Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

High-potency topical steroids such as clobetasol are commonly used as first-line treatment for psoriasis. A recent study (Sidgiddi S et al. Dermatol Ther (Heidelb). 2021 Aug 28) compared the efficacy and safety of clobetasol 0.05% vs. 0.025% cream.  Patients were randomized to receive either clobetasol 0.05% cream or one of two different formulations of clobetasol 0.025% cream twice a day for two weeks. PGA success rates (clear or almost clear skin) were higher with the 0.025% formulations (38.9% and 36.8%) than with the 0.05% cream (30.8%). Safety also appeared to be better or comparable with the 0.025% formulation as measured by the proportion of patients with an abnormal ACTH stimulation test (20.7% and 17.2% in the 0.025% group compared with 30.0% in the 0.05% group). Due to the small study size (88 subjects) these differences did not reach statistical significance, although they suggest that high efficacy and perhaps better safety (reduced hypothalamic–pituitary–adrenal axis suppression) can be achieved with lower concentration formulations of clobetasol cream.

The oral phosphodiesterase 4 inhibitor apremilast is FDA-approved to treat psoriasis and psoriatic arthritis and recent studies have shown that it is more effective than placebo in treating patients with mild-moderate psoriasis and scalp psoriasis. A recent prospective cohort study followed 45 adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more treated with apremilast 30 mg twice daily for 52 weeks (Muñoz-Santos C et al. J Dermatol. 2021 Aug 12). The primary endpoint, the percentage of patients with a Nail Assessment in Psoriasis and Psoriatic Arthritis-Patient Benefit Index of 2 or more at week 52, was achieved in 52% of patients. A median improvement of 53% in fingernail NAPSI score and a mean reduction in nail pain of 68% were observed at week 52.  These findings show that apremilast can be useful in improving the quality-of-life impairment caused by nail psoriasis.

Traditional systemic therapies such as methotrexate and acitretin are cost-effective options for many psoriasis patients. The association of psoriasis with other comorbid conditions, particularly cardiovascular disease, has raised awareness of the importance of considering how therapies impact not just skin disease but also the risk posed by these psoriasis-associated comorbidities. A large Taiwanese retrospective cohort study compared patients treated with methotrexate (13,777) or acitretin (6,020) and found that in comparison to those treated with acitretin, patients treated with methotrexate were at lower risk of experiencing adverse cardiovascular outcomes, including ischemic heart disease and stroke, (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.76-0.94) and had a lower risk of all-cause mortality (aHR, 0.75; 95% CI, 0.66-0.85).

Many disease and patient factors must be considered when choosing the right therapy for a patient. These studies provide valuable information to incorporate into this process and highlight the utility of topical and oral therapies for psoriasis.

High-potency topical steroids such as clobetasol are commonly used as first-line treatment for psoriasis. A recent study (Sidgiddi S et al. Dermatol Ther (Heidelb). 2021 Aug 28) compared the efficacy and safety of clobetasol 0.05% vs. 0.025% cream.  Patients were randomized to receive either clobetasol 0.05% cream or one of two different formulations of clobetasol 0.025% cream twice a day for two weeks. PGA success rates (clear or almost clear skin) were higher with the 0.025% formulations (38.9% and 36.8%) than with the 0.05% cream (30.8%). Safety also appeared to be better or comparable with the 0.025% formulation as measured by the proportion of patients with an abnormal ACTH stimulation test (20.7% and 17.2% in the 0.025% group compared with 30.0% in the 0.05% group). Due to the small study size (88 subjects) these differences did not reach statistical significance, although they suggest that high efficacy and perhaps better safety (reduced hypothalamic–pituitary–adrenal axis suppression) can be achieved with lower concentration formulations of clobetasol cream.

The oral phosphodiesterase 4 inhibitor apremilast is FDA-approved to treat psoriasis and psoriatic arthritis and recent studies have shown that it is more effective than placebo in treating patients with mild-moderate psoriasis and scalp psoriasis. A recent prospective cohort study followed 45 adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more treated with apremilast 30 mg twice daily for 52 weeks (Muñoz-Santos C et al. J Dermatol. 2021 Aug 12). The primary endpoint, the percentage of patients with a Nail Assessment in Psoriasis and Psoriatic Arthritis-Patient Benefit Index of 2 or more at week 52, was achieved in 52% of patients. A median improvement of 53% in fingernail NAPSI score and a mean reduction in nail pain of 68% were observed at week 52.  These findings show that apremilast can be useful in improving the quality-of-life impairment caused by nail psoriasis.

Traditional systemic therapies such as methotrexate and acitretin are cost-effective options for many psoriasis patients. The association of psoriasis with other comorbid conditions, particularly cardiovascular disease, has raised awareness of the importance of considering how therapies impact not just skin disease but also the risk posed by these psoriasis-associated comorbidities. A large Taiwanese retrospective cohort study compared patients treated with methotrexate (13,777) or acitretin (6,020) and found that in comparison to those treated with acitretin, patients treated with methotrexate were at lower risk of experiencing adverse cardiovascular outcomes, including ischemic heart disease and stroke, (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.76-0.94) and had a lower risk of all-cause mortality (aHR, 0.75; 95% CI, 0.66-0.85).

Many disease and patient factors must be considered when choosing the right therapy for a patient. These studies provide valuable information to incorporate into this process and highlight the utility of topical and oral therapies for psoriasis.

High-potency topical steroids such as clobetasol are commonly used as first-line treatment for psoriasis. A recent study (Sidgiddi S et al. Dermatol Ther (Heidelb). 2021 Aug 28) compared the efficacy and safety of clobetasol 0.05% vs. 0.025% cream.  Patients were randomized to receive either clobetasol 0.05% cream or one of two different formulations of clobetasol 0.025% cream twice a day for two weeks. PGA success rates (clear or almost clear skin) were higher with the 0.025% formulations (38.9% and 36.8%) than with the 0.05% cream (30.8%). Safety also appeared to be better or comparable with the 0.025% formulation as measured by the proportion of patients with an abnormal ACTH stimulation test (20.7% and 17.2% in the 0.025% group compared with 30.0% in the 0.05% group). Due to the small study size (88 subjects) these differences did not reach statistical significance, although they suggest that high efficacy and perhaps better safety (reduced hypothalamic–pituitary–adrenal axis suppression) can be achieved with lower concentration formulations of clobetasol cream.

The oral phosphodiesterase 4 inhibitor apremilast is FDA-approved to treat psoriasis and psoriatic arthritis and recent studies have shown that it is more effective than placebo in treating patients with mild-moderate psoriasis and scalp psoriasis. A recent prospective cohort study followed 45 adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more treated with apremilast 30 mg twice daily for 52 weeks (Muñoz-Santos C et al. J Dermatol. 2021 Aug 12). The primary endpoint, the percentage of patients with a Nail Assessment in Psoriasis and Psoriatic Arthritis-Patient Benefit Index of 2 or more at week 52, was achieved in 52% of patients. A median improvement of 53% in fingernail NAPSI score and a mean reduction in nail pain of 68% were observed at week 52.  These findings show that apremilast can be useful in improving the quality-of-life impairment caused by nail psoriasis.

Traditional systemic therapies such as methotrexate and acitretin are cost-effective options for many psoriasis patients. The association of psoriasis with other comorbid conditions, particularly cardiovascular disease, has raised awareness of the importance of considering how therapies impact not just skin disease but also the risk posed by these psoriasis-associated comorbidities. A large Taiwanese retrospective cohort study compared patients treated with methotrexate (13,777) or acitretin (6,020) and found that in comparison to those treated with acitretin, patients treated with methotrexate were at lower risk of experiencing adverse cardiovascular outcomes, including ischemic heart disease and stroke, (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.76-0.94) and had a lower risk of all-cause mortality (aHR, 0.75; 95% CI, 0.66-0.85).

Many disease and patient factors must be considered when choosing the right therapy for a patient. These studies provide valuable information to incorporate into this process and highlight the utility of topical and oral therapies for psoriasis.

This month a couple of studies evaluated the role of enasidenib and gemtuzumab in the therapy of patients with AML using clinical and non-clinical trial data. In a propensity score-matching (PSM) analysis, was enasidenib associated with better outcomes compared to standard of care (SoC). The study included adult patients with relapsed/refractory (R/R) AML with an isocitrate dehydrogenase 2 (IDH2) mutation ineligible for hematopoietic stem cell transplantation (HSCT) treated with enasidenib (n = 195) from the AG221 C-001 trial or SoC therapies (n = 78) from the French Chart Review study. The SoC regimens included azacytidine, decitabine, cytarabine containing regimens, and others. Enasidenib was associated with superior overall survival (OS) (hazard ratio [HR] 0.67; 95% CI 0.47-0.97) compared to SoC therapies in patients with R/R AML with IDH2 mutation who were ineligible for HSCT. The median OS was 9.26 months vs. 4.76 months for enasidenib and SoC respectively. The results of this study are not surprising given the data seen in clinical trials. Although not evaluated in this study, the quality of life for patients receiving enasidenib is better when compared to SoC regimens, such as 7 +3 (cytarabine + idarubicin). Other than the limitations of a PSM study, which are well acknowledged by the authors, the main weakness is this study did not include venetoclax in the SoC regimen. It remains unclear whether using venetoclax in the R/R setting in patients with IDH2 mutations would lead to similar outcomes.

The benefit of gemtuzumab ozogamicin (GO) was demonstrated again in a metanalysis that included 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk myelodysplastic syndrome (MDS) (n = 129). GO showed superior survival outcomes in patients with AML or high-risk MDS than non-GO therapy, but higher doses increased the risk for early death. GO vs. non-GO arm showed improved overall survival (HR 0.86; P = .003), event-free survival (HR 0.86; P = .015), and relapse-free survival (HR 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of ≥6 mg/m² (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018). Finally, a study by the Polish adult leukemia group demonstrated the safety and efficacy of a low dose cytarabine + cladribine regimen. Treatment consisted of 5 mg/m² cladribine intravenously on day 1-5 (in the first cycle) and on days 1 to 3 (in the second cycle) combined with low dose cytarabine (40 mg) subcutaneously once daily on days 1–10. Patients may continue on low dose cytarabine after that if they have achieved at least a partial remission. Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (HR 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

In addition to the better therapies in the last decade, allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes have also improved. In a retrospective analysis from the Japanese nationwide transplantation registry the outcomes of patients transplanted with unrelated cord blood (UCB) and Haplo transplant between 2007 to 2014 were worse when compared to patients who had a transplant between 2015 and 2018. For patients who had transplants between 2015 and 2018, the 3-year overall survival of mismatched unrelated donor (MMUD), unrelated cord blood (UCB), and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-vs. host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups. For patients with transplant between 2007 to 2014 the 3 year overall survival was 60%, 54%, and 47% for MMUD, UCB, and Haplo transplants respectively. Newer, better drugs, better tolerated regimens, and improved transplant outcomes were the result: many small gains lead to large improvements.

This month a couple of studies evaluated the role of enasidenib and gemtuzumab in the therapy of patients with AML using clinical and non-clinical trial data. In a propensity score-matching (PSM) analysis, was enasidenib associated with better outcomes compared to standard of care (SoC). The study included adult patients with relapsed/refractory (R/R) AML with an isocitrate dehydrogenase 2 (IDH2) mutation ineligible for hematopoietic stem cell transplantation (HSCT) treated with enasidenib (n = 195) from the AG221 C-001 trial or SoC therapies (n = 78) from the French Chart Review study. The SoC regimens included azacytidine, decitabine, cytarabine containing regimens, and others. Enasidenib was associated with superior overall survival (OS) (hazard ratio [HR] 0.67; 95% CI 0.47-0.97) compared to SoC therapies in patients with R/R AML with IDH2 mutation who were ineligible for HSCT. The median OS was 9.26 months vs. 4.76 months for enasidenib and SoC respectively. The results of this study are not surprising given the data seen in clinical trials. Although not evaluated in this study, the quality of life for patients receiving enasidenib is better when compared to SoC regimens, such as 7 +3 (cytarabine + idarubicin). Other than the limitations of a PSM study, which are well acknowledged by the authors, the main weakness is this study did not include venetoclax in the SoC regimen. It remains unclear whether using venetoclax in the R/R setting in patients with IDH2 mutations would lead to similar outcomes.

The benefit of gemtuzumab ozogamicin (GO) was demonstrated again in a metanalysis that included 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk myelodysplastic syndrome (MDS) (n = 129). GO showed superior survival outcomes in patients with AML or high-risk MDS than non-GO therapy, but higher doses increased the risk for early death. GO vs. non-GO arm showed improved overall survival (HR 0.86; P = .003), event-free survival (HR 0.86; P = .015), and relapse-free survival (HR 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of ≥6 mg/m² (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018). Finally, a study by the Polish adult leukemia group demonstrated the safety and efficacy of a low dose cytarabine + cladribine regimen. Treatment consisted of 5 mg/m² cladribine intravenously on day 1-5 (in the first cycle) and on days 1 to 3 (in the second cycle) combined with low dose cytarabine (40 mg) subcutaneously once daily on days 1–10. Patients may continue on low dose cytarabine after that if they have achieved at least a partial remission. Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (HR 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

In addition to the better therapies in the last decade, allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes have also improved. In a retrospective analysis from the Japanese nationwide transplantation registry the outcomes of patients transplanted with unrelated cord blood (UCB) and Haplo transplant between 2007 to 2014 were worse when compared to patients who had a transplant between 2015 and 2018. For patients who had transplants between 2015 and 2018, the 3-year overall survival of mismatched unrelated donor (MMUD), unrelated cord blood (UCB), and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-vs. host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups. For patients with transplant between 2007 to 2014 the 3 year overall survival was 60%, 54%, and 47% for MMUD, UCB, and Haplo transplants respectively. Newer, better drugs, better tolerated regimens, and improved transplant outcomes were the result: many small gains lead to large improvements.

This month a couple of studies evaluated the role of enasidenib and gemtuzumab in the therapy of patients with AML using clinical and non-clinical trial data. In a propensity score-matching (PSM) analysis, was enasidenib associated with better outcomes compared to standard of care (SoC). The study included adult patients with relapsed/refractory (R/R) AML with an isocitrate dehydrogenase 2 (IDH2) mutation ineligible for hematopoietic stem cell transplantation (HSCT) treated with enasidenib (n = 195) from the AG221 C-001 trial or SoC therapies (n = 78) from the French Chart Review study. The SoC regimens included azacytidine, decitabine, cytarabine containing regimens, and others. Enasidenib was associated with superior overall survival (OS) (hazard ratio [HR] 0.67; 95% CI 0.47-0.97) compared to SoC therapies in patients with R/R AML with IDH2 mutation who were ineligible for HSCT. The median OS was 9.26 months vs. 4.76 months for enasidenib and SoC respectively. The results of this study are not surprising given the data seen in clinical trials. Although not evaluated in this study, the quality of life for patients receiving enasidenib is better when compared to SoC regimens, such as 7 +3 (cytarabine + idarubicin). Other than the limitations of a PSM study, which are well acknowledged by the authors, the main weakness is this study did not include venetoclax in the SoC regimen. It remains unclear whether using venetoclax in the R/R setting in patients with IDH2 mutations would lead to similar outcomes.

The benefit of gemtuzumab ozogamicin (GO) was demonstrated again in a metanalysis that included 15 randomized controlled trials and 15 retrospective studies that compared GO (n = 4,768) with non-GO (n = 6,466) therapies in 11,234 patients with AML (n = 11,105) and high-risk myelodysplastic syndrome (MDS) (n = 129). GO showed superior survival outcomes in patients with AML or high-risk MDS than non-GO therapy, but higher doses increased the risk for early death. GO vs. non-GO arm showed improved overall survival (HR 0.86; P = .003), event-free survival (HR 0.86; P = .015), and relapse-free survival (HR 0.83; P = .001). However, GO vs. non-GO was associated with an increased risk for early death at a dose of ≥6 mg/m² (relative risk [RR] 2.01; P = .005), hepatic-related adverse effects (RR 1.29; P = .02), and bleeding (RR 1.13; P = .018). Finally, a study by the Polish adult leukemia group demonstrated the safety and efficacy of a low dose cytarabine + cladribine regimen. Treatment consisted of 5 mg/m² cladribine intravenously on day 1-5 (in the first cycle) and on days 1 to 3 (in the second cycle) combined with low dose cytarabine (40 mg) subcutaneously once daily on days 1–10. Patients may continue on low dose cytarabine after that if they have achieved at least a partial remission. Rates of overall response and 56-day mortality were 54.0% and 20.5%, respectively. The median overall survival was 6.9 months (95% CI 4.9-9.6) and superior in patients who achieved an objective response (HR 0.04; P < .0001) or partial remission (HR 0.31; P = .0002) compared to nonresponders.

In addition to the better therapies in the last decade, allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes have also improved. In a retrospective analysis from the Japanese nationwide transplantation registry the outcomes of patients transplanted with unrelated cord blood (UCB) and Haplo transplant between 2007 to 2014 were worse when compared to patients who had a transplant between 2015 and 2018. For patients who had transplants between 2015 and 2018, the 3-year overall survival of mismatched unrelated donor (MMUD), unrelated cord blood (UCB), and Haplo groups were 60%, 66%, and 63%, respectively (P = .693). The rates of nonrelapse mortality (P = .147), relapse (P = .075), and graft-vs. host disease-free/relapse-free survival (P = .365) were also similar between the 3 groups. For patients with transplant between 2007 to 2014 the 3 year overall survival was 60%, 54%, and 47% for MMUD, UCB, and Haplo transplants respectively. Newer, better drugs, better tolerated regimens, and improved transplant outcomes were the result: many small gains lead to large improvements.

Q2. Correct answer: A.  
 
Rationale  
Tropical sprue occurs in patients from or travelers to endemic areas near the equator, such as Puerto Rico, Haiti, Cuba, Southeast Asia, and India for at least 2 weeks to a month and has a likely infectious etiology, but the exact organism(s) has not been identified. Patients may present with malabsorption, steatorrhea, weight loss, and fatigue. Laboratory testing shows anemia, B12 and folate deficiency, and increased fecal fat. Biopsies of the small bowel during upper endoscopy show villous blunting with negative celiac serologies. Treatment is a 3- to 6-month course of tetracycline 250 mg orally four times daily with folate 5 mg orally daily. The macrocytic anemia, normal iron studies, and low vitamin B12 and folate levels argue against celiac disease, so this patient is unlikely to respond to a gluten-free diet.  
 
References  
Ghoshal UC et. al. Curr Gastroenterol Rep. 2014;16(6):391.  
Batheja MJ et. al. Case Rep Gastroenterol. 2010 May 19;4(2):168-172.  
Jansson-Knodell CL et al. Mayo Clin Proc. 2018 Apr;93(4):509-517.

Q2. Correct answer: A.  
 
Rationale  
Tropical sprue occurs in patients from or travelers to endemic areas near the equator, such as Puerto Rico, Haiti, Cuba, Southeast Asia, and India for at least 2 weeks to a month and has a likely infectious etiology, but the exact organism(s) has not been identified. Patients may present with malabsorption, steatorrhea, weight loss, and fatigue. Laboratory testing shows anemia, B12 and folate deficiency, and increased fecal fat. Biopsies of the small bowel during upper endoscopy show villous blunting with negative celiac serologies. Treatment is a 3- to 6-month course of tetracycline 250 mg orally four times daily with folate 5 mg orally daily. The macrocytic anemia, normal iron studies, and low vitamin B12 and folate levels argue against celiac disease, so this patient is unlikely to respond to a gluten-free diet.  
 
References  
Ghoshal UC et. al. Curr Gastroenterol Rep. 2014;16(6):391.  
Batheja MJ et. al. Case Rep Gastroenterol. 2010 May 19;4(2):168-172.  
Jansson-Knodell CL et al. Mayo Clin Proc. 2018 Apr;93(4):509-517.

Q2. Correct answer: A.  
 
Rationale  
Tropical sprue occurs in patients from or travelers to endemic areas near the equator, such as Puerto Rico, Haiti, Cuba, Southeast Asia, and India for at least 2 weeks to a month and has a likely infectious etiology, but the exact organism(s) has not been identified. Patients may present with malabsorption, steatorrhea, weight loss, and fatigue. Laboratory testing shows anemia, B12 and folate deficiency, and increased fecal fat. Biopsies of the small bowel during upper endoscopy show villous blunting with negative celiac serologies. Treatment is a 3- to 6-month course of tetracycline 250 mg orally four times daily with folate 5 mg orally daily. The macrocytic anemia, normal iron studies, and low vitamin B12 and folate levels argue against celiac disease, so this patient is unlikely to respond to a gluten-free diet.  
 
References  
Ghoshal UC et. al. Curr Gastroenterol Rep. 2014;16(6):391.  
Batheja MJ et. al. Case Rep Gastroenterol. 2010 May 19;4(2):168-172.  
Jansson-Knodell CL et al. Mayo Clin Proc. 2018 Apr;93(4):509-517.

Correct answer: A. 
 
Rationale  
This patient has scromboid poisoning, which occurs when histidine is converted to histamine by bacterial enzymes in improperly refrigerated fish. Most cases in the United States are reported in Hawaii, Florida, and California and involve consumption of affected tuna, mackerel, mahi-mahi, sardines, herring, and other fish. Onset of symptoms occurs about 1 hour after eating the suspect fish; the patient may experience hot flashes, facial flushing, hives, upper body rash, perioral paresthesias or edema, palpitations, lightheadedness, nausea, vomiting, and abdominal pain. Symptoms typically resolve within 1 day, though some patients may experience a longer course. Supportive care and either oral or intravenous administration of antihistamines may be used to improve symptoms. Evaluation of airway patency is also important. Scromboid poisoning may be prevented by immediate refrigeration of fresh fish to below 40°C.  
Although ACE inhibitor induced angioedema may cause facial swelling, the time course of the disease and associated risk factors favor scromboid poisoning. Ingestion of Bacillus cereus or Staphylococcus aureus would not be expected to cause flushing, tachycardia, and upper body rash. Ciguatera poisoning has a less immediate onset of symptoms, is associated with neurologic symptoms, and has a more protracted course. This patient is not likely to have an allergy to seafood.  
 
Reference  
Hungerford JM. Toxicon. 2010 Aug 15;56(2):231-43.

Correct answer: A. 
 
Rationale  
This patient has scromboid poisoning, which occurs when histidine is converted to histamine by bacterial enzymes in improperly refrigerated fish. Most cases in the United States are reported in Hawaii, Florida, and California and involve consumption of affected tuna, mackerel, mahi-mahi, sardines, herring, and other fish. Onset of symptoms occurs about 1 hour after eating the suspect fish; the patient may experience hot flashes, facial flushing, hives, upper body rash, perioral paresthesias or edema, palpitations, lightheadedness, nausea, vomiting, and abdominal pain. Symptoms typically resolve within 1 day, though some patients may experience a longer course. Supportive care and either oral or intravenous administration of antihistamines may be used to improve symptoms. Evaluation of airway patency is also important. Scromboid poisoning may be prevented by immediate refrigeration of fresh fish to below 40°C.  
Although ACE inhibitor induced angioedema may cause facial swelling, the time course of the disease and associated risk factors favor scromboid poisoning. Ingestion of Bacillus cereus or Staphylococcus aureus would not be expected to cause flushing, tachycardia, and upper body rash. Ciguatera poisoning has a less immediate onset of symptoms, is associated with neurologic symptoms, and has a more protracted course. This patient is not likely to have an allergy to seafood.  
 
Reference  
Hungerford JM. Toxicon. 2010 Aug 15;56(2):231-43.

Correct answer: A. 
 
Rationale  
This patient has scromboid poisoning, which occurs when histidine is converted to histamine by bacterial enzymes in improperly refrigerated fish. Most cases in the United States are reported in Hawaii, Florida, and California and involve consumption of affected tuna, mackerel, mahi-mahi, sardines, herring, and other fish. Onset of symptoms occurs about 1 hour after eating the suspect fish; the patient may experience hot flashes, facial flushing, hives, upper body rash, perioral paresthesias or edema, palpitations, lightheadedness, nausea, vomiting, and abdominal pain. Symptoms typically resolve within 1 day, though some patients may experience a longer course. Supportive care and either oral or intravenous administration of antihistamines may be used to improve symptoms. Evaluation of airway patency is also important. Scromboid poisoning may be prevented by immediate refrigeration of fresh fish to below 40°C.  
Although ACE inhibitor induced angioedema may cause facial swelling, the time course of the disease and associated risk factors favor scromboid poisoning. Ingestion of Bacillus cereus or Staphylococcus aureus would not be expected to cause flushing, tachycardia, and upper body rash. Ciguatera poisoning has a less immediate onset of symptoms, is associated with neurologic symptoms, and has a more protracted course. This patient is not likely to have an allergy to seafood.  
 
Reference  
Hungerford JM. Toxicon. 2010 Aug 15;56(2):231-43.

Deucravacitinib, a novel inhibitor of tyrosine kinase 2 (TYK2), continues to demonstrate strong efficacy and acceptable safety after 52 weeks of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).

“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.

The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.

For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).

By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.

By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.

The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.

When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.

On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.

Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.

“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.

In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.

Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.

In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.

The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.

“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.

Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.

“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.

“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.

The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.

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

Deucravacitinib, a novel inhibitor of tyrosine kinase 2 (TYK2), continues to demonstrate strong efficacy and acceptable safety after 52 weeks of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).

“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.

The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.

For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).

By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.

By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.

The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.

When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.

On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.

Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.

“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.

In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.

Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.

In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.

The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.

“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.

Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.

“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.

“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.

The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.

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

Deucravacitinib, a novel inhibitor of tyrosine kinase 2 (TYK2), continues to demonstrate strong efficacy and acceptable safety after 52 weeks of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).

“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.

The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.

For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).

By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.

By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.

The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.

When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.

On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.

Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.

“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.

In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.

Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.

In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.

The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.

“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.

Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.

“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.

“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.

The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.

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

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

Introduction

There have been incident reports of cardiac-related adverse events (CrAE) from immune checkpoint inhibitors (ICPI); however, the true incidence and subsequent management of these potential side effects have not been defined. It is therefore important to study ICPI related cardiac dysfunction to assist in monitoring and surveillance of these patients.

Methods

63 patients who received nivolumab and pembrolizumab at Stratton VAMC Albany between January 2015 to December 2018 were studied. Retrospective chart review was done to identify the CrAE up to two-year post-therapy completion or discontinuation. Naranjo score was used to assess drug-related side effect. IRB approval was obtained.

Results 

CrAE were defined as new onset arrythmia identified on electrocardiogram, evidence of cardiomyopathy on echocardiogram, an acute coronary event, and hospitalizations from primary cardiac disorder following ICPI administration. Of the 63 patients, 6 patients developed CrAE. Our review showed 3 patients developed new arrythmias including 1 with atrial fibrillation, and 2 with atrial flutter. There was 1 case each of new heart failure with reduced ejection fraction and pericarditis with pericardial tamponade. 1 patient developed acute coronary syndrome in addition to complete heart block. Of the 6 patients, 2 had elevated brain natriuretic peptide (BNP) prior to onset of CrAE. Elevated markers including BNP and troponin-I were also seen in 13 patients with preexisting heart conditions without CrAE. Duration of therapy was variable for all patients with CrAE. Therapy was continued for 3 patients without recurrence of CrAE. Therapy was permanently discontinued in the patient who developed pericardial effusion (grade IV toxicity). The remaining 2 patients had additional concurrent immune-related toxicities that required discontinuation of therapy. Our analysis showed 25/63 patients with pre-existing cardiac conditions (including arrhythmia, heart failure or coronary artery disease) who did not develop new CrAE; however 6 of these patients required hospitalization for exacerbation related to these pre-existing conditions.

Conclusions

CrAE can occur with ICPIs, and vigilance is required in high-risk patient including those with pre-existing cardiac comorbidity. Further studies are required to establish if baseline screening EKG and echocardiogram should be obtained for all patients starting ICPI.

On April 1, Houston Methodist Hospital in Houston, Texas, announced a new policy that all of its staff would need to be vaccinated against COVID-19 by June 7 in order to hold onto their jobs. Most responded positively but an estimated 150 staff members who did not comply either resigned or were terminated. A lawsuit by employees opposed to the vaccine mandate was dismissed by Federal District Court Judge Lynn Hughes in June, although a subsequent lawsuit was filed Aug. 16.

Vaccines have been shown to dramatically reduce both the incidence and the severity of COVID infections. Vaccinations of health care workers, especially those who have direct contact with patients, are demonstrated to be effective strategies to significantly reduce, although not eliminate, the possibility of viral transmissions to patients – or to health care workers themselves – thus saving lives.

Hospitalists, in their central role in the care of hospitalized patients, and often with primary responsibility for managing their hospital’s COVID-19 caseloads, may find themselves encountering conversations about the vaccine, its safety, effectiveness, and mandates with their peers, other hospital staff, patients, and families, and their communities. They can play key roles in advocating for the vaccine, answering questions, clarifying the science, and dispelling misinformation – for those who are willing to listen.

Becker’s Hospital Review, which has kept an ongoing tally of announced vaccine mandate policies in hospitals, health systems, and health departments nationwide, reported on Aug. 13 that 1,850 or 30% of U.S. hospitals, had announced vaccine mandates.¹ Often exceptions can be made, such as for medical or religious reasons, or with other declarations or opt-out provisions. But in many settings, mandating COVID vaccinations won’t be easy.

Amith Skandhan, MD, SFHM, FACP, a hospitalist at Southeast Health Medical Center in Dothan, Ala., and a core faculty member in the internal medicine residency program at Alabama College of Osteopathic Medicine, said that implementing vaccine mandates will be more difficult in smaller health systems, in rural communities, and in states with lower vaccination rates and greater vaccine controversy.

Alabama has the lowest vaccination rates in the country, reflected in the recent rise in COVID cases and hospitalizations, even higher than during the surge of late 2020, Dr. Skandhan said. “In June we had one COVID patient in this hospital.” By late August the number was 119 COVID patients and climbing.

But where he works, in a health system where staffing is already spread thin, a vaccine mandate would be challenging. “What if our staff started leaving? It’s only 10 minutes from here to the Florida or Georgia border,” Dr. Skandhan said. Health care workers opposed to vaccinations would have the option of easily seeking work elsewhere.

When contacted for this article, he had been off work for several days but was mentally preparing himself to go back. “I’m not even following the [COVID-19] numbers but I am prepared for the worst. I know it will be mostly COVID. People just don’t realize what goes into this work.”

Dr. Skandhan, who said he was the third or fourth person in Alabama to receive the COVID vaccine, often finds himself feeling frustrated and angry – in the midst of a surge in cases that could have been prevented – that such a beneficial medical advance for bringing the pandemic under control became so politicized. “It is imperative that we find out why this mistrust exists and work to address it. It has to be done.”

Protecting health care professionals

On July 26, the Society of Hospital Medicine joined 50 other health care organizations including the American Medical Association, American Nurses Association, and American Academy of Pediatrics in advocating for all health care employers to require their employees to be vaccinated against COVID, in order to protect the safety of all patients and residents of health care facilities.²

“As an organization, we support vaccinating health care workers, including hospitalists, to help stop the spread of COVID-19 and the increasingly dominant Delta variant,” said SHM’s chief executive officer Eric E. Howell, MD, MHM, in a prepared statement. “We aim to uphold the highest standards among hospitalists and other health care providers to help protect our fellow health care professionals, our patients, and our communities.”

To that end, Dr. Skandhan has started conversations with hospital staff who he knows are not vaccinated. “For some, we’re not able to have a civil conversation, but in most cases I can help to persuade people.” The reasons people give for not getting vaccinated are not based in science, he said. “I am worried about the safety of our hospitalists and staff nurses.” But unvaccinated frontline workers are also putting their patients at risk. “Can we say why they’re hesitating? Can we have an honest discourse? If we can’t do that with our colleagues, how can we blame the patients?”

Dr. Skandhan encourages hospitalists to start simply in their own hospitals, trying to influence their own departments and colleagues. “If you can convince one or two more every week, you can start a chain reaction. Have that conversation. Use your trust.” For some hospitalized patients, the vaccination conversation comes too late, after their infection, but even some of them might consider obtaining it down the road or trying to persuade family members to get vaccinated.

Adult hospitalists, however, may not have received training in how to effectively address vaccine fears and misconceptions among their patients, he said. Because the patients they see in the hospital are already very sick, they don’t get a lot of practice talking about vaccines except, perhaps, for the influenza vaccine.

Pediatric hospitalists have more experience with such conversations involving their patients’ parents, Dr. Skandhan said. “It comes more naturally to them. We need to learn quickly from them about how to talk about vaccines with our patients.”

Pediatric training and experience

Anika Kumar, MD, FHM, FAAP, a pediatric hospitalist at the Cleveland Clinic and the pediatric editor of The Hospitalist, agrees that pediatricians and pediatric hospitalists often have received more training in how to lead vaccination conversations. She often talks about vaccines with the parents of hospitalized children relative to chicken pox, measles, and other diseases of childhood.

Pediatric hospitalists may also ask to administer the hepatitis B vaccine to newborn babies, along with other preventive treatments such as eye drops and vitamin K shots. “I often encourage the influenza vaccine prior to the patient’s hospital discharge, especially for kids with chronic conditions, asthma, diabetes, or premature birth. We talk about how the influenza vaccine isn’t perfect, but it helps to prevent more serious disease,” she said.

“A lot of vaccine hesitancy comes from misunderstandings about the role of vaccines,” she said. People forget that for years children have been getting vaccines before starting school. “Misinformation and opinions about vaccines have existed for decades. What’s new today is the abundance of sources for obtaining these opinions. My job is to inform families of scientific facts and to address their concerns.”

It has become more common recently for parents to say they don’t want their kids to get vaccinated, Dr. Kumar said. Another group is better described as vaccine hesitant and just needs more information. “I may not, by the time they leave the hospital, convince them to allow me to administer the vaccine. But in the discharge summary, I document that I had this conversation. I’ve done my due diligence and tried to start a larger dialogue. I say: ‘I encourage you to continue this discussion with the pediatrician you trust.’ I also communicate with the outpatient team,” she said.

“But it’s our responsibility, because we’re the ones seeing these patients, to do whatever we can to keep our patients from getting sick. A lot of challenging conversations we have with families are just trying to find out where they’re at with the issue – which can lead to productive dialogue.”

Ariel Carpenter, MD, a 4th-year resident in internal medicine and pediatrics at the University of Louisville (Ky.), and a future pediatric hospitalist, agreed that her combined training in med-peds has been helpful preparation for the vaccine conversation. That training has included techniques of motivational interviewing. In pediatrics, she explained, the communication is a little softer. “I try to approach my patients in a family-centered way.”

Dr. Carpenter recently wrote a personal essay for Louisville Medicine magazine from the perspective of growing up homeschooled by a mother who didn’t believe in vaccines.³ As a teenager, she independently obtained the complete childhood vaccine series so that she could do medical shadowing and volunteering. In medical school she became a passionate vaccine advocate, eventually persuading her mother to change her mind on the subject in time for the COVID vaccine.

“There’s not one answer to the vaccination dilemma,” she said. “Different approaches are required because there are so many different reasons for it. Based on my own life experience, I try to approach patients where they are – not from a place of data and science. What worked in my own family, and works with my patients, is first to establish trust. If they trust you, they’re more likely to listen. Simply ask their worries and concerns,” Dr. Carpenter said.

“A lot of them haven’t had the opportunity before to sit down with a physician they trust and have their worries listened to. They don’t feel heard in our medical system. So I remind myself that I need to understand my patients first – before inserting myself into the conversation.”

Many patients she sees are in an information bubble, with a very different understanding of the issue than their doctors. “A lot of well-meaning people feel they are making the safer choice. Very few truly don’t care about protecting others. But they don’t feel the urgency about that and see the vaccine as the scarier option right now.”

Frontline vaccine advocates

Hospitalists are the frontline advocates within their hospital system, in a position to lead, so they need to make vaccines a priority, Dr. Carpenter said. They should also make sure that their hospitals have ready access to the vaccine, so patients who agree to receive it are able to get it quickly. “In our hospital they can get the shot within a few hours if the opportunity arises. We stocked the Johnson & Johnson vaccine so that they wouldn’t have to connect with another health care provider in order to get a second dose.”

Hospitals should also invest in access to vaccine counseling training and personnel. “Fund a nurse clinician who can screen and counsel hospitalized patients for vaccination. If they meet resistance, they can then refer to the dedicated physician of the day to have the conversation,” she said. “But if we don’t mention it, patients will assume we don’t feel strongly about it.”

Because hospitalists are front and center in treating COVID, they need to be the experts and the people offering guidance, said Shyam Odeti, MD, SFHM, FAAFP, section chief for hospital medicine at the Carilion Clinic in Roanoke, Va. “What we’re trying to do is spread awareness. We educated physician groups, learners, and clinical teams during the initial phase, and now mostly patients and their families.” COVID vaccine reluctance is hard to overcome, Dr. Odeti said. People feel the vaccine was developed very quickly. But there are different ways to present it.

“Like most doctors, I thought people would jump on a vaccine to get past the pandemic. I was surprised and then disappointed. Right now, the pandemic is among the unvaccinated. So we face these encounters, and we’re doing our best to overcome the misinformation. My organization is 100% supportive. We talk about these issues every day.”

Carilion, effective Oct. 1, has required unvaccinated employees to get weekly COVID tests and wear an N95 mask while working, and has developed Facebook pages, other social media, and an Internet presence to address these issues. “We’ve gone to the local African-American community with physician leaders active in that community. We had a Spanish language roundtable,” Dr. Odeti said.

Dr. Skandhan reported that the Wiregrass regional chapter of SHM recently organized a successful statewide community educational event aimed at empowering community leaders to address vaccine misinformation and mistrust. “We surveyed religious leaders and pastors regarding the causes of vaccine hesitancy and reached out to physicians active in community awareness.” Based on that input, a presentation by the faith leaders was developed. Legislators from the Alabama State Senate’s Healthcare Policy Committee were also invited to the presentation and discussion.
 

Trying to stay positive

It’s important to try to stay positive, Dr. Odeti said. “We have to be empathetic with every patient. We have to keep working at this, since there’s no way out of the pandemic except through vaccinations. But it all creates stress for hospitalists. Our job is made significantly more difficult by the vaccine controversy.”

Jennifer Cowart, MD, a hospitalist at Mayo Clinic in Jacksonville, Fla., has been outspoken in her community about vaccination and masking issues, talking to reporters, attending rallies and press conferences, posting on social media, and speaking in favor of mask policies at a local school board meeting. She is part of an informal local group called Doctors Fighting COVID, which meets online to strategize how to share its expertise, including writing a recent letter about masks to Jacksonville’s mayor.

“In July, when we saw the Delta variant surging locally, we held a webinar via local media, taking calls about the vaccine from the community. I’m trying not to make this a political issue, but we are health officials.” Dr. Cowart said she also tries not to raise her voice when speaking with vaccine opponents and tries to remain empathetic. “Even though inwardly I’m screaming, I try to stay calm. The misinformation is real. People are afraid and feeling pressure. I do my best, but I’m human, too.”

Hospitalists need to pull whatever levers they can to help advance understanding of vaccines, Dr. Cowart said. “In the hospital, our biggest issue is time. We often don’t have it, with a long list of patients to see. But every patient encounter is an opportunity to talk to patients, whether they have COVID or something else.” Sometimes, she might go back to a patient’s room after rounds to resume the conversation.

Hospital nurses have been trained and entrusted to do tobacco abatement counseling, she said, so why not mobilize them for vaccine education? “Or respiratory therapists, who do inhaler training, could talk about what it’s like to care for COVID patients. There’s a whole bunch of staff in the hospital who could be mobilized,” she said.

“I feel passionate about vaccines, as a hospitalist, as a medical educator, as a daughter, as a responsible member of society,” said Eileen Barrett, MD, MPH, SFHM, MACP, director of continuing medical education at the University of New Mexico, Albuquerque. “I see this as a personal and societal responsibility. When I speak about the vaccine among groups of doctors, I say we need to stay in our lane regarding our skills at interpreting the science and not undermining it.”

Some health care worker hesitancy is from distrust of pharmaceutical companies, or of federal agencies, she said. “Our research has highlighted to me the widespread inequity issues in our health care system. We should also take a long, hard look at how we teach the scientific method to health professionals. That will be part of a pandemic retrospective.”

Sometimes with people who are vaccine deliberative, whether health care workers or patients, there is a small window of opportunity. “We need to hear people and respond to them as people. Then, if they are willing to get vaccinated, we need to accomplish that as quickly and easily as possible,” Dr. Barrett said. “I see them make a face and say, ‘Well, okay, I’ll do it.’ We need to get the vaccine to them that same day. We should be able to accomplish that.”
 

References

1. Gamble M. 30% of US hospitals mandate vaccination for employment. Becker’s Hospital Review. 2021 Aug 13. www.beckershospitalreview.com/workforce/covid-19-vaccination-needed-to-work-at-30-of-us-hospitals.html .

2. Society of Hospital Medicine signs on to joint statement in support of health worker COVID-19 vaccine mandates. Press release. 2021 Jul 26. www.hospitalmedicine.org/news-publications/press-releases/society-of-hospital-medicine-signs-on-to-joint-statement-of-support-of-health-worker-covid-19-vaccine-mandates/.

3. Carpenter A. A physician’s lessons from an unvaccinated childhood. Louisville Medicine. 2021 July;69(2):26-7. https://viewer.joomag.com/louisville-medicine-volume-69-issue-2/0045988001624974172?short&.

Lessons for hospitalists from the vaccination controversy

1. Remain up-to-date on information about the COVID infection, its treatment, and vaccination efficacy data.

2. Hospitalists should take advantage of their positions to lead conversations in their facilities about the importance of COVID vaccinations.

3. Other professionals in the hospital, with some additional training and support, could take on the role of providing vaccine education and support – with a physician to back them up on difficult cases.

4. It’s important to listen to people’s concerns, try to build trust, and establish dialogue before starting to convey a lot of information. People need to feel heard.

5. If you are successful in persuading someone to take the vaccine, a shot should be promptly and easily accessible to them.

6. Pediatric hospitalists may have more experience and skill with vaccine discussions, which they should share with their peers who treat adults.

On April 1, Houston Methodist Hospital in Houston, Texas, announced a new policy that all of its staff would need to be vaccinated against COVID-19 by June 7 in order to hold onto their jobs. Most responded positively but an estimated 150 staff members who did not comply either resigned or were terminated. A lawsuit by employees opposed to the vaccine mandate was dismissed by Federal District Court Judge Lynn Hughes in June, although a subsequent lawsuit was filed Aug. 16.

Vaccines have been shown to dramatically reduce both the incidence and the severity of COVID infections. Vaccinations of health care workers, especially those who have direct contact with patients, are demonstrated to be effective strategies to significantly reduce, although not eliminate, the possibility of viral transmissions to patients – or to health care workers themselves – thus saving lives.

Hospitalists, in their central role in the care of hospitalized patients, and often with primary responsibility for managing their hospital’s COVID-19 caseloads, may find themselves encountering conversations about the vaccine, its safety, effectiveness, and mandates with their peers, other hospital staff, patients, and families, and their communities. They can play key roles in advocating for the vaccine, answering questions, clarifying the science, and dispelling misinformation – for those who are willing to listen.

Becker’s Hospital Review, which has kept an ongoing tally of announced vaccine mandate policies in hospitals, health systems, and health departments nationwide, reported on Aug. 13 that 1,850 or 30% of U.S. hospitals, had announced vaccine mandates.¹ Often exceptions can be made, such as for medical or religious reasons, or with other declarations or opt-out provisions. But in many settings, mandating COVID vaccinations won’t be easy.

Amith Skandhan, MD, SFHM, FACP, a hospitalist at Southeast Health Medical Center in Dothan, Ala., and a core faculty member in the internal medicine residency program at Alabama College of Osteopathic Medicine, said that implementing vaccine mandates will be more difficult in smaller health systems, in rural communities, and in states with lower vaccination rates and greater vaccine controversy.

Alabama has the lowest vaccination rates in the country, reflected in the recent rise in COVID cases and hospitalizations, even higher than during the surge of late 2020, Dr. Skandhan said. “In June we had one COVID patient in this hospital.” By late August the number was 119 COVID patients and climbing.

But where he works, in a health system where staffing is already spread thin, a vaccine mandate would be challenging. “What if our staff started leaving? It’s only 10 minutes from here to the Florida or Georgia border,” Dr. Skandhan said. Health care workers opposed to vaccinations would have the option of easily seeking work elsewhere.

When contacted for this article, he had been off work for several days but was mentally preparing himself to go back. “I’m not even following the [COVID-19] numbers but I am prepared for the worst. I know it will be mostly COVID. People just don’t realize what goes into this work.”

Dr. Skandhan, who said he was the third or fourth person in Alabama to receive the COVID vaccine, often finds himself feeling frustrated and angry – in the midst of a surge in cases that could have been prevented – that such a beneficial medical advance for bringing the pandemic under control became so politicized. “It is imperative that we find out why this mistrust exists and work to address it. It has to be done.”

Protecting health care professionals

On July 26, the Society of Hospital Medicine joined 50 other health care organizations including the American Medical Association, American Nurses Association, and American Academy of Pediatrics in advocating for all health care employers to require their employees to be vaccinated against COVID, in order to protect the safety of all patients and residents of health care facilities.²

“As an organization, we support vaccinating health care workers, including hospitalists, to help stop the spread of COVID-19 and the increasingly dominant Delta variant,” said SHM’s chief executive officer Eric E. Howell, MD, MHM, in a prepared statement. “We aim to uphold the highest standards among hospitalists and other health care providers to help protect our fellow health care professionals, our patients, and our communities.”

To that end, Dr. Skandhan has started conversations with hospital staff who he knows are not vaccinated. “For some, we’re not able to have a civil conversation, but in most cases I can help to persuade people.” The reasons people give for not getting vaccinated are not based in science, he said. “I am worried about the safety of our hospitalists and staff nurses.” But unvaccinated frontline workers are also putting their patients at risk. “Can we say why they’re hesitating? Can we have an honest discourse? If we can’t do that with our colleagues, how can we blame the patients?”

Dr. Skandhan encourages hospitalists to start simply in their own hospitals, trying to influence their own departments and colleagues. “If you can convince one or two more every week, you can start a chain reaction. Have that conversation. Use your trust.” For some hospitalized patients, the vaccination conversation comes too late, after their infection, but even some of them might consider obtaining it down the road or trying to persuade family members to get vaccinated.

Adult hospitalists, however, may not have received training in how to effectively address vaccine fears and misconceptions among their patients, he said. Because the patients they see in the hospital are already very sick, they don’t get a lot of practice talking about vaccines except, perhaps, for the influenza vaccine.

Pediatric hospitalists have more experience with such conversations involving their patients’ parents, Dr. Skandhan said. “It comes more naturally to them. We need to learn quickly from them about how to talk about vaccines with our patients.”

Pediatric training and experience

Anika Kumar, MD, FHM, FAAP, a pediatric hospitalist at the Cleveland Clinic and the pediatric editor of The Hospitalist, agrees that pediatricians and pediatric hospitalists often have received more training in how to lead vaccination conversations. She often talks about vaccines with the parents of hospitalized children relative to chicken pox, measles, and other diseases of childhood.

Pediatric hospitalists may also ask to administer the hepatitis B vaccine to newborn babies, along with other preventive treatments such as eye drops and vitamin K shots. “I often encourage the influenza vaccine prior to the patient’s hospital discharge, especially for kids with chronic conditions, asthma, diabetes, or premature birth. We talk about how the influenza vaccine isn’t perfect, but it helps to prevent more serious disease,” she said.

“A lot of vaccine hesitancy comes from misunderstandings about the role of vaccines,” she said. People forget that for years children have been getting vaccines before starting school. “Misinformation and opinions about vaccines have existed for decades. What’s new today is the abundance of sources for obtaining these opinions. My job is to inform families of scientific facts and to address their concerns.”

It has become more common recently for parents to say they don’t want their kids to get vaccinated, Dr. Kumar said. Another group is better described as vaccine hesitant and just needs more information. “I may not, by the time they leave the hospital, convince them to allow me to administer the vaccine. But in the discharge summary, I document that I had this conversation. I’ve done my due diligence and tried to start a larger dialogue. I say: ‘I encourage you to continue this discussion with the pediatrician you trust.’ I also communicate with the outpatient team,” she said.

“But it’s our responsibility, because we’re the ones seeing these patients, to do whatever we can to keep our patients from getting sick. A lot of challenging conversations we have with families are just trying to find out where they’re at with the issue – which can lead to productive dialogue.”

Ariel Carpenter, MD, a 4th-year resident in internal medicine and pediatrics at the University of Louisville (Ky.), and a future pediatric hospitalist, agreed that her combined training in med-peds has been helpful preparation for the vaccine conversation. That training has included techniques of motivational interviewing. In pediatrics, she explained, the communication is a little softer. “I try to approach my patients in a family-centered way.”

Dr. Carpenter recently wrote a personal essay for Louisville Medicine magazine from the perspective of growing up homeschooled by a mother who didn’t believe in vaccines.³ As a teenager, she independently obtained the complete childhood vaccine series so that she could do medical shadowing and volunteering. In medical school she became a passionate vaccine advocate, eventually persuading her mother to change her mind on the subject in time for the COVID vaccine.

“There’s not one answer to the vaccination dilemma,” she said. “Different approaches are required because there are so many different reasons for it. Based on my own life experience, I try to approach patients where they are – not from a place of data and science. What worked in my own family, and works with my patients, is first to establish trust. If they trust you, they’re more likely to listen. Simply ask their worries and concerns,” Dr. Carpenter said.

“A lot of them haven’t had the opportunity before to sit down with a physician they trust and have their worries listened to. They don’t feel heard in our medical system. So I remind myself that I need to understand my patients first – before inserting myself into the conversation.”

Many patients she sees are in an information bubble, with a very different understanding of the issue than their doctors. “A lot of well-meaning people feel they are making the safer choice. Very few truly don’t care about protecting others. But they don’t feel the urgency about that and see the vaccine as the scarier option right now.”

Frontline vaccine advocates

Hospitalists are the frontline advocates within their hospital system, in a position to lead, so they need to make vaccines a priority, Dr. Carpenter said. They should also make sure that their hospitals have ready access to the vaccine, so patients who agree to receive it are able to get it quickly. “In our hospital they can get the shot within a few hours if the opportunity arises. We stocked the Johnson & Johnson vaccine so that they wouldn’t have to connect with another health care provider in order to get a second dose.”

Hospitals should also invest in access to vaccine counseling training and personnel. “Fund a nurse clinician who can screen and counsel hospitalized patients for vaccination. If they meet resistance, they can then refer to the dedicated physician of the day to have the conversation,” she said. “But if we don’t mention it, patients will assume we don’t feel strongly about it.”

Because hospitalists are front and center in treating COVID, they need to be the experts and the people offering guidance, said Shyam Odeti, MD, SFHM, FAAFP, section chief for hospital medicine at the Carilion Clinic in Roanoke, Va. “What we’re trying to do is spread awareness. We educated physician groups, learners, and clinical teams during the initial phase, and now mostly patients and their families.” COVID vaccine reluctance is hard to overcome, Dr. Odeti said. People feel the vaccine was developed very quickly. But there are different ways to present it.

“Like most doctors, I thought people would jump on a vaccine to get past the pandemic. I was surprised and then disappointed. Right now, the pandemic is among the unvaccinated. So we face these encounters, and we’re doing our best to overcome the misinformation. My organization is 100% supportive. We talk about these issues every day.”

Carilion, effective Oct. 1, has required unvaccinated employees to get weekly COVID tests and wear an N95 mask while working, and has developed Facebook pages, other social media, and an Internet presence to address these issues. “We’ve gone to the local African-American community with physician leaders active in that community. We had a Spanish language roundtable,” Dr. Odeti said.

Dr. Skandhan reported that the Wiregrass regional chapter of SHM recently organized a successful statewide community educational event aimed at empowering community leaders to address vaccine misinformation and mistrust. “We surveyed religious leaders and pastors regarding the causes of vaccine hesitancy and reached out to physicians active in community awareness.” Based on that input, a presentation by the faith leaders was developed. Legislators from the Alabama State Senate’s Healthcare Policy Committee were also invited to the presentation and discussion.
 

Trying to stay positive

It’s important to try to stay positive, Dr. Odeti said. “We have to be empathetic with every patient. We have to keep working at this, since there’s no way out of the pandemic except through vaccinations. But it all creates stress for hospitalists. Our job is made significantly more difficult by the vaccine controversy.”

Jennifer Cowart, MD, a hospitalist at Mayo Clinic in Jacksonville, Fla., has been outspoken in her community about vaccination and masking issues, talking to reporters, attending rallies and press conferences, posting on social media, and speaking in favor of mask policies at a local school board meeting. She is part of an informal local group called Doctors Fighting COVID, which meets online to strategize how to share its expertise, including writing a recent letter about masks to Jacksonville’s mayor.

“In July, when we saw the Delta variant surging locally, we held a webinar via local media, taking calls about the vaccine from the community. I’m trying not to make this a political issue, but we are health officials.” Dr. Cowart said she also tries not to raise her voice when speaking with vaccine opponents and tries to remain empathetic. “Even though inwardly I’m screaming, I try to stay calm. The misinformation is real. People are afraid and feeling pressure. I do my best, but I’m human, too.”

Hospitalists need to pull whatever levers they can to help advance understanding of vaccines, Dr. Cowart said. “In the hospital, our biggest issue is time. We often don’t have it, with a long list of patients to see. But every patient encounter is an opportunity to talk to patients, whether they have COVID or something else.” Sometimes, she might go back to a patient’s room after rounds to resume the conversation.

Hospital nurses have been trained and entrusted to do tobacco abatement counseling, she said, so why not mobilize them for vaccine education? “Or respiratory therapists, who do inhaler training, could talk about what it’s like to care for COVID patients. There’s a whole bunch of staff in the hospital who could be mobilized,” she said.

“I feel passionate about vaccines, as a hospitalist, as a medical educator, as a daughter, as a responsible member of society,” said Eileen Barrett, MD, MPH, SFHM, MACP, director of continuing medical education at the University of New Mexico, Albuquerque. “I see this as a personal and societal responsibility. When I speak about the vaccine among groups of doctors, I say we need to stay in our lane regarding our skills at interpreting the science and not undermining it.”

Some health care worker hesitancy is from distrust of pharmaceutical companies, or of federal agencies, she said. “Our research has highlighted to me the widespread inequity issues in our health care system. We should also take a long, hard look at how we teach the scientific method to health professionals. That will be part of a pandemic retrospective.”

Sometimes with people who are vaccine deliberative, whether health care workers or patients, there is a small window of opportunity. “We need to hear people and respond to them as people. Then, if they are willing to get vaccinated, we need to accomplish that as quickly and easily as possible,” Dr. Barrett said. “I see them make a face and say, ‘Well, okay, I’ll do it.’ We need to get the vaccine to them that same day. We should be able to accomplish that.”
 

References

1. Gamble M. 30% of US hospitals mandate vaccination for employment. Becker’s Hospital Review. 2021 Aug 13. www.beckershospitalreview.com/workforce/covid-19-vaccination-needed-to-work-at-30-of-us-hospitals.html .

2. Society of Hospital Medicine signs on to joint statement in support of health worker COVID-19 vaccine mandates. Press release. 2021 Jul 26. www.hospitalmedicine.org/news-publications/press-releases/society-of-hospital-medicine-signs-on-to-joint-statement-of-support-of-health-worker-covid-19-vaccine-mandates/.

3. Carpenter A. A physician’s lessons from an unvaccinated childhood. Louisville Medicine. 2021 July;69(2):26-7. https://viewer.joomag.com/louisville-medicine-volume-69-issue-2/0045988001624974172?short&.

Lessons for hospitalists from the vaccination controversy

1. Remain up-to-date on information about the COVID infection, its treatment, and vaccination efficacy data.

2. Hospitalists should take advantage of their positions to lead conversations in their facilities about the importance of COVID vaccinations.

3. Other professionals in the hospital, with some additional training and support, could take on the role of providing vaccine education and support – with a physician to back them up on difficult cases.

4. It’s important to listen to people’s concerns, try to build trust, and establish dialogue before starting to convey a lot of information. People need to feel heard.

5. If you are successful in persuading someone to take the vaccine, a shot should be promptly and easily accessible to them.

6. Pediatric hospitalists may have more experience and skill with vaccine discussions, which they should share with their peers who treat adults.

On April 1, Houston Methodist Hospital in Houston, Texas, announced a new policy that all of its staff would need to be vaccinated against COVID-19 by June 7 in order to hold onto their jobs. Most responded positively but an estimated 150 staff members who did not comply either resigned or were terminated. A lawsuit by employees opposed to the vaccine mandate was dismissed by Federal District Court Judge Lynn Hughes in June, although a subsequent lawsuit was filed Aug. 16.

Vaccines have been shown to dramatically reduce both the incidence and the severity of COVID infections. Vaccinations of health care workers, especially those who have direct contact with patients, are demonstrated to be effective strategies to significantly reduce, although not eliminate, the possibility of viral transmissions to patients – or to health care workers themselves – thus saving lives.

Hospitalists, in their central role in the care of hospitalized patients, and often with primary responsibility for managing their hospital’s COVID-19 caseloads, may find themselves encountering conversations about the vaccine, its safety, effectiveness, and mandates with their peers, other hospital staff, patients, and families, and their communities. They can play key roles in advocating for the vaccine, answering questions, clarifying the science, and dispelling misinformation – for those who are willing to listen.

Becker’s Hospital Review, which has kept an ongoing tally of announced vaccine mandate policies in hospitals, health systems, and health departments nationwide, reported on Aug. 13 that 1,850 or 30% of U.S. hospitals, had announced vaccine mandates.¹ Often exceptions can be made, such as for medical or religious reasons, or with other declarations or opt-out provisions. But in many settings, mandating COVID vaccinations won’t be easy.

Amith Skandhan, MD, SFHM, FACP, a hospitalist at Southeast Health Medical Center in Dothan, Ala., and a core faculty member in the internal medicine residency program at Alabama College of Osteopathic Medicine, said that implementing vaccine mandates will be more difficult in smaller health systems, in rural communities, and in states with lower vaccination rates and greater vaccine controversy.

Alabama has the lowest vaccination rates in the country, reflected in the recent rise in COVID cases and hospitalizations, even higher than during the surge of late 2020, Dr. Skandhan said. “In June we had one COVID patient in this hospital.” By late August the number was 119 COVID patients and climbing.

But where he works, in a health system where staffing is already spread thin, a vaccine mandate would be challenging. “What if our staff started leaving? It’s only 10 minutes from here to the Florida or Georgia border,” Dr. Skandhan said. Health care workers opposed to vaccinations would have the option of easily seeking work elsewhere.

When contacted for this article, he had been off work for several days but was mentally preparing himself to go back. “I’m not even following the [COVID-19] numbers but I am prepared for the worst. I know it will be mostly COVID. People just don’t realize what goes into this work.”

Dr. Skandhan, who said he was the third or fourth person in Alabama to receive the COVID vaccine, often finds himself feeling frustrated and angry – in the midst of a surge in cases that could have been prevented – that such a beneficial medical advance for bringing the pandemic under control became so politicized. “It is imperative that we find out why this mistrust exists and work to address it. It has to be done.”

Protecting health care professionals

On July 26, the Society of Hospital Medicine joined 50 other health care organizations including the American Medical Association, American Nurses Association, and American Academy of Pediatrics in advocating for all health care employers to require their employees to be vaccinated against COVID, in order to protect the safety of all patients and residents of health care facilities.²

“As an organization, we support vaccinating health care workers, including hospitalists, to help stop the spread of COVID-19 and the increasingly dominant Delta variant,” said SHM’s chief executive officer Eric E. Howell, MD, MHM, in a prepared statement. “We aim to uphold the highest standards among hospitalists and other health care providers to help protect our fellow health care professionals, our patients, and our communities.”

To that end, Dr. Skandhan has started conversations with hospital staff who he knows are not vaccinated. “For some, we’re not able to have a civil conversation, but in most cases I can help to persuade people.” The reasons people give for not getting vaccinated are not based in science, he said. “I am worried about the safety of our hospitalists and staff nurses.” But unvaccinated frontline workers are also putting their patients at risk. “Can we say why they’re hesitating? Can we have an honest discourse? If we can’t do that with our colleagues, how can we blame the patients?”

Dr. Skandhan encourages hospitalists to start simply in their own hospitals, trying to influence their own departments and colleagues. “If you can convince one or two more every week, you can start a chain reaction. Have that conversation. Use your trust.” For some hospitalized patients, the vaccination conversation comes too late, after their infection, but even some of them might consider obtaining it down the road or trying to persuade family members to get vaccinated.

Adult hospitalists, however, may not have received training in how to effectively address vaccine fears and misconceptions among their patients, he said. Because the patients they see in the hospital are already very sick, they don’t get a lot of practice talking about vaccines except, perhaps, for the influenza vaccine.

Pediatric hospitalists have more experience with such conversations involving their patients’ parents, Dr. Skandhan said. “It comes more naturally to them. We need to learn quickly from them about how to talk about vaccines with our patients.”

Pediatric training and experience

Anika Kumar, MD, FHM, FAAP, a pediatric hospitalist at the Cleveland Clinic and the pediatric editor of The Hospitalist, agrees that pediatricians and pediatric hospitalists often have received more training in how to lead vaccination conversations. She often talks about vaccines with the parents of hospitalized children relative to chicken pox, measles, and other diseases of childhood.

Pediatric hospitalists may also ask to administer the hepatitis B vaccine to newborn babies, along with other preventive treatments such as eye drops and vitamin K shots. “I often encourage the influenza vaccine prior to the patient’s hospital discharge, especially for kids with chronic conditions, asthma, diabetes, or premature birth. We talk about how the influenza vaccine isn’t perfect, but it helps to prevent more serious disease,” she said.

“A lot of vaccine hesitancy comes from misunderstandings about the role of vaccines,” she said. People forget that for years children have been getting vaccines before starting school. “Misinformation and opinions about vaccines have existed for decades. What’s new today is the abundance of sources for obtaining these opinions. My job is to inform families of scientific facts and to address their concerns.”

It has become more common recently for parents to say they don’t want their kids to get vaccinated, Dr. Kumar said. Another group is better described as vaccine hesitant and just needs more information. “I may not, by the time they leave the hospital, convince them to allow me to administer the vaccine. But in the discharge summary, I document that I had this conversation. I’ve done my due diligence and tried to start a larger dialogue. I say: ‘I encourage you to continue this discussion with the pediatrician you trust.’ I also communicate with the outpatient team,” she said.

“But it’s our responsibility, because we’re the ones seeing these patients, to do whatever we can to keep our patients from getting sick. A lot of challenging conversations we have with families are just trying to find out where they’re at with the issue – which can lead to productive dialogue.”

Ariel Carpenter, MD, a 4th-year resident in internal medicine and pediatrics at the University of Louisville (Ky.), and a future pediatric hospitalist, agreed that her combined training in med-peds has been helpful preparation for the vaccine conversation. That training has included techniques of motivational interviewing. In pediatrics, she explained, the communication is a little softer. “I try to approach my patients in a family-centered way.”

Dr. Carpenter recently wrote a personal essay for Louisville Medicine magazine from the perspective of growing up homeschooled by a mother who didn’t believe in vaccines.³ As a teenager, she independently obtained the complete childhood vaccine series so that she could do medical shadowing and volunteering. In medical school she became a passionate vaccine advocate, eventually persuading her mother to change her mind on the subject in time for the COVID vaccine.

“There’s not one answer to the vaccination dilemma,” she said. “Different approaches are required because there are so many different reasons for it. Based on my own life experience, I try to approach patients where they are – not from a place of data and science. What worked in my own family, and works with my patients, is first to establish trust. If they trust you, they’re more likely to listen. Simply ask their worries and concerns,” Dr. Carpenter said.

“A lot of them haven’t had the opportunity before to sit down with a physician they trust and have their worries listened to. They don’t feel heard in our medical system. So I remind myself that I need to understand my patients first – before inserting myself into the conversation.”

Many patients she sees are in an information bubble, with a very different understanding of the issue than their doctors. “A lot of well-meaning people feel they are making the safer choice. Very few truly don’t care about protecting others. But they don’t feel the urgency about that and see the vaccine as the scarier option right now.”

Frontline vaccine advocates

Hospitalists are the frontline advocates within their hospital system, in a position to lead, so they need to make vaccines a priority, Dr. Carpenter said. They should also make sure that their hospitals have ready access to the vaccine, so patients who agree to receive it are able to get it quickly. “In our hospital they can get the shot within a few hours if the opportunity arises. We stocked the Johnson & Johnson vaccine so that they wouldn’t have to connect with another health care provider in order to get a second dose.”

Hospitals should also invest in access to vaccine counseling training and personnel. “Fund a nurse clinician who can screen and counsel hospitalized patients for vaccination. If they meet resistance, they can then refer to the dedicated physician of the day to have the conversation,” she said. “But if we don’t mention it, patients will assume we don’t feel strongly about it.”

Because hospitalists are front and center in treating COVID, they need to be the experts and the people offering guidance, said Shyam Odeti, MD, SFHM, FAAFP, section chief for hospital medicine at the Carilion Clinic in Roanoke, Va. “What we’re trying to do is spread awareness. We educated physician groups, learners, and clinical teams during the initial phase, and now mostly patients and their families.” COVID vaccine reluctance is hard to overcome, Dr. Odeti said. People feel the vaccine was developed very quickly. But there are different ways to present it.

“Like most doctors, I thought people would jump on a vaccine to get past the pandemic. I was surprised and then disappointed. Right now, the pandemic is among the unvaccinated. So we face these encounters, and we’re doing our best to overcome the misinformation. My organization is 100% supportive. We talk about these issues every day.”

Carilion, effective Oct. 1, has required unvaccinated employees to get weekly COVID tests and wear an N95 mask while working, and has developed Facebook pages, other social media, and an Internet presence to address these issues. “We’ve gone to the local African-American community with physician leaders active in that community. We had a Spanish language roundtable,” Dr. Odeti said.

Dr. Skandhan reported that the Wiregrass regional chapter of SHM recently organized a successful statewide community educational event aimed at empowering community leaders to address vaccine misinformation and mistrust. “We surveyed religious leaders and pastors regarding the causes of vaccine hesitancy and reached out to physicians active in community awareness.” Based on that input, a presentation by the faith leaders was developed. Legislators from the Alabama State Senate’s Healthcare Policy Committee were also invited to the presentation and discussion.
 

Trying to stay positive

It’s important to try to stay positive, Dr. Odeti said. “We have to be empathetic with every patient. We have to keep working at this, since there’s no way out of the pandemic except through vaccinations. But it all creates stress for hospitalists. Our job is made significantly more difficult by the vaccine controversy.”

Jennifer Cowart, MD, a hospitalist at Mayo Clinic in Jacksonville, Fla., has been outspoken in her community about vaccination and masking issues, talking to reporters, attending rallies and press conferences, posting on social media, and speaking in favor of mask policies at a local school board meeting. She is part of an informal local group called Doctors Fighting COVID, which meets online to strategize how to share its expertise, including writing a recent letter about masks to Jacksonville’s mayor.

“In July, when we saw the Delta variant surging locally, we held a webinar via local media, taking calls about the vaccine from the community. I’m trying not to make this a political issue, but we are health officials.” Dr. Cowart said she also tries not to raise her voice when speaking with vaccine opponents and tries to remain empathetic. “Even though inwardly I’m screaming, I try to stay calm. The misinformation is real. People are afraid and feeling pressure. I do my best, but I’m human, too.”

Hospitalists need to pull whatever levers they can to help advance understanding of vaccines, Dr. Cowart said. “In the hospital, our biggest issue is time. We often don’t have it, with a long list of patients to see. But every patient encounter is an opportunity to talk to patients, whether they have COVID or something else.” Sometimes, she might go back to a patient’s room after rounds to resume the conversation.

Hospital nurses have been trained and entrusted to do tobacco abatement counseling, she said, so why not mobilize them for vaccine education? “Or respiratory therapists, who do inhaler training, could talk about what it’s like to care for COVID patients. There’s a whole bunch of staff in the hospital who could be mobilized,” she said.

“I feel passionate about vaccines, as a hospitalist, as a medical educator, as a daughter, as a responsible member of society,” said Eileen Barrett, MD, MPH, SFHM, MACP, director of continuing medical education at the University of New Mexico, Albuquerque. “I see this as a personal and societal responsibility. When I speak about the vaccine among groups of doctors, I say we need to stay in our lane regarding our skills at interpreting the science and not undermining it.”

Some health care worker hesitancy is from distrust of pharmaceutical companies, or of federal agencies, she said. “Our research has highlighted to me the widespread inequity issues in our health care system. We should also take a long, hard look at how we teach the scientific method to health professionals. That will be part of a pandemic retrospective.”

Sometimes with people who are vaccine deliberative, whether health care workers or patients, there is a small window of opportunity. “We need to hear people and respond to them as people. Then, if they are willing to get vaccinated, we need to accomplish that as quickly and easily as possible,” Dr. Barrett said. “I see them make a face and say, ‘Well, okay, I’ll do it.’ We need to get the vaccine to them that same day. We should be able to accomplish that.”
 

References

1. Gamble M. 30% of US hospitals mandate vaccination for employment. Becker’s Hospital Review. 2021 Aug 13. www.beckershospitalreview.com/workforce/covid-19-vaccination-needed-to-work-at-30-of-us-hospitals.html .

2. Society of Hospital Medicine signs on to joint statement in support of health worker COVID-19 vaccine mandates. Press release. 2021 Jul 26. www.hospitalmedicine.org/news-publications/press-releases/society-of-hospital-medicine-signs-on-to-joint-statement-of-support-of-health-worker-covid-19-vaccine-mandates/.

3. Carpenter A. A physician’s lessons from an unvaccinated childhood. Louisville Medicine. 2021 July;69(2):26-7. https://viewer.joomag.com/louisville-medicine-volume-69-issue-2/0045988001624974172?short&.

Lessons for hospitalists from the vaccination controversy

1. Remain up-to-date on information about the COVID infection, its treatment, and vaccination efficacy data.

2. Hospitalists should take advantage of their positions to lead conversations in their facilities about the importance of COVID vaccinations.

3. Other professionals in the hospital, with some additional training and support, could take on the role of providing vaccine education and support – with a physician to back them up on difficult cases.

4. It’s important to listen to people’s concerns, try to build trust, and establish dialogue before starting to convey a lot of information. People need to feel heard.

5. If you are successful in persuading someone to take the vaccine, a shot should be promptly and easily accessible to them.

6. Pediatric hospitalists may have more experience and skill with vaccine discussions, which they should share with their peers who treat adults.

A novel virus engineered to target malignant gliomas, which are particularly aggressive brain tumors, may prolong survival, according to a recent phase 1 study.

The findings, published June 29 in The Lancet Oncology, show early promise in targeting malignant gliomas, which have been notoriously difficult to treat. Only 1 in 4 patients are alive 2 years after diagnosis. The median overall survival from diagnosis is 14.6-16.7 months.

In a study of a novel therapy called NSC-CRAd-S-pk7 – an oncolytic adenovirus delivered across the blood-brain barrier by neural stem cells – overall survival improved by several months for patients with malignant gliomas.

“To my knowledge, this is the first time neural stem cells have been used as a delivery strategy for an oncolytic virus,” said Terence Burns, MD, PhD, associate professor of neurosurgery at the Mayo Clinic, Rochester, Minn., who was not involved in the research.

In this open-label, dose-escalation trial, researchers enrolled 12 patients with newly diagnosed malignant gliomas between April 2017 and November 2019. After neurosurgical tumor resection, patients were placed in one of three cohorts distinguished by dose of NSC-CRAd-S-pk7. Three patients received the lowest dose of 6.25×1010 viral particles administered by 5.00×10⁷ neural stem cells (NSCs), three received a more moderate dose of 1.25×10 viral particles administered by 1.00×108 NSCs, and the remaining six patients received a dose of 1.875×1011 viral particles administered by 1.50×108 NSCs. Within 10-14 days, the investigators also initiated treatment with temozolomide and radiotherapy.

The investigators report that after a median 18-month follow-up period, median progression-free survival was 9.1 months, and median overall survival of 18.4 months. In a subgroup of patients with unmethylated MGMT promoters – DNA repair enzymes that make tumor cells more resistant to treatment – median progression-free survival was 8.8 months, and median overall survival was 18.0 months.

There was no dose-limiting toxicity, and there were no treatment-related deaths. One patient developed viral meningitis, owing to the inadvertent ventricular injection of NSC-CRAd-S-pk7, and fully recovered after hospitalization.

Patients tolerated the treatment well, which is critical because “drugs that could fight gliomas might also have serious adverse effects,” first author Jawad Fares, MD, a postdoctoral fellow in neurological surgery at Northwestern University, Chicago, said in an interview.
 

A novel approach

A significant challenge to delivering drugs to the site of malignant gliomas is the blood-brain barrier, which blocks entry of many chemotherapeutic drugs.

“Because of this barrier, physicians often employ other strategies, such as direct injection in the brain cavity, but even with an injection, it is problematic to disseminate the drug so that the medication spreads throughout the tumor mass,” said Dr. Fares. “Our innovative approach, which employs the use of neural stem cells as shuttles to deliver viruses, seeks to address this problem. Neural stem cells tend to travel within hours to areas of injury, areas of stroke or brain tumors, and could disperse the oncolytic virus.”

Gliomas create an immunosuppressive tumor microenvironment, which uses tissue cells, blood vessels, immune cells, and other parts of the body to blunt antitumor immune responses. Using NSCs to deliver NSC-CRAd-S-pk7 directly to the tumor has the advantage of “giving the virus more time to replicate and kill tumor cells,” said Marta Alonso Roldán, MD, Clinica Universidad de Navarra, in Spain, in an interview.

Although NSC-CRAd-S-pk7 appeared to improve survival in this cohort by a few months, follow-up trials with larger sample sizes and control groups are necessary to demonstrate efficacy.

Moreover, patients in this trial may not be representative of the average patient, said Dr. Burns. “For instance, three of the patients had relatively small tumors in nicely operable areas with a high likelihood of getting a gross total resection. These things do stack your odds in favor of having a longer survival.”

Moving forward, “this trial sets the stage for a phase 2/3 study in which the efficacy of NSC-CRAd-S-pk7 in eliciting an antiglioma immune response and prolonging survival in a larger cohort of patients with controlled conditions can be explored,” Dr. Fares said.

The study was funded by the U.S. National Institutes of Health. Dr. Fares, Dr. Burns, and Dr. Roldán have disclosed no relevant financial relationships.

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

A novel virus engineered to target malignant gliomas, which are particularly aggressive brain tumors, may prolong survival, according to a recent phase 1 study.

The findings, published June 29 in The Lancet Oncology, show early promise in targeting malignant gliomas, which have been notoriously difficult to treat. Only 1 in 4 patients are alive 2 years after diagnosis. The median overall survival from diagnosis is 14.6-16.7 months.

In a study of a novel therapy called NSC-CRAd-S-pk7 – an oncolytic adenovirus delivered across the blood-brain barrier by neural stem cells – overall survival improved by several months for patients with malignant gliomas.

“To my knowledge, this is the first time neural stem cells have been used as a delivery strategy for an oncolytic virus,” said Terence Burns, MD, PhD, associate professor of neurosurgery at the Mayo Clinic, Rochester, Minn., who was not involved in the research.

In this open-label, dose-escalation trial, researchers enrolled 12 patients with newly diagnosed malignant gliomas between April 2017 and November 2019. After neurosurgical tumor resection, patients were placed in one of three cohorts distinguished by dose of NSC-CRAd-S-pk7. Three patients received the lowest dose of 6.25×1010 viral particles administered by 5.00×10⁷ neural stem cells (NSCs), three received a more moderate dose of 1.25×10 viral particles administered by 1.00×108 NSCs, and the remaining six patients received a dose of 1.875×1011 viral particles administered by 1.50×108 NSCs. Within 10-14 days, the investigators also initiated treatment with temozolomide and radiotherapy.

The investigators report that after a median 18-month follow-up period, median progression-free survival was 9.1 months, and median overall survival of 18.4 months. In a subgroup of patients with unmethylated MGMT promoters – DNA repair enzymes that make tumor cells more resistant to treatment – median progression-free survival was 8.8 months, and median overall survival was 18.0 months.

There was no dose-limiting toxicity, and there were no treatment-related deaths. One patient developed viral meningitis, owing to the inadvertent ventricular injection of NSC-CRAd-S-pk7, and fully recovered after hospitalization.

Patients tolerated the treatment well, which is critical because “drugs that could fight gliomas might also have serious adverse effects,” first author Jawad Fares, MD, a postdoctoral fellow in neurological surgery at Northwestern University, Chicago, said in an interview.
 

A novel approach

A significant challenge to delivering drugs to the site of malignant gliomas is the blood-brain barrier, which blocks entry of many chemotherapeutic drugs.

“Because of this barrier, physicians often employ other strategies, such as direct injection in the brain cavity, but even with an injection, it is problematic to disseminate the drug so that the medication spreads throughout the tumor mass,” said Dr. Fares. “Our innovative approach, which employs the use of neural stem cells as shuttles to deliver viruses, seeks to address this problem. Neural stem cells tend to travel within hours to areas of injury, areas of stroke or brain tumors, and could disperse the oncolytic virus.”

Gliomas create an immunosuppressive tumor microenvironment, which uses tissue cells, blood vessels, immune cells, and other parts of the body to blunt antitumor immune responses. Using NSCs to deliver NSC-CRAd-S-pk7 directly to the tumor has the advantage of “giving the virus more time to replicate and kill tumor cells,” said Marta Alonso Roldán, MD, Clinica Universidad de Navarra, in Spain, in an interview.

Although NSC-CRAd-S-pk7 appeared to improve survival in this cohort by a few months, follow-up trials with larger sample sizes and control groups are necessary to demonstrate efficacy.

Moreover, patients in this trial may not be representative of the average patient, said Dr. Burns. “For instance, three of the patients had relatively small tumors in nicely operable areas with a high likelihood of getting a gross total resection. These things do stack your odds in favor of having a longer survival.”

Moving forward, “this trial sets the stage for a phase 2/3 study in which the efficacy of NSC-CRAd-S-pk7 in eliciting an antiglioma immune response and prolonging survival in a larger cohort of patients with controlled conditions can be explored,” Dr. Fares said.

The study was funded by the U.S. National Institutes of Health. Dr. Fares, Dr. Burns, and Dr. Roldán have disclosed no relevant financial relationships.

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

A novel virus engineered to target malignant gliomas, which are particularly aggressive brain tumors, may prolong survival, according to a recent phase 1 study.

The findings, published June 29 in The Lancet Oncology, show early promise in targeting malignant gliomas, which have been notoriously difficult to treat. Only 1 in 4 patients are alive 2 years after diagnosis. The median overall survival from diagnosis is 14.6-16.7 months.

In a study of a novel therapy called NSC-CRAd-S-pk7 – an oncolytic adenovirus delivered across the blood-brain barrier by neural stem cells – overall survival improved by several months for patients with malignant gliomas.

“To my knowledge, this is the first time neural stem cells have been used as a delivery strategy for an oncolytic virus,” said Terence Burns, MD, PhD, associate professor of neurosurgery at the Mayo Clinic, Rochester, Minn., who was not involved in the research.

In this open-label, dose-escalation trial, researchers enrolled 12 patients with newly diagnosed malignant gliomas between April 2017 and November 2019. After neurosurgical tumor resection, patients were placed in one of three cohorts distinguished by dose of NSC-CRAd-S-pk7. Three patients received the lowest dose of 6.25×1010 viral particles administered by 5.00×10⁷ neural stem cells (NSCs), three received a more moderate dose of 1.25×10 viral particles administered by 1.00×108 NSCs, and the remaining six patients received a dose of 1.875×1011 viral particles administered by 1.50×108 NSCs. Within 10-14 days, the investigators also initiated treatment with temozolomide and radiotherapy.

The investigators report that after a median 18-month follow-up period, median progression-free survival was 9.1 months, and median overall survival of 18.4 months. In a subgroup of patients with unmethylated MGMT promoters – DNA repair enzymes that make tumor cells more resistant to treatment – median progression-free survival was 8.8 months, and median overall survival was 18.0 months.

There was no dose-limiting toxicity, and there were no treatment-related deaths. One patient developed viral meningitis, owing to the inadvertent ventricular injection of NSC-CRAd-S-pk7, and fully recovered after hospitalization.

Patients tolerated the treatment well, which is critical because “drugs that could fight gliomas might also have serious adverse effects,” first author Jawad Fares, MD, a postdoctoral fellow in neurological surgery at Northwestern University, Chicago, said in an interview.
 

A novel approach

A significant challenge to delivering drugs to the site of malignant gliomas is the blood-brain barrier, which blocks entry of many chemotherapeutic drugs.

“Because of this barrier, physicians often employ other strategies, such as direct injection in the brain cavity, but even with an injection, it is problematic to disseminate the drug so that the medication spreads throughout the tumor mass,” said Dr. Fares. “Our innovative approach, which employs the use of neural stem cells as shuttles to deliver viruses, seeks to address this problem. Neural stem cells tend to travel within hours to areas of injury, areas of stroke or brain tumors, and could disperse the oncolytic virus.”

Gliomas create an immunosuppressive tumor microenvironment, which uses tissue cells, blood vessels, immune cells, and other parts of the body to blunt antitumor immune responses. Using NSCs to deliver NSC-CRAd-S-pk7 directly to the tumor has the advantage of “giving the virus more time to replicate and kill tumor cells,” said Marta Alonso Roldán, MD, Clinica Universidad de Navarra, in Spain, in an interview.

Although NSC-CRAd-S-pk7 appeared to improve survival in this cohort by a few months, follow-up trials with larger sample sizes and control groups are necessary to demonstrate efficacy.

Moreover, patients in this trial may not be representative of the average patient, said Dr. Burns. “For instance, three of the patients had relatively small tumors in nicely operable areas with a high likelihood of getting a gross total resection. These things do stack your odds in favor of having a longer survival.”

Moving forward, “this trial sets the stage for a phase 2/3 study in which the efficacy of NSC-CRAd-S-pk7 in eliciting an antiglioma immune response and prolonging survival in a larger cohort of patients with controlled conditions can be explored,” Dr. Fares said.

The study was funded by the U.S. National Institutes of Health. Dr. Fares, Dr. Burns, and Dr. Roldán have disclosed no relevant financial relationships.

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