-month intervals; boys and girls 9 to 14 given 2 doses at a 12-month interval; girls 9 to 14 given the standard 3-dose regimen; and girls and young women 16 to 26 receiving 3 doses over 6 months.

The authors assessed the antibody responses against each HPV subtype 1 month after the final vaccine dose. Data from 1,377 participants (90.7% of the original cohort) were analyzed. Prespecified antibody titers were set conservatively to ensure adequate immunogenicity. Noninferiority criteria had to be met for all 9 HPV types.

Trial results. The immune responses for the 9- to 14-year-olds were consistently higher than those for the 16- to 26-year-old age group regardless of the regimen—not a surprising finding since the initial trials for HPV vaccine demonstrated a greater response among younger vaccine recipients. In this trial, higher antibody responses were found for the 12-month dosing interval than for the 6-month interval, although both regimens produced an adequate response.

Immunogenicity remained at 6 months. Antibody levels were retested 6 months after the last dose of HPV vaccine in a post hoc analysis. In all groups the antibody titers declined; however, there was no difference between the 2- and 3-dose cohorts. All levels remained above a threshold required for immunogenicity.

Related article:
2015 Update on cervical disease: New ammo for HPV prevention and screening

Simplified dosing may help increase vaccination rates

What does this new dosing regimen mean for practice? It will be simpler to incorporate HPV vaccination routinely into the standard vaccine regimen for preadolescent boys and girls. In addition, counseling for HPV vaccine administration can be combined with counseling for the meningococcal vaccine and routine Tdap booster.

Notably, primary care physicians have reported perceiving HPV vaccine discussions with parents as burdensome, and they tend to discuss it last after conversations about Tdap and meningococcal vaccines.⁴ Brewer and colleagues⁵ documented a 5% increase in first HPV vaccine doses among patients in practices in which the providers were taught to “announce” the need for HPV vaccine along with other routine vaccines. There was no increase in HPV vaccine uptake among practices in which providers were taught to “discuss” HPV with parents and to address their concerns, or in control practices. Therefore, less conversation about HPV and the HPV vaccine, as distinct from any other recommended vaccines, is better.

With the new 2-dose regimen, it should be easier to convey that the HPV vaccine is another necessary, routine intervention for children’s health. We should be able to achieve 90% vaccination rates for HPV—similar to rates for Tdap.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

HOUSTON – Ticagrelor outperformed aspirin in preventing a combination of recurrent stroke, heart attack, and death – but only in patients whose index stroke was probably related to atherosclerosis.

The antiplatelet drug reduced the risk of the composite endpoint by 32%, compared with aspirin, in stroke patients with proven ipsilateral atherosclerotic stenosis (hazard ratio, 0.68). But ticagrelor (Brilinta) had no effect at all in those without stenosis (HR, 0.97), Pierre Amarenco, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

Copyright American Stroke Association

msullivan@frontlinemedcom.com

On Twitter @alz_gal

HOUSTON – Ticagrelor outperformed aspirin in preventing a combination of recurrent stroke, heart attack, and death – but only in patients whose index stroke was probably related to atherosclerosis.

The antiplatelet drug reduced the risk of the composite endpoint by 32%, compared with aspirin, in stroke patients with proven ipsilateral atherosclerotic stenosis (hazard ratio, 0.68). But ticagrelor (Brilinta) had no effect at all in those without stenosis (HR, 0.97), Pierre Amarenco, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

Copyright American Stroke Association

msullivan@frontlinemedcom.com

On Twitter @alz_gal

HOUSTON – Ticagrelor outperformed aspirin in preventing a combination of recurrent stroke, heart attack, and death – but only in patients whose index stroke was probably related to atherosclerosis.

The antiplatelet drug reduced the risk of the composite endpoint by 32%, compared with aspirin, in stroke patients with proven ipsilateral atherosclerotic stenosis (hazard ratio, 0.68). But ticagrelor (Brilinta) had no effect at all in those without stenosis (HR, 0.97), Pierre Amarenco, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

Copyright American Stroke Association

msullivan@frontlinemedcom.com

On Twitter @alz_gal

The increasing incidence of subdural hematoma may be linked to increasing use of antithrombotics, according to data published online Feb. 28 in JAMA.

A retrospective case-control study of 10,010 patients aged 20-89 years with a first-time subdural hematoma, matched by age, sex, and year to 400,380 general controls, showed treatment with a vitamin K antagonist was associated with a 3.69 greater risk of subdural hematoma, compared with controls, and a fourfold increase in risk when used concurrently with an antiplatelet drug (JAMA. 2017;317:836-46. doi: 10.1001/jama.2017.0639).

Low-dose aspirin alone was associated with a 24% increase in the risk of subdural hematoma; clopidogrel was associated with an 87% increase; and a direct oral anticoagulant such as dabigatran etexilate, rivaroxaban, or apixaban was associated with a 73% increase in risk.

Antithrombotic drugs were also associated with an increased risk of death from a subdural hematoma within 30 days after discharge for the hematoma’s diagnosis, an effect most evident with a direct oral anticoagulant or vitamin K antagonist.

Over the course of the Danish population-based study, which covered 2000-2015, the prevalence of antithrombotic drug use more than doubled, from 31 individuals per 1,000 to 76.9 per 1,000.

At the same time, the incidence of subdural hematoma nearly doubled (10.9 per 100,000 person-years to 19 per 100,000 person-years). The increase in subdural hematoma was greatest among older patients, from 55.1 per 100,000 person-years to 99.7 per 100,000 person-years.

“Although use of antithrombotic drugs has long been recognized as a risk factor for subdural hematoma, previous studies were either based exclusively on patients with subdural hematoma (i.e.,with no comparison group) or focused exclusively on patients treated with an anticoagulant,” wrote David Gaist, MD, PhD, of Odense University Hospital in Denmark and coauthors.

While the risk of subdural hematoma was greatest for the shortest duration of treatment with low-dose aspirin, the risk remained steady across all durations of treatment with clopidogrel and did not vary significantly for direct oral anticoagulants or vitamin K antagonists.

Women were more likely to show an increased risk of subdural hematoma with low-dose aspirin or vitamin K antagonist than men.

The analysis also showed that the association between low-dose aspirin and subdural hematoma was significantly higher for individuals aged 75-89 years than for those aged 20-64 years.

“Furthermore, the present results emphasize that the major shifts in patterns of antithrombotic drug treatment for older individuals, and the increasing use of more aggressive antithrombotic regimens, have already had a major effect on subdural hematoma incidence,” the authors wrote.

Four authors declared funds from the pharmaceutical industry, including one advisory board position. No other conflicts of interest were declared.

The increasing incidence of subdural hematoma may be linked to increasing use of antithrombotics, according to data published online Feb. 28 in JAMA.

A retrospective case-control study of 10,010 patients aged 20-89 years with a first-time subdural hematoma, matched by age, sex, and year to 400,380 general controls, showed treatment with a vitamin K antagonist was associated with a 3.69 greater risk of subdural hematoma, compared with controls, and a fourfold increase in risk when used concurrently with an antiplatelet drug (JAMA. 2017;317:836-46. doi: 10.1001/jama.2017.0639).

Low-dose aspirin alone was associated with a 24% increase in the risk of subdural hematoma; clopidogrel was associated with an 87% increase; and a direct oral anticoagulant such as dabigatran etexilate, rivaroxaban, or apixaban was associated with a 73% increase in risk.

Antithrombotic drugs were also associated with an increased risk of death from a subdural hematoma within 30 days after discharge for the hematoma’s diagnosis, an effect most evident with a direct oral anticoagulant or vitamin K antagonist.

Over the course of the Danish population-based study, which covered 2000-2015, the prevalence of antithrombotic drug use more than doubled, from 31 individuals per 1,000 to 76.9 per 1,000.

At the same time, the incidence of subdural hematoma nearly doubled (10.9 per 100,000 person-years to 19 per 100,000 person-years). The increase in subdural hematoma was greatest among older patients, from 55.1 per 100,000 person-years to 99.7 per 100,000 person-years.

“Although use of antithrombotic drugs has long been recognized as a risk factor for subdural hematoma, previous studies were either based exclusively on patients with subdural hematoma (i.e.,with no comparison group) or focused exclusively on patients treated with an anticoagulant,” wrote David Gaist, MD, PhD, of Odense University Hospital in Denmark and coauthors.

While the risk of subdural hematoma was greatest for the shortest duration of treatment with low-dose aspirin, the risk remained steady across all durations of treatment with clopidogrel and did not vary significantly for direct oral anticoagulants or vitamin K antagonists.

Women were more likely to show an increased risk of subdural hematoma with low-dose aspirin or vitamin K antagonist than men.

The analysis also showed that the association between low-dose aspirin and subdural hematoma was significantly higher for individuals aged 75-89 years than for those aged 20-64 years.

“Furthermore, the present results emphasize that the major shifts in patterns of antithrombotic drug treatment for older individuals, and the increasing use of more aggressive antithrombotic regimens, have already had a major effect on subdural hematoma incidence,” the authors wrote.

Four authors declared funds from the pharmaceutical industry, including one advisory board position. No other conflicts of interest were declared.

The increasing incidence of subdural hematoma may be linked to increasing use of antithrombotics, according to data published online Feb. 28 in JAMA.

A retrospective case-control study of 10,010 patients aged 20-89 years with a first-time subdural hematoma, matched by age, sex, and year to 400,380 general controls, showed treatment with a vitamin K antagonist was associated with a 3.69 greater risk of subdural hematoma, compared with controls, and a fourfold increase in risk when used concurrently with an antiplatelet drug (JAMA. 2017;317:836-46. doi: 10.1001/jama.2017.0639).

Low-dose aspirin alone was associated with a 24% increase in the risk of subdural hematoma; clopidogrel was associated with an 87% increase; and a direct oral anticoagulant such as dabigatran etexilate, rivaroxaban, or apixaban was associated with a 73% increase in risk.

Antithrombotic drugs were also associated with an increased risk of death from a subdural hematoma within 30 days after discharge for the hematoma’s diagnosis, an effect most evident with a direct oral anticoagulant or vitamin K antagonist.

Over the course of the Danish population-based study, which covered 2000-2015, the prevalence of antithrombotic drug use more than doubled, from 31 individuals per 1,000 to 76.9 per 1,000.

At the same time, the incidence of subdural hematoma nearly doubled (10.9 per 100,000 person-years to 19 per 100,000 person-years). The increase in subdural hematoma was greatest among older patients, from 55.1 per 100,000 person-years to 99.7 per 100,000 person-years.

“Although use of antithrombotic drugs has long been recognized as a risk factor for subdural hematoma, previous studies were either based exclusively on patients with subdural hematoma (i.e.,with no comparison group) or focused exclusively on patients treated with an anticoagulant,” wrote David Gaist, MD, PhD, of Odense University Hospital in Denmark and coauthors.

While the risk of subdural hematoma was greatest for the shortest duration of treatment with low-dose aspirin, the risk remained steady across all durations of treatment with clopidogrel and did not vary significantly for direct oral anticoagulants or vitamin K antagonists.

Women were more likely to show an increased risk of subdural hematoma with low-dose aspirin or vitamin K antagonist than men.

The analysis also showed that the association between low-dose aspirin and subdural hematoma was significantly higher for individuals aged 75-89 years than for those aged 20-64 years.

“Furthermore, the present results emphasize that the major shifts in patterns of antithrombotic drug treatment for older individuals, and the increasing use of more aggressive antithrombotic regimens, have already had a major effect on subdural hematoma incidence,” the authors wrote.

Four authors declared funds from the pharmaceutical industry, including one advisory board position. No other conflicts of interest were declared.

The purpose of screening mammography is to detect tumors when they are small and nonpalpable in order to prevent more advanced breast tumors in women. Overdiagnosis, which leads to unnecessary treatment, refers to screen-detected tumors that will not lead to symptoms. Overdiagnosis cannot be measured directly and, therefore, understanding this concept is problematic for both women and clinicians.

Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns

Observations from other types of cancer screening put overdiagnosis in perspective

To help us grasp the overall issue of overdiagnosis, we can consider screening mammography alongside cervical cancer screening and colon cancer screening. For instance, screening with cervical cytology has reduced the incidence of and mortality from invasive cervical cancer.¹ Likewise, colonoscopy repeatedly has been found to reduce colon cancer mortality.^2,3 Decades of media messaging have emphasized the benefits of screening mammograms.⁴ However, and in contrast with cervical cytology and colonoscopy, screening mammography has not reduced the incidence of breast cancer presenting with metastatic (advanced) disease.⁵ Likewise, as the Danish authors of a recent study published in Annals of Internal Medicine point out, screening mammography has not achieved the promised reduction in breast cancer mortality.

New data from Denmark highlight overdiagnosis concerns

Jørgensen and colleagues conducted a cohort study to estimate the incidence of screen-detected tumors that would not become clinically relevant (overdiagnosis) among women aged 35 to 84 years between 1980 and 2010 in Denmark.⁶ This country offers a particularly well-suited backdrop for a study of overdiagnosis because biennial screening mammography was introduced by region beginning in the early 1990s. By 2007, one-fifth of the country’s female population aged 50 to 69 years were invited to participate. In the following years, screening became universal for Danish women in this age group.

For the study, researchers identified the size of all invasive breast cancer tumors diagnosed over the study period and then compared the incidence rates of advanced tumors (more than 20-mm in size at detection) with nonadvanced tumors in screened and unscreened Danish regions. The investigators took into account regional differences not related to screening by assessing the trends in diagnosis of advanced and nonadvanced tumors in screened and unscreened regions among women older and younger than those screened. This gave them a better estimate of the incidence of overdiagnosis.⁶

Jørgensen and colleagues found that breast cancer screening resulted in an increase in the incidence of nonadvanced tumors, but that it did not reduce the incidence of advanced tumors. They estimated that 39% of the invasive tumors found among women aged 50 to 69 were overdiagnosed.⁶

These Danish study results, that more than one-third of screen-detected tumors represent overdiagnosis, are similar to those found for studies conducted in the United States and other countries.^7,8 The lengthy follow-up after initiation of screening and the assessment of trends in unscreened women represent strengths of the study by Jørgensen and colleagues, and speak to concerns voiced by those skeptical of reported overdiagnosis incidence rates.⁹

Although breast cancer mortality is declining, the lion’s share of this decline has resulted from improvements in systemic therapy rather than from screening mammography. Widespread screening mammography has resulted in a scenario in which women are more likely to have a breast cancer that was overdiagnosed than in having earlier detection of a tumor destined to grow larger.⁵ In the future, by targeting higher-risk women, screening may result in a better benefit:risk ratio. However, and as pointed out by Otis Brawley, MD, Chief Medical and Scientific Officer of the American Cancer Society, we must acknowledge that overdiagnosis is common, the benefits of screening have been overstated, and some patients considered as “cured” from breast cancer have in fact been harmed by unneeded treatment.¹⁰

Related article:
No surprises from the USPSTF with new guidance on screening mammography

My breast cancer screening approach

As Brawley indicates, we should not abandon screening.¹⁰ I continue to recommend screening based on US Preventive Services Taskforce guidance, beginning biennial screens at age 50.¹¹ I also recognize that some women prefer earlier and more frequent screens, while others may prefer less frequent or even no screening.

The purpose of screening mammography is to detect tumors when they are small and nonpalpable in order to prevent more advanced breast tumors in women. Overdiagnosis, which leads to unnecessary treatment, refers to screen-detected tumors that will not lead to symptoms. Overdiagnosis cannot be measured directly and, therefore, understanding this concept is problematic for both women and clinicians.

Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns

Observations from other types of cancer screening put overdiagnosis in perspective

To help us grasp the overall issue of overdiagnosis, we can consider screening mammography alongside cervical cancer screening and colon cancer screening. For instance, screening with cervical cytology has reduced the incidence of and mortality from invasive cervical cancer.¹ Likewise, colonoscopy repeatedly has been found to reduce colon cancer mortality.^2,3 Decades of media messaging have emphasized the benefits of screening mammograms.⁴ However, and in contrast with cervical cytology and colonoscopy, screening mammography has not reduced the incidence of breast cancer presenting with metastatic (advanced) disease.⁵ Likewise, as the Danish authors of a recent study published in Annals of Internal Medicine point out, screening mammography has not achieved the promised reduction in breast cancer mortality.

New data from Denmark highlight overdiagnosis concerns

Jørgensen and colleagues conducted a cohort study to estimate the incidence of screen-detected tumors that would not become clinically relevant (overdiagnosis) among women aged 35 to 84 years between 1980 and 2010 in Denmark.⁶ This country offers a particularly well-suited backdrop for a study of overdiagnosis because biennial screening mammography was introduced by region beginning in the early 1990s. By 2007, one-fifth of the country’s female population aged 50 to 69 years were invited to participate. In the following years, screening became universal for Danish women in this age group.

For the study, researchers identified the size of all invasive breast cancer tumors diagnosed over the study period and then compared the incidence rates of advanced tumors (more than 20-mm in size at detection) with nonadvanced tumors in screened and unscreened Danish regions. The investigators took into account regional differences not related to screening by assessing the trends in diagnosis of advanced and nonadvanced tumors in screened and unscreened regions among women older and younger than those screened. This gave them a better estimate of the incidence of overdiagnosis.⁶

Jørgensen and colleagues found that breast cancer screening resulted in an increase in the incidence of nonadvanced tumors, but that it did not reduce the incidence of advanced tumors. They estimated that 39% of the invasive tumors found among women aged 50 to 69 were overdiagnosed.⁶

These Danish study results, that more than one-third of screen-detected tumors represent overdiagnosis, are similar to those found for studies conducted in the United States and other countries.^7,8 The lengthy follow-up after initiation of screening and the assessment of trends in unscreened women represent strengths of the study by Jørgensen and colleagues, and speak to concerns voiced by those skeptical of reported overdiagnosis incidence rates.⁹

Although breast cancer mortality is declining, the lion’s share of this decline has resulted from improvements in systemic therapy rather than from screening mammography. Widespread screening mammography has resulted in a scenario in which women are more likely to have a breast cancer that was overdiagnosed than in having earlier detection of a tumor destined to grow larger.⁵ In the future, by targeting higher-risk women, screening may result in a better benefit:risk ratio. However, and as pointed out by Otis Brawley, MD, Chief Medical and Scientific Officer of the American Cancer Society, we must acknowledge that overdiagnosis is common, the benefits of screening have been overstated, and some patients considered as “cured” from breast cancer have in fact been harmed by unneeded treatment.¹⁰

Related article:
No surprises from the USPSTF with new guidance on screening mammography

My breast cancer screening approach

As Brawley indicates, we should not abandon screening.¹⁰ I continue to recommend screening based on US Preventive Services Taskforce guidance, beginning biennial screens at age 50.¹¹ I also recognize that some women prefer earlier and more frequent screens, while others may prefer less frequent or even no screening.

The purpose of screening mammography is to detect tumors when they are small and nonpalpable in order to prevent more advanced breast tumors in women. Overdiagnosis, which leads to unnecessary treatment, refers to screen-detected tumors that will not lead to symptoms. Overdiagnosis cannot be measured directly and, therefore, understanding this concept is problematic for both women and clinicians.

Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns

Observations from other types of cancer screening put overdiagnosis in perspective

To help us grasp the overall issue of overdiagnosis, we can consider screening mammography alongside cervical cancer screening and colon cancer screening. For instance, screening with cervical cytology has reduced the incidence of and mortality from invasive cervical cancer.¹ Likewise, colonoscopy repeatedly has been found to reduce colon cancer mortality.^2,3 Decades of media messaging have emphasized the benefits of screening mammograms.⁴ However, and in contrast with cervical cytology and colonoscopy, screening mammography has not reduced the incidence of breast cancer presenting with metastatic (advanced) disease.⁵ Likewise, as the Danish authors of a recent study published in Annals of Internal Medicine point out, screening mammography has not achieved the promised reduction in breast cancer mortality.

New data from Denmark highlight overdiagnosis concerns

Jørgensen and colleagues conducted a cohort study to estimate the incidence of screen-detected tumors that would not become clinically relevant (overdiagnosis) among women aged 35 to 84 years between 1980 and 2010 in Denmark.⁶ This country offers a particularly well-suited backdrop for a study of overdiagnosis because biennial screening mammography was introduced by region beginning in the early 1990s. By 2007, one-fifth of the country’s female population aged 50 to 69 years were invited to participate. In the following years, screening became universal for Danish women in this age group.

For the study, researchers identified the size of all invasive breast cancer tumors diagnosed over the study period and then compared the incidence rates of advanced tumors (more than 20-mm in size at detection) with nonadvanced tumors in screened and unscreened Danish regions. The investigators took into account regional differences not related to screening by assessing the trends in diagnosis of advanced and nonadvanced tumors in screened and unscreened regions among women older and younger than those screened. This gave them a better estimate of the incidence of overdiagnosis.⁶

Jørgensen and colleagues found that breast cancer screening resulted in an increase in the incidence of nonadvanced tumors, but that it did not reduce the incidence of advanced tumors. They estimated that 39% of the invasive tumors found among women aged 50 to 69 were overdiagnosed.⁶

These Danish study results, that more than one-third of screen-detected tumors represent overdiagnosis, are similar to those found for studies conducted in the United States and other countries.^7,8 The lengthy follow-up after initiation of screening and the assessment of trends in unscreened women represent strengths of the study by Jørgensen and colleagues, and speak to concerns voiced by those skeptical of reported overdiagnosis incidence rates.⁹

Although breast cancer mortality is declining, the lion’s share of this decline has resulted from improvements in systemic therapy rather than from screening mammography. Widespread screening mammography has resulted in a scenario in which women are more likely to have a breast cancer that was overdiagnosed than in having earlier detection of a tumor destined to grow larger.⁵ In the future, by targeting higher-risk women, screening may result in a better benefit:risk ratio. However, and as pointed out by Otis Brawley, MD, Chief Medical and Scientific Officer of the American Cancer Society, we must acknowledge that overdiagnosis is common, the benefits of screening have been overstated, and some patients considered as “cured” from breast cancer have in fact been harmed by unneeded treatment.¹⁰

Related article:
No surprises from the USPSTF with new guidance on screening mammography

My breast cancer screening approach

As Brawley indicates, we should not abandon screening.¹⁰ I continue to recommend screening based on US Preventive Services Taskforce guidance, beginning biennial screens at age 50.¹¹ I also recognize that some women prefer earlier and more frequent screens, while others may prefer less frequent or even no screening.

EXPERT COMMENTARY

Both the Centers for Disease Control and Prevention and the World Health Organization currently recommend that patients with trichomoniasis be treated with a single 2-g oral dose of metronidazole.¹ Following treatment, the reported rates of repeat infection or persistent infection range from 5% to 31%. Repeat infection rates may be even higher in HIV-infected patients.

Repeat infections presumably result from a failure to treat the patient’s sexual partner(s) or from the patient’s exposure to a new partner. Persistent infections, however, may be the result of inadequate primary therapy, even though inherent resistance of the organism to metronidazole is quite rare. To date, no single study has shown that single-dose therapy is inferior to multidose therapy, but most of these studies lack sufficient power to completely exclude the possibility of a type-2 statistical error.² To compare single-dose with multidose therapy for trichomoniasis in a more systematic manner, Howe and Kissinger conducted a meta-analysis, which was recently published in Sexually Transmitted Diseases.

Related article:
2016 Update on infectious disease

Details of the study

The investigators conducted a comprehensive literature search using Embase, Medline, and ClinicalTrials.gov; 6 articles were included in the final results, 4 of which were randomized controlled trials. Approximately 1,300 participants were included in the 6 trials. All of the patients in the single-dose treatment arms received a 2-g oral dose of metronidazole. In the multidose treatment arms for 2 studies the participants received metronidazole 250 mg orally 3 times daily for 7 days, and for 2 studies the dose was 200 mg 3 times daily for 7 days. The fifth study employed a 500-mg oral dose of metronidazole twice daily for 7 days. The final study used a 400-mg oral dose twice daily for 5 days. The key study end point was treatment failure.

Howe and Kissinger demonstrated that women who received the single 2-g dose were 1.87 times (95% CI, 1.23−2.82; P<.01) more likely to experience a treatment failure compared with women who received a multidose regimen. When the one study that focused only on HIV-infected women was excluded from analysis, the results were similar. The relative risk of treatment failure was 1.80 (95% CI, 1.07−3.02; P<.03).

Related article:
Preventing infection after cesarean delivery: Evidence-based guidance

Study limitations

The results of this meta-analysis are interesting and provocative. However, the analysis has several important limitations. Five of the 6 studies were published many years ago (1971, 1972, 1979, 1980, and 1982). The most recent study was published in 2010. The investigators used 4 different multidose regimens, with metronidazole doses ranging from 200 mg to 500 mg and duration of therapy ranging from 5 to 7 days. Four of the six investigations used saline microscopy as the definitive diagnostic test of treatment failure. Compared with culture or DNA testing, microscopy is not as accurate. Moreover, the timing of retesting varied in the studies, and some apparent treatment failures actually may have been due to reinfection. In addition, the studies did not consistently track the adequacy of treatment of the sexual partner.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Both the Centers for Disease Control and Prevention and the World Health Organization currently recommend that patients with trichomoniasis be treated with a single 2-g oral dose of metronidazole.¹ Following treatment, the reported rates of repeat infection or persistent infection range from 5% to 31%. Repeat infection rates may be even higher in HIV-infected patients.

Repeat infections presumably result from a failure to treat the patient’s sexual partner(s) or from the patient’s exposure to a new partner. Persistent infections, however, may be the result of inadequate primary therapy, even though inherent resistance of the organism to metronidazole is quite rare. To date, no single study has shown that single-dose therapy is inferior to multidose therapy, but most of these studies lack sufficient power to completely exclude the possibility of a type-2 statistical error.² To compare single-dose with multidose therapy for trichomoniasis in a more systematic manner, Howe and Kissinger conducted a meta-analysis, which was recently published in Sexually Transmitted Diseases.

Related article:
2016 Update on infectious disease

Details of the study

The investigators conducted a comprehensive literature search using Embase, Medline, and ClinicalTrials.gov; 6 articles were included in the final results, 4 of which were randomized controlled trials. Approximately 1,300 participants were included in the 6 trials. All of the patients in the single-dose treatment arms received a 2-g oral dose of metronidazole. In the multidose treatment arms for 2 studies the participants received metronidazole 250 mg orally 3 times daily for 7 days, and for 2 studies the dose was 200 mg 3 times daily for 7 days. The fifth study employed a 500-mg oral dose of metronidazole twice daily for 7 days. The final study used a 400-mg oral dose twice daily for 5 days. The key study end point was treatment failure.

Howe and Kissinger demonstrated that women who received the single 2-g dose were 1.87 times (95% CI, 1.23−2.82; P<.01) more likely to experience a treatment failure compared with women who received a multidose regimen. When the one study that focused only on HIV-infected women was excluded from analysis, the results were similar. The relative risk of treatment failure was 1.80 (95% CI, 1.07−3.02; P<.03).

Related article:
Preventing infection after cesarean delivery: Evidence-based guidance

Study limitations

The results of this meta-analysis are interesting and provocative. However, the analysis has several important limitations. Five of the 6 studies were published many years ago (1971, 1972, 1979, 1980, and 1982). The most recent study was published in 2010. The investigators used 4 different multidose regimens, with metronidazole doses ranging from 200 mg to 500 mg and duration of therapy ranging from 5 to 7 days. Four of the six investigations used saline microscopy as the definitive diagnostic test of treatment failure. Compared with culture or DNA testing, microscopy is not as accurate. Moreover, the timing of retesting varied in the studies, and some apparent treatment failures actually may have been due to reinfection. In addition, the studies did not consistently track the adequacy of treatment of the sexual partner.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Both the Centers for Disease Control and Prevention and the World Health Organization currently recommend that patients with trichomoniasis be treated with a single 2-g oral dose of metronidazole.¹ Following treatment, the reported rates of repeat infection or persistent infection range from 5% to 31%. Repeat infection rates may be even higher in HIV-infected patients.

Repeat infections presumably result from a failure to treat the patient’s sexual partner(s) or from the patient’s exposure to a new partner. Persistent infections, however, may be the result of inadequate primary therapy, even though inherent resistance of the organism to metronidazole is quite rare. To date, no single study has shown that single-dose therapy is inferior to multidose therapy, but most of these studies lack sufficient power to completely exclude the possibility of a type-2 statistical error.² To compare single-dose with multidose therapy for trichomoniasis in a more systematic manner, Howe and Kissinger conducted a meta-analysis, which was recently published in Sexually Transmitted Diseases.

Related article:
2016 Update on infectious disease

Details of the study

The investigators conducted a comprehensive literature search using Embase, Medline, and ClinicalTrials.gov; 6 articles were included in the final results, 4 of which were randomized controlled trials. Approximately 1,300 participants were included in the 6 trials. All of the patients in the single-dose treatment arms received a 2-g oral dose of metronidazole. In the multidose treatment arms for 2 studies the participants received metronidazole 250 mg orally 3 times daily for 7 days, and for 2 studies the dose was 200 mg 3 times daily for 7 days. The fifth study employed a 500-mg oral dose of metronidazole twice daily for 7 days. The final study used a 400-mg oral dose twice daily for 5 days. The key study end point was treatment failure.

Howe and Kissinger demonstrated that women who received the single 2-g dose were 1.87 times (95% CI, 1.23−2.82; P<.01) more likely to experience a treatment failure compared with women who received a multidose regimen. When the one study that focused only on HIV-infected women was excluded from analysis, the results were similar. The relative risk of treatment failure was 1.80 (95% CI, 1.07−3.02; P<.03).

Related article:
Preventing infection after cesarean delivery: Evidence-based guidance

Study limitations

The results of this meta-analysis are interesting and provocative. However, the analysis has several important limitations. Five of the 6 studies were published many years ago (1971, 1972, 1979, 1980, and 1982). The most recent study was published in 2010. The investigators used 4 different multidose regimens, with metronidazole doses ranging from 200 mg to 500 mg and duration of therapy ranging from 5 to 7 days. Four of the six investigations used saline microscopy as the definitive diagnostic test of treatment failure. Compared with culture or DNA testing, microscopy is not as accurate. Moreover, the timing of retesting varied in the studies, and some apparent treatment failures actually may have been due to reinfection. In addition, the studies did not consistently track the adequacy of treatment of the sexual partner.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The proportion of rectal cancer cases diagnosed in people younger than 55 years doubled over the past 2 decades, according to a report published online in the Journal of the National Cancer Institute.

In contrast, the proportion diagnosed in people older than 55 years has decreased over the last 4 decades, said Rebecca L. Siegel, MPH, strategic director of surveillance information services of surveillance and health services research at the American Cancer Society and her associates.

Courtesy Wikimedia Commons/nephron/Creative Commons License

AGA Resource

The AGA Colorectal Cancer Clinical Service Line provides tools to help you become more efficient, understand quality standards and improve the process of care for patients: http://www.gastro.org/patient-care/conditions-diseases/colorectal-cancer

The proportion of rectal cancer cases diagnosed in people younger than 55 years doubled over the past 2 decades, according to a report published online in the Journal of the National Cancer Institute.

In contrast, the proportion diagnosed in people older than 55 years has decreased over the last 4 decades, said Rebecca L. Siegel, MPH, strategic director of surveillance information services of surveillance and health services research at the American Cancer Society and her associates.

Courtesy Wikimedia Commons/nephron/Creative Commons License

AGA Resource

The AGA Colorectal Cancer Clinical Service Line provides tools to help you become more efficient, understand quality standards and improve the process of care for patients: http://www.gastro.org/patient-care/conditions-diseases/colorectal-cancer

The proportion of rectal cancer cases diagnosed in people younger than 55 years doubled over the past 2 decades, according to a report published online in the Journal of the National Cancer Institute.

In contrast, the proportion diagnosed in people older than 55 years has decreased over the last 4 decades, said Rebecca L. Siegel, MPH, strategic director of surveillance information services of surveillance and health services research at the American Cancer Society and her associates.

Courtesy Wikimedia Commons/nephron/Creative Commons License

AGA Resource

The AGA Colorectal Cancer Clinical Service Line provides tools to help you become more efficient, understand quality standards and improve the process of care for patients: http://www.gastro.org/patient-care/conditions-diseases/colorectal-cancer

The proportion of rectal cancer cases diagnosed in people younger than 55 years doubled over the past 2 decades, according to a report published online Feb. 28 in the Journal of the National Cancer Institute.

In contrast, the proportion diagnosed in people older than 55 years has decreased over the last 4 decades, said Rebecca L. Siegel, MPH, strategic director of surveillance information services of surveillance and health services research at the American Cancer Society and her associates.

Courtesy Wikimedia Commons/nephron/Creative Commons License

The proportion of rectal cancer cases diagnosed in people younger than 55 years doubled over the past 2 decades, according to a report published online Feb. 28 in the Journal of the National Cancer Institute.

In contrast, the proportion diagnosed in people older than 55 years has decreased over the last 4 decades, said Rebecca L. Siegel, MPH, strategic director of surveillance information services of surveillance and health services research at the American Cancer Society and her associates.

Courtesy Wikimedia Commons/nephron/Creative Commons License

The proportion of rectal cancer cases diagnosed in people younger than 55 years doubled over the past 2 decades, according to a report published online Feb. 28 in the Journal of the National Cancer Institute.

In contrast, the proportion diagnosed in people older than 55 years has decreased over the last 4 decades, said Rebecca L. Siegel, MPH, strategic director of surveillance information services of surveillance and health services research at the American Cancer Society and her associates.

Courtesy Wikimedia Commons/nephron/Creative Commons License