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Here comes bimekizumab, the newest IL-17 inhibitor
KAUAI, HAWAII –
And that’s not all: Much the same was true in patients with psoriatic arthritis in the parallel phase 2b BE ACTIVE study and for ankylosing spondylitis in the BE AGILE study. BE ABLE was a double-blind, 12-week, multicenter, five-arm, placebo-controlled, dose-ranging study of 250 psoriasis patients randomized to various doses of subcutaneous bimekizumab or placebo every 4 weeks. The primary outcome – the PASI 90 response rate at 12 weeks, rather than the lower-bar PASI 75 endpoint more typically used in clinical trials – was 79% at the optimal dose. The PASI 100 rate – complete clearance of disease – at 12 weeks was 60%, Craig L. Leonardi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
lthough Dr. Leonardi is a distinguished psoriasis clinical trialist, he wasn’t involved in the BE ABLE study. Only top line results have been announced to date, although publication of the BE ABLE, BE AGILE, and BE ACTIVE results and presentations at major medical meetings are pending.
Bimekizumab is a humanized IgG1 monoclonal antibody which uniquely neutralizes both IL-17A and IL-17F. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit IL-17A, while brodalumab (Siliq) is a pan-IL-17 receptor antagonist, inhibiting the IL-17 A, A/F, E, F, and C receptors. The impressive clinical outcomes of the three BE phase 2b studies validate the notion that IL-17F is an important cytokine in tissue inflammation across a range of dermatologic and rheumatologic diseases.
A long-term extension of BE ABLE is ongoing. In addition, a phase 3 randomized trial of bimekizumab versus adalimumab (Humira) versus placebo in 450 psoriasis patients is now recruiting, as is a separate phase 3 placebo-controlled head to head comparison of bimekizumab versus ustekinumab (Stelara).
The BE ACTIVE study included 206 psoriatic arthritis patients. At the top dose of bimekizumab, the week 12 rate of at least a 50% improvement in joint symptoms, or ACR 50 response, was 46%, compared with 7% in placebo-treated controls. Patients with concomitant psoriasis over at least 3% of their body surface area demonstrated a 65% PASI 90 response rate at 12 weeks.
BE AGILE included 303 patients with ankylosing spondylitis. Forty-seven percent of those randomized to the top-performing dose of bimekizumab had at least a 40% improvement in their Ankylosing Spondylitis Activity Score, or ASAS 40, at week 12, as did 13% in the placebo arm.
Bimekizumab is being developed by UCB, which is planning additional studies advancing the biologic in all three diseases studied in the phase 2b trials.
Dr. Leonardi reported receiving research grants from well over a dozen pharmaceutical companies and serving as a consultant to UCB and others.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII –
And that’s not all: Much the same was true in patients with psoriatic arthritis in the parallel phase 2b BE ACTIVE study and for ankylosing spondylitis in the BE AGILE study. BE ABLE was a double-blind, 12-week, multicenter, five-arm, placebo-controlled, dose-ranging study of 250 psoriasis patients randomized to various doses of subcutaneous bimekizumab or placebo every 4 weeks. The primary outcome – the PASI 90 response rate at 12 weeks, rather than the lower-bar PASI 75 endpoint more typically used in clinical trials – was 79% at the optimal dose. The PASI 100 rate – complete clearance of disease – at 12 weeks was 60%, Craig L. Leonardi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
lthough Dr. Leonardi is a distinguished psoriasis clinical trialist, he wasn’t involved in the BE ABLE study. Only top line results have been announced to date, although publication of the BE ABLE, BE AGILE, and BE ACTIVE results and presentations at major medical meetings are pending.
Bimekizumab is a humanized IgG1 monoclonal antibody which uniquely neutralizes both IL-17A and IL-17F. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit IL-17A, while brodalumab (Siliq) is a pan-IL-17 receptor antagonist, inhibiting the IL-17 A, A/F, E, F, and C receptors. The impressive clinical outcomes of the three BE phase 2b studies validate the notion that IL-17F is an important cytokine in tissue inflammation across a range of dermatologic and rheumatologic diseases.
A long-term extension of BE ABLE is ongoing. In addition, a phase 3 randomized trial of bimekizumab versus adalimumab (Humira) versus placebo in 450 psoriasis patients is now recruiting, as is a separate phase 3 placebo-controlled head to head comparison of bimekizumab versus ustekinumab (Stelara).
The BE ACTIVE study included 206 psoriatic arthritis patients. At the top dose of bimekizumab, the week 12 rate of at least a 50% improvement in joint symptoms, or ACR 50 response, was 46%, compared with 7% in placebo-treated controls. Patients with concomitant psoriasis over at least 3% of their body surface area demonstrated a 65% PASI 90 response rate at 12 weeks.
BE AGILE included 303 patients with ankylosing spondylitis. Forty-seven percent of those randomized to the top-performing dose of bimekizumab had at least a 40% improvement in their Ankylosing Spondylitis Activity Score, or ASAS 40, at week 12, as did 13% in the placebo arm.
Bimekizumab is being developed by UCB, which is planning additional studies advancing the biologic in all three diseases studied in the phase 2b trials.
Dr. Leonardi reported receiving research grants from well over a dozen pharmaceutical companies and serving as a consultant to UCB and others.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII –
And that’s not all: Much the same was true in patients with psoriatic arthritis in the parallel phase 2b BE ACTIVE study and for ankylosing spondylitis in the BE AGILE study. BE ABLE was a double-blind, 12-week, multicenter, five-arm, placebo-controlled, dose-ranging study of 250 psoriasis patients randomized to various doses of subcutaneous bimekizumab or placebo every 4 weeks. The primary outcome – the PASI 90 response rate at 12 weeks, rather than the lower-bar PASI 75 endpoint more typically used in clinical trials – was 79% at the optimal dose. The PASI 100 rate – complete clearance of disease – at 12 weeks was 60%, Craig L. Leonardi, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
lthough Dr. Leonardi is a distinguished psoriasis clinical trialist, he wasn’t involved in the BE ABLE study. Only top line results have been announced to date, although publication of the BE ABLE, BE AGILE, and BE ACTIVE results and presentations at major medical meetings are pending.
Bimekizumab is a humanized IgG1 monoclonal antibody which uniquely neutralizes both IL-17A and IL-17F. In contrast, secukinumab (Cosentyx) and ixekizumab (Taltz) specifically inhibit IL-17A, while brodalumab (Siliq) is a pan-IL-17 receptor antagonist, inhibiting the IL-17 A, A/F, E, F, and C receptors. The impressive clinical outcomes of the three BE phase 2b studies validate the notion that IL-17F is an important cytokine in tissue inflammation across a range of dermatologic and rheumatologic diseases.
A long-term extension of BE ABLE is ongoing. In addition, a phase 3 randomized trial of bimekizumab versus adalimumab (Humira) versus placebo in 450 psoriasis patients is now recruiting, as is a separate phase 3 placebo-controlled head to head comparison of bimekizumab versus ustekinumab (Stelara).
The BE ACTIVE study included 206 psoriatic arthritis patients. At the top dose of bimekizumab, the week 12 rate of at least a 50% improvement in joint symptoms, or ACR 50 response, was 46%, compared with 7% in placebo-treated controls. Patients with concomitant psoriasis over at least 3% of their body surface area demonstrated a 65% PASI 90 response rate at 12 weeks.
BE AGILE included 303 patients with ankylosing spondylitis. Forty-seven percent of those randomized to the top-performing dose of bimekizumab had at least a 40% improvement in their Ankylosing Spondylitis Activity Score, or ASAS 40, at week 12, as did 13% in the placebo arm.
Bimekizumab is being developed by UCB, which is planning additional studies advancing the biologic in all three diseases studied in the phase 2b trials.
Dr. Leonardi reported receiving research grants from well over a dozen pharmaceutical companies and serving as a consultant to UCB and others.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Dermatology practice gaps: Missed diagnoses
KAUAI, HAWAII – Up to 130,000 patients hospitalized for treatment of lower extremity cellulitis annually in the United States turn out to have been misdiagnosed – and therein lies an opportunity for dermatologists to make a difference, according to Erik J. Stratman, MD, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.
As a section editor for UptoDate, he monitors the medical literature to identify , which he defines as things he and, he suspects, many other dermatologists are “either doing or not doing in practice that we shouldn’t or should be doing,” he explained at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
At the Hawaii meeting, he zeroed in on two such practice gaps pertaining to missed diagnoses.
Lower extremity cellulitis
A 2017 American Academy of Dermatology report on the national burden of skin disease contained eye-popping figures on the heavy toll of cellulitis. Cellulitis is the most common form of skin and soft tissue infection (SSTI). To put that into perspective, the annual incidence of SSTIs is 10-fold greater than that of pneumonia. Indeed, SSTIs account for 10% of all infectious disease–related hospitalizations across the country. There are 2.3 million emergency department visits per year for cellulitis, 14%-17% of which result in hospitalization (J Am Acad Dermatol. 2017 May;76[5]:958-972.e2).
Dr. Stratman, who is on the board of directors of the American Board of Dermatology, was favorably impressed with the work of a multicenter group of investigators who scrutinized 259 consecutive patients admitted with a diagnosis of lower extremity cellulitis through the emergency department at Massachusetts General Hospital in Boston. Seventy-nine of them (30.5%), were found to be misdiagnosed. Fifty-two of the 79 misdiagnosed patients had been admitted primarily for treatment of their supposed cellulitis: 44 of these 52, or 85%, didn’t require hospitalization, and 48 of the 52, or 92%, received unnecessary antibiotics.
Extrapolating from this experience, with application of cost data provided by the U.S. Agency for Healthcare Research and Quality, the investigators estimated that misdiagnosis of cellulitis results in 50,000 to 130,000 unnecessary hospitalizations annually. These hospitalizations for what the investigators termed “pseudocellulitis,” the majority of which is stasis dermatitis, resulted in inpatient costs estimated at up to $515 million per year. The unnecessary hospitalizations also led to an estimated 9,000 nosocomial infections, up to 5,000 Clostridium difficile infections, and a projected two to six cases of anaphylaxis resulting from exposure to the unnecessary antibiotics (JAMA Dermatol. 2017;153[2]:141-6).
Dr. Stratman said that the large Massachusetts General Hospital study mirrors his own experience when called upon to do a hospital consultation, as well as that of other dermatologists he has spoken with: “The number-one reason we get consulted is for stuff that is wrongfully admitted, mainly cellulitis.”
The investigators then went on to develop a simple prediction model for lower extremity cellulitis based upon their data. It’s called the ALT-70 score, an acronym for Asymmetric, Leukocytosis, Tachycardia, and Age greater than 70. A patient gets 3 points if one leg is affected, zero if both are. Age 70 or more is worth 2 points. A heart rate of 90 beats per minute or higher gets 1 point, as does a WBC of at least 10,000 per uL. A score of 0-2 spells at least an 83% likelihood that the patient has pseudocellulitis, while a score of 5 or points indicates at least an 82% likelihood of true cellulitis (J Am Acad Dermatol. 2017 Apr;76[4]:618-625.e2).
“If you don’t reach a score of 3, you’d better think a little bit harder before you hang that bag of vancomycin,” Dr. Stratman observed.
He ascribed the huge problem of misdiagnosed lower extremity cellulitis to several causes: emergency medicine physicians, hospitalists, and primary care physicians receive minimal dermatology training. In addition, there are no reliable diagnostic studies for the infection, and dermatologists are seldom consulted on patients with red legs, either because there are no dermatologists in a particular community or they don’t want to be consulted.
“It’s not all the dermatologists’ fault. Have you tried to get credentialed at a hospital lately? It’s a 1½-inch stack of papers and 8½ hours of electronic medical record training, if you’re lucky. So there are definitely barriers to overcoming this gap,” Dr. Stratman pointed out.
The best solution, he continued, is for dermatologists to take the initiative in educating hospitalists, emergency medicine specialists, and primary care physicians on the common mimickers of cellulitis, especially stasis dermatitis and contact dermatitis. This can happen through grand rounds presentations and feedback to consulting physicians.
“I think dermatologists have to take the lead on this,” Dr. Stratman said.
Underscreening for autoimmune thyroid disease in vitiligo patients
The international Vitiligo Working Group, citing evidence that 19% of patients with vitiligo have concomitant autoimmune thyroid disease and that the risk of developing this endocrine disease doubles every 5 years that a patient has vitiligo, has issued a call to action for dermatologists to ensure that their patients with vitiligo undergo periodic screening (J Am Acad Dermatol. 2017 Jul;77[1]:1-13).
This recommendation was based upon insights provided by a French prospective, observational study of 626 patients with vitiligo. The French investigators found that the risk of autoimmune thyroid disease doubled every 5 years and was associated with female sex, younger age at vitiligo onset, vitiligo on the trunk, and a personal history of autoimmune disease. They recommended screening every 2 years for thyroid-stimulating hormone and free thyroxine levels, as well as checking for serum antithyroperoxidase antibodies (Br J Dermatol. 2013 Apr;168[4]:756-61).
Dr. Stratman noted that some dermatologists may feel that ordering thyroid screening tests is outside their scope of practice. In that case, it’s important to engage with their vitiligo patient’s primary care physician to make sure the screening gets done.
He reported having no financial conflicts of interest regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Up to 130,000 patients hospitalized for treatment of lower extremity cellulitis annually in the United States turn out to have been misdiagnosed – and therein lies an opportunity for dermatologists to make a difference, according to Erik J. Stratman, MD, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.
As a section editor for UptoDate, he monitors the medical literature to identify , which he defines as things he and, he suspects, many other dermatologists are “either doing or not doing in practice that we shouldn’t or should be doing,” he explained at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
At the Hawaii meeting, he zeroed in on two such practice gaps pertaining to missed diagnoses.
Lower extremity cellulitis
A 2017 American Academy of Dermatology report on the national burden of skin disease contained eye-popping figures on the heavy toll of cellulitis. Cellulitis is the most common form of skin and soft tissue infection (SSTI). To put that into perspective, the annual incidence of SSTIs is 10-fold greater than that of pneumonia. Indeed, SSTIs account for 10% of all infectious disease–related hospitalizations across the country. There are 2.3 million emergency department visits per year for cellulitis, 14%-17% of which result in hospitalization (J Am Acad Dermatol. 2017 May;76[5]:958-972.e2).
Dr. Stratman, who is on the board of directors of the American Board of Dermatology, was favorably impressed with the work of a multicenter group of investigators who scrutinized 259 consecutive patients admitted with a diagnosis of lower extremity cellulitis through the emergency department at Massachusetts General Hospital in Boston. Seventy-nine of them (30.5%), were found to be misdiagnosed. Fifty-two of the 79 misdiagnosed patients had been admitted primarily for treatment of their supposed cellulitis: 44 of these 52, or 85%, didn’t require hospitalization, and 48 of the 52, or 92%, received unnecessary antibiotics.
Extrapolating from this experience, with application of cost data provided by the U.S. Agency for Healthcare Research and Quality, the investigators estimated that misdiagnosis of cellulitis results in 50,000 to 130,000 unnecessary hospitalizations annually. These hospitalizations for what the investigators termed “pseudocellulitis,” the majority of which is stasis dermatitis, resulted in inpatient costs estimated at up to $515 million per year. The unnecessary hospitalizations also led to an estimated 9,000 nosocomial infections, up to 5,000 Clostridium difficile infections, and a projected two to six cases of anaphylaxis resulting from exposure to the unnecessary antibiotics (JAMA Dermatol. 2017;153[2]:141-6).
Dr. Stratman said that the large Massachusetts General Hospital study mirrors his own experience when called upon to do a hospital consultation, as well as that of other dermatologists he has spoken with: “The number-one reason we get consulted is for stuff that is wrongfully admitted, mainly cellulitis.”
The investigators then went on to develop a simple prediction model for lower extremity cellulitis based upon their data. It’s called the ALT-70 score, an acronym for Asymmetric, Leukocytosis, Tachycardia, and Age greater than 70. A patient gets 3 points if one leg is affected, zero if both are. Age 70 or more is worth 2 points. A heart rate of 90 beats per minute or higher gets 1 point, as does a WBC of at least 10,000 per uL. A score of 0-2 spells at least an 83% likelihood that the patient has pseudocellulitis, while a score of 5 or points indicates at least an 82% likelihood of true cellulitis (J Am Acad Dermatol. 2017 Apr;76[4]:618-625.e2).
“If you don’t reach a score of 3, you’d better think a little bit harder before you hang that bag of vancomycin,” Dr. Stratman observed.
He ascribed the huge problem of misdiagnosed lower extremity cellulitis to several causes: emergency medicine physicians, hospitalists, and primary care physicians receive minimal dermatology training. In addition, there are no reliable diagnostic studies for the infection, and dermatologists are seldom consulted on patients with red legs, either because there are no dermatologists in a particular community or they don’t want to be consulted.
“It’s not all the dermatologists’ fault. Have you tried to get credentialed at a hospital lately? It’s a 1½-inch stack of papers and 8½ hours of electronic medical record training, if you’re lucky. So there are definitely barriers to overcoming this gap,” Dr. Stratman pointed out.
The best solution, he continued, is for dermatologists to take the initiative in educating hospitalists, emergency medicine specialists, and primary care physicians on the common mimickers of cellulitis, especially stasis dermatitis and contact dermatitis. This can happen through grand rounds presentations and feedback to consulting physicians.
“I think dermatologists have to take the lead on this,” Dr. Stratman said.
Underscreening for autoimmune thyroid disease in vitiligo patients
The international Vitiligo Working Group, citing evidence that 19% of patients with vitiligo have concomitant autoimmune thyroid disease and that the risk of developing this endocrine disease doubles every 5 years that a patient has vitiligo, has issued a call to action for dermatologists to ensure that their patients with vitiligo undergo periodic screening (J Am Acad Dermatol. 2017 Jul;77[1]:1-13).
This recommendation was based upon insights provided by a French prospective, observational study of 626 patients with vitiligo. The French investigators found that the risk of autoimmune thyroid disease doubled every 5 years and was associated with female sex, younger age at vitiligo onset, vitiligo on the trunk, and a personal history of autoimmune disease. They recommended screening every 2 years for thyroid-stimulating hormone and free thyroxine levels, as well as checking for serum antithyroperoxidase antibodies (Br J Dermatol. 2013 Apr;168[4]:756-61).
Dr. Stratman noted that some dermatologists may feel that ordering thyroid screening tests is outside their scope of practice. In that case, it’s important to engage with their vitiligo patient’s primary care physician to make sure the screening gets done.
He reported having no financial conflicts of interest regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Up to 130,000 patients hospitalized for treatment of lower extremity cellulitis annually in the United States turn out to have been misdiagnosed – and therein lies an opportunity for dermatologists to make a difference, according to Erik J. Stratman, MD, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.
As a section editor for UptoDate, he monitors the medical literature to identify , which he defines as things he and, he suspects, many other dermatologists are “either doing or not doing in practice that we shouldn’t or should be doing,” he explained at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
At the Hawaii meeting, he zeroed in on two such practice gaps pertaining to missed diagnoses.
Lower extremity cellulitis
A 2017 American Academy of Dermatology report on the national burden of skin disease contained eye-popping figures on the heavy toll of cellulitis. Cellulitis is the most common form of skin and soft tissue infection (SSTI). To put that into perspective, the annual incidence of SSTIs is 10-fold greater than that of pneumonia. Indeed, SSTIs account for 10% of all infectious disease–related hospitalizations across the country. There are 2.3 million emergency department visits per year for cellulitis, 14%-17% of which result in hospitalization (J Am Acad Dermatol. 2017 May;76[5]:958-972.e2).
Dr. Stratman, who is on the board of directors of the American Board of Dermatology, was favorably impressed with the work of a multicenter group of investigators who scrutinized 259 consecutive patients admitted with a diagnosis of lower extremity cellulitis through the emergency department at Massachusetts General Hospital in Boston. Seventy-nine of them (30.5%), were found to be misdiagnosed. Fifty-two of the 79 misdiagnosed patients had been admitted primarily for treatment of their supposed cellulitis: 44 of these 52, or 85%, didn’t require hospitalization, and 48 of the 52, or 92%, received unnecessary antibiotics.
Extrapolating from this experience, with application of cost data provided by the U.S. Agency for Healthcare Research and Quality, the investigators estimated that misdiagnosis of cellulitis results in 50,000 to 130,000 unnecessary hospitalizations annually. These hospitalizations for what the investigators termed “pseudocellulitis,” the majority of which is stasis dermatitis, resulted in inpatient costs estimated at up to $515 million per year. The unnecessary hospitalizations also led to an estimated 9,000 nosocomial infections, up to 5,000 Clostridium difficile infections, and a projected two to six cases of anaphylaxis resulting from exposure to the unnecessary antibiotics (JAMA Dermatol. 2017;153[2]:141-6).
Dr. Stratman said that the large Massachusetts General Hospital study mirrors his own experience when called upon to do a hospital consultation, as well as that of other dermatologists he has spoken with: “The number-one reason we get consulted is for stuff that is wrongfully admitted, mainly cellulitis.”
The investigators then went on to develop a simple prediction model for lower extremity cellulitis based upon their data. It’s called the ALT-70 score, an acronym for Asymmetric, Leukocytosis, Tachycardia, and Age greater than 70. A patient gets 3 points if one leg is affected, zero if both are. Age 70 or more is worth 2 points. A heart rate of 90 beats per minute or higher gets 1 point, as does a WBC of at least 10,000 per uL. A score of 0-2 spells at least an 83% likelihood that the patient has pseudocellulitis, while a score of 5 or points indicates at least an 82% likelihood of true cellulitis (J Am Acad Dermatol. 2017 Apr;76[4]:618-625.e2).
“If you don’t reach a score of 3, you’d better think a little bit harder before you hang that bag of vancomycin,” Dr. Stratman observed.
He ascribed the huge problem of misdiagnosed lower extremity cellulitis to several causes: emergency medicine physicians, hospitalists, and primary care physicians receive minimal dermatology training. In addition, there are no reliable diagnostic studies for the infection, and dermatologists are seldom consulted on patients with red legs, either because there are no dermatologists in a particular community or they don’t want to be consulted.
“It’s not all the dermatologists’ fault. Have you tried to get credentialed at a hospital lately? It’s a 1½-inch stack of papers and 8½ hours of electronic medical record training, if you’re lucky. So there are definitely barriers to overcoming this gap,” Dr. Stratman pointed out.
The best solution, he continued, is for dermatologists to take the initiative in educating hospitalists, emergency medicine specialists, and primary care physicians on the common mimickers of cellulitis, especially stasis dermatitis and contact dermatitis. This can happen through grand rounds presentations and feedback to consulting physicians.
“I think dermatologists have to take the lead on this,” Dr. Stratman said.
Underscreening for autoimmune thyroid disease in vitiligo patients
The international Vitiligo Working Group, citing evidence that 19% of patients with vitiligo have concomitant autoimmune thyroid disease and that the risk of developing this endocrine disease doubles every 5 years that a patient has vitiligo, has issued a call to action for dermatologists to ensure that their patients with vitiligo undergo periodic screening (J Am Acad Dermatol. 2017 Jul;77[1]:1-13).
This recommendation was based upon insights provided by a French prospective, observational study of 626 patients with vitiligo. The French investigators found that the risk of autoimmune thyroid disease doubled every 5 years and was associated with female sex, younger age at vitiligo onset, vitiligo on the trunk, and a personal history of autoimmune disease. They recommended screening every 2 years for thyroid-stimulating hormone and free thyroxine levels, as well as checking for serum antithyroperoxidase antibodies (Br J Dermatol. 2013 Apr;168[4]:756-61).
Dr. Stratman noted that some dermatologists may feel that ordering thyroid screening tests is outside their scope of practice. In that case, it’s important to engage with their vitiligo patient’s primary care physician to make sure the screening gets done.
He reported having no financial conflicts of interest regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Promising outcomes of thrombolysis for caval extension of iliofemoral DVT
CHICAGO – Caval extension of an acute iliofemoral deep vein thrombosis paradoxically portends better treatment outcomes than does thrombolysis of a DVT without involvement of the inferior vena cava, according to Rabih A. Chaer, MD, professor of surgery at the University of Pittsburgh.
This finding from a retrospective analysis of the University of Pittsburgh experience might seem counterintuitive. After all, caval extension clearly indicates a greater clot burden. One possible explanation: Clearing a thrombus from a large vessel, such as the inferior vena cava (IVC), provides an added protective effect. Also, since the caval segments don’t have valves – their flow is based upon negative pressure in the chest – they may not contribute as much to postthrombotic morbidity to the same extent as do thrombosed iliofemoral segments, Dr. Chaer speculated at a symposium on vascular surgery sponsored by Northwestern University.
The impetus for Dr. Chaer and coinvestigators to review the Pittsburgh experience was a lack of clarity in the literature as to the effect IVC thrombosis has on thrombolysis outcomes in patients with acute iliofemoral DVT. Even though caval thrombus extension is present in up to 22% of patients with iliofemoral DVT, current guidelines issued by the American College of Chest Physicians, the American Heart Association, and the Society for Vascular Surgery don’t address the distinction between iliofemoral DVT with and without IVC extension in regard to the occurrence of postthrombotic syndrome (PTS), the most common complication of DVT.
The incidence of PTS in patients whose iliofemoral DVT is treated by anticoagulation and compression alone is up to 50%. Mounting evidence indicates that catheter-directed thrombolysis and pharmacomechanical thrombolysis aimed at achieving early thrombus removal and symptom relief help maintain valvular competence and reduce the risk of PTS, the surgeon noted.
PTS is diagnosed using the validated Villalta scale, which incorporates clinical signs including pain on calf compression, skin edema and redness, and ulcers, as well as symptoms such as leg cramping, heaviness, itching, and paresthesia.
The Pittsburgh series included 102 consecutive patients treated with various combinations of catheter-directed or pharmacomechanical thrombolysis in 127 limbs with acute iliofemoral thrombosis. In 46 patients, the thrombus extended into the IVC, all the way up to the renal veins in most cases.
The groups with and without caval extension were similar in terms of age and prevalence of malignancy, hypercoagulable state, and clot age. However, a history of previous DVT was significantly more common in the group with IVC thrombus. Also, more than 60% of patients with caval extension got an IVC filter, a rate more than 10-fold greater than that in patients without caval extension.
In this series, caval thrombosis had no effect on the technical success of thrombolysis. The technical success rate –defined as at least 50% clot lysis – was 89% in both groups. Rates of recurrent DVT within 30 days were similar in the two groups as well: 11% in the caval thrombosis group and 14% in the noncaval group. At 2 years postintervention, 77%-78% of patients in both groups remained free of DVT recurrence. The rate of PTS – defined by a Villalta score of 5 or more – at 2 years was 34% in the noncaval group, which was significantly higher than the 11% rate in patients with IVC thrombus extension. Ultrasound-identified valve reflux was present in 51% of the noncaval group at 2 years, compared with 51% of the noncaval group.
On multivariate analysis, incomplete clot lysis was associated with nearly a 23-fold increased risk of recurrent DVT and a 5.6-fold increased risk of PTS. Caval involvement was independently associated with a 78% reduction in PTS risk.
The Society for Vascular Surgery’s guidelines recommend pharmacomechanical thrombolysis over catheter-directed thrombolysis if the expertise is available. The Pittsburgh experience speaks to the worth of that recommendation.
“Pharmacomechanical techniques can be advantageous. They can expedite the lysis process by clearing most of the clot. In our series, 20 patients were treated with pharmacomechanical techniques in a single session,” Dr. Chaer noted.
The use of IVC filters in the setting of caval extension of iliofemoral DVT is controversial, according to the surgeon: A thrombus that gets trapped in the filter is tough to remove, precluding successful recanalization.
“One-third of the patients in our series got a filter, but we’ve become more conservative nowadays. We don’t use filters anymore. But I think those patients who might benefit from an IVC filter are those who present with a PE [pulmonary embolism], because that’s telling you they might develop another PE, as well as those patients in whom pharmacomechanical thrombolysis is anticipated because we’ve seen that those patients are also more likely to develop a PE,” he said.
The University of Pittsburgh study on the effect of IVC thrombus extension has been published (J Vasc Surg Venous Lymphat Disord. 2016 Oct;4[4]:385-91).
Dr. Chaer reported serving as a paid speaker for Boston Scientific.
SOURCE: Chaer RA. Northwestern Vascular Symposium 2017.
CHICAGO – Caval extension of an acute iliofemoral deep vein thrombosis paradoxically portends better treatment outcomes than does thrombolysis of a DVT without involvement of the inferior vena cava, according to Rabih A. Chaer, MD, professor of surgery at the University of Pittsburgh.
This finding from a retrospective analysis of the University of Pittsburgh experience might seem counterintuitive. After all, caval extension clearly indicates a greater clot burden. One possible explanation: Clearing a thrombus from a large vessel, such as the inferior vena cava (IVC), provides an added protective effect. Also, since the caval segments don’t have valves – their flow is based upon negative pressure in the chest – they may not contribute as much to postthrombotic morbidity to the same extent as do thrombosed iliofemoral segments, Dr. Chaer speculated at a symposium on vascular surgery sponsored by Northwestern University.
The impetus for Dr. Chaer and coinvestigators to review the Pittsburgh experience was a lack of clarity in the literature as to the effect IVC thrombosis has on thrombolysis outcomes in patients with acute iliofemoral DVT. Even though caval thrombus extension is present in up to 22% of patients with iliofemoral DVT, current guidelines issued by the American College of Chest Physicians, the American Heart Association, and the Society for Vascular Surgery don’t address the distinction between iliofemoral DVT with and without IVC extension in regard to the occurrence of postthrombotic syndrome (PTS), the most common complication of DVT.
The incidence of PTS in patients whose iliofemoral DVT is treated by anticoagulation and compression alone is up to 50%. Mounting evidence indicates that catheter-directed thrombolysis and pharmacomechanical thrombolysis aimed at achieving early thrombus removal and symptom relief help maintain valvular competence and reduce the risk of PTS, the surgeon noted.
PTS is diagnosed using the validated Villalta scale, which incorporates clinical signs including pain on calf compression, skin edema and redness, and ulcers, as well as symptoms such as leg cramping, heaviness, itching, and paresthesia.
The Pittsburgh series included 102 consecutive patients treated with various combinations of catheter-directed or pharmacomechanical thrombolysis in 127 limbs with acute iliofemoral thrombosis. In 46 patients, the thrombus extended into the IVC, all the way up to the renal veins in most cases.
The groups with and without caval extension were similar in terms of age and prevalence of malignancy, hypercoagulable state, and clot age. However, a history of previous DVT was significantly more common in the group with IVC thrombus. Also, more than 60% of patients with caval extension got an IVC filter, a rate more than 10-fold greater than that in patients without caval extension.
In this series, caval thrombosis had no effect on the technical success of thrombolysis. The technical success rate –defined as at least 50% clot lysis – was 89% in both groups. Rates of recurrent DVT within 30 days were similar in the two groups as well: 11% in the caval thrombosis group and 14% in the noncaval group. At 2 years postintervention, 77%-78% of patients in both groups remained free of DVT recurrence. The rate of PTS – defined by a Villalta score of 5 or more – at 2 years was 34% in the noncaval group, which was significantly higher than the 11% rate in patients with IVC thrombus extension. Ultrasound-identified valve reflux was present in 51% of the noncaval group at 2 years, compared with 51% of the noncaval group.
On multivariate analysis, incomplete clot lysis was associated with nearly a 23-fold increased risk of recurrent DVT and a 5.6-fold increased risk of PTS. Caval involvement was independently associated with a 78% reduction in PTS risk.
The Society for Vascular Surgery’s guidelines recommend pharmacomechanical thrombolysis over catheter-directed thrombolysis if the expertise is available. The Pittsburgh experience speaks to the worth of that recommendation.
“Pharmacomechanical techniques can be advantageous. They can expedite the lysis process by clearing most of the clot. In our series, 20 patients were treated with pharmacomechanical techniques in a single session,” Dr. Chaer noted.
The use of IVC filters in the setting of caval extension of iliofemoral DVT is controversial, according to the surgeon: A thrombus that gets trapped in the filter is tough to remove, precluding successful recanalization.
“One-third of the patients in our series got a filter, but we’ve become more conservative nowadays. We don’t use filters anymore. But I think those patients who might benefit from an IVC filter are those who present with a PE [pulmonary embolism], because that’s telling you they might develop another PE, as well as those patients in whom pharmacomechanical thrombolysis is anticipated because we’ve seen that those patients are also more likely to develop a PE,” he said.
The University of Pittsburgh study on the effect of IVC thrombus extension has been published (J Vasc Surg Venous Lymphat Disord. 2016 Oct;4[4]:385-91).
Dr. Chaer reported serving as a paid speaker for Boston Scientific.
SOURCE: Chaer RA. Northwestern Vascular Symposium 2017.
CHICAGO – Caval extension of an acute iliofemoral deep vein thrombosis paradoxically portends better treatment outcomes than does thrombolysis of a DVT without involvement of the inferior vena cava, according to Rabih A. Chaer, MD, professor of surgery at the University of Pittsburgh.
This finding from a retrospective analysis of the University of Pittsburgh experience might seem counterintuitive. After all, caval extension clearly indicates a greater clot burden. One possible explanation: Clearing a thrombus from a large vessel, such as the inferior vena cava (IVC), provides an added protective effect. Also, since the caval segments don’t have valves – their flow is based upon negative pressure in the chest – they may not contribute as much to postthrombotic morbidity to the same extent as do thrombosed iliofemoral segments, Dr. Chaer speculated at a symposium on vascular surgery sponsored by Northwestern University.
The impetus for Dr. Chaer and coinvestigators to review the Pittsburgh experience was a lack of clarity in the literature as to the effect IVC thrombosis has on thrombolysis outcomes in patients with acute iliofemoral DVT. Even though caval thrombus extension is present in up to 22% of patients with iliofemoral DVT, current guidelines issued by the American College of Chest Physicians, the American Heart Association, and the Society for Vascular Surgery don’t address the distinction between iliofemoral DVT with and without IVC extension in regard to the occurrence of postthrombotic syndrome (PTS), the most common complication of DVT.
The incidence of PTS in patients whose iliofemoral DVT is treated by anticoagulation and compression alone is up to 50%. Mounting evidence indicates that catheter-directed thrombolysis and pharmacomechanical thrombolysis aimed at achieving early thrombus removal and symptom relief help maintain valvular competence and reduce the risk of PTS, the surgeon noted.
PTS is diagnosed using the validated Villalta scale, which incorporates clinical signs including pain on calf compression, skin edema and redness, and ulcers, as well as symptoms such as leg cramping, heaviness, itching, and paresthesia.
The Pittsburgh series included 102 consecutive patients treated with various combinations of catheter-directed or pharmacomechanical thrombolysis in 127 limbs with acute iliofemoral thrombosis. In 46 patients, the thrombus extended into the IVC, all the way up to the renal veins in most cases.
The groups with and without caval extension were similar in terms of age and prevalence of malignancy, hypercoagulable state, and clot age. However, a history of previous DVT was significantly more common in the group with IVC thrombus. Also, more than 60% of patients with caval extension got an IVC filter, a rate more than 10-fold greater than that in patients without caval extension.
In this series, caval thrombosis had no effect on the technical success of thrombolysis. The technical success rate –defined as at least 50% clot lysis – was 89% in both groups. Rates of recurrent DVT within 30 days were similar in the two groups as well: 11% in the caval thrombosis group and 14% in the noncaval group. At 2 years postintervention, 77%-78% of patients in both groups remained free of DVT recurrence. The rate of PTS – defined by a Villalta score of 5 or more – at 2 years was 34% in the noncaval group, which was significantly higher than the 11% rate in patients with IVC thrombus extension. Ultrasound-identified valve reflux was present in 51% of the noncaval group at 2 years, compared with 51% of the noncaval group.
On multivariate analysis, incomplete clot lysis was associated with nearly a 23-fold increased risk of recurrent DVT and a 5.6-fold increased risk of PTS. Caval involvement was independently associated with a 78% reduction in PTS risk.
The Society for Vascular Surgery’s guidelines recommend pharmacomechanical thrombolysis over catheter-directed thrombolysis if the expertise is available. The Pittsburgh experience speaks to the worth of that recommendation.
“Pharmacomechanical techniques can be advantageous. They can expedite the lysis process by clearing most of the clot. In our series, 20 patients were treated with pharmacomechanical techniques in a single session,” Dr. Chaer noted.
The use of IVC filters in the setting of caval extension of iliofemoral DVT is controversial, according to the surgeon: A thrombus that gets trapped in the filter is tough to remove, precluding successful recanalization.
“One-third of the patients in our series got a filter, but we’ve become more conservative nowadays. We don’t use filters anymore. But I think those patients who might benefit from an IVC filter are those who present with a PE [pulmonary embolism], because that’s telling you they might develop another PE, as well as those patients in whom pharmacomechanical thrombolysis is anticipated because we’ve seen that those patients are also more likely to develop a PE,” he said.
The University of Pittsburgh study on the effect of IVC thrombus extension has been published (J Vasc Surg Venous Lymphat Disord. 2016 Oct;4[4]:385-91).
Dr. Chaer reported serving as a paid speaker for Boston Scientific.
SOURCE: Chaer RA. Northwestern Vascular Symposium 2017.
REPORTING FROM THE NORTHWESTERN VASCULAR SYMPOSIUM
Get ready for certolizumab for psoriasis
KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“ ” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by Alexa B. Kimball, MD, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
CRIB was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlled CIMPASI-1 and CIMPASI-2 trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published (Ann Rheum Dis. 2018 Feb;77[2]:228-33).
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“ ” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by Alexa B. Kimball, MD, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
CRIB was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlled CIMPASI-1 and CIMPASI-2 trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published (Ann Rheum Dis. 2018 Feb;77[2]:228-33).
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“ ” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by Alexa B. Kimball, MD, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
CRIB was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlled CIMPASI-1 and CIMPASI-2 trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published (Ann Rheum Dis. 2018 Feb;77[2]:228-33).
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Make a PEST of your psoriasis patients
KAUAI, HAWAII – for the rheumatologic disease once per year, advised Jashin J. Wu, MD. The PEST is a simple, validated, five-question yes/no screening tool. It’s geared towards nonrheumatologists who may not feel competent to diagnose psoriatic arthritis or who just don’t have time to do so. Three or more “yes” answers is deemed a positive result warranting consideration of referral to a rheumatologist, explained Dr. Wu, the director of the psoriasis clinic and director of dermatology research at Kaiser Permanente Los Angeles Medical Center.
The five PEST questions are:
- Have you ever had a swollen joint (or joints)?
- Has a doctor ever told you that you have arthritis?
- Do your fingernails or toenails have holes or pits?
- Have you had pain in your heel?
- Have you had a finger or toe that was completely swollen and painful for no apparent reason?
The PEST has been shown to have 92% sensitivity and 78% specificity for diagnosis of psoriatic arthritis (Clin Exp Rheumatol. 2009 May-Jun;27[3]:469-74).
Dr. Wu’s call for regular screening for psoriatic arthritis resonated with another psoriasis expert at the meeting, Craig L. Leonardi, MD.
“It’s our moral obligation to be on the lookout for that disease. Remember that patients who develop psoriatic arthritis usually have their skin disease for 10 years before they develop their first signs and symptoms of psoriatic arthritis. So that means they should be in the dermatologist’s office getting their skin treated as they start to have problems with their joints,” observed Dr. Leonardi, of Saint Louis University.
Dr. Wu reported receiving research funding from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, and Regeneron.
The SDEF and this news organization are owned by the same parent company.
KAUAI, HAWAII – for the rheumatologic disease once per year, advised Jashin J. Wu, MD. The PEST is a simple, validated, five-question yes/no screening tool. It’s geared towards nonrheumatologists who may not feel competent to diagnose psoriatic arthritis or who just don’t have time to do so. Three or more “yes” answers is deemed a positive result warranting consideration of referral to a rheumatologist, explained Dr. Wu, the director of the psoriasis clinic and director of dermatology research at Kaiser Permanente Los Angeles Medical Center.
The five PEST questions are:
- Have you ever had a swollen joint (or joints)?
- Has a doctor ever told you that you have arthritis?
- Do your fingernails or toenails have holes or pits?
- Have you had pain in your heel?
- Have you had a finger or toe that was completely swollen and painful for no apparent reason?
The PEST has been shown to have 92% sensitivity and 78% specificity for diagnosis of psoriatic arthritis (Clin Exp Rheumatol. 2009 May-Jun;27[3]:469-74).
Dr. Wu’s call for regular screening for psoriatic arthritis resonated with another psoriasis expert at the meeting, Craig L. Leonardi, MD.
“It’s our moral obligation to be on the lookout for that disease. Remember that patients who develop psoriatic arthritis usually have their skin disease for 10 years before they develop their first signs and symptoms of psoriatic arthritis. So that means they should be in the dermatologist’s office getting their skin treated as they start to have problems with their joints,” observed Dr. Leonardi, of Saint Louis University.
Dr. Wu reported receiving research funding from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, and Regeneron.
The SDEF and this news organization are owned by the same parent company.
KAUAI, HAWAII – for the rheumatologic disease once per year, advised Jashin J. Wu, MD. The PEST is a simple, validated, five-question yes/no screening tool. It’s geared towards nonrheumatologists who may not feel competent to diagnose psoriatic arthritis or who just don’t have time to do so. Three or more “yes” answers is deemed a positive result warranting consideration of referral to a rheumatologist, explained Dr. Wu, the director of the psoriasis clinic and director of dermatology research at Kaiser Permanente Los Angeles Medical Center.
The five PEST questions are:
- Have you ever had a swollen joint (or joints)?
- Has a doctor ever told you that you have arthritis?
- Do your fingernails or toenails have holes or pits?
- Have you had pain in your heel?
- Have you had a finger or toe that was completely swollen and painful for no apparent reason?
The PEST has been shown to have 92% sensitivity and 78% specificity for diagnosis of psoriatic arthritis (Clin Exp Rheumatol. 2009 May-Jun;27[3]:469-74).
Dr. Wu’s call for regular screening for psoriatic arthritis resonated with another psoriasis expert at the meeting, Craig L. Leonardi, MD.
“It’s our moral obligation to be on the lookout for that disease. Remember that patients who develop psoriatic arthritis usually have their skin disease for 10 years before they develop their first signs and symptoms of psoriatic arthritis. So that means they should be in the dermatologist’s office getting their skin treated as they start to have problems with their joints,” observed Dr. Leonardi, of Saint Louis University.
Dr. Wu reported receiving research funding from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, and Regeneron.
The SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
STEMI success stagnating
SNOWMASS, COLO. – , Ajay J. Kirtane, MD, declared at the Annual Cardiovascular Conference at Snowmass.
“We have to recognize the fact that our success has somewhat plateaued. We’ve made great strides in shortening door-to-balloon times, but further reductions in [that measure] are not translating into further reductions in adverse outcomes,” observed Dr. Kirtane of Columbia University, New York.
He and others have identified a number of reasons why ST-elevation myocardial infarction (STEMI) mortality has flattened. One is the continued protracted lag time from symptom onset to arrival at the emergency department. Progress here will require effective public education programs.
“By the time patients are getting to the cath lab, we’re sort of running out of time to salvage the myocardium,” Dr. Kirtane said. “We need to get people to the lab really, really quickly and recognize that symptom onset is still an area in need of improvement.”
The greatest limitation of primary percutaneous coronary intervention (PCI) for treatment of STEMI, however, is poor recovery of left ventricular function. As STEMI mortality has fallen over the years, rates of heart failure caused by suboptimal salvage of myocardium have climbed. Only about two-thirds of patients undergoing primary PCI obtain successful reperfusion; that’s in part due to distal embolization, a problem that hasn’t yet been solved.
One hope for improved reperfusion success that has been dashed is aspiration thrombectomy. It was an attractive concept, but optical coherence imaging has shown that after aspiration, there is still a good deal of thrombus remaining in the vessel. And large randomized trials failed to show a reduction in ischemic events. Thus, the current American College of Cardiology/American Heart Association STEMI guidelines give routine aspiration thrombectomy before primary PCI a class III rating, meaning don’t do it (J Am Coll Cardiol. 2013 Jan. doi: 10.1016/j.jacc.2012.11.019).
What about nonculprit lesions?
A hot topic in STEMI management is what to do about residual disease in nonculprit vessels after primary PCI.
“Some people have drawn upon trials like COURAGE to inform their decision making, saying ‘Now the patient is stabilized, we’ve treated the STEMI, so we could now treat the patient like a COURAGE patient [with optimal medical therapy alone].’ I would caution against extrapolating the results of COURAGE and other stable ischemic heart disease paradigms to these types of patients. They’ve already presented with a very high risk feature – STEMI – and in addition, in the COURAGE trial there were only 118 patients that had acute coronary syndrome of less than 2 weeks’ duration out of more than 2,000 subjects,” Dr. Kirtane said.
“Intravascular ultrasound studies show that nonculprit plaques in stable angina are very different from those in STEMI: They’re typically fibrotic and stable, while even the nonculprit plaques in STEMI or non-STEMI ACS are much more inflamed and vulnerable,” he added.
He predicted clarity regarding best management in this area will come from the ongoing COMPLETE trial, a multinational study of nearly 4,000 patients randomized to staged nonculprit lesion PCI versus medical therapy plus culprit lesion-only revascularization. The study is due to be completed late in 2018.
Improving pharmacotherapy
Rates of hospital discharge on guideline-directed optimal medical therapy after primary PCI have risen steadily in recent years. However, studies indicate a significant minority of patients drop from dual-antiplatelet therapy to aspirin alone within a month after leaving the hospital.
Also, it’s essential to effectively inhibit both platelets and thrombus in the catheterization lab. But is that happening consistently? There is now evidence of delayed absorption of the potent oral antiplatelet agents in STEMI patients. Moreover, that delay is exacerbated by having morphine or fentanyl on board.
“It’s been shown that even with ticagrelor and prasugrel, in STEMI patients at 2 hours, you still don’t have sufficient inhibition of platelet aggregation, whereas if I gave one of those drugs to any of us here in the audience now we’d have full effect within an hour or 2 max. That’s one of the reasons why there’s a rationale for using an intravenous agent such as cangrelor [Kengreal], a nonthienopyridine direct P2Y12 inhibitor,” Dr. Kirtane said.
Transradial access for primary PCI
Dr. Kirtane argued in a recent editorial that widespread adoption of transradial PCI for STEMI will provide the next major advance in STEMI systems of care resulting in improved clinical outcomes (JAMA Cardiol. 2017 Oct 1;2[10]:1057-8).
This is a controversial issue, he acknowledged. “There are interventional cardiologists who say, ‘No way.’ ” But studies indicate that transradial PCI for STEMI reduces mortality by 16%-48% compared with transfemoral access, without a significant cost in terms of door-to-balloon time. For now, transfemoral access PCI remains the most common strategy for STEMI patients in the United States, although the use of transradial primary PCI is growing.
Dr. Kirtane reported receiving research grants from more than half a dozen medical device companies.
SNOWMASS, COLO. – , Ajay J. Kirtane, MD, declared at the Annual Cardiovascular Conference at Snowmass.
“We have to recognize the fact that our success has somewhat plateaued. We’ve made great strides in shortening door-to-balloon times, but further reductions in [that measure] are not translating into further reductions in adverse outcomes,” observed Dr. Kirtane of Columbia University, New York.
He and others have identified a number of reasons why ST-elevation myocardial infarction (STEMI) mortality has flattened. One is the continued protracted lag time from symptom onset to arrival at the emergency department. Progress here will require effective public education programs.
“By the time patients are getting to the cath lab, we’re sort of running out of time to salvage the myocardium,” Dr. Kirtane said. “We need to get people to the lab really, really quickly and recognize that symptom onset is still an area in need of improvement.”
The greatest limitation of primary percutaneous coronary intervention (PCI) for treatment of STEMI, however, is poor recovery of left ventricular function. As STEMI mortality has fallen over the years, rates of heart failure caused by suboptimal salvage of myocardium have climbed. Only about two-thirds of patients undergoing primary PCI obtain successful reperfusion; that’s in part due to distal embolization, a problem that hasn’t yet been solved.
One hope for improved reperfusion success that has been dashed is aspiration thrombectomy. It was an attractive concept, but optical coherence imaging has shown that after aspiration, there is still a good deal of thrombus remaining in the vessel. And large randomized trials failed to show a reduction in ischemic events. Thus, the current American College of Cardiology/American Heart Association STEMI guidelines give routine aspiration thrombectomy before primary PCI a class III rating, meaning don’t do it (J Am Coll Cardiol. 2013 Jan. doi: 10.1016/j.jacc.2012.11.019).
What about nonculprit lesions?
A hot topic in STEMI management is what to do about residual disease in nonculprit vessels after primary PCI.
“Some people have drawn upon trials like COURAGE to inform their decision making, saying ‘Now the patient is stabilized, we’ve treated the STEMI, so we could now treat the patient like a COURAGE patient [with optimal medical therapy alone].’ I would caution against extrapolating the results of COURAGE and other stable ischemic heart disease paradigms to these types of patients. They’ve already presented with a very high risk feature – STEMI – and in addition, in the COURAGE trial there were only 118 patients that had acute coronary syndrome of less than 2 weeks’ duration out of more than 2,000 subjects,” Dr. Kirtane said.
“Intravascular ultrasound studies show that nonculprit plaques in stable angina are very different from those in STEMI: They’re typically fibrotic and stable, while even the nonculprit plaques in STEMI or non-STEMI ACS are much more inflamed and vulnerable,” he added.
He predicted clarity regarding best management in this area will come from the ongoing COMPLETE trial, a multinational study of nearly 4,000 patients randomized to staged nonculprit lesion PCI versus medical therapy plus culprit lesion-only revascularization. The study is due to be completed late in 2018.
Improving pharmacotherapy
Rates of hospital discharge on guideline-directed optimal medical therapy after primary PCI have risen steadily in recent years. However, studies indicate a significant minority of patients drop from dual-antiplatelet therapy to aspirin alone within a month after leaving the hospital.
Also, it’s essential to effectively inhibit both platelets and thrombus in the catheterization lab. But is that happening consistently? There is now evidence of delayed absorption of the potent oral antiplatelet agents in STEMI patients. Moreover, that delay is exacerbated by having morphine or fentanyl on board.
“It’s been shown that even with ticagrelor and prasugrel, in STEMI patients at 2 hours, you still don’t have sufficient inhibition of platelet aggregation, whereas if I gave one of those drugs to any of us here in the audience now we’d have full effect within an hour or 2 max. That’s one of the reasons why there’s a rationale for using an intravenous agent such as cangrelor [Kengreal], a nonthienopyridine direct P2Y12 inhibitor,” Dr. Kirtane said.
Transradial access for primary PCI
Dr. Kirtane argued in a recent editorial that widespread adoption of transradial PCI for STEMI will provide the next major advance in STEMI systems of care resulting in improved clinical outcomes (JAMA Cardiol. 2017 Oct 1;2[10]:1057-8).
This is a controversial issue, he acknowledged. “There are interventional cardiologists who say, ‘No way.’ ” But studies indicate that transradial PCI for STEMI reduces mortality by 16%-48% compared with transfemoral access, without a significant cost in terms of door-to-balloon time. For now, transfemoral access PCI remains the most common strategy for STEMI patients in the United States, although the use of transradial primary PCI is growing.
Dr. Kirtane reported receiving research grants from more than half a dozen medical device companies.
SNOWMASS, COLO. – , Ajay J. Kirtane, MD, declared at the Annual Cardiovascular Conference at Snowmass.
“We have to recognize the fact that our success has somewhat plateaued. We’ve made great strides in shortening door-to-balloon times, but further reductions in [that measure] are not translating into further reductions in adverse outcomes,” observed Dr. Kirtane of Columbia University, New York.
He and others have identified a number of reasons why ST-elevation myocardial infarction (STEMI) mortality has flattened. One is the continued protracted lag time from symptom onset to arrival at the emergency department. Progress here will require effective public education programs.
“By the time patients are getting to the cath lab, we’re sort of running out of time to salvage the myocardium,” Dr. Kirtane said. “We need to get people to the lab really, really quickly and recognize that symptom onset is still an area in need of improvement.”
The greatest limitation of primary percutaneous coronary intervention (PCI) for treatment of STEMI, however, is poor recovery of left ventricular function. As STEMI mortality has fallen over the years, rates of heart failure caused by suboptimal salvage of myocardium have climbed. Only about two-thirds of patients undergoing primary PCI obtain successful reperfusion; that’s in part due to distal embolization, a problem that hasn’t yet been solved.
One hope for improved reperfusion success that has been dashed is aspiration thrombectomy. It was an attractive concept, but optical coherence imaging has shown that after aspiration, there is still a good deal of thrombus remaining in the vessel. And large randomized trials failed to show a reduction in ischemic events. Thus, the current American College of Cardiology/American Heart Association STEMI guidelines give routine aspiration thrombectomy before primary PCI a class III rating, meaning don’t do it (J Am Coll Cardiol. 2013 Jan. doi: 10.1016/j.jacc.2012.11.019).
What about nonculprit lesions?
A hot topic in STEMI management is what to do about residual disease in nonculprit vessels after primary PCI.
“Some people have drawn upon trials like COURAGE to inform their decision making, saying ‘Now the patient is stabilized, we’ve treated the STEMI, so we could now treat the patient like a COURAGE patient [with optimal medical therapy alone].’ I would caution against extrapolating the results of COURAGE and other stable ischemic heart disease paradigms to these types of patients. They’ve already presented with a very high risk feature – STEMI – and in addition, in the COURAGE trial there were only 118 patients that had acute coronary syndrome of less than 2 weeks’ duration out of more than 2,000 subjects,” Dr. Kirtane said.
“Intravascular ultrasound studies show that nonculprit plaques in stable angina are very different from those in STEMI: They’re typically fibrotic and stable, while even the nonculprit plaques in STEMI or non-STEMI ACS are much more inflamed and vulnerable,” he added.
He predicted clarity regarding best management in this area will come from the ongoing COMPLETE trial, a multinational study of nearly 4,000 patients randomized to staged nonculprit lesion PCI versus medical therapy plus culprit lesion-only revascularization. The study is due to be completed late in 2018.
Improving pharmacotherapy
Rates of hospital discharge on guideline-directed optimal medical therapy after primary PCI have risen steadily in recent years. However, studies indicate a significant minority of patients drop from dual-antiplatelet therapy to aspirin alone within a month after leaving the hospital.
Also, it’s essential to effectively inhibit both platelets and thrombus in the catheterization lab. But is that happening consistently? There is now evidence of delayed absorption of the potent oral antiplatelet agents in STEMI patients. Moreover, that delay is exacerbated by having morphine or fentanyl on board.
“It’s been shown that even with ticagrelor and prasugrel, in STEMI patients at 2 hours, you still don’t have sufficient inhibition of platelet aggregation, whereas if I gave one of those drugs to any of us here in the audience now we’d have full effect within an hour or 2 max. That’s one of the reasons why there’s a rationale for using an intravenous agent such as cangrelor [Kengreal], a nonthienopyridine direct P2Y12 inhibitor,” Dr. Kirtane said.
Transradial access for primary PCI
Dr. Kirtane argued in a recent editorial that widespread adoption of transradial PCI for STEMI will provide the next major advance in STEMI systems of care resulting in improved clinical outcomes (JAMA Cardiol. 2017 Oct 1;2[10]:1057-8).
This is a controversial issue, he acknowledged. “There are interventional cardiologists who say, ‘No way.’ ” But studies indicate that transradial PCI for STEMI reduces mortality by 16%-48% compared with transfemoral access, without a significant cost in terms of door-to-balloon time. For now, transfemoral access PCI remains the most common strategy for STEMI patients in the United States, although the use of transradial primary PCI is growing.
Dr. Kirtane reported receiving research grants from more than half a dozen medical device companies.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
The shrinking role of surgical aortic valve replacement
SNOWMASS, COLO. – Michael J. Mack, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
That’s assuming, hypothetically, that two ongoing randomized trials – PARTNER 3 and EVOLUT R – comparing TAVR (transcatheter aortic valve replacement) and SAVR (surgical aortic valve replacement) in low-surgical-risk patients have positive results. If so, TAVR will be proven noninferior to SAVR, as has already been convincingly shown in randomized trials conducted in high- and intermediate-surgical-risk patients.
Several factors are working against universal adoption of TAVR. There are unresolved concerns about TAVR’s durability, its issues with valve thrombosis, and its greater need for new pacemaker implantation relative to SAVR. Those questions are among the issues being addressed in nearly two dozen ongoing or upcoming TAVR trials, said Dr. Mack, director of the cardiovascular service line at Baylor Scott & White Health System, Houston.
Here are the patients Dr. Mack predicts will likely stick with SAVR for the foreseeable future:
- Younger patients. Many younger, low-surgical-risk patients will be concerned about TAVR valves’ durability and the current higher pacemaker rate.
“We have some idea of what durability is in the surgical population. What we usually quote is 12-15 years. There has been no major signal of early valve deterioration in TAVR, but there aren’t yet a significant number of patients alive for more than 5 years. Be that as it may, no significant concerns yet, but the other shoe hasn’t dropped,” the cardiothoracic surgeon observed.
Both PARTNER 3 and the EVOLUT R low-risk trial will follow participants annually for 10 years, eventually providing a robust, combined 2,000-patient database to assess comparative device durability.
The 30-day rates of permanent pacemaker implantation in TAVR recipients without a preexisting pacemaker is in the 12%-16% range with the newer-generation Evolut R and Sapien 3 valves. The indication is often new-onset left bundle branch block or complete heart block.
“I don’t think the increased pacemaker incidence is a huge problem now, but with the younger population I think it’s going to be more of an issue,” according to Dr. Mack. “It’s one thing to need a pacemaker if you’re 80-85 years old, but it’s totally different in somebody who’s 55 or 65 that has 30-35 years to live. Pacemaker leads are not benign in that population.”
“On the other hand, there is a thought that younger patients have less intrinsic conduction system disease. It may be that they are less prone to needing a new pacemaker afterward,” he added.
TAVR valve leaflet thrombosis is a concern. While a change in transvalvular gradient on echocardiography provides a signal for this complication, the actual diagnosis of valve thrombosis requires four-dimensional CT. Much better data on the true incidence and clinical ramifications of valve thrombosis in both TAVR and SAVR are coming. For example, the PARTNER 3 and EVOLUT R LR trials will each include 400-patient substudies with four-dimensional CT aimed at answering questions about valve thrombosis. The GALILEO trial, involving 1,520 TAVR patients, is designed to determine whether low-dose rivaroxaban prevents valve thrombosis and periprocedural embolization. Results of this randomized trial are due in about a year. Similarly, the 1,509-patient randomized ATLANTIS trial is looking at the effects of apixaban versus warfarin versus dual or single antiplatelet therapy.
If long-term anticoagulation in TAVR patients is found to be beneficial, that may steer some patients toward SAVR, especially if they are physically active or at high bleeding risk.
- Aortic stenosis patients with a high Syntax score and multivessel coronary artery disease. This group is best served by concomitant SAVR and coronary artery bypass grafting surgery.
- Patients with low or intermediate surgical risk with multivalve disease. “We know that patients with moderate to severe mitral regurgitation and/or moderate to severe tricuspid regurgitation do not do well after TAVR,” the surgeon said.
- Rheumatic valve disease patients.
- Patients who present at a site that offers SAVR only. “There are about 1,150 cardiac surgery programs in the United States and about 560 TAVR programs. There is concern that patients who don’t come in to a center that offers TAVR will not be offered TAVR as an option. I think there’s probably some truth to that,” Dr. Mack said.
- Patients going to sites without a well-functioning collaborative heart team. “In institutions where surgeons and cardiologists don’t get along, turf is much more of an issue, and surgeons are going to hold on to those patients more closely,” he observed.
- Patient’s with certain preferences. “All other things being equal, the patient is always going to choose the less invasive option. However, we do see some patients – I think it’s about 1 out of 10 – who express a preference to stay with the tried and true surgery,” according to Dr. Mack.
He reported receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.
SNOWMASS, COLO. – Michael J. Mack, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
That’s assuming, hypothetically, that two ongoing randomized trials – PARTNER 3 and EVOLUT R – comparing TAVR (transcatheter aortic valve replacement) and SAVR (surgical aortic valve replacement) in low-surgical-risk patients have positive results. If so, TAVR will be proven noninferior to SAVR, as has already been convincingly shown in randomized trials conducted in high- and intermediate-surgical-risk patients.
Several factors are working against universal adoption of TAVR. There are unresolved concerns about TAVR’s durability, its issues with valve thrombosis, and its greater need for new pacemaker implantation relative to SAVR. Those questions are among the issues being addressed in nearly two dozen ongoing or upcoming TAVR trials, said Dr. Mack, director of the cardiovascular service line at Baylor Scott & White Health System, Houston.
Here are the patients Dr. Mack predicts will likely stick with SAVR for the foreseeable future:
- Younger patients. Many younger, low-surgical-risk patients will be concerned about TAVR valves’ durability and the current higher pacemaker rate.
“We have some idea of what durability is in the surgical population. What we usually quote is 12-15 years. There has been no major signal of early valve deterioration in TAVR, but there aren’t yet a significant number of patients alive for more than 5 years. Be that as it may, no significant concerns yet, but the other shoe hasn’t dropped,” the cardiothoracic surgeon observed.
Both PARTNER 3 and the EVOLUT R low-risk trial will follow participants annually for 10 years, eventually providing a robust, combined 2,000-patient database to assess comparative device durability.
The 30-day rates of permanent pacemaker implantation in TAVR recipients without a preexisting pacemaker is in the 12%-16% range with the newer-generation Evolut R and Sapien 3 valves. The indication is often new-onset left bundle branch block or complete heart block.
“I don’t think the increased pacemaker incidence is a huge problem now, but with the younger population I think it’s going to be more of an issue,” according to Dr. Mack. “It’s one thing to need a pacemaker if you’re 80-85 years old, but it’s totally different in somebody who’s 55 or 65 that has 30-35 years to live. Pacemaker leads are not benign in that population.”
“On the other hand, there is a thought that younger patients have less intrinsic conduction system disease. It may be that they are less prone to needing a new pacemaker afterward,” he added.
TAVR valve leaflet thrombosis is a concern. While a change in transvalvular gradient on echocardiography provides a signal for this complication, the actual diagnosis of valve thrombosis requires four-dimensional CT. Much better data on the true incidence and clinical ramifications of valve thrombosis in both TAVR and SAVR are coming. For example, the PARTNER 3 and EVOLUT R LR trials will each include 400-patient substudies with four-dimensional CT aimed at answering questions about valve thrombosis. The GALILEO trial, involving 1,520 TAVR patients, is designed to determine whether low-dose rivaroxaban prevents valve thrombosis and periprocedural embolization. Results of this randomized trial are due in about a year. Similarly, the 1,509-patient randomized ATLANTIS trial is looking at the effects of apixaban versus warfarin versus dual or single antiplatelet therapy.
If long-term anticoagulation in TAVR patients is found to be beneficial, that may steer some patients toward SAVR, especially if they are physically active or at high bleeding risk.
- Aortic stenosis patients with a high Syntax score and multivessel coronary artery disease. This group is best served by concomitant SAVR and coronary artery bypass grafting surgery.
- Patients with low or intermediate surgical risk with multivalve disease. “We know that patients with moderate to severe mitral regurgitation and/or moderate to severe tricuspid regurgitation do not do well after TAVR,” the surgeon said.
- Rheumatic valve disease patients.
- Patients who present at a site that offers SAVR only. “There are about 1,150 cardiac surgery programs in the United States and about 560 TAVR programs. There is concern that patients who don’t come in to a center that offers TAVR will not be offered TAVR as an option. I think there’s probably some truth to that,” Dr. Mack said.
- Patients going to sites without a well-functioning collaborative heart team. “In institutions where surgeons and cardiologists don’t get along, turf is much more of an issue, and surgeons are going to hold on to those patients more closely,” he observed.
- Patient’s with certain preferences. “All other things being equal, the patient is always going to choose the less invasive option. However, we do see some patients – I think it’s about 1 out of 10 – who express a preference to stay with the tried and true surgery,” according to Dr. Mack.
He reported receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.
SNOWMASS, COLO. – Michael J. Mack, MD, predicted at the Annual Cardiovascular Conference at Snowmass.
That’s assuming, hypothetically, that two ongoing randomized trials – PARTNER 3 and EVOLUT R – comparing TAVR (transcatheter aortic valve replacement) and SAVR (surgical aortic valve replacement) in low-surgical-risk patients have positive results. If so, TAVR will be proven noninferior to SAVR, as has already been convincingly shown in randomized trials conducted in high- and intermediate-surgical-risk patients.
Several factors are working against universal adoption of TAVR. There are unresolved concerns about TAVR’s durability, its issues with valve thrombosis, and its greater need for new pacemaker implantation relative to SAVR. Those questions are among the issues being addressed in nearly two dozen ongoing or upcoming TAVR trials, said Dr. Mack, director of the cardiovascular service line at Baylor Scott & White Health System, Houston.
Here are the patients Dr. Mack predicts will likely stick with SAVR for the foreseeable future:
- Younger patients. Many younger, low-surgical-risk patients will be concerned about TAVR valves’ durability and the current higher pacemaker rate.
“We have some idea of what durability is in the surgical population. What we usually quote is 12-15 years. There has been no major signal of early valve deterioration in TAVR, but there aren’t yet a significant number of patients alive for more than 5 years. Be that as it may, no significant concerns yet, but the other shoe hasn’t dropped,” the cardiothoracic surgeon observed.
Both PARTNER 3 and the EVOLUT R low-risk trial will follow participants annually for 10 years, eventually providing a robust, combined 2,000-patient database to assess comparative device durability.
The 30-day rates of permanent pacemaker implantation in TAVR recipients without a preexisting pacemaker is in the 12%-16% range with the newer-generation Evolut R and Sapien 3 valves. The indication is often new-onset left bundle branch block or complete heart block.
“I don’t think the increased pacemaker incidence is a huge problem now, but with the younger population I think it’s going to be more of an issue,” according to Dr. Mack. “It’s one thing to need a pacemaker if you’re 80-85 years old, but it’s totally different in somebody who’s 55 or 65 that has 30-35 years to live. Pacemaker leads are not benign in that population.”
“On the other hand, there is a thought that younger patients have less intrinsic conduction system disease. It may be that they are less prone to needing a new pacemaker afterward,” he added.
TAVR valve leaflet thrombosis is a concern. While a change in transvalvular gradient on echocardiography provides a signal for this complication, the actual diagnosis of valve thrombosis requires four-dimensional CT. Much better data on the true incidence and clinical ramifications of valve thrombosis in both TAVR and SAVR are coming. For example, the PARTNER 3 and EVOLUT R LR trials will each include 400-patient substudies with four-dimensional CT aimed at answering questions about valve thrombosis. The GALILEO trial, involving 1,520 TAVR patients, is designed to determine whether low-dose rivaroxaban prevents valve thrombosis and periprocedural embolization. Results of this randomized trial are due in about a year. Similarly, the 1,509-patient randomized ATLANTIS trial is looking at the effects of apixaban versus warfarin versus dual or single antiplatelet therapy.
If long-term anticoagulation in TAVR patients is found to be beneficial, that may steer some patients toward SAVR, especially if they are physically active or at high bleeding risk.
- Aortic stenosis patients with a high Syntax score and multivessel coronary artery disease. This group is best served by concomitant SAVR and coronary artery bypass grafting surgery.
- Patients with low or intermediate surgical risk with multivalve disease. “We know that patients with moderate to severe mitral regurgitation and/or moderate to severe tricuspid regurgitation do not do well after TAVR,” the surgeon said.
- Rheumatic valve disease patients.
- Patients who present at a site that offers SAVR only. “There are about 1,150 cardiac surgery programs in the United States and about 560 TAVR programs. There is concern that patients who don’t come in to a center that offers TAVR will not be offered TAVR as an option. I think there’s probably some truth to that,” Dr. Mack said.
- Patients going to sites without a well-functioning collaborative heart team. “In institutions where surgeons and cardiologists don’t get along, turf is much more of an issue, and surgeons are going to hold on to those patients more closely,” he observed.
- Patient’s with certain preferences. “All other things being equal, the patient is always going to choose the less invasive option. However, we do see some patients – I think it’s about 1 out of 10 – who express a preference to stay with the tried and true surgery,” according to Dr. Mack.
He reported receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.
EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS
Embracing Life’s Simple 7 slashes PAD risk
ANAHEIM, CALIF. – Adherence to the American Heart Association’s widely publicized “Life’s Simple 7” program addressing key modifiable cardiovascular health factors substantially reduces the risk of developing peripheral arterial disease, Parveen Garg, MD, said at the American Heart Association scientific sessions.
This is new evidence-supported information. Until this new analysis from the landmark ARIC (Atherosclerosis Risk in Communities) study, the relationship between Life’s Simple 7 and peripheral arterial disease (PAD) hadn’t been studied. It’s a relationship worthy of examination, considering that more than 8 million Americans have PAD, and nearly 40% of them don’t have concomitant coronary or cerebrovascular disease, which raised the question of whether Life’s Simple 7 applied to PAD risk, noted Dr. Garg of the University of Southern California, Los Angeles.
ARIC is a National Heart, Lung, and Blood Institute–sponsored prospective study of nearly 16,000 black or white individuals who were middle-aged at enrollment and have been followed for more than 2 decades. Dr. Garg’s analysis focused on 12,865 participants who were free of CHD, heart failure, prior stroke, and PAD at baseline, and have been followed for a median of 24 years.
As background, the metrics for Life’s Simple 7 consist of total cholesterol, blood pressure, blood glucose, smoking status, body mass index, physical activity, and adherence to a healthy diet score. Each element can be scored 2 points for ideal, 1 for intermediate, and 0 for poor. The composite Life’s Simple 7 score is rated optimal at 10-14 points, average at 5-9, and inadequate at 0-4.
During follow-up, 3.4% of ARIC participants developed PAD sufficiently severe to involve hospitalization. The incidence rate was 5.2 cases per 1,000 person-years for the 1,008 subjects categorized as having an inadequate Life’s Simple 7 score, 1.1/1,000 person-years for the 8,395 people in the average category, and just 0.4 cases/1,000 person-years for the 3,462 individuals in the optimal Life’s Simple 7 group.
Compared with subjects in the inadequate category, those in the average group were 56% less likely to develop PAD. Those in the optimal Life’s Simple 7 category had an 86% reduction in risk.
For each of the seven components of Life’s Simple 7 a person scored ideally in, the risk of incident PAD was reduced by 28% in a multivariate analysis fully adjusted for demographics, alcohol consumption, aspirin use, study site, left ventricular hypertrophy, and other potential confounders.
The inverse relationship between Life’s Simple 7 score and PAD risk was stronger in women than men. However, the association didn’t differ by race.
Dr. Garg noted that his study undoubtedly underestimates the true incidence of PAD in the ARIC population, since a hospital diagnosis was required. Also, to date he and his coinvestigators have only analyzed the results in terms of baseline Life’s Simple 7 score. It would be useful to also document the impact of change in the score over time.
Session moderator David C. Goff Jr., MD, observed, “This is very consistent with evidence in CHD that people who are in ideal cardiovascular health status have about an 80%-90% lower risk of cardiovascular mortality and a 70%-80% reduction in risk of total mortality compared with people who are in poor cardiovascular health status.”
“This study really does provide additional evidence that if we could get more people into the ideal cardiovascular health range, we’d probably see less atherosclerotic cardiovascular disease in general,” added Dr. Goff, who is director of the division of cardiovascular sciences at the National Heart, Lung, and Blood Institute.
Dr. Garg reported having no financial conflicts of interest.
ANAHEIM, CALIF. – Adherence to the American Heart Association’s widely publicized “Life’s Simple 7” program addressing key modifiable cardiovascular health factors substantially reduces the risk of developing peripheral arterial disease, Parveen Garg, MD, said at the American Heart Association scientific sessions.
This is new evidence-supported information. Until this new analysis from the landmark ARIC (Atherosclerosis Risk in Communities) study, the relationship between Life’s Simple 7 and peripheral arterial disease (PAD) hadn’t been studied. It’s a relationship worthy of examination, considering that more than 8 million Americans have PAD, and nearly 40% of them don’t have concomitant coronary or cerebrovascular disease, which raised the question of whether Life’s Simple 7 applied to PAD risk, noted Dr. Garg of the University of Southern California, Los Angeles.
ARIC is a National Heart, Lung, and Blood Institute–sponsored prospective study of nearly 16,000 black or white individuals who were middle-aged at enrollment and have been followed for more than 2 decades. Dr. Garg’s analysis focused on 12,865 participants who were free of CHD, heart failure, prior stroke, and PAD at baseline, and have been followed for a median of 24 years.
As background, the metrics for Life’s Simple 7 consist of total cholesterol, blood pressure, blood glucose, smoking status, body mass index, physical activity, and adherence to a healthy diet score. Each element can be scored 2 points for ideal, 1 for intermediate, and 0 for poor. The composite Life’s Simple 7 score is rated optimal at 10-14 points, average at 5-9, and inadequate at 0-4.
During follow-up, 3.4% of ARIC participants developed PAD sufficiently severe to involve hospitalization. The incidence rate was 5.2 cases per 1,000 person-years for the 1,008 subjects categorized as having an inadequate Life’s Simple 7 score, 1.1/1,000 person-years for the 8,395 people in the average category, and just 0.4 cases/1,000 person-years for the 3,462 individuals in the optimal Life’s Simple 7 group.
Compared with subjects in the inadequate category, those in the average group were 56% less likely to develop PAD. Those in the optimal Life’s Simple 7 category had an 86% reduction in risk.
For each of the seven components of Life’s Simple 7 a person scored ideally in, the risk of incident PAD was reduced by 28% in a multivariate analysis fully adjusted for demographics, alcohol consumption, aspirin use, study site, left ventricular hypertrophy, and other potential confounders.
The inverse relationship between Life’s Simple 7 score and PAD risk was stronger in women than men. However, the association didn’t differ by race.
Dr. Garg noted that his study undoubtedly underestimates the true incidence of PAD in the ARIC population, since a hospital diagnosis was required. Also, to date he and his coinvestigators have only analyzed the results in terms of baseline Life’s Simple 7 score. It would be useful to also document the impact of change in the score over time.
Session moderator David C. Goff Jr., MD, observed, “This is very consistent with evidence in CHD that people who are in ideal cardiovascular health status have about an 80%-90% lower risk of cardiovascular mortality and a 70%-80% reduction in risk of total mortality compared with people who are in poor cardiovascular health status.”
“This study really does provide additional evidence that if we could get more people into the ideal cardiovascular health range, we’d probably see less atherosclerotic cardiovascular disease in general,” added Dr. Goff, who is director of the division of cardiovascular sciences at the National Heart, Lung, and Blood Institute.
Dr. Garg reported having no financial conflicts of interest.
ANAHEIM, CALIF. – Adherence to the American Heart Association’s widely publicized “Life’s Simple 7” program addressing key modifiable cardiovascular health factors substantially reduces the risk of developing peripheral arterial disease, Parveen Garg, MD, said at the American Heart Association scientific sessions.
This is new evidence-supported information. Until this new analysis from the landmark ARIC (Atherosclerosis Risk in Communities) study, the relationship between Life’s Simple 7 and peripheral arterial disease (PAD) hadn’t been studied. It’s a relationship worthy of examination, considering that more than 8 million Americans have PAD, and nearly 40% of them don’t have concomitant coronary or cerebrovascular disease, which raised the question of whether Life’s Simple 7 applied to PAD risk, noted Dr. Garg of the University of Southern California, Los Angeles.
ARIC is a National Heart, Lung, and Blood Institute–sponsored prospective study of nearly 16,000 black or white individuals who were middle-aged at enrollment and have been followed for more than 2 decades. Dr. Garg’s analysis focused on 12,865 participants who were free of CHD, heart failure, prior stroke, and PAD at baseline, and have been followed for a median of 24 years.
As background, the metrics for Life’s Simple 7 consist of total cholesterol, blood pressure, blood glucose, smoking status, body mass index, physical activity, and adherence to a healthy diet score. Each element can be scored 2 points for ideal, 1 for intermediate, and 0 for poor. The composite Life’s Simple 7 score is rated optimal at 10-14 points, average at 5-9, and inadequate at 0-4.
During follow-up, 3.4% of ARIC participants developed PAD sufficiently severe to involve hospitalization. The incidence rate was 5.2 cases per 1,000 person-years for the 1,008 subjects categorized as having an inadequate Life’s Simple 7 score, 1.1/1,000 person-years for the 8,395 people in the average category, and just 0.4 cases/1,000 person-years for the 3,462 individuals in the optimal Life’s Simple 7 group.
Compared with subjects in the inadequate category, those in the average group were 56% less likely to develop PAD. Those in the optimal Life’s Simple 7 category had an 86% reduction in risk.
For each of the seven components of Life’s Simple 7 a person scored ideally in, the risk of incident PAD was reduced by 28% in a multivariate analysis fully adjusted for demographics, alcohol consumption, aspirin use, study site, left ventricular hypertrophy, and other potential confounders.
The inverse relationship between Life’s Simple 7 score and PAD risk was stronger in women than men. However, the association didn’t differ by race.
Dr. Garg noted that his study undoubtedly underestimates the true incidence of PAD in the ARIC population, since a hospital diagnosis was required. Also, to date he and his coinvestigators have only analyzed the results in terms of baseline Life’s Simple 7 score. It would be useful to also document the impact of change in the score over time.
Session moderator David C. Goff Jr., MD, observed, “This is very consistent with evidence in CHD that people who are in ideal cardiovascular health status have about an 80%-90% lower risk of cardiovascular mortality and a 70%-80% reduction in risk of total mortality compared with people who are in poor cardiovascular health status.”
“This study really does provide additional evidence that if we could get more people into the ideal cardiovascular health range, we’d probably see less atherosclerotic cardiovascular disease in general,” added Dr. Goff, who is director of the division of cardiovascular sciences at the National Heart, Lung, and Blood Institute.
Dr. Garg reported having no financial conflicts of interest.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point: The Life’s Simple 7 public health program points the way to reduced risk of PAD.
Major finding: Being in the top tertile of cardiovascular health by the American Heart Association’s Life’s Simple 7 metric is associated with an 86% lower risk of developing PAD than for those in poor cardiovascular health.
Study details: This biracial prospective observational study includes nearly 16,000 white and black Americans.
Disclosures: The ARIC study is funded by the NHLBI. The presenter reported having no financial conflicts.
Maximizing topical toenail fungus therapy
KAUAI, HAWAII – Two keys to effective topical treatment of onychomycosis are treat it early and address coexisting tinea pedis, according to Theodore Rosen, MD.
A third element in achieving treatment success is to use one of the newer topical agents: efinaconazole (Jublia) or tavaborole (Kerydin). The efficacy of efinaconazole approaches that of terbinafine, the most effective and widely prescribed oral agent, which has a 59% rate of almost complete cure, defined as less than 10% residual abnormal nail with no requirement for mycologic cure.
And while tavaborole isn’t quite as effective, it’s definitely better than previous topical agents, Dr. Rosen said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Both of these topicals are well tolerated and feature good nail permeation. They also allow for spread to the lateral nail folds and hyponychium. They even penetrate nail polish, although efinaconazole often causes the polish to lose its spiffy gloss, said Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.
To underscore the importance of early treatment and addressing concomitant tinea pedis, he cited published secondary analyses of two identical double-blind, multicenter, 48-week clinical trials totaling 1,655 adults with onychomycosis who were randomized 3:1 to once-daily efinaconazole 10% topical solution or its vehicle.
Treat early
Phoebe Rich, MD, of the Oregon Dermatology and Research Center, Portland, broke down the outcomes according to disease duration, in a study of more than 1,500 patients with onychomycosis. She found that the complete cure rate at 52 weeks dropped off markedly in patients with a history of onychomycosis for 1 year or longer at baseline.
Complete cure – defined as no clinical involvement of the target toenail along with both a negative potassium hydroxide examination and a negative fungal culture at 52 weeks – was achieved in 43% of efinaconazole-treated patients with onychomycosis for less than 1 year. The rate then plunged to 17% in those with a disease duration of 1-5 years and 16% in patients with onychomycosis for more than 5 years. Nevertheless, the topical antifungal was significantly more effective than was the vehicle, across the board, with complete cure rates in the vehicle group of roughly 18%, 5%, and 2%, respectively, in patients with onychomycosis for less than 1 year, 1-5 years, and more than 5 years (J Drugs Dermatol. 2015 Jan;14[1]:58-62).
Tackle coexisting tinea pedis
Podiatrists analyzed the combined efinaconazole outcome data based on whether participants had no coexisting tinea pedis, baseline tinea pedis treated concomitantly with an investigator-approved topical antifungal, or tinea pedis left untreated. They concluded that treatment of coexisting tinea pedis decisively enhanced the efficacy of efinaconazole for onychomycosis.
A total of 21% of study participants had concomitant tinea pedis, and 61% of them were treated for it. At week 52, the onychomycosis complete cure rate was 29% in the efinaconazole group concurrently treated for tinea pedis, compared with just 16% if their tinea pedis was untreated (J Am Podiatr Med Assoc. 2015 Sep;105[5]:407-11).
“If you see tinea pedis, don’t blow it off. Treat it. Otherwise, you’re not getting rid of the fungal reservoir,” Dr. Rosen emphasized.
He noted that two topical agents approved for tinea pedis – naftifine 2% cream or gel and luliconazole 1% cream – are effective as once-daily therapy for 2 weeks, a considerably briefer regimen than with other approved topicals. And short-course therapy spells improved adherence, he added.
In the pivotal trials, naftifine had an effective treatment rate – a clinically useful endpoint defined as a small amount of residual scaling and/or redness but no itching – of 57%, while for luliconazole the rates were 33%-48%.
These two agents also are approved for treatment of tinea corporis and tinea cruris. Naftifine is approved as a once-daily treatment for 2 weeks, while luliconazole is, notably, a 7-day treatment. Luliconazole, in particular, is a relatively expensive drug, Dr. Rosen added, so insurers may require prior failure on clotrimazole.
When to treat onychomycosis topically
The pivotal trials of tavaborole and efinaconazole were conducted in patients with 20%-60% nail involvement. The infection didn’t extend to the matrix, and nail thickness and crumbly subungual debris were modest at baseline.
“There are always potential safety issues – drug interactions, GI disturbance, taste loss, headache, teratogenicity, cardiotoxicity, hepatotoxicity – anytime you put a pill in your mouth. So if you have a patient who’s dedicated enough to use a topical for 48 weeks and it’s a modestly affected nail, think about it,” Dr. Rosen advised.
He reported serving on scientific advisory boards for Aclaris, Anacor, Cipla, and Valeant.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Two keys to effective topical treatment of onychomycosis are treat it early and address coexisting tinea pedis, according to Theodore Rosen, MD.
A third element in achieving treatment success is to use one of the newer topical agents: efinaconazole (Jublia) or tavaborole (Kerydin). The efficacy of efinaconazole approaches that of terbinafine, the most effective and widely prescribed oral agent, which has a 59% rate of almost complete cure, defined as less than 10% residual abnormal nail with no requirement for mycologic cure.
And while tavaborole isn’t quite as effective, it’s definitely better than previous topical agents, Dr. Rosen said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Both of these topicals are well tolerated and feature good nail permeation. They also allow for spread to the lateral nail folds and hyponychium. They even penetrate nail polish, although efinaconazole often causes the polish to lose its spiffy gloss, said Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.
To underscore the importance of early treatment and addressing concomitant tinea pedis, he cited published secondary analyses of two identical double-blind, multicenter, 48-week clinical trials totaling 1,655 adults with onychomycosis who were randomized 3:1 to once-daily efinaconazole 10% topical solution or its vehicle.
Treat early
Phoebe Rich, MD, of the Oregon Dermatology and Research Center, Portland, broke down the outcomes according to disease duration, in a study of more than 1,500 patients with onychomycosis. She found that the complete cure rate at 52 weeks dropped off markedly in patients with a history of onychomycosis for 1 year or longer at baseline.
Complete cure – defined as no clinical involvement of the target toenail along with both a negative potassium hydroxide examination and a negative fungal culture at 52 weeks – was achieved in 43% of efinaconazole-treated patients with onychomycosis for less than 1 year. The rate then plunged to 17% in those with a disease duration of 1-5 years and 16% in patients with onychomycosis for more than 5 years. Nevertheless, the topical antifungal was significantly more effective than was the vehicle, across the board, with complete cure rates in the vehicle group of roughly 18%, 5%, and 2%, respectively, in patients with onychomycosis for less than 1 year, 1-5 years, and more than 5 years (J Drugs Dermatol. 2015 Jan;14[1]:58-62).
Tackle coexisting tinea pedis
Podiatrists analyzed the combined efinaconazole outcome data based on whether participants had no coexisting tinea pedis, baseline tinea pedis treated concomitantly with an investigator-approved topical antifungal, or tinea pedis left untreated. They concluded that treatment of coexisting tinea pedis decisively enhanced the efficacy of efinaconazole for onychomycosis.
A total of 21% of study participants had concomitant tinea pedis, and 61% of them were treated for it. At week 52, the onychomycosis complete cure rate was 29% in the efinaconazole group concurrently treated for tinea pedis, compared with just 16% if their tinea pedis was untreated (J Am Podiatr Med Assoc. 2015 Sep;105[5]:407-11).
“If you see tinea pedis, don’t blow it off. Treat it. Otherwise, you’re not getting rid of the fungal reservoir,” Dr. Rosen emphasized.
He noted that two topical agents approved for tinea pedis – naftifine 2% cream or gel and luliconazole 1% cream – are effective as once-daily therapy for 2 weeks, a considerably briefer regimen than with other approved topicals. And short-course therapy spells improved adherence, he added.
In the pivotal trials, naftifine had an effective treatment rate – a clinically useful endpoint defined as a small amount of residual scaling and/or redness but no itching – of 57%, while for luliconazole the rates were 33%-48%.
These two agents also are approved for treatment of tinea corporis and tinea cruris. Naftifine is approved as a once-daily treatment for 2 weeks, while luliconazole is, notably, a 7-day treatment. Luliconazole, in particular, is a relatively expensive drug, Dr. Rosen added, so insurers may require prior failure on clotrimazole.
When to treat onychomycosis topically
The pivotal trials of tavaborole and efinaconazole were conducted in patients with 20%-60% nail involvement. The infection didn’t extend to the matrix, and nail thickness and crumbly subungual debris were modest at baseline.
“There are always potential safety issues – drug interactions, GI disturbance, taste loss, headache, teratogenicity, cardiotoxicity, hepatotoxicity – anytime you put a pill in your mouth. So if you have a patient who’s dedicated enough to use a topical for 48 weeks and it’s a modestly affected nail, think about it,” Dr. Rosen advised.
He reported serving on scientific advisory boards for Aclaris, Anacor, Cipla, and Valeant.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Two keys to effective topical treatment of onychomycosis are treat it early and address coexisting tinea pedis, according to Theodore Rosen, MD.
A third element in achieving treatment success is to use one of the newer topical agents: efinaconazole (Jublia) or tavaborole (Kerydin). The efficacy of efinaconazole approaches that of terbinafine, the most effective and widely prescribed oral agent, which has a 59% rate of almost complete cure, defined as less than 10% residual abnormal nail with no requirement for mycologic cure.
And while tavaborole isn’t quite as effective, it’s definitely better than previous topical agents, Dr. Rosen said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Both of these topicals are well tolerated and feature good nail permeation. They also allow for spread to the lateral nail folds and hyponychium. They even penetrate nail polish, although efinaconazole often causes the polish to lose its spiffy gloss, said Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.
To underscore the importance of early treatment and addressing concomitant tinea pedis, he cited published secondary analyses of two identical double-blind, multicenter, 48-week clinical trials totaling 1,655 adults with onychomycosis who were randomized 3:1 to once-daily efinaconazole 10% topical solution or its vehicle.
Treat early
Phoebe Rich, MD, of the Oregon Dermatology and Research Center, Portland, broke down the outcomes according to disease duration, in a study of more than 1,500 patients with onychomycosis. She found that the complete cure rate at 52 weeks dropped off markedly in patients with a history of onychomycosis for 1 year or longer at baseline.
Complete cure – defined as no clinical involvement of the target toenail along with both a negative potassium hydroxide examination and a negative fungal culture at 52 weeks – was achieved in 43% of efinaconazole-treated patients with onychomycosis for less than 1 year. The rate then plunged to 17% in those with a disease duration of 1-5 years and 16% in patients with onychomycosis for more than 5 years. Nevertheless, the topical antifungal was significantly more effective than was the vehicle, across the board, with complete cure rates in the vehicle group of roughly 18%, 5%, and 2%, respectively, in patients with onychomycosis for less than 1 year, 1-5 years, and more than 5 years (J Drugs Dermatol. 2015 Jan;14[1]:58-62).
Tackle coexisting tinea pedis
Podiatrists analyzed the combined efinaconazole outcome data based on whether participants had no coexisting tinea pedis, baseline tinea pedis treated concomitantly with an investigator-approved topical antifungal, or tinea pedis left untreated. They concluded that treatment of coexisting tinea pedis decisively enhanced the efficacy of efinaconazole for onychomycosis.
A total of 21% of study participants had concomitant tinea pedis, and 61% of them were treated for it. At week 52, the onychomycosis complete cure rate was 29% in the efinaconazole group concurrently treated for tinea pedis, compared with just 16% if their tinea pedis was untreated (J Am Podiatr Med Assoc. 2015 Sep;105[5]:407-11).
“If you see tinea pedis, don’t blow it off. Treat it. Otherwise, you’re not getting rid of the fungal reservoir,” Dr. Rosen emphasized.
He noted that two topical agents approved for tinea pedis – naftifine 2% cream or gel and luliconazole 1% cream – are effective as once-daily therapy for 2 weeks, a considerably briefer regimen than with other approved topicals. And short-course therapy spells improved adherence, he added.
In the pivotal trials, naftifine had an effective treatment rate – a clinically useful endpoint defined as a small amount of residual scaling and/or redness but no itching – of 57%, while for luliconazole the rates were 33%-48%.
These two agents also are approved for treatment of tinea corporis and tinea cruris. Naftifine is approved as a once-daily treatment for 2 weeks, while luliconazole is, notably, a 7-day treatment. Luliconazole, in particular, is a relatively expensive drug, Dr. Rosen added, so insurers may require prior failure on clotrimazole.
When to treat onychomycosis topically
The pivotal trials of tavaborole and efinaconazole were conducted in patients with 20%-60% nail involvement. The infection didn’t extend to the matrix, and nail thickness and crumbly subungual debris were modest at baseline.
“There are always potential safety issues – drug interactions, GI disturbance, taste loss, headache, teratogenicity, cardiotoxicity, hepatotoxicity – anytime you put a pill in your mouth. So if you have a patient who’s dedicated enough to use a topical for 48 weeks and it’s a modestly affected nail, think about it,” Dr. Rosen advised.
He reported serving on scientific advisory boards for Aclaris, Anacor, Cipla, and Valeant.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Canagliflozin falls short for primary CV prevention in T2DM
ANAHEIM, CALIF. – The first large randomized trial to report results on a sodium glucose cotransporter 2 inhibitor for primary prevention of cardiovascular events in patients with type 2 diabetes who are at risk for cardiovascular events or death failed to show a significant benefit in the CANVAS program, Kenneth W. Mahaffey, MD, said at the American Heart Association scientific sessions.
The impressive reductions in cardiovascular and renal events seen in the overall CANVAS (Canagliflozin Cardiovascular Assessment Study) program turned out to be focused in the two-thirds of participants with a prior cardiovascular event at enrollment, according to Dr. Mahaffey, a cardiologist who is professor and vice chair of the department of medicine at Stanford (Calif.) University.
The primary outcome has previously been reported: The canagliflozin group had a highly significant 14% reduction in the risk of the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (N Engl J Med. 2017 Aug 17;377[7]:644-57).
At the AHA scientific sessions, Dr. Mahaffey presented a prespecified subgroup analysis comparing the impact of SGLT2 inhibitor for primary versus secondary cardiovascular prevention. Canagliflozin proved to be a big win for secondary prevention: The composite primary endpoint was reduced by 18%, compared with placebo; the composite renal outcome of worsening estimated glomerular filtration rate (eGFR), renal replacement, or renal death was reduced by 41%; and heart failure hospitalizations were reduced by 32%.
All of those benefits were strongly statistically significant. They came at the cost of roughly a fourfold increase in readily treatable male and female genital infections – a known class effect of the SGLT2 inhibitors – as well as an unexpected twofold increase in lower extremity amputations, which fortunately were uncommon. Of the amputations, 29% were above the ankle; the other 71% were less drastic toe or transmetatarsal procedures.
Dr. Mahaffey estimated that for every 1,000 patients with type 2 diabetes who were taking canagliflozin for secondary cardiovascular prevention for 5 years, there would be 36 fewer cardiovascular deaths, nonfatal MIs, or nonfatal strokes; 20 fewer hospitalizations for heart failure; 21 fewer patients who experienced the composite renal outcome; and 21 additional patients with a lower extremity amputation.
Rates of cardiovascular and renal endpoints were at least twofold higher in the secondary prevention group than in the primary prevention cohort. For prevention, the size of the relative risk reductions in heart failure hospitalizations and renal outcomes with canagliflozin, compared with placebo, were similar to the secondary prevention experience. So was the magnitude of the increased risk of lower extremity amputation. However, none of these differences achieved statistical significance, perhaps because of the lower absolute event rates in the primary prevention group.
Moreover, there was no signal of benefit for canagliflozin in terms of the composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke in the primary prevention group; those event rates were virtually identical to those seen in the placebo-treated controls.
That being said, the CANVAS Program wasn’t designed with sufficient statistical power to draw definitive conclusions regarding outcome differences in the primary and secondary prevention groups, Dr. Mahaffey noted.
Putting the SGLT2 cardiovascular prevention results in perspective
Discussant Angelyn Bethel, MD, said the impressive outcomes for canagliflozin for secondary prevention in the CANVAS Program are consistent with the results of the earlier 7,020-patient EMPA-REG trial of the SGLT2 inhibitor empagliflozin (Jardiance) versus placebo for secondary prevention in type 2 diabetes (N Engl J Med. 2015 Nov 26;373[22]:2117-28). The relative risk reductions in the primary composite endpoint, as well as in heart failure hospitalizations and renal outcomes, were quite similar in the secondary prevention setting in the two large trials.
The one difference was in all-cause mortality: a striking 32% reduction with empagliflozin, compared with placebo, versus a more modest 11% relative risk reduction in the CANVAS program, which narrowly missed statistical significance.
The mechanisms for the important cardiovascular benefits seen in the secondary prevention setting in the two large SGLT2 trials are still under debate, according to Dr. Bethel, an endocrinologist who is deputy director of the diabetes trial unit at the University of Oxford (England).
“I think what’s obvious to most of us is that we’ve moved now beyond the conventional risk factors. These drugs cause only very small reductions in weight, systolic blood pressure, and diastolic blood pressure; they result in small increases in LDL and HDL; and the timeline of the impact that we see for the SGLT2 inhibitors on the cardiovascular outcomes in particular is much too short to be looking for glucose- or atherosclerotic-mediated processes,” she said.
“The mechanisms probably involve invoking the cardiorenal axis in some way,” Dr. Bethel speculated. “We know these drugs have a diuretic effect and we believe that some of the mortality benefit is probably mediated by heart failure outcomes, with changes in volume status. And there’s also a drive toward ketone metabolism, which is more efficient for the compromised heart.”
As for canagliflozin’s lack of significant benefit for primary prevention in the CANVAS program, it’s possible that this was a statistical power problem, Dr. Bethel said, but she has her doubts.
“If we had more people followed for longer in the primary prevention cohort, would we get there? I think it’s a big ask, but we do have more data coming,” she noted.
Indeed, two major phase 3 clinical trials of SGLT2 inhibitors for both primary and secondary cardiovascular prevention in mixed populations are due to report results in 2019: the roughly 4,500-patient CREDENCE trial of canagliflozin and the 17,0000-patient DECLARE trial, featuring dapagliflozin. Both involve about 5 years of follow-up.
Dr. Bethel advocated waiting until those studies report their primary prevention outcomes before introducing SGLT2-inhibitor therapy for primary cardiovascular prevention in clinical practice.
“In this instance, we do have some evidence that there may be a difference in the way that various events behave in the primary and secondary prevention settings, and we may have an overestimate of the benefits for primary prevention if we were to put this stuff in the water and give it to everybody,” she cautioned.
The CANVAS program analysis of primary versus secondary prevention has been published (Circulation. 2018 Jan 23;137[4]:323-34).
The CANVAS program was supported by Janssen. Dr. Mahaffey reported receiving research grants from and serving as a consultant to Janssen and numerous other companies.
SOURCE: Mahaffey KW et al. AHA Scientific Sessions.
ANAHEIM, CALIF. – The first large randomized trial to report results on a sodium glucose cotransporter 2 inhibitor for primary prevention of cardiovascular events in patients with type 2 diabetes who are at risk for cardiovascular events or death failed to show a significant benefit in the CANVAS program, Kenneth W. Mahaffey, MD, said at the American Heart Association scientific sessions.
The impressive reductions in cardiovascular and renal events seen in the overall CANVAS (Canagliflozin Cardiovascular Assessment Study) program turned out to be focused in the two-thirds of participants with a prior cardiovascular event at enrollment, according to Dr. Mahaffey, a cardiologist who is professor and vice chair of the department of medicine at Stanford (Calif.) University.
The primary outcome has previously been reported: The canagliflozin group had a highly significant 14% reduction in the risk of the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (N Engl J Med. 2017 Aug 17;377[7]:644-57).
At the AHA scientific sessions, Dr. Mahaffey presented a prespecified subgroup analysis comparing the impact of SGLT2 inhibitor for primary versus secondary cardiovascular prevention. Canagliflozin proved to be a big win for secondary prevention: The composite primary endpoint was reduced by 18%, compared with placebo; the composite renal outcome of worsening estimated glomerular filtration rate (eGFR), renal replacement, or renal death was reduced by 41%; and heart failure hospitalizations were reduced by 32%.
All of those benefits were strongly statistically significant. They came at the cost of roughly a fourfold increase in readily treatable male and female genital infections – a known class effect of the SGLT2 inhibitors – as well as an unexpected twofold increase in lower extremity amputations, which fortunately were uncommon. Of the amputations, 29% were above the ankle; the other 71% were less drastic toe or transmetatarsal procedures.
Dr. Mahaffey estimated that for every 1,000 patients with type 2 diabetes who were taking canagliflozin for secondary cardiovascular prevention for 5 years, there would be 36 fewer cardiovascular deaths, nonfatal MIs, or nonfatal strokes; 20 fewer hospitalizations for heart failure; 21 fewer patients who experienced the composite renal outcome; and 21 additional patients with a lower extremity amputation.
Rates of cardiovascular and renal endpoints were at least twofold higher in the secondary prevention group than in the primary prevention cohort. For prevention, the size of the relative risk reductions in heart failure hospitalizations and renal outcomes with canagliflozin, compared with placebo, were similar to the secondary prevention experience. So was the magnitude of the increased risk of lower extremity amputation. However, none of these differences achieved statistical significance, perhaps because of the lower absolute event rates in the primary prevention group.
Moreover, there was no signal of benefit for canagliflozin in terms of the composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke in the primary prevention group; those event rates were virtually identical to those seen in the placebo-treated controls.
That being said, the CANVAS Program wasn’t designed with sufficient statistical power to draw definitive conclusions regarding outcome differences in the primary and secondary prevention groups, Dr. Mahaffey noted.
Putting the SGLT2 cardiovascular prevention results in perspective
Discussant Angelyn Bethel, MD, said the impressive outcomes for canagliflozin for secondary prevention in the CANVAS Program are consistent with the results of the earlier 7,020-patient EMPA-REG trial of the SGLT2 inhibitor empagliflozin (Jardiance) versus placebo for secondary prevention in type 2 diabetes (N Engl J Med. 2015 Nov 26;373[22]:2117-28). The relative risk reductions in the primary composite endpoint, as well as in heart failure hospitalizations and renal outcomes, were quite similar in the secondary prevention setting in the two large trials.
The one difference was in all-cause mortality: a striking 32% reduction with empagliflozin, compared with placebo, versus a more modest 11% relative risk reduction in the CANVAS program, which narrowly missed statistical significance.
The mechanisms for the important cardiovascular benefits seen in the secondary prevention setting in the two large SGLT2 trials are still under debate, according to Dr. Bethel, an endocrinologist who is deputy director of the diabetes trial unit at the University of Oxford (England).
“I think what’s obvious to most of us is that we’ve moved now beyond the conventional risk factors. These drugs cause only very small reductions in weight, systolic blood pressure, and diastolic blood pressure; they result in small increases in LDL and HDL; and the timeline of the impact that we see for the SGLT2 inhibitors on the cardiovascular outcomes in particular is much too short to be looking for glucose- or atherosclerotic-mediated processes,” she said.
“The mechanisms probably involve invoking the cardiorenal axis in some way,” Dr. Bethel speculated. “We know these drugs have a diuretic effect and we believe that some of the mortality benefit is probably mediated by heart failure outcomes, with changes in volume status. And there’s also a drive toward ketone metabolism, which is more efficient for the compromised heart.”
As for canagliflozin’s lack of significant benefit for primary prevention in the CANVAS program, it’s possible that this was a statistical power problem, Dr. Bethel said, but she has her doubts.
“If we had more people followed for longer in the primary prevention cohort, would we get there? I think it’s a big ask, but we do have more data coming,” she noted.
Indeed, two major phase 3 clinical trials of SGLT2 inhibitors for both primary and secondary cardiovascular prevention in mixed populations are due to report results in 2019: the roughly 4,500-patient CREDENCE trial of canagliflozin and the 17,0000-patient DECLARE trial, featuring dapagliflozin. Both involve about 5 years of follow-up.
Dr. Bethel advocated waiting until those studies report their primary prevention outcomes before introducing SGLT2-inhibitor therapy for primary cardiovascular prevention in clinical practice.
“In this instance, we do have some evidence that there may be a difference in the way that various events behave in the primary and secondary prevention settings, and we may have an overestimate of the benefits for primary prevention if we were to put this stuff in the water and give it to everybody,” she cautioned.
The CANVAS program analysis of primary versus secondary prevention has been published (Circulation. 2018 Jan 23;137[4]:323-34).
The CANVAS program was supported by Janssen. Dr. Mahaffey reported receiving research grants from and serving as a consultant to Janssen and numerous other companies.
SOURCE: Mahaffey KW et al. AHA Scientific Sessions.
ANAHEIM, CALIF. – The first large randomized trial to report results on a sodium glucose cotransporter 2 inhibitor for primary prevention of cardiovascular events in patients with type 2 diabetes who are at risk for cardiovascular events or death failed to show a significant benefit in the CANVAS program, Kenneth W. Mahaffey, MD, said at the American Heart Association scientific sessions.
The impressive reductions in cardiovascular and renal events seen in the overall CANVAS (Canagliflozin Cardiovascular Assessment Study) program turned out to be focused in the two-thirds of participants with a prior cardiovascular event at enrollment, according to Dr. Mahaffey, a cardiologist who is professor and vice chair of the department of medicine at Stanford (Calif.) University.
The primary outcome has previously been reported: The canagliflozin group had a highly significant 14% reduction in the risk of the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (N Engl J Med. 2017 Aug 17;377[7]:644-57).
At the AHA scientific sessions, Dr. Mahaffey presented a prespecified subgroup analysis comparing the impact of SGLT2 inhibitor for primary versus secondary cardiovascular prevention. Canagliflozin proved to be a big win for secondary prevention: The composite primary endpoint was reduced by 18%, compared with placebo; the composite renal outcome of worsening estimated glomerular filtration rate (eGFR), renal replacement, or renal death was reduced by 41%; and heart failure hospitalizations were reduced by 32%.
All of those benefits were strongly statistically significant. They came at the cost of roughly a fourfold increase in readily treatable male and female genital infections – a known class effect of the SGLT2 inhibitors – as well as an unexpected twofold increase in lower extremity amputations, which fortunately were uncommon. Of the amputations, 29% were above the ankle; the other 71% were less drastic toe or transmetatarsal procedures.
Dr. Mahaffey estimated that for every 1,000 patients with type 2 diabetes who were taking canagliflozin for secondary cardiovascular prevention for 5 years, there would be 36 fewer cardiovascular deaths, nonfatal MIs, or nonfatal strokes; 20 fewer hospitalizations for heart failure; 21 fewer patients who experienced the composite renal outcome; and 21 additional patients with a lower extremity amputation.
Rates of cardiovascular and renal endpoints were at least twofold higher in the secondary prevention group than in the primary prevention cohort. For prevention, the size of the relative risk reductions in heart failure hospitalizations and renal outcomes with canagliflozin, compared with placebo, were similar to the secondary prevention experience. So was the magnitude of the increased risk of lower extremity amputation. However, none of these differences achieved statistical significance, perhaps because of the lower absolute event rates in the primary prevention group.
Moreover, there was no signal of benefit for canagliflozin in terms of the composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke in the primary prevention group; those event rates were virtually identical to those seen in the placebo-treated controls.
That being said, the CANVAS Program wasn’t designed with sufficient statistical power to draw definitive conclusions regarding outcome differences in the primary and secondary prevention groups, Dr. Mahaffey noted.
Putting the SGLT2 cardiovascular prevention results in perspective
Discussant Angelyn Bethel, MD, said the impressive outcomes for canagliflozin for secondary prevention in the CANVAS Program are consistent with the results of the earlier 7,020-patient EMPA-REG trial of the SGLT2 inhibitor empagliflozin (Jardiance) versus placebo for secondary prevention in type 2 diabetes (N Engl J Med. 2015 Nov 26;373[22]:2117-28). The relative risk reductions in the primary composite endpoint, as well as in heart failure hospitalizations and renal outcomes, were quite similar in the secondary prevention setting in the two large trials.
The one difference was in all-cause mortality: a striking 32% reduction with empagliflozin, compared with placebo, versus a more modest 11% relative risk reduction in the CANVAS program, which narrowly missed statistical significance.
The mechanisms for the important cardiovascular benefits seen in the secondary prevention setting in the two large SGLT2 trials are still under debate, according to Dr. Bethel, an endocrinologist who is deputy director of the diabetes trial unit at the University of Oxford (England).
“I think what’s obvious to most of us is that we’ve moved now beyond the conventional risk factors. These drugs cause only very small reductions in weight, systolic blood pressure, and diastolic blood pressure; they result in small increases in LDL and HDL; and the timeline of the impact that we see for the SGLT2 inhibitors on the cardiovascular outcomes in particular is much too short to be looking for glucose- or atherosclerotic-mediated processes,” she said.
“The mechanisms probably involve invoking the cardiorenal axis in some way,” Dr. Bethel speculated. “We know these drugs have a diuretic effect and we believe that some of the mortality benefit is probably mediated by heart failure outcomes, with changes in volume status. And there’s also a drive toward ketone metabolism, which is more efficient for the compromised heart.”
As for canagliflozin’s lack of significant benefit for primary prevention in the CANVAS program, it’s possible that this was a statistical power problem, Dr. Bethel said, but she has her doubts.
“If we had more people followed for longer in the primary prevention cohort, would we get there? I think it’s a big ask, but we do have more data coming,” she noted.
Indeed, two major phase 3 clinical trials of SGLT2 inhibitors for both primary and secondary cardiovascular prevention in mixed populations are due to report results in 2019: the roughly 4,500-patient CREDENCE trial of canagliflozin and the 17,0000-patient DECLARE trial, featuring dapagliflozin. Both involve about 5 years of follow-up.
Dr. Bethel advocated waiting until those studies report their primary prevention outcomes before introducing SGLT2-inhibitor therapy for primary cardiovascular prevention in clinical practice.
“In this instance, we do have some evidence that there may be a difference in the way that various events behave in the primary and secondary prevention settings, and we may have an overestimate of the benefits for primary prevention if we were to put this stuff in the water and give it to everybody,” she cautioned.
The CANVAS program analysis of primary versus secondary prevention has been published (Circulation. 2018 Jan 23;137[4]:323-34).
The CANVAS program was supported by Janssen. Dr. Mahaffey reported receiving research grants from and serving as a consultant to Janssen and numerous other companies.
SOURCE: Mahaffey KW et al. AHA Scientific Sessions.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: The primary composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke in the primary prevention cohort was virtually identical with canagliflozin and placebo.
Study details: The CANVAS program included 10,142 patients with type 2 diabetes randomized to canagliflozin or placebo and prospectively followed for a mean of 3.6 years. One-third of participants had no prior cardiovascular event at baseline.
Disclosures: The CANVAS program was supported by Janssen. The study presenter reported receiving research grants from and serving as a consultant to Janssen and numerous other companies.
Source: Mahaffey KW et al. AHA Scientific Sessions.