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Incorporate steroid dose into lupus disease activity score, expert says
MELBOURNE – Adding a patient’s current dose of glucocorticoids as a new metric in the systemic lupus erythematosus disease activity index score could make it a better predictor of damage accrual, Dafna Gladman, MD, told an international congress on systemic lupus erythematosus.
Dr. Gladman and her colleagues from the University of Toronto Lupus Clinic at Toronto Western Hospital conducted a three-part study that aimed to incorporate glucocorticoid dose into the existing systemic lupus erythematosus disease activity index (SLEDAI)-2K score.
“In clinical trials, the use of standard of care, which includes the use of corticosteroids, often confounds the results, and we see that in a number of trials, so there has been an unmet need to develop an index that incorporates the glucocorticoid dose into a disease activity measure.”
The first part of the study involved identification of 131 patient scenarios from a longitudinal cohort followed at the clinic for 20 years that included eight categories based on glucocorticoid dose, ranging from 5 to 60 mg/day.
In the second phase, three rheumatologists ranked the disease activity for each patient scenario using the Physician Global Assessment, and the study team used these rankings to derive a formula to explain the association between SLEDAI and glucocorticoid category.
The third phase used data from an inception cohort of patients from the clinic with 10 years of follow-up to validate the new score – called SLEDAI-2KG – by predicting the accrual of damage over the course of follow-up.
Researchers found that the modified score was significantly better at predicting damage accrual than was the original score.
“If somebody may have a very low disease activity measurable by the instrument, SLEDAI, but they’re still taking 10-15 mg prednisone, we need to somehow take it into account,” Dr. Gladman said in an interview. “It tells you that thinking that the patient is doing well but still taking 15 mg of prednisone is not appropriate.”
Session cochair Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne, questioned whether incorporating a treatment into a score for disease activity was too circular.
However, Dr. Gladman stressed that the glucocorticoid score was not based on what the physician planned to do, but what the patient was taking at the time of the consultation.
“If a patient has a rash and is currently taking 40 mg of prednisone, the value of the SLEDAI would be increased because of that dose,” she said. “On the other hand, somebody might come in with pleurisy, and some people might treat that with 60 mg, but they are only taking 20 mg; that suggests that the value would be lower in that particular patient.”
The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.
MELBOURNE – Adding a patient’s current dose of glucocorticoids as a new metric in the systemic lupus erythematosus disease activity index score could make it a better predictor of damage accrual, Dafna Gladman, MD, told an international congress on systemic lupus erythematosus.
Dr. Gladman and her colleagues from the University of Toronto Lupus Clinic at Toronto Western Hospital conducted a three-part study that aimed to incorporate glucocorticoid dose into the existing systemic lupus erythematosus disease activity index (SLEDAI)-2K score.
“In clinical trials, the use of standard of care, which includes the use of corticosteroids, often confounds the results, and we see that in a number of trials, so there has been an unmet need to develop an index that incorporates the glucocorticoid dose into a disease activity measure.”
The first part of the study involved identification of 131 patient scenarios from a longitudinal cohort followed at the clinic for 20 years that included eight categories based on glucocorticoid dose, ranging from 5 to 60 mg/day.
In the second phase, three rheumatologists ranked the disease activity for each patient scenario using the Physician Global Assessment, and the study team used these rankings to derive a formula to explain the association between SLEDAI and glucocorticoid category.
The third phase used data from an inception cohort of patients from the clinic with 10 years of follow-up to validate the new score – called SLEDAI-2KG – by predicting the accrual of damage over the course of follow-up.
Researchers found that the modified score was significantly better at predicting damage accrual than was the original score.
“If somebody may have a very low disease activity measurable by the instrument, SLEDAI, but they’re still taking 10-15 mg prednisone, we need to somehow take it into account,” Dr. Gladman said in an interview. “It tells you that thinking that the patient is doing well but still taking 15 mg of prednisone is not appropriate.”
Session cochair Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne, questioned whether incorporating a treatment into a score for disease activity was too circular.
However, Dr. Gladman stressed that the glucocorticoid score was not based on what the physician planned to do, but what the patient was taking at the time of the consultation.
“If a patient has a rash and is currently taking 40 mg of prednisone, the value of the SLEDAI would be increased because of that dose,” she said. “On the other hand, somebody might come in with pleurisy, and some people might treat that with 60 mg, but they are only taking 20 mg; that suggests that the value would be lower in that particular patient.”
The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.
MELBOURNE – Adding a patient’s current dose of glucocorticoids as a new metric in the systemic lupus erythematosus disease activity index score could make it a better predictor of damage accrual, Dafna Gladman, MD, told an international congress on systemic lupus erythematosus.
Dr. Gladman and her colleagues from the University of Toronto Lupus Clinic at Toronto Western Hospital conducted a three-part study that aimed to incorporate glucocorticoid dose into the existing systemic lupus erythematosus disease activity index (SLEDAI)-2K score.
“In clinical trials, the use of standard of care, which includes the use of corticosteroids, often confounds the results, and we see that in a number of trials, so there has been an unmet need to develop an index that incorporates the glucocorticoid dose into a disease activity measure.”
The first part of the study involved identification of 131 patient scenarios from a longitudinal cohort followed at the clinic for 20 years that included eight categories based on glucocorticoid dose, ranging from 5 to 60 mg/day.
In the second phase, three rheumatologists ranked the disease activity for each patient scenario using the Physician Global Assessment, and the study team used these rankings to derive a formula to explain the association between SLEDAI and glucocorticoid category.
The third phase used data from an inception cohort of patients from the clinic with 10 years of follow-up to validate the new score – called SLEDAI-2KG – by predicting the accrual of damage over the course of follow-up.
Researchers found that the modified score was significantly better at predicting damage accrual than was the original score.
“If somebody may have a very low disease activity measurable by the instrument, SLEDAI, but they’re still taking 10-15 mg prednisone, we need to somehow take it into account,” Dr. Gladman said in an interview. “It tells you that thinking that the patient is doing well but still taking 15 mg of prednisone is not appropriate.”
Session cochair Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne, questioned whether incorporating a treatment into a score for disease activity was too circular.
However, Dr. Gladman stressed that the glucocorticoid score was not based on what the physician planned to do, but what the patient was taking at the time of the consultation.
“If a patient has a rash and is currently taking 40 mg of prednisone, the value of the SLEDAI would be increased because of that dose,” she said. “On the other hand, somebody might come in with pleurisy, and some people might treat that with 60 mg, but they are only taking 20 mg; that suggests that the value would be lower in that particular patient.”
The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.
AT LUPUS 2017
Key clinical point:
Major finding: A revised SLEDAI incorporating glucocorticoid dose was significantly better at predicting damage accrual.
Data source: Development of a new disease activity index from 131 patient scenarios derived from a longitudinal cohort and validated in a separate inception cohort.
Disclosures: The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.
Lupus nephritis expert offers management tips
MELBOURNE – Multidisciplinary management of comorbidities is one of the most important aspects of the care of patients with lupus nephritis, Frédéric Houssiau, MD, PhD, said at an international congress on systemic lupus erythematosus.
In his presentation describing his top 10 tips for the management of lupus nephritis, Dr. Houssiau said traditional risk factors do not explain the two- to threefold higher risk of cardiovascular disease in patients with lupus, making it important to address known cardiovascular disease risk factors.
Dr. Houssiau also stressed the importance of paying attention to clotting disorders, preventing glucocorticoid-related intraocular pressure, ensuring patients are immunized against influenza, and enabling patient access to an intensive care unit in the event of severe sepsis.
He also called for physicians to “unmask” nonadherence to therapy, saying it was the most common cause of treatment failure.
“We don’t look enough to nonadherence to therapy, and we have no good clue to sort that out,” he said in an interview. “We can identify nonadherent patients, but it’s very difficult to change their mind, to make them adherent, and we have nurses, nurse-practitioners, questionnaires for adherence, but none of them, I think, so far have changed practice.”
Dr. Houssiau argued for the importance of having a good connection with a nephrologist and always performing a renal biopsy in patients with lupus nephritis.
“The reason for that is first to identify the immune deposits, either mesangial or subendothelial or subepithelial, and another reason is clearly not to miss the antiphospholipid syndrome,” he told the audience. “The third very good reason to perform the renal biopsy is clearly to classify the patient.”
Echoing other presentations at the conference, Dr. Houssiau said there was a need to define treatment targets in lupus nephritis.
“In diabetes, in hypertension, in rheumatoid arthritis, the target is well known by all of us,” he said. “What is the target that we should achieve in the lupus nephritis patient? That is much more difficult.”
He cited data from the recent MAINTAIN trial, which suggested that proteinuria levels at 12 months after initiation of treatment were highly predictive of patients who were likely to have a good renal prognosis. Patients with a 24-hour proteinuria level of around 0.7-0.8 g/day had a significantly greater likelihood of normal serum creatinine 7 years later, he said.
“Yet, we need more, we need better markers, because the negative predictive value is very bad, which means that a lot of patients who do not reach that target still, fortunately, will end up without renal failure.”
Dr. Houssiau also emphasized the need to minimize the use of steroids where possible, as data from an inception cohort run by him and his colleagues have shown that patients who failed to taper down to 4 mg of prednisone or less, after 1 year, had significantly more damage accrual.
He also advocated using either mycophenolate mofetil or intravenous cyclophosphamide as induction therapy based on data suggesting the two are equally efficacious at 6 months. Dr. Houssiau suggested favoring intravenous cyclophosphamide if fertility was a concern because it has been shown to not affect ovarian reserve and has the added advantage of better compliance.
Maintaining immunosuppression is also vital, Dr. Houssiau told the conference, and patients should be treated with immunosuppressants for at least 5, and possibly even up to 10, years.
“There is a small study showing an inverse correlation between the length of therapy and remission on the one hand, and risk of relapse, so the more you treat, the more the period of remission is long, the lower risk of relapse,” he said. However, there are little trial data on withdrawing immunosuppression or trials of immunosuppressant withdrawal, he noted.
Commenting on the future prospects for new treatments for lupus nephritis, Dr. Houssiau advised keeping faith in targeted therapies and precision medicine despite a slew of failed phase III clinical trials, and watching the development of calcineurin inhibitors, such as voclosporin.
Dr. Houssiau declared receiving research grants and honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Roche, Serono, and UCB.
MELBOURNE – Multidisciplinary management of comorbidities is one of the most important aspects of the care of patients with lupus nephritis, Frédéric Houssiau, MD, PhD, said at an international congress on systemic lupus erythematosus.
In his presentation describing his top 10 tips for the management of lupus nephritis, Dr. Houssiau said traditional risk factors do not explain the two- to threefold higher risk of cardiovascular disease in patients with lupus, making it important to address known cardiovascular disease risk factors.
Dr. Houssiau also stressed the importance of paying attention to clotting disorders, preventing glucocorticoid-related intraocular pressure, ensuring patients are immunized against influenza, and enabling patient access to an intensive care unit in the event of severe sepsis.
He also called for physicians to “unmask” nonadherence to therapy, saying it was the most common cause of treatment failure.
“We don’t look enough to nonadherence to therapy, and we have no good clue to sort that out,” he said in an interview. “We can identify nonadherent patients, but it’s very difficult to change their mind, to make them adherent, and we have nurses, nurse-practitioners, questionnaires for adherence, but none of them, I think, so far have changed practice.”
Dr. Houssiau argued for the importance of having a good connection with a nephrologist and always performing a renal biopsy in patients with lupus nephritis.
“The reason for that is first to identify the immune deposits, either mesangial or subendothelial or subepithelial, and another reason is clearly not to miss the antiphospholipid syndrome,” he told the audience. “The third very good reason to perform the renal biopsy is clearly to classify the patient.”
Echoing other presentations at the conference, Dr. Houssiau said there was a need to define treatment targets in lupus nephritis.
“In diabetes, in hypertension, in rheumatoid arthritis, the target is well known by all of us,” he said. “What is the target that we should achieve in the lupus nephritis patient? That is much more difficult.”
He cited data from the recent MAINTAIN trial, which suggested that proteinuria levels at 12 months after initiation of treatment were highly predictive of patients who were likely to have a good renal prognosis. Patients with a 24-hour proteinuria level of around 0.7-0.8 g/day had a significantly greater likelihood of normal serum creatinine 7 years later, he said.
“Yet, we need more, we need better markers, because the negative predictive value is very bad, which means that a lot of patients who do not reach that target still, fortunately, will end up without renal failure.”
Dr. Houssiau also emphasized the need to minimize the use of steroids where possible, as data from an inception cohort run by him and his colleagues have shown that patients who failed to taper down to 4 mg of prednisone or less, after 1 year, had significantly more damage accrual.
He also advocated using either mycophenolate mofetil or intravenous cyclophosphamide as induction therapy based on data suggesting the two are equally efficacious at 6 months. Dr. Houssiau suggested favoring intravenous cyclophosphamide if fertility was a concern because it has been shown to not affect ovarian reserve and has the added advantage of better compliance.
Maintaining immunosuppression is also vital, Dr. Houssiau told the conference, and patients should be treated with immunosuppressants for at least 5, and possibly even up to 10, years.
“There is a small study showing an inverse correlation between the length of therapy and remission on the one hand, and risk of relapse, so the more you treat, the more the period of remission is long, the lower risk of relapse,” he said. However, there are little trial data on withdrawing immunosuppression or trials of immunosuppressant withdrawal, he noted.
Commenting on the future prospects for new treatments for lupus nephritis, Dr. Houssiau advised keeping faith in targeted therapies and precision medicine despite a slew of failed phase III clinical trials, and watching the development of calcineurin inhibitors, such as voclosporin.
Dr. Houssiau declared receiving research grants and honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Roche, Serono, and UCB.
MELBOURNE – Multidisciplinary management of comorbidities is one of the most important aspects of the care of patients with lupus nephritis, Frédéric Houssiau, MD, PhD, said at an international congress on systemic lupus erythematosus.
In his presentation describing his top 10 tips for the management of lupus nephritis, Dr. Houssiau said traditional risk factors do not explain the two- to threefold higher risk of cardiovascular disease in patients with lupus, making it important to address known cardiovascular disease risk factors.
Dr. Houssiau also stressed the importance of paying attention to clotting disorders, preventing glucocorticoid-related intraocular pressure, ensuring patients are immunized against influenza, and enabling patient access to an intensive care unit in the event of severe sepsis.
He also called for physicians to “unmask” nonadherence to therapy, saying it was the most common cause of treatment failure.
“We don’t look enough to nonadherence to therapy, and we have no good clue to sort that out,” he said in an interview. “We can identify nonadherent patients, but it’s very difficult to change their mind, to make them adherent, and we have nurses, nurse-practitioners, questionnaires for adherence, but none of them, I think, so far have changed practice.”
Dr. Houssiau argued for the importance of having a good connection with a nephrologist and always performing a renal biopsy in patients with lupus nephritis.
“The reason for that is first to identify the immune deposits, either mesangial or subendothelial or subepithelial, and another reason is clearly not to miss the antiphospholipid syndrome,” he told the audience. “The third very good reason to perform the renal biopsy is clearly to classify the patient.”
Echoing other presentations at the conference, Dr. Houssiau said there was a need to define treatment targets in lupus nephritis.
“In diabetes, in hypertension, in rheumatoid arthritis, the target is well known by all of us,” he said. “What is the target that we should achieve in the lupus nephritis patient? That is much more difficult.”
He cited data from the recent MAINTAIN trial, which suggested that proteinuria levels at 12 months after initiation of treatment were highly predictive of patients who were likely to have a good renal prognosis. Patients with a 24-hour proteinuria level of around 0.7-0.8 g/day had a significantly greater likelihood of normal serum creatinine 7 years later, he said.
“Yet, we need more, we need better markers, because the negative predictive value is very bad, which means that a lot of patients who do not reach that target still, fortunately, will end up without renal failure.”
Dr. Houssiau also emphasized the need to minimize the use of steroids where possible, as data from an inception cohort run by him and his colleagues have shown that patients who failed to taper down to 4 mg of prednisone or less, after 1 year, had significantly more damage accrual.
He also advocated using either mycophenolate mofetil or intravenous cyclophosphamide as induction therapy based on data suggesting the two are equally efficacious at 6 months. Dr. Houssiau suggested favoring intravenous cyclophosphamide if fertility was a concern because it has been shown to not affect ovarian reserve and has the added advantage of better compliance.
Maintaining immunosuppression is also vital, Dr. Houssiau told the conference, and patients should be treated with immunosuppressants for at least 5, and possibly even up to 10, years.
“There is a small study showing an inverse correlation between the length of therapy and remission on the one hand, and risk of relapse, so the more you treat, the more the period of remission is long, the lower risk of relapse,” he said. However, there are little trial data on withdrawing immunosuppression or trials of immunosuppressant withdrawal, he noted.
Commenting on the future prospects for new treatments for lupus nephritis, Dr. Houssiau advised keeping faith in targeted therapies and precision medicine despite a slew of failed phase III clinical trials, and watching the development of calcineurin inhibitors, such as voclosporin.
Dr. Houssiau declared receiving research grants and honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Roche, Serono, and UCB.
EXPERT ANALYSIS FROM LUPUS 2017
Approach to covert recording by patients of encounters with gastroenterology providers
Last year, while sedated for colonoscopy, a patient covertly recorded conversations between endoscopy staff and providers. Comments about the patient were egregious and resulted in loss of employment for those involved and a large financial settlement. The reality of today’s world is that we all are subject to constant (real or potential) surveillance. Nothing is private and nothing recorded is temporary, yet physicians value private conversations with our patients. When a patient records a visit, either covertly or overtly, most physicians pause and have some emotional reaction (either positive or negative). Some welcome the ability to communicate accurately to a wider audience, while others believe the act of recording violates an interpersonal bond. In this month’s issue, Dr. Adams discusses the legal and ethical ramifications when a patient records our clinical interactions. She offers an excellent analysis and practical risk management strategies. Personally, I follow my wife’s dictum to act as if I am always on camera.
John I. Allen, MD, MBA, AGAF
Editor in Chief
Patients and physicians were collectively horrified last year when news broke of a Virginia man who recorded conversations between his gastroenterologist, his anesthesiologist, and other endoscopy unit staff, including a number of disparaging remarks about the patient, while sedated for his colonoscopy. Among other objectionable comments, providers mocked the patient for being demanding in the preprocedure area and for the amount of sedation he required, made comments implying that he had syphilis or tuberculosis, and discussed avoiding the patient following the procedure via an urgent “fake page.”1 The patient sued, resulting in a $500,000 judgment against the anesthesiologist for defamation and malpractice, including punitive damages. Although this case clearly represents an extreme example of unprofessional behavior, it also raises thought-provoking questions regarding the evolving relationship between patients and their physicians, as well as the legal and ethical implications of covert recording that deserve further discussion.
This article reviews the current state of knowledge regarding the frequency of and motivation for covert patient recording of medical encounters, and the legal and ethical principles informing this area. It concludes by proposing several strategies gastroenterologists can use to mitigate risk of liability while also preserving the patient-physician relationship and upholding professional autonomy.
Weighing the benefits and harms of patient electronic recording
Patient recording of medical encounters, whether covert or overt, presents both benefits and risks of harm. Theoretically, recording medical encounters could assist patients in remembering and/or better understanding recommendations provided by their physicians. It may also secondarily improve patient compliance and overall engagement in medical care and help patients accurately communicate recommendations to family members and other caregivers who are not immediately available during the clinical encounter. Patients may also view these recordings as a mechanism for empowerment, allowing them to shift the power dynamic between patient and provider.2,3 However, there is also the potential for recorded comments to be taken out of context or misinterpreted, leading to confusion on the part of the patient or family. Overt recording of medical encounters also may alter physician decision-making, leading to more aggressive testing and expense for the patient and the healthcare system. Even worse, covert recording of medical encounters (if discovered) may irreparably harm the physician-patient relationship by introducing distrust and causing the physician to take a more defensive posture in subsequent dealings with a given patient.
Recent research has shed new light on the potential frequency of patient covert recording of medical encounters, suggesting that it is alarmingly common. In a mixed-methods study of 130 patients in the United Kingdom who were recruited via radio and social media, 15% of respondents indicated that they had secretly recorded a clinical encounter, and an additional 11% personally knew someone who had covertly recorded.4 Those who reported having covertly recorded were significantly more likely to be less educated and male than those who had not. An additional 35% of respondents indicated that they would consider covertly recording a clinical encounter in the future. Although the generalizability of these results may be challenged based on the potential for sampling bias, the results suggest a shifting paradigm in the way in which patients view the physician-patient relationship and a fundamental breakdown in communication and erosion of trust.
The underlying motivations for patient recording of medical encounters are complex and multifaceted. These recordings seem to be a relatively new phenomenon and one that elicits strong reactions, positive and negative, on the part of patients, physicians, and society.2 Qualitative studies reveal that, whether covertly or overtly recording, most patients are driven by a common desire to replay, relisten, and/or share the recording with family, friends, and other caregivers.4 Indeed, the patient involved in the previously mentioned litigation purportedly intended to record the postcolonoscopy discharge instructions from his gastroenterologist, only to later discover much more. Patients who record covertly report being motivated by a fear of being denied permission to record or by prior experiences of poor quality care and the prospect of gathering verifiable evidence to support their experience. In contrast, patients who ask permission to record seem to be motivated primarily by a desire to preserve or enhance the physician-patient relationship.4 These insights are valuable in that they allow clinicians to view medical encounters from the perspective of patients, understand the power-dynamics at play, and ultimately, use this information to enlighten future care.
Legal guidance: “One-party” versus “all-party” consent
Although the prospect of covert patient recording may be unsettling to physicians, is it illegal? Because of a paucity of legal precedent in this area, the legal landscape is rather murky. Through the provisions of the Electronic Communications Privacy Act, federal law prohibits the interception and disclosure of wire, oral, or electronic communications without specific consent of at least one party to the conversation.5 This so-called “one-party” consent standard affords a baseline level of legal protection. A handful of states offer additional protection under state law by requiring all parties to the conversation to consent to the recording (so-called “all-party” consent). Virginia, where the audio recording of the previously mentioned colonoscopy took place, is a “one-party” consent state.6 In contrast, states such as California and Florida have adopted an “all-party” consent rule.7,8
However, uncertainty remains. For instance, if medical providers have a conversation in the same room as a sedated patient during a medical procedure on that patient, is the patient a “party” to the conversation? Furthermore, can such a conversation be considered private when held in front of a patient during a medical procedure? Is the patient in such a scenario “eavesdropping”? Given a lack of legal precedent in the form of case law and given the unique features of each clinical scenario, this is likely to remain an area of significant legal ambiguity. Although the possibility of covert patient recording may be unnerving for providers, the reality is that, in most cases, it is likely legally permissible.
Ethical principles: Navigating an evolving physician-patient relationship
The relationship between physician and patient, a core aspect of medical ethics, has evolved markedly over time. This relationship was historically paternalistic: The patient was seen to be dependent on the physician’s professional authority in determining the appropriateness of care, and patient’s preferences were seen as secondary to physician judgment. In recent years, however, the physician-patient relationship has evolved toward one privileging patient-centered care and shared decision-making based on a patient’s unique values, beliefs, and preferences.9,10
Concomitantly, the public’s view of doctoring has transitioned from “unquestioning acceptance of physician authority to a more ‘consumerist’ view accompanied by a questioning and bargaining approach to medicine, physicians and the medical encounter,” according to a 2001 study published in the Journal of Health and Social Behavior.11 In this context, many patients, attorneys, bioethicists, and patient advocates see patient recording of medical encounters as a legitimate check on the health care system, ensuring transparency and honesty and empowering patients to become more active participants in their medical care.2
Policy responses
Although recognition of patient recording of medical encounters has been growing, there have been few direct policy responses to date. One notable example was an effort by Wisconsin legislators in 2015 to mandate that any place where surgery is performed (including hospitals, ambulatory surgical centers, and other sites) offer patients the option to have their procedure videotaped and audiotaped.12 The proposed legislation was written broadly enough to include locations where gastroenterologists perform routine endoscopic procedures under sedation. Recordings would have been treated as part of the patient’s health care record and been admissible as evidence in subsequent legal proceedings relating to the medical care provided. Although this bill ultimately failed to pass pursuant to a Joint Resolution in the Wisconsin Senate in April 2016, it is a poignant example of the possible policy actions that may govern this area in the future.
In 2012, the National Institute for Health and Clinical Excellence, England, issued a guidance document focused on improving the patient care experience, which recommends that clinicians routinely ask patients if they would like to take notes and/or record the clinical encounter.13 Although not explicitly referencing covert recording, this guidance effectively aims to promote increased transparency by openly encouraging recording as a component of optimal medical practice. Although the American Medical Association Code of Ethics offers guidance regarding physicians recording patient encounters, it does not comment on patient-initiated recordings.14
Risk management strategies for gastroenterology providers
So, how can gastroenterologists and other providers protect themselves in a world of covert recording, while also preserving their relationships with patients and optimizing medical care? First, despite their harried days and varied responsibilities, gastroenterologists must recognize the possibility of covert recording and seek to maintain professionalism in all clinical environments, whether in an examination room or in an endoscopy suite with a sedated patient. Physicians set the tone for the entire team and also have an obligation to intervene if other members of the medical team are not adhering to professional standards. Although physicians and other medical providers often use cynical and derogatory humor as a coping mechanism given the heavy workload and amplified stressors of the clinical environment, it is important to be mindful of how such comments are perceived by patient bystanders.15,16 Although achieving a robust therapeutic alliance with a patient can take months, this trust can be easily broken by a single flippant remark by the physician.
Second, rather than assuming a defensive posture driven by fear of medical liability, it is vital for gastroenterologists to directly confront situations in which covert recording is suspected while also preserving the physician-patient relationship. In fact, by openly encouraging patient recording as a matter of routine practice, gastroenterologists can promote an environment of trust and transparency and bolster the therapeutic alliance between patient and provider.15 This approach also encourages providers to hone their communication skills and ensure they are communicating essential medical information clearly and succinctly and conveying medical nuance where appropriate. For example, in a clinic setting, a patient with inflammatory bowel disease who records might better remember or understand the risks and benefits of various treatment strategies and the common side effects of medications such as azathioprine and biologics. Patients recording medical encounters in the endoscopy suite might better recall postprocedure instructions, including recommended follow-up intervals and risks of postendoscopy complications. In this era of shared decision-making and patient-centered care, optimizing both physician delivery and patient understanding and recall of essential medical information is of critical importance.
Finally, although adoption of the above practices would serve the dual goals of enhancing patient-provider communication and mitigating legal risk, certain system interventions may further minimize the risk of covert recording. For instance, endoscopy units can store patients’ personal effects, including electronic devices, in a locker outside the endoscopy room rather than on the gurney. Retrieving patient belongings before postprocedure instructions are delivered would protect the patient’s ability to record this advice for future recall.
Conclusions
Recording by patients of clinical encounters, whether covert or overt, has become increasingly common as a result of the digital revolution. These recordings most often represent an attempt by the patient to gain more information relevant to their medical care. Rather than being threatened by this new reality, gastroenterologists should consider embracing this practice as an opportunity to enhance effective communication with patients, encourage shared decision making, and deliver truly patient-centered care.
Acknowledgments
This article is intended as general commentary and should not be interpreted as legal advice applicable to individual circumstances. Do not act or rely on information contained in this article without first seeking the advice of a personal attorney.
References
1. Washington Post. (2015 June 24). Audio: Anesthesiologist trashes sedated patient. Available at: https://youtu.be/Kar52idHgho. Accessed May 15, 2016.
2. Tsulukidze, M., Grande, S.W., Thompson, R., et al. Patients covertly recording clinical encounters: threat or opportunity? A qualitative analysis of online texts. PLoS One. 2015;10:e0125824.
3. Rodriguez, M., Morrow, J., Selfi, A. Ethical implications of patients and families secretly recording conversations with physicians. JAMA. 2015;313(16):1615-6.
4. Elwyn, G., Barr, P.J., Grande, S.W. Patients recording clinical encounters: a path to empowerment? Assessment by mixed methods. BMJ Open. 2015;5(8):e008566.
5. 18 U.S.C. §2511(2)(d).
6. VA Code §19.2-62.
7. Cal. Penal Code §632.
8. Fla. Stat. Ann. §934.03(3)(d).
9. Truog, R.D. Patients and doctors: the evolution of a relationship. N Engl J Med. 2012;366:581-5.
10. Barry, M.J., Edgman-Levitan, S. Shared decision making: the pinnacle of patient-centered care. N Engl J Med. 2012;366:780-1.
11. Pescosolido, B.A., Tuch, S.A., Martin, J.K. The profession of medicine and the public: examining Americans’ changing confidence in physician authority from the beginning of the ‘health care crisis’ to the era of health care reform. J Health Social Behavior. 2001;42(1):1-16.
12. Wisconsin Assembly Bill 255. (2015). Available at: https://docs.legis.wisconsin.gov/2015/proposals/ab255. Accessed June 29, 2016.
13. National Institute for Health and Clinical Excellence. (2012 Feb). Patient experience in adult NHS services: improving the experience of care for people using adult NHS service. Available at: https://www.nice.org.uk/guidance/cg138/chapter/1-guidance. Accessed June 29, 2016.
14. American Medical Association Code of Medical Ethics, Opinion 5.045 - Filming Patients in Health Care Settings. Updated June 2006. Available at: http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion5045.page? Accessed June 29, 2016.
15. Aultman, J.M. When humor in the hospital is no laughing matter. J Clin Ethics. 2009;20:227-35.
15. Sobel, R.K. Does laughter make good medicine? N Engl J Med. 2006;354:1114-5.
Dr. Adams is a clinical lecturer in the division of gastroenterology, University of Michigan, Ann Arbor, an investigator with the VA Center for Clinical Management Research, a staff physician in the VA Ann Arbor Healthcare System, and a member of the Institute for Healthcare Policy and Innovation, Ann Arbor. She has no conflicts of interest.
Last year, while sedated for colonoscopy, a patient covertly recorded conversations between endoscopy staff and providers. Comments about the patient were egregious and resulted in loss of employment for those involved and a large financial settlement. The reality of today’s world is that we all are subject to constant (real or potential) surveillance. Nothing is private and nothing recorded is temporary, yet physicians value private conversations with our patients. When a patient records a visit, either covertly or overtly, most physicians pause and have some emotional reaction (either positive or negative). Some welcome the ability to communicate accurately to a wider audience, while others believe the act of recording violates an interpersonal bond. In this month’s issue, Dr. Adams discusses the legal and ethical ramifications when a patient records our clinical interactions. She offers an excellent analysis and practical risk management strategies. Personally, I follow my wife’s dictum to act as if I am always on camera.
John I. Allen, MD, MBA, AGAF
Editor in Chief
Patients and physicians were collectively horrified last year when news broke of a Virginia man who recorded conversations between his gastroenterologist, his anesthesiologist, and other endoscopy unit staff, including a number of disparaging remarks about the patient, while sedated for his colonoscopy. Among other objectionable comments, providers mocked the patient for being demanding in the preprocedure area and for the amount of sedation he required, made comments implying that he had syphilis or tuberculosis, and discussed avoiding the patient following the procedure via an urgent “fake page.”1 The patient sued, resulting in a $500,000 judgment against the anesthesiologist for defamation and malpractice, including punitive damages. Although this case clearly represents an extreme example of unprofessional behavior, it also raises thought-provoking questions regarding the evolving relationship between patients and their physicians, as well as the legal and ethical implications of covert recording that deserve further discussion.
This article reviews the current state of knowledge regarding the frequency of and motivation for covert patient recording of medical encounters, and the legal and ethical principles informing this area. It concludes by proposing several strategies gastroenterologists can use to mitigate risk of liability while also preserving the patient-physician relationship and upholding professional autonomy.
Weighing the benefits and harms of patient electronic recording
Patient recording of medical encounters, whether covert or overt, presents both benefits and risks of harm. Theoretically, recording medical encounters could assist patients in remembering and/or better understanding recommendations provided by their physicians. It may also secondarily improve patient compliance and overall engagement in medical care and help patients accurately communicate recommendations to family members and other caregivers who are not immediately available during the clinical encounter. Patients may also view these recordings as a mechanism for empowerment, allowing them to shift the power dynamic between patient and provider.2,3 However, there is also the potential for recorded comments to be taken out of context or misinterpreted, leading to confusion on the part of the patient or family. Overt recording of medical encounters also may alter physician decision-making, leading to more aggressive testing and expense for the patient and the healthcare system. Even worse, covert recording of medical encounters (if discovered) may irreparably harm the physician-patient relationship by introducing distrust and causing the physician to take a more defensive posture in subsequent dealings with a given patient.
Recent research has shed new light on the potential frequency of patient covert recording of medical encounters, suggesting that it is alarmingly common. In a mixed-methods study of 130 patients in the United Kingdom who were recruited via radio and social media, 15% of respondents indicated that they had secretly recorded a clinical encounter, and an additional 11% personally knew someone who had covertly recorded.4 Those who reported having covertly recorded were significantly more likely to be less educated and male than those who had not. An additional 35% of respondents indicated that they would consider covertly recording a clinical encounter in the future. Although the generalizability of these results may be challenged based on the potential for sampling bias, the results suggest a shifting paradigm in the way in which patients view the physician-patient relationship and a fundamental breakdown in communication and erosion of trust.
The underlying motivations for patient recording of medical encounters are complex and multifaceted. These recordings seem to be a relatively new phenomenon and one that elicits strong reactions, positive and negative, on the part of patients, physicians, and society.2 Qualitative studies reveal that, whether covertly or overtly recording, most patients are driven by a common desire to replay, relisten, and/or share the recording with family, friends, and other caregivers.4 Indeed, the patient involved in the previously mentioned litigation purportedly intended to record the postcolonoscopy discharge instructions from his gastroenterologist, only to later discover much more. Patients who record covertly report being motivated by a fear of being denied permission to record or by prior experiences of poor quality care and the prospect of gathering verifiable evidence to support their experience. In contrast, patients who ask permission to record seem to be motivated primarily by a desire to preserve or enhance the physician-patient relationship.4 These insights are valuable in that they allow clinicians to view medical encounters from the perspective of patients, understand the power-dynamics at play, and ultimately, use this information to enlighten future care.
Legal guidance: “One-party” versus “all-party” consent
Although the prospect of covert patient recording may be unsettling to physicians, is it illegal? Because of a paucity of legal precedent in this area, the legal landscape is rather murky. Through the provisions of the Electronic Communications Privacy Act, federal law prohibits the interception and disclosure of wire, oral, or electronic communications without specific consent of at least one party to the conversation.5 This so-called “one-party” consent standard affords a baseline level of legal protection. A handful of states offer additional protection under state law by requiring all parties to the conversation to consent to the recording (so-called “all-party” consent). Virginia, where the audio recording of the previously mentioned colonoscopy took place, is a “one-party” consent state.6 In contrast, states such as California and Florida have adopted an “all-party” consent rule.7,8
However, uncertainty remains. For instance, if medical providers have a conversation in the same room as a sedated patient during a medical procedure on that patient, is the patient a “party” to the conversation? Furthermore, can such a conversation be considered private when held in front of a patient during a medical procedure? Is the patient in such a scenario “eavesdropping”? Given a lack of legal precedent in the form of case law and given the unique features of each clinical scenario, this is likely to remain an area of significant legal ambiguity. Although the possibility of covert patient recording may be unnerving for providers, the reality is that, in most cases, it is likely legally permissible.
Ethical principles: Navigating an evolving physician-patient relationship
The relationship between physician and patient, a core aspect of medical ethics, has evolved markedly over time. This relationship was historically paternalistic: The patient was seen to be dependent on the physician’s professional authority in determining the appropriateness of care, and patient’s preferences were seen as secondary to physician judgment. In recent years, however, the physician-patient relationship has evolved toward one privileging patient-centered care and shared decision-making based on a patient’s unique values, beliefs, and preferences.9,10
Concomitantly, the public’s view of doctoring has transitioned from “unquestioning acceptance of physician authority to a more ‘consumerist’ view accompanied by a questioning and bargaining approach to medicine, physicians and the medical encounter,” according to a 2001 study published in the Journal of Health and Social Behavior.11 In this context, many patients, attorneys, bioethicists, and patient advocates see patient recording of medical encounters as a legitimate check on the health care system, ensuring transparency and honesty and empowering patients to become more active participants in their medical care.2
Policy responses
Although recognition of patient recording of medical encounters has been growing, there have been few direct policy responses to date. One notable example was an effort by Wisconsin legislators in 2015 to mandate that any place where surgery is performed (including hospitals, ambulatory surgical centers, and other sites) offer patients the option to have their procedure videotaped and audiotaped.12 The proposed legislation was written broadly enough to include locations where gastroenterologists perform routine endoscopic procedures under sedation. Recordings would have been treated as part of the patient’s health care record and been admissible as evidence in subsequent legal proceedings relating to the medical care provided. Although this bill ultimately failed to pass pursuant to a Joint Resolution in the Wisconsin Senate in April 2016, it is a poignant example of the possible policy actions that may govern this area in the future.
In 2012, the National Institute for Health and Clinical Excellence, England, issued a guidance document focused on improving the patient care experience, which recommends that clinicians routinely ask patients if they would like to take notes and/or record the clinical encounter.13 Although not explicitly referencing covert recording, this guidance effectively aims to promote increased transparency by openly encouraging recording as a component of optimal medical practice. Although the American Medical Association Code of Ethics offers guidance regarding physicians recording patient encounters, it does not comment on patient-initiated recordings.14
Risk management strategies for gastroenterology providers
So, how can gastroenterologists and other providers protect themselves in a world of covert recording, while also preserving their relationships with patients and optimizing medical care? First, despite their harried days and varied responsibilities, gastroenterologists must recognize the possibility of covert recording and seek to maintain professionalism in all clinical environments, whether in an examination room or in an endoscopy suite with a sedated patient. Physicians set the tone for the entire team and also have an obligation to intervene if other members of the medical team are not adhering to professional standards. Although physicians and other medical providers often use cynical and derogatory humor as a coping mechanism given the heavy workload and amplified stressors of the clinical environment, it is important to be mindful of how such comments are perceived by patient bystanders.15,16 Although achieving a robust therapeutic alliance with a patient can take months, this trust can be easily broken by a single flippant remark by the physician.
Second, rather than assuming a defensive posture driven by fear of medical liability, it is vital for gastroenterologists to directly confront situations in which covert recording is suspected while also preserving the physician-patient relationship. In fact, by openly encouraging patient recording as a matter of routine practice, gastroenterologists can promote an environment of trust and transparency and bolster the therapeutic alliance between patient and provider.15 This approach also encourages providers to hone their communication skills and ensure they are communicating essential medical information clearly and succinctly and conveying medical nuance where appropriate. For example, in a clinic setting, a patient with inflammatory bowel disease who records might better remember or understand the risks and benefits of various treatment strategies and the common side effects of medications such as azathioprine and biologics. Patients recording medical encounters in the endoscopy suite might better recall postprocedure instructions, including recommended follow-up intervals and risks of postendoscopy complications. In this era of shared decision-making and patient-centered care, optimizing both physician delivery and patient understanding and recall of essential medical information is of critical importance.
Finally, although adoption of the above practices would serve the dual goals of enhancing patient-provider communication and mitigating legal risk, certain system interventions may further minimize the risk of covert recording. For instance, endoscopy units can store patients’ personal effects, including electronic devices, in a locker outside the endoscopy room rather than on the gurney. Retrieving patient belongings before postprocedure instructions are delivered would protect the patient’s ability to record this advice for future recall.
Conclusions
Recording by patients of clinical encounters, whether covert or overt, has become increasingly common as a result of the digital revolution. These recordings most often represent an attempt by the patient to gain more information relevant to their medical care. Rather than being threatened by this new reality, gastroenterologists should consider embracing this practice as an opportunity to enhance effective communication with patients, encourage shared decision making, and deliver truly patient-centered care.
Acknowledgments
This article is intended as general commentary and should not be interpreted as legal advice applicable to individual circumstances. Do not act or rely on information contained in this article without first seeking the advice of a personal attorney.
References
1. Washington Post. (2015 June 24). Audio: Anesthesiologist trashes sedated patient. Available at: https://youtu.be/Kar52idHgho. Accessed May 15, 2016.
2. Tsulukidze, M., Grande, S.W., Thompson, R., et al. Patients covertly recording clinical encounters: threat or opportunity? A qualitative analysis of online texts. PLoS One. 2015;10:e0125824.
3. Rodriguez, M., Morrow, J., Selfi, A. Ethical implications of patients and families secretly recording conversations with physicians. JAMA. 2015;313(16):1615-6.
4. Elwyn, G., Barr, P.J., Grande, S.W. Patients recording clinical encounters: a path to empowerment? Assessment by mixed methods. BMJ Open. 2015;5(8):e008566.
5. 18 U.S.C. §2511(2)(d).
6. VA Code §19.2-62.
7. Cal. Penal Code §632.
8. Fla. Stat. Ann. §934.03(3)(d).
9. Truog, R.D. Patients and doctors: the evolution of a relationship. N Engl J Med. 2012;366:581-5.
10. Barry, M.J., Edgman-Levitan, S. Shared decision making: the pinnacle of patient-centered care. N Engl J Med. 2012;366:780-1.
11. Pescosolido, B.A., Tuch, S.A., Martin, J.K. The profession of medicine and the public: examining Americans’ changing confidence in physician authority from the beginning of the ‘health care crisis’ to the era of health care reform. J Health Social Behavior. 2001;42(1):1-16.
12. Wisconsin Assembly Bill 255. (2015). Available at: https://docs.legis.wisconsin.gov/2015/proposals/ab255. Accessed June 29, 2016.
13. National Institute for Health and Clinical Excellence. (2012 Feb). Patient experience in adult NHS services: improving the experience of care for people using adult NHS service. Available at: https://www.nice.org.uk/guidance/cg138/chapter/1-guidance. Accessed June 29, 2016.
14. American Medical Association Code of Medical Ethics, Opinion 5.045 - Filming Patients in Health Care Settings. Updated June 2006. Available at: http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion5045.page? Accessed June 29, 2016.
15. Aultman, J.M. When humor in the hospital is no laughing matter. J Clin Ethics. 2009;20:227-35.
15. Sobel, R.K. Does laughter make good medicine? N Engl J Med. 2006;354:1114-5.
Dr. Adams is a clinical lecturer in the division of gastroenterology, University of Michigan, Ann Arbor, an investigator with the VA Center for Clinical Management Research, a staff physician in the VA Ann Arbor Healthcare System, and a member of the Institute for Healthcare Policy and Innovation, Ann Arbor. She has no conflicts of interest.
Last year, while sedated for colonoscopy, a patient covertly recorded conversations between endoscopy staff and providers. Comments about the patient were egregious and resulted in loss of employment for those involved and a large financial settlement. The reality of today’s world is that we all are subject to constant (real or potential) surveillance. Nothing is private and nothing recorded is temporary, yet physicians value private conversations with our patients. When a patient records a visit, either covertly or overtly, most physicians pause and have some emotional reaction (either positive or negative). Some welcome the ability to communicate accurately to a wider audience, while others believe the act of recording violates an interpersonal bond. In this month’s issue, Dr. Adams discusses the legal and ethical ramifications when a patient records our clinical interactions. She offers an excellent analysis and practical risk management strategies. Personally, I follow my wife’s dictum to act as if I am always on camera.
John I. Allen, MD, MBA, AGAF
Editor in Chief
Patients and physicians were collectively horrified last year when news broke of a Virginia man who recorded conversations between his gastroenterologist, his anesthesiologist, and other endoscopy unit staff, including a number of disparaging remarks about the patient, while sedated for his colonoscopy. Among other objectionable comments, providers mocked the patient for being demanding in the preprocedure area and for the amount of sedation he required, made comments implying that he had syphilis or tuberculosis, and discussed avoiding the patient following the procedure via an urgent “fake page.”1 The patient sued, resulting in a $500,000 judgment against the anesthesiologist for defamation and malpractice, including punitive damages. Although this case clearly represents an extreme example of unprofessional behavior, it also raises thought-provoking questions regarding the evolving relationship between patients and their physicians, as well as the legal and ethical implications of covert recording that deserve further discussion.
This article reviews the current state of knowledge regarding the frequency of and motivation for covert patient recording of medical encounters, and the legal and ethical principles informing this area. It concludes by proposing several strategies gastroenterologists can use to mitigate risk of liability while also preserving the patient-physician relationship and upholding professional autonomy.
Weighing the benefits and harms of patient electronic recording
Patient recording of medical encounters, whether covert or overt, presents both benefits and risks of harm. Theoretically, recording medical encounters could assist patients in remembering and/or better understanding recommendations provided by their physicians. It may also secondarily improve patient compliance and overall engagement in medical care and help patients accurately communicate recommendations to family members and other caregivers who are not immediately available during the clinical encounter. Patients may also view these recordings as a mechanism for empowerment, allowing them to shift the power dynamic between patient and provider.2,3 However, there is also the potential for recorded comments to be taken out of context or misinterpreted, leading to confusion on the part of the patient or family. Overt recording of medical encounters also may alter physician decision-making, leading to more aggressive testing and expense for the patient and the healthcare system. Even worse, covert recording of medical encounters (if discovered) may irreparably harm the physician-patient relationship by introducing distrust and causing the physician to take a more defensive posture in subsequent dealings with a given patient.
Recent research has shed new light on the potential frequency of patient covert recording of medical encounters, suggesting that it is alarmingly common. In a mixed-methods study of 130 patients in the United Kingdom who were recruited via radio and social media, 15% of respondents indicated that they had secretly recorded a clinical encounter, and an additional 11% personally knew someone who had covertly recorded.4 Those who reported having covertly recorded were significantly more likely to be less educated and male than those who had not. An additional 35% of respondents indicated that they would consider covertly recording a clinical encounter in the future. Although the generalizability of these results may be challenged based on the potential for sampling bias, the results suggest a shifting paradigm in the way in which patients view the physician-patient relationship and a fundamental breakdown in communication and erosion of trust.
The underlying motivations for patient recording of medical encounters are complex and multifaceted. These recordings seem to be a relatively new phenomenon and one that elicits strong reactions, positive and negative, on the part of patients, physicians, and society.2 Qualitative studies reveal that, whether covertly or overtly recording, most patients are driven by a common desire to replay, relisten, and/or share the recording with family, friends, and other caregivers.4 Indeed, the patient involved in the previously mentioned litigation purportedly intended to record the postcolonoscopy discharge instructions from his gastroenterologist, only to later discover much more. Patients who record covertly report being motivated by a fear of being denied permission to record or by prior experiences of poor quality care and the prospect of gathering verifiable evidence to support their experience. In contrast, patients who ask permission to record seem to be motivated primarily by a desire to preserve or enhance the physician-patient relationship.4 These insights are valuable in that they allow clinicians to view medical encounters from the perspective of patients, understand the power-dynamics at play, and ultimately, use this information to enlighten future care.
Legal guidance: “One-party” versus “all-party” consent
Although the prospect of covert patient recording may be unsettling to physicians, is it illegal? Because of a paucity of legal precedent in this area, the legal landscape is rather murky. Through the provisions of the Electronic Communications Privacy Act, federal law prohibits the interception and disclosure of wire, oral, or electronic communications without specific consent of at least one party to the conversation.5 This so-called “one-party” consent standard affords a baseline level of legal protection. A handful of states offer additional protection under state law by requiring all parties to the conversation to consent to the recording (so-called “all-party” consent). Virginia, where the audio recording of the previously mentioned colonoscopy took place, is a “one-party” consent state.6 In contrast, states such as California and Florida have adopted an “all-party” consent rule.7,8
However, uncertainty remains. For instance, if medical providers have a conversation in the same room as a sedated patient during a medical procedure on that patient, is the patient a “party” to the conversation? Furthermore, can such a conversation be considered private when held in front of a patient during a medical procedure? Is the patient in such a scenario “eavesdropping”? Given a lack of legal precedent in the form of case law and given the unique features of each clinical scenario, this is likely to remain an area of significant legal ambiguity. Although the possibility of covert patient recording may be unnerving for providers, the reality is that, in most cases, it is likely legally permissible.
Ethical principles: Navigating an evolving physician-patient relationship
The relationship between physician and patient, a core aspect of medical ethics, has evolved markedly over time. This relationship was historically paternalistic: The patient was seen to be dependent on the physician’s professional authority in determining the appropriateness of care, and patient’s preferences were seen as secondary to physician judgment. In recent years, however, the physician-patient relationship has evolved toward one privileging patient-centered care and shared decision-making based on a patient’s unique values, beliefs, and preferences.9,10
Concomitantly, the public’s view of doctoring has transitioned from “unquestioning acceptance of physician authority to a more ‘consumerist’ view accompanied by a questioning and bargaining approach to medicine, physicians and the medical encounter,” according to a 2001 study published in the Journal of Health and Social Behavior.11 In this context, many patients, attorneys, bioethicists, and patient advocates see patient recording of medical encounters as a legitimate check on the health care system, ensuring transparency and honesty and empowering patients to become more active participants in their medical care.2
Policy responses
Although recognition of patient recording of medical encounters has been growing, there have been few direct policy responses to date. One notable example was an effort by Wisconsin legislators in 2015 to mandate that any place where surgery is performed (including hospitals, ambulatory surgical centers, and other sites) offer patients the option to have their procedure videotaped and audiotaped.12 The proposed legislation was written broadly enough to include locations where gastroenterologists perform routine endoscopic procedures under sedation. Recordings would have been treated as part of the patient’s health care record and been admissible as evidence in subsequent legal proceedings relating to the medical care provided. Although this bill ultimately failed to pass pursuant to a Joint Resolution in the Wisconsin Senate in April 2016, it is a poignant example of the possible policy actions that may govern this area in the future.
In 2012, the National Institute for Health and Clinical Excellence, England, issued a guidance document focused on improving the patient care experience, which recommends that clinicians routinely ask patients if they would like to take notes and/or record the clinical encounter.13 Although not explicitly referencing covert recording, this guidance effectively aims to promote increased transparency by openly encouraging recording as a component of optimal medical practice. Although the American Medical Association Code of Ethics offers guidance regarding physicians recording patient encounters, it does not comment on patient-initiated recordings.14
Risk management strategies for gastroenterology providers
So, how can gastroenterologists and other providers protect themselves in a world of covert recording, while also preserving their relationships with patients and optimizing medical care? First, despite their harried days and varied responsibilities, gastroenterologists must recognize the possibility of covert recording and seek to maintain professionalism in all clinical environments, whether in an examination room or in an endoscopy suite with a sedated patient. Physicians set the tone for the entire team and also have an obligation to intervene if other members of the medical team are not adhering to professional standards. Although physicians and other medical providers often use cynical and derogatory humor as a coping mechanism given the heavy workload and amplified stressors of the clinical environment, it is important to be mindful of how such comments are perceived by patient bystanders.15,16 Although achieving a robust therapeutic alliance with a patient can take months, this trust can be easily broken by a single flippant remark by the physician.
Second, rather than assuming a defensive posture driven by fear of medical liability, it is vital for gastroenterologists to directly confront situations in which covert recording is suspected while also preserving the physician-patient relationship. In fact, by openly encouraging patient recording as a matter of routine practice, gastroenterologists can promote an environment of trust and transparency and bolster the therapeutic alliance between patient and provider.15 This approach also encourages providers to hone their communication skills and ensure they are communicating essential medical information clearly and succinctly and conveying medical nuance where appropriate. For example, in a clinic setting, a patient with inflammatory bowel disease who records might better remember or understand the risks and benefits of various treatment strategies and the common side effects of medications such as azathioprine and biologics. Patients recording medical encounters in the endoscopy suite might better recall postprocedure instructions, including recommended follow-up intervals and risks of postendoscopy complications. In this era of shared decision-making and patient-centered care, optimizing both physician delivery and patient understanding and recall of essential medical information is of critical importance.
Finally, although adoption of the above practices would serve the dual goals of enhancing patient-provider communication and mitigating legal risk, certain system interventions may further minimize the risk of covert recording. For instance, endoscopy units can store patients’ personal effects, including electronic devices, in a locker outside the endoscopy room rather than on the gurney. Retrieving patient belongings before postprocedure instructions are delivered would protect the patient’s ability to record this advice for future recall.
Conclusions
Recording by patients of clinical encounters, whether covert or overt, has become increasingly common as a result of the digital revolution. These recordings most often represent an attempt by the patient to gain more information relevant to their medical care. Rather than being threatened by this new reality, gastroenterologists should consider embracing this practice as an opportunity to enhance effective communication with patients, encourage shared decision making, and deliver truly patient-centered care.
Acknowledgments
This article is intended as general commentary and should not be interpreted as legal advice applicable to individual circumstances. Do not act or rely on information contained in this article without first seeking the advice of a personal attorney.
References
1. Washington Post. (2015 June 24). Audio: Anesthesiologist trashes sedated patient. Available at: https://youtu.be/Kar52idHgho. Accessed May 15, 2016.
2. Tsulukidze, M., Grande, S.W., Thompson, R., et al. Patients covertly recording clinical encounters: threat or opportunity? A qualitative analysis of online texts. PLoS One. 2015;10:e0125824.
3. Rodriguez, M., Morrow, J., Selfi, A. Ethical implications of patients and families secretly recording conversations with physicians. JAMA. 2015;313(16):1615-6.
4. Elwyn, G., Barr, P.J., Grande, S.W. Patients recording clinical encounters: a path to empowerment? Assessment by mixed methods. BMJ Open. 2015;5(8):e008566.
5. 18 U.S.C. §2511(2)(d).
6. VA Code §19.2-62.
7. Cal. Penal Code §632.
8. Fla. Stat. Ann. §934.03(3)(d).
9. Truog, R.D. Patients and doctors: the evolution of a relationship. N Engl J Med. 2012;366:581-5.
10. Barry, M.J., Edgman-Levitan, S. Shared decision making: the pinnacle of patient-centered care. N Engl J Med. 2012;366:780-1.
11. Pescosolido, B.A., Tuch, S.A., Martin, J.K. The profession of medicine and the public: examining Americans’ changing confidence in physician authority from the beginning of the ‘health care crisis’ to the era of health care reform. J Health Social Behavior. 2001;42(1):1-16.
12. Wisconsin Assembly Bill 255. (2015). Available at: https://docs.legis.wisconsin.gov/2015/proposals/ab255. Accessed June 29, 2016.
13. National Institute for Health and Clinical Excellence. (2012 Feb). Patient experience in adult NHS services: improving the experience of care for people using adult NHS service. Available at: https://www.nice.org.uk/guidance/cg138/chapter/1-guidance. Accessed June 29, 2016.
14. American Medical Association Code of Medical Ethics, Opinion 5.045 - Filming Patients in Health Care Settings. Updated June 2006. Available at: http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion5045.page? Accessed June 29, 2016.
15. Aultman, J.M. When humor in the hospital is no laughing matter. J Clin Ethics. 2009;20:227-35.
15. Sobel, R.K. Does laughter make good medicine? N Engl J Med. 2006;354:1114-5.
Dr. Adams is a clinical lecturer in the division of gastroenterology, University of Michigan, Ann Arbor, an investigator with the VA Center for Clinical Management Research, a staff physician in the VA Ann Arbor Healthcare System, and a member of the Institute for Healthcare Policy and Innovation, Ann Arbor. She has no conflicts of interest.
Long-acting growth hormone moves forward based on positive phase II data
ORLANDO – An extended-release human growth hormone formulation proved safe and effective in both children and adults, offering the prospect of a less-rigorous dosing schedule and potentially better patient compliance with treatment.
The two phase II studies examined somavaratan, which is being developed by Versartis of Menlo Park, Calif. Kevin Yuen, MD, an endocrinologist at the Swedish Medical Center, Seattle, and Wayne V. Moore, MD, a pediatric endocrinologist at Children’s Mercy Hospital, Kansas City, Mo., presented the data at the annual meeting of the Endocrine Society.
“Despite the fact that human growth hormone is a proven treatment for growth hormone deficiency, daily use of our current formulations can be a factor that affects compliance,” said Dr. Yuen. He cited a 2008 study of 158 men taking growth hormone, which found that only one-third were highly compliant (Endocr Pract. 2008 Mar;14[2]:143-54). “And even among this group, there were 21 doses missed over just a 3-month period.”
The group of 55 international experts described several strategies for creating long-acting growth hormone formulations, including depot formulations, pegylation, prodrugs, noncovalent albumin binding growth hormone compounds, and growth hormone fusion proteins. These preparations are currently in various stages of development, with some already approved in Europe and Asia.
Somavaratan (VRS-317) is a fusion protein produced in Escherichia coli. The active portion is recombinant human growth hormone, which is bound to long chains of hydrophilic amino acids. This reduces renal filtration, Dr. Yuen said. The growth hormone loses some potency in this construct, but its delayed clearance, with a half-life 30-60 times longer than recombinant human growth hormone (rhGH) allows it to exert a prolonged effect in target tissue.
Of the two phase II studies of the molecule, one was conducted in 64 prepubertal children who were naive to any growth hormone treatment, and one in 36 adults with adult-onset growth hormone deficiency. The company also has made these presentations available online.
The pediatric study reported 3-year data on the cohort, which began treatment of children at a mean age of 7 years. At baseline, the children were about 2.6 standard deviations (SDs) below their expected height, and their mean IGF-1 levels, about 1.7 SDs below. They showed a mean maximum stimulated growth hormone level of 5.4 ng/mL. Although they were a mean of 7.8 years chronologically at the study’s outset, their mean bone age was 6.4 years.
The first 12 months of the study consisted of dose-ranging trials, with initial doses of 5 mg/kg each month, then 2.5 mg/kg twice a month, and then 1.15 mg/kg weekly. During the last 2 years of the study, all children were taking 3.5 mg/kg, once a month.
Within the first year, all children taking the 3.5-mg/kg dose had achieved normal IGF-1 levels, which were consistent with levels achieved in the ANSWER registry dataset of somatropin (rDNA origin) injection (Norditropin) recombinant human growth hormone (Clin Epidemiol. 2013;5:119-27).
Height velocity improved, as did height standard deviation. By year 3, patients were a mean of 1.25 SDs below expected height – a significant improvement over baseline. These findings were almost superimposable with those in the ANSWER registry. Bone age and chronological age came into alignment within the first year and that association was maintained throughout the study – again, in almost superimposable curves with the registry data.
Somavaratan exerted no untoward metabolic effects. There were no adverse changes in body mass index. At baseline, the mean hemoglobin A1c was 5.2%; this was unchanged at 3 years. No patient developed diabetes. The most commonly reported adverse event was injection site pain (48%). Injection site erythema was reported in 5% of patients, but no injection site nodules occurred.
Other adverse events were headache, extremity pain, arthralgia, and musculoskeletal pain. Although the numbers were small overall, reports did increase after all the children were switched to the 3.5-mg/kg dose. However, they occurred in 5% or less of the patient group. There were no withdrawals due to adverse events.
The second trial was a dose-ranging study conducted in 49 adults aged 23-70 years. They all had been diagnosed with adult-onset growth hormone deficiency, but had stable pituitary function. If they were on any growth hormone therapy, they underwent a 14-day washout period.
The subjects were divided and dosed by age and gender. All subjects received one injection per month for 5 months.
Cohort A comprised 21 men and women aged 35 years or older, who took 0.6 mg/kg per month. Cohort B comprised six men and women younger than 35 years, who took 0.8 mg/kg per month. Cohort C comprised eight women taking oral estrogen contraceptives. These women received 1 mg/kg per month.
The cohorts were similar in body mass index and weight, but they did differ significantly in baseline IGF-1 levels. In cohort A, the level was 0.52 SDs below normal. In cohort B, it was 2.89 SDs below normal, and in cohort C, it was 2.29 SDs below.
Overall, somavaratan induced a rapid and dramatic increase in IGF-1 that tailed off over 30 days. By day 8 after injection, IGF-1 had risen from a mean baseline of -1 SDs to more than 2 SDs above. By day 22, it had returned to baseline levels. The response to the fifth injection was identical to that of the first, Dr. Yuen said.
Response varied somewhat by cohort, with the younger, mixed-gender group responding the most dramatically, with a mean increase of about 4 SDs from baseline. This put the group above the maximum response target of 1.5 SDs.
The older, mixed-gender cohort experienced about a 3 SDs increase – also above the target level. The women taking estrogen experienced the flattest response, gaining about 2 SDs. However, the response curve was nearly identical, with a rapid, sharp increase in IGF-1 within the first week, followed by a gradual decline to baseline by 22 days.
The adverse event profile was not quite as benign as it was in the pediatric study. Virtually all patients experienced at least one adverse event. A third were mild and 58% moderate. The rest were serious, with one severe and one life-threatening event. Dr. Yuen did not discuss adverse events; these were, however, included in supplementary slides available on the Versartis Inc. slide set.
The finding of a predictable, 3-week tailing-off of efficacy, combined with the fact that patients responded so dramatically, exceeding the maximum target of a 1.5 SDs increase in IGF-1, has prompted a new dosing protocol for the somavaratan open-label extension study, which includes all the phase II completers, plus an additional 40 adult patients.
Doses will be titrated to each subject’s individual IGF-1 responses, based on the IGF-I level 7 days post dose until a maintenance dose is reached. Subjects receiving somavaratan in a previous somavaratan study will have their dose decreased by half (minimum dose of 20 mg, or 40 mg for women on estrogen).
Dr. Yuen is a member of the Versartis advisory board. Dr. Moore has received research support from the company.
[email protected]
On Twitter @Alz_Gal
ORLANDO – An extended-release human growth hormone formulation proved safe and effective in both children and adults, offering the prospect of a less-rigorous dosing schedule and potentially better patient compliance with treatment.
The two phase II studies examined somavaratan, which is being developed by Versartis of Menlo Park, Calif. Kevin Yuen, MD, an endocrinologist at the Swedish Medical Center, Seattle, and Wayne V. Moore, MD, a pediatric endocrinologist at Children’s Mercy Hospital, Kansas City, Mo., presented the data at the annual meeting of the Endocrine Society.
“Despite the fact that human growth hormone is a proven treatment for growth hormone deficiency, daily use of our current formulations can be a factor that affects compliance,” said Dr. Yuen. He cited a 2008 study of 158 men taking growth hormone, which found that only one-third were highly compliant (Endocr Pract. 2008 Mar;14[2]:143-54). “And even among this group, there were 21 doses missed over just a 3-month period.”
The group of 55 international experts described several strategies for creating long-acting growth hormone formulations, including depot formulations, pegylation, prodrugs, noncovalent albumin binding growth hormone compounds, and growth hormone fusion proteins. These preparations are currently in various stages of development, with some already approved in Europe and Asia.
Somavaratan (VRS-317) is a fusion protein produced in Escherichia coli. The active portion is recombinant human growth hormone, which is bound to long chains of hydrophilic amino acids. This reduces renal filtration, Dr. Yuen said. The growth hormone loses some potency in this construct, but its delayed clearance, with a half-life 30-60 times longer than recombinant human growth hormone (rhGH) allows it to exert a prolonged effect in target tissue.
Of the two phase II studies of the molecule, one was conducted in 64 prepubertal children who were naive to any growth hormone treatment, and one in 36 adults with adult-onset growth hormone deficiency. The company also has made these presentations available online.
The pediatric study reported 3-year data on the cohort, which began treatment of children at a mean age of 7 years. At baseline, the children were about 2.6 standard deviations (SDs) below their expected height, and their mean IGF-1 levels, about 1.7 SDs below. They showed a mean maximum stimulated growth hormone level of 5.4 ng/mL. Although they were a mean of 7.8 years chronologically at the study’s outset, their mean bone age was 6.4 years.
The first 12 months of the study consisted of dose-ranging trials, with initial doses of 5 mg/kg each month, then 2.5 mg/kg twice a month, and then 1.15 mg/kg weekly. During the last 2 years of the study, all children were taking 3.5 mg/kg, once a month.
Within the first year, all children taking the 3.5-mg/kg dose had achieved normal IGF-1 levels, which were consistent with levels achieved in the ANSWER registry dataset of somatropin (rDNA origin) injection (Norditropin) recombinant human growth hormone (Clin Epidemiol. 2013;5:119-27).
Height velocity improved, as did height standard deviation. By year 3, patients were a mean of 1.25 SDs below expected height – a significant improvement over baseline. These findings were almost superimposable with those in the ANSWER registry. Bone age and chronological age came into alignment within the first year and that association was maintained throughout the study – again, in almost superimposable curves with the registry data.
Somavaratan exerted no untoward metabolic effects. There were no adverse changes in body mass index. At baseline, the mean hemoglobin A1c was 5.2%; this was unchanged at 3 years. No patient developed diabetes. The most commonly reported adverse event was injection site pain (48%). Injection site erythema was reported in 5% of patients, but no injection site nodules occurred.
Other adverse events were headache, extremity pain, arthralgia, and musculoskeletal pain. Although the numbers were small overall, reports did increase after all the children were switched to the 3.5-mg/kg dose. However, they occurred in 5% or less of the patient group. There were no withdrawals due to adverse events.
The second trial was a dose-ranging study conducted in 49 adults aged 23-70 years. They all had been diagnosed with adult-onset growth hormone deficiency, but had stable pituitary function. If they were on any growth hormone therapy, they underwent a 14-day washout period.
The subjects were divided and dosed by age and gender. All subjects received one injection per month for 5 months.
Cohort A comprised 21 men and women aged 35 years or older, who took 0.6 mg/kg per month. Cohort B comprised six men and women younger than 35 years, who took 0.8 mg/kg per month. Cohort C comprised eight women taking oral estrogen contraceptives. These women received 1 mg/kg per month.
The cohorts were similar in body mass index and weight, but they did differ significantly in baseline IGF-1 levels. In cohort A, the level was 0.52 SDs below normal. In cohort B, it was 2.89 SDs below normal, and in cohort C, it was 2.29 SDs below.
Overall, somavaratan induced a rapid and dramatic increase in IGF-1 that tailed off over 30 days. By day 8 after injection, IGF-1 had risen from a mean baseline of -1 SDs to more than 2 SDs above. By day 22, it had returned to baseline levels. The response to the fifth injection was identical to that of the first, Dr. Yuen said.
Response varied somewhat by cohort, with the younger, mixed-gender group responding the most dramatically, with a mean increase of about 4 SDs from baseline. This put the group above the maximum response target of 1.5 SDs.
The older, mixed-gender cohort experienced about a 3 SDs increase – also above the target level. The women taking estrogen experienced the flattest response, gaining about 2 SDs. However, the response curve was nearly identical, with a rapid, sharp increase in IGF-1 within the first week, followed by a gradual decline to baseline by 22 days.
The adverse event profile was not quite as benign as it was in the pediatric study. Virtually all patients experienced at least one adverse event. A third were mild and 58% moderate. The rest were serious, with one severe and one life-threatening event. Dr. Yuen did not discuss adverse events; these were, however, included in supplementary slides available on the Versartis Inc. slide set.
The finding of a predictable, 3-week tailing-off of efficacy, combined with the fact that patients responded so dramatically, exceeding the maximum target of a 1.5 SDs increase in IGF-1, has prompted a new dosing protocol for the somavaratan open-label extension study, which includes all the phase II completers, plus an additional 40 adult patients.
Doses will be titrated to each subject’s individual IGF-1 responses, based on the IGF-I level 7 days post dose until a maintenance dose is reached. Subjects receiving somavaratan in a previous somavaratan study will have their dose decreased by half (minimum dose of 20 mg, or 40 mg for women on estrogen).
Dr. Yuen is a member of the Versartis advisory board. Dr. Moore has received research support from the company.
[email protected]
On Twitter @Alz_Gal
ORLANDO – An extended-release human growth hormone formulation proved safe and effective in both children and adults, offering the prospect of a less-rigorous dosing schedule and potentially better patient compliance with treatment.
The two phase II studies examined somavaratan, which is being developed by Versartis of Menlo Park, Calif. Kevin Yuen, MD, an endocrinologist at the Swedish Medical Center, Seattle, and Wayne V. Moore, MD, a pediatric endocrinologist at Children’s Mercy Hospital, Kansas City, Mo., presented the data at the annual meeting of the Endocrine Society.
“Despite the fact that human growth hormone is a proven treatment for growth hormone deficiency, daily use of our current formulations can be a factor that affects compliance,” said Dr. Yuen. He cited a 2008 study of 158 men taking growth hormone, which found that only one-third were highly compliant (Endocr Pract. 2008 Mar;14[2]:143-54). “And even among this group, there were 21 doses missed over just a 3-month period.”
The group of 55 international experts described several strategies for creating long-acting growth hormone formulations, including depot formulations, pegylation, prodrugs, noncovalent albumin binding growth hormone compounds, and growth hormone fusion proteins. These preparations are currently in various stages of development, with some already approved in Europe and Asia.
Somavaratan (VRS-317) is a fusion protein produced in Escherichia coli. The active portion is recombinant human growth hormone, which is bound to long chains of hydrophilic amino acids. This reduces renal filtration, Dr. Yuen said. The growth hormone loses some potency in this construct, but its delayed clearance, with a half-life 30-60 times longer than recombinant human growth hormone (rhGH) allows it to exert a prolonged effect in target tissue.
Of the two phase II studies of the molecule, one was conducted in 64 prepubertal children who were naive to any growth hormone treatment, and one in 36 adults with adult-onset growth hormone deficiency. The company also has made these presentations available online.
The pediatric study reported 3-year data on the cohort, which began treatment of children at a mean age of 7 years. At baseline, the children were about 2.6 standard deviations (SDs) below their expected height, and their mean IGF-1 levels, about 1.7 SDs below. They showed a mean maximum stimulated growth hormone level of 5.4 ng/mL. Although they were a mean of 7.8 years chronologically at the study’s outset, their mean bone age was 6.4 years.
The first 12 months of the study consisted of dose-ranging trials, with initial doses of 5 mg/kg each month, then 2.5 mg/kg twice a month, and then 1.15 mg/kg weekly. During the last 2 years of the study, all children were taking 3.5 mg/kg, once a month.
Within the first year, all children taking the 3.5-mg/kg dose had achieved normal IGF-1 levels, which were consistent with levels achieved in the ANSWER registry dataset of somatropin (rDNA origin) injection (Norditropin) recombinant human growth hormone (Clin Epidemiol. 2013;5:119-27).
Height velocity improved, as did height standard deviation. By year 3, patients were a mean of 1.25 SDs below expected height – a significant improvement over baseline. These findings were almost superimposable with those in the ANSWER registry. Bone age and chronological age came into alignment within the first year and that association was maintained throughout the study – again, in almost superimposable curves with the registry data.
Somavaratan exerted no untoward metabolic effects. There were no adverse changes in body mass index. At baseline, the mean hemoglobin A1c was 5.2%; this was unchanged at 3 years. No patient developed diabetes. The most commonly reported adverse event was injection site pain (48%). Injection site erythema was reported in 5% of patients, but no injection site nodules occurred.
Other adverse events were headache, extremity pain, arthralgia, and musculoskeletal pain. Although the numbers were small overall, reports did increase after all the children were switched to the 3.5-mg/kg dose. However, they occurred in 5% or less of the patient group. There were no withdrawals due to adverse events.
The second trial was a dose-ranging study conducted in 49 adults aged 23-70 years. They all had been diagnosed with adult-onset growth hormone deficiency, but had stable pituitary function. If they were on any growth hormone therapy, they underwent a 14-day washout period.
The subjects were divided and dosed by age and gender. All subjects received one injection per month for 5 months.
Cohort A comprised 21 men and women aged 35 years or older, who took 0.6 mg/kg per month. Cohort B comprised six men and women younger than 35 years, who took 0.8 mg/kg per month. Cohort C comprised eight women taking oral estrogen contraceptives. These women received 1 mg/kg per month.
The cohorts were similar in body mass index and weight, but they did differ significantly in baseline IGF-1 levels. In cohort A, the level was 0.52 SDs below normal. In cohort B, it was 2.89 SDs below normal, and in cohort C, it was 2.29 SDs below.
Overall, somavaratan induced a rapid and dramatic increase in IGF-1 that tailed off over 30 days. By day 8 after injection, IGF-1 had risen from a mean baseline of -1 SDs to more than 2 SDs above. By day 22, it had returned to baseline levels. The response to the fifth injection was identical to that of the first, Dr. Yuen said.
Response varied somewhat by cohort, with the younger, mixed-gender group responding the most dramatically, with a mean increase of about 4 SDs from baseline. This put the group above the maximum response target of 1.5 SDs.
The older, mixed-gender cohort experienced about a 3 SDs increase – also above the target level. The women taking estrogen experienced the flattest response, gaining about 2 SDs. However, the response curve was nearly identical, with a rapid, sharp increase in IGF-1 within the first week, followed by a gradual decline to baseline by 22 days.
The adverse event profile was not quite as benign as it was in the pediatric study. Virtually all patients experienced at least one adverse event. A third were mild and 58% moderate. The rest were serious, with one severe and one life-threatening event. Dr. Yuen did not discuss adverse events; these were, however, included in supplementary slides available on the Versartis Inc. slide set.
The finding of a predictable, 3-week tailing-off of efficacy, combined with the fact that patients responded so dramatically, exceeding the maximum target of a 1.5 SDs increase in IGF-1, has prompted a new dosing protocol for the somavaratan open-label extension study, which includes all the phase II completers, plus an additional 40 adult patients.
Doses will be titrated to each subject’s individual IGF-1 responses, based on the IGF-I level 7 days post dose until a maintenance dose is reached. Subjects receiving somavaratan in a previous somavaratan study will have their dose decreased by half (minimum dose of 20 mg, or 40 mg for women on estrogen).
Dr. Yuen is a member of the Versartis advisory board. Dr. Moore has received research support from the company.
[email protected]
On Twitter @Alz_Gal
AT ENDO 2017
Key clinical point:
Major finding: In the 64-patient pediatric study, the molecule raised growth velocity and IGF-1 levels by several standard deviations. In the 48-patient adult study, it raised IGF-1 levels by up to 4 standard deviations.
Data source: A 64-patient pediatric dose-ranging study and a 48-patient adult study.
Disclosures: Versartis sponsored the studies. Dr. Yuen is on the company’s advisory board. Dr. Moore has received research support from the company.
Hard road disproving that statins make you dumb
The impact of lipid-lowering drugs on patients’ mental states was on the minds of many attendees at the American College of Cardiology’s annual meeting in March.
The highest-profile report came from EBBINGHAUS (Evaluating PCSK9 Binding Antibody Influence on Cognitive Health in High Cardiovascular Risk Subjects), a substudy of the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial, the meeting’s blockbuster. For the first time, it proved that profoundly lowering low density lipoprotein cholesterol with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab led to a significant reduction in adverse clinical events. EBBINGHAUS focused on about 2,000 of the 27,000 FOURIER patients and subjected equal numbers of placebo and evolocumab patients to a battery of cognitive and memory tests over a median of 20 months. The results showed no hint of a decrement in brain function in the patients taking evolocumab, compared with either their baseline state or the controls who received placebo.
That perception wasn’t helped when, in 2012, the Food and Drug Administration required the labels of all statins to include a reference to postmarketing reports of cognitive side effects such as memory impairment and confusion. The current label for one statin says: “There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins.”
Following the FDA’s action, a series of analyses appeared that reviewed the evidence and found nothing to substantiate the concern. For example, a 2012 review done in direct response to the FDA labeling change looked at case reports, observational studies, and randomized trials and found “no convincing evidence for change in cognitive function” with statin use (J Am Coll Cardiol. 2012 Sept 4;60[10]:875-81). A 2015 meta-analysis that reviewed 14 studies with cognitive testing on more than 27,000 people randomized to either a statin or placebo also found no evidence for a statin effect on mental function (J Gen Intern Med. 2015 March;30[3]:348-58). “Given these results, it is questionable whether the FDA class warning about potential cognitive adverse effects of statins is still warranted,” the meta-analysis authors concluded.
Despite this, concerns about the impact of statins on cognition and memory linger for many patients, witness the anecdotal experiences of clinicians at the meeting. This led a team of researchers at the University of Connecticut and Hartford Hospital to try to directly address the controversy. They also reported their findings at the ACC meeting.
They ran their study as part of a larger trial, STOMP (Effect of Statins on Skeletal Muscle Function and Performance), which randomized 420 healthy and statin-naive individuals to 6 months of treatment with 80 mg atorvastatin or placebo (Circulation. 2013 Jan 2;127[1]:96-103). Their memory substudy included 66 people from the atorvastatin group and 84 placebo-treated controls who averaged 49 years old. Participants underwent a battery of eight memory, cognitive, attention, and executive function tests after 6 months on treatment and again 2 months after statin treatment stopped.
She and her associates took testing a step further and used an assessment never before applied to people taking statins. They ran functional MRIs on a subgroup of the participants while they took two additional memory tests at the end of 6 months on atorvastatin and again 2 months after atorvastatin stopped. They ran MRI scans during a figural memory task test on 42 placebo participants and 35 atorvastatin patients and during a Sternberg Task to test short-term memory on 68 people from the placebo group and 52 who received atorvastatin.
The functional MRI results showed some small but statistically significant changes during both tests in patterns of regional neural activation among those in the statin groups while on and off statins and also when compared with those who received placebo, but Dr. Taylor stressed that her group saw MRI differences between the statin and placebo subjects not only when people were on atorvastatin but also when they had been off the drug for 2 months. She also cautioned that “the clinical implications of the findings are unclear.”
Overall, the entire study’s results showed “no convincing evidence of measurable verbal or nonverbal memory dysfunction” linked with statin use, but Dr. Taylor also noted that the study was relatively small.
Proving the absence of a problem is always difficult. Adding Dr. Taylor’s new evidence to the case that statins really are safe when it comes to cognition and memory will undoubtedly fail to convince committed skeptics.
[email protected]
On Twitter @mitchelzoler
The impact of lipid-lowering drugs on patients’ mental states was on the minds of many attendees at the American College of Cardiology’s annual meeting in March.
The highest-profile report came from EBBINGHAUS (Evaluating PCSK9 Binding Antibody Influence on Cognitive Health in High Cardiovascular Risk Subjects), a substudy of the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial, the meeting’s blockbuster. For the first time, it proved that profoundly lowering low density lipoprotein cholesterol with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab led to a significant reduction in adverse clinical events. EBBINGHAUS focused on about 2,000 of the 27,000 FOURIER patients and subjected equal numbers of placebo and evolocumab patients to a battery of cognitive and memory tests over a median of 20 months. The results showed no hint of a decrement in brain function in the patients taking evolocumab, compared with either their baseline state or the controls who received placebo.
That perception wasn’t helped when, in 2012, the Food and Drug Administration required the labels of all statins to include a reference to postmarketing reports of cognitive side effects such as memory impairment and confusion. The current label for one statin says: “There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins.”
Following the FDA’s action, a series of analyses appeared that reviewed the evidence and found nothing to substantiate the concern. For example, a 2012 review done in direct response to the FDA labeling change looked at case reports, observational studies, and randomized trials and found “no convincing evidence for change in cognitive function” with statin use (J Am Coll Cardiol. 2012 Sept 4;60[10]:875-81). A 2015 meta-analysis that reviewed 14 studies with cognitive testing on more than 27,000 people randomized to either a statin or placebo also found no evidence for a statin effect on mental function (J Gen Intern Med. 2015 March;30[3]:348-58). “Given these results, it is questionable whether the FDA class warning about potential cognitive adverse effects of statins is still warranted,” the meta-analysis authors concluded.
Despite this, concerns about the impact of statins on cognition and memory linger for many patients, witness the anecdotal experiences of clinicians at the meeting. This led a team of researchers at the University of Connecticut and Hartford Hospital to try to directly address the controversy. They also reported their findings at the ACC meeting.
They ran their study as part of a larger trial, STOMP (Effect of Statins on Skeletal Muscle Function and Performance), which randomized 420 healthy and statin-naive individuals to 6 months of treatment with 80 mg atorvastatin or placebo (Circulation. 2013 Jan 2;127[1]:96-103). Their memory substudy included 66 people from the atorvastatin group and 84 placebo-treated controls who averaged 49 years old. Participants underwent a battery of eight memory, cognitive, attention, and executive function tests after 6 months on treatment and again 2 months after statin treatment stopped.
She and her associates took testing a step further and used an assessment never before applied to people taking statins. They ran functional MRIs on a subgroup of the participants while they took two additional memory tests at the end of 6 months on atorvastatin and again 2 months after atorvastatin stopped. They ran MRI scans during a figural memory task test on 42 placebo participants and 35 atorvastatin patients and during a Sternberg Task to test short-term memory on 68 people from the placebo group and 52 who received atorvastatin.
The functional MRI results showed some small but statistically significant changes during both tests in patterns of regional neural activation among those in the statin groups while on and off statins and also when compared with those who received placebo, but Dr. Taylor stressed that her group saw MRI differences between the statin and placebo subjects not only when people were on atorvastatin but also when they had been off the drug for 2 months. She also cautioned that “the clinical implications of the findings are unclear.”
Overall, the entire study’s results showed “no convincing evidence of measurable verbal or nonverbal memory dysfunction” linked with statin use, but Dr. Taylor also noted that the study was relatively small.
Proving the absence of a problem is always difficult. Adding Dr. Taylor’s new evidence to the case that statins really are safe when it comes to cognition and memory will undoubtedly fail to convince committed skeptics.
[email protected]
On Twitter @mitchelzoler
The impact of lipid-lowering drugs on patients’ mental states was on the minds of many attendees at the American College of Cardiology’s annual meeting in March.
The highest-profile report came from EBBINGHAUS (Evaluating PCSK9 Binding Antibody Influence on Cognitive Health in High Cardiovascular Risk Subjects), a substudy of the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial, the meeting’s blockbuster. For the first time, it proved that profoundly lowering low density lipoprotein cholesterol with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab led to a significant reduction in adverse clinical events. EBBINGHAUS focused on about 2,000 of the 27,000 FOURIER patients and subjected equal numbers of placebo and evolocumab patients to a battery of cognitive and memory tests over a median of 20 months. The results showed no hint of a decrement in brain function in the patients taking evolocumab, compared with either their baseline state or the controls who received placebo.
That perception wasn’t helped when, in 2012, the Food and Drug Administration required the labels of all statins to include a reference to postmarketing reports of cognitive side effects such as memory impairment and confusion. The current label for one statin says: “There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins.”
Following the FDA’s action, a series of analyses appeared that reviewed the evidence and found nothing to substantiate the concern. For example, a 2012 review done in direct response to the FDA labeling change looked at case reports, observational studies, and randomized trials and found “no convincing evidence for change in cognitive function” with statin use (J Am Coll Cardiol. 2012 Sept 4;60[10]:875-81). A 2015 meta-analysis that reviewed 14 studies with cognitive testing on more than 27,000 people randomized to either a statin or placebo also found no evidence for a statin effect on mental function (J Gen Intern Med. 2015 March;30[3]:348-58). “Given these results, it is questionable whether the FDA class warning about potential cognitive adverse effects of statins is still warranted,” the meta-analysis authors concluded.
Despite this, concerns about the impact of statins on cognition and memory linger for many patients, witness the anecdotal experiences of clinicians at the meeting. This led a team of researchers at the University of Connecticut and Hartford Hospital to try to directly address the controversy. They also reported their findings at the ACC meeting.
They ran their study as part of a larger trial, STOMP (Effect of Statins on Skeletal Muscle Function and Performance), which randomized 420 healthy and statin-naive individuals to 6 months of treatment with 80 mg atorvastatin or placebo (Circulation. 2013 Jan 2;127[1]:96-103). Their memory substudy included 66 people from the atorvastatin group and 84 placebo-treated controls who averaged 49 years old. Participants underwent a battery of eight memory, cognitive, attention, and executive function tests after 6 months on treatment and again 2 months after statin treatment stopped.
She and her associates took testing a step further and used an assessment never before applied to people taking statins. They ran functional MRIs on a subgroup of the participants while they took two additional memory tests at the end of 6 months on atorvastatin and again 2 months after atorvastatin stopped. They ran MRI scans during a figural memory task test on 42 placebo participants and 35 atorvastatin patients and during a Sternberg Task to test short-term memory on 68 people from the placebo group and 52 who received atorvastatin.
The functional MRI results showed some small but statistically significant changes during both tests in patterns of regional neural activation among those in the statin groups while on and off statins and also when compared with those who received placebo, but Dr. Taylor stressed that her group saw MRI differences between the statin and placebo subjects not only when people were on atorvastatin but also when they had been off the drug for 2 months. She also cautioned that “the clinical implications of the findings are unclear.”
Overall, the entire study’s results showed “no convincing evidence of measurable verbal or nonverbal memory dysfunction” linked with statin use, but Dr. Taylor also noted that the study was relatively small.
Proving the absence of a problem is always difficult. Adding Dr. Taylor’s new evidence to the case that statins really are safe when it comes to cognition and memory will undoubtedly fail to convince committed skeptics.
[email protected]
On Twitter @mitchelzoler
VA Secretary Shulkin Calls for New Powers to Fire VA Employees
Citing his inability to immediately remove a VA employee who was caught watching pornography while with a patient, VA Secretary David J. Shulkin, MD, has called on Congress to enact legislation that makes it easier and faster to remove employees at the VA. “This is an example of why we need accountability legislation as soon as possible,” Dr. Shulkin said in a statement. “It’s unacceptable that VA has to wait 30 days to act on a proposed removal.”
Currently, VA employees receive at least 30 days notice of firing, have a right to a grievance hearing, and must be paid throughout the final adjudication as long as there is no evidence of a crime. However, employees can be removed from patient interaction or placed on administrative leave.
In March, the House of Representatives passed the VA Accountability First Act of 2017 (HR 1259), which would reduce the advanced warning time to 10 days and speed up the appeals process, but the bill has yet to be considered by Senate. “This situation underscores the need for Congress to get VA accountability legislation to President Trump's desk, and I thank Secretary Shulkin for making this a top priority,” Rep. David P. “Phil” Roe, MD (R-Tenn.), chairman of the House Veterans’ Affairs Committee concurred. “I was proud my bill, the VA Accountability First Act of 2017, passed the House with bipartisan support earlier this month. Veterans deserve better. I encourage my Senate colleagues to consider my legislation, and I look forward to working with Secretary Shulkin to change the way VA does business.”
Despite the bipartisan support cited by Rep. Roe, many Democrats have indicated that they are wary of the bill because it strips VA civil servant employees of many employment protections. Ranking Democratic House committee on Veterans’ Affairs member Rep. Tim Walz (D-Minn) warned that the changes in employee protections in the bill make it less likely it will pass through the Senate and that it could face court challenges. “By refusing to compromise on the 1 percent of this legislation we disagree on, Republicans have made it harder to pass the 99 percent of the legislation that is vital to making improvements,” according to a report in Stars and Stripes.
Organizations that represent VA workers also have voiced opposition. The American Federation of Government Employees (AFGE), which represents 270,000 VA employees, also argued that the bill “would render useless” the process that providers use “to protect their voice at work and defend themselves against managers’ retaliation and discrimination.” In a letter to the House committee, AFGE argued that the bill, “weakens the critical protections that VA employees need to speak up against mismanagement and patient harm.”
Citing his inability to immediately remove a VA employee who was caught watching pornography while with a patient, VA Secretary David J. Shulkin, MD, has called on Congress to enact legislation that makes it easier and faster to remove employees at the VA. “This is an example of why we need accountability legislation as soon as possible,” Dr. Shulkin said in a statement. “It’s unacceptable that VA has to wait 30 days to act on a proposed removal.”
Currently, VA employees receive at least 30 days notice of firing, have a right to a grievance hearing, and must be paid throughout the final adjudication as long as there is no evidence of a crime. However, employees can be removed from patient interaction or placed on administrative leave.
In March, the House of Representatives passed the VA Accountability First Act of 2017 (HR 1259), which would reduce the advanced warning time to 10 days and speed up the appeals process, but the bill has yet to be considered by Senate. “This situation underscores the need for Congress to get VA accountability legislation to President Trump's desk, and I thank Secretary Shulkin for making this a top priority,” Rep. David P. “Phil” Roe, MD (R-Tenn.), chairman of the House Veterans’ Affairs Committee concurred. “I was proud my bill, the VA Accountability First Act of 2017, passed the House with bipartisan support earlier this month. Veterans deserve better. I encourage my Senate colleagues to consider my legislation, and I look forward to working with Secretary Shulkin to change the way VA does business.”
Despite the bipartisan support cited by Rep. Roe, many Democrats have indicated that they are wary of the bill because it strips VA civil servant employees of many employment protections. Ranking Democratic House committee on Veterans’ Affairs member Rep. Tim Walz (D-Minn) warned that the changes in employee protections in the bill make it less likely it will pass through the Senate and that it could face court challenges. “By refusing to compromise on the 1 percent of this legislation we disagree on, Republicans have made it harder to pass the 99 percent of the legislation that is vital to making improvements,” according to a report in Stars and Stripes.
Organizations that represent VA workers also have voiced opposition. The American Federation of Government Employees (AFGE), which represents 270,000 VA employees, also argued that the bill “would render useless” the process that providers use “to protect their voice at work and defend themselves against managers’ retaliation and discrimination.” In a letter to the House committee, AFGE argued that the bill, “weakens the critical protections that VA employees need to speak up against mismanagement and patient harm.”
Citing his inability to immediately remove a VA employee who was caught watching pornography while with a patient, VA Secretary David J. Shulkin, MD, has called on Congress to enact legislation that makes it easier and faster to remove employees at the VA. “This is an example of why we need accountability legislation as soon as possible,” Dr. Shulkin said in a statement. “It’s unacceptable that VA has to wait 30 days to act on a proposed removal.”
Currently, VA employees receive at least 30 days notice of firing, have a right to a grievance hearing, and must be paid throughout the final adjudication as long as there is no evidence of a crime. However, employees can be removed from patient interaction or placed on administrative leave.
In March, the House of Representatives passed the VA Accountability First Act of 2017 (HR 1259), which would reduce the advanced warning time to 10 days and speed up the appeals process, but the bill has yet to be considered by Senate. “This situation underscores the need for Congress to get VA accountability legislation to President Trump's desk, and I thank Secretary Shulkin for making this a top priority,” Rep. David P. “Phil” Roe, MD (R-Tenn.), chairman of the House Veterans’ Affairs Committee concurred. “I was proud my bill, the VA Accountability First Act of 2017, passed the House with bipartisan support earlier this month. Veterans deserve better. I encourage my Senate colleagues to consider my legislation, and I look forward to working with Secretary Shulkin to change the way VA does business.”
Despite the bipartisan support cited by Rep. Roe, many Democrats have indicated that they are wary of the bill because it strips VA civil servant employees of many employment protections. Ranking Democratic House committee on Veterans’ Affairs member Rep. Tim Walz (D-Minn) warned that the changes in employee protections in the bill make it less likely it will pass through the Senate and that it could face court challenges. “By refusing to compromise on the 1 percent of this legislation we disagree on, Republicans have made it harder to pass the 99 percent of the legislation that is vital to making improvements,” according to a report in Stars and Stripes.
Organizations that represent VA workers also have voiced opposition. The American Federation of Government Employees (AFGE), which represents 270,000 VA employees, also argued that the bill “would render useless” the process that providers use “to protect their voice at work and defend themselves against managers’ retaliation and discrimination.” In a letter to the House committee, AFGE argued that the bill, “weakens the critical protections that VA employees need to speak up against mismanagement and patient harm.”
Strontium, ketamine target troublesome itch
ORLANDO – Two drugs that target ion channels in nerves are being used to quiet neurogenic itch.
The powerful anesthetic ketamine and the element strontium have both been formulated into topical compounds that do very well in quelling itches that have been stubbornly resistant to other therapies, Gil Yosipovitch, MD, said at the annual meeting of the American Academy of Dermatology.
Both studies employed a 4% strontium hydrogel that is available over the counter (TriCalm). The product is designed to alleviate skin irritation (itching, burning, or stinging sensations), according to the manufacturer’s website.
The first study, published in 2013, comprised 32 healthy subjects in whom itch was induced with cowhage before and after skin treatment with the strontium gel, a control vehicle, topical 1% hydrocortisone, and topical 2% diphenhydramine (Acta Derm Venereol. 2013 Sep 4;93[5]:520-6).
Strontium significantly reduced the peak intensity and duration of itch relative to all three of the comparators.
A confirmatory study was published in 2015. The vehicle-controlled, randomized, crossover study recorded cowhage-induced itch intensity and duration in 48 healthy subjects before and after skin treatment with TriCalm, 2% diphenhydramine, 1% hydrocortisone, and hydrogel vehicle (Clin Cosmet Investig Dermatol. 2015 Apr 24;8:223-9). The results were similar, Dr. Yosipovitch said.
TriCalm effectively reduced peak itch intensity by about 3 points on a visual analog scale – a 41% reduction. Itch duration was reduced by 40%. These results were both clinically and statistically significantly better than those achieved by the other active comparators and the vehicle control.
Dr. Yosipovitch said the gel is most effective on nonhistaminergic itches, including those with a neurogenic component, nummular eczema, and facial itch.
“The most powerful antipruritic we have seen in the last 3 years, however, is topical ketamine,” Dr. Yosipovitch said. Typically formulated in 2%-10% creams, the anesthetic is usually combined with amitriptyline and lidocaine. “I see this as the most effective topical antipruritic and antinociceptive we have been using.”
Ketamine is an antagonist of the n-methyl-D-aspartate (NMDA) glutamate receptor and an ion channel protein. Amitriptyline serves primarily as a voltage-gated sodium channel antagonist, and lidocaine as a local anesthetic.
Mark Davis, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., and associates initially investigated 0.5% ketamine in a topical combination with amitriptyline 1% in a cream. The compound was remarkably effective for a 41-year-old man with a recalcitrant case of brachioradial pruritus – a neuropathic condition characterized by upper-extremity itching (JAMA Dermatol. 2013;149[2]:148-50). The patient had already failed treatment with halobetasol propionate, pimecrolimus, capsaicin, doxepin hydrochloride creams, and oral hydroxyzine hydrochloride and desloratadine. However, he had complete resolution of the itch soon after using the combination cream two to three times daily. At last follow-up, 4 years later, he was still using it at least once daily and continued to obtain complete relief.
Dr. Yosipovitch said this case was followed by a retrospective study of 16 patients who had used the 0.5% ketamine cream with either 1% or 2% amitriptyline for recalcitrant pruritus. The etiologies included neurodermatitis, pruritus caused by postherpetic neuralgia, nostalgia paresthetica, anesthesia dolorosa, nasal pruritus, and diabetic neuropathy (J Am Acad Dermatol. 2013 Aug;69[2]:320-1).
They used the medication one to five times per day for a mean duration of 10 months. Of the 16 patients, two had complete relief; two had substantial relief; six had some relief; five had no relief; and one reported increased itching.
Most recently, Dr. Yosipovitch and associates reported the results of a retrospective case review of 96 patients with a variety of pruritic conditions. The most frequent indications were neuropathic conditions (29%) and prurigo nodularis (19%). Most patients got a compounded cream of 10% ketamine, 5% amitriptyline, and 2% lidocaine;16 patients got a compound with 5% ketamine. The medication worked quickly, providing itch relief within a median of about 4 minutes, with an average of about a 50% decrease in itch rating (J Am Acad Dermatol. 2017 Apr;76[4]:760-1).
Forty patients participated in a pharmacy-administered telephone survey that assessed medication tolerability and efficacy. Of these, 23 patients (58%) had relief “to a great extent” and 14 (35%) “to a moderate extent.”
There were mild side effects (burning and redness at the application site) in 16 patients. “We attributed this mainly to the lidocaine component,” Dr. Yosipovitch said. “Itch reduction lasted from 30 minutes to 7 hours, so we think this is quite a powerful tool. I now often use this topical for patients with severe intractable itch.”
He added that a case report of encephalopathy associated with the cream has recently surfaced. The patient was an elderly man with Parkinson’s disease who had been using 10% ketamine compounded with amitriptyline and lidocaine for 4 days. He gradually increased the use until he was applying it onto almost all of his upper body. The day after this extensive application, the patient presented to an emergency department with slurred speech, ataxia, and altered mental status (JAMA Dermatol. 2016;152[12]:1390-1).
“So a word of warning here: I don’t recommend using it all over the body,” Dr. Yosipovitch said.
Dr. Yosipovitch has financial relationships with numerous companies that are investigating antipruritic compounds, including strontium.
[email protected]
On Twitter @alz_gal
ORLANDO – Two drugs that target ion channels in nerves are being used to quiet neurogenic itch.
The powerful anesthetic ketamine and the element strontium have both been formulated into topical compounds that do very well in quelling itches that have been stubbornly resistant to other therapies, Gil Yosipovitch, MD, said at the annual meeting of the American Academy of Dermatology.
Both studies employed a 4% strontium hydrogel that is available over the counter (TriCalm). The product is designed to alleviate skin irritation (itching, burning, or stinging sensations), according to the manufacturer’s website.
The first study, published in 2013, comprised 32 healthy subjects in whom itch was induced with cowhage before and after skin treatment with the strontium gel, a control vehicle, topical 1% hydrocortisone, and topical 2% diphenhydramine (Acta Derm Venereol. 2013 Sep 4;93[5]:520-6).
Strontium significantly reduced the peak intensity and duration of itch relative to all three of the comparators.
A confirmatory study was published in 2015. The vehicle-controlled, randomized, crossover study recorded cowhage-induced itch intensity and duration in 48 healthy subjects before and after skin treatment with TriCalm, 2% diphenhydramine, 1% hydrocortisone, and hydrogel vehicle (Clin Cosmet Investig Dermatol. 2015 Apr 24;8:223-9). The results were similar, Dr. Yosipovitch said.
TriCalm effectively reduced peak itch intensity by about 3 points on a visual analog scale – a 41% reduction. Itch duration was reduced by 40%. These results were both clinically and statistically significantly better than those achieved by the other active comparators and the vehicle control.
Dr. Yosipovitch said the gel is most effective on nonhistaminergic itches, including those with a neurogenic component, nummular eczema, and facial itch.
“The most powerful antipruritic we have seen in the last 3 years, however, is topical ketamine,” Dr. Yosipovitch said. Typically formulated in 2%-10% creams, the anesthetic is usually combined with amitriptyline and lidocaine. “I see this as the most effective topical antipruritic and antinociceptive we have been using.”
Ketamine is an antagonist of the n-methyl-D-aspartate (NMDA) glutamate receptor and an ion channel protein. Amitriptyline serves primarily as a voltage-gated sodium channel antagonist, and lidocaine as a local anesthetic.
Mark Davis, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., and associates initially investigated 0.5% ketamine in a topical combination with amitriptyline 1% in a cream. The compound was remarkably effective for a 41-year-old man with a recalcitrant case of brachioradial pruritus – a neuropathic condition characterized by upper-extremity itching (JAMA Dermatol. 2013;149[2]:148-50). The patient had already failed treatment with halobetasol propionate, pimecrolimus, capsaicin, doxepin hydrochloride creams, and oral hydroxyzine hydrochloride and desloratadine. However, he had complete resolution of the itch soon after using the combination cream two to three times daily. At last follow-up, 4 years later, he was still using it at least once daily and continued to obtain complete relief.
Dr. Yosipovitch said this case was followed by a retrospective study of 16 patients who had used the 0.5% ketamine cream with either 1% or 2% amitriptyline for recalcitrant pruritus. The etiologies included neurodermatitis, pruritus caused by postherpetic neuralgia, nostalgia paresthetica, anesthesia dolorosa, nasal pruritus, and diabetic neuropathy (J Am Acad Dermatol. 2013 Aug;69[2]:320-1).
They used the medication one to five times per day for a mean duration of 10 months. Of the 16 patients, two had complete relief; two had substantial relief; six had some relief; five had no relief; and one reported increased itching.
Most recently, Dr. Yosipovitch and associates reported the results of a retrospective case review of 96 patients with a variety of pruritic conditions. The most frequent indications were neuropathic conditions (29%) and prurigo nodularis (19%). Most patients got a compounded cream of 10% ketamine, 5% amitriptyline, and 2% lidocaine;16 patients got a compound with 5% ketamine. The medication worked quickly, providing itch relief within a median of about 4 minutes, with an average of about a 50% decrease in itch rating (J Am Acad Dermatol. 2017 Apr;76[4]:760-1).
Forty patients participated in a pharmacy-administered telephone survey that assessed medication tolerability and efficacy. Of these, 23 patients (58%) had relief “to a great extent” and 14 (35%) “to a moderate extent.”
There were mild side effects (burning and redness at the application site) in 16 patients. “We attributed this mainly to the lidocaine component,” Dr. Yosipovitch said. “Itch reduction lasted from 30 minutes to 7 hours, so we think this is quite a powerful tool. I now often use this topical for patients with severe intractable itch.”
He added that a case report of encephalopathy associated with the cream has recently surfaced. The patient was an elderly man with Parkinson’s disease who had been using 10% ketamine compounded with amitriptyline and lidocaine for 4 days. He gradually increased the use until he was applying it onto almost all of his upper body. The day after this extensive application, the patient presented to an emergency department with slurred speech, ataxia, and altered mental status (JAMA Dermatol. 2016;152[12]:1390-1).
“So a word of warning here: I don’t recommend using it all over the body,” Dr. Yosipovitch said.
Dr. Yosipovitch has financial relationships with numerous companies that are investigating antipruritic compounds, including strontium.
[email protected]
On Twitter @alz_gal
ORLANDO – Two drugs that target ion channels in nerves are being used to quiet neurogenic itch.
The powerful anesthetic ketamine and the element strontium have both been formulated into topical compounds that do very well in quelling itches that have been stubbornly resistant to other therapies, Gil Yosipovitch, MD, said at the annual meeting of the American Academy of Dermatology.
Both studies employed a 4% strontium hydrogel that is available over the counter (TriCalm). The product is designed to alleviate skin irritation (itching, burning, or stinging sensations), according to the manufacturer’s website.
The first study, published in 2013, comprised 32 healthy subjects in whom itch was induced with cowhage before and after skin treatment with the strontium gel, a control vehicle, topical 1% hydrocortisone, and topical 2% diphenhydramine (Acta Derm Venereol. 2013 Sep 4;93[5]:520-6).
Strontium significantly reduced the peak intensity and duration of itch relative to all three of the comparators.
A confirmatory study was published in 2015. The vehicle-controlled, randomized, crossover study recorded cowhage-induced itch intensity and duration in 48 healthy subjects before and after skin treatment with TriCalm, 2% diphenhydramine, 1% hydrocortisone, and hydrogel vehicle (Clin Cosmet Investig Dermatol. 2015 Apr 24;8:223-9). The results were similar, Dr. Yosipovitch said.
TriCalm effectively reduced peak itch intensity by about 3 points on a visual analog scale – a 41% reduction. Itch duration was reduced by 40%. These results were both clinically and statistically significantly better than those achieved by the other active comparators and the vehicle control.
Dr. Yosipovitch said the gel is most effective on nonhistaminergic itches, including those with a neurogenic component, nummular eczema, and facial itch.
“The most powerful antipruritic we have seen in the last 3 years, however, is topical ketamine,” Dr. Yosipovitch said. Typically formulated in 2%-10% creams, the anesthetic is usually combined with amitriptyline and lidocaine. “I see this as the most effective topical antipruritic and antinociceptive we have been using.”
Ketamine is an antagonist of the n-methyl-D-aspartate (NMDA) glutamate receptor and an ion channel protein. Amitriptyline serves primarily as a voltage-gated sodium channel antagonist, and lidocaine as a local anesthetic.
Mark Davis, MD, professor of dermatology at the Mayo Clinic, Rochester, Minn., and associates initially investigated 0.5% ketamine in a topical combination with amitriptyline 1% in a cream. The compound was remarkably effective for a 41-year-old man with a recalcitrant case of brachioradial pruritus – a neuropathic condition characterized by upper-extremity itching (JAMA Dermatol. 2013;149[2]:148-50). The patient had already failed treatment with halobetasol propionate, pimecrolimus, capsaicin, doxepin hydrochloride creams, and oral hydroxyzine hydrochloride and desloratadine. However, he had complete resolution of the itch soon after using the combination cream two to three times daily. At last follow-up, 4 years later, he was still using it at least once daily and continued to obtain complete relief.
Dr. Yosipovitch said this case was followed by a retrospective study of 16 patients who had used the 0.5% ketamine cream with either 1% or 2% amitriptyline for recalcitrant pruritus. The etiologies included neurodermatitis, pruritus caused by postherpetic neuralgia, nostalgia paresthetica, anesthesia dolorosa, nasal pruritus, and diabetic neuropathy (J Am Acad Dermatol. 2013 Aug;69[2]:320-1).
They used the medication one to five times per day for a mean duration of 10 months. Of the 16 patients, two had complete relief; two had substantial relief; six had some relief; five had no relief; and one reported increased itching.
Most recently, Dr. Yosipovitch and associates reported the results of a retrospective case review of 96 patients with a variety of pruritic conditions. The most frequent indications were neuropathic conditions (29%) and prurigo nodularis (19%). Most patients got a compounded cream of 10% ketamine, 5% amitriptyline, and 2% lidocaine;16 patients got a compound with 5% ketamine. The medication worked quickly, providing itch relief within a median of about 4 minutes, with an average of about a 50% decrease in itch rating (J Am Acad Dermatol. 2017 Apr;76[4]:760-1).
Forty patients participated in a pharmacy-administered telephone survey that assessed medication tolerability and efficacy. Of these, 23 patients (58%) had relief “to a great extent” and 14 (35%) “to a moderate extent.”
There were mild side effects (burning and redness at the application site) in 16 patients. “We attributed this mainly to the lidocaine component,” Dr. Yosipovitch said. “Itch reduction lasted from 30 minutes to 7 hours, so we think this is quite a powerful tool. I now often use this topical for patients with severe intractable itch.”
He added that a case report of encephalopathy associated with the cream has recently surfaced. The patient was an elderly man with Parkinson’s disease who had been using 10% ketamine compounded with amitriptyline and lidocaine for 4 days. He gradually increased the use until he was applying it onto almost all of his upper body. The day after this extensive application, the patient presented to an emergency department with slurred speech, ataxia, and altered mental status (JAMA Dermatol. 2016;152[12]:1390-1).
“So a word of warning here: I don’t recommend using it all over the body,” Dr. Yosipovitch said.
Dr. Yosipovitch has financial relationships with numerous companies that are investigating antipruritic compounds, including strontium.
[email protected]
On Twitter @alz_gal
EXPERT ANALYSIS FROM AAD 17
ABIM turns MOC page with open-book 2-year exams
SAN DIEGO – The way the president of the American Board of Internal Medicine, Richard J. Baron, MD, sees it, maintenance of certification is more important than ever, because trust in the medical profession “is under assault right now in all kinds of ways.”
So, to help “bring clarity to uncertainty,” ABIM is continuing its makeover of the maintenance of certification (MOC) process. Beginning in 2018, an open-book option to test every 2 years will be available for physicians who are certified in internal medicine and for those in the subspecialty of nephrology. These options become available to gastroenterologists in 2019.
Both the 10-year long-form assessment and the shorter 2-year assessment options will be open book, “meaning physicians will have access to an online reference while they’re taking the exam,” said Yul D. Ejnes, MD, who is a member of ABIM’s board of directors and serves on the ABIM’s internal medicine specialty board.
Known as the “Knowledge Check-In,” the 2-year assessment is a shorter, “lower stakes” option that can be taken at home, in an office, or at a testing facility. The check-ins will be scheduled 4-6 times per year, with 10-year exams remaining available twice per year. The open-book 2-year assessments will be about 3 hours in length.
“It’s a more continuous way of learning and assessing, because the way we’ll do feedback is going to change,” explained Dr. Ejnes, who practices in Cranston, R.I. “Specifically, you’ll know right away whether you were successful or not with the assessment, as opposed to having to wait a couple of months, which happens with the 10-year assessment. Then you’ll get more feedback later helping to identify areas where you may be a little weaker and need to work out things.”
“It remains to be seen whether this new system is an improvement for GI learners. AGA’s educators will compare the changes offered by ABIM against our principles for MOC reform,” said Timothy C. Wang, MD, AGAF, President of AGA. “Reforming the MOC process is a high and long-standing priority for AGA. We have pushed ABIM to offer a system that reflects the realities of practice and how adults learn – and we’ll continue to fight for these principles.”
In general, physicians will need to either take the 2-year assessments or pass the 10-year assessment within 10 years of their last pass of the 10-year exam. Those who fail two successive 2-year assessments will have to take the 10-year exam. However, unsuccessful performance on the 2-year assessment in 2018 will not have a negative impact on certification or MOC participation status.
“It won’t count as one of the two opportunities you have before you have to go to the 10-year exam,” Dr. Ejnes said. “It allows people to try it out and lets us learn from what happens and do whatever we need to do to make things better.”
Why a 2-year period instead of a 5-year option, for example? A shorter time frame will allow the ABIM to move to a more modular approach to test material, Dr. Ejnes explained. For now, the 2-year assessments will be breadth-of-discipline exams.
Physicians whose certification expires in 2017 will need to take the 10-year exam – as Dr. Ejnes noted he himself was forced to do. “You cannot wait until 2018,” he cautioned. “That’s important, because if you let your certification lapse, you can’t enter the certification pathway. The prerequisite is that you need to be in good standing with your certification.”
The open-book Knowledge Check-Ins and 10-year assessments are slated to expand to eight subspecialties in 2019 and nine more in 2020.
Linking MOC and trust
Speaking at the annual meeting of the American College of Physicians, Dr. Baron said that false and misleading information circulated widely on Facebook and other social media channels runs the gamut of health issues, from falsified studies about purported links between vaccines and autism and public health scares on impostor websites, to stories of miracle cures for any number of ailments.
“It’s not just vaccines people are questioning,” said Dr. Baron, ABIM’s president and CEO. “There are erosions of trust in government, and there’s the tenacity and power of wildly inaccurate information. You will be dealing with patients who tenaciously believe things that you know not to be true. You will need to find ways to build trust, credibility, and relationships based on their trusting that what you’re saying is really in their interest.”
U.S. physicians aren’t secure in the shaky trust landscape. In fact, globally, the United States ranks 24th in public trust level of physicians by country (N. Eng. J. Med. 2014 Oct 23;371[17]:1570-2).
“The confidence in the medical system today is lower than the confidence in police or in small business,” Dr. Baron said. “That’s [the view] people are bringing into your offices every day. I don’t think we can assume that deference and trust are given to doctors, that the privileged role that society affords us is something that we’re going to have forever. We all have to think how trust is built in the new world.”
Will patients value MOC?
During a question and answer session at the ACP session, Anne Cummings, MD, an internist who practices in Greenbrae, Calif., asked the ABIM for support in educating the general public about what it means to be treated by a board-certified physician.
“I had a naturopath tell me the other day that she had the same training as I had,” Dr. Cummings said. “I was floored, but I think that patients don’t know the difference [between board-certified and not board-certified].”
Dr. Baron agreed ABIM needs to do more to promote the value of certification among patients. But he also called on board-certified physicians to deliver the value message directly to their own patients.
Other attendees recommended that ABIM expand the number of ways physicians can earn MOC points, and they expressed concern about the time MOC takes away from their daily practice.
For regular updates on the MOC process, physicians can subscribe to the ABIM’s blog at transforming.abim.org.
SAN DIEGO – The way the president of the American Board of Internal Medicine, Richard J. Baron, MD, sees it, maintenance of certification is more important than ever, because trust in the medical profession “is under assault right now in all kinds of ways.”
So, to help “bring clarity to uncertainty,” ABIM is continuing its makeover of the maintenance of certification (MOC) process. Beginning in 2018, an open-book option to test every 2 years will be available for physicians who are certified in internal medicine and for those in the subspecialty of nephrology. These options become available to gastroenterologists in 2019.
Both the 10-year long-form assessment and the shorter 2-year assessment options will be open book, “meaning physicians will have access to an online reference while they’re taking the exam,” said Yul D. Ejnes, MD, who is a member of ABIM’s board of directors and serves on the ABIM’s internal medicine specialty board.
Known as the “Knowledge Check-In,” the 2-year assessment is a shorter, “lower stakes” option that can be taken at home, in an office, or at a testing facility. The check-ins will be scheduled 4-6 times per year, with 10-year exams remaining available twice per year. The open-book 2-year assessments will be about 3 hours in length.
“It’s a more continuous way of learning and assessing, because the way we’ll do feedback is going to change,” explained Dr. Ejnes, who practices in Cranston, R.I. “Specifically, you’ll know right away whether you were successful or not with the assessment, as opposed to having to wait a couple of months, which happens with the 10-year assessment. Then you’ll get more feedback later helping to identify areas where you may be a little weaker and need to work out things.”
“It remains to be seen whether this new system is an improvement for GI learners. AGA’s educators will compare the changes offered by ABIM against our principles for MOC reform,” said Timothy C. Wang, MD, AGAF, President of AGA. “Reforming the MOC process is a high and long-standing priority for AGA. We have pushed ABIM to offer a system that reflects the realities of practice and how adults learn – and we’ll continue to fight for these principles.”
In general, physicians will need to either take the 2-year assessments or pass the 10-year assessment within 10 years of their last pass of the 10-year exam. Those who fail two successive 2-year assessments will have to take the 10-year exam. However, unsuccessful performance on the 2-year assessment in 2018 will not have a negative impact on certification or MOC participation status.
“It won’t count as one of the two opportunities you have before you have to go to the 10-year exam,” Dr. Ejnes said. “It allows people to try it out and lets us learn from what happens and do whatever we need to do to make things better.”
Why a 2-year period instead of a 5-year option, for example? A shorter time frame will allow the ABIM to move to a more modular approach to test material, Dr. Ejnes explained. For now, the 2-year assessments will be breadth-of-discipline exams.
Physicians whose certification expires in 2017 will need to take the 10-year exam – as Dr. Ejnes noted he himself was forced to do. “You cannot wait until 2018,” he cautioned. “That’s important, because if you let your certification lapse, you can’t enter the certification pathway. The prerequisite is that you need to be in good standing with your certification.”
The open-book Knowledge Check-Ins and 10-year assessments are slated to expand to eight subspecialties in 2019 and nine more in 2020.
Linking MOC and trust
Speaking at the annual meeting of the American College of Physicians, Dr. Baron said that false and misleading information circulated widely on Facebook and other social media channels runs the gamut of health issues, from falsified studies about purported links between vaccines and autism and public health scares on impostor websites, to stories of miracle cures for any number of ailments.
“It’s not just vaccines people are questioning,” said Dr. Baron, ABIM’s president and CEO. “There are erosions of trust in government, and there’s the tenacity and power of wildly inaccurate information. You will be dealing with patients who tenaciously believe things that you know not to be true. You will need to find ways to build trust, credibility, and relationships based on their trusting that what you’re saying is really in their interest.”
U.S. physicians aren’t secure in the shaky trust landscape. In fact, globally, the United States ranks 24th in public trust level of physicians by country (N. Eng. J. Med. 2014 Oct 23;371[17]:1570-2).
“The confidence in the medical system today is lower than the confidence in police or in small business,” Dr. Baron said. “That’s [the view] people are bringing into your offices every day. I don’t think we can assume that deference and trust are given to doctors, that the privileged role that society affords us is something that we’re going to have forever. We all have to think how trust is built in the new world.”
Will patients value MOC?
During a question and answer session at the ACP session, Anne Cummings, MD, an internist who practices in Greenbrae, Calif., asked the ABIM for support in educating the general public about what it means to be treated by a board-certified physician.
“I had a naturopath tell me the other day that she had the same training as I had,” Dr. Cummings said. “I was floored, but I think that patients don’t know the difference [between board-certified and not board-certified].”
Dr. Baron agreed ABIM needs to do more to promote the value of certification among patients. But he also called on board-certified physicians to deliver the value message directly to their own patients.
Other attendees recommended that ABIM expand the number of ways physicians can earn MOC points, and they expressed concern about the time MOC takes away from their daily practice.
For regular updates on the MOC process, physicians can subscribe to the ABIM’s blog at transforming.abim.org.
SAN DIEGO – The way the president of the American Board of Internal Medicine, Richard J. Baron, MD, sees it, maintenance of certification is more important than ever, because trust in the medical profession “is under assault right now in all kinds of ways.”
So, to help “bring clarity to uncertainty,” ABIM is continuing its makeover of the maintenance of certification (MOC) process. Beginning in 2018, an open-book option to test every 2 years will be available for physicians who are certified in internal medicine and for those in the subspecialty of nephrology. These options become available to gastroenterologists in 2019.
Both the 10-year long-form assessment and the shorter 2-year assessment options will be open book, “meaning physicians will have access to an online reference while they’re taking the exam,” said Yul D. Ejnes, MD, who is a member of ABIM’s board of directors and serves on the ABIM’s internal medicine specialty board.
Known as the “Knowledge Check-In,” the 2-year assessment is a shorter, “lower stakes” option that can be taken at home, in an office, or at a testing facility. The check-ins will be scheduled 4-6 times per year, with 10-year exams remaining available twice per year. The open-book 2-year assessments will be about 3 hours in length.
“It’s a more continuous way of learning and assessing, because the way we’ll do feedback is going to change,” explained Dr. Ejnes, who practices in Cranston, R.I. “Specifically, you’ll know right away whether you were successful or not with the assessment, as opposed to having to wait a couple of months, which happens with the 10-year assessment. Then you’ll get more feedback later helping to identify areas where you may be a little weaker and need to work out things.”
“It remains to be seen whether this new system is an improvement for GI learners. AGA’s educators will compare the changes offered by ABIM against our principles for MOC reform,” said Timothy C. Wang, MD, AGAF, President of AGA. “Reforming the MOC process is a high and long-standing priority for AGA. We have pushed ABIM to offer a system that reflects the realities of practice and how adults learn – and we’ll continue to fight for these principles.”
In general, physicians will need to either take the 2-year assessments or pass the 10-year assessment within 10 years of their last pass of the 10-year exam. Those who fail two successive 2-year assessments will have to take the 10-year exam. However, unsuccessful performance on the 2-year assessment in 2018 will not have a negative impact on certification or MOC participation status.
“It won’t count as one of the two opportunities you have before you have to go to the 10-year exam,” Dr. Ejnes said. “It allows people to try it out and lets us learn from what happens and do whatever we need to do to make things better.”
Why a 2-year period instead of a 5-year option, for example? A shorter time frame will allow the ABIM to move to a more modular approach to test material, Dr. Ejnes explained. For now, the 2-year assessments will be breadth-of-discipline exams.
Physicians whose certification expires in 2017 will need to take the 10-year exam – as Dr. Ejnes noted he himself was forced to do. “You cannot wait until 2018,” he cautioned. “That’s important, because if you let your certification lapse, you can’t enter the certification pathway. The prerequisite is that you need to be in good standing with your certification.”
The open-book Knowledge Check-Ins and 10-year assessments are slated to expand to eight subspecialties in 2019 and nine more in 2020.
Linking MOC and trust
Speaking at the annual meeting of the American College of Physicians, Dr. Baron said that false and misleading information circulated widely on Facebook and other social media channels runs the gamut of health issues, from falsified studies about purported links between vaccines and autism and public health scares on impostor websites, to stories of miracle cures for any number of ailments.
“It’s not just vaccines people are questioning,” said Dr. Baron, ABIM’s president and CEO. “There are erosions of trust in government, and there’s the tenacity and power of wildly inaccurate information. You will be dealing with patients who tenaciously believe things that you know not to be true. You will need to find ways to build trust, credibility, and relationships based on their trusting that what you’re saying is really in their interest.”
U.S. physicians aren’t secure in the shaky trust landscape. In fact, globally, the United States ranks 24th in public trust level of physicians by country (N. Eng. J. Med. 2014 Oct 23;371[17]:1570-2).
“The confidence in the medical system today is lower than the confidence in police or in small business,” Dr. Baron said. “That’s [the view] people are bringing into your offices every day. I don’t think we can assume that deference and trust are given to doctors, that the privileged role that society affords us is something that we’re going to have forever. We all have to think how trust is built in the new world.”
Will patients value MOC?
During a question and answer session at the ACP session, Anne Cummings, MD, an internist who practices in Greenbrae, Calif., asked the ABIM for support in educating the general public about what it means to be treated by a board-certified physician.
“I had a naturopath tell me the other day that she had the same training as I had,” Dr. Cummings said. “I was floored, but I think that patients don’t know the difference [between board-certified and not board-certified].”
Dr. Baron agreed ABIM needs to do more to promote the value of certification among patients. But he also called on board-certified physicians to deliver the value message directly to their own patients.
Other attendees recommended that ABIM expand the number of ways physicians can earn MOC points, and they expressed concern about the time MOC takes away from their daily practice.
For regular updates on the MOC process, physicians can subscribe to the ABIM’s blog at transforming.abim.org.
First treat-to-target gout trial supports allopurinol dose escalation
Gradual dose escalation of allopurinol achieved target serum urate levels without causing excess adverse effects in patients with gout who tolerated but responded inadequately to creatinine clearance–based dosing, including in patients with chronic kidney disease, investigators reported in Annals of the Rheumatic Diseases.
The study is the first randomized, controlled trial to examine treat-to-target allopurinol dose escalation in gout. “We believe this approach can be undertaken in all patients who tolerate allopurinol,” lead investigator Lisa Stamp, MD, said in an interview. However, it is important to monitor kidney and liver function.”
To help settle these debates, Dr. Stamp and her associates recruited 183 patients with gout whose serum urate levels averaged 7.15 mg/dL (standard deviation, 1.6 mg/dL) despite at least 1 month of at least a creatinine clearance–based allopurinol dose (average, 269 mg/day). For the next 12 months, patients either continued this dose or increased it monthly until serum urate fell below 6 mg/dL (Ann Rheum Dis. 2017 March 17. doi: 10.1136/annrheumdis-2016-210872).
At month 12, 69% of dose-escalation patients and 32% of controls reached this target (P less than .001; odds ratio, 4.3; 95% confidence interval, 2.4-7.9). Serum urate levels dropped by a mean of 1.5 mg/dL with dose escalation and by 0.34 mg/dL in controls (P less than .001). Thus, dose escalation cut serum urate levels by an additional 1.2 mg/dL (95% CI, 0.67-1.5 mg/dL; P less than .001). The average final daily allopurinol dose was 413 mg (range, 0-900 mg) with dose escalation and 288 mg (0-600 mg) for controls.
Notably, renal function measures did not differ between arms. “There has been long-standing concern about whether it is safe to escalate allopurinol doses in persons with chronic kidney disease,” said Kenneth Saag, MD, of the University of Alabama at Birmingham, who was not involved in the trial. “This study contributes to the limited literature supporting the practice of treating to serum urate targets, even in patients with underlying kidney disease.”
Fully 52% of trial participants had chronic kidney disease, and 44% had tophi. “Thus, our population is representative of people with gout, represents real-life clinical practice, and the results are generalizable to other gout populations,” the investigators wrote.
The findings support the ACR recommendation to gradually titrate urate-lowering therapy while performing close laboratory monitoring, said Tuhina Neogi, MD, of Boston University, who was not involved in the study. This approach is “efficacious and relatively safe for patients who have already tolerated lower doses of allopurinol, but have not yet achieved their serum urate target,” she said. “This is akin to finding the right regimen and titrating doses of medications for patients with diabetes or hypertension in a patient-centered manner.”
Patients in both groups developed mild increases in liver function tests, and a few in the dose escalation group developed more pronounced rises in gamma glutamyl transferase (GGT), as previously reported in the LASSO trial (Semin Arthritis Rheum. 2015 Oct;45[2]:174-83). Allopurinol has been linked to liver enzyme abnormalities, and the GGT finding is of unclear significance, but laboratory monitoring is important, Dr. Neogi said. If primary care providers who treat gout cannot routinely measure serum urate and other relevant laboratory measures, they should consider referring patients to a rheumatologist, she added.
Gradual dose escalation meant that patients did not reach the serum urate target until month 7, Dr. Neogi added. “Since the trial was 12 months long, the time over which serum urate was less than 6 mg/dL was not long enough to demonstrate the benefits on flares and tophi,” she said. The open-label extension phase of the trial should shed more insight on these important questions, she added.
For now, providers should know that “patients with gout are not well served if their serum urate levels remain elevated, as that means they are at ongoing risk for flares and tophi,” Dr. Neogi said. “This trial provides evidence and further support for the feasibility, efficacy, and relative safety of escalating allopurinol beyond creatinine-clearance dosing to achieve this important and critical goal for gout management.”
The Health Research Council of New Zealand funded the study. Dr. Stamp and two coinvestigators disclosed grant support from the Health Research Council of New Zealand. Dr. Stamp also disclosed grants from Ardea Biosciences and the Health Research Council of New Zealand outside the submitted work, and her coinvestigators disclosed grants and personal fees from AstraZeneca, Ardea Biosciences, Takeda, and several other pharmaceutical companies. Dr. Neogi had no disclosures. Dr. Saag has received meal compensation from Eli Lilly.
Gradual dose escalation of allopurinol achieved target serum urate levels without causing excess adverse effects in patients with gout who tolerated but responded inadequately to creatinine clearance–based dosing, including in patients with chronic kidney disease, investigators reported in Annals of the Rheumatic Diseases.
The study is the first randomized, controlled trial to examine treat-to-target allopurinol dose escalation in gout. “We believe this approach can be undertaken in all patients who tolerate allopurinol,” lead investigator Lisa Stamp, MD, said in an interview. However, it is important to monitor kidney and liver function.”
To help settle these debates, Dr. Stamp and her associates recruited 183 patients with gout whose serum urate levels averaged 7.15 mg/dL (standard deviation, 1.6 mg/dL) despite at least 1 month of at least a creatinine clearance–based allopurinol dose (average, 269 mg/day). For the next 12 months, patients either continued this dose or increased it monthly until serum urate fell below 6 mg/dL (Ann Rheum Dis. 2017 March 17. doi: 10.1136/annrheumdis-2016-210872).
At month 12, 69% of dose-escalation patients and 32% of controls reached this target (P less than .001; odds ratio, 4.3; 95% confidence interval, 2.4-7.9). Serum urate levels dropped by a mean of 1.5 mg/dL with dose escalation and by 0.34 mg/dL in controls (P less than .001). Thus, dose escalation cut serum urate levels by an additional 1.2 mg/dL (95% CI, 0.67-1.5 mg/dL; P less than .001). The average final daily allopurinol dose was 413 mg (range, 0-900 mg) with dose escalation and 288 mg (0-600 mg) for controls.
Notably, renal function measures did not differ between arms. “There has been long-standing concern about whether it is safe to escalate allopurinol doses in persons with chronic kidney disease,” said Kenneth Saag, MD, of the University of Alabama at Birmingham, who was not involved in the trial. “This study contributes to the limited literature supporting the practice of treating to serum urate targets, even in patients with underlying kidney disease.”
Fully 52% of trial participants had chronic kidney disease, and 44% had tophi. “Thus, our population is representative of people with gout, represents real-life clinical practice, and the results are generalizable to other gout populations,” the investigators wrote.
The findings support the ACR recommendation to gradually titrate urate-lowering therapy while performing close laboratory monitoring, said Tuhina Neogi, MD, of Boston University, who was not involved in the study. This approach is “efficacious and relatively safe for patients who have already tolerated lower doses of allopurinol, but have not yet achieved their serum urate target,” she said. “This is akin to finding the right regimen and titrating doses of medications for patients with diabetes or hypertension in a patient-centered manner.”
Patients in both groups developed mild increases in liver function tests, and a few in the dose escalation group developed more pronounced rises in gamma glutamyl transferase (GGT), as previously reported in the LASSO trial (Semin Arthritis Rheum. 2015 Oct;45[2]:174-83). Allopurinol has been linked to liver enzyme abnormalities, and the GGT finding is of unclear significance, but laboratory monitoring is important, Dr. Neogi said. If primary care providers who treat gout cannot routinely measure serum urate and other relevant laboratory measures, they should consider referring patients to a rheumatologist, she added.
Gradual dose escalation meant that patients did not reach the serum urate target until month 7, Dr. Neogi added. “Since the trial was 12 months long, the time over which serum urate was less than 6 mg/dL was not long enough to demonstrate the benefits on flares and tophi,” she said. The open-label extension phase of the trial should shed more insight on these important questions, she added.
For now, providers should know that “patients with gout are not well served if their serum urate levels remain elevated, as that means they are at ongoing risk for flares and tophi,” Dr. Neogi said. “This trial provides evidence and further support for the feasibility, efficacy, and relative safety of escalating allopurinol beyond creatinine-clearance dosing to achieve this important and critical goal for gout management.”
The Health Research Council of New Zealand funded the study. Dr. Stamp and two coinvestigators disclosed grant support from the Health Research Council of New Zealand. Dr. Stamp also disclosed grants from Ardea Biosciences and the Health Research Council of New Zealand outside the submitted work, and her coinvestigators disclosed grants and personal fees from AstraZeneca, Ardea Biosciences, Takeda, and several other pharmaceutical companies. Dr. Neogi had no disclosures. Dr. Saag has received meal compensation from Eli Lilly.
Gradual dose escalation of allopurinol achieved target serum urate levels without causing excess adverse effects in patients with gout who tolerated but responded inadequately to creatinine clearance–based dosing, including in patients with chronic kidney disease, investigators reported in Annals of the Rheumatic Diseases.
The study is the first randomized, controlled trial to examine treat-to-target allopurinol dose escalation in gout. “We believe this approach can be undertaken in all patients who tolerate allopurinol,” lead investigator Lisa Stamp, MD, said in an interview. However, it is important to monitor kidney and liver function.”
To help settle these debates, Dr. Stamp and her associates recruited 183 patients with gout whose serum urate levels averaged 7.15 mg/dL (standard deviation, 1.6 mg/dL) despite at least 1 month of at least a creatinine clearance–based allopurinol dose (average, 269 mg/day). For the next 12 months, patients either continued this dose or increased it monthly until serum urate fell below 6 mg/dL (Ann Rheum Dis. 2017 March 17. doi: 10.1136/annrheumdis-2016-210872).
At month 12, 69% of dose-escalation patients and 32% of controls reached this target (P less than .001; odds ratio, 4.3; 95% confidence interval, 2.4-7.9). Serum urate levels dropped by a mean of 1.5 mg/dL with dose escalation and by 0.34 mg/dL in controls (P less than .001). Thus, dose escalation cut serum urate levels by an additional 1.2 mg/dL (95% CI, 0.67-1.5 mg/dL; P less than .001). The average final daily allopurinol dose was 413 mg (range, 0-900 mg) with dose escalation and 288 mg (0-600 mg) for controls.
Notably, renal function measures did not differ between arms. “There has been long-standing concern about whether it is safe to escalate allopurinol doses in persons with chronic kidney disease,” said Kenneth Saag, MD, of the University of Alabama at Birmingham, who was not involved in the trial. “This study contributes to the limited literature supporting the practice of treating to serum urate targets, even in patients with underlying kidney disease.”
Fully 52% of trial participants had chronic kidney disease, and 44% had tophi. “Thus, our population is representative of people with gout, represents real-life clinical practice, and the results are generalizable to other gout populations,” the investigators wrote.
The findings support the ACR recommendation to gradually titrate urate-lowering therapy while performing close laboratory monitoring, said Tuhina Neogi, MD, of Boston University, who was not involved in the study. This approach is “efficacious and relatively safe for patients who have already tolerated lower doses of allopurinol, but have not yet achieved their serum urate target,” she said. “This is akin to finding the right regimen and titrating doses of medications for patients with diabetes or hypertension in a patient-centered manner.”
Patients in both groups developed mild increases in liver function tests, and a few in the dose escalation group developed more pronounced rises in gamma glutamyl transferase (GGT), as previously reported in the LASSO trial (Semin Arthritis Rheum. 2015 Oct;45[2]:174-83). Allopurinol has been linked to liver enzyme abnormalities, and the GGT finding is of unclear significance, but laboratory monitoring is important, Dr. Neogi said. If primary care providers who treat gout cannot routinely measure serum urate and other relevant laboratory measures, they should consider referring patients to a rheumatologist, she added.
Gradual dose escalation meant that patients did not reach the serum urate target until month 7, Dr. Neogi added. “Since the trial was 12 months long, the time over which serum urate was less than 6 mg/dL was not long enough to demonstrate the benefits on flares and tophi,” she said. The open-label extension phase of the trial should shed more insight on these important questions, she added.
For now, providers should know that “patients with gout are not well served if their serum urate levels remain elevated, as that means they are at ongoing risk for flares and tophi,” Dr. Neogi said. “This trial provides evidence and further support for the feasibility, efficacy, and relative safety of escalating allopurinol beyond creatinine-clearance dosing to achieve this important and critical goal for gout management.”
The Health Research Council of New Zealand funded the study. Dr. Stamp and two coinvestigators disclosed grant support from the Health Research Council of New Zealand. Dr. Stamp also disclosed grants from Ardea Biosciences and the Health Research Council of New Zealand outside the submitted work, and her coinvestigators disclosed grants and personal fees from AstraZeneca, Ardea Biosciences, Takeda, and several other pharmaceutical companies. Dr. Neogi had no disclosures. Dr. Saag has received meal compensation from Eli Lilly.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: At month 12, 69% of dose escalation patients and 32% of controls had serum urate levels below 6 mg/dL (P less than .001). Dose escalation did not increase the risk of serious adverse effects.
Data source: A 12-month, open-label, randomized, controlled, parallel-group, comparative trial of 186 patients with gout.
Disclosures: The Health Research Council of New Zealand funded the study. Dr. Stamp and two coinvestigators disclosed grant support from Health Research Council of New Zealand. Dr. Stamp also disclosed grants from Ardea Biosciences and Health Research Council of New Zealand outside the submitted work, and her coinvestigators disclosed grants and personal fees from AstraZeneca, Ardea Biosciences, Takeda, and several other pharmaceutical companies. Dr. Neogi had no disclosures. Dr. Saag has received meal compensation from Eli Lilly.
Omalizumab effects rapid, often complete, clearance of refractory bullous pemphigoid
ORLANDO – Omalizumab, a monoclonal anti-IgE antibody, may be a good option for patients with treatment-refractory bullous pemphigoid.
Patients who received omalizumab (Xolair) experienced rapid improvements, with 30%-50% lesion clearance within a week and complete clearance by 3 weeks, Kenneth Yu, MD, said at the annual meeting of the American Academy of Dermatology. With regular injections, they were kept symptom free for months. Some patients did flare, but were then easily controlled on standard treatment. Omalizumab, approved by the Food and Drug Administration in 2003, is indicated for moderate to severe persistent asthma and chronic idiopathic urticaria.
“We have now treated six patients with omalizumab with very good results with five of them. These are not your garden-variety BP patients, but people with very treatment-resistant disease who have failed treatment with corticosteroids alone, and in combination with other immunosuppressants.”
The rapid clinical improvements, along with observations that eosinophilia decreased with treatment, “strengthen the evidence that BP is an IgE-mediated, organ-specific autoimmune disease,” said Dr. Yu, senior resident in dermatology at the University of Michigan, Ann Arbor.
“Would I use this as a first-line treatment for BP? Probably not. But if you are seeing someone who’s nonresponsive to therapy, you might want to check IgE and eosinophil levels and if those are elevated, you might consider omalizumab as an adjunct treatment – and you might observe a fairly dramatic response.”
Three of Dr. Yu’s patients received omalizumab as monotherapy, and three received it in conjunction with other immunosuppressants. He described their disease presentation, treatment, and progression.
In general, Dr. Yu reserves omalizumab for patients with refractory disease and two particular clinical characteristics: high eosinophil count and elevated serum IgE. The initial dosing is based on the asthma treatment nomogram for the drug; he titrates it according to clinical response. “We don’t alter the total dose given, but we do adjust the frequency with which we give it.”
His first patient was a 70-year-old woman with a 1-year history of poorly controlled BP; she had failed prednisone, azathioprine, and minocycline. She also had a history of steroid-related vertebral compression fractures. She presented with an eosinophil count of over 400 cells/microL.
“We treated her with subcutaneous injections of 300 mg every 2 weeks for 16 weeks,” Dr. Yu said. Within 1 week, she had a 44% reduction in blisters; within 4 weeks, she had gone from 50% body surface area involvement to 5%.
After eight injections, the patient was disease free and Dr. Yu discontinued treatment. She remained clear until week 32 after treatment initiation; she had a flare manifested by increased pruritus and recurrence of lesions. Dr. Yu restarted omalizumab and the lesions cleared within 2 weeks. From weeks 35-72, the patient received five more injections and remained disease free.
“After that, she did have another flare, so we used omalizumab again,” but without the same excellent results. “She had an initial decrease in pruritus, and symptom improvement, but her disease subsequently worsened. We restarted her on prednisone and azathioprine and she has done well.”
Dr. Yu said he made “a couple of interesting observations on this case.”
“We saw no real correlation between disease activity score, and the levels of serum IgG antibodies. But we did notice a parallel correlation with the level of eosinophil and disease severity and also treatment response,” he said. “It was quite clear that immediately after injection, she had a dramatic drop in eosinophils” from 1,600 to 60 cells/microL within 24 hours.
His next case was a 72-year-old woman with a history of somewhat controlled essential tremor, and 6 months of highly pruritic BP blistering. She had been treated with 60 mg/day prednisone, but didn’t tolerate it well, developing steroid-induced psychosis with agitation and violence, and a worsening of her tremor. The steroid was tapered to 40 mg/day and azathioprine was added, but she was did not respond to this change and continued to develop new blisters each day. She was admitted to the hospital for plasmapheresis, which was not helpful. Nor did she respond to six cycles of cyclophosphamide.
At that point, Dr. Yu drew IgE and eosinophil levels: Her absolute eosinophil count was 1,600 cells/microL and IgE was 287 units/mL. He then gave the patient 300 mg omalizumab subcutaneously.
“Ten days after a single injection, her blisters had almost completely resolved,” he said. “To briefly describe her disease course, the blisters went away, and she had resolution of her pruritus. She was discharged with 1 month of prednisone, but we tapered that and have been able to maintain her on omalizumab alone. She had one mild flare, which was readily controlled with prednisone. The last time we saw her, she was disease free.”
He also described four other steroid-refractory BP patients treated with omalizumab.“Their commonalities were that they all had steroid-refractory disease that was resistant to immunosuppressants, had a high level of IgE, and most of them also had eosinophilia.”
Dr. Yu’s descriptions:
• A 78-year-old woman with refractory BP of 1.5 years responded well to three initial injections spaced 6 and 4 weeks apart, and has been well maintained for 20 months with 300-mL injections administered once a month. One relapse was easily controlled.
• A 72-year-old woman with 3.5 years of refractory BP responded well to 375 mg injections every 4 weeks and has been symptom free for a year on that maintenance dose.
• A 55-year-old woman with a 7-month history of refractory BP experienced a 30% reduction in body surface area blistering within 1 week of her first 375-mg injection. By 3 weeks, she was clear. She had three injections, 2 weeks apart, and was disease free for 3 months.
• An 86-year-old woman with longstanding refractory BP experienced a 22% reduction in blister count within a week of her first 375-mL injection. After a series of injections every 2 weeks, however, she developed an exacerbation of her preexisting chronic obstructive pulmonary disease, which was due primarily to tapering her prednisone. However, she no longer uses omalizumab.
“It is difficult to make recommendations because of the limitations of our data,” Dr. Yu said. “But based on the small number of patients we have treated, I would consider using omalizumab in patients with resistant disease who have an elevated IgE and eosinophil count. The optimal dosing regimen is not yet determined. Our approach is to start out with the asthma dosing and titrate until we see improvement. We use the highest dose indicated for the patient’s weight and IgE levels, typically 300-375 mg subcutaneously every 2-8 weeks, and start tapering when the patient gets control.”
He had no financial disclosures.
[email protected]
On Twitter @Alz_Gal
ORLANDO – Omalizumab, a monoclonal anti-IgE antibody, may be a good option for patients with treatment-refractory bullous pemphigoid.
Patients who received omalizumab (Xolair) experienced rapid improvements, with 30%-50% lesion clearance within a week and complete clearance by 3 weeks, Kenneth Yu, MD, said at the annual meeting of the American Academy of Dermatology. With regular injections, they were kept symptom free for months. Some patients did flare, but were then easily controlled on standard treatment. Omalizumab, approved by the Food and Drug Administration in 2003, is indicated for moderate to severe persistent asthma and chronic idiopathic urticaria.
“We have now treated six patients with omalizumab with very good results with five of them. These are not your garden-variety BP patients, but people with very treatment-resistant disease who have failed treatment with corticosteroids alone, and in combination with other immunosuppressants.”
The rapid clinical improvements, along with observations that eosinophilia decreased with treatment, “strengthen the evidence that BP is an IgE-mediated, organ-specific autoimmune disease,” said Dr. Yu, senior resident in dermatology at the University of Michigan, Ann Arbor.
“Would I use this as a first-line treatment for BP? Probably not. But if you are seeing someone who’s nonresponsive to therapy, you might want to check IgE and eosinophil levels and if those are elevated, you might consider omalizumab as an adjunct treatment – and you might observe a fairly dramatic response.”
Three of Dr. Yu’s patients received omalizumab as monotherapy, and three received it in conjunction with other immunosuppressants. He described their disease presentation, treatment, and progression.
In general, Dr. Yu reserves omalizumab for patients with refractory disease and two particular clinical characteristics: high eosinophil count and elevated serum IgE. The initial dosing is based on the asthma treatment nomogram for the drug; he titrates it according to clinical response. “We don’t alter the total dose given, but we do adjust the frequency with which we give it.”
His first patient was a 70-year-old woman with a 1-year history of poorly controlled BP; she had failed prednisone, azathioprine, and minocycline. She also had a history of steroid-related vertebral compression fractures. She presented with an eosinophil count of over 400 cells/microL.
“We treated her with subcutaneous injections of 300 mg every 2 weeks for 16 weeks,” Dr. Yu said. Within 1 week, she had a 44% reduction in blisters; within 4 weeks, she had gone from 50% body surface area involvement to 5%.
After eight injections, the patient was disease free and Dr. Yu discontinued treatment. She remained clear until week 32 after treatment initiation; she had a flare manifested by increased pruritus and recurrence of lesions. Dr. Yu restarted omalizumab and the lesions cleared within 2 weeks. From weeks 35-72, the patient received five more injections and remained disease free.
“After that, she did have another flare, so we used omalizumab again,” but without the same excellent results. “She had an initial decrease in pruritus, and symptom improvement, but her disease subsequently worsened. We restarted her on prednisone and azathioprine and she has done well.”
Dr. Yu said he made “a couple of interesting observations on this case.”
“We saw no real correlation between disease activity score, and the levels of serum IgG antibodies. But we did notice a parallel correlation with the level of eosinophil and disease severity and also treatment response,” he said. “It was quite clear that immediately after injection, she had a dramatic drop in eosinophils” from 1,600 to 60 cells/microL within 24 hours.
His next case was a 72-year-old woman with a history of somewhat controlled essential tremor, and 6 months of highly pruritic BP blistering. She had been treated with 60 mg/day prednisone, but didn’t tolerate it well, developing steroid-induced psychosis with agitation and violence, and a worsening of her tremor. The steroid was tapered to 40 mg/day and azathioprine was added, but she was did not respond to this change and continued to develop new blisters each day. She was admitted to the hospital for plasmapheresis, which was not helpful. Nor did she respond to six cycles of cyclophosphamide.
At that point, Dr. Yu drew IgE and eosinophil levels: Her absolute eosinophil count was 1,600 cells/microL and IgE was 287 units/mL. He then gave the patient 300 mg omalizumab subcutaneously.
“Ten days after a single injection, her blisters had almost completely resolved,” he said. “To briefly describe her disease course, the blisters went away, and she had resolution of her pruritus. She was discharged with 1 month of prednisone, but we tapered that and have been able to maintain her on omalizumab alone. She had one mild flare, which was readily controlled with prednisone. The last time we saw her, she was disease free.”
He also described four other steroid-refractory BP patients treated with omalizumab.“Their commonalities were that they all had steroid-refractory disease that was resistant to immunosuppressants, had a high level of IgE, and most of them also had eosinophilia.”
Dr. Yu’s descriptions:
• A 78-year-old woman with refractory BP of 1.5 years responded well to three initial injections spaced 6 and 4 weeks apart, and has been well maintained for 20 months with 300-mL injections administered once a month. One relapse was easily controlled.
• A 72-year-old woman with 3.5 years of refractory BP responded well to 375 mg injections every 4 weeks and has been symptom free for a year on that maintenance dose.
• A 55-year-old woman with a 7-month history of refractory BP experienced a 30% reduction in body surface area blistering within 1 week of her first 375-mg injection. By 3 weeks, she was clear. She had three injections, 2 weeks apart, and was disease free for 3 months.
• An 86-year-old woman with longstanding refractory BP experienced a 22% reduction in blister count within a week of her first 375-mL injection. After a series of injections every 2 weeks, however, she developed an exacerbation of her preexisting chronic obstructive pulmonary disease, which was due primarily to tapering her prednisone. However, she no longer uses omalizumab.
“It is difficult to make recommendations because of the limitations of our data,” Dr. Yu said. “But based on the small number of patients we have treated, I would consider using omalizumab in patients with resistant disease who have an elevated IgE and eosinophil count. The optimal dosing regimen is not yet determined. Our approach is to start out with the asthma dosing and titrate until we see improvement. We use the highest dose indicated for the patient’s weight and IgE levels, typically 300-375 mg subcutaneously every 2-8 weeks, and start tapering when the patient gets control.”
He had no financial disclosures.
[email protected]
On Twitter @Alz_Gal
ORLANDO – Omalizumab, a monoclonal anti-IgE antibody, may be a good option for patients with treatment-refractory bullous pemphigoid.
Patients who received omalizumab (Xolair) experienced rapid improvements, with 30%-50% lesion clearance within a week and complete clearance by 3 weeks, Kenneth Yu, MD, said at the annual meeting of the American Academy of Dermatology. With regular injections, they were kept symptom free for months. Some patients did flare, but were then easily controlled on standard treatment. Omalizumab, approved by the Food and Drug Administration in 2003, is indicated for moderate to severe persistent asthma and chronic idiopathic urticaria.
“We have now treated six patients with omalizumab with very good results with five of them. These are not your garden-variety BP patients, but people with very treatment-resistant disease who have failed treatment with corticosteroids alone, and in combination with other immunosuppressants.”
The rapid clinical improvements, along with observations that eosinophilia decreased with treatment, “strengthen the evidence that BP is an IgE-mediated, organ-specific autoimmune disease,” said Dr. Yu, senior resident in dermatology at the University of Michigan, Ann Arbor.
“Would I use this as a first-line treatment for BP? Probably not. But if you are seeing someone who’s nonresponsive to therapy, you might want to check IgE and eosinophil levels and if those are elevated, you might consider omalizumab as an adjunct treatment – and you might observe a fairly dramatic response.”
Three of Dr. Yu’s patients received omalizumab as monotherapy, and three received it in conjunction with other immunosuppressants. He described their disease presentation, treatment, and progression.
In general, Dr. Yu reserves omalizumab for patients with refractory disease and two particular clinical characteristics: high eosinophil count and elevated serum IgE. The initial dosing is based on the asthma treatment nomogram for the drug; he titrates it according to clinical response. “We don’t alter the total dose given, but we do adjust the frequency with which we give it.”
His first patient was a 70-year-old woman with a 1-year history of poorly controlled BP; she had failed prednisone, azathioprine, and minocycline. She also had a history of steroid-related vertebral compression fractures. She presented with an eosinophil count of over 400 cells/microL.
“We treated her with subcutaneous injections of 300 mg every 2 weeks for 16 weeks,” Dr. Yu said. Within 1 week, she had a 44% reduction in blisters; within 4 weeks, she had gone from 50% body surface area involvement to 5%.
After eight injections, the patient was disease free and Dr. Yu discontinued treatment. She remained clear until week 32 after treatment initiation; she had a flare manifested by increased pruritus and recurrence of lesions. Dr. Yu restarted omalizumab and the lesions cleared within 2 weeks. From weeks 35-72, the patient received five more injections and remained disease free.
“After that, she did have another flare, so we used omalizumab again,” but without the same excellent results. “She had an initial decrease in pruritus, and symptom improvement, but her disease subsequently worsened. We restarted her on prednisone and azathioprine and she has done well.”
Dr. Yu said he made “a couple of interesting observations on this case.”
“We saw no real correlation between disease activity score, and the levels of serum IgG antibodies. But we did notice a parallel correlation with the level of eosinophil and disease severity and also treatment response,” he said. “It was quite clear that immediately after injection, she had a dramatic drop in eosinophils” from 1,600 to 60 cells/microL within 24 hours.
His next case was a 72-year-old woman with a history of somewhat controlled essential tremor, and 6 months of highly pruritic BP blistering. She had been treated with 60 mg/day prednisone, but didn’t tolerate it well, developing steroid-induced psychosis with agitation and violence, and a worsening of her tremor. The steroid was tapered to 40 mg/day and azathioprine was added, but she was did not respond to this change and continued to develop new blisters each day. She was admitted to the hospital for plasmapheresis, which was not helpful. Nor did she respond to six cycles of cyclophosphamide.
At that point, Dr. Yu drew IgE and eosinophil levels: Her absolute eosinophil count was 1,600 cells/microL and IgE was 287 units/mL. He then gave the patient 300 mg omalizumab subcutaneously.
“Ten days after a single injection, her blisters had almost completely resolved,” he said. “To briefly describe her disease course, the blisters went away, and she had resolution of her pruritus. She was discharged with 1 month of prednisone, but we tapered that and have been able to maintain her on omalizumab alone. She had one mild flare, which was readily controlled with prednisone. The last time we saw her, she was disease free.”
He also described four other steroid-refractory BP patients treated with omalizumab.“Their commonalities were that they all had steroid-refractory disease that was resistant to immunosuppressants, had a high level of IgE, and most of them also had eosinophilia.”
Dr. Yu’s descriptions:
• A 78-year-old woman with refractory BP of 1.5 years responded well to three initial injections spaced 6 and 4 weeks apart, and has been well maintained for 20 months with 300-mL injections administered once a month. One relapse was easily controlled.
• A 72-year-old woman with 3.5 years of refractory BP responded well to 375 mg injections every 4 weeks and has been symptom free for a year on that maintenance dose.
• A 55-year-old woman with a 7-month history of refractory BP experienced a 30% reduction in body surface area blistering within 1 week of her first 375-mg injection. By 3 weeks, she was clear. She had three injections, 2 weeks apart, and was disease free for 3 months.
• An 86-year-old woman with longstanding refractory BP experienced a 22% reduction in blister count within a week of her first 375-mL injection. After a series of injections every 2 weeks, however, she developed an exacerbation of her preexisting chronic obstructive pulmonary disease, which was due primarily to tapering her prednisone. However, she no longer uses omalizumab.
“It is difficult to make recommendations because of the limitations of our data,” Dr. Yu said. “But based on the small number of patients we have treated, I would consider using omalizumab in patients with resistant disease who have an elevated IgE and eosinophil count. The optimal dosing regimen is not yet determined. Our approach is to start out with the asthma dosing and titrate until we see improvement. We use the highest dose indicated for the patient’s weight and IgE levels, typically 300-375 mg subcutaneously every 2-8 weeks, and start tapering when the patient gets control.”
He had no financial disclosures.
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