Key clinical point: Asthma is associated with an increased risk of osteoporosis and fragility fractures (FF), particularly vertebral and humerus fractures.

Major finding: The risk of osteoporosis and FF was higher in asthma vs. non-asthma group (adjusted hazard ratio [aHR]: 1.18 and 1.12, respectively). The effect was stronger in younger age groups (P_interaction less than .0001). Forearm-wrist (aHR, 1.21) and vertebra (aHR, 1.19) were the sites associated with a higher risk. Among patients with asthma, a single oral corticosteroid course increased the risk of osteoporosis, and greater use of inhaled corticosteroids increased the risk of both bone diseases.

Study details: This population-based matched cohort study included 138,123 patients with asthma and 520,626 age-, sex-, and practice-matched people without asthma using data from the U.K. Clinical Practice Research Datalink.

Disclosures: The study was funded by a research grant from the British Medical Association. The authors declared no conflicts of interest.

Source: Chalitsios CV et al. Eur Respir J. 2020 Aug 6. doi: 10.1183/13993003.01251-2020.

Key clinical point: Asthma is associated with an increased risk of osteoporosis and fragility fractures (FF), particularly vertebral and humerus fractures.

Major finding: The risk of osteoporosis and FF was higher in asthma vs. non-asthma group (adjusted hazard ratio [aHR]: 1.18 and 1.12, respectively). The effect was stronger in younger age groups (P_interaction less than .0001). Forearm-wrist (aHR, 1.21) and vertebra (aHR, 1.19) were the sites associated with a higher risk. Among patients with asthma, a single oral corticosteroid course increased the risk of osteoporosis, and greater use of inhaled corticosteroids increased the risk of both bone diseases.

Study details: This population-based matched cohort study included 138,123 patients with asthma and 520,626 age-, sex-, and practice-matched people without asthma using data from the U.K. Clinical Practice Research Datalink.

Disclosures: The study was funded by a research grant from the British Medical Association. The authors declared no conflicts of interest.

Source: Chalitsios CV et al. Eur Respir J. 2020 Aug 6. doi: 10.1183/13993003.01251-2020.

Key clinical point: Asthma is associated with an increased risk of osteoporosis and fragility fractures (FF), particularly vertebral and humerus fractures.

Major finding: The risk of osteoporosis and FF was higher in asthma vs. non-asthma group (adjusted hazard ratio [aHR]: 1.18 and 1.12, respectively). The effect was stronger in younger age groups (P_interaction less than .0001). Forearm-wrist (aHR, 1.21) and vertebra (aHR, 1.19) were the sites associated with a higher risk. Among patients with asthma, a single oral corticosteroid course increased the risk of osteoporosis, and greater use of inhaled corticosteroids increased the risk of both bone diseases.

Study details: This population-based matched cohort study included 138,123 patients with asthma and 520,626 age-, sex-, and practice-matched people without asthma using data from the U.K. Clinical Practice Research Datalink.

Disclosures: The study was funded by a research grant from the British Medical Association. The authors declared no conflicts of interest.

Source: Chalitsios CV et al. Eur Respir J. 2020 Aug 6. doi: 10.1183/13993003.01251-2020.

Application of oil to the hair and scalp – purported to promote increased shine, health, and growth, and decrease graying of the hair – is used in many different cultures worldwide, including in India and among people of the African diaspora. Hair oiling typically entails combing the hair, followed by applying oil from the roots to the ends about once a week prior to shampooing. Hair oiling daily or every other day, often with a hair braid, is also practiced, using coconut oil or other oils. Oil is found in various hair products and has been popular in the United States, particularly as hot oil treatments in the 1980s.

Oils are used as part of Abhyanga massage, either by an Ayurvedic practitioner or as self-massage, as part of ancient Indian Ayurvedic medicine practice. The type of oil used is determined by the practitioner depending on the individual’s needs; cold-pressed sesame oil or coconut oil is often used as the base oil. Abhyanga is often performed with oil on the entire body as an act of self-care, which includes massage of the hair and scalp. The oil and herbs that are often added to the oil, as well as the scalp massage itself, are explained by practitioners as having therapeutic effects on the hair, including exfoliation of a dry scalp and on overall well-being. Outside of Ayurvedic medicine, hair oiling is also sometimes performed in India as part of routine hair care and can be a bonding experience among parents, grandparents, and children.

Amla oil, which is derived from Indian gooseberry (Phyllanthus emblica L.) and is often used in India on the hair, contains Vitamin C and has been shown to have activity against dermatophytes. In a study conducted in India, amla oil was found to have the most activity against Microsporum canis, M. gypseum, and Trichophyton rubrum, followed by cantharidine and coconut oil, while T. mentagrophytes was most susceptible to coconut oil, followed by amla and cantharidine oil.¹ A study conducted in mice in Thailand found that 5-alpha-reductase was reduced with the dried form of the herb Phyllanthus emblica L, as well as with some other traditional Thai herbs used as hair treatments.²

Castor oil has been utilized in many cultures to promote hair growth. Ricinoleic acid, an unsaturated omega-9 fatty acid and hydroxy acid, is the major component of seed oil obtained from mature castor plants. It has anti-inflammatory and antimicrobial effects, and in one study,³ was found to inhibit prostaglandin D2, which has been implicated in the pathogenesis of androgenetic alopecia.⁴ Jamaican black castor oil is darker in color and has a more alkaline pH compared with traditional castor oil (both contain ricinoleic acid). To produce Jamaican black castor oil, the seed is roasted, ground to a thick paste, boiled in a pot of hot water, then the oil is skimmed off of the top into individual bottles, whereas regular castor oil is cold pressed. The alkalinity of Jamaican black castor oil may play a role in opening up the hair cuticle, which may be beneficial, but application also needs to be followed by a routine that includes closing the cuticle to avoid increasing hair fragility; such a routine could include, for example, leave-in conditioner or rinsing conditioner with colder water.

Castor oil is sometimes used on its own or in combination with other oils, and it is also an ingredient in some hair care products. However, publicly available peer-reviewed research articles demonstrating the effects of castor oil when applied directly to the hair and scalp for hair growth are needed.

Different types of hair oils are used in African American hair care products and, worldwide, by people of the African diaspora as part of regular hair care and hair styling. Common oils include jojoba, coconut, castor, argan, olive, sunflower, and almond oils. Very curly hair often dries out more easily, especially in drier climates; and sebum build-up on the scalp does not occur as quickly, so hair typically does not need to be shampooed frequently. As such, over-shampooing also often dries the hair out faster, especially if hair has been chemically processed. Thus, oils help to coat and protect the hair, and smooth the cuticle. Oils themselves do not moisturize, but can seal moisture into the hair or act as humectants and draw moisture in. Rather than applying on dry hair, oils, when used as daily care as opposed to before shampooing, are often applied on clean hair after shampooing and after a leave-in conditioner has been applied to help seal in moisture for the most benefit. For treatment of scalp conditions, depending on the type of hair care practice performed at home, oils may be preferred over potentially drying solutions and foams if available, for optimum hair care.

Hair oiling is a long-standing practice which, when used correctly, can be beneficial for hair management and health. There are, however, caveats to hair oiling, which include being careful not to excessively brush or comb hair that has a lot of oil in it because the hair is slick, which can cause hair to fall out during combing. Some oils have elevated levels of lauric acid (coconut oil has 50%), which has a high affinity for hair proteins.⁵ While this can support hair strength, care should be taken not to overuse some oils or other products known as “protein packs,” which should be used as directed. Since hair is protein, excess protein build-up coating the hair can block needed moisture, making the hair more knotted and brittle, potentially resulting in more breakage with brushing or other hair care practices.

Some oil-containing hair products also contain artificial fragrances and/or dyes, which in some individuals, may promote an immunogenic effect, such as contact dermatitis. Certain oils, particularly olive oil, can promote an environment favorable to yeast growth, especially Malassezia species, implicated in seborrheic dermatitis. Practices that involve excessive application of oil to the scalp can also result in build up if not shampooed regularly. Sulfonated castor oil (also known as Turkey Red oil) has been reported to cause contact dermatitis.⁶
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

Application of oil to the hair and scalp – purported to promote increased shine, health, and growth, and decrease graying of the hair – is used in many different cultures worldwide, including in India and among people of the African diaspora. Hair oiling typically entails combing the hair, followed by applying oil from the roots to the ends about once a week prior to shampooing. Hair oiling daily or every other day, often with a hair braid, is also practiced, using coconut oil or other oils. Oil is found in various hair products and has been popular in the United States, particularly as hot oil treatments in the 1980s.

Oils are used as part of Abhyanga massage, either by an Ayurvedic practitioner or as self-massage, as part of ancient Indian Ayurvedic medicine practice. The type of oil used is determined by the practitioner depending on the individual’s needs; cold-pressed sesame oil or coconut oil is often used as the base oil. Abhyanga is often performed with oil on the entire body as an act of self-care, which includes massage of the hair and scalp. The oil and herbs that are often added to the oil, as well as the scalp massage itself, are explained by practitioners as having therapeutic effects on the hair, including exfoliation of a dry scalp and on overall well-being. Outside of Ayurvedic medicine, hair oiling is also sometimes performed in India as part of routine hair care and can be a bonding experience among parents, grandparents, and children.

Amla oil, which is derived from Indian gooseberry (Phyllanthus emblica L.) and is often used in India on the hair, contains Vitamin C and has been shown to have activity against dermatophytes. In a study conducted in India, amla oil was found to have the most activity against Microsporum canis, M. gypseum, and Trichophyton rubrum, followed by cantharidine and coconut oil, while T. mentagrophytes was most susceptible to coconut oil, followed by amla and cantharidine oil.¹ A study conducted in mice in Thailand found that 5-alpha-reductase was reduced with the dried form of the herb Phyllanthus emblica L, as well as with some other traditional Thai herbs used as hair treatments.²

Castor oil has been utilized in many cultures to promote hair growth. Ricinoleic acid, an unsaturated omega-9 fatty acid and hydroxy acid, is the major component of seed oil obtained from mature castor plants. It has anti-inflammatory and antimicrobial effects, and in one study,³ was found to inhibit prostaglandin D2, which has been implicated in the pathogenesis of androgenetic alopecia.⁴ Jamaican black castor oil is darker in color and has a more alkaline pH compared with traditional castor oil (both contain ricinoleic acid). To produce Jamaican black castor oil, the seed is roasted, ground to a thick paste, boiled in a pot of hot water, then the oil is skimmed off of the top into individual bottles, whereas regular castor oil is cold pressed. The alkalinity of Jamaican black castor oil may play a role in opening up the hair cuticle, which may be beneficial, but application also needs to be followed by a routine that includes closing the cuticle to avoid increasing hair fragility; such a routine could include, for example, leave-in conditioner or rinsing conditioner with colder water.

Castor oil is sometimes used on its own or in combination with other oils, and it is also an ingredient in some hair care products. However, publicly available peer-reviewed research articles demonstrating the effects of castor oil when applied directly to the hair and scalp for hair growth are needed.

Different types of hair oils are used in African American hair care products and, worldwide, by people of the African diaspora as part of regular hair care and hair styling. Common oils include jojoba, coconut, castor, argan, olive, sunflower, and almond oils. Very curly hair often dries out more easily, especially in drier climates; and sebum build-up on the scalp does not occur as quickly, so hair typically does not need to be shampooed frequently. As such, over-shampooing also often dries the hair out faster, especially if hair has been chemically processed. Thus, oils help to coat and protect the hair, and smooth the cuticle. Oils themselves do not moisturize, but can seal moisture into the hair or act as humectants and draw moisture in. Rather than applying on dry hair, oils, when used as daily care as opposed to before shampooing, are often applied on clean hair after shampooing and after a leave-in conditioner has been applied to help seal in moisture for the most benefit. For treatment of scalp conditions, depending on the type of hair care practice performed at home, oils may be preferred over potentially drying solutions and foams if available, for optimum hair care.

Hair oiling is a long-standing practice which, when used correctly, can be beneficial for hair management and health. There are, however, caveats to hair oiling, which include being careful not to excessively brush or comb hair that has a lot of oil in it because the hair is slick, which can cause hair to fall out during combing. Some oils have elevated levels of lauric acid (coconut oil has 50%), which has a high affinity for hair proteins.⁵ While this can support hair strength, care should be taken not to overuse some oils or other products known as “protein packs,” which should be used as directed. Since hair is protein, excess protein build-up coating the hair can block needed moisture, making the hair more knotted and brittle, potentially resulting in more breakage with brushing or other hair care practices.

Some oil-containing hair products also contain artificial fragrances and/or dyes, which in some individuals, may promote an immunogenic effect, such as contact dermatitis. Certain oils, particularly olive oil, can promote an environment favorable to yeast growth, especially Malassezia species, implicated in seborrheic dermatitis. Practices that involve excessive application of oil to the scalp can also result in build up if not shampooed regularly. Sulfonated castor oil (also known as Turkey Red oil) has been reported to cause contact dermatitis.⁶
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

Application of oil to the hair and scalp – purported to promote increased shine, health, and growth, and decrease graying of the hair – is used in many different cultures worldwide, including in India and among people of the African diaspora. Hair oiling typically entails combing the hair, followed by applying oil from the roots to the ends about once a week prior to shampooing. Hair oiling daily or every other day, often with a hair braid, is also practiced, using coconut oil or other oils. Oil is found in various hair products and has been popular in the United States, particularly as hot oil treatments in the 1980s.

Oils are used as part of Abhyanga massage, either by an Ayurvedic practitioner or as self-massage, as part of ancient Indian Ayurvedic medicine practice. The type of oil used is determined by the practitioner depending on the individual’s needs; cold-pressed sesame oil or coconut oil is often used as the base oil. Abhyanga is often performed with oil on the entire body as an act of self-care, which includes massage of the hair and scalp. The oil and herbs that are often added to the oil, as well as the scalp massage itself, are explained by practitioners as having therapeutic effects on the hair, including exfoliation of a dry scalp and on overall well-being. Outside of Ayurvedic medicine, hair oiling is also sometimes performed in India as part of routine hair care and can be a bonding experience among parents, grandparents, and children.

Amla oil, which is derived from Indian gooseberry (Phyllanthus emblica L.) and is often used in India on the hair, contains Vitamin C and has been shown to have activity against dermatophytes. In a study conducted in India, amla oil was found to have the most activity against Microsporum canis, M. gypseum, and Trichophyton rubrum, followed by cantharidine and coconut oil, while T. mentagrophytes was most susceptible to coconut oil, followed by amla and cantharidine oil.¹ A study conducted in mice in Thailand found that 5-alpha-reductase was reduced with the dried form of the herb Phyllanthus emblica L, as well as with some other traditional Thai herbs used as hair treatments.²

Castor oil has been utilized in many cultures to promote hair growth. Ricinoleic acid, an unsaturated omega-9 fatty acid and hydroxy acid, is the major component of seed oil obtained from mature castor plants. It has anti-inflammatory and antimicrobial effects, and in one study,³ was found to inhibit prostaglandin D2, which has been implicated in the pathogenesis of androgenetic alopecia.⁴ Jamaican black castor oil is darker in color and has a more alkaline pH compared with traditional castor oil (both contain ricinoleic acid). To produce Jamaican black castor oil, the seed is roasted, ground to a thick paste, boiled in a pot of hot water, then the oil is skimmed off of the top into individual bottles, whereas regular castor oil is cold pressed. The alkalinity of Jamaican black castor oil may play a role in opening up the hair cuticle, which may be beneficial, but application also needs to be followed by a routine that includes closing the cuticle to avoid increasing hair fragility; such a routine could include, for example, leave-in conditioner or rinsing conditioner with colder water.

Castor oil is sometimes used on its own or in combination with other oils, and it is also an ingredient in some hair care products. However, publicly available peer-reviewed research articles demonstrating the effects of castor oil when applied directly to the hair and scalp for hair growth are needed.

Different types of hair oils are used in African American hair care products and, worldwide, by people of the African diaspora as part of regular hair care and hair styling. Common oils include jojoba, coconut, castor, argan, olive, sunflower, and almond oils. Very curly hair often dries out more easily, especially in drier climates; and sebum build-up on the scalp does not occur as quickly, so hair typically does not need to be shampooed frequently. As such, over-shampooing also often dries the hair out faster, especially if hair has been chemically processed. Thus, oils help to coat and protect the hair, and smooth the cuticle. Oils themselves do not moisturize, but can seal moisture into the hair or act as humectants and draw moisture in. Rather than applying on dry hair, oils, when used as daily care as opposed to before shampooing, are often applied on clean hair after shampooing and after a leave-in conditioner has been applied to help seal in moisture for the most benefit. For treatment of scalp conditions, depending on the type of hair care practice performed at home, oils may be preferred over potentially drying solutions and foams if available, for optimum hair care.

Hair oiling is a long-standing practice which, when used correctly, can be beneficial for hair management and health. There are, however, caveats to hair oiling, which include being careful not to excessively brush or comb hair that has a lot of oil in it because the hair is slick, which can cause hair to fall out during combing. Some oils have elevated levels of lauric acid (coconut oil has 50%), which has a high affinity for hair proteins.⁵ While this can support hair strength, care should be taken not to overuse some oils or other products known as “protein packs,” which should be used as directed. Since hair is protein, excess protein build-up coating the hair can block needed moisture, making the hair more knotted and brittle, potentially resulting in more breakage with brushing or other hair care practices.

Some oil-containing hair products also contain artificial fragrances and/or dyes, which in some individuals, may promote an immunogenic effect, such as contact dermatitis. Certain oils, particularly olive oil, can promote an environment favorable to yeast growth, especially Malassezia species, implicated in seborrheic dermatitis. Practices that involve excessive application of oil to the scalp can also result in build up if not shampooed regularly. Sulfonated castor oil (also known as Turkey Red oil) has been reported to cause contact dermatitis.⁶
 

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

In this historical portrait, I am focusing mainly on dermatologists who have developed a skin care line, and I am loosely following a chronological order. Thanks to all the readers of Part 1 (The interesting history of dermatologist-developed skin care), who gave me interesting feedback on my Facebook and LinkedIn accounts. There was so much interest that I will write Part 3 next month. Feel free to DM me your ideas on LinkedIn.

The history of dermatologist-developed skin care continues as more dermatologists become interested in developing a skin care line or retailing skin care in their medical practice. A report in July 2020 showed that physician-dispensed skin care is the largest growing segment of the skin care business with a projected compound annual growth rate of 9.9% from 2020 to 2027. I have not seen national sales numbers since this July report, but we have noticed a large increase in online sales for the doctors using my Skin Type Solutions System. This is most likely because, in a national crisis, the self-care and beauty business segments often see growth. So as you can see, dermatologist-dispensed skin care is becoming a major player in national skin care sales. Let’s get back to the story of how this came to be the case.

Peter Elias, MD. Dr. Elias is professor in the department of dermatology at the University of California, San Francisco. In 1996, Dr. Elias published a landmark paper in the Journal of Investigative Dermatology demonstrating that a 1:1:1 ratio of ceramides, fatty acids, and cholesterol is required to repair a damaged skin barrier. He filed multiple patents for using these lipids in moisturizers as early as 1992. His lipid research has stood the test of time, and this paper is still frequently cited. Dr. Elias has authored over 500 peer reviewed articles on the skin barrier, has edited or coauthored three books on skin barrier science, and developed EpiCeram, a product that utilizes ceramide, the fatty acid linoleic acid, and cholesterol. EpiCeram is the only barrier repair moisturizer approved by the Food and Drug Administration and is available by prescription only.

Kathy Fields, MD, and Katie Rodan, MD. Dr. Fields and Dr. Rodan met at Stanford (Calif.) University. In the 1980s, these entrepreneurial dermatologists realized that patients did not understand the role of preventing acne rather than just treating it. As dermatologists, they knew that a consistent daily routine to prevent acne was much more effective than waiting for an outbreak and spot-treating lesions. They took an already available OTC medication – benzoyl peroxide – and educated consumers through infomercials that they needed to stay ahead of acne instead of waiting for a breakout. Using infomercials to sell skin care, selling skin care kits, and educating patients about the need to prevent acne rather than spot treat it was very unusual at the time. As we all know, reeducating your patients is a huge challenge. Dr. Fields and Dr. Rodan changed consumers thinking in a genius way that continues to resonate today by choosing a brand name to make their point: Proactiv. Their simple 3-step acne kit encouraged patients to be proactive about their acne and encouraged compliance. (Patients love exact skin care steps as demonstrated again by the success of the skin care line from plastic surgeon Suzan Obagi, MD, which became available around 1988).

Dr. Fields and Dr. Rodan first offered Proactiv to Neutrogena, which turned it down. This early disappointment did not deter them and ended up benefiting them because this gave them the idea to do infomercials. Guthy Renker agreed to market and distribute the product, and the first Proactiv infomercial appeared on TV in 1995. It quickly became popular and is still one of the best selling skin care lines of all time. It’s important to note that the “overnight success” of Proactiv took at least a decade of effort.

Heather Woolery Lloyd, MD. Dr. Woolery Lloyd got her medical degree at the University of Miami where she also completed her dermatology residency. Her interest in skin of color led to her appointment as director of Ethnic Skin Care at the University of Miami, the country’s first cosmetic ethnic skin care department at a major university. She spent years lecturing around the world on skin of color issues and performing clinical trials before she developed the “Specific Beauty” skin care line for melanin rich skin types. Specific Beauty was acquired by Guthy Renker and is available online. It is the most popular dermatologist developed skin care line for skin of color.

In the late 1980s and early 1990s, other dermatologists threw their hats into the ring and came out with skin care lines – some successful and some not. Unfortunately, many skin care lines at that time were based on “pseudoscience” and exaggerated claims, which fueled the fire of those who felt dermatologists should steer clear of these entrepreneurial pursuits. A debate about the ethics of doctors retailing skin care began, and the controversy led to this 2010 statement by the American Medical Association: “In-office sale of health-related products by physicians presents a financial conflict of interest, risks placing undue pressure on the patient, and threatens to erode patient trust and undermine the primary obligation of physicians to serve the interests of their patients before their own.”

Many dermatologists dropped out of the AMA as a result because they felt the organization was no longer representing dermatologist’s interests. After all, we know skin care science better than anyone, and many dermatologists were insulted by the suggestion that we would place our personal financial gain over the best interests of our patients.

This is a perfect example of how the actions of a few unscrupulous dermatologists can affect the entire specialty. I like to focus on the ethical entrepreneurial dermatologists who made great contributions to the skin care industry based on science, efficacy, and patient education and encourage the ethical among us to provide this science-based information to our patients to protect them from pseudoscience-based opportunists. It is obvious that I believe that dermatologists have a responsibility to provide medical advice on skin care to their patients. If not us, who will do it as ethically as we will? But I plead with those of you out there who are promoting foolish stem cell–containing creams and other impossible technologies to remember that you are hurting the credibility of our entire dermatology profession.

In my next column, I will discuss dermatologists who have played a significant role behind the scenes in the development of the skin care industry.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].  

References

Castanedo-Tardan MP, Baumann L. Clin Dermatol. Jul-Aug 2009;27(4):355-8.

Gormley DE. Arch Dermatol. 1999 Jul;135(7):765-6.

Miller RC. Arch Dermatol. 1999 Mar;135(3):255-6.

Virtual Mentor. 2010;12(12):925-7.
 

In this historical portrait, I am focusing mainly on dermatologists who have developed a skin care line, and I am loosely following a chronological order. Thanks to all the readers of Part 1 (The interesting history of dermatologist-developed skin care), who gave me interesting feedback on my Facebook and LinkedIn accounts. There was so much interest that I will write Part 3 next month. Feel free to DM me your ideas on LinkedIn.

The history of dermatologist-developed skin care continues as more dermatologists become interested in developing a skin care line or retailing skin care in their medical practice. A report in July 2020 showed that physician-dispensed skin care is the largest growing segment of the skin care business with a projected compound annual growth rate of 9.9% from 2020 to 2027. I have not seen national sales numbers since this July report, but we have noticed a large increase in online sales for the doctors using my Skin Type Solutions System. This is most likely because, in a national crisis, the self-care and beauty business segments often see growth. So as you can see, dermatologist-dispensed skin care is becoming a major player in national skin care sales. Let’s get back to the story of how this came to be the case.

Peter Elias, MD. Dr. Elias is professor in the department of dermatology at the University of California, San Francisco. In 1996, Dr. Elias published a landmark paper in the Journal of Investigative Dermatology demonstrating that a 1:1:1 ratio of ceramides, fatty acids, and cholesterol is required to repair a damaged skin barrier. He filed multiple patents for using these lipids in moisturizers as early as 1992. His lipid research has stood the test of time, and this paper is still frequently cited. Dr. Elias has authored over 500 peer reviewed articles on the skin barrier, has edited or coauthored three books on skin barrier science, and developed EpiCeram, a product that utilizes ceramide, the fatty acid linoleic acid, and cholesterol. EpiCeram is the only barrier repair moisturizer approved by the Food and Drug Administration and is available by prescription only.

Kathy Fields, MD, and Katie Rodan, MD. Dr. Fields and Dr. Rodan met at Stanford (Calif.) University. In the 1980s, these entrepreneurial dermatologists realized that patients did not understand the role of preventing acne rather than just treating it. As dermatologists, they knew that a consistent daily routine to prevent acne was much more effective than waiting for an outbreak and spot-treating lesions. They took an already available OTC medication – benzoyl peroxide – and educated consumers through infomercials that they needed to stay ahead of acne instead of waiting for a breakout. Using infomercials to sell skin care, selling skin care kits, and educating patients about the need to prevent acne rather than spot treat it was very unusual at the time. As we all know, reeducating your patients is a huge challenge. Dr. Fields and Dr. Rodan changed consumers thinking in a genius way that continues to resonate today by choosing a brand name to make their point: Proactiv. Their simple 3-step acne kit encouraged patients to be proactive about their acne and encouraged compliance. (Patients love exact skin care steps as demonstrated again by the success of the skin care line from plastic surgeon Suzan Obagi, MD, which became available around 1988).

Dr. Fields and Dr. Rodan first offered Proactiv to Neutrogena, which turned it down. This early disappointment did not deter them and ended up benefiting them because this gave them the idea to do infomercials. Guthy Renker agreed to market and distribute the product, and the first Proactiv infomercial appeared on TV in 1995. It quickly became popular and is still one of the best selling skin care lines of all time. It’s important to note that the “overnight success” of Proactiv took at least a decade of effort.

Heather Woolery Lloyd, MD. Dr. Woolery Lloyd got her medical degree at the University of Miami where she also completed her dermatology residency. Her interest in skin of color led to her appointment as director of Ethnic Skin Care at the University of Miami, the country’s first cosmetic ethnic skin care department at a major university. She spent years lecturing around the world on skin of color issues and performing clinical trials before she developed the “Specific Beauty” skin care line for melanin rich skin types. Specific Beauty was acquired by Guthy Renker and is available online. It is the most popular dermatologist developed skin care line for skin of color.

In the late 1980s and early 1990s, other dermatologists threw their hats into the ring and came out with skin care lines – some successful and some not. Unfortunately, many skin care lines at that time were based on “pseudoscience” and exaggerated claims, which fueled the fire of those who felt dermatologists should steer clear of these entrepreneurial pursuits. A debate about the ethics of doctors retailing skin care began, and the controversy led to this 2010 statement by the American Medical Association: “In-office sale of health-related products by physicians presents a financial conflict of interest, risks placing undue pressure on the patient, and threatens to erode patient trust and undermine the primary obligation of physicians to serve the interests of their patients before their own.”

Many dermatologists dropped out of the AMA as a result because they felt the organization was no longer representing dermatologist’s interests. After all, we know skin care science better than anyone, and many dermatologists were insulted by the suggestion that we would place our personal financial gain over the best interests of our patients.

This is a perfect example of how the actions of a few unscrupulous dermatologists can affect the entire specialty. I like to focus on the ethical entrepreneurial dermatologists who made great contributions to the skin care industry based on science, efficacy, and patient education and encourage the ethical among us to provide this science-based information to our patients to protect them from pseudoscience-based opportunists. It is obvious that I believe that dermatologists have a responsibility to provide medical advice on skin care to their patients. If not us, who will do it as ethically as we will? But I plead with those of you out there who are promoting foolish stem cell–containing creams and other impossible technologies to remember that you are hurting the credibility of our entire dermatology profession.

In my next column, I will discuss dermatologists who have played a significant role behind the scenes in the development of the skin care industry.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].  

References

Castanedo-Tardan MP, Baumann L. Clin Dermatol. Jul-Aug 2009;27(4):355-8.

Gormley DE. Arch Dermatol. 1999 Jul;135(7):765-6.

Miller RC. Arch Dermatol. 1999 Mar;135(3):255-6.

Virtual Mentor. 2010;12(12):925-7.
 

In this historical portrait, I am focusing mainly on dermatologists who have developed a skin care line, and I am loosely following a chronological order. Thanks to all the readers of Part 1 (The interesting history of dermatologist-developed skin care), who gave me interesting feedback on my Facebook and LinkedIn accounts. There was so much interest that I will write Part 3 next month. Feel free to DM me your ideas on LinkedIn.

The history of dermatologist-developed skin care continues as more dermatologists become interested in developing a skin care line or retailing skin care in their medical practice. A report in July 2020 showed that physician-dispensed skin care is the largest growing segment of the skin care business with a projected compound annual growth rate of 9.9% from 2020 to 2027. I have not seen national sales numbers since this July report, but we have noticed a large increase in online sales for the doctors using my Skin Type Solutions System. This is most likely because, in a national crisis, the self-care and beauty business segments often see growth. So as you can see, dermatologist-dispensed skin care is becoming a major player in national skin care sales. Let’s get back to the story of how this came to be the case.

Peter Elias, MD. Dr. Elias is professor in the department of dermatology at the University of California, San Francisco. In 1996, Dr. Elias published a landmark paper in the Journal of Investigative Dermatology demonstrating that a 1:1:1 ratio of ceramides, fatty acids, and cholesterol is required to repair a damaged skin barrier. He filed multiple patents for using these lipids in moisturizers as early as 1992. His lipid research has stood the test of time, and this paper is still frequently cited. Dr. Elias has authored over 500 peer reviewed articles on the skin barrier, has edited or coauthored three books on skin barrier science, and developed EpiCeram, a product that utilizes ceramide, the fatty acid linoleic acid, and cholesterol. EpiCeram is the only barrier repair moisturizer approved by the Food and Drug Administration and is available by prescription only.

Kathy Fields, MD, and Katie Rodan, MD. Dr. Fields and Dr. Rodan met at Stanford (Calif.) University. In the 1980s, these entrepreneurial dermatologists realized that patients did not understand the role of preventing acne rather than just treating it. As dermatologists, they knew that a consistent daily routine to prevent acne was much more effective than waiting for an outbreak and spot-treating lesions. They took an already available OTC medication – benzoyl peroxide – and educated consumers through infomercials that they needed to stay ahead of acne instead of waiting for a breakout. Using infomercials to sell skin care, selling skin care kits, and educating patients about the need to prevent acne rather than spot treat it was very unusual at the time. As we all know, reeducating your patients is a huge challenge. Dr. Fields and Dr. Rodan changed consumers thinking in a genius way that continues to resonate today by choosing a brand name to make their point: Proactiv. Their simple 3-step acne kit encouraged patients to be proactive about their acne and encouraged compliance. (Patients love exact skin care steps as demonstrated again by the success of the skin care line from plastic surgeon Suzan Obagi, MD, which became available around 1988).

Dr. Fields and Dr. Rodan first offered Proactiv to Neutrogena, which turned it down. This early disappointment did not deter them and ended up benefiting them because this gave them the idea to do infomercials. Guthy Renker agreed to market and distribute the product, and the first Proactiv infomercial appeared on TV in 1995. It quickly became popular and is still one of the best selling skin care lines of all time. It’s important to note that the “overnight success” of Proactiv took at least a decade of effort.

Heather Woolery Lloyd, MD. Dr. Woolery Lloyd got her medical degree at the University of Miami where she also completed her dermatology residency. Her interest in skin of color led to her appointment as director of Ethnic Skin Care at the University of Miami, the country’s first cosmetic ethnic skin care department at a major university. She spent years lecturing around the world on skin of color issues and performing clinical trials before she developed the “Specific Beauty” skin care line for melanin rich skin types. Specific Beauty was acquired by Guthy Renker and is available online. It is the most popular dermatologist developed skin care line for skin of color.

In the late 1980s and early 1990s, other dermatologists threw their hats into the ring and came out with skin care lines – some successful and some not. Unfortunately, many skin care lines at that time were based on “pseudoscience” and exaggerated claims, which fueled the fire of those who felt dermatologists should steer clear of these entrepreneurial pursuits. A debate about the ethics of doctors retailing skin care began, and the controversy led to this 2010 statement by the American Medical Association: “In-office sale of health-related products by physicians presents a financial conflict of interest, risks placing undue pressure on the patient, and threatens to erode patient trust and undermine the primary obligation of physicians to serve the interests of their patients before their own.”

Many dermatologists dropped out of the AMA as a result because they felt the organization was no longer representing dermatologist’s interests. After all, we know skin care science better than anyone, and many dermatologists were insulted by the suggestion that we would place our personal financial gain over the best interests of our patients.

This is a perfect example of how the actions of a few unscrupulous dermatologists can affect the entire specialty. I like to focus on the ethical entrepreneurial dermatologists who made great contributions to the skin care industry based on science, efficacy, and patient education and encourage the ethical among us to provide this science-based information to our patients to protect them from pseudoscience-based opportunists. It is obvious that I believe that dermatologists have a responsibility to provide medical advice on skin care to their patients. If not us, who will do it as ethically as we will? But I plead with those of you out there who are promoting foolish stem cell–containing creams and other impossible technologies to remember that you are hurting the credibility of our entire dermatology profession.

In my next column, I will discuss dermatologists who have played a significant role behind the scenes in the development of the skin care industry.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].  

References

Castanedo-Tardan MP, Baumann L. Clin Dermatol. Jul-Aug 2009;27(4):355-8.

Gormley DE. Arch Dermatol. 1999 Jul;135(7):765-6.

Miller RC. Arch Dermatol. 1999 Mar;135(3):255-6.

Virtual Mentor. 2010;12(12):925-7.
 

Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.

He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.

It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.

The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.

“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.

The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.

“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.

The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.

Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.

Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.

“For some young kids, the fear that they will contaminate their parents or grandparents is horrifying. You can kill your grandfather by coughing,” Dr. Zalsman said.
 

Older people also seek help

A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.

The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.

“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.

Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.

[email protected]

SOURCE: Zalsman G. ECNP 2020, Session TP.06.

Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.

He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.

It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.

The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.

“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.

The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.

“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.

The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.

Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.

Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.

“For some young kids, the fear that they will contaminate their parents or grandparents is horrifying. You can kill your grandfather by coughing,” Dr. Zalsman said.
 

Older people also seek help

A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.

The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.

“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.

Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.

[email protected]

SOURCE: Zalsman G. ECNP 2020, Session TP.06.

Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.

He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.

It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.

The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.

“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.

The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.

“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.

The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.

Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.

Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.

“For some young kids, the fear that they will contaminate their parents or grandparents is horrifying. You can kill your grandfather by coughing,” Dr. Zalsman said.
 

Older people also seek help

A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.

The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.

“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.

Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.

[email protected]

SOURCE: Zalsman G. ECNP 2020, Session TP.06.

Further data suggesting that a lower dose of rituximab seems to offer similar effectiveness with a better safety profile than higher doses commonly used in multiple sclerosis (MS), according to a new observational study. “We showed similar numbers of relapses, MRI new/active lesions, and effects on disability with a higher and lower dose of rituximab over a median follow of 16 months,” said lead author, Luciana Midaglia, MD, Multiple Sclerosis Centre of Catalonia (Cemcat) at Vall d’Hebron University Hospital, Barcelona. “But adverse effects – particularly frequency of infection – were increased in the high-dose group.”

Dr. Midaglia presented the findings at the recent Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“There haven’t been large studies of rituximab in MS as the company [Genentech/Roche] prioritized development of ocrelizumab over rituximab,” she explained. Rituximab has, therefore, never been approved for this indication. But it is available for several other conditions, and it is often used off label for MS.

“Although we now have a lot of experience with rituximab in MS, a dosage regimen has not been standardized,” Dr. Midaglia noted.

The current study was conducted to compare the efficacy and safety of two different dosage regimens of rituximab used at two different Catalan MS centers.

In the Barcelona center, 249 patients received a regimen of 2 g IV for the first three 6-month cycles followed by 1 g every 6 months thereafter (higher-dose group). In the Girona center, 54 patients received just one loading dose of 2 g followed by 500 mg every 6 months thereafter (lower-dose group).

Patients were followed up clinically every 6 months, and MRI brain scans were performed at baseline and yearly thereafter. Blood samples for safety and B cell/immunoglobulin monitoring were drawn at 3 months after rituximab infusions.

Results showed that the annualized relapse rate reduced by 87% (from 0.4 to 0.05; P < .001) in the higher-dose cohort, and by 90% (from 0.31 to 0.03; P = .018) in the lower-dose cohort.

The Expanded Disability Status Scale score remained stable or improved in 83% of the higher-dose group versus 72% of the lower-dose group (P = .09).

Contrast-enhancing lesions were reduced by 92% by 12 months and by 100% by 36 months in the higher-dose group and by 81% and 100%, respectively, in the lower-dose group.

New T2 lesions were present in 19% of patients at 12 months and in 12% at 36 months in the higher-dose group and in 16% and 0%, respectively, in the lower-dose group.

Reductions in B cell levels were similar with both doses. However, a reduced rate of adverse effects, mainly infections, was seen in the lower-dose group.

Infections were reported in 7.2% of the higher-dose group and 3.7% of the lower-dose group at 1 year, in 9.7% versus 0% in the second year, and in 9.7% versus 0% in the third year. Urinary tract infections, followed by respiratory infections, were the most prevalent.

A randomized phase 3 study is now underway testing an even lower dose of rituximab. The trial, known as RIDOSE-MS, is comparing maintenance doses of 500 mg every 6 months and 500 mg every 12 months.

Dr. Midaglia said that most centers are using higher doses of rituximab – similar to the Barcelona cohort in this study.

“After this study, we will we now start a new protocol and use the lower dose for all MS patients,” she said.

She reported that her hospital has been using rituximab extensively in MS.

“There were delays to ocrelizumab being introduced in Spain, and while we were waiting, we started using rituximab,” she said. “We believe it is similarly effective to ocrelizumab. It has exactly the same mechanism of action. The only difference is that rituximab is a chimeric antibody while ocrelizumab is fully humanized.”

While rituximab has not had the validation of a full phase 3 trial, she added, “there are data available from several smaller studies and we feel we have learned how to use it in the real world, but we don’t have an approved dosage schedule. We started off using the dose approved for use in rheumatological and hematological conditions.”

Now that ocrelizumab is approved, Dr. Midaglia said they are using that drug for the patients who meet the approved criteria, but there are many patients who don’t qualify.

“For example, in progressive MS, ocrelizumab has quite a narrow indication – it is not reimbursed for patients without any inflammatory activity. So for these patients, we tend to use rituximab,” she noted.

“While there is no good data on its efficacy in these patients, we believe it has some effect and there is no other option at present. Rituximab is an inexpensive drug and has a long safety record in other conditions, so we feel it’s worth a try,” Dr. Midaglia concluded. “And now we have better data on the optimal dosage.”

Commenting on the study, Daniel Ontaneda, MD, comoderator of the session at which the study was presented, said: “Rituximab is not an [Food and Drug Administration]–approved medication for MS, but it has been used in clinical practice quite extensively in the U.S. and also in Europe. The study is of interest as it showed that the lower dose of rituximab achieved good control of disease activity.”

Dr. Ontaneda, a neurologist at the Mellen Center for MS at the Cleveland Clinic, Ohio, added: “Many centers have been using lower doses or less frequent infusions and this study supports this practice. Some degree of residual confounding in the study in the differences in side effects may be related to the two different sites, but overall I think these results add to the real-world observational data now available for anti-CD20 therapies.”

Dr. Midaglia reported receiving travel funding from Genzyme, Roche, Biogen Idec, and Novartis, and personal fees for lectures from Roche.
 

A version of this article originally appeared on Medscape.com.

Further data suggesting that a lower dose of rituximab seems to offer similar effectiveness with a better safety profile than higher doses commonly used in multiple sclerosis (MS), according to a new observational study. “We showed similar numbers of relapses, MRI new/active lesions, and effects on disability with a higher and lower dose of rituximab over a median follow of 16 months,” said lead author, Luciana Midaglia, MD, Multiple Sclerosis Centre of Catalonia (Cemcat) at Vall d’Hebron University Hospital, Barcelona. “But adverse effects – particularly frequency of infection – were increased in the high-dose group.”

Dr. Midaglia presented the findings at the recent Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“There haven’t been large studies of rituximab in MS as the company [Genentech/Roche] prioritized development of ocrelizumab over rituximab,” she explained. Rituximab has, therefore, never been approved for this indication. But it is available for several other conditions, and it is often used off label for MS.

“Although we now have a lot of experience with rituximab in MS, a dosage regimen has not been standardized,” Dr. Midaglia noted.

The current study was conducted to compare the efficacy and safety of two different dosage regimens of rituximab used at two different Catalan MS centers.

In the Barcelona center, 249 patients received a regimen of 2 g IV for the first three 6-month cycles followed by 1 g every 6 months thereafter (higher-dose group). In the Girona center, 54 patients received just one loading dose of 2 g followed by 500 mg every 6 months thereafter (lower-dose group).

Patients were followed up clinically every 6 months, and MRI brain scans were performed at baseline and yearly thereafter. Blood samples for safety and B cell/immunoglobulin monitoring were drawn at 3 months after rituximab infusions.

Results showed that the annualized relapse rate reduced by 87% (from 0.4 to 0.05; P < .001) in the higher-dose cohort, and by 90% (from 0.31 to 0.03; P = .018) in the lower-dose cohort.

The Expanded Disability Status Scale score remained stable or improved in 83% of the higher-dose group versus 72% of the lower-dose group (P = .09).

Contrast-enhancing lesions were reduced by 92% by 12 months and by 100% by 36 months in the higher-dose group and by 81% and 100%, respectively, in the lower-dose group.

New T2 lesions were present in 19% of patients at 12 months and in 12% at 36 months in the higher-dose group and in 16% and 0%, respectively, in the lower-dose group.

Reductions in B cell levels were similar with both doses. However, a reduced rate of adverse effects, mainly infections, was seen in the lower-dose group.

Infections were reported in 7.2% of the higher-dose group and 3.7% of the lower-dose group at 1 year, in 9.7% versus 0% in the second year, and in 9.7% versus 0% in the third year. Urinary tract infections, followed by respiratory infections, were the most prevalent.

A randomized phase 3 study is now underway testing an even lower dose of rituximab. The trial, known as RIDOSE-MS, is comparing maintenance doses of 500 mg every 6 months and 500 mg every 12 months.

Dr. Midaglia said that most centers are using higher doses of rituximab – similar to the Barcelona cohort in this study.

“After this study, we will we now start a new protocol and use the lower dose for all MS patients,” she said.

She reported that her hospital has been using rituximab extensively in MS.

“There were delays to ocrelizumab being introduced in Spain, and while we were waiting, we started using rituximab,” she said. “We believe it is similarly effective to ocrelizumab. It has exactly the same mechanism of action. The only difference is that rituximab is a chimeric antibody while ocrelizumab is fully humanized.”

While rituximab has not had the validation of a full phase 3 trial, she added, “there are data available from several smaller studies and we feel we have learned how to use it in the real world, but we don’t have an approved dosage schedule. We started off using the dose approved for use in rheumatological and hematological conditions.”

Now that ocrelizumab is approved, Dr. Midaglia said they are using that drug for the patients who meet the approved criteria, but there are many patients who don’t qualify.

“For example, in progressive MS, ocrelizumab has quite a narrow indication – it is not reimbursed for patients without any inflammatory activity. So for these patients, we tend to use rituximab,” she noted.

“While there is no good data on its efficacy in these patients, we believe it has some effect and there is no other option at present. Rituximab is an inexpensive drug and has a long safety record in other conditions, so we feel it’s worth a try,” Dr. Midaglia concluded. “And now we have better data on the optimal dosage.”

Commenting on the study, Daniel Ontaneda, MD, comoderator of the session at which the study was presented, said: “Rituximab is not an [Food and Drug Administration]–approved medication for MS, but it has been used in clinical practice quite extensively in the U.S. and also in Europe. The study is of interest as it showed that the lower dose of rituximab achieved good control of disease activity.”

Dr. Ontaneda, a neurologist at the Mellen Center for MS at the Cleveland Clinic, Ohio, added: “Many centers have been using lower doses or less frequent infusions and this study supports this practice. Some degree of residual confounding in the study in the differences in side effects may be related to the two different sites, but overall I think these results add to the real-world observational data now available for anti-CD20 therapies.”

Dr. Midaglia reported receiving travel funding from Genzyme, Roche, Biogen Idec, and Novartis, and personal fees for lectures from Roche.
 

A version of this article originally appeared on Medscape.com.

Further data suggesting that a lower dose of rituximab seems to offer similar effectiveness with a better safety profile than higher doses commonly used in multiple sclerosis (MS), according to a new observational study. “We showed similar numbers of relapses, MRI new/active lesions, and effects on disability with a higher and lower dose of rituximab over a median follow of 16 months,” said lead author, Luciana Midaglia, MD, Multiple Sclerosis Centre of Catalonia (Cemcat) at Vall d’Hebron University Hospital, Barcelona. “But adverse effects – particularly frequency of infection – were increased in the high-dose group.”

Dr. Midaglia presented the findings at the recent Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“There haven’t been large studies of rituximab in MS as the company [Genentech/Roche] prioritized development of ocrelizumab over rituximab,” she explained. Rituximab has, therefore, never been approved for this indication. But it is available for several other conditions, and it is often used off label for MS.

“Although we now have a lot of experience with rituximab in MS, a dosage regimen has not been standardized,” Dr. Midaglia noted.

The current study was conducted to compare the efficacy and safety of two different dosage regimens of rituximab used at two different Catalan MS centers.

In the Barcelona center, 249 patients received a regimen of 2 g IV for the first three 6-month cycles followed by 1 g every 6 months thereafter (higher-dose group). In the Girona center, 54 patients received just one loading dose of 2 g followed by 500 mg every 6 months thereafter (lower-dose group).

Patients were followed up clinically every 6 months, and MRI brain scans were performed at baseline and yearly thereafter. Blood samples for safety and B cell/immunoglobulin monitoring were drawn at 3 months after rituximab infusions.

Results showed that the annualized relapse rate reduced by 87% (from 0.4 to 0.05; P < .001) in the higher-dose cohort, and by 90% (from 0.31 to 0.03; P = .018) in the lower-dose cohort.

The Expanded Disability Status Scale score remained stable or improved in 83% of the higher-dose group versus 72% of the lower-dose group (P = .09).

Contrast-enhancing lesions were reduced by 92% by 12 months and by 100% by 36 months in the higher-dose group and by 81% and 100%, respectively, in the lower-dose group.

New T2 lesions were present in 19% of patients at 12 months and in 12% at 36 months in the higher-dose group and in 16% and 0%, respectively, in the lower-dose group.

Reductions in B cell levels were similar with both doses. However, a reduced rate of adverse effects, mainly infections, was seen in the lower-dose group.

Infections were reported in 7.2% of the higher-dose group and 3.7% of the lower-dose group at 1 year, in 9.7% versus 0% in the second year, and in 9.7% versus 0% in the third year. Urinary tract infections, followed by respiratory infections, were the most prevalent.

A randomized phase 3 study is now underway testing an even lower dose of rituximab. The trial, known as RIDOSE-MS, is comparing maintenance doses of 500 mg every 6 months and 500 mg every 12 months.

Dr. Midaglia said that most centers are using higher doses of rituximab – similar to the Barcelona cohort in this study.

“After this study, we will we now start a new protocol and use the lower dose for all MS patients,” she said.

She reported that her hospital has been using rituximab extensively in MS.

“There were delays to ocrelizumab being introduced in Spain, and while we were waiting, we started using rituximab,” she said. “We believe it is similarly effective to ocrelizumab. It has exactly the same mechanism of action. The only difference is that rituximab is a chimeric antibody while ocrelizumab is fully humanized.”

While rituximab has not had the validation of a full phase 3 trial, she added, “there are data available from several smaller studies and we feel we have learned how to use it in the real world, but we don’t have an approved dosage schedule. We started off using the dose approved for use in rheumatological and hematological conditions.”

Now that ocrelizumab is approved, Dr. Midaglia said they are using that drug for the patients who meet the approved criteria, but there are many patients who don’t qualify.

“For example, in progressive MS, ocrelizumab has quite a narrow indication – it is not reimbursed for patients without any inflammatory activity. So for these patients, we tend to use rituximab,” she noted.

“While there is no good data on its efficacy in these patients, we believe it has some effect and there is no other option at present. Rituximab is an inexpensive drug and has a long safety record in other conditions, so we feel it’s worth a try,” Dr. Midaglia concluded. “And now we have better data on the optimal dosage.”

Commenting on the study, Daniel Ontaneda, MD, comoderator of the session at which the study was presented, said: “Rituximab is not an [Food and Drug Administration]–approved medication for MS, but it has been used in clinical practice quite extensively in the U.S. and also in Europe. The study is of interest as it showed that the lower dose of rituximab achieved good control of disease activity.”

Dr. Ontaneda, a neurologist at the Mellen Center for MS at the Cleveland Clinic, Ohio, added: “Many centers have been using lower doses or less frequent infusions and this study supports this practice. Some degree of residual confounding in the study in the differences in side effects may be related to the two different sites, but overall I think these results add to the real-world observational data now available for anti-CD20 therapies.”

Dr. Midaglia reported receiving travel funding from Genzyme, Roche, Biogen Idec, and Novartis, and personal fees for lectures from Roche.
 

A version of this article originally appeared on Medscape.com.

In March 2020, following the announcement of the United States’ first death related to COVID-19, many physicians began using their voices to discuss the shortage of personal protective equipment (PPE). Many physicians, myself included, petitioned elected leaders at the community, state, and federal levels to address the PPE shortage.

Historically, physicians have advocated for improved public health. From seat belt laws in the 1980s and 1990s to the Affordable Care Act in the 2000s, physicians have testified at the community, state, and federal levels to advocate for the health and safety of our patients and the public. Yet while we have been making our voices heard, we are often silent at the ballot box.

In the 1996 and 2000 elections, physicians voted 9% less often than the general public, and compared with lawyers – professionals with similar educational attainment and finances – physicians voted 22% less often.¹ It is unclear why physicians are less likely to vote. In a 2016 article, David Grande, MD, and Katrina Armstrong, MD, postulated that physicians may not vote because our work hours create barriers to visiting polls.²

Despite our lack of engagement at the ballot box, voting is important to improving our patients’ social determinants of health. In a recently published systematic review, the authors found several studies supporting the association between voting and social determinants of health. Their review found that, when large numbers of people from communities participated in voting, it translated into greater influence over determining who held political power in that community. Those with power introduced and supported policies responding to their constituents’ needs, ultimately influencing their constituents’ social determinants of health.³ By voting, we as physicians are helping to address the social determinants of health in our communities.

Many medical students have been doing their part to improve the social determinants of health in their communities by pledging to vote. In 2018, the American Medical Student Association launched their “Med Out the Vote” initiative prior to the election. The organization called on all health care providers and providers in training to pledge to vote in the election.⁴ They are continuing these efforts for the 2020 elections.

We should join our nation’s medical students by also pledging to vote. To begin, we can all Make A Plan To Vote. Each plan should include the following:

• Register to vote: In many states eligible voters can register online.
• Request an absentee ballot: Many states require registered voters to request absentee ballots online or by mail.
• Vote: Submit an absentee ballot prior to election or vote in-person on election day. Some counties allow voting early in person.

In practice, our plans will differ slightly because each state has its own election laws.

This election season let us ensure all physician voices are heard. Make A Plan To Vote for your patients and communities.
 

Dr. Kumar is the pediatric editor of The Hospitalist. She is clinical assistant professor of pediatrics at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University and a pediatric hospitalist at Cleveland Clinic Children’s.

References

1. Grande D et al. Do Doctors Vote? J Gen Intern Med. 2007 May;22(5):585-9.

2. Grande D, Armstrong K. Will Physicians Vote? Ann Intern Med. 2016;165:814-5.

3. Brown CL et al. Voting, health and interventions in healthcare settings: A scoping review. Public Health Rev. 2020 Jul. doi: 10.1186/s40985-020-00133-6.

4. American Medical Student Association. AMSA Launches Med Out the Vote Campaign, Call to Action. 2018 Jul 29. Accessed 2020 Sep 14. https://www.amsa.org/about/amsa-press-room/amsa-launches-med-out-the-vote-campaign-call-to-action/

In March 2020, following the announcement of the United States’ first death related to COVID-19, many physicians began using their voices to discuss the shortage of personal protective equipment (PPE). Many physicians, myself included, petitioned elected leaders at the community, state, and federal levels to address the PPE shortage.

Historically, physicians have advocated for improved public health. From seat belt laws in the 1980s and 1990s to the Affordable Care Act in the 2000s, physicians have testified at the community, state, and federal levels to advocate for the health and safety of our patients and the public. Yet while we have been making our voices heard, we are often silent at the ballot box.

In the 1996 and 2000 elections, physicians voted 9% less often than the general public, and compared with lawyers – professionals with similar educational attainment and finances – physicians voted 22% less often.¹ It is unclear why physicians are less likely to vote. In a 2016 article, David Grande, MD, and Katrina Armstrong, MD, postulated that physicians may not vote because our work hours create barriers to visiting polls.²

Despite our lack of engagement at the ballot box, voting is important to improving our patients’ social determinants of health. In a recently published systematic review, the authors found several studies supporting the association between voting and social determinants of health. Their review found that, when large numbers of people from communities participated in voting, it translated into greater influence over determining who held political power in that community. Those with power introduced and supported policies responding to their constituents’ needs, ultimately influencing their constituents’ social determinants of health.³ By voting, we as physicians are helping to address the social determinants of health in our communities.

Many medical students have been doing their part to improve the social determinants of health in their communities by pledging to vote. In 2018, the American Medical Student Association launched their “Med Out the Vote” initiative prior to the election. The organization called on all health care providers and providers in training to pledge to vote in the election.⁴ They are continuing these efforts for the 2020 elections.

We should join our nation’s medical students by also pledging to vote. To begin, we can all Make A Plan To Vote. Each plan should include the following:

• Register to vote: In many states eligible voters can register online.
• Request an absentee ballot: Many states require registered voters to request absentee ballots online or by mail.
• Vote: Submit an absentee ballot prior to election or vote in-person on election day. Some counties allow voting early in person.

In practice, our plans will differ slightly because each state has its own election laws.

This election season let us ensure all physician voices are heard. Make A Plan To Vote for your patients and communities.
 

Dr. Kumar is the pediatric editor of The Hospitalist. She is clinical assistant professor of pediatrics at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University and a pediatric hospitalist at Cleveland Clinic Children’s.

References

1. Grande D et al. Do Doctors Vote? J Gen Intern Med. 2007 May;22(5):585-9.

2. Grande D, Armstrong K. Will Physicians Vote? Ann Intern Med. 2016;165:814-5.

3. Brown CL et al. Voting, health and interventions in healthcare settings: A scoping review. Public Health Rev. 2020 Jul. doi: 10.1186/s40985-020-00133-6.

4. American Medical Student Association. AMSA Launches Med Out the Vote Campaign, Call to Action. 2018 Jul 29. Accessed 2020 Sep 14. https://www.amsa.org/about/amsa-press-room/amsa-launches-med-out-the-vote-campaign-call-to-action/

In March 2020, following the announcement of the United States’ first death related to COVID-19, many physicians began using their voices to discuss the shortage of personal protective equipment (PPE). Many physicians, myself included, petitioned elected leaders at the community, state, and federal levels to address the PPE shortage.

Historically, physicians have advocated for improved public health. From seat belt laws in the 1980s and 1990s to the Affordable Care Act in the 2000s, physicians have testified at the community, state, and federal levels to advocate for the health and safety of our patients and the public. Yet while we have been making our voices heard, we are often silent at the ballot box.

In the 1996 and 2000 elections, physicians voted 9% less often than the general public, and compared with lawyers – professionals with similar educational attainment and finances – physicians voted 22% less often.¹ It is unclear why physicians are less likely to vote. In a 2016 article, David Grande, MD, and Katrina Armstrong, MD, postulated that physicians may not vote because our work hours create barriers to visiting polls.²

Despite our lack of engagement at the ballot box, voting is important to improving our patients’ social determinants of health. In a recently published systematic review, the authors found several studies supporting the association between voting and social determinants of health. Their review found that, when large numbers of people from communities participated in voting, it translated into greater influence over determining who held political power in that community. Those with power introduced and supported policies responding to their constituents’ needs, ultimately influencing their constituents’ social determinants of health.³ By voting, we as physicians are helping to address the social determinants of health in our communities.

Many medical students have been doing their part to improve the social determinants of health in their communities by pledging to vote. In 2018, the American Medical Student Association launched their “Med Out the Vote” initiative prior to the election. The organization called on all health care providers and providers in training to pledge to vote in the election.⁴ They are continuing these efforts for the 2020 elections.

We should join our nation’s medical students by also pledging to vote. To begin, we can all Make A Plan To Vote. Each plan should include the following:

• Register to vote: In many states eligible voters can register online.
• Request an absentee ballot: Many states require registered voters to request absentee ballots online or by mail.
• Vote: Submit an absentee ballot prior to election or vote in-person on election day. Some counties allow voting early in person.

In practice, our plans will differ slightly because each state has its own election laws.

This election season let us ensure all physician voices are heard. Make A Plan To Vote for your patients and communities.
 

Dr. Kumar is the pediatric editor of The Hospitalist. She is clinical assistant professor of pediatrics at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University and a pediatric hospitalist at Cleveland Clinic Children’s.

References

1. Grande D et al. Do Doctors Vote? J Gen Intern Med. 2007 May;22(5):585-9.

2. Grande D, Armstrong K. Will Physicians Vote? Ann Intern Med. 2016;165:814-5.

3. Brown CL et al. Voting, health and interventions in healthcare settings: A scoping review. Public Health Rev. 2020 Jul. doi: 10.1186/s40985-020-00133-6.

4. American Medical Student Association. AMSA Launches Med Out the Vote Campaign, Call to Action. 2018 Jul 29. Accessed 2020 Sep 14. https://www.amsa.org/about/amsa-press-room/amsa-launches-med-out-the-vote-campaign-call-to-action/

There is no evidence to support the idea that previous autoimmunity before or after alemtuzumab treatment predicts subsequent rare but serious and possibly life-threatening autoimmune events that have recently been linked to the drug, a new study has shown.

These latest data were reported by Alasdair J. Coles, MD, University of Cambridge (England), at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.

Dr. Coles, who led the initial research to develop alemtuzumab in partnership with Genzyme, explained that autoimmune disease is a well-described and common adverse event with the drug, manifesting mainly as autoimmune thyroid events that can occur in up to 40% of patients.

But as postmarketing experience has grown, it has become clear that there is a low frequency of more serious autoimmune disease, he noted. In an effort to understand this better, regulators have suggested that the presence of non–multiple sclerosis (MS) autoimmune disease before alemtuzumab treatment and the emergence of autoimmune disease after alemtuzumab treatment may define a group that is at higher risk of one of the rare but serious autoimmune events for those on the drug.

To investigate if this was the case, Dr. Coles and colleagues analyzed data on 1,216 patients who received alemtuzumab in the clinical development program. Of these, 96 had preexisting non-MS autoimmunity.

Results showed that up to 9 years after alemtuzumab initiation, the percentage of patients with new autoimmune disease was similar in those with (35.4%) versus without (35.3%) preexisting autoimmunity.

Similar percentages of patients with versus without preexisting autoimmunity had two or more new autoimmune events (5.2% vs. 8.2%, respectively). And most patients with thyroid disorders at baseline did not experience new autoimmunity after alemtuzumab.

In addition, treatment-emergent thyroid autoimmunity after the first alemtuzumab course was not associated with subsequent nonthyroid autoimmunity after the second course. Similarly, thyroid autoimmunity after the second course did not predict non-thyroid autoimmunity after the third course.

In another analysis of the incidence of serious autoimmune events from postmarketing data on 25,292 patients treated with alemtuzumab, immune thrombocytopenic purpura was reported in 43 patients, newly identified autoimmune hepatitis in 11 patients, and hemophagocytic lymphohistiocytosis in 9 patients.

There was “no hint at all” that baseline thyroid disorders or postalemtuzumab thyroid disorders are associated with increased risk of these serious autoimmune adverse events, Dr. Coles said.

He calculated that the incidence of serious autoimmune diseases that could be life-threatening after alemtuzumab treatment was 10.7 per 10,000 patients treated for autoimmune hepatitis and 2.7 per 10,000 patients treated for hemophagocytic lymphohistiocytosis.

“From two separate data sources – phase 2/3 trials populations combined and postmarketing data – there is no evidence to support the hypothesis that preexisting non-MS autoimmunity predisposes to the serious but rare autoimmune events that have newly been described, nor does thyroid autoimmunity following the use of alemtuzumab,” Dr. Coles stated.

“In my opinion it is not appropriate to preclude the use of alemtuzumab to patients who have had previous autoimmune disease before treatment or who develop thyroid autoimmunity after alemtuzumab,” he said.

“It remains in my view a reasonable treatment option for patients with active MS to receive this highly effective therapy in the face of well-managed, well-understood thyroid autoimmunity and the very unlikely, rare, but serious autoimmune disease,” he concluded.
 

Risk stratification

Commenting on the presentation, Robert J. Fox, MD, a neurologist at the Mellen Center for Multiple Sclerosis, Cleveland Clinic, Ohio, explained that, whenever there is a serious risk of a complication, clinicians like to try to stratify that risk.

“We like to identify those at higher risk [and perhaps not use the therapy] and those at lower risk [and perhaps consider more likely the use of that therapy],” he said.

With regard to alemtuzumab, Dr. Fox noted: “We’d like to stratify the risk of autoimmune complications, which could help guide us regarding the patients in whom therapy may be safer. Unfortunately, these findings did not point to a risk stratification to help guide its use towards lower-risk patients.

“I view this as an unfortunate result, because it leaves me without a way to stratify the risks of alemtuzumab, which are quite significant and currently limit my use of that MS therapy only to those with no other treatment options,” he added.

On Dr. Coles’ view of alemtuzumab as a “reasonable” treatment option, Dr. Fox commented: “I guess it depends upon how that’s interpreted. Given the risks of serious, life-threatening immune and infectious complications, I only consider alemtuzumab when all other immune-modulating therapies have been tried or are not a reasonable treatment option. So, yes, I see it as ‘reasonable,’ but only when there are no other available treatment options.”

The current work was supported by Sanofi and Bayer HealthCare. Dr. Coles reported sitting on advisory boards for Genzyme (Sanofi). He is credited as an inventor on several patents related to the technology on which alemtuzumab is based. Dr. Fox has disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

There is no evidence to support the idea that previous autoimmunity before or after alemtuzumab treatment predicts subsequent rare but serious and possibly life-threatening autoimmune events that have recently been linked to the drug, a new study has shown.

These latest data were reported by Alasdair J. Coles, MD, University of Cambridge (England), at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.

Dr. Coles, who led the initial research to develop alemtuzumab in partnership with Genzyme, explained that autoimmune disease is a well-described and common adverse event with the drug, manifesting mainly as autoimmune thyroid events that can occur in up to 40% of patients.

But as postmarketing experience has grown, it has become clear that there is a low frequency of more serious autoimmune disease, he noted. In an effort to understand this better, regulators have suggested that the presence of non–multiple sclerosis (MS) autoimmune disease before alemtuzumab treatment and the emergence of autoimmune disease after alemtuzumab treatment may define a group that is at higher risk of one of the rare but serious autoimmune events for those on the drug.

To investigate if this was the case, Dr. Coles and colleagues analyzed data on 1,216 patients who received alemtuzumab in the clinical development program. Of these, 96 had preexisting non-MS autoimmunity.

Results showed that up to 9 years after alemtuzumab initiation, the percentage of patients with new autoimmune disease was similar in those with (35.4%) versus without (35.3%) preexisting autoimmunity.

Similar percentages of patients with versus without preexisting autoimmunity had two or more new autoimmune events (5.2% vs. 8.2%, respectively). And most patients with thyroid disorders at baseline did not experience new autoimmunity after alemtuzumab.

In addition, treatment-emergent thyroid autoimmunity after the first alemtuzumab course was not associated with subsequent nonthyroid autoimmunity after the second course. Similarly, thyroid autoimmunity after the second course did not predict non-thyroid autoimmunity after the third course.

In another analysis of the incidence of serious autoimmune events from postmarketing data on 25,292 patients treated with alemtuzumab, immune thrombocytopenic purpura was reported in 43 patients, newly identified autoimmune hepatitis in 11 patients, and hemophagocytic lymphohistiocytosis in 9 patients.

There was “no hint at all” that baseline thyroid disorders or postalemtuzumab thyroid disorders are associated with increased risk of these serious autoimmune adverse events, Dr. Coles said.

He calculated that the incidence of serious autoimmune diseases that could be life-threatening after alemtuzumab treatment was 10.7 per 10,000 patients treated for autoimmune hepatitis and 2.7 per 10,000 patients treated for hemophagocytic lymphohistiocytosis.

“From two separate data sources – phase 2/3 trials populations combined and postmarketing data – there is no evidence to support the hypothesis that preexisting non-MS autoimmunity predisposes to the serious but rare autoimmune events that have newly been described, nor does thyroid autoimmunity following the use of alemtuzumab,” Dr. Coles stated.

“In my opinion it is not appropriate to preclude the use of alemtuzumab to patients who have had previous autoimmune disease before treatment or who develop thyroid autoimmunity after alemtuzumab,” he said.

“It remains in my view a reasonable treatment option for patients with active MS to receive this highly effective therapy in the face of well-managed, well-understood thyroid autoimmunity and the very unlikely, rare, but serious autoimmune disease,” he concluded.
 

Risk stratification

Commenting on the presentation, Robert J. Fox, MD, a neurologist at the Mellen Center for Multiple Sclerosis, Cleveland Clinic, Ohio, explained that, whenever there is a serious risk of a complication, clinicians like to try to stratify that risk.

“We like to identify those at higher risk [and perhaps not use the therapy] and those at lower risk [and perhaps consider more likely the use of that therapy],” he said.

With regard to alemtuzumab, Dr. Fox noted: “We’d like to stratify the risk of autoimmune complications, which could help guide us regarding the patients in whom therapy may be safer. Unfortunately, these findings did not point to a risk stratification to help guide its use towards lower-risk patients.

“I view this as an unfortunate result, because it leaves me without a way to stratify the risks of alemtuzumab, which are quite significant and currently limit my use of that MS therapy only to those with no other treatment options,” he added.

On Dr. Coles’ view of alemtuzumab as a “reasonable” treatment option, Dr. Fox commented: “I guess it depends upon how that’s interpreted. Given the risks of serious, life-threatening immune and infectious complications, I only consider alemtuzumab when all other immune-modulating therapies have been tried or are not a reasonable treatment option. So, yes, I see it as ‘reasonable,’ but only when there are no other available treatment options.”

The current work was supported by Sanofi and Bayer HealthCare. Dr. Coles reported sitting on advisory boards for Genzyme (Sanofi). He is credited as an inventor on several patents related to the technology on which alemtuzumab is based. Dr. Fox has disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

There is no evidence to support the idea that previous autoimmunity before or after alemtuzumab treatment predicts subsequent rare but serious and possibly life-threatening autoimmune events that have recently been linked to the drug, a new study has shown.

These latest data were reported by Alasdair J. Coles, MD, University of Cambridge (England), at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.

Dr. Coles, who led the initial research to develop alemtuzumab in partnership with Genzyme, explained that autoimmune disease is a well-described and common adverse event with the drug, manifesting mainly as autoimmune thyroid events that can occur in up to 40% of patients.

But as postmarketing experience has grown, it has become clear that there is a low frequency of more serious autoimmune disease, he noted. In an effort to understand this better, regulators have suggested that the presence of non–multiple sclerosis (MS) autoimmune disease before alemtuzumab treatment and the emergence of autoimmune disease after alemtuzumab treatment may define a group that is at higher risk of one of the rare but serious autoimmune events for those on the drug.

To investigate if this was the case, Dr. Coles and colleagues analyzed data on 1,216 patients who received alemtuzumab in the clinical development program. Of these, 96 had preexisting non-MS autoimmunity.

Results showed that up to 9 years after alemtuzumab initiation, the percentage of patients with new autoimmune disease was similar in those with (35.4%) versus without (35.3%) preexisting autoimmunity.

Similar percentages of patients with versus without preexisting autoimmunity had two or more new autoimmune events (5.2% vs. 8.2%, respectively). And most patients with thyroid disorders at baseline did not experience new autoimmunity after alemtuzumab.

In addition, treatment-emergent thyroid autoimmunity after the first alemtuzumab course was not associated with subsequent nonthyroid autoimmunity after the second course. Similarly, thyroid autoimmunity after the second course did not predict non-thyroid autoimmunity after the third course.

In another analysis of the incidence of serious autoimmune events from postmarketing data on 25,292 patients treated with alemtuzumab, immune thrombocytopenic purpura was reported in 43 patients, newly identified autoimmune hepatitis in 11 patients, and hemophagocytic lymphohistiocytosis in 9 patients.

There was “no hint at all” that baseline thyroid disorders or postalemtuzumab thyroid disorders are associated with increased risk of these serious autoimmune adverse events, Dr. Coles said.

He calculated that the incidence of serious autoimmune diseases that could be life-threatening after alemtuzumab treatment was 10.7 per 10,000 patients treated for autoimmune hepatitis and 2.7 per 10,000 patients treated for hemophagocytic lymphohistiocytosis.

“From two separate data sources – phase 2/3 trials populations combined and postmarketing data – there is no evidence to support the hypothesis that preexisting non-MS autoimmunity predisposes to the serious but rare autoimmune events that have newly been described, nor does thyroid autoimmunity following the use of alemtuzumab,” Dr. Coles stated.

“In my opinion it is not appropriate to preclude the use of alemtuzumab to patients who have had previous autoimmune disease before treatment or who develop thyroid autoimmunity after alemtuzumab,” he said.

“It remains in my view a reasonable treatment option for patients with active MS to receive this highly effective therapy in the face of well-managed, well-understood thyroid autoimmunity and the very unlikely, rare, but serious autoimmune disease,” he concluded.
 

Risk stratification

Commenting on the presentation, Robert J. Fox, MD, a neurologist at the Mellen Center for Multiple Sclerosis, Cleveland Clinic, Ohio, explained that, whenever there is a serious risk of a complication, clinicians like to try to stratify that risk.

“We like to identify those at higher risk [and perhaps not use the therapy] and those at lower risk [and perhaps consider more likely the use of that therapy],” he said.

With regard to alemtuzumab, Dr. Fox noted: “We’d like to stratify the risk of autoimmune complications, which could help guide us regarding the patients in whom therapy may be safer. Unfortunately, these findings did not point to a risk stratification to help guide its use towards lower-risk patients.

“I view this as an unfortunate result, because it leaves me without a way to stratify the risks of alemtuzumab, which are quite significant and currently limit my use of that MS therapy only to those with no other treatment options,” he added.

On Dr. Coles’ view of alemtuzumab as a “reasonable” treatment option, Dr. Fox commented: “I guess it depends upon how that’s interpreted. Given the risks of serious, life-threatening immune and infectious complications, I only consider alemtuzumab when all other immune-modulating therapies have been tried or are not a reasonable treatment option. So, yes, I see it as ‘reasonable,’ but only when there are no other available treatment options.”

The current work was supported by Sanofi and Bayer HealthCare. Dr. Coles reported sitting on advisory boards for Genzyme (Sanofi). He is credited as an inventor on several patents related to the technology on which alemtuzumab is based. Dr. Fox has disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

“When we think about bisphosphonates, we have to think about whether they are good players or bad players,” Marcy B. Bolster, MD, of Harvard Medical School, Boston, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Although bisphosphonates are a first-line treatment for many patients to reduce fracture risk, rheumatology patients have distinct concerns about these medications, said Dr. Bolster, who is director of the Rheumatology Fellowship Training Program at Massachusetts General Hospital, Boston, and medical lead for the Fracture Liaison Service there.

She shared her insights on four questions most often asked by patients in her practice:

How long do I need to take this medication?

When discussing bisphosphonates with a patient for the first time, “I typically start with the benefits, and include the risks,” she said. “Then I outline my plans for treatment, which would include treatment duration.”

Setting expectations with the patient about planned duration of therapy, reviewing risks and benefits, and preparing to be flexible if changes are needed can help relieve patients’ concerns, she said.

For example, in a hypothetical case of a 69-year-old woman with a 17% chance of a major osteoporotic fracture and 3.8% chance of hip fracture in the next 10 years based on FRAX scores, Dr. Bolster said she would treat with alendronate or zoledronic acid.

Duration must be a clinical decision individualized to the patient, she noted. Research studies support that some patients benefit from a longer duration of therapy. In the Fracture Intervention Trial (FIT) Long-Term Extension, which included 1,099 women, the risk of clinical vertebral fractures significantly declined with 10 years of alendronate treatment, compared with 5 years of treatment, she said.

In the HORIZON trial of 1,233 postmenopausal women, the risk of new morphometric vertebral fractures was significantly lower in those treated with IV zoledronic acid for 6 years versus those treated for 3 years. These studies support that patients at particularly high risk for vertebral fractures may benefit from a longer duration of bisphosphonate therapy, she said.
 

What should I know about infusion side effects?

Infusion side effects remain a concern, and the acute phase reaction of zoledronic acid occurs in about 30% of patients, but most of these are mild and not recurring, Dr. Bolster said. “I tell patients that 90% report mild to moderate infusion side effects, and that it usually occurs only with the first infusion,” she noted.

To potentially prevent an acute-phase reaction, Dr. Bolster has advised patients to take acetaminophen prior to infusion. “I would tend to recommend acetaminophen over NSAIDs to avoid gastric and renal toxicities,” she said.

“Determining the risks of atypical femoral fractures are challenging” but are another potential side effect that worries patients, she said. An atypical femoral fracture (AFF) is a femur fracture in the proximal third of the shaft, she said.

AFF may occur in patients with osteoporosis even in the absence of bisphosphonate use, Dr. Bolster noted. However, AFF “may occur at increased frequency in those patients with osteoporosis and prolonged bisphosphonate use,” she said. AFF is rare overall, and known risk factors include Asian race (in North America), as well as femoral bowing and glucocorticoid use, she said.

A 2019 meta-analysis favored fracture prevention benefits over potential risk associated with bisphosphonate use. Predicting the risk of AFF remains difficult given several factors, including the low incidence of AFF, the unavailability of radiographs in all studies, not accounting for potential confounding by indication in some studies, and lack of adjustment for low bone mineral density or fracture risk, she added.

Osteonecrosis of the jaw has been linked to bisphosphonate use, and some patients ask about it, Dr. Bolster said. Current data show an incidence of 1 in 10,000 to 1 in 100,000 in patients with osteoporosis, while the incidence in the general population is 1 in 100,000, she noted. The highest risk is associated with use of IV bisphosphonates, although it does occur in patients on oral bisphosphonates and denosumab (Prolia), she added. Given the relatively low risk, the American Dental Association states that there is “no need to discontinue bisphosphonates prior to procedures.” Based on current evidence, bisphosphonate treatment outweighs the low risk of medication-related osteonecrosis of the jaw in patients in need of osteoporosis treatment because of the high risk of fragility fractures in the osteoporosis population, she emphasized.
 

When will I need another dual x-ray absorptiometry scan?

Osteoporosis develops in fewer than 10% of older postmenopausal women using a 15-year screening interval for those with normal bone mineral density or mild osteopenia at an initial scan, with T-scores of –1.49 or higher, she noted. Therefore, the need for repeat dual x-ray absorptiometry (DXA) scans should be individualized, so some patients with normal bone density or osteopenia and few comorbidities and risk factors for osteoporosis may not need frequent DXA scans, she added.

Although little evidence exists to specifically demonstrate the value of monitoring bone mineral density during a 5-year drug treatment period, as is noted by the American College of Physicians 2017 clinical practice guideline published in Annals of Internal Medicine, Dr. Bolster said that a DXA scan showing loss of bone mineral density during treatment could indicate incorrect drug use or noncompliance, or a secondary cause for bone loss that may otherwise go unnoticed. For IV zoledronic acid in particular, a DXA scan at 3-4 years can determine whether a drug holiday is warranted, or for patients with severe osteoporosis, whether another 3 years of treatment is necessary. She suggested considering a DXA scan at 2-3 years with alendronate and at 3-4 years with IV zoledronic acid.

Will I need a new medication if I fracture while on treatment?

For patients who ask whether to change medications following a new fracture, Dr. Bolster said it is important to evaluate the patient’s compliance with the treatment regimen and also consider the presence of secondary causes of bone loss. Consideration can be given to keeping the patient on the same regimen because osteoporosis treatment regimens have demonstrated a 50%-70% fracture-risk reduction so they do not prevent all fractures, she said. “It is therefore reasonable, after confirming compliance and ruling out secondary causes of bone loss, to keep a patient on the same regimen following a fracture. For patients using denosumab, there is an increased risk of rapid bone loss and sustaining multiple vertebral fracture with missed doses or discontinuation,” she said.

It is important to evaluate patients who fracture while on therapy for secondary causes of bone loss, assess compliance, and consider strategies such as modifying the route of administration, seeking a different mechanism of action, or continuing on the same regimen, Dr. Bolster noted.

Dr. Bolster disclosed participation in clinical trials for Corbus, Cumberland, and Genentech, as well as research grants from the Rheumatology Research Foundation. She also disclosed serving on advisory boards for Gilead Sciences and Clinical Learning Designs, serving on the American College of Rheumatology’s Committee on Marketing and Communications, and holding investments in Johnson & Johnson.

Global Academy for Medical Education and this news organization are owned by the same parent company.

“When we think about bisphosphonates, we have to think about whether they are good players or bad players,” Marcy B. Bolster, MD, of Harvard Medical School, Boston, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Although bisphosphonates are a first-line treatment for many patients to reduce fracture risk, rheumatology patients have distinct concerns about these medications, said Dr. Bolster, who is director of the Rheumatology Fellowship Training Program at Massachusetts General Hospital, Boston, and medical lead for the Fracture Liaison Service there.

She shared her insights on four questions most often asked by patients in her practice:

How long do I need to take this medication?

When discussing bisphosphonates with a patient for the first time, “I typically start with the benefits, and include the risks,” she said. “Then I outline my plans for treatment, which would include treatment duration.”

Setting expectations with the patient about planned duration of therapy, reviewing risks and benefits, and preparing to be flexible if changes are needed can help relieve patients’ concerns, she said.

For example, in a hypothetical case of a 69-year-old woman with a 17% chance of a major osteoporotic fracture and 3.8% chance of hip fracture in the next 10 years based on FRAX scores, Dr. Bolster said she would treat with alendronate or zoledronic acid.

Duration must be a clinical decision individualized to the patient, she noted. Research studies support that some patients benefit from a longer duration of therapy. In the Fracture Intervention Trial (FIT) Long-Term Extension, which included 1,099 women, the risk of clinical vertebral fractures significantly declined with 10 years of alendronate treatment, compared with 5 years of treatment, she said.

In the HORIZON trial of 1,233 postmenopausal women, the risk of new morphometric vertebral fractures was significantly lower in those treated with IV zoledronic acid for 6 years versus those treated for 3 years. These studies support that patients at particularly high risk for vertebral fractures may benefit from a longer duration of bisphosphonate therapy, she said.
 

What should I know about infusion side effects?

Infusion side effects remain a concern, and the acute phase reaction of zoledronic acid occurs in about 30% of patients, but most of these are mild and not recurring, Dr. Bolster said. “I tell patients that 90% report mild to moderate infusion side effects, and that it usually occurs only with the first infusion,” she noted.

To potentially prevent an acute-phase reaction, Dr. Bolster has advised patients to take acetaminophen prior to infusion. “I would tend to recommend acetaminophen over NSAIDs to avoid gastric and renal toxicities,” she said.

“Determining the risks of atypical femoral fractures are challenging” but are another potential side effect that worries patients, she said. An atypical femoral fracture (AFF) is a femur fracture in the proximal third of the shaft, she said.

AFF may occur in patients with osteoporosis even in the absence of bisphosphonate use, Dr. Bolster noted. However, AFF “may occur at increased frequency in those patients with osteoporosis and prolonged bisphosphonate use,” she said. AFF is rare overall, and known risk factors include Asian race (in North America), as well as femoral bowing and glucocorticoid use, she said.

A 2019 meta-analysis favored fracture prevention benefits over potential risk associated with bisphosphonate use. Predicting the risk of AFF remains difficult given several factors, including the low incidence of AFF, the unavailability of radiographs in all studies, not accounting for potential confounding by indication in some studies, and lack of adjustment for low bone mineral density or fracture risk, she added.

Osteonecrosis of the jaw has been linked to bisphosphonate use, and some patients ask about it, Dr. Bolster said. Current data show an incidence of 1 in 10,000 to 1 in 100,000 in patients with osteoporosis, while the incidence in the general population is 1 in 100,000, she noted. The highest risk is associated with use of IV bisphosphonates, although it does occur in patients on oral bisphosphonates and denosumab (Prolia), she added. Given the relatively low risk, the American Dental Association states that there is “no need to discontinue bisphosphonates prior to procedures.” Based on current evidence, bisphosphonate treatment outweighs the low risk of medication-related osteonecrosis of the jaw in patients in need of osteoporosis treatment because of the high risk of fragility fractures in the osteoporosis population, she emphasized.
 

When will I need another dual x-ray absorptiometry scan?

Osteoporosis develops in fewer than 10% of older postmenopausal women using a 15-year screening interval for those with normal bone mineral density or mild osteopenia at an initial scan, with T-scores of –1.49 or higher, she noted. Therefore, the need for repeat dual x-ray absorptiometry (DXA) scans should be individualized, so some patients with normal bone density or osteopenia and few comorbidities and risk factors for osteoporosis may not need frequent DXA scans, she added.

Although little evidence exists to specifically demonstrate the value of monitoring bone mineral density during a 5-year drug treatment period, as is noted by the American College of Physicians 2017 clinical practice guideline published in Annals of Internal Medicine, Dr. Bolster said that a DXA scan showing loss of bone mineral density during treatment could indicate incorrect drug use or noncompliance, or a secondary cause for bone loss that may otherwise go unnoticed. For IV zoledronic acid in particular, a DXA scan at 3-4 years can determine whether a drug holiday is warranted, or for patients with severe osteoporosis, whether another 3 years of treatment is necessary. She suggested considering a DXA scan at 2-3 years with alendronate and at 3-4 years with IV zoledronic acid.

Will I need a new medication if I fracture while on treatment?

For patients who ask whether to change medications following a new fracture, Dr. Bolster said it is important to evaluate the patient’s compliance with the treatment regimen and also consider the presence of secondary causes of bone loss. Consideration can be given to keeping the patient on the same regimen because osteoporosis treatment regimens have demonstrated a 50%-70% fracture-risk reduction so they do not prevent all fractures, she said. “It is therefore reasonable, after confirming compliance and ruling out secondary causes of bone loss, to keep a patient on the same regimen following a fracture. For patients using denosumab, there is an increased risk of rapid bone loss and sustaining multiple vertebral fracture with missed doses or discontinuation,” she said.

It is important to evaluate patients who fracture while on therapy for secondary causes of bone loss, assess compliance, and consider strategies such as modifying the route of administration, seeking a different mechanism of action, or continuing on the same regimen, Dr. Bolster noted.

Dr. Bolster disclosed participation in clinical trials for Corbus, Cumberland, and Genentech, as well as research grants from the Rheumatology Research Foundation. She also disclosed serving on advisory boards for Gilead Sciences and Clinical Learning Designs, serving on the American College of Rheumatology’s Committee on Marketing and Communications, and holding investments in Johnson & Johnson.

Global Academy for Medical Education and this news organization are owned by the same parent company.

“When we think about bisphosphonates, we have to think about whether they are good players or bad players,” Marcy B. Bolster, MD, of Harvard Medical School, Boston, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Although bisphosphonates are a first-line treatment for many patients to reduce fracture risk, rheumatology patients have distinct concerns about these medications, said Dr. Bolster, who is director of the Rheumatology Fellowship Training Program at Massachusetts General Hospital, Boston, and medical lead for the Fracture Liaison Service there.

She shared her insights on four questions most often asked by patients in her practice:

How long do I need to take this medication?

When discussing bisphosphonates with a patient for the first time, “I typically start with the benefits, and include the risks,” she said. “Then I outline my plans for treatment, which would include treatment duration.”

Setting expectations with the patient about planned duration of therapy, reviewing risks and benefits, and preparing to be flexible if changes are needed can help relieve patients’ concerns, she said.

For example, in a hypothetical case of a 69-year-old woman with a 17% chance of a major osteoporotic fracture and 3.8% chance of hip fracture in the next 10 years based on FRAX scores, Dr. Bolster said she would treat with alendronate or zoledronic acid.

Duration must be a clinical decision individualized to the patient, she noted. Research studies support that some patients benefit from a longer duration of therapy. In the Fracture Intervention Trial (FIT) Long-Term Extension, which included 1,099 women, the risk of clinical vertebral fractures significantly declined with 10 years of alendronate treatment, compared with 5 years of treatment, she said.

In the HORIZON trial of 1,233 postmenopausal women, the risk of new morphometric vertebral fractures was significantly lower in those treated with IV zoledronic acid for 6 years versus those treated for 3 years. These studies support that patients at particularly high risk for vertebral fractures may benefit from a longer duration of bisphosphonate therapy, she said.
 

What should I know about infusion side effects?

Infusion side effects remain a concern, and the acute phase reaction of zoledronic acid occurs in about 30% of patients, but most of these are mild and not recurring, Dr. Bolster said. “I tell patients that 90% report mild to moderate infusion side effects, and that it usually occurs only with the first infusion,” she noted.

To potentially prevent an acute-phase reaction, Dr. Bolster has advised patients to take acetaminophen prior to infusion. “I would tend to recommend acetaminophen over NSAIDs to avoid gastric and renal toxicities,” she said.

“Determining the risks of atypical femoral fractures are challenging” but are another potential side effect that worries patients, she said. An atypical femoral fracture (AFF) is a femur fracture in the proximal third of the shaft, she said.

AFF may occur in patients with osteoporosis even in the absence of bisphosphonate use, Dr. Bolster noted. However, AFF “may occur at increased frequency in those patients with osteoporosis and prolonged bisphosphonate use,” she said. AFF is rare overall, and known risk factors include Asian race (in North America), as well as femoral bowing and glucocorticoid use, she said.

A 2019 meta-analysis favored fracture prevention benefits over potential risk associated with bisphosphonate use. Predicting the risk of AFF remains difficult given several factors, including the low incidence of AFF, the unavailability of radiographs in all studies, not accounting for potential confounding by indication in some studies, and lack of adjustment for low bone mineral density or fracture risk, she added.

Osteonecrosis of the jaw has been linked to bisphosphonate use, and some patients ask about it, Dr. Bolster said. Current data show an incidence of 1 in 10,000 to 1 in 100,000 in patients with osteoporosis, while the incidence in the general population is 1 in 100,000, she noted. The highest risk is associated with use of IV bisphosphonates, although it does occur in patients on oral bisphosphonates and denosumab (Prolia), she added. Given the relatively low risk, the American Dental Association states that there is “no need to discontinue bisphosphonates prior to procedures.” Based on current evidence, bisphosphonate treatment outweighs the low risk of medication-related osteonecrosis of the jaw in patients in need of osteoporosis treatment because of the high risk of fragility fractures in the osteoporosis population, she emphasized.
 

When will I need another dual x-ray absorptiometry scan?

Osteoporosis develops in fewer than 10% of older postmenopausal women using a 15-year screening interval for those with normal bone mineral density or mild osteopenia at an initial scan, with T-scores of –1.49 or higher, she noted. Therefore, the need for repeat dual x-ray absorptiometry (DXA) scans should be individualized, so some patients with normal bone density or osteopenia and few comorbidities and risk factors for osteoporosis may not need frequent DXA scans, she added.

Although little evidence exists to specifically demonstrate the value of monitoring bone mineral density during a 5-year drug treatment period, as is noted by the American College of Physicians 2017 clinical practice guideline published in Annals of Internal Medicine, Dr. Bolster said that a DXA scan showing loss of bone mineral density during treatment could indicate incorrect drug use or noncompliance, or a secondary cause for bone loss that may otherwise go unnoticed. For IV zoledronic acid in particular, a DXA scan at 3-4 years can determine whether a drug holiday is warranted, or for patients with severe osteoporosis, whether another 3 years of treatment is necessary. She suggested considering a DXA scan at 2-3 years with alendronate and at 3-4 years with IV zoledronic acid.

Will I need a new medication if I fracture while on treatment?

For patients who ask whether to change medications following a new fracture, Dr. Bolster said it is important to evaluate the patient’s compliance with the treatment regimen and also consider the presence of secondary causes of bone loss. Consideration can be given to keeping the patient on the same regimen because osteoporosis treatment regimens have demonstrated a 50%-70% fracture-risk reduction so they do not prevent all fractures, she said. “It is therefore reasonable, after confirming compliance and ruling out secondary causes of bone loss, to keep a patient on the same regimen following a fracture. For patients using denosumab, there is an increased risk of rapid bone loss and sustaining multiple vertebral fracture with missed doses or discontinuation,” she said.

It is important to evaluate patients who fracture while on therapy for secondary causes of bone loss, assess compliance, and consider strategies such as modifying the route of administration, seeking a different mechanism of action, or continuing on the same regimen, Dr. Bolster noted.

Dr. Bolster disclosed participation in clinical trials for Corbus, Cumberland, and Genentech, as well as research grants from the Rheumatology Research Foundation. She also disclosed serving on advisory boards for Gilead Sciences and Clinical Learning Designs, serving on the American College of Rheumatology’s Committee on Marketing and Communications, and holding investments in Johnson & Johnson.

Global Academy for Medical Education and this news organization are owned by the same parent company.

A common adverse effect of the multiple sclerosis (MS) treatment alemtuzumab (Lemtrada) may be predicted by pretreatment levels of certain types of B cells, a new study suggests.

“Alemtuzumab has proven to be an effective treatment for patients with highly active remitting relapsing MS, but adverse events may limit the use of this drug, particularly autoimmune adverse events, which are the most prevalent, occurring in about 30% of patients. Reliable biomarkers to assess patient risk for developing this complication would be of great importance,” said lead author Paulette Walo, MD.

“Our results suggest that a higher percentage of total B cells, and in particular plasmablasts, could be a very predictive biomarker for autoimmunity after alemtuzumab treatment. This could help us in choosing the patients for this drug,” said Dr. Walo, an immunologist at Ramon y Cajal University Hospital, Madrid. She presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The objective of this study was to explore if patient blood lymphocyte profile before alemtuzumab treatment initiation can identify patients with an increased risk of developing later autoimmunity, Dr. Walo explained.

The study included 54 patients from five hospitals throughout Spain who had received treatment with alemtuzumab. Of these, the vast majority had received the normal two-dose cycle and two patients had received a third dose because of worsening MS activity.

Blood samples were collected before initiating treatment with alemtuzumab. Peripheral blood mononuclear cells were obtained and cryopreserved. Leukocyte populations were assessed by flow cytometry.

Autoimmune adverse events were defined as the development, at any point within 2 years of follow-up, of any autoimmune thyroid-associated event, immune thrombocytopenia, and/or autoimmune nephropathy.

Over the 2 years of follow-up, 14 patients (25.9%) experienced autoimmune adverse events, all of which were dysthyroidism. No immune thrombocytopenia or nephropathies were observed.

No statistical differences were found in clinical and demographic characteristics between patients who developed autoimmune adverse events and those who did not. Previous treatments did not influence B-cell percentages.

Analysis of blood lymphocyte profiles showed no difference in T-cell subsets between those who had an autoimmune event and those who did not.

Still, there were important differences in the B-cell profile, Dr. Walo said. “Total B cells were higher in patients who had an autoimmune event mainly due to naive B cells and plasmablasts.”

Patients who experienced autoimmune adverse events before treatment onset had a higher percentage of blood CD19+ B cells (P = .001), with a higher relative percentage of naive B cells and plasmablasts.

When individual types of cell numbers were explored, only plasmablast levels remained significant (P = .02).

The researchers calculated a CD19+ B-cell predictive value for autoimmunity of 7.6%. If patients had more than 7.6% B cells, they were at higher risk of an autoimmune adverse event after alemtuzumab treatment versus those with lower levels (odds ratio, 14.67; P ≤ .0001).

Similarly, the predictive value for plasmablasts was 0.13%. If patients had levels higher than 0.13% they had a higher risk of an autoimmune event after alemtuzumab treatment (P = .002). Plasmablasts are a category of B cells which are very differentiated and have the capacity to produce antibodies; they are a very active and aggressive subtype of B cells, Dr. Walo noted. 

She explained that, as was the case in this study, autoimmune events after alemtuzumab treatment normally manifests as the development of antibodies against the thyroid gland, with the development of either hyperthyroidism or hypothyroidism, necessitating long-term treatment to manage these conditions.

“Autoimmunity develops at variable timescales. It can appear in the first year after alemtuzumab treatment but it can also appear later on,” she said.

Dr. Walo’s group is hoping to validate their results in a larger study. “This is only a small study so we need to replicate these findings in a larger cohort. We are in the process of doing this, collaborating with other hospitals,” she commented. 

She said that, if the results are validated, then patients could undergo blood tests before alemtuzumab treatment to analyze their B-cell counts.

“For those with high levels of B cells – and particularly plasmablasts – alemtuzumab may not be the best treatment to choose,” Dr. Walo said.
 

Personalized strategy

During the postpresentation discussion, the suggestion was raised of giving an anti–B-cell drug before alemtuzumab to try and prevent autoimmunity. Dr. Walo responded that this is a possibility. “This is something that we are going to look into. If our larger study validates our initial results, then we would plan a study to give an anti–B-cell treatment such as rituximab before alemtuzumab and see whether this reduces the risk of autoimmunity.”

Commenting on the study, session comoderator Darin Okuda, MD, professor in the department of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center, Dallas, said: “This is an intriguing approach and suggests a more personalized strategy for sure if we can identify patients who are at higher risk of developing autoimmunity.”

Also commenting, ACTRIMS president Jeffrey Cohen, MD, said: “One of the main drawbacks of alemtuzumab is the risk of antibody-mediated autoimmune conditions, so the ability to predict who is at risk for autoimmune adverse events prior to initiating alemtuzumab would be useful. Not surprisingly, factors related to B-cell number and profile were predictive.”

Dr. Cohen, who is a director of experimental neurotherapeutics at the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, added however that the suggestion of pretreating patients with an anti-CD20 monoclonal antibody “does not seem tenable to me,” because of the potential cost of such a strategy, and “no efficacy advantage for most patients over an anti-CD20 antibody alone.”

Commenting on this presentation, Alasdair J. Coles, MD, University of Cambridge (England), who was one of the co-inventors of alemtuzumab, said observations of an increased B-cell count before treatment as a risk predictor of thyroid autoimmunity after alemtuzumab had not been replicated in the clinical trial datasets of the drug. “So I fear we still do not have a reliable biomarker,” he added.

The study had no specific funding listed. Dr. Walo has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A common adverse effect of the multiple sclerosis (MS) treatment alemtuzumab (Lemtrada) may be predicted by pretreatment levels of certain types of B cells, a new study suggests.

“Alemtuzumab has proven to be an effective treatment for patients with highly active remitting relapsing MS, but adverse events may limit the use of this drug, particularly autoimmune adverse events, which are the most prevalent, occurring in about 30% of patients. Reliable biomarkers to assess patient risk for developing this complication would be of great importance,” said lead author Paulette Walo, MD.

“Our results suggest that a higher percentage of total B cells, and in particular plasmablasts, could be a very predictive biomarker for autoimmunity after alemtuzumab treatment. This could help us in choosing the patients for this drug,” said Dr. Walo, an immunologist at Ramon y Cajal University Hospital, Madrid. She presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The objective of this study was to explore if patient blood lymphocyte profile before alemtuzumab treatment initiation can identify patients with an increased risk of developing later autoimmunity, Dr. Walo explained.

The study included 54 patients from five hospitals throughout Spain who had received treatment with alemtuzumab. Of these, the vast majority had received the normal two-dose cycle and two patients had received a third dose because of worsening MS activity.

Blood samples were collected before initiating treatment with alemtuzumab. Peripheral blood mononuclear cells were obtained and cryopreserved. Leukocyte populations were assessed by flow cytometry.

Autoimmune adverse events were defined as the development, at any point within 2 years of follow-up, of any autoimmune thyroid-associated event, immune thrombocytopenia, and/or autoimmune nephropathy.

Over the 2 years of follow-up, 14 patients (25.9%) experienced autoimmune adverse events, all of which were dysthyroidism. No immune thrombocytopenia or nephropathies were observed.

No statistical differences were found in clinical and demographic characteristics between patients who developed autoimmune adverse events and those who did not. Previous treatments did not influence B-cell percentages.

Analysis of blood lymphocyte profiles showed no difference in T-cell subsets between those who had an autoimmune event and those who did not.

Still, there were important differences in the B-cell profile, Dr. Walo said. “Total B cells were higher in patients who had an autoimmune event mainly due to naive B cells and plasmablasts.”

Patients who experienced autoimmune adverse events before treatment onset had a higher percentage of blood CD19+ B cells (P = .001), with a higher relative percentage of naive B cells and plasmablasts.

When individual types of cell numbers were explored, only plasmablast levels remained significant (P = .02).

The researchers calculated a CD19+ B-cell predictive value for autoimmunity of 7.6%. If patients had more than 7.6% B cells, they were at higher risk of an autoimmune adverse event after alemtuzumab treatment versus those with lower levels (odds ratio, 14.67; P ≤ .0001).

Similarly, the predictive value for plasmablasts was 0.13%. If patients had levels higher than 0.13% they had a higher risk of an autoimmune event after alemtuzumab treatment (P = .002). Plasmablasts are a category of B cells which are very differentiated and have the capacity to produce antibodies; they are a very active and aggressive subtype of B cells, Dr. Walo noted. 

She explained that, as was the case in this study, autoimmune events after alemtuzumab treatment normally manifests as the development of antibodies against the thyroid gland, with the development of either hyperthyroidism or hypothyroidism, necessitating long-term treatment to manage these conditions.

“Autoimmunity develops at variable timescales. It can appear in the first year after alemtuzumab treatment but it can also appear later on,” she said.

Dr. Walo’s group is hoping to validate their results in a larger study. “This is only a small study so we need to replicate these findings in a larger cohort. We are in the process of doing this, collaborating with other hospitals,” she commented. 

She said that, if the results are validated, then patients could undergo blood tests before alemtuzumab treatment to analyze their B-cell counts.

“For those with high levels of B cells – and particularly plasmablasts – alemtuzumab may not be the best treatment to choose,” Dr. Walo said.
 

Personalized strategy

During the postpresentation discussion, the suggestion was raised of giving an anti–B-cell drug before alemtuzumab to try and prevent autoimmunity. Dr. Walo responded that this is a possibility. “This is something that we are going to look into. If our larger study validates our initial results, then we would plan a study to give an anti–B-cell treatment such as rituximab before alemtuzumab and see whether this reduces the risk of autoimmunity.”

Commenting on the study, session comoderator Darin Okuda, MD, professor in the department of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center, Dallas, said: “This is an intriguing approach and suggests a more personalized strategy for sure if we can identify patients who are at higher risk of developing autoimmunity.”

Also commenting, ACTRIMS president Jeffrey Cohen, MD, said: “One of the main drawbacks of alemtuzumab is the risk of antibody-mediated autoimmune conditions, so the ability to predict who is at risk for autoimmune adverse events prior to initiating alemtuzumab would be useful. Not surprisingly, factors related to B-cell number and profile were predictive.”

Dr. Cohen, who is a director of experimental neurotherapeutics at the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, added however that the suggestion of pretreating patients with an anti-CD20 monoclonal antibody “does not seem tenable to me,” because of the potential cost of such a strategy, and “no efficacy advantage for most patients over an anti-CD20 antibody alone.”

Commenting on this presentation, Alasdair J. Coles, MD, University of Cambridge (England), who was one of the co-inventors of alemtuzumab, said observations of an increased B-cell count before treatment as a risk predictor of thyroid autoimmunity after alemtuzumab had not been replicated in the clinical trial datasets of the drug. “So I fear we still do not have a reliable biomarker,” he added.

The study had no specific funding listed. Dr. Walo has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A common adverse effect of the multiple sclerosis (MS) treatment alemtuzumab (Lemtrada) may be predicted by pretreatment levels of certain types of B cells, a new study suggests.

“Alemtuzumab has proven to be an effective treatment for patients with highly active remitting relapsing MS, but adverse events may limit the use of this drug, particularly autoimmune adverse events, which are the most prevalent, occurring in about 30% of patients. Reliable biomarkers to assess patient risk for developing this complication would be of great importance,” said lead author Paulette Walo, MD.

“Our results suggest that a higher percentage of total B cells, and in particular plasmablasts, could be a very predictive biomarker for autoimmunity after alemtuzumab treatment. This could help us in choosing the patients for this drug,” said Dr. Walo, an immunologist at Ramon y Cajal University Hospital, Madrid. She presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

The objective of this study was to explore if patient blood lymphocyte profile before alemtuzumab treatment initiation can identify patients with an increased risk of developing later autoimmunity, Dr. Walo explained.

The study included 54 patients from five hospitals throughout Spain who had received treatment with alemtuzumab. Of these, the vast majority had received the normal two-dose cycle and two patients had received a third dose because of worsening MS activity.

Blood samples were collected before initiating treatment with alemtuzumab. Peripheral blood mononuclear cells were obtained and cryopreserved. Leukocyte populations were assessed by flow cytometry.

Autoimmune adverse events were defined as the development, at any point within 2 years of follow-up, of any autoimmune thyroid-associated event, immune thrombocytopenia, and/or autoimmune nephropathy.

Over the 2 years of follow-up, 14 patients (25.9%) experienced autoimmune adverse events, all of which were dysthyroidism. No immune thrombocytopenia or nephropathies were observed.

No statistical differences were found in clinical and demographic characteristics between patients who developed autoimmune adverse events and those who did not. Previous treatments did not influence B-cell percentages.

Analysis of blood lymphocyte profiles showed no difference in T-cell subsets between those who had an autoimmune event and those who did not.

Still, there were important differences in the B-cell profile, Dr. Walo said. “Total B cells were higher in patients who had an autoimmune event mainly due to naive B cells and plasmablasts.”

Patients who experienced autoimmune adverse events before treatment onset had a higher percentage of blood CD19+ B cells (P = .001), with a higher relative percentage of naive B cells and plasmablasts.

When individual types of cell numbers were explored, only plasmablast levels remained significant (P = .02).

The researchers calculated a CD19+ B-cell predictive value for autoimmunity of 7.6%. If patients had more than 7.6% B cells, they were at higher risk of an autoimmune adverse event after alemtuzumab treatment versus those with lower levels (odds ratio, 14.67; P ≤ .0001).

Similarly, the predictive value for plasmablasts was 0.13%. If patients had levels higher than 0.13% they had a higher risk of an autoimmune event after alemtuzumab treatment (P = .002). Plasmablasts are a category of B cells which are very differentiated and have the capacity to produce antibodies; they are a very active and aggressive subtype of B cells, Dr. Walo noted. 

She explained that, as was the case in this study, autoimmune events after alemtuzumab treatment normally manifests as the development of antibodies against the thyroid gland, with the development of either hyperthyroidism or hypothyroidism, necessitating long-term treatment to manage these conditions.

“Autoimmunity develops at variable timescales. It can appear in the first year after alemtuzumab treatment but it can also appear later on,” she said.

Dr. Walo’s group is hoping to validate their results in a larger study. “This is only a small study so we need to replicate these findings in a larger cohort. We are in the process of doing this, collaborating with other hospitals,” she commented. 

She said that, if the results are validated, then patients could undergo blood tests before alemtuzumab treatment to analyze their B-cell counts.

“For those with high levels of B cells – and particularly plasmablasts – alemtuzumab may not be the best treatment to choose,” Dr. Walo said.
 

Personalized strategy

During the postpresentation discussion, the suggestion was raised of giving an anti–B-cell drug before alemtuzumab to try and prevent autoimmunity. Dr. Walo responded that this is a possibility. “This is something that we are going to look into. If our larger study validates our initial results, then we would plan a study to give an anti–B-cell treatment such as rituximab before alemtuzumab and see whether this reduces the risk of autoimmunity.”

Commenting on the study, session comoderator Darin Okuda, MD, professor in the department of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center, Dallas, said: “This is an intriguing approach and suggests a more personalized strategy for sure if we can identify patients who are at higher risk of developing autoimmunity.”

Also commenting, ACTRIMS president Jeffrey Cohen, MD, said: “One of the main drawbacks of alemtuzumab is the risk of antibody-mediated autoimmune conditions, so the ability to predict who is at risk for autoimmune adverse events prior to initiating alemtuzumab would be useful. Not surprisingly, factors related to B-cell number and profile were predictive.”

Dr. Cohen, who is a director of experimental neurotherapeutics at the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, added however that the suggestion of pretreating patients with an anti-CD20 monoclonal antibody “does not seem tenable to me,” because of the potential cost of such a strategy, and “no efficacy advantage for most patients over an anti-CD20 antibody alone.”

Commenting on this presentation, Alasdair J. Coles, MD, University of Cambridge (England), who was one of the co-inventors of alemtuzumab, said observations of an increased B-cell count before treatment as a risk predictor of thyroid autoimmunity after alemtuzumab had not been replicated in the clinical trial datasets of the drug. “So I fear we still do not have a reliable biomarker,” he added.

The study had no specific funding listed. Dr. Walo has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

As approaches to airway management of patients with suspected or confirmed COVID-19 continue to evolve, practicing vigilant transmission-based infection control precautions remains essential.

This starts with observing droplet precautions to prevent exposure to droplets larger than 5 microns in size, Charles Griffis, PhD, CRNA, said at a Society for Critical Care Medicine virtual meeting: COVID-19: What’s Next. “These are particles exhaled from infected persons and which fall within around 6 feet and involve an exposure time of 15 or more minutes of contact,” said Dr. Griffis, of the department of anesthesiology at the University of Southern California, Los Angeles. “We will always observe standard precautions, which include hand hygiene, gloves, hair and eye cover, medical mask, and face shield. We will observe these at all times for all patients and layer our transmission-based precautions on top.”

During aerosol-producing procedures such as airway management maneuvers, tracheostomies, and bronchoscopies, very fine microscopic particles less than 5 microns in size are produced, which remain airborne for potentially many hours and travel long distances. “We will add an N95 mask or a powered air-purifying respirator (PAPR) device to filter out tiny particles in addition to our ever-present standard precautions,” he said. “Contact precautions are indicated for direct contact with patient saliva, blood, urine, and stool. In addition to standard precautions, we’re going to add an impermeable gown and we’ll continue with gloves, eye protection, and shoe covers. The message is to all of us. We have to observe all of the infection precautions that all of us have learned and trained in to avoid exposure.”

In terms of airway management for infected patients for elective procedures and surgery, recommendations based on current and previous coronavirus outbreaks suggest that all patients get polymerase chain reaction (PCR) tested within 24-48 hours of elective procedures or surgeries. If positive, they should be quarantined for 10-14 days and then, if asymptomatic, these patients may be retested or they can be regarded as negative. “Patients who are PCR positive with active infection and active symptoms receive only urgent or emergent care in most settings,” said Dr. Griffis, a member of the American Association of Nurse Anesthetists Infection Control Advisory Panel. “The care provided to our patients, whether they’re positive or not, is individualized per patient needs and institutional policy. Some folks have made the decision to treat all patients as infected and to use airborne precautions for all aerosol-producing procedures for all patients all the time.”

When a COVID-19 patient requires emergent or urgent airway management because of respiratory failure or some other surgical or procedural intervention necessitating airway management, preprocedural planning is key, he continued. This means establishing the steps in airway management scenarios for infected patients and rehearsing those steps in each ICU setting with key personnel such as nurses, respiratory therapists, and medical staff. “You want to make sure that the PPE is readily available and determine and limit the number of personnel that are going to enter the patient’s room or area for airway management,” Dr. Griffis said. “Have all the airway equipment and drugs immediately available. Perhaps you could organize them in a cart which is decontaminated after every use.”

He also recommends forming an intubation team for ICUs and perhaps even for ORs, where the most experienced clinicians perform airway management. “This helps to avoid unnecessary airway manipulation and minimizes personnel exposure and time to airway establishment,” he said.

Always attempt to house the infected patient in an airborne isolation, negative-pressure room, with a minimum of 12 exchanges per hour and which will take 35 minutes for 99.99% removal of airborne contaminants after airway management. “These numbers are important to remember for room turnover safety,” he said.

Patient factors to review during airway management include assessing the past medical history, inspecting the airway and considering the patient’s current physiological status as time permits. Previously in the pandemic, intubation was used earlier in the disease course, but now data suggest that patients do better without intubation if possible (Am J Trop Med Hyg. 2020;102[6]. doi: 10.4269/aitmh.20-0283). “This is because the pathophysiology of COVID-19 is such that the lung tissue is predisposed to iatrogenic barotrauma damage from positive-pressure ventilation,” Dr. Griffis said. “In addition, COVID patients appear to tolerate significant hypoxemia without distress in many cases. Therefore, many clinicians now hold off on intubation until the hypoxemic patient begins exhibiting signs and symptoms of respiratory distress.”

Options for delivering noninvasive airway support for COVID-19 patients include high-flow nasal cannula and noninvasive positive-pressure ventilation via CPAP or BiPAP. To mitigate the associated aerosol production, consider applying a surgical mask, helmet, or face mask over the airway device/patient’s face. “Another measure that has proven helpful in general respiratory support is to actually put the patient in a prone position to help redistribute ventilation throughout the lungs,” Dr. Griffis said (see Resp Care. 2015;60[11]:1660-87).

To prepare for the actual intubation procedure, gather two expert intubators who are going to be entering the patient’s room. The team should perform hand hygiene and don full PPE prior to entry. “It’s recommended that you consider wearing double gloves for the intubation,” he said. “Have the airway equipment easily accessible in a central location on a cart or in a kit, and use disposable, single-use equipment if possible. All of the usual intubation equipment to maintain a clear airway and give positive pressure ventilation should be arranged for easy access. A video laryngoscope should be used, if possible, for greater accuracy and reduced procedure time. Ready access to sedation and muscle relaxant drugs must be assured at all times.”

For the intubation procedure itself, Dr. Griffis recommends ensuring that an oxygen source, positive-pressure ventilation, and suction and resuscitation drugs and equipment are available per institutional protocol. Assign one person outside the room to coordinate supplies and assistance. “Preoxygenate the patient as permitted by clinical status,” he said. “A nonrebreathing oxygen mask can be used if sufficient spontaneous ventilation is present. Assess the airway, check and arrange equipment for easy access, and develop the safest airway management plan. Consider a rapid sequence induction and intubation as the first option.” Avoid positive-pressure ventilation or awake fiber optic intubation unless absolutely necessary, thus avoiding aerosol production. “Only ventilate the patient after the endotracheal tube cuff is inflated, to avoid aerosol release,” he said.

For intubation, administer airway procedural drugs and insert the laryngoscope – ideally a video laryngoscope if available. Intubate the trachea under direct vision, inflate the cuff, and remove outer gloves. Then attach the Ambu bag with a 99% filtration efficiency, heat-and-moisture exchange filter; and proceed to ventilate the patient, checking for chest rise, breath sounds, and CO₂ production. “Discard contaminated equipment in designated bins and secure the tube,” Dr. Griffis advised. “Attach the ventilator with an HMEF filter to protect the ventilator circuit and inner parts of the machine. Recheck your breath sounds, CO₂ production, and oxygen saturation, and adjust your vent settings as indicated.”

For post intubation, Dr. Griffis recommends securing contaminated discardable equipment in biohazard-labeled bins or bags, safely doffing your PPE, and retaining your N95 mask in the room. Remove your inner gloves, perform hand hygiene with soap and water if available, with alcohol-based hand rub if not, then don clean gloves. Exit the room, safely transporting any contaminated equipment that will be reused such as a cart or video laryngoscope to decontamination areas for processing. “Once clear of the room, order your chest x-ray to confirm your tube position per institutional protocol, understanding that radiology techs are all going to be following infection control procedures and wearing their PPE,” he said.

For extubation, Dr. Griffis recommends excusing all nonessential personnel from the patient room and assigning an assistant outside the room for necessary help. An experienced airway management expert should evaluate the patient wearing full PPE and be double-gloved. “If the extubation criteria are met, suction the pharynx and extubate,” he said. “Remove outer gloves and apply desired oxygen delivery equipment to the patient and assess respiratory status and vital signs for stability.” Next, discard all contaminated equipment in designated bins, doff contaminated PPE, and retain your N95 mask. Doff inner gloves, perform hand hygiene, and don clean gloves. “Exit the room, hand off contaminated equipment that is reusable, doff your gloves outside, do hand hygiene, then proceed to change your scrubs and complete your own personal hygiene measures,” he said.

Dr. Griffis reported having no financial disclosures.

“While the PPE used for intubation of a coronavirus patient is certainly more than the typical droplet precautions observed when intubating any other patient, the process and best practices aren’t terribly different from usual standard of care: Ensuring all necessary equipment is readily available with backup plans should the airway be difficult,” said Megan Conroy, MD, assistant professor of clinical medicine at The Ohio State University.

“We’ve been streamlining the team that’s present in the room for intubations of COVID patients, but I’m always amazed at the team members that stand at the ready to lend additional assistance just from the other side of the door. So while fewer personnel may be exposed, I wouldn’t consider the team needed for intubation to actually be much smaller, we’re just functioning differently.

In my practice the decision of when to intubate, clinically, doesn’t vary too much from any other form of severe ARDS. We may tolerate higher FiO₂ requirements on heated high-flow nasal cannula if the patient exhibits acceptable work of breathing, but I wouldn’t advise allowing a patient to remain hypoxemic with oxygen needs unmet by noninvasive methods out of fear of intubation or ventilator management. In my opinion, this simply delays a necessary therapy and only makes for a higher risk intubation. Certainly, the decision to intubate is never based on only one single data point, but takes an expert assessment of the whole clinical picture.

I’d assert that it’s true in every disease that patients do better if it’s possible to avoid intubation – but I would argue that the ability to avoid intubation is determined primarily by the disease course and clinical scenario, and not by whether the physician wishes to avoid intubation or not. If I can safely manage a patient off of a ventilator, I will always do so, COVID or otherwise. I think in this phase of the pandemic, patients ‘do better without intubation’ because those who didn’t require intubation were inherently doing better!”

[email protected]

As approaches to airway management of patients with suspected or confirmed COVID-19 continue to evolve, practicing vigilant transmission-based infection control precautions remains essential.

This starts with observing droplet precautions to prevent exposure to droplets larger than 5 microns in size, Charles Griffis, PhD, CRNA, said at a Society for Critical Care Medicine virtual meeting: COVID-19: What’s Next. “These are particles exhaled from infected persons and which fall within around 6 feet and involve an exposure time of 15 or more minutes of contact,” said Dr. Griffis, of the department of anesthesiology at the University of Southern California, Los Angeles. “We will always observe standard precautions, which include hand hygiene, gloves, hair and eye cover, medical mask, and face shield. We will observe these at all times for all patients and layer our transmission-based precautions on top.”

During aerosol-producing procedures such as airway management maneuvers, tracheostomies, and bronchoscopies, very fine microscopic particles less than 5 microns in size are produced, which remain airborne for potentially many hours and travel long distances. “We will add an N95 mask or a powered air-purifying respirator (PAPR) device to filter out tiny particles in addition to our ever-present standard precautions,” he said. “Contact precautions are indicated for direct contact with patient saliva, blood, urine, and stool. In addition to standard precautions, we’re going to add an impermeable gown and we’ll continue with gloves, eye protection, and shoe covers. The message is to all of us. We have to observe all of the infection precautions that all of us have learned and trained in to avoid exposure.”

In terms of airway management for infected patients for elective procedures and surgery, recommendations based on current and previous coronavirus outbreaks suggest that all patients get polymerase chain reaction (PCR) tested within 24-48 hours of elective procedures or surgeries. If positive, they should be quarantined for 10-14 days and then, if asymptomatic, these patients may be retested or they can be regarded as negative. “Patients who are PCR positive with active infection and active symptoms receive only urgent or emergent care in most settings,” said Dr. Griffis, a member of the American Association of Nurse Anesthetists Infection Control Advisory Panel. “The care provided to our patients, whether they’re positive or not, is individualized per patient needs and institutional policy. Some folks have made the decision to treat all patients as infected and to use airborne precautions for all aerosol-producing procedures for all patients all the time.”

When a COVID-19 patient requires emergent or urgent airway management because of respiratory failure or some other surgical or procedural intervention necessitating airway management, preprocedural planning is key, he continued. This means establishing the steps in airway management scenarios for infected patients and rehearsing those steps in each ICU setting with key personnel such as nurses, respiratory therapists, and medical staff. “You want to make sure that the PPE is readily available and determine and limit the number of personnel that are going to enter the patient’s room or area for airway management,” Dr. Griffis said. “Have all the airway equipment and drugs immediately available. Perhaps you could organize them in a cart which is decontaminated after every use.”

He also recommends forming an intubation team for ICUs and perhaps even for ORs, where the most experienced clinicians perform airway management. “This helps to avoid unnecessary airway manipulation and minimizes personnel exposure and time to airway establishment,” he said.

Always attempt to house the infected patient in an airborne isolation, negative-pressure room, with a minimum of 12 exchanges per hour and which will take 35 minutes for 99.99% removal of airborne contaminants after airway management. “These numbers are important to remember for room turnover safety,” he said.

Patient factors to review during airway management include assessing the past medical history, inspecting the airway and considering the patient’s current physiological status as time permits. Previously in the pandemic, intubation was used earlier in the disease course, but now data suggest that patients do better without intubation if possible (Am J Trop Med Hyg. 2020;102[6]. doi: 10.4269/aitmh.20-0283). “This is because the pathophysiology of COVID-19 is such that the lung tissue is predisposed to iatrogenic barotrauma damage from positive-pressure ventilation,” Dr. Griffis said. “In addition, COVID patients appear to tolerate significant hypoxemia without distress in many cases. Therefore, many clinicians now hold off on intubation until the hypoxemic patient begins exhibiting signs and symptoms of respiratory distress.”

Options for delivering noninvasive airway support for COVID-19 patients include high-flow nasal cannula and noninvasive positive-pressure ventilation via CPAP or BiPAP. To mitigate the associated aerosol production, consider applying a surgical mask, helmet, or face mask over the airway device/patient’s face. “Another measure that has proven helpful in general respiratory support is to actually put the patient in a prone position to help redistribute ventilation throughout the lungs,” Dr. Griffis said (see Resp Care. 2015;60[11]:1660-87).

To prepare for the actual intubation procedure, gather two expert intubators who are going to be entering the patient’s room. The team should perform hand hygiene and don full PPE prior to entry. “It’s recommended that you consider wearing double gloves for the intubation,” he said. “Have the airway equipment easily accessible in a central location on a cart or in a kit, and use disposable, single-use equipment if possible. All of the usual intubation equipment to maintain a clear airway and give positive pressure ventilation should be arranged for easy access. A video laryngoscope should be used, if possible, for greater accuracy and reduced procedure time. Ready access to sedation and muscle relaxant drugs must be assured at all times.”

For the intubation procedure itself, Dr. Griffis recommends ensuring that an oxygen source, positive-pressure ventilation, and suction and resuscitation drugs and equipment are available per institutional protocol. Assign one person outside the room to coordinate supplies and assistance. “Preoxygenate the patient as permitted by clinical status,” he said. “A nonrebreathing oxygen mask can be used if sufficient spontaneous ventilation is present. Assess the airway, check and arrange equipment for easy access, and develop the safest airway management plan. Consider a rapid sequence induction and intubation as the first option.” Avoid positive-pressure ventilation or awake fiber optic intubation unless absolutely necessary, thus avoiding aerosol production. “Only ventilate the patient after the endotracheal tube cuff is inflated, to avoid aerosol release,” he said.

For intubation, administer airway procedural drugs and insert the laryngoscope – ideally a video laryngoscope if available. Intubate the trachea under direct vision, inflate the cuff, and remove outer gloves. Then attach the Ambu bag with a 99% filtration efficiency, heat-and-moisture exchange filter; and proceed to ventilate the patient, checking for chest rise, breath sounds, and CO₂ production. “Discard contaminated equipment in designated bins and secure the tube,” Dr. Griffis advised. “Attach the ventilator with an HMEF filter to protect the ventilator circuit and inner parts of the machine. Recheck your breath sounds, CO₂ production, and oxygen saturation, and adjust your vent settings as indicated.”

For post intubation, Dr. Griffis recommends securing contaminated discardable equipment in biohazard-labeled bins or bags, safely doffing your PPE, and retaining your N95 mask in the room. Remove your inner gloves, perform hand hygiene with soap and water if available, with alcohol-based hand rub if not, then don clean gloves. Exit the room, safely transporting any contaminated equipment that will be reused such as a cart or video laryngoscope to decontamination areas for processing. “Once clear of the room, order your chest x-ray to confirm your tube position per institutional protocol, understanding that radiology techs are all going to be following infection control procedures and wearing their PPE,” he said.

For extubation, Dr. Griffis recommends excusing all nonessential personnel from the patient room and assigning an assistant outside the room for necessary help. An experienced airway management expert should evaluate the patient wearing full PPE and be double-gloved. “If the extubation criteria are met, suction the pharynx and extubate,” he said. “Remove outer gloves and apply desired oxygen delivery equipment to the patient and assess respiratory status and vital signs for stability.” Next, discard all contaminated equipment in designated bins, doff contaminated PPE, and retain your N95 mask. Doff inner gloves, perform hand hygiene, and don clean gloves. “Exit the room, hand off contaminated equipment that is reusable, doff your gloves outside, do hand hygiene, then proceed to change your scrubs and complete your own personal hygiene measures,” he said.

Dr. Griffis reported having no financial disclosures.

“While the PPE used for intubation of a coronavirus patient is certainly more than the typical droplet precautions observed when intubating any other patient, the process and best practices aren’t terribly different from usual standard of care: Ensuring all necessary equipment is readily available with backup plans should the airway be difficult,” said Megan Conroy, MD, assistant professor of clinical medicine at The Ohio State University.

“We’ve been streamlining the team that’s present in the room for intubations of COVID patients, but I’m always amazed at the team members that stand at the ready to lend additional assistance just from the other side of the door. So while fewer personnel may be exposed, I wouldn’t consider the team needed for intubation to actually be much smaller, we’re just functioning differently.

In my practice the decision of when to intubate, clinically, doesn’t vary too much from any other form of severe ARDS. We may tolerate higher FiO₂ requirements on heated high-flow nasal cannula if the patient exhibits acceptable work of breathing, but I wouldn’t advise allowing a patient to remain hypoxemic with oxygen needs unmet by noninvasive methods out of fear of intubation or ventilator management. In my opinion, this simply delays a necessary therapy and only makes for a higher risk intubation. Certainly, the decision to intubate is never based on only one single data point, but takes an expert assessment of the whole clinical picture.

I’d assert that it’s true in every disease that patients do better if it’s possible to avoid intubation – but I would argue that the ability to avoid intubation is determined primarily by the disease course and clinical scenario, and not by whether the physician wishes to avoid intubation or not. If I can safely manage a patient off of a ventilator, I will always do so, COVID or otherwise. I think in this phase of the pandemic, patients ‘do better without intubation’ because those who didn’t require intubation were inherently doing better!”

[email protected]

As approaches to airway management of patients with suspected or confirmed COVID-19 continue to evolve, practicing vigilant transmission-based infection control precautions remains essential.

This starts with observing droplet precautions to prevent exposure to droplets larger than 5 microns in size, Charles Griffis, PhD, CRNA, said at a Society for Critical Care Medicine virtual meeting: COVID-19: What’s Next. “These are particles exhaled from infected persons and which fall within around 6 feet and involve an exposure time of 15 or more minutes of contact,” said Dr. Griffis, of the department of anesthesiology at the University of Southern California, Los Angeles. “We will always observe standard precautions, which include hand hygiene, gloves, hair and eye cover, medical mask, and face shield. We will observe these at all times for all patients and layer our transmission-based precautions on top.”

During aerosol-producing procedures such as airway management maneuvers, tracheostomies, and bronchoscopies, very fine microscopic particles less than 5 microns in size are produced, which remain airborne for potentially many hours and travel long distances. “We will add an N95 mask or a powered air-purifying respirator (PAPR) device to filter out tiny particles in addition to our ever-present standard precautions,” he said. “Contact precautions are indicated for direct contact with patient saliva, blood, urine, and stool. In addition to standard precautions, we’re going to add an impermeable gown and we’ll continue with gloves, eye protection, and shoe covers. The message is to all of us. We have to observe all of the infection precautions that all of us have learned and trained in to avoid exposure.”

In terms of airway management for infected patients for elective procedures and surgery, recommendations based on current and previous coronavirus outbreaks suggest that all patients get polymerase chain reaction (PCR) tested within 24-48 hours of elective procedures or surgeries. If positive, they should be quarantined for 10-14 days and then, if asymptomatic, these patients may be retested or they can be regarded as negative. “Patients who are PCR positive with active infection and active symptoms receive only urgent or emergent care in most settings,” said Dr. Griffis, a member of the American Association of Nurse Anesthetists Infection Control Advisory Panel. “The care provided to our patients, whether they’re positive or not, is individualized per patient needs and institutional policy. Some folks have made the decision to treat all patients as infected and to use airborne precautions for all aerosol-producing procedures for all patients all the time.”

When a COVID-19 patient requires emergent or urgent airway management because of respiratory failure or some other surgical or procedural intervention necessitating airway management, preprocedural planning is key, he continued. This means establishing the steps in airway management scenarios for infected patients and rehearsing those steps in each ICU setting with key personnel such as nurses, respiratory therapists, and medical staff. “You want to make sure that the PPE is readily available and determine and limit the number of personnel that are going to enter the patient’s room or area for airway management,” Dr. Griffis said. “Have all the airway equipment and drugs immediately available. Perhaps you could organize them in a cart which is decontaminated after every use.”

He also recommends forming an intubation team for ICUs and perhaps even for ORs, where the most experienced clinicians perform airway management. “This helps to avoid unnecessary airway manipulation and minimizes personnel exposure and time to airway establishment,” he said.

Always attempt to house the infected patient in an airborne isolation, negative-pressure room, with a minimum of 12 exchanges per hour and which will take 35 minutes for 99.99% removal of airborne contaminants after airway management. “These numbers are important to remember for room turnover safety,” he said.

Patient factors to review during airway management include assessing the past medical history, inspecting the airway and considering the patient’s current physiological status as time permits. Previously in the pandemic, intubation was used earlier in the disease course, but now data suggest that patients do better without intubation if possible (Am J Trop Med Hyg. 2020;102[6]. doi: 10.4269/aitmh.20-0283). “This is because the pathophysiology of COVID-19 is such that the lung tissue is predisposed to iatrogenic barotrauma damage from positive-pressure ventilation,” Dr. Griffis said. “In addition, COVID patients appear to tolerate significant hypoxemia without distress in many cases. Therefore, many clinicians now hold off on intubation until the hypoxemic patient begins exhibiting signs and symptoms of respiratory distress.”

Options for delivering noninvasive airway support for COVID-19 patients include high-flow nasal cannula and noninvasive positive-pressure ventilation via CPAP or BiPAP. To mitigate the associated aerosol production, consider applying a surgical mask, helmet, or face mask over the airway device/patient’s face. “Another measure that has proven helpful in general respiratory support is to actually put the patient in a prone position to help redistribute ventilation throughout the lungs,” Dr. Griffis said (see Resp Care. 2015;60[11]:1660-87).

To prepare for the actual intubation procedure, gather two expert intubators who are going to be entering the patient’s room. The team should perform hand hygiene and don full PPE prior to entry. “It’s recommended that you consider wearing double gloves for the intubation,” he said. “Have the airway equipment easily accessible in a central location on a cart or in a kit, and use disposable, single-use equipment if possible. All of the usual intubation equipment to maintain a clear airway and give positive pressure ventilation should be arranged for easy access. A video laryngoscope should be used, if possible, for greater accuracy and reduced procedure time. Ready access to sedation and muscle relaxant drugs must be assured at all times.”

For the intubation procedure itself, Dr. Griffis recommends ensuring that an oxygen source, positive-pressure ventilation, and suction and resuscitation drugs and equipment are available per institutional protocol. Assign one person outside the room to coordinate supplies and assistance. “Preoxygenate the patient as permitted by clinical status,” he said. “A nonrebreathing oxygen mask can be used if sufficient spontaneous ventilation is present. Assess the airway, check and arrange equipment for easy access, and develop the safest airway management plan. Consider a rapid sequence induction and intubation as the first option.” Avoid positive-pressure ventilation or awake fiber optic intubation unless absolutely necessary, thus avoiding aerosol production. “Only ventilate the patient after the endotracheal tube cuff is inflated, to avoid aerosol release,” he said.

For intubation, administer airway procedural drugs and insert the laryngoscope – ideally a video laryngoscope if available. Intubate the trachea under direct vision, inflate the cuff, and remove outer gloves. Then attach the Ambu bag with a 99% filtration efficiency, heat-and-moisture exchange filter; and proceed to ventilate the patient, checking for chest rise, breath sounds, and CO₂ production. “Discard contaminated equipment in designated bins and secure the tube,” Dr. Griffis advised. “Attach the ventilator with an HMEF filter to protect the ventilator circuit and inner parts of the machine. Recheck your breath sounds, CO₂ production, and oxygen saturation, and adjust your vent settings as indicated.”

For post intubation, Dr. Griffis recommends securing contaminated discardable equipment in biohazard-labeled bins or bags, safely doffing your PPE, and retaining your N95 mask in the room. Remove your inner gloves, perform hand hygiene with soap and water if available, with alcohol-based hand rub if not, then don clean gloves. Exit the room, safely transporting any contaminated equipment that will be reused such as a cart or video laryngoscope to decontamination areas for processing. “Once clear of the room, order your chest x-ray to confirm your tube position per institutional protocol, understanding that radiology techs are all going to be following infection control procedures and wearing their PPE,” he said.

For extubation, Dr. Griffis recommends excusing all nonessential personnel from the patient room and assigning an assistant outside the room for necessary help. An experienced airway management expert should evaluate the patient wearing full PPE and be double-gloved. “If the extubation criteria are met, suction the pharynx and extubate,” he said. “Remove outer gloves and apply desired oxygen delivery equipment to the patient and assess respiratory status and vital signs for stability.” Next, discard all contaminated equipment in designated bins, doff contaminated PPE, and retain your N95 mask. Doff inner gloves, perform hand hygiene, and don clean gloves. “Exit the room, hand off contaminated equipment that is reusable, doff your gloves outside, do hand hygiene, then proceed to change your scrubs and complete your own personal hygiene measures,” he said.

Dr. Griffis reported having no financial disclosures.

“While the PPE used for intubation of a coronavirus patient is certainly more than the typical droplet precautions observed when intubating any other patient, the process and best practices aren’t terribly different from usual standard of care: Ensuring all necessary equipment is readily available with backup plans should the airway be difficult,” said Megan Conroy, MD, assistant professor of clinical medicine at The Ohio State University.

“We’ve been streamlining the team that’s present in the room for intubations of COVID patients, but I’m always amazed at the team members that stand at the ready to lend additional assistance just from the other side of the door. So while fewer personnel may be exposed, I wouldn’t consider the team needed for intubation to actually be much smaller, we’re just functioning differently.

In my practice the decision of when to intubate, clinically, doesn’t vary too much from any other form of severe ARDS. We may tolerate higher FiO₂ requirements on heated high-flow nasal cannula if the patient exhibits acceptable work of breathing, but I wouldn’t advise allowing a patient to remain hypoxemic with oxygen needs unmet by noninvasive methods out of fear of intubation or ventilator management. In my opinion, this simply delays a necessary therapy and only makes for a higher risk intubation. Certainly, the decision to intubate is never based on only one single data point, but takes an expert assessment of the whole clinical picture.

I’d assert that it’s true in every disease that patients do better if it’s possible to avoid intubation – but I would argue that the ability to avoid intubation is determined primarily by the disease course and clinical scenario, and not by whether the physician wishes to avoid intubation or not. If I can safely manage a patient off of a ventilator, I will always do so, COVID or otherwise. I think in this phase of the pandemic, patients ‘do better without intubation’ because those who didn’t require intubation were inherently doing better!”

[email protected]