The Food and Drug Administration has accepted the JAK1/JAK2 inhibitor ruxolitinib (Jakafi) for priority review.

Incyte is seeking approval for ruxolitinib as a treatment for patients with acute graft-versus-host disease (GVHD) who have had an inadequate response to corticosteroids.

Wikimedia Commons/FitzColinGerald/Creative Commons License

“If approved, ruxolitinib will be the first and only treatment available in the U.S. for patients with acute GVHD who have not responded adequately to corticosteroid therapy,” Steven Stein, MD, chief medical officer at Incyte, said in a statement.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The designation generally means that the agency will act on the application within 6 months, rather than 10 months.

In addition to priority review, the FDA previously granted ruxolitinib breakthrough therapy and orphan drug designations.

The application is based on data from the ongoing, phase 2 REACH1 trial (NCT02953678), which is evaluating ruxolitinib in combination with corticosteroids in patients who have steroid-refractory acute GVHD.

Incyte announced top-line results from REACH1 in June, reporting on outcomes in 71 patients.

The study’s primary endpoint – overall response rate at day 28 – was met. Ruxolitinib produced an overall response rate of 55% at that time. However, 73% of patients responded to ruxolitinib at some point during the trial. Incyte said the most common treatment-emergent adverse events were anemia, thrombocytopenia, and neutropenia.

[email protected]

The Food and Drug Administration has accepted the JAK1/JAK2 inhibitor ruxolitinib (Jakafi) for priority review.

Incyte is seeking approval for ruxolitinib as a treatment for patients with acute graft-versus-host disease (GVHD) who have had an inadequate response to corticosteroids.

Wikimedia Commons/FitzColinGerald/Creative Commons License

“If approved, ruxolitinib will be the first and only treatment available in the U.S. for patients with acute GVHD who have not responded adequately to corticosteroid therapy,” Steven Stein, MD, chief medical officer at Incyte, said in a statement.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The designation generally means that the agency will act on the application within 6 months, rather than 10 months.

In addition to priority review, the FDA previously granted ruxolitinib breakthrough therapy and orphan drug designations.

The application is based on data from the ongoing, phase 2 REACH1 trial (NCT02953678), which is evaluating ruxolitinib in combination with corticosteroids in patients who have steroid-refractory acute GVHD.

Incyte announced top-line results from REACH1 in June, reporting on outcomes in 71 patients.

The study’s primary endpoint – overall response rate at day 28 – was met. Ruxolitinib produced an overall response rate of 55% at that time. However, 73% of patients responded to ruxolitinib at some point during the trial. Incyte said the most common treatment-emergent adverse events were anemia, thrombocytopenia, and neutropenia.

[email protected]

The Food and Drug Administration has accepted the JAK1/JAK2 inhibitor ruxolitinib (Jakafi) for priority review.

Incyte is seeking approval for ruxolitinib as a treatment for patients with acute graft-versus-host disease (GVHD) who have had an inadequate response to corticosteroids.

Wikimedia Commons/FitzColinGerald/Creative Commons License

“If approved, ruxolitinib will be the first and only treatment available in the U.S. for patients with acute GVHD who have not responded adequately to corticosteroid therapy,” Steven Stein, MD, chief medical officer at Incyte, said in a statement.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The designation generally means that the agency will act on the application within 6 months, rather than 10 months.

In addition to priority review, the FDA previously granted ruxolitinib breakthrough therapy and orphan drug designations.

The application is based on data from the ongoing, phase 2 REACH1 trial (NCT02953678), which is evaluating ruxolitinib in combination with corticosteroids in patients who have steroid-refractory acute GVHD.

Incyte announced top-line results from REACH1 in June, reporting on outcomes in 71 patients.

The study’s primary endpoint – overall response rate at day 28 – was met. Ruxolitinib produced an overall response rate of 55% at that time. However, 73% of patients responded to ruxolitinib at some point during the trial. Incyte said the most common treatment-emergent adverse events were anemia, thrombocytopenia, and neutropenia.

[email protected]

The Food and Drug Administration has granted OMS721 orphan designation for the treatment of hematopoietic stem cell transplant–associated thrombotic microangiopathy (HSCT-TMA).

OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.

The FDA previously granted OMS721 breakthrough therapy designation for HSCT-TMA and orphan designation for the prevention of complement-mediated TMA, including HSCT-TMA.

Omeros, the company developing OMS721, has established a compassionate use program for OMS721, which is active in the United States and Europe.

Phase 3 clinical programs are in progress for OMS721 in atypical hemolytic uremic syndrome, immunoglobulin A nephropathy, and HSCT-TMA. Two phase 2 trials of OMS721 – one in TMA and one in immunoglobulin A nephropathy – are ongoing.

Omeros announced results from the phase 2 TMA trial (NCT02222545) in February. The study includes adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post transplant. Patients receive weekly OMS721 treatments for 4-8 weeks at the discretion of the investigator.

At the time of Omeros’s announcement, 18 HSCT-TMA patients had been treated.

These patients had a significantly longer median overall survival at 347 days, compared with historical controls at 21 days (P less than .0001).

Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.

The mean platelet count increased from 18,100 x 10⁶/mL at baseline to 52,300 x 10⁶/mL (P = .017). The mean lactate dehydrogenase decreased from 591 U/L to 250 U/L (P less than .001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P = .003).

The most commonly reported adverse events were diarrhea and neutropenia. Four deaths occurred during the study. One of these – attributable to acute renal and respiratory failure – was considered possibly related to OMS721.

[email protected]

The Food and Drug Administration has granted OMS721 orphan designation for the treatment of hematopoietic stem cell transplant–associated thrombotic microangiopathy (HSCT-TMA).

OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.

The FDA previously granted OMS721 breakthrough therapy designation for HSCT-TMA and orphan designation for the prevention of complement-mediated TMA, including HSCT-TMA.

Omeros, the company developing OMS721, has established a compassionate use program for OMS721, which is active in the United States and Europe.

Phase 3 clinical programs are in progress for OMS721 in atypical hemolytic uremic syndrome, immunoglobulin A nephropathy, and HSCT-TMA. Two phase 2 trials of OMS721 – one in TMA and one in immunoglobulin A nephropathy – are ongoing.

Omeros announced results from the phase 2 TMA trial (NCT02222545) in February. The study includes adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post transplant. Patients receive weekly OMS721 treatments for 4-8 weeks at the discretion of the investigator.

At the time of Omeros’s announcement, 18 HSCT-TMA patients had been treated.

These patients had a significantly longer median overall survival at 347 days, compared with historical controls at 21 days (P less than .0001).

Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.

The mean platelet count increased from 18,100 x 10⁶/mL at baseline to 52,300 x 10⁶/mL (P = .017). The mean lactate dehydrogenase decreased from 591 U/L to 250 U/L (P less than .001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P = .003).

The most commonly reported adverse events were diarrhea and neutropenia. Four deaths occurred during the study. One of these – attributable to acute renal and respiratory failure – was considered possibly related to OMS721.

[email protected]

The Food and Drug Administration has granted OMS721 orphan designation for the treatment of hematopoietic stem cell transplant–associated thrombotic microangiopathy (HSCT-TMA).

OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.

The FDA previously granted OMS721 breakthrough therapy designation for HSCT-TMA and orphan designation for the prevention of complement-mediated TMA, including HSCT-TMA.

Omeros, the company developing OMS721, has established a compassionate use program for OMS721, which is active in the United States and Europe.

Phase 3 clinical programs are in progress for OMS721 in atypical hemolytic uremic syndrome, immunoglobulin A nephropathy, and HSCT-TMA. Two phase 2 trials of OMS721 – one in TMA and one in immunoglobulin A nephropathy – are ongoing.

Omeros announced results from the phase 2 TMA trial (NCT02222545) in February. The study includes adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post transplant. Patients receive weekly OMS721 treatments for 4-8 weeks at the discretion of the investigator.

At the time of Omeros’s announcement, 18 HSCT-TMA patients had been treated.

These patients had a significantly longer median overall survival at 347 days, compared with historical controls at 21 days (P less than .0001).

Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.

The mean platelet count increased from 18,100 x 10⁶/mL at baseline to 52,300 x 10⁶/mL (P = .017). The mean lactate dehydrogenase decreased from 591 U/L to 250 U/L (P less than .001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P = .003).

The most commonly reported adverse events were diarrhea and neutropenia. Four deaths occurred during the study. One of these – attributable to acute renal and respiratory failure – was considered possibly related to OMS721.

[email protected]

The Diagnosis: Pediculosis Pubis

Dermoscopy of the pubic hair demonstrated a louse clutching multiple shafts of hairs (Figure) as well as scattered nits, confirming the presence of Phthirus pubis and diagnosis of pediculosis pubis. The key clinical diagnostic feature in this case was severe itching of the pubic area, with visible nits present on pubic hairs. Itching and infestation also can involve other hair-bearing areas such as the chest, legs, and axillae. The patient was treated with permethrin cream 5% applied to the pubic area and chest. Symptoms and infestation were resolved at 1-week follow-up.

Pediculosis pubis is an infestation of pubic hairs by the pubic (crab) louse P pubis, which feeds on host blood. Other body areas covered with dense hair also may be involved; 60% of patients are infested in at least 2 different sites.¹ Pediculosis pubis is most commonly sexually transmitted through direct contact.² Worldwide prevalence has been estimated at approximately 2% of the adult population, and a survey of 817 US college students in 2009 indicated a lifetime prevalence of 1.3%.³ The prevalence is slightly higher in men, highest in men who have sex with men, and rare in individuals with shaved pubic hair.¹ The most common symptom is pruritus of the genital area. Infested patients also may develop asymptomatic bluish gray macules (maculae ceruleae) secondary to hemosiderin deposition from louse bites.⁴

The diagnosis of pediculosis pubis is made by identification of P pubis, either by examination with the naked eye or confirmation with dermoscopy or microscopy. Although the 0.8- to 1.2-mm lice are visible to the naked eye, they can be difficult to see if not filled with blood, and nits on the hairs can be mistaken for white piedra (fungal infection of the hair shafts) or trichomycosis pubis (bacterial infection of the hair shafts).⁴ Scabies and tinea cruris do not present with attachments to the hairs. Scabies may present with papules and burrows and tinea cruris with scaly erythematous plaques. Small numbers of lice and nits may be missed by the naked eye or a traditional magnifying glass.⁵ The use of dermoscopy allows for fast and accurate identification of the characteristic lice and nits, even in these more challenging cases.⁵ Accurate diagnosis is important, as approximately 31% of infested patients have other concurrent sexually transmitted infections that warrant screening.⁶

The Centers for Disease Control and Prevention recommends first-line treatment with permethrin cream (1% or 5%) or pyrethrin with piperonyl butoxide applied to all affected areas and washed off after 10 minutes.⁷ Patients should be reevaluated after 1 week if symptoms persist and re-treated if lice are found on examination.^7,8 Malathion lotion 0.5% (applied and washed off after 8-12 hours) or oral ivermectin (250 µg/kg, repeated after 2 weeks) may be used for alternative therapies or cases of permethrin or pyrethrin resistance.⁷ Ivermectin also is effective for involvement of eyelashes where topical insecticides should not be used.⁹ Sexual partners should be treated to prevent repeat transmission.^7,8 Bedding and clothing can be decontaminated by machine wash on hot cycle or isolating from body contact for 72 hours.⁷ Patients also should be screened for other sexually transmitted infections, including human immunodeficiency virus.⁶

The Diagnosis: Pediculosis Pubis

Dermoscopy of the pubic hair demonstrated a louse clutching multiple shafts of hairs (Figure) as well as scattered nits, confirming the presence of Phthirus pubis and diagnosis of pediculosis pubis. The key clinical diagnostic feature in this case was severe itching of the pubic area, with visible nits present on pubic hairs. Itching and infestation also can involve other hair-bearing areas such as the chest, legs, and axillae. The patient was treated with permethrin cream 5% applied to the pubic area and chest. Symptoms and infestation were resolved at 1-week follow-up.

Pediculosis pubis is an infestation of pubic hairs by the pubic (crab) louse P pubis, which feeds on host blood. Other body areas covered with dense hair also may be involved; 60% of patients are infested in at least 2 different sites.¹ Pediculosis pubis is most commonly sexually transmitted through direct contact.² Worldwide prevalence has been estimated at approximately 2% of the adult population, and a survey of 817 US college students in 2009 indicated a lifetime prevalence of 1.3%.³ The prevalence is slightly higher in men, highest in men who have sex with men, and rare in individuals with shaved pubic hair.¹ The most common symptom is pruritus of the genital area. Infested patients also may develop asymptomatic bluish gray macules (maculae ceruleae) secondary to hemosiderin deposition from louse bites.⁴

The diagnosis of pediculosis pubis is made by identification of P pubis, either by examination with the naked eye or confirmation with dermoscopy or microscopy. Although the 0.8- to 1.2-mm lice are visible to the naked eye, they can be difficult to see if not filled with blood, and nits on the hairs can be mistaken for white piedra (fungal infection of the hair shafts) or trichomycosis pubis (bacterial infection of the hair shafts).⁴ Scabies and tinea cruris do not present with attachments to the hairs. Scabies may present with papules and burrows and tinea cruris with scaly erythematous plaques. Small numbers of lice and nits may be missed by the naked eye or a traditional magnifying glass.⁵ The use of dermoscopy allows for fast and accurate identification of the characteristic lice and nits, even in these more challenging cases.⁵ Accurate diagnosis is important, as approximately 31% of infested patients have other concurrent sexually transmitted infections that warrant screening.⁶

The Centers for Disease Control and Prevention recommends first-line treatment with permethrin cream (1% or 5%) or pyrethrin with piperonyl butoxide applied to all affected areas and washed off after 10 minutes.⁷ Patients should be reevaluated after 1 week if symptoms persist and re-treated if lice are found on examination.^7,8 Malathion lotion 0.5% (applied and washed off after 8-12 hours) or oral ivermectin (250 µg/kg, repeated after 2 weeks) may be used for alternative therapies or cases of permethrin or pyrethrin resistance.⁷ Ivermectin also is effective for involvement of eyelashes where topical insecticides should not be used.⁹ Sexual partners should be treated to prevent repeat transmission.^7,8 Bedding and clothing can be decontaminated by machine wash on hot cycle or isolating from body contact for 72 hours.⁷ Patients also should be screened for other sexually transmitted infections, including human immunodeficiency virus.⁶

The Diagnosis: Pediculosis Pubis

Dermoscopy of the pubic hair demonstrated a louse clutching multiple shafts of hairs (Figure) as well as scattered nits, confirming the presence of Phthirus pubis and diagnosis of pediculosis pubis. The key clinical diagnostic feature in this case was severe itching of the pubic area, with visible nits present on pubic hairs. Itching and infestation also can involve other hair-bearing areas such as the chest, legs, and axillae. The patient was treated with permethrin cream 5% applied to the pubic area and chest. Symptoms and infestation were resolved at 1-week follow-up.

Pediculosis pubis is an infestation of pubic hairs by the pubic (crab) louse P pubis, which feeds on host blood. Other body areas covered with dense hair also may be involved; 60% of patients are infested in at least 2 different sites.¹ Pediculosis pubis is most commonly sexually transmitted through direct contact.² Worldwide prevalence has been estimated at approximately 2% of the adult population, and a survey of 817 US college students in 2009 indicated a lifetime prevalence of 1.3%.³ The prevalence is slightly higher in men, highest in men who have sex with men, and rare in individuals with shaved pubic hair.¹ The most common symptom is pruritus of the genital area. Infested patients also may develop asymptomatic bluish gray macules (maculae ceruleae) secondary to hemosiderin deposition from louse bites.⁴

The diagnosis of pediculosis pubis is made by identification of P pubis, either by examination with the naked eye or confirmation with dermoscopy or microscopy. Although the 0.8- to 1.2-mm lice are visible to the naked eye, they can be difficult to see if not filled with blood, and nits on the hairs can be mistaken for white piedra (fungal infection of the hair shafts) or trichomycosis pubis (bacterial infection of the hair shafts).⁴ Scabies and tinea cruris do not present with attachments to the hairs. Scabies may present with papules and burrows and tinea cruris with scaly erythematous plaques. Small numbers of lice and nits may be missed by the naked eye or a traditional magnifying glass.⁵ The use of dermoscopy allows for fast and accurate identification of the characteristic lice and nits, even in these more challenging cases.⁵ Accurate diagnosis is important, as approximately 31% of infested patients have other concurrent sexually transmitted infections that warrant screening.⁶

The Centers for Disease Control and Prevention recommends first-line treatment with permethrin cream (1% or 5%) or pyrethrin with piperonyl butoxide applied to all affected areas and washed off after 10 minutes.⁷ Patients should be reevaluated after 1 week if symptoms persist and re-treated if lice are found on examination.^7,8 Malathion lotion 0.5% (applied and washed off after 8-12 hours) or oral ivermectin (250 µg/kg, repeated after 2 weeks) may be used for alternative therapies or cases of permethrin or pyrethrin resistance.⁷ Ivermectin also is effective for involvement of eyelashes where topical insecticides should not be used.⁹ Sexual partners should be treated to prevent repeat transmission.^7,8 Bedding and clothing can be decontaminated by machine wash on hot cycle or isolating from body contact for 72 hours.⁷ Patients also should be screened for other sexually transmitted infections, including human immunodeficiency virus.⁶

Lack of knowledge about ovarian cancer prevents many women from seeking medical attention, which delays diagnosis and treatment and may prove increasingly dangerous as incidence rises by an expected 55% over the next 2 decades, according to the World Ovarian Cancer Coalition.

Data from the coalition’s 2018 survey of women with ovarian cancer show that 18% had never heard of the disease before their diagnosis and 51% had heard of it but did not know anything about it. The Every Women Study survey, completed by 1,531 women in 44 countries, also reveals that nine out of ten had experienced symptoms prior to diagnosis but fewer than half saw a physician within a month of noticing those symptoms, the coalition said.

“This study, for the first time, provides powerful evidence of the challenges faced by women diagnosed with ovarian cancer across the world and sets an agenda for global change. We were especially shocked by the widespread, woeful lack of awareness of ovarian cancer,” Annwen Jones, coalition vice-chair and cochair of the study, said in a separate written statement.

Results varied considerably by country, and only 10 countries provided enough responses to allow comparisons: Australia (120), Brazil (52), Canada (167), Germany (141), Hungary (58), Italy (92), Japan (250), Spain (70), the United Kingdom (176), and the United States (248).

Among those comparisons, women in Germany (5.5 weeks) and Spain (7.9 weeks) were the first to visit a physician after first experiencing symptoms, while those in Italy (15.2 weeks) and the United States (12.9 weeks) were last. The United States was also longest in time from first visit to diagnosis (23.6 weeks), and Japan was the shortest (11 weeks). Despite that world-longest time to diagnosis, however, over 69% of U.S. women said that their care around the time of diagnosis was very good, which was higher than any other country, the coalition reported.

Surgery statistics were closer among countries, with an average of 94% of all women undergoing surgery to treat their ovarian cancer. The United States, at 98.3%, was second to Spain’s 98.5%, and Hungary was the largest outlier on the low side at 59%. Over 87% of all women reported having chemotherapy to treat or control their cancer, and 9.8% of women said that they had received intraperitoneal chemotherapy. In the United States, 22.5% of women received intraperitoneal therapy, compared with 0.7% for the United Kingdom.

“No one country has all the answers, and whilst there is still an urgent need for a step-change in the level of investment in research for better treatments and tools for early diagnosis, there are significant opportunities to improve survival and quality of life for women in the immediate and short term to make a series of marginal gains if these variations are addressed by individual countries,” the coalition said in the report.

[email protected]

Lack of knowledge about ovarian cancer prevents many women from seeking medical attention, which delays diagnosis and treatment and may prove increasingly dangerous as incidence rises by an expected 55% over the next 2 decades, according to the World Ovarian Cancer Coalition.

Data from the coalition’s 2018 survey of women with ovarian cancer show that 18% had never heard of the disease before their diagnosis and 51% had heard of it but did not know anything about it. The Every Women Study survey, completed by 1,531 women in 44 countries, also reveals that nine out of ten had experienced symptoms prior to diagnosis but fewer than half saw a physician within a month of noticing those symptoms, the coalition said.

“This study, for the first time, provides powerful evidence of the challenges faced by women diagnosed with ovarian cancer across the world and sets an agenda for global change. We were especially shocked by the widespread, woeful lack of awareness of ovarian cancer,” Annwen Jones, coalition vice-chair and cochair of the study, said in a separate written statement.

Results varied considerably by country, and only 10 countries provided enough responses to allow comparisons: Australia (120), Brazil (52), Canada (167), Germany (141), Hungary (58), Italy (92), Japan (250), Spain (70), the United Kingdom (176), and the United States (248).

Among those comparisons, women in Germany (5.5 weeks) and Spain (7.9 weeks) were the first to visit a physician after first experiencing symptoms, while those in Italy (15.2 weeks) and the United States (12.9 weeks) were last. The United States was also longest in time from first visit to diagnosis (23.6 weeks), and Japan was the shortest (11 weeks). Despite that world-longest time to diagnosis, however, over 69% of U.S. women said that their care around the time of diagnosis was very good, which was higher than any other country, the coalition reported.

Surgery statistics were closer among countries, with an average of 94% of all women undergoing surgery to treat their ovarian cancer. The United States, at 98.3%, was second to Spain’s 98.5%, and Hungary was the largest outlier on the low side at 59%. Over 87% of all women reported having chemotherapy to treat or control their cancer, and 9.8% of women said that they had received intraperitoneal chemotherapy. In the United States, 22.5% of women received intraperitoneal therapy, compared with 0.7% for the United Kingdom.

“No one country has all the answers, and whilst there is still an urgent need for a step-change in the level of investment in research for better treatments and tools for early diagnosis, there are significant opportunities to improve survival and quality of life for women in the immediate and short term to make a series of marginal gains if these variations are addressed by individual countries,” the coalition said in the report.

[email protected]

Lack of knowledge about ovarian cancer prevents many women from seeking medical attention, which delays diagnosis and treatment and may prove increasingly dangerous as incidence rises by an expected 55% over the next 2 decades, according to the World Ovarian Cancer Coalition.

Data from the coalition’s 2018 survey of women with ovarian cancer show that 18% had never heard of the disease before their diagnosis and 51% had heard of it but did not know anything about it. The Every Women Study survey, completed by 1,531 women in 44 countries, also reveals that nine out of ten had experienced symptoms prior to diagnosis but fewer than half saw a physician within a month of noticing those symptoms, the coalition said.

“This study, for the first time, provides powerful evidence of the challenges faced by women diagnosed with ovarian cancer across the world and sets an agenda for global change. We were especially shocked by the widespread, woeful lack of awareness of ovarian cancer,” Annwen Jones, coalition vice-chair and cochair of the study, said in a separate written statement.

Results varied considerably by country, and only 10 countries provided enough responses to allow comparisons: Australia (120), Brazil (52), Canada (167), Germany (141), Hungary (58), Italy (92), Japan (250), Spain (70), the United Kingdom (176), and the United States (248).

Among those comparisons, women in Germany (5.5 weeks) and Spain (7.9 weeks) were the first to visit a physician after first experiencing symptoms, while those in Italy (15.2 weeks) and the United States (12.9 weeks) were last. The United States was also longest in time from first visit to diagnosis (23.6 weeks), and Japan was the shortest (11 weeks). Despite that world-longest time to diagnosis, however, over 69% of U.S. women said that their care around the time of diagnosis was very good, which was higher than any other country, the coalition reported.

Surgery statistics were closer among countries, with an average of 94% of all women undergoing surgery to treat their ovarian cancer. The United States, at 98.3%, was second to Spain’s 98.5%, and Hungary was the largest outlier on the low side at 59%. Over 87% of all women reported having chemotherapy to treat or control their cancer, and 9.8% of women said that they had received intraperitoneal chemotherapy. In the United States, 22.5% of women received intraperitoneal therapy, compared with 0.7% for the United Kingdom.

“No one country has all the answers, and whilst there is still an urgent need for a step-change in the level of investment in research for better treatments and tools for early diagnosis, there are significant opportunities to improve survival and quality of life for women in the immediate and short term to make a series of marginal gains if these variations are addressed by individual countries,” the coalition said in the report.

[email protected]

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

[email protected]

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

[email protected]

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

[email protected]

A proposed Trump administration plan for paying for drugs under Medicare Part B has raised red flags for doctors.

Mathier/Thinkstock

The Centers for Medicare & Medicaid Services announced Oct. 25 that it will test paying for Part B drugs by more closely aligning those payments with international rates.

The so-called International Price Index (IPI) model “would test whether increasing competition for private-sector vendors to negotiate drug prices, and aligning Medicare payments for drugs with prices that are paid in foreign countries, improves beneficiary access and quality of care while reducing expenditures,” according to a government fact sheet.

Under the test, private vendors would “procure drugs, distribute them to physicians and hospitals, and take on the responsibility of billing Medicare. Vendors would aggregate purchasing, seek volume-based discounts, and compete for providers’ business, thereby creating competition where none exists today.”

Health care professionals and hospitals in certain geographic areas would receive their Part B drugs under this program, while the rest of the country would continue under the current buy-and-bill system. Eventually, over the 5-year phase-in period, half of the geographic regions would fall under this IPI model.

CMS officials note that the IPI model “would maintain beneficiaries’ choice of provider and treatments and would have meaningful beneficiary protections such as enhanced monitoring and Medicare Beneficiary Ombudsman supports.”

Initially, only single-source drugs and biologics with available international pricing data would be provided under the IPI model, which could be expanded over time to include drugs available via multiple sources.

Currently, Medicare typically pays average sales price (ASP) plus a 6% add-on for drugs under Part B. Under IPI, if the international price is determined to be lower than the ASP, the CMS would reimburse based on a target price derived from an international price index, with the hope that manufacturers would match the international price. The target price would be phased in over a 5-year period.

The plan also calls for an add-on price similar to the current buy-and-bill system; however, the CMS aims to bring the add-on back to 6% rather than the actual 4.3% under the budget sequestration.

Other add-ons are also under consideration, such as paying a fixed amount per encounter or per month as well as a unique payment based on drug class, physician specialty, or physician practice.

Early takes on the proposal were met with skepticism.

The Community Oncology Alliance (COA) said in a statement that it is “concerned that the IPI will either repeat past reform mistakes [such as the Competitive Acquisition Program] or introduce the same cancer treatment access challenges experienced by cancer patients today with pharmacy benefit managers and other middlemen under Medicare Part D.”

“What the administration is proposing is incredibly complex and extremely difficult to comprehend how it would be implemented in the real-world of medical practice,” said Ted Okon, executive director of the COA. “It is also disturbing that the administration is trying to end-run the Congress by forcing a mandatory CMS Innovation Center demonstration that will effectively change Medicare reimbursement, as the sequester cut to Part B drug reimbursement has already done.”

The American College of Rheumatology was more measured in its reaction, noting that any change in policy needs to be thoughtful in its process to ensure that patient care is not adversely affected.

“Efforts to address high costs can sometimes create significant access issues for patients while penalizing doctors for providing quality care,” ACR officials said in a statement. “These proposals include those restructuring reimbursement for Medicare Part B drugs through either flat fee payments or a competitive acquisition program, or allowing utilization management such as step therapy or ‘fail first’ protocols in the Medicare Part B program. It is imperative that policy makers stay focused on the players who control drug prices and not penalize Medicare patients who depend on timely access to needed therapies.”

The American Medical Association raised some concerns as well.

“The administration’s proposal for an International Pricing Index Model for Part B drugs raises a number of questions, and we need to have a greater understanding of the potential impact of the proposal on patients, physicians, and the health care system,” AMA President Barbara McAneny, MD, said in a statement. “We look forward to working constructively with the Administration as it seeks feedback.”

The advanced notice of proposed rulemaking was posted to the Federal Register website on Oct. 25 and is scheduled to be formally published in the publication on Oct. 30. Comments are due Dec. 24. The CMS plans to issue the proposed rule related to this model in the spring of 2019.

[email protected]

A proposed Trump administration plan for paying for drugs under Medicare Part B has raised red flags for doctors.

Mathier/Thinkstock

The Centers for Medicare & Medicaid Services announced Oct. 25 that it will test paying for Part B drugs by more closely aligning those payments with international rates.

The so-called International Price Index (IPI) model “would test whether increasing competition for private-sector vendors to negotiate drug prices, and aligning Medicare payments for drugs with prices that are paid in foreign countries, improves beneficiary access and quality of care while reducing expenditures,” according to a government fact sheet.

Under the test, private vendors would “procure drugs, distribute them to physicians and hospitals, and take on the responsibility of billing Medicare. Vendors would aggregate purchasing, seek volume-based discounts, and compete for providers’ business, thereby creating competition where none exists today.”

Health care professionals and hospitals in certain geographic areas would receive their Part B drugs under this program, while the rest of the country would continue under the current buy-and-bill system. Eventually, over the 5-year phase-in period, half of the geographic regions would fall under this IPI model.

CMS officials note that the IPI model “would maintain beneficiaries’ choice of provider and treatments and would have meaningful beneficiary protections such as enhanced monitoring and Medicare Beneficiary Ombudsman supports.”

Initially, only single-source drugs and biologics with available international pricing data would be provided under the IPI model, which could be expanded over time to include drugs available via multiple sources.

Currently, Medicare typically pays average sales price (ASP) plus a 6% add-on for drugs under Part B. Under IPI, if the international price is determined to be lower than the ASP, the CMS would reimburse based on a target price derived from an international price index, with the hope that manufacturers would match the international price. The target price would be phased in over a 5-year period.

The plan also calls for an add-on price similar to the current buy-and-bill system; however, the CMS aims to bring the add-on back to 6% rather than the actual 4.3% under the budget sequestration.

Other add-ons are also under consideration, such as paying a fixed amount per encounter or per month as well as a unique payment based on drug class, physician specialty, or physician practice.

Early takes on the proposal were met with skepticism.

The Community Oncology Alliance (COA) said in a statement that it is “concerned that the IPI will either repeat past reform mistakes [such as the Competitive Acquisition Program] or introduce the same cancer treatment access challenges experienced by cancer patients today with pharmacy benefit managers and other middlemen under Medicare Part D.”

“What the administration is proposing is incredibly complex and extremely difficult to comprehend how it would be implemented in the real-world of medical practice,” said Ted Okon, executive director of the COA. “It is also disturbing that the administration is trying to end-run the Congress by forcing a mandatory CMS Innovation Center demonstration that will effectively change Medicare reimbursement, as the sequester cut to Part B drug reimbursement has already done.”

The American College of Rheumatology was more measured in its reaction, noting that any change in policy needs to be thoughtful in its process to ensure that patient care is not adversely affected.

“Efforts to address high costs can sometimes create significant access issues for patients while penalizing doctors for providing quality care,” ACR officials said in a statement. “These proposals include those restructuring reimbursement for Medicare Part B drugs through either flat fee payments or a competitive acquisition program, or allowing utilization management such as step therapy or ‘fail first’ protocols in the Medicare Part B program. It is imperative that policy makers stay focused on the players who control drug prices and not penalize Medicare patients who depend on timely access to needed therapies.”

The American Medical Association raised some concerns as well.

“The administration’s proposal for an International Pricing Index Model for Part B drugs raises a number of questions, and we need to have a greater understanding of the potential impact of the proposal on patients, physicians, and the health care system,” AMA President Barbara McAneny, MD, said in a statement. “We look forward to working constructively with the Administration as it seeks feedback.”

The advanced notice of proposed rulemaking was posted to the Federal Register website on Oct. 25 and is scheduled to be formally published in the publication on Oct. 30. Comments are due Dec. 24. The CMS plans to issue the proposed rule related to this model in the spring of 2019.

[email protected]

A proposed Trump administration plan for paying for drugs under Medicare Part B has raised red flags for doctors.

Mathier/Thinkstock

The Centers for Medicare & Medicaid Services announced Oct. 25 that it will test paying for Part B drugs by more closely aligning those payments with international rates.

The so-called International Price Index (IPI) model “would test whether increasing competition for private-sector vendors to negotiate drug prices, and aligning Medicare payments for drugs with prices that are paid in foreign countries, improves beneficiary access and quality of care while reducing expenditures,” according to a government fact sheet.

Under the test, private vendors would “procure drugs, distribute them to physicians and hospitals, and take on the responsibility of billing Medicare. Vendors would aggregate purchasing, seek volume-based discounts, and compete for providers’ business, thereby creating competition where none exists today.”

Health care professionals and hospitals in certain geographic areas would receive their Part B drugs under this program, while the rest of the country would continue under the current buy-and-bill system. Eventually, over the 5-year phase-in period, half of the geographic regions would fall under this IPI model.

CMS officials note that the IPI model “would maintain beneficiaries’ choice of provider and treatments and would have meaningful beneficiary protections such as enhanced monitoring and Medicare Beneficiary Ombudsman supports.”

Initially, only single-source drugs and biologics with available international pricing data would be provided under the IPI model, which could be expanded over time to include drugs available via multiple sources.

Currently, Medicare typically pays average sales price (ASP) plus a 6% add-on for drugs under Part B. Under IPI, if the international price is determined to be lower than the ASP, the CMS would reimburse based on a target price derived from an international price index, with the hope that manufacturers would match the international price. The target price would be phased in over a 5-year period.

The plan also calls for an add-on price similar to the current buy-and-bill system; however, the CMS aims to bring the add-on back to 6% rather than the actual 4.3% under the budget sequestration.

Other add-ons are also under consideration, such as paying a fixed amount per encounter or per month as well as a unique payment based on drug class, physician specialty, or physician practice.

Early takes on the proposal were met with skepticism.

The Community Oncology Alliance (COA) said in a statement that it is “concerned that the IPI will either repeat past reform mistakes [such as the Competitive Acquisition Program] or introduce the same cancer treatment access challenges experienced by cancer patients today with pharmacy benefit managers and other middlemen under Medicare Part D.”

“What the administration is proposing is incredibly complex and extremely difficult to comprehend how it would be implemented in the real-world of medical practice,” said Ted Okon, executive director of the COA. “It is also disturbing that the administration is trying to end-run the Congress by forcing a mandatory CMS Innovation Center demonstration that will effectively change Medicare reimbursement, as the sequester cut to Part B drug reimbursement has already done.”

The American College of Rheumatology was more measured in its reaction, noting that any change in policy needs to be thoughtful in its process to ensure that patient care is not adversely affected.

“Efforts to address high costs can sometimes create significant access issues for patients while penalizing doctors for providing quality care,” ACR officials said in a statement. “These proposals include those restructuring reimbursement for Medicare Part B drugs through either flat fee payments or a competitive acquisition program, or allowing utilization management such as step therapy or ‘fail first’ protocols in the Medicare Part B program. It is imperative that policy makers stay focused on the players who control drug prices and not penalize Medicare patients who depend on timely access to needed therapies.”

The American Medical Association raised some concerns as well.

“The administration’s proposal for an International Pricing Index Model for Part B drugs raises a number of questions, and we need to have a greater understanding of the potential impact of the proposal on patients, physicians, and the health care system,” AMA President Barbara McAneny, MD, said in a statement. “We look forward to working constructively with the Administration as it seeks feedback.”

The advanced notice of proposed rulemaking was posted to the Federal Register website on Oct. 25 and is scheduled to be formally published in the publication on Oct. 30. Comments are due Dec. 24. The CMS plans to issue the proposed rule related to this model in the spring of 2019.

[email protected]

SAN DIEGO – Hospitalized patients who developed acute kidney injury and fully recovered faced triple the risk of dementia of other hospitalized patients.

That’s according to a new study offering more evidence of a link between kidney disease and neurological problems.

“Clinicians should know that AKI is associated with poor long-term outcomes,” said lead author Jessica B. Kendrick MD, associate professor of medicine at the University of Colorado, Aurora. “We need to identify ways to prevent these long-term consequences.”

The findings were presented at Kidney Week 2018, sponsored by the American Society of Nephrology.

According to Dr. Kendrick, the acute neurological effects of AKI are well known. But no previous studies have examined the potential long-term cerebrovascular complications of AKI.

For the new study, Dr. Kendrick and her colleagues retrospectively analyzed 2,082 hospitalized patients in Utah from 1999 to 2009: 1,041 who completely recovered from AKI by discharge, and 1,041 who did not have AKI.

The average age was 61 years, and the average baseline creatinine was 0.9 ± 0.2 mg/dL. Over a median follow-up of 6 years, 97 patients developed dementia.

Those with AKI were more likely to develop dementia compared with the control group: 7% vs. 2% (hazard ratio, 3.4; 95% confidence interval, 2.14-5.40).

Other studies have linked kidney disease to cognitive impairment.

“There are a lot of theories as to why this is,” nephrologist Daniel Weiner, MD, of Tufts University, Boston, said in an interview. “It is most likely that the presence of kidney disease identifies individuals with a high burden of vascular disease, and that vascular disease, particularly of the small blood vessels, is an important contributor to cognitive impairment and dementia.”

That appears to be most notable in people who have protein in their urine, Dr. Weiner added. “The presence of protein in the urine identifies a severe enough process to affect the blood vessels in the kidney, and there is no reason to think that blood vessels elsewhere in the body, including in the brain, are not similarly affected.”

As for the current study, Dr. Weiner said it could support the vascular disease theory.

“People with vulnerable kidneys to acute injury also have vulnerable brains to acute injury,” he said. “People who get AKI usually have susceptibility to perfusion-related kidney injury. In other words, the small blood vessels that supply the kidney are unable to compensate to maintain sufficient blood flow during a time of low blood pressure or other systemic illness.”

That vulnerability “suggests to me that small blood vessels elsewhere in the body are less likely to be able to respond to challenges like low blood pressure,” Dr. Weiner explained. “If this occurs in the brain, it leads to microvascular disease and greater abnormal white-matter burden. This change in the brain anatomy is highly correlated with cognitive impairment.”

How can physicians put these finding to use? “These patients may require more monitoring,” Dr. Kendrick said. “For example, patients with AKI and complete recovery may not have any follow-up with a nephrologist, and perhaps they should.”

Moving forward, she said, “we are examining the association of AKI with cognitive dysfunction in different patient populations.” Researchers also are planning studies to better understand the mechanisms that are at work, she said.

The National Heart, Lung, and Blood Institute funded the study. The study authors had no disclosures.
 

SOURCE: Kendrick JB et al. Kidney Week 2018. Abstract TH-OR116.

SAN DIEGO – Hospitalized patients who developed acute kidney injury and fully recovered faced triple the risk of dementia of other hospitalized patients.

That’s according to a new study offering more evidence of a link between kidney disease and neurological problems.

“Clinicians should know that AKI is associated with poor long-term outcomes,” said lead author Jessica B. Kendrick MD, associate professor of medicine at the University of Colorado, Aurora. “We need to identify ways to prevent these long-term consequences.”

The findings were presented at Kidney Week 2018, sponsored by the American Society of Nephrology.

According to Dr. Kendrick, the acute neurological effects of AKI are well known. But no previous studies have examined the potential long-term cerebrovascular complications of AKI.

For the new study, Dr. Kendrick and her colleagues retrospectively analyzed 2,082 hospitalized patients in Utah from 1999 to 2009: 1,041 who completely recovered from AKI by discharge, and 1,041 who did not have AKI.

The average age was 61 years, and the average baseline creatinine was 0.9 ± 0.2 mg/dL. Over a median follow-up of 6 years, 97 patients developed dementia.

Those with AKI were more likely to develop dementia compared with the control group: 7% vs. 2% (hazard ratio, 3.4; 95% confidence interval, 2.14-5.40).

Other studies have linked kidney disease to cognitive impairment.

“There are a lot of theories as to why this is,” nephrologist Daniel Weiner, MD, of Tufts University, Boston, said in an interview. “It is most likely that the presence of kidney disease identifies individuals with a high burden of vascular disease, and that vascular disease, particularly of the small blood vessels, is an important contributor to cognitive impairment and dementia.”

That appears to be most notable in people who have protein in their urine, Dr. Weiner added. “The presence of protein in the urine identifies a severe enough process to affect the blood vessels in the kidney, and there is no reason to think that blood vessels elsewhere in the body, including in the brain, are not similarly affected.”

As for the current study, Dr. Weiner said it could support the vascular disease theory.

“People with vulnerable kidneys to acute injury also have vulnerable brains to acute injury,” he said. “People who get AKI usually have susceptibility to perfusion-related kidney injury. In other words, the small blood vessels that supply the kidney are unable to compensate to maintain sufficient blood flow during a time of low blood pressure or other systemic illness.”

That vulnerability “suggests to me that small blood vessels elsewhere in the body are less likely to be able to respond to challenges like low blood pressure,” Dr. Weiner explained. “If this occurs in the brain, it leads to microvascular disease and greater abnormal white-matter burden. This change in the brain anatomy is highly correlated with cognitive impairment.”

How can physicians put these finding to use? “These patients may require more monitoring,” Dr. Kendrick said. “For example, patients with AKI and complete recovery may not have any follow-up with a nephrologist, and perhaps they should.”

Moving forward, she said, “we are examining the association of AKI with cognitive dysfunction in different patient populations.” Researchers also are planning studies to better understand the mechanisms that are at work, she said.

The National Heart, Lung, and Blood Institute funded the study. The study authors had no disclosures.
 

SOURCE: Kendrick JB et al. Kidney Week 2018. Abstract TH-OR116.

SAN DIEGO – Hospitalized patients who developed acute kidney injury and fully recovered faced triple the risk of dementia of other hospitalized patients.

That’s according to a new study offering more evidence of a link between kidney disease and neurological problems.

“Clinicians should know that AKI is associated with poor long-term outcomes,” said lead author Jessica B. Kendrick MD, associate professor of medicine at the University of Colorado, Aurora. “We need to identify ways to prevent these long-term consequences.”

The findings were presented at Kidney Week 2018, sponsored by the American Society of Nephrology.

According to Dr. Kendrick, the acute neurological effects of AKI are well known. But no previous studies have examined the potential long-term cerebrovascular complications of AKI.

For the new study, Dr. Kendrick and her colleagues retrospectively analyzed 2,082 hospitalized patients in Utah from 1999 to 2009: 1,041 who completely recovered from AKI by discharge, and 1,041 who did not have AKI.

The average age was 61 years, and the average baseline creatinine was 0.9 ± 0.2 mg/dL. Over a median follow-up of 6 years, 97 patients developed dementia.

Those with AKI were more likely to develop dementia compared with the control group: 7% vs. 2% (hazard ratio, 3.4; 95% confidence interval, 2.14-5.40).

Other studies have linked kidney disease to cognitive impairment.

“There are a lot of theories as to why this is,” nephrologist Daniel Weiner, MD, of Tufts University, Boston, said in an interview. “It is most likely that the presence of kidney disease identifies individuals with a high burden of vascular disease, and that vascular disease, particularly of the small blood vessels, is an important contributor to cognitive impairment and dementia.”

That appears to be most notable in people who have protein in their urine, Dr. Weiner added. “The presence of protein in the urine identifies a severe enough process to affect the blood vessels in the kidney, and there is no reason to think that blood vessels elsewhere in the body, including in the brain, are not similarly affected.”

As for the current study, Dr. Weiner said it could support the vascular disease theory.

“People with vulnerable kidneys to acute injury also have vulnerable brains to acute injury,” he said. “People who get AKI usually have susceptibility to perfusion-related kidney injury. In other words, the small blood vessels that supply the kidney are unable to compensate to maintain sufficient blood flow during a time of low blood pressure or other systemic illness.”

That vulnerability “suggests to me that small blood vessels elsewhere in the body are less likely to be able to respond to challenges like low blood pressure,” Dr. Weiner explained. “If this occurs in the brain, it leads to microvascular disease and greater abnormal white-matter burden. This change in the brain anatomy is highly correlated with cognitive impairment.”

How can physicians put these finding to use? “These patients may require more monitoring,” Dr. Kendrick said. “For example, patients with AKI and complete recovery may not have any follow-up with a nephrologist, and perhaps they should.”

Moving forward, she said, “we are examining the association of AKI with cognitive dysfunction in different patient populations.” Researchers also are planning studies to better understand the mechanisms that are at work, she said.

The National Heart, Lung, and Blood Institute funded the study. The study authors had no disclosures.
 

SOURCE: Kendrick JB et al. Kidney Week 2018. Abstract TH-OR116.

Urinary retention following laparoscopic total extraperitoneal (TEP) inguinal hernia repair was more likely in patients aged more than 60 years, patients with benign prostatic hyperplasia, and patients with a decreased body mass index, according to findings published in the Journal of Surgical Research.

Courtesy Wikimedia Commons/Samuel Bendet, US Air Force/Creative Commons License

The researchers note that, while laparoscopic TEP is growing in popularity for inguinal hernia repair, postop urinary retention (POUR) is estimated at 2%-30%, but for open procedures, it is estimated at 0.4%-3%. POUR is linked to the development of urinary tract infections and also hospital readmissions. Since TEP may eventually become the norm, the study authors suggest that identifying patients at higher risk for POUR would contribute to the safety and quality of care for this operation.

In a retrospective chart review of 578 patients who had the procedure between 2009 and 2016, patients over age 60 years, patients with benign prostatic hyperplasia, and those with a body mass index (BMI) of less than or equal to 25.8 kg/m² were more likely to develop postoperative urinary retention (POUR). Patients with these risk factors were also more likely to develop a urinary tract infection within 30 days, reported Daniel Roadman, a medical student in the department of surgery at Medical College of Wisconsin in Milwaukee, and coauthors.

Investigators conducted a retrospective chart review of patients 18 years of age or older with a direct, indirect, and/or femoral inguinal hernia. POUR was defined as “inability to void spontaneously prior to hospital discharge, requiring straight or indwelling catheter placement,” the authors wrote.

Patients were required to void before being discharged. For patients unable to void, an indwelling catheter was placed and removed the following morning. Patients still unable to void at this point were discharged with an indwelling catheter and scheduled for follow-up within 1 week.

POUR occurred in 64 of the 578 patients (11.1%), and was significantly associated with benign prostatic hyperplasia, age of 60 years or older, development of urinary tract infection (UTI) within 30 days, and decreased BMI. Patients with POUR had increased incidence of UTI (6.3%), compared with patients without POUR (0.6%; P less than .0001).

Among patients who developed POUR, 54 (84.3%) were admitted for overnight observation with a stay of approximately 1.5 days. Three of these patients (5.6%) had a straight catheterization, and 51 (94.4%) had an indwelling urinary catheter placed. Two patients developed a UTI.

Of the 10 patients discharged home, six (60%) returned to the emergency department for catheterization; two (33.3%) patients had straight catheterization, and four (66.7%) were discharged home with an indwelling catheter. Two of these patients developed a UTI. In both groups, all patients who developed a UTI had an indwelling catheter placed, Mr. Roadman and colleagues reported.

During the study period, institutional protocol changed from routine intraoperative urinary catheterization to catheterization per surgeon discretion, though this did not affect POUR incidence.

“This is the first study to show a significant increase in UTI within 30 days after POUR,” the authors wrote. “Urinary stasis within the bladder due to the inability to void could lead to increased bacterial load and risk of infection.”

“It is important for providers, especially surgeons, to understand the risk of POUR and therefore increased risk of UTI after laparoscopic TEP inguinal hernia repair,” they added. “Identifying patients at higher risk … can help with patient education and expectations.”

No disclosures were reported by the study authors.
 

SOURCE: Roadman D et al. J Surg Res. 2018;11(231):309-15.

Urinary retention following laparoscopic total extraperitoneal (TEP) inguinal hernia repair was more likely in patients aged more than 60 years, patients with benign prostatic hyperplasia, and patients with a decreased body mass index, according to findings published in the Journal of Surgical Research.

Courtesy Wikimedia Commons/Samuel Bendet, US Air Force/Creative Commons License

The researchers note that, while laparoscopic TEP is growing in popularity for inguinal hernia repair, postop urinary retention (POUR) is estimated at 2%-30%, but for open procedures, it is estimated at 0.4%-3%. POUR is linked to the development of urinary tract infections and also hospital readmissions. Since TEP may eventually become the norm, the study authors suggest that identifying patients at higher risk for POUR would contribute to the safety and quality of care for this operation.

In a retrospective chart review of 578 patients who had the procedure between 2009 and 2016, patients over age 60 years, patients with benign prostatic hyperplasia, and those with a body mass index (BMI) of less than or equal to 25.8 kg/m² were more likely to develop postoperative urinary retention (POUR). Patients with these risk factors were also more likely to develop a urinary tract infection within 30 days, reported Daniel Roadman, a medical student in the department of surgery at Medical College of Wisconsin in Milwaukee, and coauthors.

Investigators conducted a retrospective chart review of patients 18 years of age or older with a direct, indirect, and/or femoral inguinal hernia. POUR was defined as “inability to void spontaneously prior to hospital discharge, requiring straight or indwelling catheter placement,” the authors wrote.

Patients were required to void before being discharged. For patients unable to void, an indwelling catheter was placed and removed the following morning. Patients still unable to void at this point were discharged with an indwelling catheter and scheduled for follow-up within 1 week.

POUR occurred in 64 of the 578 patients (11.1%), and was significantly associated with benign prostatic hyperplasia, age of 60 years or older, development of urinary tract infection (UTI) within 30 days, and decreased BMI. Patients with POUR had increased incidence of UTI (6.3%), compared with patients without POUR (0.6%; P less than .0001).

Among patients who developed POUR, 54 (84.3%) were admitted for overnight observation with a stay of approximately 1.5 days. Three of these patients (5.6%) had a straight catheterization, and 51 (94.4%) had an indwelling urinary catheter placed. Two patients developed a UTI.

Of the 10 patients discharged home, six (60%) returned to the emergency department for catheterization; two (33.3%) patients had straight catheterization, and four (66.7%) were discharged home with an indwelling catheter. Two of these patients developed a UTI. In both groups, all patients who developed a UTI had an indwelling catheter placed, Mr. Roadman and colleagues reported.

During the study period, institutional protocol changed from routine intraoperative urinary catheterization to catheterization per surgeon discretion, though this did not affect POUR incidence.

“This is the first study to show a significant increase in UTI within 30 days after POUR,” the authors wrote. “Urinary stasis within the bladder due to the inability to void could lead to increased bacterial load and risk of infection.”

“It is important for providers, especially surgeons, to understand the risk of POUR and therefore increased risk of UTI after laparoscopic TEP inguinal hernia repair,” they added. “Identifying patients at higher risk … can help with patient education and expectations.”

No disclosures were reported by the study authors.
 

SOURCE: Roadman D et al. J Surg Res. 2018;11(231):309-15.

Urinary retention following laparoscopic total extraperitoneal (TEP) inguinal hernia repair was more likely in patients aged more than 60 years, patients with benign prostatic hyperplasia, and patients with a decreased body mass index, according to findings published in the Journal of Surgical Research.

Courtesy Wikimedia Commons/Samuel Bendet, US Air Force/Creative Commons License

The researchers note that, while laparoscopic TEP is growing in popularity for inguinal hernia repair, postop urinary retention (POUR) is estimated at 2%-30%, but for open procedures, it is estimated at 0.4%-3%. POUR is linked to the development of urinary tract infections and also hospital readmissions. Since TEP may eventually become the norm, the study authors suggest that identifying patients at higher risk for POUR would contribute to the safety and quality of care for this operation.

In a retrospective chart review of 578 patients who had the procedure between 2009 and 2016, patients over age 60 years, patients with benign prostatic hyperplasia, and those with a body mass index (BMI) of less than or equal to 25.8 kg/m² were more likely to develop postoperative urinary retention (POUR). Patients with these risk factors were also more likely to develop a urinary tract infection within 30 days, reported Daniel Roadman, a medical student in the department of surgery at Medical College of Wisconsin in Milwaukee, and coauthors.

Investigators conducted a retrospective chart review of patients 18 years of age or older with a direct, indirect, and/or femoral inguinal hernia. POUR was defined as “inability to void spontaneously prior to hospital discharge, requiring straight or indwelling catheter placement,” the authors wrote.

Patients were required to void before being discharged. For patients unable to void, an indwelling catheter was placed and removed the following morning. Patients still unable to void at this point were discharged with an indwelling catheter and scheduled for follow-up within 1 week.

POUR occurred in 64 of the 578 patients (11.1%), and was significantly associated with benign prostatic hyperplasia, age of 60 years or older, development of urinary tract infection (UTI) within 30 days, and decreased BMI. Patients with POUR had increased incidence of UTI (6.3%), compared with patients without POUR (0.6%; P less than .0001).

Among patients who developed POUR, 54 (84.3%) were admitted for overnight observation with a stay of approximately 1.5 days. Three of these patients (5.6%) had a straight catheterization, and 51 (94.4%) had an indwelling urinary catheter placed. Two patients developed a UTI.

Of the 10 patients discharged home, six (60%) returned to the emergency department for catheterization; two (33.3%) patients had straight catheterization, and four (66.7%) were discharged home with an indwelling catheter. Two of these patients developed a UTI. In both groups, all patients who developed a UTI had an indwelling catheter placed, Mr. Roadman and colleagues reported.

During the study period, institutional protocol changed from routine intraoperative urinary catheterization to catheterization per surgeon discretion, though this did not affect POUR incidence.

“This is the first study to show a significant increase in UTI within 30 days after POUR,” the authors wrote. “Urinary stasis within the bladder due to the inability to void could lead to increased bacterial load and risk of infection.”

“It is important for providers, especially surgeons, to understand the risk of POUR and therefore increased risk of UTI after laparoscopic TEP inguinal hernia repair,” they added. “Identifying patients at higher risk … can help with patient education and expectations.”

No disclosures were reported by the study authors.
 

SOURCE: Roadman D et al. J Surg Res. 2018;11(231):309-15.

PARIS – Treatment with the fixed combination adapalene 0.3%/benzoyl peroxide 2.5% gel not only reduced facial acne lesions, it also decreased the atrophic acne scar count in a multicenter, randomized trial, Brigitte Dreno, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“To my knowledge, this is the first time that we have seen a topical therapy showing a reduction in atrophic acne scars,” said Dr. Dreno, professor and chair of the department of dermatology at Nantes (France) University Hospital.

She reported on 67 adolescents and adults with mainly moderate facial acne randomized to treat half their face with adapalene 0.3%/benzoyl peroxide 2.5% gel (Epiduo Forte) and the other half with the product’s vehicle daily for 6 months. Investigators were blinded as to which side was which. At baseline, patients averaged 40 acne lesions and 12 scars per half face.

The primary efficacy endpoint was the atrophic acne scar count per half face at week 24. At that point, the mean total was 9.5 scars on the active treatment side, compared with 13.3 on the control side. This translated to a statistically significant and clinically meaningful 15.5% decrease in scars with active treatment versus a 14.4% increase with vehicle. The between-side difference achieved statistical significance at week 1 and remained so at all follow-up visits through week 24.

By Scar Global Assessment at week 24, 32.9% of half faces treated with the combination product were rated clear or almost clear, compared with 16.4% with vehicle.

At 24 weeks, 24.1% of participants reported having moderately or very visible holes or indents on the active treatment side of their face, compared with 51.8% on the control side. The number of inflammatory acne lesions fell by 86.7% with the active treatment and 57.9% with vehicle over the course of 24 weeks. Again, the difference became statistically significant starting at week 1. By the Investigator’s Global Assessment at week 24, 64.2% of adapalene/benzoyl peroxide gel–treated faces were rated clear or almost clear, as were 19.4% with vehicle. In addition, 32% of patients reported a marked improvement in skin texture on their active treatment side at 24 weeks, as did 14% on the control side.

The salutary effect on acne scars documented with a topical therapy in this study represents a real advance in clinical care.

“Facial acne scars are a very important and difficult problem for our patients and also for dermatologists,” Dr. Dreno observed, adding that the evidence base for procedural interventions for acne scars, such as dermabrasion and laser resurfacing, is not top quality.

Not surprisingly with a topical retinoid, skin irritation was the most common treatment-emergent adverse event, reported by 14.9% of patients on their active treatment side and 6% with vehicle. This side effect was typically mild and resolved within the first 2-3 weeks.

The improvement in preexisting acne scars documented in this trial was probably caused by drug-induced remodeling of the dermal matrix, according to Dr. Dreno.

The study was funded by Galderma. Dr. Dreno reported receiving research grants from and/or serving as a consultant to Galderma, Bioderma, Pierre Fabre, and La Roche–Posay.

[email protected]

PARIS – Treatment with the fixed combination adapalene 0.3%/benzoyl peroxide 2.5% gel not only reduced facial acne lesions, it also decreased the atrophic acne scar count in a multicenter, randomized trial, Brigitte Dreno, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“To my knowledge, this is the first time that we have seen a topical therapy showing a reduction in atrophic acne scars,” said Dr. Dreno, professor and chair of the department of dermatology at Nantes (France) University Hospital.

She reported on 67 adolescents and adults with mainly moderate facial acne randomized to treat half their face with adapalene 0.3%/benzoyl peroxide 2.5% gel (Epiduo Forte) and the other half with the product’s vehicle daily for 6 months. Investigators were blinded as to which side was which. At baseline, patients averaged 40 acne lesions and 12 scars per half face.

The primary efficacy endpoint was the atrophic acne scar count per half face at week 24. At that point, the mean total was 9.5 scars on the active treatment side, compared with 13.3 on the control side. This translated to a statistically significant and clinically meaningful 15.5% decrease in scars with active treatment versus a 14.4% increase with vehicle. The between-side difference achieved statistical significance at week 1 and remained so at all follow-up visits through week 24.

By Scar Global Assessment at week 24, 32.9% of half faces treated with the combination product were rated clear or almost clear, compared with 16.4% with vehicle.

At 24 weeks, 24.1% of participants reported having moderately or very visible holes or indents on the active treatment side of their face, compared with 51.8% on the control side. The number of inflammatory acne lesions fell by 86.7% with the active treatment and 57.9% with vehicle over the course of 24 weeks. Again, the difference became statistically significant starting at week 1. By the Investigator’s Global Assessment at week 24, 64.2% of adapalene/benzoyl peroxide gel–treated faces were rated clear or almost clear, as were 19.4% with vehicle. In addition, 32% of patients reported a marked improvement in skin texture on their active treatment side at 24 weeks, as did 14% on the control side.

The salutary effect on acne scars documented with a topical therapy in this study represents a real advance in clinical care.

“Facial acne scars are a very important and difficult problem for our patients and also for dermatologists,” Dr. Dreno observed, adding that the evidence base for procedural interventions for acne scars, such as dermabrasion and laser resurfacing, is not top quality.

Not surprisingly with a topical retinoid, skin irritation was the most common treatment-emergent adverse event, reported by 14.9% of patients on their active treatment side and 6% with vehicle. This side effect was typically mild and resolved within the first 2-3 weeks.

The improvement in preexisting acne scars documented in this trial was probably caused by drug-induced remodeling of the dermal matrix, according to Dr. Dreno.

The study was funded by Galderma. Dr. Dreno reported receiving research grants from and/or serving as a consultant to Galderma, Bioderma, Pierre Fabre, and La Roche–Posay.

[email protected]

PARIS – Treatment with the fixed combination adapalene 0.3%/benzoyl peroxide 2.5% gel not only reduced facial acne lesions, it also decreased the atrophic acne scar count in a multicenter, randomized trial, Brigitte Dreno, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“To my knowledge, this is the first time that we have seen a topical therapy showing a reduction in atrophic acne scars,” said Dr. Dreno, professor and chair of the department of dermatology at Nantes (France) University Hospital.

She reported on 67 adolescents and adults with mainly moderate facial acne randomized to treat half their face with adapalene 0.3%/benzoyl peroxide 2.5% gel (Epiduo Forte) and the other half with the product’s vehicle daily for 6 months. Investigators were blinded as to which side was which. At baseline, patients averaged 40 acne lesions and 12 scars per half face.

The primary efficacy endpoint was the atrophic acne scar count per half face at week 24. At that point, the mean total was 9.5 scars on the active treatment side, compared with 13.3 on the control side. This translated to a statistically significant and clinically meaningful 15.5% decrease in scars with active treatment versus a 14.4% increase with vehicle. The between-side difference achieved statistical significance at week 1 and remained so at all follow-up visits through week 24.

By Scar Global Assessment at week 24, 32.9% of half faces treated with the combination product were rated clear or almost clear, compared with 16.4% with vehicle.

At 24 weeks, 24.1% of participants reported having moderately or very visible holes or indents on the active treatment side of their face, compared with 51.8% on the control side. The number of inflammatory acne lesions fell by 86.7% with the active treatment and 57.9% with vehicle over the course of 24 weeks. Again, the difference became statistically significant starting at week 1. By the Investigator’s Global Assessment at week 24, 64.2% of adapalene/benzoyl peroxide gel–treated faces were rated clear or almost clear, as were 19.4% with vehicle. In addition, 32% of patients reported a marked improvement in skin texture on their active treatment side at 24 weeks, as did 14% on the control side.

The salutary effect on acne scars documented with a topical therapy in this study represents a real advance in clinical care.

“Facial acne scars are a very important and difficult problem for our patients and also for dermatologists,” Dr. Dreno observed, adding that the evidence base for procedural interventions for acne scars, such as dermabrasion and laser resurfacing, is not top quality.

Not surprisingly with a topical retinoid, skin irritation was the most common treatment-emergent adverse event, reported by 14.9% of patients on their active treatment side and 6% with vehicle. This side effect was typically mild and resolved within the first 2-3 weeks.

The improvement in preexisting acne scars documented in this trial was probably caused by drug-induced remodeling of the dermal matrix, according to Dr. Dreno.

The study was funded by Galderma. Dr. Dreno reported receiving research grants from and/or serving as a consultant to Galderma, Bioderma, Pierre Fabre, and La Roche–Posay.

[email protected]

Clinical implications

Nonadherence with oral antipsychotics is a common problem for patients with schizophrenia, one that is often underappreciated by clinicians.⁵ Whether one uses 70% or 80% as the measure of oral medication adherence, at least 50% of schizophrenia patients are nonadherent, with resultant increased risks for symptom exacerbation and hospitalization.^5,6 Although 2 LAI forms of aripiprazole have been introduced over the past few years, neither was designed to be loaded, resulting in the need for 2 or 3 weeks of oral antipsychotic coverage following the first injectable dose.¹ The primary reason for LAI antipsychotic therapy is oral medication nonadherence, and thus the need for 14 to 21 days of oral coverage at the outset of treatment creates a risk for symptom exacerbation if the patient is nonadherent with this oral bridging therapy which is needed to achieve the necessary serum concentrations until the long-acting formulation takes over.

One approach was to create a new form of AL using smaller nanomolecular particles rather than the micron-sized particles used for maintenance AL injections.^3,4 This nanocrystal suspension is called Aristada Initio (ALncd) and has a median T_max that ranges from 16 to 35 days, compared with 41 days for single-dose injections of AL. ALncd also has a much shorter median half-life of 15 to 18 days, compared with 53.9 to 57.2 days for AL (Table 2^7,8). Utilizing these kinetic differences, a 1-day initiation regimen was developed to dispense with the need for 3 weeks of oral medication coverage when commencing AL treatment.^3,4 In lieu of 3 weeks of oral coverage starting at the time of the first AL injection, patients instead will receive an injection of ALncd 675 mg, and a single oral 30 mg aripiprazole dose. The combination of ALncd and the single 30 mg oral dose when added to the initial AL injection provides aripiprazole levels in the first weeks of therapy that are comparable to those seen in the previous paradigm, when patients took 21 days of oral aripiprazole after the first AL injection.³

Use in adults with schizophrenia. After establishing tolerability with oral aripiprazole, ALncd675 mg is administered as an IM injection by a health care professional, and the patient is concomitantly given a single 30 mg oral dose of aripiprazole. Only one dosage form of ALncd is available: 675 mg. The maintenance AL dose chosen by the clinician (441, 662, 882, or 1,064 mg) is also administered at the same time, but must be injected in the other deltoid or gluteal muscle. The injection volume for ALncd is 2.4 mL and can be administered in the deltoid or gluteus muscle.⁹ If the patient prefers not to have 2 injections on the same day, the AL dose can be administered up to 10 days thereafter.⁹ This 10-day window for administering AL relates to the long time to maximum plasma levels from single AL injections. The relevant drug levels during the first weeks are provided predominantly from the initiation regimen of ALncd injection plus the single 30 mg oral dose.³ In instances when a patient agrees to receive both ALncd and AL injections but refuses the 30 mg oral dose, effective plasma levels will be seen in the middle of the second week of therapy.

Continue to: Pharmacologic profile, adverse reactions

Aripiprazole is a dopamine partial agonist atypical antipsychotic that has been commercially available in the United States since November 15, 2002, and its adverse effect profile is well characterized. The LAI formulation AL was approved on October 5, 2015. In the pivotal, 12-week, fixed-dose, placebo-controlled clinical trial of AL 441 mg or 882 mg monthly for adults with an acute exacerbation of schizophrenia, the only adverse effect that occurred in ≥5% of AL-treated patients and a rate at least twice that of placebo was akathisia (441 mg: 11%; 882 mg: 11%; placebo: 4%).¹⁰ Only 2 of 415 AL-treated patients discontinued the study due to akathisia. Injection-site reactions were reported by 4%, 5%, and 2% of patients treated with AL 441 mg, AL 882 mg, and placebo, respectively. Most of these were injection-site pain associated with the first injection, and decreased with each subsequent injection. Other injection-site reactions (induration, swelling, and redness) occurred at rates <1%.¹¹

Having established that the range of plasma aripiprazole levels consistent with effective treatment is bounded by levels seen with AL 441 mg or 882 mg monthly, the FDA did not require additional efficacy studies for new AL doses provided that pharmacokinetic (PK) studies could demonstrate levels within the effective range. This is consistent with how new doses of other LAI antipsychotic preparations have been addressed in the past. For example, the 37.5 mg dose of risperidone microspheres was approved based on PK data, although the pivotal efficacy trials included doses of 25 mg, 50 mg, and 75 mg.¹² Based on PK studies, AL doses of 662 mg monthly, 882 mg every 6 weeks, and 1,064 mg every 8 weeks were previously approved.¹³ The approval process for ALncd followed a similar pathway, and is based on PK results combined with tolerability data amassed during the PK studies. The package insert thus notes that in PK studies the safety profile of ALncd was generally consistent with that observed for AL (see Tolerability).

Pharmacokinetic outcomes. A comparative phase 1 PK study was performed to evaluate initiation regimens: either 21 days of oral aripiprazole (15 mg/d) and one AL dose (n = 81) or one injection of ALncd plus a single dose of 30 mg oral aripiprazole and one AL dose (n = 80). Patients were randomized 1:1:1:1 to receive an AL dose of either 441 mg or 882 mg combined with the oral or the new ALncdinitiation regimen. As shown in Figure 1 and Figure 2, the mean plasma levels seen with 675 mg IM ALncd plus a single dose of 30 mg oral aripiprazole were comparable with levels achieved using 21 days of oral aripiprazole coverage, regardless of whether the regimen was paired with a maintenance AL dose of 441 mg or 882 mg.⁴

Tolerability. In PK studies, the safety profile and incidences of injection site reactions of ALncd were generally consistent with those observed for aripiprazole lauroxil.⁹ In the phase I PK study comparing oral initiation with ALncd plus a single 30 mg oral aripiprazole dose, there were 2 mild cases of akathisia in the 21-day oral aripiprazole groups (n = 81) and 4 cases in the ALncd groups (n = 80) (3 mild cases, 1 moderate case). None of the adverse events related to akathisia were deemed serious, and no patients discontinued participation in the trial due to akathisia.⁹

Continue to: Clinical considerations

ALncd is not a substitute for AL due to the very different kinetic properties of the 2 preparations. ALncd is approved only to be used for initiating treatment with AL, or in those instances where the revised missed dose guidelines for AL permit use of ALncd to obviate the need for oral coverage.⁹ Table 3⁹ presents these revised AL missed dose guidelines focusing on those time periods when some form of supplementation is required in addition to the established maintenance AL dose. Clinicians should be reminded that ALncd must be paired with a dose of AL, although the latter can be given up to 10 days later when commencing therapy.

• it obviates the need for 21 days of oral coverage previously required at the initiation of AL treatment
• clinically relevant plasma levels are seen within the first week when ALncd is combined with a single 30 mg oral aripiprazole dose
• per the revised missed dose guidelines for AL, it can be used in those situations that previously demanded 7 days of oral coverage, and, when combined with a single 30 mg oral dose, can be used for resumption of therapy after prolonged absences that required 21 days of oral coverage. In all instances, the patient will also receive their usual maintenance dose of AL.

Dosing. There is only one dose available for ALncd, 675 mg IM. As the dose cannot be modified, the package insert contains cautionary language regarding situations with less-than-expected drug exposure (use of cytochrome P450 [CYP] 3A4 inducers), greater-than-expected drug exposure (strong CYP3A4 or 2D6 inhibitors or known 2D6 poor metabolizers), or increased pharmacodynamic effects (concurrent use of antihypertensives or benzodiazepines).

Contraindications. The only contraindication is a known hypersensitivity to aripiprazole.

Bottom Line

Aripiprazole lauroxil nanocrystal suspension (Aristada Initio) was specifically developed to obviate the need for 21 days of oral aripiprazole coverage when commencing treatment with aripiprazole lauroxil (Aristada). The plasma levels achieved when an injection of aripiprazole lauroxil nanocrystal suspension is combined with a single 30 mg oral dose are comparable to those achieved with 21 days of oral coverage. This initiation regimen, including a aripiprazole lauroxil nanocrystal injection and a 30 mg oral dose, should be administered on the same day as the maintenance aripiprazole lauroxil injection, although the latter can be administered on any of the next 10 days.

Related Resource

• Khan AY, Ovais DM. Long-acting injectable aripiprazole lauroxil for schizophrenia. Current Psychiatry. 2016;15(7):50-52,58.

Drug Brand Names
Aripiprazole lauroxil • Aristada
Aripiprazole lauroxil nanocrystal • Aristada Initio
Risperidone microspheres • Risperdal Consta

Clinical implications

Nonadherence with oral antipsychotics is a common problem for patients with schizophrenia, one that is often underappreciated by clinicians.⁵ Whether one uses 70% or 80% as the measure of oral medication adherence, at least 50% of schizophrenia patients are nonadherent, with resultant increased risks for symptom exacerbation and hospitalization.^5,6 Although 2 LAI forms of aripiprazole have been introduced over the past few years, neither was designed to be loaded, resulting in the need for 2 or 3 weeks of oral antipsychotic coverage following the first injectable dose.¹ The primary reason for LAI antipsychotic therapy is oral medication nonadherence, and thus the need for 14 to 21 days of oral coverage at the outset of treatment creates a risk for symptom exacerbation if the patient is nonadherent with this oral bridging therapy which is needed to achieve the necessary serum concentrations until the long-acting formulation takes over.

One approach was to create a new form of AL using smaller nanomolecular particles rather than the micron-sized particles used for maintenance AL injections.^3,4 This nanocrystal suspension is called Aristada Initio (ALncd) and has a median T_max that ranges from 16 to 35 days, compared with 41 days for single-dose injections of AL. ALncd also has a much shorter median half-life of 15 to 18 days, compared with 53.9 to 57.2 days for AL (Table 2^7,8). Utilizing these kinetic differences, a 1-day initiation regimen was developed to dispense with the need for 3 weeks of oral medication coverage when commencing AL treatment.^3,4 In lieu of 3 weeks of oral coverage starting at the time of the first AL injection, patients instead will receive an injection of ALncd 675 mg, and a single oral 30 mg aripiprazole dose. The combination of ALncd and the single 30 mg oral dose when added to the initial AL injection provides aripiprazole levels in the first weeks of therapy that are comparable to those seen in the previous paradigm, when patients took 21 days of oral aripiprazole after the first AL injection.³

Use in adults with schizophrenia. After establishing tolerability with oral aripiprazole, ALncd675 mg is administered as an IM injection by a health care professional, and the patient is concomitantly given a single 30 mg oral dose of aripiprazole. Only one dosage form of ALncd is available: 675 mg. The maintenance AL dose chosen by the clinician (441, 662, 882, or 1,064 mg) is also administered at the same time, but must be injected in the other deltoid or gluteal muscle. The injection volume for ALncd is 2.4 mL and can be administered in the deltoid or gluteus muscle.⁹ If the patient prefers not to have 2 injections on the same day, the AL dose can be administered up to 10 days thereafter.⁹ This 10-day window for administering AL relates to the long time to maximum plasma levels from single AL injections. The relevant drug levels during the first weeks are provided predominantly from the initiation regimen of ALncd injection plus the single 30 mg oral dose.³ In instances when a patient agrees to receive both ALncd and AL injections but refuses the 30 mg oral dose, effective plasma levels will be seen in the middle of the second week of therapy.

Continue to: Pharmacologic profile, adverse reactions

Aripiprazole is a dopamine partial agonist atypical antipsychotic that has been commercially available in the United States since November 15, 2002, and its adverse effect profile is well characterized. The LAI formulation AL was approved on October 5, 2015. In the pivotal, 12-week, fixed-dose, placebo-controlled clinical trial of AL 441 mg or 882 mg monthly for adults with an acute exacerbation of schizophrenia, the only adverse effect that occurred in ≥5% of AL-treated patients and a rate at least twice that of placebo was akathisia (441 mg: 11%; 882 mg: 11%; placebo: 4%).¹⁰ Only 2 of 415 AL-treated patients discontinued the study due to akathisia. Injection-site reactions were reported by 4%, 5%, and 2% of patients treated with AL 441 mg, AL 882 mg, and placebo, respectively. Most of these were injection-site pain associated with the first injection, and decreased with each subsequent injection. Other injection-site reactions (induration, swelling, and redness) occurred at rates <1%.¹¹

Having established that the range of plasma aripiprazole levels consistent with effective treatment is bounded by levels seen with AL 441 mg or 882 mg monthly, the FDA did not require additional efficacy studies for new AL doses provided that pharmacokinetic (PK) studies could demonstrate levels within the effective range. This is consistent with how new doses of other LAI antipsychotic preparations have been addressed in the past. For example, the 37.5 mg dose of risperidone microspheres was approved based on PK data, although the pivotal efficacy trials included doses of 25 mg, 50 mg, and 75 mg.¹² Based on PK studies, AL doses of 662 mg monthly, 882 mg every 6 weeks, and 1,064 mg every 8 weeks were previously approved.¹³ The approval process for ALncd followed a similar pathway, and is based on PK results combined with tolerability data amassed during the PK studies. The package insert thus notes that in PK studies the safety profile of ALncd was generally consistent with that observed for AL (see Tolerability).

Pharmacokinetic outcomes. A comparative phase 1 PK study was performed to evaluate initiation regimens: either 21 days of oral aripiprazole (15 mg/d) and one AL dose (n = 81) or one injection of ALncd plus a single dose of 30 mg oral aripiprazole and one AL dose (n = 80). Patients were randomized 1:1:1:1 to receive an AL dose of either 441 mg or 882 mg combined with the oral or the new ALncdinitiation regimen. As shown in Figure 1 and Figure 2, the mean plasma levels seen with 675 mg IM ALncd plus a single dose of 30 mg oral aripiprazole were comparable with levels achieved using 21 days of oral aripiprazole coverage, regardless of whether the regimen was paired with a maintenance AL dose of 441 mg or 882 mg.⁴

Tolerability. In PK studies, the safety profile and incidences of injection site reactions of ALncd were generally consistent with those observed for aripiprazole lauroxil.⁹ In the phase I PK study comparing oral initiation with ALncd plus a single 30 mg oral aripiprazole dose, there were 2 mild cases of akathisia in the 21-day oral aripiprazole groups (n = 81) and 4 cases in the ALncd groups (n = 80) (3 mild cases, 1 moderate case). None of the adverse events related to akathisia were deemed serious, and no patients discontinued participation in the trial due to akathisia.⁹

Continue to: Clinical considerations

ALncd is not a substitute for AL due to the very different kinetic properties of the 2 preparations. ALncd is approved only to be used for initiating treatment with AL, or in those instances where the revised missed dose guidelines for AL permit use of ALncd to obviate the need for oral coverage.⁹ Table 3⁹ presents these revised AL missed dose guidelines focusing on those time periods when some form of supplementation is required in addition to the established maintenance AL dose. Clinicians should be reminded that ALncd must be paired with a dose of AL, although the latter can be given up to 10 days later when commencing therapy.

• it obviates the need for 21 days of oral coverage previously required at the initiation of AL treatment
• clinically relevant plasma levels are seen within the first week when ALncd is combined with a single 30 mg oral aripiprazole dose
• per the revised missed dose guidelines for AL, it can be used in those situations that previously demanded 7 days of oral coverage, and, when combined with a single 30 mg oral dose, can be used for resumption of therapy after prolonged absences that required 21 days of oral coverage. In all instances, the patient will also receive their usual maintenance dose of AL.

Dosing. There is only one dose available for ALncd, 675 mg IM. As the dose cannot be modified, the package insert contains cautionary language regarding situations with less-than-expected drug exposure (use of cytochrome P450 [CYP] 3A4 inducers), greater-than-expected drug exposure (strong CYP3A4 or 2D6 inhibitors or known 2D6 poor metabolizers), or increased pharmacodynamic effects (concurrent use of antihypertensives or benzodiazepines).

Contraindications. The only contraindication is a known hypersensitivity to aripiprazole.

Bottom Line

Aripiprazole lauroxil nanocrystal suspension (Aristada Initio) was specifically developed to obviate the need for 21 days of oral aripiprazole coverage when commencing treatment with aripiprazole lauroxil (Aristada). The plasma levels achieved when an injection of aripiprazole lauroxil nanocrystal suspension is combined with a single 30 mg oral dose are comparable to those achieved with 21 days of oral coverage. This initiation regimen, including a aripiprazole lauroxil nanocrystal injection and a 30 mg oral dose, should be administered on the same day as the maintenance aripiprazole lauroxil injection, although the latter can be administered on any of the next 10 days.

Related Resource

• Khan AY, Ovais DM. Long-acting injectable aripiprazole lauroxil for schizophrenia. Current Psychiatry. 2016;15(7):50-52,58.

Drug Brand Names
Aripiprazole lauroxil • Aristada
Aripiprazole lauroxil nanocrystal • Aristada Initio
Risperidone microspheres • Risperdal Consta

Clinical implications

Nonadherence with oral antipsychotics is a common problem for patients with schizophrenia, one that is often underappreciated by clinicians.⁵ Whether one uses 70% or 80% as the measure of oral medication adherence, at least 50% of schizophrenia patients are nonadherent, with resultant increased risks for symptom exacerbation and hospitalization.^5,6 Although 2 LAI forms of aripiprazole have been introduced over the past few years, neither was designed to be loaded, resulting in the need for 2 or 3 weeks of oral antipsychotic coverage following the first injectable dose.¹ The primary reason for LAI antipsychotic therapy is oral medication nonadherence, and thus the need for 14 to 21 days of oral coverage at the outset of treatment creates a risk for symptom exacerbation if the patient is nonadherent with this oral bridging therapy which is needed to achieve the necessary serum concentrations until the long-acting formulation takes over.

One approach was to create a new form of AL using smaller nanomolecular particles rather than the micron-sized particles used for maintenance AL injections.^3,4 This nanocrystal suspension is called Aristada Initio (ALncd) and has a median T_max that ranges from 16 to 35 days, compared with 41 days for single-dose injections of AL. ALncd also has a much shorter median half-life of 15 to 18 days, compared with 53.9 to 57.2 days for AL (Table 2^7,8). Utilizing these kinetic differences, a 1-day initiation regimen was developed to dispense with the need for 3 weeks of oral medication coverage when commencing AL treatment.^3,4 In lieu of 3 weeks of oral coverage starting at the time of the first AL injection, patients instead will receive an injection of ALncd 675 mg, and a single oral 30 mg aripiprazole dose. The combination of ALncd and the single 30 mg oral dose when added to the initial AL injection provides aripiprazole levels in the first weeks of therapy that are comparable to those seen in the previous paradigm, when patients took 21 days of oral aripiprazole after the first AL injection.³

Use in adults with schizophrenia. After establishing tolerability with oral aripiprazole, ALncd675 mg is administered as an IM injection by a health care professional, and the patient is concomitantly given a single 30 mg oral dose of aripiprazole. Only one dosage form of ALncd is available: 675 mg. The maintenance AL dose chosen by the clinician (441, 662, 882, or 1,064 mg) is also administered at the same time, but must be injected in the other deltoid or gluteal muscle. The injection volume for ALncd is 2.4 mL and can be administered in the deltoid or gluteus muscle.⁹ If the patient prefers not to have 2 injections on the same day, the AL dose can be administered up to 10 days thereafter.⁹ This 10-day window for administering AL relates to the long time to maximum plasma levels from single AL injections. The relevant drug levels during the first weeks are provided predominantly from the initiation regimen of ALncd injection plus the single 30 mg oral dose.³ In instances when a patient agrees to receive both ALncd and AL injections but refuses the 30 mg oral dose, effective plasma levels will be seen in the middle of the second week of therapy.

Continue to: Pharmacologic profile, adverse reactions

Aripiprazole is a dopamine partial agonist atypical antipsychotic that has been commercially available in the United States since November 15, 2002, and its adverse effect profile is well characterized. The LAI formulation AL was approved on October 5, 2015. In the pivotal, 12-week, fixed-dose, placebo-controlled clinical trial of AL 441 mg or 882 mg monthly for adults with an acute exacerbation of schizophrenia, the only adverse effect that occurred in ≥5% of AL-treated patients and a rate at least twice that of placebo was akathisia (441 mg: 11%; 882 mg: 11%; placebo: 4%).¹⁰ Only 2 of 415 AL-treated patients discontinued the study due to akathisia. Injection-site reactions were reported by 4%, 5%, and 2% of patients treated with AL 441 mg, AL 882 mg, and placebo, respectively. Most of these were injection-site pain associated with the first injection, and decreased with each subsequent injection. Other injection-site reactions (induration, swelling, and redness) occurred at rates <1%.¹¹

Having established that the range of plasma aripiprazole levels consistent with effective treatment is bounded by levels seen with AL 441 mg or 882 mg monthly, the FDA did not require additional efficacy studies for new AL doses provided that pharmacokinetic (PK) studies could demonstrate levels within the effective range. This is consistent with how new doses of other LAI antipsychotic preparations have been addressed in the past. For example, the 37.5 mg dose of risperidone microspheres was approved based on PK data, although the pivotal efficacy trials included doses of 25 mg, 50 mg, and 75 mg.¹² Based on PK studies, AL doses of 662 mg monthly, 882 mg every 6 weeks, and 1,064 mg every 8 weeks were previously approved.¹³ The approval process for ALncd followed a similar pathway, and is based on PK results combined with tolerability data amassed during the PK studies. The package insert thus notes that in PK studies the safety profile of ALncd was generally consistent with that observed for AL (see Tolerability).

Pharmacokinetic outcomes. A comparative phase 1 PK study was performed to evaluate initiation regimens: either 21 days of oral aripiprazole (15 mg/d) and one AL dose (n = 81) or one injection of ALncd plus a single dose of 30 mg oral aripiprazole and one AL dose (n = 80). Patients were randomized 1:1:1:1 to receive an AL dose of either 441 mg or 882 mg combined with the oral or the new ALncdinitiation regimen. As shown in Figure 1 and Figure 2, the mean plasma levels seen with 675 mg IM ALncd plus a single dose of 30 mg oral aripiprazole were comparable with levels achieved using 21 days of oral aripiprazole coverage, regardless of whether the regimen was paired with a maintenance AL dose of 441 mg or 882 mg.⁴

Tolerability. In PK studies, the safety profile and incidences of injection site reactions of ALncd were generally consistent with those observed for aripiprazole lauroxil.⁹ In the phase I PK study comparing oral initiation with ALncd plus a single 30 mg oral aripiprazole dose, there were 2 mild cases of akathisia in the 21-day oral aripiprazole groups (n = 81) and 4 cases in the ALncd groups (n = 80) (3 mild cases, 1 moderate case). None of the adverse events related to akathisia were deemed serious, and no patients discontinued participation in the trial due to akathisia.⁹

Continue to: Clinical considerations

ALncd is not a substitute for AL due to the very different kinetic properties of the 2 preparations. ALncd is approved only to be used for initiating treatment with AL, or in those instances where the revised missed dose guidelines for AL permit use of ALncd to obviate the need for oral coverage.⁹ Table 3⁹ presents these revised AL missed dose guidelines focusing on those time periods when some form of supplementation is required in addition to the established maintenance AL dose. Clinicians should be reminded that ALncd must be paired with a dose of AL, although the latter can be given up to 10 days later when commencing therapy.

• it obviates the need for 21 days of oral coverage previously required at the initiation of AL treatment
• clinically relevant plasma levels are seen within the first week when ALncd is combined with a single 30 mg oral aripiprazole dose
• per the revised missed dose guidelines for AL, it can be used in those situations that previously demanded 7 days of oral coverage, and, when combined with a single 30 mg oral dose, can be used for resumption of therapy after prolonged absences that required 21 days of oral coverage. In all instances, the patient will also receive their usual maintenance dose of AL.

Dosing. There is only one dose available for ALncd, 675 mg IM. As the dose cannot be modified, the package insert contains cautionary language regarding situations with less-than-expected drug exposure (use of cytochrome P450 [CYP] 3A4 inducers), greater-than-expected drug exposure (strong CYP3A4 or 2D6 inhibitors or known 2D6 poor metabolizers), or increased pharmacodynamic effects (concurrent use of antihypertensives or benzodiazepines).

Contraindications. The only contraindication is a known hypersensitivity to aripiprazole.

Bottom Line

Aripiprazole lauroxil nanocrystal suspension (Aristada Initio) was specifically developed to obviate the need for 21 days of oral aripiprazole coverage when commencing treatment with aripiprazole lauroxil (Aristada). The plasma levels achieved when an injection of aripiprazole lauroxil nanocrystal suspension is combined with a single 30 mg oral dose are comparable to those achieved with 21 days of oral coverage. This initiation regimen, including a aripiprazole lauroxil nanocrystal injection and a 30 mg oral dose, should be administered on the same day as the maintenance aripiprazole lauroxil injection, although the latter can be administered on any of the next 10 days.

Related Resource

• Khan AY, Ovais DM. Long-acting injectable aripiprazole lauroxil for schizophrenia. Current Psychiatry. 2016;15(7):50-52,58.

Drug Brand Names
Aripiprazole lauroxil • Aristada
Aripiprazole lauroxil nanocrystal • Aristada Initio
Risperidone microspheres • Risperdal Consta