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FDA approves new drug for relapsed/refractory multiple myeloma
The U.S. Food and Drug Administration today approved isatuximab (Sarclisa, Sanofi) in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of adult patients with multiple myeloma who have received two or more prior therapies including lenalidomide and a proteasome inhibitor.
Isatuximab is an anti-CD38 monoclonal antibody administered by intravenous infusion that works by helping the immune system attack multiple myeloma cancer cells.
“While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
“In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he added.
The new approval is based on results from ICARIA-MM, an open-label, randomized phase 3 clinical trial of isatuximab among 307 patients in this setting.
In the trial, at a median follow-up of 11.6 months, median progression-free survival was 11.5 months in the isatuximab-pomalidomide-dexamethasone group versus 6.5 months in the pomalidomide-dexamethasone group (hazard ratio, 0.60; P = .001), as reported last year. Overall response rates were 60.4% for the triplet-treated group versus 35.3% for the doublet-treated group.
The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia.
Deaths because of treatment-related adverse events were reported for one patient (less than 1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two patients (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).
The drug can also cause serious side effects, including IV infusion-related reactions. In the case of a grade 3 or higher reaction, the drug should be permanently discontinued and health care professionals should institute appropriate medical management.
The FDA notes there have been higher incidences of second primary malignancies observed in a controlled clinical trial of patients with multiple myeloma receiving the drug.
The FDA also highlighted that laboratory test interference may be caused by isatuximab and that blood banks should be informed that patients are receiving the drug. Isatuximab may interfere with, for example, antibody screening for patients who need a blood transfusion. Isatuximab may also interfere with the assays used to monitor M-protein, which may impact the determination of complete response.
This article originally appeared on Medscape.com.
The U.S. Food and Drug Administration today approved isatuximab (Sarclisa, Sanofi) in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of adult patients with multiple myeloma who have received two or more prior therapies including lenalidomide and a proteasome inhibitor.
Isatuximab is an anti-CD38 monoclonal antibody administered by intravenous infusion that works by helping the immune system attack multiple myeloma cancer cells.
“While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
“In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he added.
The new approval is based on results from ICARIA-MM, an open-label, randomized phase 3 clinical trial of isatuximab among 307 patients in this setting.
In the trial, at a median follow-up of 11.6 months, median progression-free survival was 11.5 months in the isatuximab-pomalidomide-dexamethasone group versus 6.5 months in the pomalidomide-dexamethasone group (hazard ratio, 0.60; P = .001), as reported last year. Overall response rates were 60.4% for the triplet-treated group versus 35.3% for the doublet-treated group.
The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia.
Deaths because of treatment-related adverse events were reported for one patient (less than 1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two patients (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).
The drug can also cause serious side effects, including IV infusion-related reactions. In the case of a grade 3 or higher reaction, the drug should be permanently discontinued and health care professionals should institute appropriate medical management.
The FDA notes there have been higher incidences of second primary malignancies observed in a controlled clinical trial of patients with multiple myeloma receiving the drug.
The FDA also highlighted that laboratory test interference may be caused by isatuximab and that blood banks should be informed that patients are receiving the drug. Isatuximab may interfere with, for example, antibody screening for patients who need a blood transfusion. Isatuximab may also interfere with the assays used to monitor M-protein, which may impact the determination of complete response.
This article originally appeared on Medscape.com.
The U.S. Food and Drug Administration today approved isatuximab (Sarclisa, Sanofi) in combination with pomalidomide (Revlimid, Celgene) and dexamethasone for the treatment of adult patients with multiple myeloma who have received two or more prior therapies including lenalidomide and a proteasome inhibitor.
Isatuximab is an anti-CD38 monoclonal antibody administered by intravenous infusion that works by helping the immune system attack multiple myeloma cancer cells.
“While there is no cure for multiple myeloma, Sarclisa is now another CD38-directed treatment option added to the list of FDA-approved treatments of patients with multiple myeloma who have progressive disease after previous therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
“In the clinical trial, there was a 40% reduction in the risk of disease progression or death with this therapy,” he added.
The new approval is based on results from ICARIA-MM, an open-label, randomized phase 3 clinical trial of isatuximab among 307 patients in this setting.
In the trial, at a median follow-up of 11.6 months, median progression-free survival was 11.5 months in the isatuximab-pomalidomide-dexamethasone group versus 6.5 months in the pomalidomide-dexamethasone group (hazard ratio, 0.60; P = .001), as reported last year. Overall response rates were 60.4% for the triplet-treated group versus 35.3% for the doublet-treated group.
The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia.
Deaths because of treatment-related adverse events were reported for one patient (less than 1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two patients (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).
The drug can also cause serious side effects, including IV infusion-related reactions. In the case of a grade 3 or higher reaction, the drug should be permanently discontinued and health care professionals should institute appropriate medical management.
The FDA notes there have been higher incidences of second primary malignancies observed in a controlled clinical trial of patients with multiple myeloma receiving the drug.
The FDA also highlighted that laboratory test interference may be caused by isatuximab and that blood banks should be informed that patients are receiving the drug. Isatuximab may interfere with, for example, antibody screening for patients who need a blood transfusion. Isatuximab may also interfere with the assays used to monitor M-protein, which may impact the determination of complete response.
This article originally appeared on Medscape.com.
New guideline offers recommendations for reproductive health in patients with rheumatic diseases
A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).
“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.
To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.
In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”
“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.
“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
Contraception
In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.
For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
Assisted reproductive technology
In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.
For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
Fertility preservation
In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.
Hormone therapy
In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.
Pregnancy assessment and management
Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.
For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”
Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily
For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.
For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.
Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.
Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.
The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.
The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.
The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.
SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.
A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).
“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.
To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.
In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”
“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.
“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
Contraception
In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.
For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
Assisted reproductive technology
In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.
For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
Fertility preservation
In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.
Hormone therapy
In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.
Pregnancy assessment and management
Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.
For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”
Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily
For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.
For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.
Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.
Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.
The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.
The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.
The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.
SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.
A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).
“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.
To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.
In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”
“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.
“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
Contraception
In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.
For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
Assisted reproductive technology
In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.
For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
Fertility preservation
In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.
Hormone therapy
In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.
Pregnancy assessment and management
Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.
For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”
Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily
For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.
For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.
Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.
Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.
The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.
The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.
The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.
SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.
FROM ARTHRITIS & RHEUMATOLOGY
Cancer increase observed in modern era of MS drugs
WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”
With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.
“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.
In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.
The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).
Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”
“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”
However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.
Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.
And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”
“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.
WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”
With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.
“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.
In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.
The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).
Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”
“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”
However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.
Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.
And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”
“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.
WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.
“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”
With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.
“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.
“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.
In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.
The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.
For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.
The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.
Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).
And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).
Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).
Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”
Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”
“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”
However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.
Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.
And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.
“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”
In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”
Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”
“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.
Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.
SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.
REPORTING FROM ACTRIMS FORUM 2020
FDA OKs first orally disintegrating agent for rapid migraine relief
In clinical testing, a single 75-mg dose of rimegepant provided rapid migraine pain relief with patients returning to normal activities within 1 hour, with sustained benefit lasting up to 2 days in many patients. The majority of patients (86%) treated with a single dose did not need a migraine rescue medication within 24 hours.
“I see many patients in my practice whose lives are disrupted by migraine, afraid to go about everyday life in case of a migraine attack,” Peter Goadsby, MD, PhD, professor of neurology and director of the King’s Clinical Research Facility, King’s College Hospital, London, UK, said in a news release from Biohaven.
“Many feel unsure if their acute treatment will work and if they can manage the side effects. With the FDA approval of Nurtec ODT, there is renewed hope for people living with migraine that they can get back to living their lives without fear of the next attack,” said Goadsby.
More than 3100 patients have been treated with rimegepant with more than 113,000 doses administered in clinical trials, including a 1-year long-term safety study, the company said.
In the phase 3 trial, rimegepant achieved statistical significance on the co-primary endpoints of pain freedom and freedom from most bothersome symptom (MBS) 2 hours after administration compared with placebo.
Rimegepant also showed statistical superiority at 1 hour for pain relief (reduction of moderate or severe pain to no pain or mild pain) and return to normal function.
In many patients, the benefits of pain freedom, pain relief, return to normal function, and freedom from MBS with a single dose lasted up to 48 hours.
Rimegepant was generally well tolerated. The most common adverse reaction was nausea (2%) in patients who received rimegepant compared with 0.4% of patients who received placebo.
“Everyone knows someone living with migraine, yet it remains an invisible disease that is often overlooked and misunderstood,” Mary Franklin, executive director of the National Headache Foundation, commented in the news release.
“The approval of Nurtec ODT is exciting for people with migraine as it provides a new treatment option to help people regain control of their attacks and their lives,” said Franklin.
Nurtec ODT will be available in pharmacies in early March in packs of eight tablets. Each eight-tablet pack covers treatment of eight migraine attacks with one dose, as needed, up to once daily. Sample packs containing two tablets will also be made available to healthcare providers.
Rimegepant is not indicated for the preventive treatment of migraine. The company expects to report top-line results from its prevention of migraine trial later this quarter.
This story first appeared on Medscape.com.
In clinical testing, a single 75-mg dose of rimegepant provided rapid migraine pain relief with patients returning to normal activities within 1 hour, with sustained benefit lasting up to 2 days in many patients. The majority of patients (86%) treated with a single dose did not need a migraine rescue medication within 24 hours.
“I see many patients in my practice whose lives are disrupted by migraine, afraid to go about everyday life in case of a migraine attack,” Peter Goadsby, MD, PhD, professor of neurology and director of the King’s Clinical Research Facility, King’s College Hospital, London, UK, said in a news release from Biohaven.
“Many feel unsure if their acute treatment will work and if they can manage the side effects. With the FDA approval of Nurtec ODT, there is renewed hope for people living with migraine that they can get back to living their lives without fear of the next attack,” said Goadsby.
More than 3100 patients have been treated with rimegepant with more than 113,000 doses administered in clinical trials, including a 1-year long-term safety study, the company said.
In the phase 3 trial, rimegepant achieved statistical significance on the co-primary endpoints of pain freedom and freedom from most bothersome symptom (MBS) 2 hours after administration compared with placebo.
Rimegepant also showed statistical superiority at 1 hour for pain relief (reduction of moderate or severe pain to no pain or mild pain) and return to normal function.
In many patients, the benefits of pain freedom, pain relief, return to normal function, and freedom from MBS with a single dose lasted up to 48 hours.
Rimegepant was generally well tolerated. The most common adverse reaction was nausea (2%) in patients who received rimegepant compared with 0.4% of patients who received placebo.
“Everyone knows someone living with migraine, yet it remains an invisible disease that is often overlooked and misunderstood,” Mary Franklin, executive director of the National Headache Foundation, commented in the news release.
“The approval of Nurtec ODT is exciting for people with migraine as it provides a new treatment option to help people regain control of their attacks and their lives,” said Franklin.
Nurtec ODT will be available in pharmacies in early March in packs of eight tablets. Each eight-tablet pack covers treatment of eight migraine attacks with one dose, as needed, up to once daily. Sample packs containing two tablets will also be made available to healthcare providers.
Rimegepant is not indicated for the preventive treatment of migraine. The company expects to report top-line results from its prevention of migraine trial later this quarter.
This story first appeared on Medscape.com.
In clinical testing, a single 75-mg dose of rimegepant provided rapid migraine pain relief with patients returning to normal activities within 1 hour, with sustained benefit lasting up to 2 days in many patients. The majority of patients (86%) treated with a single dose did not need a migraine rescue medication within 24 hours.
“I see many patients in my practice whose lives are disrupted by migraine, afraid to go about everyday life in case of a migraine attack,” Peter Goadsby, MD, PhD, professor of neurology and director of the King’s Clinical Research Facility, King’s College Hospital, London, UK, said in a news release from Biohaven.
“Many feel unsure if their acute treatment will work and if they can manage the side effects. With the FDA approval of Nurtec ODT, there is renewed hope for people living with migraine that they can get back to living their lives without fear of the next attack,” said Goadsby.
More than 3100 patients have been treated with rimegepant with more than 113,000 doses administered in clinical trials, including a 1-year long-term safety study, the company said.
In the phase 3 trial, rimegepant achieved statistical significance on the co-primary endpoints of pain freedom and freedom from most bothersome symptom (MBS) 2 hours after administration compared with placebo.
Rimegepant also showed statistical superiority at 1 hour for pain relief (reduction of moderate or severe pain to no pain or mild pain) and return to normal function.
In many patients, the benefits of pain freedom, pain relief, return to normal function, and freedom from MBS with a single dose lasted up to 48 hours.
Rimegepant was generally well tolerated. The most common adverse reaction was nausea (2%) in patients who received rimegepant compared with 0.4% of patients who received placebo.
“Everyone knows someone living with migraine, yet it remains an invisible disease that is often overlooked and misunderstood,” Mary Franklin, executive director of the National Headache Foundation, commented in the news release.
“The approval of Nurtec ODT is exciting for people with migraine as it provides a new treatment option to help people regain control of their attacks and their lives,” said Franklin.
Nurtec ODT will be available in pharmacies in early March in packs of eight tablets. Each eight-tablet pack covers treatment of eight migraine attacks with one dose, as needed, up to once daily. Sample packs containing two tablets will also be made available to healthcare providers.
Rimegepant is not indicated for the preventive treatment of migraine. The company expects to report top-line results from its prevention of migraine trial later this quarter.
This story first appeared on Medscape.com.
Endocrine Society advises on use of romosozumab for osteoporosis
Latest guidelines on the treatment of osteoporosis have been released that include new recommendations for the use of romosozumab (Evenity) in postmenopausal women with severe osteoporosis, but they contain caveats as to which women should – and should not – receive the drug.
The updated clinical practice guideline from the Endocrine Society is in response to the approval of romosozumab by the Food and Drug Administration (FDA) in April 2019, and more recently, by the European Medicines Agency.
It was published online February 18 in the Journal of Clinical Endocrinology & Metabolism.
In the new guidelines, committee members recommend the use of romosozumab for postmenopausal women with osteoporosis at very high risk of fracture. Candidates would include women with severe osteoporosis (T-score of less than –2.5 and a prior fracture) or women with a history of multiple vertebral fractures.
Women should be treated with romosozumab for up to 1 year, followed by an antiresorptive agent to maintain bone mineral density gains and further reduce fracture risk.
“The recommended dosage is 210 mg monthly by subcutaneous injection for 12 months,” the authors wrote.
However, and very importantly, romosozumab should not be considered for women at high risk of cardiovascular disease (CVD) or cerebrovascular disease. A high risk of CVD includes women who have had a previous myocardial infarction (MI) or stroke.
Experts questioned by Medscape Medical News stressed that romosozumab should not be a first-line, or even generally a second-line, option for osteoporosis, but it can be a considered for select patients with severe osteoporosis, taking into account CV risk.
Boxed warning
In the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH), there were more major adverse cardiovascular events (MACE) in the first year of the trial with romosozumab, and patients had a 31% higher risk of MACE with romosozumab, compared with the bisphosphonate alendronate.
As a result, the drug was initially rejected by a number of regulatory agencies.
In the United States and Canada, it was eventually approved with a boxed warning, which cautions against the use of the drug in patients at risk for myocardial infarction, stroke, and CVD-related death.
“Romosozumab offers promising results for postmenopausal women with severe osteoporosis or who have a history of fractures,” Clifford Rosen, MD, Maine Medical Center Research Institute in Scarborough and chair of the writing committee, said in an Endocrine Society statement. “It does, however, come with a risk of heart disease, so clinicians need to be careful when selecting patients for this therapy.”
Exact risk unknown
Asked by Medscape Medical News to comment, Kenneth Saag, MD, professor of medicine, University of Alabama at Birmingham and principle investigator of the ARCH study, said that physicians needed more data from real-world studies to resolve the issue around whether romosozumab heightens the risk of CV events in women with osteoporosis or whether that particular finding from ARCH was an artifact.
“Women who have had a recent cardiovascular event should not receive the drug,” he said, agreeing with the new guidelines.
But it remains unclear, for example, whether women who are at slightly higher risk of having a CV event by virtue of their age alone, are also at risk, he noted.
In the meantime, results from the ARCH study clearly showed that not only was romosozumab more effective than alendronate, “but it is more effective than other bone-building drugs as well,” Dr. Saag observed, and it leads to a significantly greater reduction in vertebral, nonvertebral, and hip fractures, compared with the alendronate, the current standard of care in osteoporosis.
“In patients who have very severe osteoporosis and who have had a recent fracture or who are at risk for imminent future fracture, physicians need to balance the benefit versus the risk in favor of using romosozumab,” Dr. Saag suggested.
“And while I would say most women prefer not to inject themselves, the women I have put on this medicine have all had recent fractures and they are very aware of the pain and the disability of having a broken bone, so it is something they are willing to do,” he added.
Not for all women
Giving his opinion, Bart Clarke, MD, of the Mayo Clinic in Rochester, Minnesota, underscored the fact that the Fracture Study in Postmenopausal Women With Osteoporosis (FRAME), again conducted in postmenopausal women, showed no increase in CV events in patients treated with romosozumab compared with placebo.
“So there are questions about what this means, because if these events really were a drug effect, then that effect would be even more evident compared with placebo and they did not see any signal of CV events [in FRAME],” said Dr. Clarke, past president of the American Society of Bone and Mineral Research.
Like everything else in medicine, “there is always some risk,” Dr. Clarke observed.
However, what physicians should do is talk to women, ensure they have not had either an MI or stroke in the last year, and if patients have severe osteoporosis and a high risk of fracture, “then we can say, here’s another option,” he suggested.
“Then, if a woman develops chest pain or shortness of breath while on the drug, [she needs] to let us know ,and then we’ll stop the drug and reassess the situation,” he added.
Dr. Clarke also pointed out that if the FDA had received further reports of CV events linked to romosozumab, physicians would know about it by now, but to his knowledge, there has been no change to the drug’s current warning label.
Furthermore, neither he nor any of his colleagues who treat metabolic bone disease at the Mayo Clinic has seen a single CV event in patients prescribed the agent.
“This is not a drug we would use as first-line for most patients, and we don’t even use it as second-line for most patients, but in people who have not responded to other drugs or who have had terrible things happen to them already, hip fracture especially, then we are saying, you can consider this, he concluded.
The guidelines were supported by the Endocrine Society. Dr. Rosen and Dr. Clarke reported no relevant financial relationships. Dr. Saag reported receiving grants and personal fees from Amgen, personal fees from Radius, and is a consultant for Amgen, Radius, Roche, and Daiichi Sankyo.
This article first appeared on Medscape.com.
Latest guidelines on the treatment of osteoporosis have been released that include new recommendations for the use of romosozumab (Evenity) in postmenopausal women with severe osteoporosis, but they contain caveats as to which women should – and should not – receive the drug.
The updated clinical practice guideline from the Endocrine Society is in response to the approval of romosozumab by the Food and Drug Administration (FDA) in April 2019, and more recently, by the European Medicines Agency.
It was published online February 18 in the Journal of Clinical Endocrinology & Metabolism.
In the new guidelines, committee members recommend the use of romosozumab for postmenopausal women with osteoporosis at very high risk of fracture. Candidates would include women with severe osteoporosis (T-score of less than –2.5 and a prior fracture) or women with a history of multiple vertebral fractures.
Women should be treated with romosozumab for up to 1 year, followed by an antiresorptive agent to maintain bone mineral density gains and further reduce fracture risk.
“The recommended dosage is 210 mg monthly by subcutaneous injection for 12 months,” the authors wrote.
However, and very importantly, romosozumab should not be considered for women at high risk of cardiovascular disease (CVD) or cerebrovascular disease. A high risk of CVD includes women who have had a previous myocardial infarction (MI) or stroke.
Experts questioned by Medscape Medical News stressed that romosozumab should not be a first-line, or even generally a second-line, option for osteoporosis, but it can be a considered for select patients with severe osteoporosis, taking into account CV risk.
Boxed warning
In the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH), there were more major adverse cardiovascular events (MACE) in the first year of the trial with romosozumab, and patients had a 31% higher risk of MACE with romosozumab, compared with the bisphosphonate alendronate.
As a result, the drug was initially rejected by a number of regulatory agencies.
In the United States and Canada, it was eventually approved with a boxed warning, which cautions against the use of the drug in patients at risk for myocardial infarction, stroke, and CVD-related death.
“Romosozumab offers promising results for postmenopausal women with severe osteoporosis or who have a history of fractures,” Clifford Rosen, MD, Maine Medical Center Research Institute in Scarborough and chair of the writing committee, said in an Endocrine Society statement. “It does, however, come with a risk of heart disease, so clinicians need to be careful when selecting patients for this therapy.”
Exact risk unknown
Asked by Medscape Medical News to comment, Kenneth Saag, MD, professor of medicine, University of Alabama at Birmingham and principle investigator of the ARCH study, said that physicians needed more data from real-world studies to resolve the issue around whether romosozumab heightens the risk of CV events in women with osteoporosis or whether that particular finding from ARCH was an artifact.
“Women who have had a recent cardiovascular event should not receive the drug,” he said, agreeing with the new guidelines.
But it remains unclear, for example, whether women who are at slightly higher risk of having a CV event by virtue of their age alone, are also at risk, he noted.
In the meantime, results from the ARCH study clearly showed that not only was romosozumab more effective than alendronate, “but it is more effective than other bone-building drugs as well,” Dr. Saag observed, and it leads to a significantly greater reduction in vertebral, nonvertebral, and hip fractures, compared with the alendronate, the current standard of care in osteoporosis.
“In patients who have very severe osteoporosis and who have had a recent fracture or who are at risk for imminent future fracture, physicians need to balance the benefit versus the risk in favor of using romosozumab,” Dr. Saag suggested.
“And while I would say most women prefer not to inject themselves, the women I have put on this medicine have all had recent fractures and they are very aware of the pain and the disability of having a broken bone, so it is something they are willing to do,” he added.
Not for all women
Giving his opinion, Bart Clarke, MD, of the Mayo Clinic in Rochester, Minnesota, underscored the fact that the Fracture Study in Postmenopausal Women With Osteoporosis (FRAME), again conducted in postmenopausal women, showed no increase in CV events in patients treated with romosozumab compared with placebo.
“So there are questions about what this means, because if these events really were a drug effect, then that effect would be even more evident compared with placebo and they did not see any signal of CV events [in FRAME],” said Dr. Clarke, past president of the American Society of Bone and Mineral Research.
Like everything else in medicine, “there is always some risk,” Dr. Clarke observed.
However, what physicians should do is talk to women, ensure they have not had either an MI or stroke in the last year, and if patients have severe osteoporosis and a high risk of fracture, “then we can say, here’s another option,” he suggested.
“Then, if a woman develops chest pain or shortness of breath while on the drug, [she needs] to let us know ,and then we’ll stop the drug and reassess the situation,” he added.
Dr. Clarke also pointed out that if the FDA had received further reports of CV events linked to romosozumab, physicians would know about it by now, but to his knowledge, there has been no change to the drug’s current warning label.
Furthermore, neither he nor any of his colleagues who treat metabolic bone disease at the Mayo Clinic has seen a single CV event in patients prescribed the agent.
“This is not a drug we would use as first-line for most patients, and we don’t even use it as second-line for most patients, but in people who have not responded to other drugs or who have had terrible things happen to them already, hip fracture especially, then we are saying, you can consider this, he concluded.
The guidelines were supported by the Endocrine Society. Dr. Rosen and Dr. Clarke reported no relevant financial relationships. Dr. Saag reported receiving grants and personal fees from Amgen, personal fees from Radius, and is a consultant for Amgen, Radius, Roche, and Daiichi Sankyo.
This article first appeared on Medscape.com.
Latest guidelines on the treatment of osteoporosis have been released that include new recommendations for the use of romosozumab (Evenity) in postmenopausal women with severe osteoporosis, but they contain caveats as to which women should – and should not – receive the drug.
The updated clinical practice guideline from the Endocrine Society is in response to the approval of romosozumab by the Food and Drug Administration (FDA) in April 2019, and more recently, by the European Medicines Agency.
It was published online February 18 in the Journal of Clinical Endocrinology & Metabolism.
In the new guidelines, committee members recommend the use of romosozumab for postmenopausal women with osteoporosis at very high risk of fracture. Candidates would include women with severe osteoporosis (T-score of less than –2.5 and a prior fracture) or women with a history of multiple vertebral fractures.
Women should be treated with romosozumab for up to 1 year, followed by an antiresorptive agent to maintain bone mineral density gains and further reduce fracture risk.
“The recommended dosage is 210 mg monthly by subcutaneous injection for 12 months,” the authors wrote.
However, and very importantly, romosozumab should not be considered for women at high risk of cardiovascular disease (CVD) or cerebrovascular disease. A high risk of CVD includes women who have had a previous myocardial infarction (MI) or stroke.
Experts questioned by Medscape Medical News stressed that romosozumab should not be a first-line, or even generally a second-line, option for osteoporosis, but it can be a considered for select patients with severe osteoporosis, taking into account CV risk.
Boxed warning
In the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH), there were more major adverse cardiovascular events (MACE) in the first year of the trial with romosozumab, and patients had a 31% higher risk of MACE with romosozumab, compared with the bisphosphonate alendronate.
As a result, the drug was initially rejected by a number of regulatory agencies.
In the United States and Canada, it was eventually approved with a boxed warning, which cautions against the use of the drug in patients at risk for myocardial infarction, stroke, and CVD-related death.
“Romosozumab offers promising results for postmenopausal women with severe osteoporosis or who have a history of fractures,” Clifford Rosen, MD, Maine Medical Center Research Institute in Scarborough and chair of the writing committee, said in an Endocrine Society statement. “It does, however, come with a risk of heart disease, so clinicians need to be careful when selecting patients for this therapy.”
Exact risk unknown
Asked by Medscape Medical News to comment, Kenneth Saag, MD, professor of medicine, University of Alabama at Birmingham and principle investigator of the ARCH study, said that physicians needed more data from real-world studies to resolve the issue around whether romosozumab heightens the risk of CV events in women with osteoporosis or whether that particular finding from ARCH was an artifact.
“Women who have had a recent cardiovascular event should not receive the drug,” he said, agreeing with the new guidelines.
But it remains unclear, for example, whether women who are at slightly higher risk of having a CV event by virtue of their age alone, are also at risk, he noted.
In the meantime, results from the ARCH study clearly showed that not only was romosozumab more effective than alendronate, “but it is more effective than other bone-building drugs as well,” Dr. Saag observed, and it leads to a significantly greater reduction in vertebral, nonvertebral, and hip fractures, compared with the alendronate, the current standard of care in osteoporosis.
“In patients who have very severe osteoporosis and who have had a recent fracture or who are at risk for imminent future fracture, physicians need to balance the benefit versus the risk in favor of using romosozumab,” Dr. Saag suggested.
“And while I would say most women prefer not to inject themselves, the women I have put on this medicine have all had recent fractures and they are very aware of the pain and the disability of having a broken bone, so it is something they are willing to do,” he added.
Not for all women
Giving his opinion, Bart Clarke, MD, of the Mayo Clinic in Rochester, Minnesota, underscored the fact that the Fracture Study in Postmenopausal Women With Osteoporosis (FRAME), again conducted in postmenopausal women, showed no increase in CV events in patients treated with romosozumab compared with placebo.
“So there are questions about what this means, because if these events really were a drug effect, then that effect would be even more evident compared with placebo and they did not see any signal of CV events [in FRAME],” said Dr. Clarke, past president of the American Society of Bone and Mineral Research.
Like everything else in medicine, “there is always some risk,” Dr. Clarke observed.
However, what physicians should do is talk to women, ensure they have not had either an MI or stroke in the last year, and if patients have severe osteoporosis and a high risk of fracture, “then we can say, here’s another option,” he suggested.
“Then, if a woman develops chest pain or shortness of breath while on the drug, [she needs] to let us know ,and then we’ll stop the drug and reassess the situation,” he added.
Dr. Clarke also pointed out that if the FDA had received further reports of CV events linked to romosozumab, physicians would know about it by now, but to his knowledge, there has been no change to the drug’s current warning label.
Furthermore, neither he nor any of his colleagues who treat metabolic bone disease at the Mayo Clinic has seen a single CV event in patients prescribed the agent.
“This is not a drug we would use as first-line for most patients, and we don’t even use it as second-line for most patients, but in people who have not responded to other drugs or who have had terrible things happen to them already, hip fracture especially, then we are saying, you can consider this, he concluded.
The guidelines were supported by the Endocrine Society. Dr. Rosen and Dr. Clarke reported no relevant financial relationships. Dr. Saag reported receiving grants and personal fees from Amgen, personal fees from Radius, and is a consultant for Amgen, Radius, Roche, and Daiichi Sankyo.
This article first appeared on Medscape.com.
FROM JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
FDA, FTC uniting to promote biosimilars
The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.
The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.
“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”
“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”
The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.
“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”
The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.
Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.
“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”
Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.
Dr. Edgerton highlighted why this agreement between the two agencies is so important.
“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”
Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.
The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.
The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.
The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.
“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”
“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”
The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.
“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”
The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.
Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.
“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”
Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.
Dr. Edgerton highlighted why this agreement between the two agencies is so important.
“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”
Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.
The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.
The Food and Drug Administration is collaborating with the Federal Trade Commission (FTC) to expand the biosimilars market.
The two agencies signed a joint statement on Feb. 3, 2020, outlining four sets of goals aimed at creating meaningful competition from biosimilars against their reference biologic products.
“Competition is key for helping American patients have access to affordable medicines,” FDA Commissioner Stephen Hahn, MD, said in a statement. “Strengthening efforts to curtail and discourage anticompetitive behavior is key for facilitating robust competition for patients in the biologics marketplace, including through biosimilars, bringing down the costs of these crucial products for patients.”
“We appreciate and applaud the FDA and FTC in recognizing that biosimilar development and approval has not been as robust as many stakeholders had hoped,” said Colin Edgerton, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We continue to see anticompetitive activities that prevent manufacturers from developing biosimilar products. We hope that a greater focus on these practices will pave the way for more biosimilars to be developed.”
The statement highlighted four goals. First is that the agencies will coordinate to promote greater competition in the biologic market, including the development of materials to educate the market about biosimilars. The FDA and FTC also will be sponsoring a public workshop on March 9 to discuss competition for biologics.
“This workshop is the first step,” Dr. Edgerton said. “ACR will continue to work with other organizations and patient groups to help educate providers and patients on the scientific rigor that is required in developing and approving biosimilars. Additionally, we look forward to working with the FDA and FTC to continue this conversation on ways to encourage more development of biosimilar products and greater education for the providers and patients.”
The second goal has the FDA and FTC working together “to deter behavior that impedes access to samples needed for the development of biologics, including biosimilars,” the joint statement notes.
Third, the agencies will crack down on “false or misleading communications about biologics, including biosimilars, within their respective authorities,” according to the joint statement.
“FDA and FTC, as authorized by their respective statutes, will work together to address false or misleading communications about biologics, including biosimilars,” the statement continues. “In particular, if a communication makes a false or misleading comparison between a reference product and a biosimilar in a manner that misrepresents the safety or efficacy of biosimilars, deceives consumers, or deters competition, FDA and FTC intend to take appropriate action within their respective authorities. FDA intends to take appropriate action to address such communications where those communications have the potential to impact public health.”
Finally, the FTC committed to review patent settlement agreements involving biologics, including biosimilars, for antitrust violations.
Dr. Edgerton highlighted why this agreement between the two agencies is so important.
“Biologics are life-changing treatments for many of our patients,” he said. “Due to the high cost of discovery and development, the cost of biologics has resulted in delayed access and financial hardships for so many. It has always been our hope that biosimilars would offer the same life-changing treatment for patients at a lower price point. A robust biosimilars market is imperative to allow greater access to these treatments that can help patients to have a better quality of life.”
Separately, the FDA issued a draft guidance document for comment on manufacturers seeking licensure of biosimilar products that do not cover all the approved uses of the reference product, as well as how to add uses over time that were not part of the initial license of the biosimilar product. The draft guidance covers licensure of products, labeling of biosimilars with fewer indications than the reference product, supplemental applications for indications not on the initial biosimilar application but covered by the reference product, and the timing of applications.
The FDA notes in the draft guidance that this is needed to cover situations such as when some indications on the reference product are covered by exclusivity, although it does encourage a biosimilar manufacturer to seek licensure for all indications that the reference product does have.
FDA approves first IV migraine prevention drug
As previously reported by Medscape Medical News, the drug’s approval is based on results from two clinical studies – PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine.
The recommended dose is 100 mg every 3 months although some patients may benefit from a dose of 300 mg, the company notes. Lundbeck reports that the drug will likely be available in early April.
Roger Cady, MD, vice-president of neurology at Lundbeck, told Medscape Medical News the drug has almost immediate efficacy.
“Because it’s an IV [medication], it has very rapid benefit. In fact, we were able to demonstrate benefit on Day 1. Truly, it is going to impact on the unmet need for patients because of its profile, the way it’s delivered, and its uniqueness,” Cady said.
“Having preventive activity the day following an infusion is really important. We have in our data, if you take that time between the first day and the 28th day, whether they have episodic migraine or chronic migraine, that about 30% of the population had a 75% or more reduction in migraine days through that first month,” he added.
The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti than with placebo for most of the first 7 days, the company reports.
The safety of Vyepti was evaluated in 2076 patients with migraine who received at least one dose of the drug. The most common adverse reactions were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment as a result of adverse reactions.
“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Peter Goadsby, MD, professor of neurology at King’s College, London, UK, and the University of California, San Francisco, in a press release. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
This article first appeared on Medscape.com.
As previously reported by Medscape Medical News, the drug’s approval is based on results from two clinical studies – PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine.
The recommended dose is 100 mg every 3 months although some patients may benefit from a dose of 300 mg, the company notes. Lundbeck reports that the drug will likely be available in early April.
Roger Cady, MD, vice-president of neurology at Lundbeck, told Medscape Medical News the drug has almost immediate efficacy.
“Because it’s an IV [medication], it has very rapid benefit. In fact, we were able to demonstrate benefit on Day 1. Truly, it is going to impact on the unmet need for patients because of its profile, the way it’s delivered, and its uniqueness,” Cady said.
“Having preventive activity the day following an infusion is really important. We have in our data, if you take that time between the first day and the 28th day, whether they have episodic migraine or chronic migraine, that about 30% of the population had a 75% or more reduction in migraine days through that first month,” he added.
The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti than with placebo for most of the first 7 days, the company reports.
The safety of Vyepti was evaluated in 2076 patients with migraine who received at least one dose of the drug. The most common adverse reactions were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment as a result of adverse reactions.
“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Peter Goadsby, MD, professor of neurology at King’s College, London, UK, and the University of California, San Francisco, in a press release. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
This article first appeared on Medscape.com.
As previously reported by Medscape Medical News, the drug’s approval is based on results from two clinical studies – PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine.
The recommended dose is 100 mg every 3 months although some patients may benefit from a dose of 300 mg, the company notes. Lundbeck reports that the drug will likely be available in early April.
Roger Cady, MD, vice-president of neurology at Lundbeck, told Medscape Medical News the drug has almost immediate efficacy.
“Because it’s an IV [medication], it has very rapid benefit. In fact, we were able to demonstrate benefit on Day 1. Truly, it is going to impact on the unmet need for patients because of its profile, the way it’s delivered, and its uniqueness,” Cady said.
“Having preventive activity the day following an infusion is really important. We have in our data, if you take that time between the first day and the 28th day, whether they have episodic migraine or chronic migraine, that about 30% of the population had a 75% or more reduction in migraine days through that first month,” he added.
The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti than with placebo for most of the first 7 days, the company reports.
The safety of Vyepti was evaluated in 2076 patients with migraine who received at least one dose of the drug. The most common adverse reactions were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti discontinued treatment as a result of adverse reactions.
“The PROMISE-2 data showed that many patients can achieve reduction in migraine days of at least 75% and experience a sustained migraine improvement through 6 months, which is clinically meaningful to both physicians and patients,” said Peter Goadsby, MD, professor of neurology at King’s College, London, UK, and the University of California, San Francisco, in a press release. “Vyepti is a valuable addition for the treatment of migraine, which can help reduce the burden of this serious disease.”
This article first appeared on Medscape.com.
FROM MEDSCAPE.COM
FDA opens the door to biosimilar insulin
The Food and Drug Administration published Feb. 21 in the Federal Register a final rule that transitions insulin and other products from regulation as a drug to a biologic. This will provide manufacturers access to the biosimilars approval pathway and is expected to bring more competition to the insulin market. The move comes as insulin manufacturers continue to get increased scrutiny over the significantly increased pricing of their products in recent years.
The transition was required under a provision of the Biologics Price Competition and Innovation Act of 2009.
The move is expected to have no impact on the distribution of insulin and other products affected by the transition.
“In general, prescribers should continue to prescribe and order insulin and other biological products the same way they did before the transition,” the FDA said in an FAQ on the transition for physicians and other health care workers. “In general, pharmacists should continue to dispense and counsel about insulin and other biological products the same way they did before the transition. Prescribers and pharmacists should ensure their patients understand there are no changes to the product and they should continue to use the product the same way as before the transition.”
Other products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins. Information on all the transitioning products will move from the Orange Book (which lists FDA-approved drug products with therapeutic equivalent evaluations) to the Purple Book (which lists FDA-licensed biological products with reference product exclusivity data and biosimilar/interchangeability evaluations).
The FDA in the FAQ reiterated its commitment to reviewing any applications for these transition products within 12 months of submission.
The Food and Drug Administration published Feb. 21 in the Federal Register a final rule that transitions insulin and other products from regulation as a drug to a biologic. This will provide manufacturers access to the biosimilars approval pathway and is expected to bring more competition to the insulin market. The move comes as insulin manufacturers continue to get increased scrutiny over the significantly increased pricing of their products in recent years.
The transition was required under a provision of the Biologics Price Competition and Innovation Act of 2009.
The move is expected to have no impact on the distribution of insulin and other products affected by the transition.
“In general, prescribers should continue to prescribe and order insulin and other biological products the same way they did before the transition,” the FDA said in an FAQ on the transition for physicians and other health care workers. “In general, pharmacists should continue to dispense and counsel about insulin and other biological products the same way they did before the transition. Prescribers and pharmacists should ensure their patients understand there are no changes to the product and they should continue to use the product the same way as before the transition.”
Other products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins. Information on all the transitioning products will move from the Orange Book (which lists FDA-approved drug products with therapeutic equivalent evaluations) to the Purple Book (which lists FDA-licensed biological products with reference product exclusivity data and biosimilar/interchangeability evaluations).
The FDA in the FAQ reiterated its commitment to reviewing any applications for these transition products within 12 months of submission.
The Food and Drug Administration published Feb. 21 in the Federal Register a final rule that transitions insulin and other products from regulation as a drug to a biologic. This will provide manufacturers access to the biosimilars approval pathway and is expected to bring more competition to the insulin market. The move comes as insulin manufacturers continue to get increased scrutiny over the significantly increased pricing of their products in recent years.
The transition was required under a provision of the Biologics Price Competition and Innovation Act of 2009.
The move is expected to have no impact on the distribution of insulin and other products affected by the transition.
“In general, prescribers should continue to prescribe and order insulin and other biological products the same way they did before the transition,” the FDA said in an FAQ on the transition for physicians and other health care workers. “In general, pharmacists should continue to dispense and counsel about insulin and other biological products the same way they did before the transition. Prescribers and pharmacists should ensure their patients understand there are no changes to the product and they should continue to use the product the same way as before the transition.”
Other products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins. Information on all the transitioning products will move from the Orange Book (which lists FDA-approved drug products with therapeutic equivalent evaluations) to the Purple Book (which lists FDA-licensed biological products with reference product exclusivity data and biosimilar/interchangeability evaluations).
The FDA in the FAQ reiterated its commitment to reviewing any applications for these transition products within 12 months of submission.
New lipid-lowering drug earns FDA approval
The Food and Drug Administration has approved bempedoic acid (Nexletol) for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL cholesterol lowering.
The oral adenosine triphosphate–citrate lyase (ACL) inhibitor is indicated as an adjunct to diet and maximally tolerated statin therapy in these patients, and approved at the 180 mg once daily dose, the agency announced today.
The safety and efficacy of bempedoic acid were demonstrated over 52 weeks in two multicenter randomized, clinical trials involving 3,009 adults with HeFH or established ASCVD on maximally tolerated statin therapy.
The difference between bempedoic acid and placebo for the primary outcome of change in LDL cholesterol from baseline to week 12 was –18% in the first trial, CLEAR Harmony (95% confidence interval, –20% to –16%; P less than .001), and –17% in the second trial, CLEAR Wisdom (95% CI, –21% to –14%; P less than .001).
The label notes that the effect on cardiovascular morbidity and mortality has not been determined. The label also includes warnings stating that bempedoic acid may increase blood uric acid levels and is associated with an increased risk of tendon rupture or injury.
In clinical trials, 26% of bempedoic acid–treated patients with normal baseline uric acid values versus 9.5% of placebo-treated patients experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction versus 1.1% with placebo, according to the label. Gout was reported in 1.5% of patients treated with bempedoic acid and 0.4% of those treated with placebo.
Also in clinical trials, the risk of tendon rupture was 0.5% with bempedoic acid and 0% with placebo. Tendon rupture involved the rotator cuff, biceps tendon, or Achilles tendon, and occurred within weeks to months of starting the drug. Rupture may “occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders,” the label states.
The label also advises that patients avoid concomitant use of bempedoic acid with simvastatin greater than 20 mg or pravastatin greater than 40 mg because it causes an increase in statin concentrations and may increase the risk of related myopathy.
A decision is expected shortly on a new drug application submitted by Esperion for an LDL cholesterol–lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet.
Full prescribing information is available online.
This article first appeared on Medscape.com.
The Food and Drug Administration has approved bempedoic acid (Nexletol) for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL cholesterol lowering.
The oral adenosine triphosphate–citrate lyase (ACL) inhibitor is indicated as an adjunct to diet and maximally tolerated statin therapy in these patients, and approved at the 180 mg once daily dose, the agency announced today.
The safety and efficacy of bempedoic acid were demonstrated over 52 weeks in two multicenter randomized, clinical trials involving 3,009 adults with HeFH or established ASCVD on maximally tolerated statin therapy.
The difference between bempedoic acid and placebo for the primary outcome of change in LDL cholesterol from baseline to week 12 was –18% in the first trial, CLEAR Harmony (95% confidence interval, –20% to –16%; P less than .001), and –17% in the second trial, CLEAR Wisdom (95% CI, –21% to –14%; P less than .001).
The label notes that the effect on cardiovascular morbidity and mortality has not been determined. The label also includes warnings stating that bempedoic acid may increase blood uric acid levels and is associated with an increased risk of tendon rupture or injury.
In clinical trials, 26% of bempedoic acid–treated patients with normal baseline uric acid values versus 9.5% of placebo-treated patients experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction versus 1.1% with placebo, according to the label. Gout was reported in 1.5% of patients treated with bempedoic acid and 0.4% of those treated with placebo.
Also in clinical trials, the risk of tendon rupture was 0.5% with bempedoic acid and 0% with placebo. Tendon rupture involved the rotator cuff, biceps tendon, or Achilles tendon, and occurred within weeks to months of starting the drug. Rupture may “occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders,” the label states.
The label also advises that patients avoid concomitant use of bempedoic acid with simvastatin greater than 20 mg or pravastatin greater than 40 mg because it causes an increase in statin concentrations and may increase the risk of related myopathy.
A decision is expected shortly on a new drug application submitted by Esperion for an LDL cholesterol–lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet.
Full prescribing information is available online.
This article first appeared on Medscape.com.
The Food and Drug Administration has approved bempedoic acid (Nexletol) for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL cholesterol lowering.
The oral adenosine triphosphate–citrate lyase (ACL) inhibitor is indicated as an adjunct to diet and maximally tolerated statin therapy in these patients, and approved at the 180 mg once daily dose, the agency announced today.
The safety and efficacy of bempedoic acid were demonstrated over 52 weeks in two multicenter randomized, clinical trials involving 3,009 adults with HeFH or established ASCVD on maximally tolerated statin therapy.
The difference between bempedoic acid and placebo for the primary outcome of change in LDL cholesterol from baseline to week 12 was –18% in the first trial, CLEAR Harmony (95% confidence interval, –20% to –16%; P less than .001), and –17% in the second trial, CLEAR Wisdom (95% CI, –21% to –14%; P less than .001).
The label notes that the effect on cardiovascular morbidity and mortality has not been determined. The label also includes warnings stating that bempedoic acid may increase blood uric acid levels and is associated with an increased risk of tendon rupture or injury.
In clinical trials, 26% of bempedoic acid–treated patients with normal baseline uric acid values versus 9.5% of placebo-treated patients experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction versus 1.1% with placebo, according to the label. Gout was reported in 1.5% of patients treated with bempedoic acid and 0.4% of those treated with placebo.
Also in clinical trials, the risk of tendon rupture was 0.5% with bempedoic acid and 0% with placebo. Tendon rupture involved the rotator cuff, biceps tendon, or Achilles tendon, and occurred within weeks to months of starting the drug. Rupture may “occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders,” the label states.
The label also advises that patients avoid concomitant use of bempedoic acid with simvastatin greater than 20 mg or pravastatin greater than 40 mg because it causes an increase in statin concentrations and may increase the risk of related myopathy.
A decision is expected shortly on a new drug application submitted by Esperion for an LDL cholesterol–lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet.
Full prescribing information is available online.
This article first appeared on Medscape.com.
As costs for neurologic drugs rise, adherence to therapy drops
For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.
The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.
Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.
Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.
Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.
“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.
Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.
The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.
SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.
For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.
The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.
Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.
Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.
Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.
“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.
Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.
The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.
SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.
For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.
The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.
Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.
Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.
Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.
“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.
Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.
The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.
SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.
FROM NEUROLOGY