Psoriatic Arthritis

Psoriasis patients with symptoms of psychological distress and depression reported lower satisfaction with their clinicians than did those without mental health comorbidities, according to a retrospective analysis of survey data.

The findings highlight the importance of clinicians being supportive and adaptable in their communication style when interacting with psoriasis patients with mental illness.

“This study aims to evaluate whether an association exists between a patient’s psychological state and the perception of patient-clinician encounters,” wrote Charlotte Read, MBBS, of Imperial College London, and April W. Armstrong, MD, MPH, of the University of Southern California, Los Angeles, in JAMA Dermatology.

The researchers retrospectively analyzed longitudinal data from over 8.8 million U.S. adults (unweighted, 652) with psoriasis who participated in the Medical Expenditure Panel Survey from 2004 to 2017. The nationally representative database includes various clinical information, such as data on patient demographics, health care use, and mental health comorbidities.

The primary outcome, patient satisfaction with their physician, was assessed using a patient-physician communication composite score. Mental health comorbidities were evaluated using standard questionnaires.

The mean age of study patients was 52.1 years (range, 0.7 years), and most were female (54%). In all, 73% of participants had no or mild psychological distress symptoms, and 27% had moderate or severe symptoms.

After analysis, the researchers found that patients with moderate psychological distress symptoms were 2.8 times more likely to report lower satisfaction with their physician than were those with no or mild symptoms (adjusted odds ratio, 2.8; P = .001). They also reported that patients with severe symptoms were more likely to report lower satisfaction (aOR, 2.3; P = .03).

“Patients with moderate or severe depression symptoms were less satisfied with their clinicians, compared with those with no or mild depression symptoms,” they further explained.

Based on the results, the coinvestigators emphasized the importance of bettering the patient experience for those with mental illness given the potential association with improved health outcomes.

“Because depressed patients can be more sensitive to negative communication, the clinician needs to be more conscious about using a positive and supportive communication style,” they recommended.

The authors acknowledged the inadequacy of evaluating clinician performance using patient satisfaction alone. As a result, the findings may not be generalizable to all clinical settings.

The study was funded by the National Psoriasis Foundation. Dr. Armstrong reported financial affiliations with several pharmaceutical companies.

SOURCE: Read C, Armstrong AW. JAMA Dermatol. 2020 May 6. doi: 10.1001/jamadermatol.2020.1054.

Psoriasis patients with symptoms of psychological distress and depression reported lower satisfaction with their clinicians than did those without mental health comorbidities, according to a retrospective analysis of survey data.

The findings highlight the importance of clinicians being supportive and adaptable in their communication style when interacting with psoriasis patients with mental illness.

“This study aims to evaluate whether an association exists between a patient’s psychological state and the perception of patient-clinician encounters,” wrote Charlotte Read, MBBS, of Imperial College London, and April W. Armstrong, MD, MPH, of the University of Southern California, Los Angeles, in JAMA Dermatology.

The researchers retrospectively analyzed longitudinal data from over 8.8 million U.S. adults (unweighted, 652) with psoriasis who participated in the Medical Expenditure Panel Survey from 2004 to 2017. The nationally representative database includes various clinical information, such as data on patient demographics, health care use, and mental health comorbidities.

The primary outcome, patient satisfaction with their physician, was assessed using a patient-physician communication composite score. Mental health comorbidities were evaluated using standard questionnaires.

The mean age of study patients was 52.1 years (range, 0.7 years), and most were female (54%). In all, 73% of participants had no or mild psychological distress symptoms, and 27% had moderate or severe symptoms.

After analysis, the researchers found that patients with moderate psychological distress symptoms were 2.8 times more likely to report lower satisfaction with their physician than were those with no or mild symptoms (adjusted odds ratio, 2.8; P = .001). They also reported that patients with severe symptoms were more likely to report lower satisfaction (aOR, 2.3; P = .03).

“Patients with moderate or severe depression symptoms were less satisfied with their clinicians, compared with those with no or mild depression symptoms,” they further explained.

Based on the results, the coinvestigators emphasized the importance of bettering the patient experience for those with mental illness given the potential association with improved health outcomes.

“Because depressed patients can be more sensitive to negative communication, the clinician needs to be more conscious about using a positive and supportive communication style,” they recommended.

The authors acknowledged the inadequacy of evaluating clinician performance using patient satisfaction alone. As a result, the findings may not be generalizable to all clinical settings.

The study was funded by the National Psoriasis Foundation. Dr. Armstrong reported financial affiliations with several pharmaceutical companies.

SOURCE: Read C, Armstrong AW. JAMA Dermatol. 2020 May 6. doi: 10.1001/jamadermatol.2020.1054.

Psoriasis patients with symptoms of psychological distress and depression reported lower satisfaction with their clinicians than did those without mental health comorbidities, according to a retrospective analysis of survey data.

The findings highlight the importance of clinicians being supportive and adaptable in their communication style when interacting with psoriasis patients with mental illness.

“This study aims to evaluate whether an association exists between a patient’s psychological state and the perception of patient-clinician encounters,” wrote Charlotte Read, MBBS, of Imperial College London, and April W. Armstrong, MD, MPH, of the University of Southern California, Los Angeles, in JAMA Dermatology.

The researchers retrospectively analyzed longitudinal data from over 8.8 million U.S. adults (unweighted, 652) with psoriasis who participated in the Medical Expenditure Panel Survey from 2004 to 2017. The nationally representative database includes various clinical information, such as data on patient demographics, health care use, and mental health comorbidities.

The primary outcome, patient satisfaction with their physician, was assessed using a patient-physician communication composite score. Mental health comorbidities were evaluated using standard questionnaires.

The mean age of study patients was 52.1 years (range, 0.7 years), and most were female (54%). In all, 73% of participants had no or mild psychological distress symptoms, and 27% had moderate or severe symptoms.

After analysis, the researchers found that patients with moderate psychological distress symptoms were 2.8 times more likely to report lower satisfaction with their physician than were those with no or mild symptoms (adjusted odds ratio, 2.8; P = .001). They also reported that patients with severe symptoms were more likely to report lower satisfaction (aOR, 2.3; P = .03).

“Patients with moderate or severe depression symptoms were less satisfied with their clinicians, compared with those with no or mild depression symptoms,” they further explained.

Based on the results, the coinvestigators emphasized the importance of bettering the patient experience for those with mental illness given the potential association with improved health outcomes.

“Because depressed patients can be more sensitive to negative communication, the clinician needs to be more conscious about using a positive and supportive communication style,” they recommended.

The authors acknowledged the inadequacy of evaluating clinician performance using patient satisfaction alone. As a result, the findings may not be generalizable to all clinical settings.

The study was funded by the National Psoriasis Foundation. Dr. Armstrong reported financial affiliations with several pharmaceutical companies.

SOURCE: Read C, Armstrong AW. JAMA Dermatol. 2020 May 6. doi: 10.1001/jamadermatol.2020.1054.

The COVID-19 pandemic continues to pose an unprecedented challenge to health care systems worldwide. In addition to the direct impact of the disease itself, there is a growing concern related to ensuring adequate health care utilization and addressing the needs of vulnerable populations, such as those with chronic illness.

Emanuel et al. have advocated a framework of fair allocation of resources, led by the principles of equity, maximizing benefits, and prioritizing the vulnerable. In these uncertain times, patients with rheumatic diseases represent a vulnerable population whose health and wellness are particularly threatened, not only by the risk of COVID-19, but also by reduced access to usual medical care (e.g., in-person clinic visits), potential treatment interruptions (e.g., planned infusion therapies), and the ongoing shortage of hydroxychloroquine, to name a few.

As rheumatologists, we are now tasked with the development of best practices for caring for patients with rheumatic conditions in this uncertain, evolving, and nearly data-free landscape. We also must maintain an active role as advocates for our patients to help them navigate this pandemic. Herein, we discuss our approach to caring for patients with rheumatic diseases within our practice in New York City, an epicenter of the COVID-19 pandemic.

Communication with patients

Maintaining an open line of communication with our patients (by phone, patient portal, telemedicine, and so on) has become more essential than ever. It is through these communications that we best understand our patients’ concerns and provide support and personalized treatment decisions. The most common questions we have received during recent weeks are:

• Should I stop my medication to lower my risk for infection?
• Are my current symptoms caused by coronavirus, and what should I do next?
• Where can I fill my hydroxychloroquine prescription?

The American College of Rheumatology has deployed a number of task forces aimed at advocating for rheumatologists and patients with rheumatic diseases and is doing an exemplary job guiding us. For patients, several other organizations (e.g., CreakyJoints, Arthritis Foundation, Lupus Research Alliance, Vasculitis Foundation, and Scleroderma Foundation) are also providing accurate information regarding hygiene practices, social distancing, management of medications, and other guidance related to specific rheumatic diseases. In line with ACR recommendations, we encourage a personalized, shared decision-making process with each of our patients.

Patients with rheumatic disease at risk for COVID-19 infection

First, for rheumatology patients who have no COVID-19 symptoms, our management approach is individualized. For patients who are able to maintain social distancing, we have not routinely stopped immunosuppressive medications, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents. However, we discuss the risks and benefits of continuing immunosuppressive therapy during this time with all of our patients.

In certain cases of stable, non–life-threatening disease, we may consider spacing or temporarily interrupting immunosuppressive therapy, using individualized, shared decision making. Yet, it is important to recognize that, for some patients, achieving adequate disease control can require a substantial amount of time.

Furthermore, it is important to acknowledge that disease flares requiring steroid therapy may increase the risk for infection even more, keeping in mind that, in some rheumatic diseases, high disease activity itself can increase infection risk. We advise patients who are continuing therapy to maintain at least a 1-month supply of their medications.

Decisions regarding infusions in the hospital and outpatient settings are similarly made on an individual basis, weighing the risk for virus exposure against that of disease flare. The more limited availability of appropriately distanced infusion chairs in some already overburdened systems must be considered in this discussion. We agree with the ACR, whose infusion guidance recommends that “possible changes might include temporary interruption of therapy, temporary initiation of a bridge therapy such as a less potent anti-inflammatory or immune-modulating agent, or temporary change to an alternative therapy.”

We also reinforce recommended behaviors for preventing infection, including social distancing, frequent handwashing, and avoiding touching one’s face.

Patients with rheumatic disease and confirmed or suspected COVID-19 infection

With the worldwide spread of COVID-19, patients with rheumatic diseases will undoubtedly be among those exposed and infected. Though current data are limited, within a cohort from China, 1% had an autoimmune disease. Testing recommendations to confirm COVID-19 and decision guidelines for outpatient versus inpatient management are evolving, and we consult the most up-to-date, local information regarding testing as individual potential cases arise.

For patients who develop COVID-19 and are currently taking DMARDs and biologics, we recommend that they discontinue these medications, with the exception of hydroxychloroquine (HCQ). HCQ may be continued because its mechanism is not expected to worsen infection, and it plays a key role in the management of patients with systemic lupus erythematosus (SLE). In addition, in vitro antiviral effects have been reported and there is growing interest for its use in the management of COVID-19. However, there are conflicting data and methodological concerns about the nonrandomized human studies that suggest a benefit of HCQ against COVID-19.

The decision regarding management of glucocorticoids in the setting of new COVID-19 infection is challenging and should be individualized. At present, expert panels recommend against the use of glucocorticoids among individuals with COVID-19 who do not have acute respiratory distress syndrome. However, adrenal insufficiency must be considered among patients with COVID-19 who are treated with chronic glucocorticoids. Again, these decisions should be made on an individual, case-by-case basis.

Implications of a hydroxychloroquine shortage

The use of HCQ in rheumatology is supported by years of research. Particularly in SLE, HCQ has been shown to reduce disease activity and damage and to improve survival. Furthermore, for pregnant patients with SLE, numerous studies have demonstrated the safety and benefit of HCQ for both the mother and fetus; thus, it is strongly recommended. By contrast, despite the growing interest for HCQ in patients with COVID-19, the evidence is inconclusive and limited.

The ACR suggests that decisions regarding HCQ dose reductions to extend individual patients supplies should be tailored to each patient’s need and risk in the unfortunate setting of medication shortages. Even in patients with stable SLE, however, disease flares at 6 months are more common among individuals who discontinue HCQ. Of note, these flares may incorporate novel and severe disease manifestations.

Unfortunately, other therapeutic options for SLE are associated with more adverse effects (including increased susceptibility to infection) or are largely unavailable (e.g., quinacrine). Thus, we strive to continue standard dosing of HCQ for patients who are currently flaring or recently flared, and we make shared, individualized decisions for those patients with stable disease as the HCQ shortage evolves.

Future research on COVID-19 and rheumatic disease

While we might expect that an underlying rheumatic disease and associated treatments may predispose individuals to developing COVID-19, current data do not indicate which, if any, rheumatic diseases and associated therapies convey the greatest risk.

To address this uncertainty, the rheumatology community created the COVID-19 Global Rheumatology Alliance, an international effort to initiate and maintain a deidentified patient registry for individuals with rheumatic disease who develop COVID-19. These efforts will allow us to gain essential insights regarding which patient demographics, underlying diseases, and medications are most common among patients who develop COVID-19.

This alliance encourages rheumatologists and those caring for patients with rheumatic diseases to report their patient cases to this registry. As we are confronted with making management decisions with a scarcity of supporting data, efforts like these will improve our ability to make individualized treatment recommendations.

The COVID-19 pandemic has presented us all with unprecedented challenges. As rheumatologists, it is our duty to lead our patients through this uncharted territory with close communication, information, advocacy, and personalized treatment decisions. Each of these is central to the management of rheumatology patients during the COVID-19 pandemic.

With the growing interest in immunomodulatory therapies for the complications of this infection, we have the unique opportunity to share our expertise, recommendations, and caution with our colleagues. As clinicians and scientists, we must advocate for data collection and studies that will allow us to develop novel, data-driven disease management approaches while providing the best care possible for our patients.

Stephen Paget, MD, is physician in chief emeritus for the Center for Rheumatology at Hospital for Special Surgery in New York. Kimberly Showalter, MD, is a third-year rheumatology fellow at Hospital for Special Surgery. Sebastian E. Sattui, MD, is a third-year rheumatology and 1-year vasculitis fellow at Hospital for Special Surgery.

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

The COVID-19 pandemic continues to pose an unprecedented challenge to health care systems worldwide. In addition to the direct impact of the disease itself, there is a growing concern related to ensuring adequate health care utilization and addressing the needs of vulnerable populations, such as those with chronic illness.

Emanuel et al. have advocated a framework of fair allocation of resources, led by the principles of equity, maximizing benefits, and prioritizing the vulnerable. In these uncertain times, patients with rheumatic diseases represent a vulnerable population whose health and wellness are particularly threatened, not only by the risk of COVID-19, but also by reduced access to usual medical care (e.g., in-person clinic visits), potential treatment interruptions (e.g., planned infusion therapies), and the ongoing shortage of hydroxychloroquine, to name a few.

As rheumatologists, we are now tasked with the development of best practices for caring for patients with rheumatic conditions in this uncertain, evolving, and nearly data-free landscape. We also must maintain an active role as advocates for our patients to help them navigate this pandemic. Herein, we discuss our approach to caring for patients with rheumatic diseases within our practice in New York City, an epicenter of the COVID-19 pandemic.

Communication with patients

Maintaining an open line of communication with our patients (by phone, patient portal, telemedicine, and so on) has become more essential than ever. It is through these communications that we best understand our patients’ concerns and provide support and personalized treatment decisions. The most common questions we have received during recent weeks are:

• Should I stop my medication to lower my risk for infection?
• Are my current symptoms caused by coronavirus, and what should I do next?
• Where can I fill my hydroxychloroquine prescription?

The American College of Rheumatology has deployed a number of task forces aimed at advocating for rheumatologists and patients with rheumatic diseases and is doing an exemplary job guiding us. For patients, several other organizations (e.g., CreakyJoints, Arthritis Foundation, Lupus Research Alliance, Vasculitis Foundation, and Scleroderma Foundation) are also providing accurate information regarding hygiene practices, social distancing, management of medications, and other guidance related to specific rheumatic diseases. In line with ACR recommendations, we encourage a personalized, shared decision-making process with each of our patients.

Patients with rheumatic disease at risk for COVID-19 infection

First, for rheumatology patients who have no COVID-19 symptoms, our management approach is individualized. For patients who are able to maintain social distancing, we have not routinely stopped immunosuppressive medications, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents. However, we discuss the risks and benefits of continuing immunosuppressive therapy during this time with all of our patients.

In certain cases of stable, non–life-threatening disease, we may consider spacing or temporarily interrupting immunosuppressive therapy, using individualized, shared decision making. Yet, it is important to recognize that, for some patients, achieving adequate disease control can require a substantial amount of time.

Furthermore, it is important to acknowledge that disease flares requiring steroid therapy may increase the risk for infection even more, keeping in mind that, in some rheumatic diseases, high disease activity itself can increase infection risk. We advise patients who are continuing therapy to maintain at least a 1-month supply of their medications.

Decisions regarding infusions in the hospital and outpatient settings are similarly made on an individual basis, weighing the risk for virus exposure against that of disease flare. The more limited availability of appropriately distanced infusion chairs in some already overburdened systems must be considered in this discussion. We agree with the ACR, whose infusion guidance recommends that “possible changes might include temporary interruption of therapy, temporary initiation of a bridge therapy such as a less potent anti-inflammatory or immune-modulating agent, or temporary change to an alternative therapy.”

We also reinforce recommended behaviors for preventing infection, including social distancing, frequent handwashing, and avoiding touching one’s face.

Patients with rheumatic disease and confirmed or suspected COVID-19 infection

With the worldwide spread of COVID-19, patients with rheumatic diseases will undoubtedly be among those exposed and infected. Though current data are limited, within a cohort from China, 1% had an autoimmune disease. Testing recommendations to confirm COVID-19 and decision guidelines for outpatient versus inpatient management are evolving, and we consult the most up-to-date, local information regarding testing as individual potential cases arise.

For patients who develop COVID-19 and are currently taking DMARDs and biologics, we recommend that they discontinue these medications, with the exception of hydroxychloroquine (HCQ). HCQ may be continued because its mechanism is not expected to worsen infection, and it plays a key role in the management of patients with systemic lupus erythematosus (SLE). In addition, in vitro antiviral effects have been reported and there is growing interest for its use in the management of COVID-19. However, there are conflicting data and methodological concerns about the nonrandomized human studies that suggest a benefit of HCQ against COVID-19.

The decision regarding management of glucocorticoids in the setting of new COVID-19 infection is challenging and should be individualized. At present, expert panels recommend against the use of glucocorticoids among individuals with COVID-19 who do not have acute respiratory distress syndrome. However, adrenal insufficiency must be considered among patients with COVID-19 who are treated with chronic glucocorticoids. Again, these decisions should be made on an individual, case-by-case basis.

Implications of a hydroxychloroquine shortage

The use of HCQ in rheumatology is supported by years of research. Particularly in SLE, HCQ has been shown to reduce disease activity and damage and to improve survival. Furthermore, for pregnant patients with SLE, numerous studies have demonstrated the safety and benefit of HCQ for both the mother and fetus; thus, it is strongly recommended. By contrast, despite the growing interest for HCQ in patients with COVID-19, the evidence is inconclusive and limited.

The ACR suggests that decisions regarding HCQ dose reductions to extend individual patients supplies should be tailored to each patient’s need and risk in the unfortunate setting of medication shortages. Even in patients with stable SLE, however, disease flares at 6 months are more common among individuals who discontinue HCQ. Of note, these flares may incorporate novel and severe disease manifestations.

Unfortunately, other therapeutic options for SLE are associated with more adverse effects (including increased susceptibility to infection) or are largely unavailable (e.g., quinacrine). Thus, we strive to continue standard dosing of HCQ for patients who are currently flaring or recently flared, and we make shared, individualized decisions for those patients with stable disease as the HCQ shortage evolves.

Future research on COVID-19 and rheumatic disease

While we might expect that an underlying rheumatic disease and associated treatments may predispose individuals to developing COVID-19, current data do not indicate which, if any, rheumatic diseases and associated therapies convey the greatest risk.

To address this uncertainty, the rheumatology community created the COVID-19 Global Rheumatology Alliance, an international effort to initiate and maintain a deidentified patient registry for individuals with rheumatic disease who develop COVID-19. These efforts will allow us to gain essential insights regarding which patient demographics, underlying diseases, and medications are most common among patients who develop COVID-19.

This alliance encourages rheumatologists and those caring for patients with rheumatic diseases to report their patient cases to this registry. As we are confronted with making management decisions with a scarcity of supporting data, efforts like these will improve our ability to make individualized treatment recommendations.

The COVID-19 pandemic has presented us all with unprecedented challenges. As rheumatologists, it is our duty to lead our patients through this uncharted territory with close communication, information, advocacy, and personalized treatment decisions. Each of these is central to the management of rheumatology patients during the COVID-19 pandemic.

With the growing interest in immunomodulatory therapies for the complications of this infection, we have the unique opportunity to share our expertise, recommendations, and caution with our colleagues. As clinicians and scientists, we must advocate for data collection and studies that will allow us to develop novel, data-driven disease management approaches while providing the best care possible for our patients.

Stephen Paget, MD, is physician in chief emeritus for the Center for Rheumatology at Hospital for Special Surgery in New York. Kimberly Showalter, MD, is a third-year rheumatology fellow at Hospital for Special Surgery. Sebastian E. Sattui, MD, is a third-year rheumatology and 1-year vasculitis fellow at Hospital for Special Surgery.

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

The COVID-19 pandemic continues to pose an unprecedented challenge to health care systems worldwide. In addition to the direct impact of the disease itself, there is a growing concern related to ensuring adequate health care utilization and addressing the needs of vulnerable populations, such as those with chronic illness.

Emanuel et al. have advocated a framework of fair allocation of resources, led by the principles of equity, maximizing benefits, and prioritizing the vulnerable. In these uncertain times, patients with rheumatic diseases represent a vulnerable population whose health and wellness are particularly threatened, not only by the risk of COVID-19, but also by reduced access to usual medical care (e.g., in-person clinic visits), potential treatment interruptions (e.g., planned infusion therapies), and the ongoing shortage of hydroxychloroquine, to name a few.

As rheumatologists, we are now tasked with the development of best practices for caring for patients with rheumatic conditions in this uncertain, evolving, and nearly data-free landscape. We also must maintain an active role as advocates for our patients to help them navigate this pandemic. Herein, we discuss our approach to caring for patients with rheumatic diseases within our practice in New York City, an epicenter of the COVID-19 pandemic.

Communication with patients

Maintaining an open line of communication with our patients (by phone, patient portal, telemedicine, and so on) has become more essential than ever. It is through these communications that we best understand our patients’ concerns and provide support and personalized treatment decisions. The most common questions we have received during recent weeks are:

• Should I stop my medication to lower my risk for infection?
• Are my current symptoms caused by coronavirus, and what should I do next?
• Where can I fill my hydroxychloroquine prescription?

The American College of Rheumatology has deployed a number of task forces aimed at advocating for rheumatologists and patients with rheumatic diseases and is doing an exemplary job guiding us. For patients, several other organizations (e.g., CreakyJoints, Arthritis Foundation, Lupus Research Alliance, Vasculitis Foundation, and Scleroderma Foundation) are also providing accurate information regarding hygiene practices, social distancing, management of medications, and other guidance related to specific rheumatic diseases. In line with ACR recommendations, we encourage a personalized, shared decision-making process with each of our patients.

Patients with rheumatic disease at risk for COVID-19 infection

First, for rheumatology patients who have no COVID-19 symptoms, our management approach is individualized. For patients who are able to maintain social distancing, we have not routinely stopped immunosuppressive medications, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents. However, we discuss the risks and benefits of continuing immunosuppressive therapy during this time with all of our patients.

In certain cases of stable, non–life-threatening disease, we may consider spacing or temporarily interrupting immunosuppressive therapy, using individualized, shared decision making. Yet, it is important to recognize that, for some patients, achieving adequate disease control can require a substantial amount of time.

Furthermore, it is important to acknowledge that disease flares requiring steroid therapy may increase the risk for infection even more, keeping in mind that, in some rheumatic diseases, high disease activity itself can increase infection risk. We advise patients who are continuing therapy to maintain at least a 1-month supply of their medications.

Decisions regarding infusions in the hospital and outpatient settings are similarly made on an individual basis, weighing the risk for virus exposure against that of disease flare. The more limited availability of appropriately distanced infusion chairs in some already overburdened systems must be considered in this discussion. We agree with the ACR, whose infusion guidance recommends that “possible changes might include temporary interruption of therapy, temporary initiation of a bridge therapy such as a less potent anti-inflammatory or immune-modulating agent, or temporary change to an alternative therapy.”

We also reinforce recommended behaviors for preventing infection, including social distancing, frequent handwashing, and avoiding touching one’s face.

Patients with rheumatic disease and confirmed or suspected COVID-19 infection

With the worldwide spread of COVID-19, patients with rheumatic diseases will undoubtedly be among those exposed and infected. Though current data are limited, within a cohort from China, 1% had an autoimmune disease. Testing recommendations to confirm COVID-19 and decision guidelines for outpatient versus inpatient management are evolving, and we consult the most up-to-date, local information regarding testing as individual potential cases arise.

For patients who develop COVID-19 and are currently taking DMARDs and biologics, we recommend that they discontinue these medications, with the exception of hydroxychloroquine (HCQ). HCQ may be continued because its mechanism is not expected to worsen infection, and it plays a key role in the management of patients with systemic lupus erythematosus (SLE). In addition, in vitro antiviral effects have been reported and there is growing interest for its use in the management of COVID-19. However, there are conflicting data and methodological concerns about the nonrandomized human studies that suggest a benefit of HCQ against COVID-19.

The decision regarding management of glucocorticoids in the setting of new COVID-19 infection is challenging and should be individualized. At present, expert panels recommend against the use of glucocorticoids among individuals with COVID-19 who do not have acute respiratory distress syndrome. However, adrenal insufficiency must be considered among patients with COVID-19 who are treated with chronic glucocorticoids. Again, these decisions should be made on an individual, case-by-case basis.

Implications of a hydroxychloroquine shortage

The use of HCQ in rheumatology is supported by years of research. Particularly in SLE, HCQ has been shown to reduce disease activity and damage and to improve survival. Furthermore, for pregnant patients with SLE, numerous studies have demonstrated the safety and benefit of HCQ for both the mother and fetus; thus, it is strongly recommended. By contrast, despite the growing interest for HCQ in patients with COVID-19, the evidence is inconclusive and limited.

The ACR suggests that decisions regarding HCQ dose reductions to extend individual patients supplies should be tailored to each patient’s need and risk in the unfortunate setting of medication shortages. Even in patients with stable SLE, however, disease flares at 6 months are more common among individuals who discontinue HCQ. Of note, these flares may incorporate novel and severe disease manifestations.

Unfortunately, other therapeutic options for SLE are associated with more adverse effects (including increased susceptibility to infection) or are largely unavailable (e.g., quinacrine). Thus, we strive to continue standard dosing of HCQ for patients who are currently flaring or recently flared, and we make shared, individualized decisions for those patients with stable disease as the HCQ shortage evolves.

Future research on COVID-19 and rheumatic disease

While we might expect that an underlying rheumatic disease and associated treatments may predispose individuals to developing COVID-19, current data do not indicate which, if any, rheumatic diseases and associated therapies convey the greatest risk.

To address this uncertainty, the rheumatology community created the COVID-19 Global Rheumatology Alliance, an international effort to initiate and maintain a deidentified patient registry for individuals with rheumatic disease who develop COVID-19. These efforts will allow us to gain essential insights regarding which patient demographics, underlying diseases, and medications are most common among patients who develop COVID-19.

This alliance encourages rheumatologists and those caring for patients with rheumatic diseases to report their patient cases to this registry. As we are confronted with making management decisions with a scarcity of supporting data, efforts like these will improve our ability to make individualized treatment recommendations.

The COVID-19 pandemic has presented us all with unprecedented challenges. As rheumatologists, it is our duty to lead our patients through this uncharted territory with close communication, information, advocacy, and personalized treatment decisions. Each of these is central to the management of rheumatology patients during the COVID-19 pandemic.

With the growing interest in immunomodulatory therapies for the complications of this infection, we have the unique opportunity to share our expertise, recommendations, and caution with our colleagues. As clinicians and scientists, we must advocate for data collection and studies that will allow us to develop novel, data-driven disease management approaches while providing the best care possible for our patients.

Stephen Paget, MD, is physician in chief emeritus for the Center for Rheumatology at Hospital for Special Surgery in New York. Kimberly Showalter, MD, is a third-year rheumatology fellow at Hospital for Special Surgery. Sebastian E. Sattui, MD, is a third-year rheumatology and 1-year vasculitis fellow at Hospital for Special Surgery.

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

When COVID-19 is suspected or confirmed in a patient with a rheumatic disease, treatment with hydroxychloroquine may be continued, but other treatments may need to be stopped or held temporarily, according to new guidance issued by the American College of Rheumatology.

That includes disease-modifying treatment with antirheumatic drugs such as sulfasalazine, methotrexate, leflunomide, and the Janus kinase (JAK) inhibitors, as well as immunosuppressants and non-interleukin (IL)-6 biologics, and this is regardless of how severe the COVID-19 illness is. NSAIDs should also be stopped if there are respiratory symptoms.

The advice is slightly less drastic if someone with stable rheumatic disease has probably been exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or are asymptomatic. In those patients, DMARDs may be continued, although there is uncertainty over whether there is a need to temporarily stop methotrexate or leflunomide. Interruption of immunosuppressive, non–IL-6, and JAK inhibitor treatment is advised pending a negative SARS-CoV-2 test result, assuming the patient’s rheumatic disease is stable.
 

Impetus for ACR COVID-19 guidance

“One of the earliest challenges for rheumatologists during the COVID-19 pandemic was determining how to advise our patients who were taking immunosuppressive medications and were concerned as to whether or not to discontinue their therapy,” ACR President Ellen Gravallese, MD, said in an interview about the ACR Clinical Guidance Document, which is published online in Arthritis & Rheumatology.

“A second challenge was keeping our patients safe from exposure to the virus, while still seeing those patients in person who required office visits,” added Dr. Gravallese, who is chief of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital in Boston.

She continued: “The ACR Clinical Guidance Document was prepared in order to assist rheumatologists with decisions as to how to handle current medications during different phases of a patient’s exposure to the SARS-CoV-2 virus.”

But with very little evidence available on how to manage COVID-19 patients generally, let alone specifically in those with rheumatic diseases, “it became evident that any recommendations made would need to be done in a thoughtful and organized manner, evaluating the evidence that was available and obtaining the advice of experts in infectious disease, epidemiology, and in the use of biologic and nonbiologic agents for rheumatic disease,” she said.

As such, the ACR convened a task force of 10 rheumatologists and 4 infectious disease specialists from North America to look at how best to manage patients with rheumatic disease during the COVID-19 pandemic.

“Our charge was to develop a guidance document for the care of adult rheumatic disease patients in the context of COVID-19 and not per se to provide guidance for the treatment of COVID-19,” explained task force member and the corresponding author for the guidance, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center, Omaha.

Dr. Mikuls, who was speaking at a virtual town hall meeting hosted by the ACR on May 6, noted that the guidance was obviously based on the best consensus of the available data and as such represented a “living document” that “would change and be added to” as necessary.
 

General recommendations for adult rheumatic disease management

In terms of general recommendations for the management of adult rheumatic disease patients, Dr. Mikuls said that six statements had been made “specific to risk assessment, prevention of infection, and best practices related to glucocorticoid use and the use of ACE [angiotensin-converting enzyme] inhibitors and ARBs [angiotensin II receptor blockers] during the pandemic.”

For example, general advice is to counsel patients to keep up general preventive measures such as social distancing and regular hand washing, reducing the number of in-person health care visits, and undertaking other means to try to prevent potential SARS-CoV-2 exposure. As for general treatment advice, glucocorticoids should be used at their lowest doses possible and should not be abruptly stopped, and antihypertensive treatment should be used as indicated.

Additional guidance statements include those that address the treatment of patients with stable rheumatic disease in the absence of infection or known exposure to SARS-CoV-2, with guidance specific to the treatment of systemic lupus erythematosus (SLE), and those with newly diagnosed or active rheumatic disease.
 

SLE and inflammatory arthritis recommendations

“There are several sections within the guidance document that address the treatment of patients with systemic lupus erythematosus during this pandemic,” Dr. Gravallese pointed out. “In general, it is recommended that lupus patients who are currently taking hydroxychloroquine can remain on the therapy prior to and during infection and that newly diagnosed patients with lupus can be placed on this medication at full dose. It is recommended that pregnant patients with lupus remain on therapy with this drug.”

She also observed that, for the treatment of active inflammatory arthritis, “the recommendations were written to address specific medications that could be used in this setting. In general, the task force recommendations were guided by the importance of controlling inflammation prior to exposure to the virus, even during this pandemic.
 

Guidance raises questions

During the ACR’s town hall meeting, the task force answered several questions raised by the guidance, such as the reasoning behind recommending that the use of traditional DMARDs be discontinued in patients with confirmed SARS-CoV-2 infection.

Dr. Mikuls observed: “Maybe if you just read the guidance statements it isn’t terribly intuitive.” There was a lot of discussion about whether or not conventional DMARDs were immunosuppressive, and even though they may not have such effects, it was decided to err on the side of caution.

“I think the task force felt that, with a COVID-19–positive patient, there is a concern of potentially confusing adverse effects related to medicines or conflate those with problems from the infection,” he said. Although rare, examples of those issues could be drug-induced hypersensitivity, hypersensitivity pneumonitis, or gastrointestinal side effects of hepatitis, all of which have been described in COVID-19. “Not only could it cause confusion, but it could maybe worsen those sequalae of COVID-19,” he said.

“I think the other part of this answer was that the panel really felt that the risk in terms of the flaring of the underlying rheumatic disease was likely to be pretty low given the finite time frame you’d be taking about – usually a time frame of 2-3 weeks you’d be holding the agent – so I think that is really why the task force ended up with that recommendation.”

Similarly, for the JAK inhibitors, the decision was to err on the side of caution when COVID-19 was suspected or confirmed. “Not so much because of the risk of thromboembolic disease, but concerns over immunosuppression that these drugs carry with them and also the fact the JAK inhibitors are probably inhibitors of type 1 interferons, which play a significant role in viral immunity and could potentially have a negative impact,” said Stanley Cohen, MD, who practices rheumatology in the Dallas area.

“On the flipside, there is interest in some of the JAK inhibitors as a potential treatment for COVID-19,” Dr. Cohen said, referring to anecdotal evidence for baricitinib (Olumiant).

Michael Weinblatt, MD, of Brigham and Women’s Hospital, addressed the recent concern over the use of NSAIDs by the public.

“There’s been a lot in the lay press that NSAIDs – because of the effects on receptors in the lung – could lead to deleterious outcomes in patients with COVID and there’s very little data to support this.

“We did recommend that NSAIDs be held in the hospitalized patient and that wasn’t because of the COVID-19 issue, it really was just medical practice, and we didn’t want to confound the care of these really sick patients with potential toxicities from NSAIDs. But as far as routine rheumatological care in your outpatients, we did not recommend that nonsteroidals be stopped if they were tolerated.”

One part of the guidance that might already need revision is the recommendation on the continued use of hydroxychloroquine in patients who develop COVID-19.

“Our guidance document says it’s OK; we were all in very strong agreement to continue hydroxychloroquine in our patients with COVID-19 because at that point, just a couple of weeks ago, we thought it was part of the potential treatment,” Karen Costenbader, MD, MPH, of Brigham and Women’s Hospital, said during the town hall meeting.

“Now the pendulum has swung the other way, and we’re worried about maybe we shouldn’t be continuing it because COVID-19 patients will be getting many other medications,” Dr. Costenbader said, and these may affect the QT-interval. “They will not be getting azithromycin because the pendulum swung the other way on that one too, but definitely on many other medications when they are sick.”

Potentially, she added, “if the rheumatic disease is under good control the inpatient physicians could decide whether they should continue [hydroxychloroquine] or not. If the COVID-19 is a mild disease, I would say we probably could continue in accordance with what we put in the document, but we will have to revisit this as well.”
 

Guidance is a ‘living document’

“We will be providing updates to the Clinical Guidance Document as the need arises,” Dr. Gravallese emphasized. While the general recommendations are unlikely to change very much, “the task force will be interested in seeing the results of all new data, but the results of randomized, clinical trials will be particularly important as they become available,” she said. In particular, randomized, controlled trials of glucocorticoids and IL-6 receptor blockade for use in COVID-19 will be of great importance.

“In this initial document, we could not take on all of the medical scenarios our members will face. For example, we could not take on recommendations for the pediatric population as this group of patients has a very different response than adults to the SARS-CoV-2 virus,” Dr. Gravallese acknowledged. The plan is to provide guidance for that group of patients soon.

In addition, the ACR Executive Committee has appointed a Practice and Advocacy Task Force that will “address issues rheumatologists face on the practice side, including advice regarding how to effectively use telemedicine, address the frequency and safety of infusions, determine urgent versus nonurgent issues that would or would not require face-to-face visits, and help with financial challenges.”

The American College of Rheumatology supported the guidance-development process. Dr. Mikuls, Dr. Weinblatt, Dr. Cohen, and Dr. Costenbader each disclosed research support or consultancies with multiple pharmaceutical companies. Dr. Gravallese had no disclosures.

SOURCE: Mikuls TR et al. Arthritis Rheumatol. 2020 Apr 29. doi: 10.1002/art.41301.

When COVID-19 is suspected or confirmed in a patient with a rheumatic disease, treatment with hydroxychloroquine may be continued, but other treatments may need to be stopped or held temporarily, according to new guidance issued by the American College of Rheumatology.

That includes disease-modifying treatment with antirheumatic drugs such as sulfasalazine, methotrexate, leflunomide, and the Janus kinase (JAK) inhibitors, as well as immunosuppressants and non-interleukin (IL)-6 biologics, and this is regardless of how severe the COVID-19 illness is. NSAIDs should also be stopped if there are respiratory symptoms.

The advice is slightly less drastic if someone with stable rheumatic disease has probably been exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or are asymptomatic. In those patients, DMARDs may be continued, although there is uncertainty over whether there is a need to temporarily stop methotrexate or leflunomide. Interruption of immunosuppressive, non–IL-6, and JAK inhibitor treatment is advised pending a negative SARS-CoV-2 test result, assuming the patient’s rheumatic disease is stable.
 

Impetus for ACR COVID-19 guidance

“One of the earliest challenges for rheumatologists during the COVID-19 pandemic was determining how to advise our patients who were taking immunosuppressive medications and were concerned as to whether or not to discontinue their therapy,” ACR President Ellen Gravallese, MD, said in an interview about the ACR Clinical Guidance Document, which is published online in Arthritis & Rheumatology.

“A second challenge was keeping our patients safe from exposure to the virus, while still seeing those patients in person who required office visits,” added Dr. Gravallese, who is chief of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital in Boston.

She continued: “The ACR Clinical Guidance Document was prepared in order to assist rheumatologists with decisions as to how to handle current medications during different phases of a patient’s exposure to the SARS-CoV-2 virus.”

But with very little evidence available on how to manage COVID-19 patients generally, let alone specifically in those with rheumatic diseases, “it became evident that any recommendations made would need to be done in a thoughtful and organized manner, evaluating the evidence that was available and obtaining the advice of experts in infectious disease, epidemiology, and in the use of biologic and nonbiologic agents for rheumatic disease,” she said.

As such, the ACR convened a task force of 10 rheumatologists and 4 infectious disease specialists from North America to look at how best to manage patients with rheumatic disease during the COVID-19 pandemic.

“Our charge was to develop a guidance document for the care of adult rheumatic disease patients in the context of COVID-19 and not per se to provide guidance for the treatment of COVID-19,” explained task force member and the corresponding author for the guidance, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center, Omaha.

Dr. Mikuls, who was speaking at a virtual town hall meeting hosted by the ACR on May 6, noted that the guidance was obviously based on the best consensus of the available data and as such represented a “living document” that “would change and be added to” as necessary.
 

General recommendations for adult rheumatic disease management

In terms of general recommendations for the management of adult rheumatic disease patients, Dr. Mikuls said that six statements had been made “specific to risk assessment, prevention of infection, and best practices related to glucocorticoid use and the use of ACE [angiotensin-converting enzyme] inhibitors and ARBs [angiotensin II receptor blockers] during the pandemic.”

For example, general advice is to counsel patients to keep up general preventive measures such as social distancing and regular hand washing, reducing the number of in-person health care visits, and undertaking other means to try to prevent potential SARS-CoV-2 exposure. As for general treatment advice, glucocorticoids should be used at their lowest doses possible and should not be abruptly stopped, and antihypertensive treatment should be used as indicated.

Additional guidance statements include those that address the treatment of patients with stable rheumatic disease in the absence of infection or known exposure to SARS-CoV-2, with guidance specific to the treatment of systemic lupus erythematosus (SLE), and those with newly diagnosed or active rheumatic disease.
 

SLE and inflammatory arthritis recommendations

“There are several sections within the guidance document that address the treatment of patients with systemic lupus erythematosus during this pandemic,” Dr. Gravallese pointed out. “In general, it is recommended that lupus patients who are currently taking hydroxychloroquine can remain on the therapy prior to and during infection and that newly diagnosed patients with lupus can be placed on this medication at full dose. It is recommended that pregnant patients with lupus remain on therapy with this drug.”

She also observed that, for the treatment of active inflammatory arthritis, “the recommendations were written to address specific medications that could be used in this setting. In general, the task force recommendations were guided by the importance of controlling inflammation prior to exposure to the virus, even during this pandemic.
 

Guidance raises questions

During the ACR’s town hall meeting, the task force answered several questions raised by the guidance, such as the reasoning behind recommending that the use of traditional DMARDs be discontinued in patients with confirmed SARS-CoV-2 infection.

Dr. Mikuls observed: “Maybe if you just read the guidance statements it isn’t terribly intuitive.” There was a lot of discussion about whether or not conventional DMARDs were immunosuppressive, and even though they may not have such effects, it was decided to err on the side of caution.

“I think the task force felt that, with a COVID-19–positive patient, there is a concern of potentially confusing adverse effects related to medicines or conflate those with problems from the infection,” he said. Although rare, examples of those issues could be drug-induced hypersensitivity, hypersensitivity pneumonitis, or gastrointestinal side effects of hepatitis, all of which have been described in COVID-19. “Not only could it cause confusion, but it could maybe worsen those sequalae of COVID-19,” he said.

“I think the other part of this answer was that the panel really felt that the risk in terms of the flaring of the underlying rheumatic disease was likely to be pretty low given the finite time frame you’d be taking about – usually a time frame of 2-3 weeks you’d be holding the agent – so I think that is really why the task force ended up with that recommendation.”

Similarly, for the JAK inhibitors, the decision was to err on the side of caution when COVID-19 was suspected or confirmed. “Not so much because of the risk of thromboembolic disease, but concerns over immunosuppression that these drugs carry with them and also the fact the JAK inhibitors are probably inhibitors of type 1 interferons, which play a significant role in viral immunity and could potentially have a negative impact,” said Stanley Cohen, MD, who practices rheumatology in the Dallas area.

“On the flipside, there is interest in some of the JAK inhibitors as a potential treatment for COVID-19,” Dr. Cohen said, referring to anecdotal evidence for baricitinib (Olumiant).

Michael Weinblatt, MD, of Brigham and Women’s Hospital, addressed the recent concern over the use of NSAIDs by the public.

“There’s been a lot in the lay press that NSAIDs – because of the effects on receptors in the lung – could lead to deleterious outcomes in patients with COVID and there’s very little data to support this.

“We did recommend that NSAIDs be held in the hospitalized patient and that wasn’t because of the COVID-19 issue, it really was just medical practice, and we didn’t want to confound the care of these really sick patients with potential toxicities from NSAIDs. But as far as routine rheumatological care in your outpatients, we did not recommend that nonsteroidals be stopped if they were tolerated.”

One part of the guidance that might already need revision is the recommendation on the continued use of hydroxychloroquine in patients who develop COVID-19.

“Our guidance document says it’s OK; we were all in very strong agreement to continue hydroxychloroquine in our patients with COVID-19 because at that point, just a couple of weeks ago, we thought it was part of the potential treatment,” Karen Costenbader, MD, MPH, of Brigham and Women’s Hospital, said during the town hall meeting.

“Now the pendulum has swung the other way, and we’re worried about maybe we shouldn’t be continuing it because COVID-19 patients will be getting many other medications,” Dr. Costenbader said, and these may affect the QT-interval. “They will not be getting azithromycin because the pendulum swung the other way on that one too, but definitely on many other medications when they are sick.”

Potentially, she added, “if the rheumatic disease is under good control the inpatient physicians could decide whether they should continue [hydroxychloroquine] or not. If the COVID-19 is a mild disease, I would say we probably could continue in accordance with what we put in the document, but we will have to revisit this as well.”
 

Guidance is a ‘living document’

“We will be providing updates to the Clinical Guidance Document as the need arises,” Dr. Gravallese emphasized. While the general recommendations are unlikely to change very much, “the task force will be interested in seeing the results of all new data, but the results of randomized, clinical trials will be particularly important as they become available,” she said. In particular, randomized, controlled trials of glucocorticoids and IL-6 receptor blockade for use in COVID-19 will be of great importance.

“In this initial document, we could not take on all of the medical scenarios our members will face. For example, we could not take on recommendations for the pediatric population as this group of patients has a very different response than adults to the SARS-CoV-2 virus,” Dr. Gravallese acknowledged. The plan is to provide guidance for that group of patients soon.

In addition, the ACR Executive Committee has appointed a Practice and Advocacy Task Force that will “address issues rheumatologists face on the practice side, including advice regarding how to effectively use telemedicine, address the frequency and safety of infusions, determine urgent versus nonurgent issues that would or would not require face-to-face visits, and help with financial challenges.”

The American College of Rheumatology supported the guidance-development process. Dr. Mikuls, Dr. Weinblatt, Dr. Cohen, and Dr. Costenbader each disclosed research support or consultancies with multiple pharmaceutical companies. Dr. Gravallese had no disclosures.

SOURCE: Mikuls TR et al. Arthritis Rheumatol. 2020 Apr 29. doi: 10.1002/art.41301.

When COVID-19 is suspected or confirmed in a patient with a rheumatic disease, treatment with hydroxychloroquine may be continued, but other treatments may need to be stopped or held temporarily, according to new guidance issued by the American College of Rheumatology.

That includes disease-modifying treatment with antirheumatic drugs such as sulfasalazine, methotrexate, leflunomide, and the Janus kinase (JAK) inhibitors, as well as immunosuppressants and non-interleukin (IL)-6 biologics, and this is regardless of how severe the COVID-19 illness is. NSAIDs should also be stopped if there are respiratory symptoms.

The advice is slightly less drastic if someone with stable rheumatic disease has probably been exposed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or are asymptomatic. In those patients, DMARDs may be continued, although there is uncertainty over whether there is a need to temporarily stop methotrexate or leflunomide. Interruption of immunosuppressive, non–IL-6, and JAK inhibitor treatment is advised pending a negative SARS-CoV-2 test result, assuming the patient’s rheumatic disease is stable.
 

Impetus for ACR COVID-19 guidance

“One of the earliest challenges for rheumatologists during the COVID-19 pandemic was determining how to advise our patients who were taking immunosuppressive medications and were concerned as to whether or not to discontinue their therapy,” ACR President Ellen Gravallese, MD, said in an interview about the ACR Clinical Guidance Document, which is published online in Arthritis & Rheumatology.

“A second challenge was keeping our patients safe from exposure to the virus, while still seeing those patients in person who required office visits,” added Dr. Gravallese, who is chief of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital in Boston.

She continued: “The ACR Clinical Guidance Document was prepared in order to assist rheumatologists with decisions as to how to handle current medications during different phases of a patient’s exposure to the SARS-CoV-2 virus.”

But with very little evidence available on how to manage COVID-19 patients generally, let alone specifically in those with rheumatic diseases, “it became evident that any recommendations made would need to be done in a thoughtful and organized manner, evaluating the evidence that was available and obtaining the advice of experts in infectious disease, epidemiology, and in the use of biologic and nonbiologic agents for rheumatic disease,” she said.

As such, the ACR convened a task force of 10 rheumatologists and 4 infectious disease specialists from North America to look at how best to manage patients with rheumatic disease during the COVID-19 pandemic.

“Our charge was to develop a guidance document for the care of adult rheumatic disease patients in the context of COVID-19 and not per se to provide guidance for the treatment of COVID-19,” explained task force member and the corresponding author for the guidance, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center, Omaha.

Dr. Mikuls, who was speaking at a virtual town hall meeting hosted by the ACR on May 6, noted that the guidance was obviously based on the best consensus of the available data and as such represented a “living document” that “would change and be added to” as necessary.
 

General recommendations for adult rheumatic disease management

In terms of general recommendations for the management of adult rheumatic disease patients, Dr. Mikuls said that six statements had been made “specific to risk assessment, prevention of infection, and best practices related to glucocorticoid use and the use of ACE [angiotensin-converting enzyme] inhibitors and ARBs [angiotensin II receptor blockers] during the pandemic.”

For example, general advice is to counsel patients to keep up general preventive measures such as social distancing and regular hand washing, reducing the number of in-person health care visits, and undertaking other means to try to prevent potential SARS-CoV-2 exposure. As for general treatment advice, glucocorticoids should be used at their lowest doses possible and should not be abruptly stopped, and antihypertensive treatment should be used as indicated.

Additional guidance statements include those that address the treatment of patients with stable rheumatic disease in the absence of infection or known exposure to SARS-CoV-2, with guidance specific to the treatment of systemic lupus erythematosus (SLE), and those with newly diagnosed or active rheumatic disease.
 

SLE and inflammatory arthritis recommendations

“There are several sections within the guidance document that address the treatment of patients with systemic lupus erythematosus during this pandemic,” Dr. Gravallese pointed out. “In general, it is recommended that lupus patients who are currently taking hydroxychloroquine can remain on the therapy prior to and during infection and that newly diagnosed patients with lupus can be placed on this medication at full dose. It is recommended that pregnant patients with lupus remain on therapy with this drug.”

She also observed that, for the treatment of active inflammatory arthritis, “the recommendations were written to address specific medications that could be used in this setting. In general, the task force recommendations were guided by the importance of controlling inflammation prior to exposure to the virus, even during this pandemic.
 

Guidance raises questions

During the ACR’s town hall meeting, the task force answered several questions raised by the guidance, such as the reasoning behind recommending that the use of traditional DMARDs be discontinued in patients with confirmed SARS-CoV-2 infection.

Dr. Mikuls observed: “Maybe if you just read the guidance statements it isn’t terribly intuitive.” There was a lot of discussion about whether or not conventional DMARDs were immunosuppressive, and even though they may not have such effects, it was decided to err on the side of caution.

“I think the task force felt that, with a COVID-19–positive patient, there is a concern of potentially confusing adverse effects related to medicines or conflate those with problems from the infection,” he said. Although rare, examples of those issues could be drug-induced hypersensitivity, hypersensitivity pneumonitis, or gastrointestinal side effects of hepatitis, all of which have been described in COVID-19. “Not only could it cause confusion, but it could maybe worsen those sequalae of COVID-19,” he said.

“I think the other part of this answer was that the panel really felt that the risk in terms of the flaring of the underlying rheumatic disease was likely to be pretty low given the finite time frame you’d be taking about – usually a time frame of 2-3 weeks you’d be holding the agent – so I think that is really why the task force ended up with that recommendation.”

Similarly, for the JAK inhibitors, the decision was to err on the side of caution when COVID-19 was suspected or confirmed. “Not so much because of the risk of thromboembolic disease, but concerns over immunosuppression that these drugs carry with them and also the fact the JAK inhibitors are probably inhibitors of type 1 interferons, which play a significant role in viral immunity and could potentially have a negative impact,” said Stanley Cohen, MD, who practices rheumatology in the Dallas area.

“On the flipside, there is interest in some of the JAK inhibitors as a potential treatment for COVID-19,” Dr. Cohen said, referring to anecdotal evidence for baricitinib (Olumiant).

Michael Weinblatt, MD, of Brigham and Women’s Hospital, addressed the recent concern over the use of NSAIDs by the public.

“There’s been a lot in the lay press that NSAIDs – because of the effects on receptors in the lung – could lead to deleterious outcomes in patients with COVID and there’s very little data to support this.

“We did recommend that NSAIDs be held in the hospitalized patient and that wasn’t because of the COVID-19 issue, it really was just medical practice, and we didn’t want to confound the care of these really sick patients with potential toxicities from NSAIDs. But as far as routine rheumatological care in your outpatients, we did not recommend that nonsteroidals be stopped if they were tolerated.”

One part of the guidance that might already need revision is the recommendation on the continued use of hydroxychloroquine in patients who develop COVID-19.

“Our guidance document says it’s OK; we were all in very strong agreement to continue hydroxychloroquine in our patients with COVID-19 because at that point, just a couple of weeks ago, we thought it was part of the potential treatment,” Karen Costenbader, MD, MPH, of Brigham and Women’s Hospital, said during the town hall meeting.

“Now the pendulum has swung the other way, and we’re worried about maybe we shouldn’t be continuing it because COVID-19 patients will be getting many other medications,” Dr. Costenbader said, and these may affect the QT-interval. “They will not be getting azithromycin because the pendulum swung the other way on that one too, but definitely on many other medications when they are sick.”

Potentially, she added, “if the rheumatic disease is under good control the inpatient physicians could decide whether they should continue [hydroxychloroquine] or not. If the COVID-19 is a mild disease, I would say we probably could continue in accordance with what we put in the document, but we will have to revisit this as well.”
 

Guidance is a ‘living document’

“We will be providing updates to the Clinical Guidance Document as the need arises,” Dr. Gravallese emphasized. While the general recommendations are unlikely to change very much, “the task force will be interested in seeing the results of all new data, but the results of randomized, clinical trials will be particularly important as they become available,” she said. In particular, randomized, controlled trials of glucocorticoids and IL-6 receptor blockade for use in COVID-19 will be of great importance.

“In this initial document, we could not take on all of the medical scenarios our members will face. For example, we could not take on recommendations for the pediatric population as this group of patients has a very different response than adults to the SARS-CoV-2 virus,” Dr. Gravallese acknowledged. The plan is to provide guidance for that group of patients soon.

In addition, the ACR Executive Committee has appointed a Practice and Advocacy Task Force that will “address issues rheumatologists face on the practice side, including advice regarding how to effectively use telemedicine, address the frequency and safety of infusions, determine urgent versus nonurgent issues that would or would not require face-to-face visits, and help with financial challenges.”

The American College of Rheumatology supported the guidance-development process. Dr. Mikuls, Dr. Weinblatt, Dr. Cohen, and Dr. Costenbader each disclosed research support or consultancies with multiple pharmaceutical companies. Dr. Gravallese had no disclosures.

SOURCE: Mikuls TR et al. Arthritis Rheumatol. 2020 Apr 29. doi: 10.1002/art.41301.

Ustekinumab or a tumor necrosis factor inhibitor (TNFi) are better used alone than with methotrexate in the treatment of psoriatic arthritis suggest the results of PsABio (A Study on Assessment of STELARA and Tumor Necrosis Factor Alpha Inhibitor Therapies in Participants With Psoriatic Arthritis), a large, ongoing, prospective observational study.

The percentages of patients achieving multiple psoriatic arthritis disease activity outcome measures at 6 months were higher if biologic monotherapy was used rather than a biologic in combination with methotrexate.

For example, minimal disease activity (MDA) was achieved by 27.5% of patients taking ustekinumab as monotherapy and by 32.1% of those taking a TNFi alone. When methotrexate was used in combination, the respective percentages of patients achieving MDA were 23.7% and 27.8%.

A similar pattern was seen for very-low disease activity (VLDA), with 9.8% of patients in the ustekinumab monotherapy arm and 12% of those in the TNFi monotherapy arm achieving this target, compared with 5.7% and 5.4% when these drugs were combined with methotrexate.

MDA is defined as meeting five or more cutoffs for seven domains of disease activity, and VLDA for all seven: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area Severity Index 1 or less or body surface area involved 3% or less, 0-1 tender entheseal points, Health Assessment Questionnaire score of 0.5 or less, patient global disease activity visual analog scale score of 20 or lower, and patient pain visual analog scale score of 15 or lower.

Other outcome measures used that showed no advantage of adding methotrexate to these biologics were the Clinical Disease Activity in Psoriatic Arthritis low disease activity and remission scores, the patient acceptable symptoms rate of the 12-item Psoriatic Arthritis Impact of Disease Questionnaire, and improvement in skin involvement.

“Patients were no more likely to achieve lower disease activity or a remission target having received methotrexate than they did just on the biologic drug on its own,” Stefan Siebert, MBBCh, PhD, one of the PsABio investigators, said in an interview.

Dr. Siebert, who is clinical senior lecturer in inflammation and rheumatology at the University of Glasgow (Scotland), was scheduled to present the findings at the British Society for Rheumatology annual conference. The meeting was canceled because of the ongoing COVID-19 crisis. Abstracts and ePosters from the meeting have since been released in a supplement to Rheumatology and via the BSR’s conference app.
 

First data for ustekinumab

“There certainly doesn’t appear to be any added benefit from using methotrexate on a group level in patients getting ustekinumab and TNF inhibitors,” Dr. Siebert said. “We’ve looked at everything,” he emphasized, and “none of the single domains or composite measures were improved by the addition of methotrexate. I think we knew that for TNF inhibitors, but the key thing is we’ve never known that for ustekinumab, and this is the first study to show that.”

Indeed, the findings match up with those from the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study in which patients who were treated with the TNFi etanercept as monotherapy did much better than those given the TNFi in combination with methotrexate or methotrexate alone. While not a randomized trial, PsABio now shows that the same is true for ustekinumab.

Obviously, there are some clear differences between a clinical trial and an observational study such as PsABio. For one thing, there was no randomization and patients taking methotrexate were presumably doing so for good reason, Dr. Siebert said. Secondly, there was no methotrexate-only arm.

PsABio recruited patients who were starting treatment with either ustekinumab or a new TNFi as first-, second-, or third-line biologic disease-modifying antirheumatic therapy (DMARD). “These are all people starting on a biologic, so they’ve already got severe disease and have failed methotrexate on some level. So everything we’ve done is biologic without methotrexate or biologic with methotrexate,” Dr. Siebert explained. Patients may not have been taking methotrexate for a variety of reasons, such as inefficacy or side effects, so PsABio “doesn’t tell us anything about methotrexate on its own.”

Time to rethink ingrained methotrexate use

The rationale for using methotrexate in combination with biologics in psoriatic arthritis comes from its long-standing use in rheumatoid arthritis. Much of what is advocated in guidelines comes from experience in RA, Dr. Siebert said.

“In rheumatoid arthritis, we know that the TNF inhibitors work much better if you use methotrexate, that’s a given,” he noted. “We’ve been trained that you have to have methotrexate to have a biologic. However, PsABio, together with other studies, show that you don’t have to, and you should have a good reason to add methotrexate.”

Individual patients may still benefit from methotrexate use, but the decision to treat all patients the same is not supported by the current evidence. “It’s good that it shows that, actually, once you get someone on a decent biologic, it’s working: It’s doing what it ‘says on the tin’ for a lot of patients. I really think that is the key message, here, that you don’t have to; this reassures clinicians and actually makes them think ‘should this patient be on methotrexate?’ ” Dr. Siebert said.

The PsABio study was funded by Janssen. Dr. Siebert has acted as a consultant to and received research funding from Janssen, UCB, Pfizer, Boehringer Ingelheim, Novartis, and Celgene. He has also acted as a consultant for AbbVie and received research support from Bristol-Myers Squibb.

SOURCE: Siebert S et al. Rheumatology. 2020;59(Suppl 2). doi: 10.1093/rheumatology/keaa110.023, Abstract O24.

Ustekinumab or a tumor necrosis factor inhibitor (TNFi) are better used alone than with methotrexate in the treatment of psoriatic arthritis suggest the results of PsABio (A Study on Assessment of STELARA and Tumor Necrosis Factor Alpha Inhibitor Therapies in Participants With Psoriatic Arthritis), a large, ongoing, prospective observational study.

The percentages of patients achieving multiple psoriatic arthritis disease activity outcome measures at 6 months were higher if biologic monotherapy was used rather than a biologic in combination with methotrexate.

For example, minimal disease activity (MDA) was achieved by 27.5% of patients taking ustekinumab as monotherapy and by 32.1% of those taking a TNFi alone. When methotrexate was used in combination, the respective percentages of patients achieving MDA were 23.7% and 27.8%.

A similar pattern was seen for very-low disease activity (VLDA), with 9.8% of patients in the ustekinumab monotherapy arm and 12% of those in the TNFi monotherapy arm achieving this target, compared with 5.7% and 5.4% when these drugs were combined with methotrexate.

MDA is defined as meeting five or more cutoffs for seven domains of disease activity, and VLDA for all seven: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area Severity Index 1 or less or body surface area involved 3% or less, 0-1 tender entheseal points, Health Assessment Questionnaire score of 0.5 or less, patient global disease activity visual analog scale score of 20 or lower, and patient pain visual analog scale score of 15 or lower.

Other outcome measures used that showed no advantage of adding methotrexate to these biologics were the Clinical Disease Activity in Psoriatic Arthritis low disease activity and remission scores, the patient acceptable symptoms rate of the 12-item Psoriatic Arthritis Impact of Disease Questionnaire, and improvement in skin involvement.

“Patients were no more likely to achieve lower disease activity or a remission target having received methotrexate than they did just on the biologic drug on its own,” Stefan Siebert, MBBCh, PhD, one of the PsABio investigators, said in an interview.

Dr. Siebert, who is clinical senior lecturer in inflammation and rheumatology at the University of Glasgow (Scotland), was scheduled to present the findings at the British Society for Rheumatology annual conference. The meeting was canceled because of the ongoing COVID-19 crisis. Abstracts and ePosters from the meeting have since been released in a supplement to Rheumatology and via the BSR’s conference app.
 

First data for ustekinumab

“There certainly doesn’t appear to be any added benefit from using methotrexate on a group level in patients getting ustekinumab and TNF inhibitors,” Dr. Siebert said. “We’ve looked at everything,” he emphasized, and “none of the single domains or composite measures were improved by the addition of methotrexate. I think we knew that for TNF inhibitors, but the key thing is we’ve never known that for ustekinumab, and this is the first study to show that.”

Indeed, the findings match up with those from the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study in which patients who were treated with the TNFi etanercept as monotherapy did much better than those given the TNFi in combination with methotrexate or methotrexate alone. While not a randomized trial, PsABio now shows that the same is true for ustekinumab.

Obviously, there are some clear differences between a clinical trial and an observational study such as PsABio. For one thing, there was no randomization and patients taking methotrexate were presumably doing so for good reason, Dr. Siebert said. Secondly, there was no methotrexate-only arm.

PsABio recruited patients who were starting treatment with either ustekinumab or a new TNFi as first-, second-, or third-line biologic disease-modifying antirheumatic therapy (DMARD). “These are all people starting on a biologic, so they’ve already got severe disease and have failed methotrexate on some level. So everything we’ve done is biologic without methotrexate or biologic with methotrexate,” Dr. Siebert explained. Patients may not have been taking methotrexate for a variety of reasons, such as inefficacy or side effects, so PsABio “doesn’t tell us anything about methotrexate on its own.”

Time to rethink ingrained methotrexate use

The rationale for using methotrexate in combination with biologics in psoriatic arthritis comes from its long-standing use in rheumatoid arthritis. Much of what is advocated in guidelines comes from experience in RA, Dr. Siebert said.

“In rheumatoid arthritis, we know that the TNF inhibitors work much better if you use methotrexate, that’s a given,” he noted. “We’ve been trained that you have to have methotrexate to have a biologic. However, PsABio, together with other studies, show that you don’t have to, and you should have a good reason to add methotrexate.”

Individual patients may still benefit from methotrexate use, but the decision to treat all patients the same is not supported by the current evidence. “It’s good that it shows that, actually, once you get someone on a decent biologic, it’s working: It’s doing what it ‘says on the tin’ for a lot of patients. I really think that is the key message, here, that you don’t have to; this reassures clinicians and actually makes them think ‘should this patient be on methotrexate?’ ” Dr. Siebert said.

The PsABio study was funded by Janssen. Dr. Siebert has acted as a consultant to and received research funding from Janssen, UCB, Pfizer, Boehringer Ingelheim, Novartis, and Celgene. He has also acted as a consultant for AbbVie and received research support from Bristol-Myers Squibb.

SOURCE: Siebert S et al. Rheumatology. 2020;59(Suppl 2). doi: 10.1093/rheumatology/keaa110.023, Abstract O24.

Ustekinumab or a tumor necrosis factor inhibitor (TNFi) are better used alone than with methotrexate in the treatment of psoriatic arthritis suggest the results of PsABio (A Study on Assessment of STELARA and Tumor Necrosis Factor Alpha Inhibitor Therapies in Participants With Psoriatic Arthritis), a large, ongoing, prospective observational study.

The percentages of patients achieving multiple psoriatic arthritis disease activity outcome measures at 6 months were higher if biologic monotherapy was used rather than a biologic in combination with methotrexate.

For example, minimal disease activity (MDA) was achieved by 27.5% of patients taking ustekinumab as monotherapy and by 32.1% of those taking a TNFi alone. When methotrexate was used in combination, the respective percentages of patients achieving MDA were 23.7% and 27.8%.

A similar pattern was seen for very-low disease activity (VLDA), with 9.8% of patients in the ustekinumab monotherapy arm and 12% of those in the TNFi monotherapy arm achieving this target, compared with 5.7% and 5.4% when these drugs were combined with methotrexate.

MDA is defined as meeting five or more cutoffs for seven domains of disease activity, and VLDA for all seven: 0-1 tender joints, 0-1 swollen joints, Psoriasis Area Severity Index 1 or less or body surface area involved 3% or less, 0-1 tender entheseal points, Health Assessment Questionnaire score of 0.5 or less, patient global disease activity visual analog scale score of 20 or lower, and patient pain visual analog scale score of 15 or lower.

Other outcome measures used that showed no advantage of adding methotrexate to these biologics were the Clinical Disease Activity in Psoriatic Arthritis low disease activity and remission scores, the patient acceptable symptoms rate of the 12-item Psoriatic Arthritis Impact of Disease Questionnaire, and improvement in skin involvement.

“Patients were no more likely to achieve lower disease activity or a remission target having received methotrexate than they did just on the biologic drug on its own,” Stefan Siebert, MBBCh, PhD, one of the PsABio investigators, said in an interview.

Dr. Siebert, who is clinical senior lecturer in inflammation and rheumatology at the University of Glasgow (Scotland), was scheduled to present the findings at the British Society for Rheumatology annual conference. The meeting was canceled because of the ongoing COVID-19 crisis. Abstracts and ePosters from the meeting have since been released in a supplement to Rheumatology and via the BSR’s conference app.
 

First data for ustekinumab

“There certainly doesn’t appear to be any added benefit from using methotrexate on a group level in patients getting ustekinumab and TNF inhibitors,” Dr. Siebert said. “We’ve looked at everything,” he emphasized, and “none of the single domains or composite measures were improved by the addition of methotrexate. I think we knew that for TNF inhibitors, but the key thing is we’ve never known that for ustekinumab, and this is the first study to show that.”

Indeed, the findings match up with those from the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study in which patients who were treated with the TNFi etanercept as monotherapy did much better than those given the TNFi in combination with methotrexate or methotrexate alone. While not a randomized trial, PsABio now shows that the same is true for ustekinumab.

Obviously, there are some clear differences between a clinical trial and an observational study such as PsABio. For one thing, there was no randomization and patients taking methotrexate were presumably doing so for good reason, Dr. Siebert said. Secondly, there was no methotrexate-only arm.

PsABio recruited patients who were starting treatment with either ustekinumab or a new TNFi as first-, second-, or third-line biologic disease-modifying antirheumatic therapy (DMARD). “These are all people starting on a biologic, so they’ve already got severe disease and have failed methotrexate on some level. So everything we’ve done is biologic without methotrexate or biologic with methotrexate,” Dr. Siebert explained. Patients may not have been taking methotrexate for a variety of reasons, such as inefficacy or side effects, so PsABio “doesn’t tell us anything about methotrexate on its own.”

Time to rethink ingrained methotrexate use

The rationale for using methotrexate in combination with biologics in psoriatic arthritis comes from its long-standing use in rheumatoid arthritis. Much of what is advocated in guidelines comes from experience in RA, Dr. Siebert said.

“In rheumatoid arthritis, we know that the TNF inhibitors work much better if you use methotrexate, that’s a given,” he noted. “We’ve been trained that you have to have methotrexate to have a biologic. However, PsABio, together with other studies, show that you don’t have to, and you should have a good reason to add methotrexate.”

Individual patients may still benefit from methotrexate use, but the decision to treat all patients the same is not supported by the current evidence. “It’s good that it shows that, actually, once you get someone on a decent biologic, it’s working: It’s doing what it ‘says on the tin’ for a lot of patients. I really think that is the key message, here, that you don’t have to; this reassures clinicians and actually makes them think ‘should this patient be on methotrexate?’ ” Dr. Siebert said.

The PsABio study was funded by Janssen. Dr. Siebert has acted as a consultant to and received research funding from Janssen, UCB, Pfizer, Boehringer Ingelheim, Novartis, and Celgene. He has also acted as a consultant for AbbVie and received research support from Bristol-Myers Squibb.

SOURCE: Siebert S et al. Rheumatology. 2020;59(Suppl 2). doi: 10.1093/rheumatology/keaa110.023, Abstract O24.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

[email protected]

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

An international registry of adult and pediatric rheumatology patients is beginning to identify trends in the types of patients with COVID-19 and who is recovering.

The COVID-19 Global Rheumatology Alliance (GRA) has created pediatric and adult registries for health care providers to enter information on their rheumatology patients with COVID-19. The adult registry is hosted by the University of California, San Francisco, Research Electronic Data Capture system, while the Childhood Arthritis and Rheumatology Research Alliance is supporting the pediatric registry. A separate path for data entry of both adult and pediatric cases has been established through the European League Against Rheumatism for European countries and countries with EULAR member organizations.

Prior to the creation of the registries, there were no data available to guide rheumatologists in clinical decision making for their patients, noted Jinoos Yazdany, MD, MPH, COVID-19 GRA steering committee member and chief of the division of rheumatology at Zuckerberg San Francisco General Hospital. “COVID-19 has potential to severely affect those with rheumatologic diseases or those taking immunosuppressive drugs,” she said in an interview. “The GRA registries were designed to answer critical questions that will inform the medical care of this population.”

The GRA began on Twitter, with conversations between Leonard H. Calabrese, DO, of the Cleveland Clinic; Paul Sufka, MD, of HealthPartners in St. Paul, Minn.; Philip Robinson, MBChB, PhD, of the Royal Brisbane (Australia) Hospital; and herself, Dr. Yazdany said. Dr. Robinson started work on the governance of the GRA, Dr. Yazdany designed the data infrastructure, and Dr. Sufka approached his professional networks and social media followings to promote the effort and ask for support. The COVID-19 GRA steering committee representatives include patients, private practice rheumatologists, and international investigators. Listed among official supporters of the alliance are the American College of Rheumatology and EULAR along with more than 290 medical societies, institutions, journals, and other organizations in rheumatology.

The goal of the registries is to examine the health outcomes of patients with rheumatic diseases and COVID-19 based on sociodemographic factors, comorbidities, and clinical presentations of COVID-19 as well as what role taking immunosuppressive drugs prior to a COVID-19 infection play in helping or hindering outcomes. Hydroxychloroquine, used to treat lupus and arthritis, is a potential treatment candidate for COVID-19. Biologics such as tocilizumab (Actemra) and sarilumab (Kevzara), which target interleukin-6, and anakinra (Kineret), which targets IL-1, are treatment candidates for patients who have experienced COVID-related cytokine storm syndrome, which researchers believe may contribute to worsening or fatal cases.

Dr. Yazdany, who is also vice chair of real-world data infrastructure, registry, and institutional review board/ethics for the GRA, said that there are some important high-level trends in the data thus far. “People with lupus and those taking hydroxychloroquine are becoming infected with SARS-CoV-2, which is counter to misinformation on social media. Most people with rheumatic diseases on immunosuppression are recovering, which is great news for our patients.”

One of the major strengths of the registries is that each case is entered by the rheumatologist treating the patient and contains detailed clinical information, Dr. Yazdany said. However, the registry has no control group, it is not a population surveillance study, and it may contain selection bias through rheumatologists omitting milder, undiagnosed cases.

“The Global Alliance case reporting registry represents the collective effort of hundreds of rheumatologists across the world. I have never been more inspired by the strength and collaboration of the rheumatology community,” Dr. Yazdany said.

According to a paper published in the Lancet Rheumatology, which references data on 110 cases from the combined databases up to April 1, about three-fourths of cases presented with fever (79%) and cough (77%), and about half presented with shortness of breath (50%) and myalgia (45%).
 

Results from the global and UCSF registries

As of April 18, 334 cases were in the global and UCSF registries, with 121 patients (36%) in the database having both COVID-19 and RA, 33 patients (10%) with psoriatic arthritis, 58 patients (17%) with systemic lupus erythematosus, 28 patients (8%) with axial spondyloarthritis, 27 patients (8%) with vasculitis, and 19 patients (6%) with Sjögren’s syndrome. There were less than five cases reported for patients with the following rheumatic diseases: inflammatory myopathy, ocular inflammation, other inflammatory arthritis, polymyalgia rheumatica, sarcoidosis, systemic sclerosis, osteoporosis, psoriasis, isolated pulmonary capillaritis, gout, and autoinflammatory disease. A majority of the patients in the registries are women (74%) aged younger than 65 years (78%) and are white (52%).

The most common comorbid conditions among patients in the registry are hypertension (33%), lung disease (18%), diabetes (11%), cardiovascular disease (10%), chronic renal insufficiency or end-stage renal disease (7%), morbid obesity (7%), and cancer (4%). Before being diagnosed with COVID-19, 219 patients (66%) in the registry were taking conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), which included antimalarials, azathioprine, cyclophosphamide, cyclosporine, leflunomide, methotrexate, mycophenolate mofetil/mycophenolic acid, sulfasalazine, and tacrolimus. A total of 122 patients (37%) were taking biologic DMARDs, 101 patients were taking glucocorticoids (30%), 86 patients (26%) were taking hydroxychloroquine, 41 patients (12%) were taking NSAIDs, and 18 patients (5%) were taking a Janus kinase inhibitor.

The most recent data from the registry show that 128 patients (38%) have been hospitalized for COVID-19, and 19 patients (6%) have died. Although 104 patients (31%) resolved their infections, 177 patients (53%) have a COVID-19 infection status of “unresolved,” and 53 patients (16%) have an unknown infection status.
 

EULAR registry results

As of April 21, 249 cases were in the EULAR registry, including 110 hospitalizations (44%) and 37 deaths (15%). Overall, 64% of these patients were women, and they had a median age of 60 years.

The top five diagnoses of these patients were RA (39%), psoriatic arthritis (15%), spondyloarthritis (9%), systemic lupus erythematosus (9%), and gout (5%). A total of 27% had no reported comorbidities, while lung disease occurred in 26%, hypertension in 34%, diabetes in 11%, and cardiovascular disease on 11%. The registry also reported use of any DMARD in 80%, including 62% on csDMARDs, 31% on biologics, and 2% on targeted synthetic DMARDs.

Ten authors in the Lancet Rheumatology paper reported personal and institutional relationships in the form of grants, corporate sponsorships, advisory board memberships, investigator appointments, speaker’s bureau positions, personal fees, and consultancies for a variety of pharmaceutical companies, agencies, societies, and other organizations. The other authors reported no relevant conflicts of interest.

An international registry of adult and pediatric rheumatology patients is beginning to identify trends in the types of patients with COVID-19 and who is recovering.

The COVID-19 Global Rheumatology Alliance (GRA) has created pediatric and adult registries for health care providers to enter information on their rheumatology patients with COVID-19. The adult registry is hosted by the University of California, San Francisco, Research Electronic Data Capture system, while the Childhood Arthritis and Rheumatology Research Alliance is supporting the pediatric registry. A separate path for data entry of both adult and pediatric cases has been established through the European League Against Rheumatism for European countries and countries with EULAR member organizations.

Prior to the creation of the registries, there were no data available to guide rheumatologists in clinical decision making for their patients, noted Jinoos Yazdany, MD, MPH, COVID-19 GRA steering committee member and chief of the division of rheumatology at Zuckerberg San Francisco General Hospital. “COVID-19 has potential to severely affect those with rheumatologic diseases or those taking immunosuppressive drugs,” she said in an interview. “The GRA registries were designed to answer critical questions that will inform the medical care of this population.”

The GRA began on Twitter, with conversations between Leonard H. Calabrese, DO, of the Cleveland Clinic; Paul Sufka, MD, of HealthPartners in St. Paul, Minn.; Philip Robinson, MBChB, PhD, of the Royal Brisbane (Australia) Hospital; and herself, Dr. Yazdany said. Dr. Robinson started work on the governance of the GRA, Dr. Yazdany designed the data infrastructure, and Dr. Sufka approached his professional networks and social media followings to promote the effort and ask for support. The COVID-19 GRA steering committee representatives include patients, private practice rheumatologists, and international investigators. Listed among official supporters of the alliance are the American College of Rheumatology and EULAR along with more than 290 medical societies, institutions, journals, and other organizations in rheumatology.

The goal of the registries is to examine the health outcomes of patients with rheumatic diseases and COVID-19 based on sociodemographic factors, comorbidities, and clinical presentations of COVID-19 as well as what role taking immunosuppressive drugs prior to a COVID-19 infection play in helping or hindering outcomes. Hydroxychloroquine, used to treat lupus and arthritis, is a potential treatment candidate for COVID-19. Biologics such as tocilizumab (Actemra) and sarilumab (Kevzara), which target interleukin-6, and anakinra (Kineret), which targets IL-1, are treatment candidates for patients who have experienced COVID-related cytokine storm syndrome, which researchers believe may contribute to worsening or fatal cases.

Dr. Yazdany, who is also vice chair of real-world data infrastructure, registry, and institutional review board/ethics for the GRA, said that there are some important high-level trends in the data thus far. “People with lupus and those taking hydroxychloroquine are becoming infected with SARS-CoV-2, which is counter to misinformation on social media. Most people with rheumatic diseases on immunosuppression are recovering, which is great news for our patients.”

One of the major strengths of the registries is that each case is entered by the rheumatologist treating the patient and contains detailed clinical information, Dr. Yazdany said. However, the registry has no control group, it is not a population surveillance study, and it may contain selection bias through rheumatologists omitting milder, undiagnosed cases.

“The Global Alliance case reporting registry represents the collective effort of hundreds of rheumatologists across the world. I have never been more inspired by the strength and collaboration of the rheumatology community,” Dr. Yazdany said.

According to a paper published in the Lancet Rheumatology, which references data on 110 cases from the combined databases up to April 1, about three-fourths of cases presented with fever (79%) and cough (77%), and about half presented with shortness of breath (50%) and myalgia (45%).
 

Results from the global and UCSF registries

As of April 18, 334 cases were in the global and UCSF registries, with 121 patients (36%) in the database having both COVID-19 and RA, 33 patients (10%) with psoriatic arthritis, 58 patients (17%) with systemic lupus erythematosus, 28 patients (8%) with axial spondyloarthritis, 27 patients (8%) with vasculitis, and 19 patients (6%) with Sjögren’s syndrome. There were less than five cases reported for patients with the following rheumatic diseases: inflammatory myopathy, ocular inflammation, other inflammatory arthritis, polymyalgia rheumatica, sarcoidosis, systemic sclerosis, osteoporosis, psoriasis, isolated pulmonary capillaritis, gout, and autoinflammatory disease. A majority of the patients in the registries are women (74%) aged younger than 65 years (78%) and are white (52%).

The most common comorbid conditions among patients in the registry are hypertension (33%), lung disease (18%), diabetes (11%), cardiovascular disease (10%), chronic renal insufficiency or end-stage renal disease (7%), morbid obesity (7%), and cancer (4%). Before being diagnosed with COVID-19, 219 patients (66%) in the registry were taking conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), which included antimalarials, azathioprine, cyclophosphamide, cyclosporine, leflunomide, methotrexate, mycophenolate mofetil/mycophenolic acid, sulfasalazine, and tacrolimus. A total of 122 patients (37%) were taking biologic DMARDs, 101 patients were taking glucocorticoids (30%), 86 patients (26%) were taking hydroxychloroquine, 41 patients (12%) were taking NSAIDs, and 18 patients (5%) were taking a Janus kinase inhibitor.

The most recent data from the registry show that 128 patients (38%) have been hospitalized for COVID-19, and 19 patients (6%) have died. Although 104 patients (31%) resolved their infections, 177 patients (53%) have a COVID-19 infection status of “unresolved,” and 53 patients (16%) have an unknown infection status.
 

EULAR registry results

As of April 21, 249 cases were in the EULAR registry, including 110 hospitalizations (44%) and 37 deaths (15%). Overall, 64% of these patients were women, and they had a median age of 60 years.

The top five diagnoses of these patients were RA (39%), psoriatic arthritis (15%), spondyloarthritis (9%), systemic lupus erythematosus (9%), and gout (5%). A total of 27% had no reported comorbidities, while lung disease occurred in 26%, hypertension in 34%, diabetes in 11%, and cardiovascular disease on 11%. The registry also reported use of any DMARD in 80%, including 62% on csDMARDs, 31% on biologics, and 2% on targeted synthetic DMARDs.

Ten authors in the Lancet Rheumatology paper reported personal and institutional relationships in the form of grants, corporate sponsorships, advisory board memberships, investigator appointments, speaker’s bureau positions, personal fees, and consultancies for a variety of pharmaceutical companies, agencies, societies, and other organizations. The other authors reported no relevant conflicts of interest.

An international registry of adult and pediatric rheumatology patients is beginning to identify trends in the types of patients with COVID-19 and who is recovering.

The COVID-19 Global Rheumatology Alliance (GRA) has created pediatric and adult registries for health care providers to enter information on their rheumatology patients with COVID-19. The adult registry is hosted by the University of California, San Francisco, Research Electronic Data Capture system, while the Childhood Arthritis and Rheumatology Research Alliance is supporting the pediatric registry. A separate path for data entry of both adult and pediatric cases has been established through the European League Against Rheumatism for European countries and countries with EULAR member organizations.

Prior to the creation of the registries, there were no data available to guide rheumatologists in clinical decision making for their patients, noted Jinoos Yazdany, MD, MPH, COVID-19 GRA steering committee member and chief of the division of rheumatology at Zuckerberg San Francisco General Hospital. “COVID-19 has potential to severely affect those with rheumatologic diseases or those taking immunosuppressive drugs,” she said in an interview. “The GRA registries were designed to answer critical questions that will inform the medical care of this population.”

The GRA began on Twitter, with conversations between Leonard H. Calabrese, DO, of the Cleveland Clinic; Paul Sufka, MD, of HealthPartners in St. Paul, Minn.; Philip Robinson, MBChB, PhD, of the Royal Brisbane (Australia) Hospital; and herself, Dr. Yazdany said. Dr. Robinson started work on the governance of the GRA, Dr. Yazdany designed the data infrastructure, and Dr. Sufka approached his professional networks and social media followings to promote the effort and ask for support. The COVID-19 GRA steering committee representatives include patients, private practice rheumatologists, and international investigators. Listed among official supporters of the alliance are the American College of Rheumatology and EULAR along with more than 290 medical societies, institutions, journals, and other organizations in rheumatology.

The goal of the registries is to examine the health outcomes of patients with rheumatic diseases and COVID-19 based on sociodemographic factors, comorbidities, and clinical presentations of COVID-19 as well as what role taking immunosuppressive drugs prior to a COVID-19 infection play in helping or hindering outcomes. Hydroxychloroquine, used to treat lupus and arthritis, is a potential treatment candidate for COVID-19. Biologics such as tocilizumab (Actemra) and sarilumab (Kevzara), which target interleukin-6, and anakinra (Kineret), which targets IL-1, are treatment candidates for patients who have experienced COVID-related cytokine storm syndrome, which researchers believe may contribute to worsening or fatal cases.

Dr. Yazdany, who is also vice chair of real-world data infrastructure, registry, and institutional review board/ethics for the GRA, said that there are some important high-level trends in the data thus far. “People with lupus and those taking hydroxychloroquine are becoming infected with SARS-CoV-2, which is counter to misinformation on social media. Most people with rheumatic diseases on immunosuppression are recovering, which is great news for our patients.”

One of the major strengths of the registries is that each case is entered by the rheumatologist treating the patient and contains detailed clinical information, Dr. Yazdany said. However, the registry has no control group, it is not a population surveillance study, and it may contain selection bias through rheumatologists omitting milder, undiagnosed cases.

“The Global Alliance case reporting registry represents the collective effort of hundreds of rheumatologists across the world. I have never been more inspired by the strength and collaboration of the rheumatology community,” Dr. Yazdany said.

According to a paper published in the Lancet Rheumatology, which references data on 110 cases from the combined databases up to April 1, about three-fourths of cases presented with fever (79%) and cough (77%), and about half presented with shortness of breath (50%) and myalgia (45%).
 

Results from the global and UCSF registries

As of April 18, 334 cases were in the global and UCSF registries, with 121 patients (36%) in the database having both COVID-19 and RA, 33 patients (10%) with psoriatic arthritis, 58 patients (17%) with systemic lupus erythematosus, 28 patients (8%) with axial spondyloarthritis, 27 patients (8%) with vasculitis, and 19 patients (6%) with Sjögren’s syndrome. There were less than five cases reported for patients with the following rheumatic diseases: inflammatory myopathy, ocular inflammation, other inflammatory arthritis, polymyalgia rheumatica, sarcoidosis, systemic sclerosis, osteoporosis, psoriasis, isolated pulmonary capillaritis, gout, and autoinflammatory disease. A majority of the patients in the registries are women (74%) aged younger than 65 years (78%) and are white (52%).

The most common comorbid conditions among patients in the registry are hypertension (33%), lung disease (18%), diabetes (11%), cardiovascular disease (10%), chronic renal insufficiency or end-stage renal disease (7%), morbid obesity (7%), and cancer (4%). Before being diagnosed with COVID-19, 219 patients (66%) in the registry were taking conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), which included antimalarials, azathioprine, cyclophosphamide, cyclosporine, leflunomide, methotrexate, mycophenolate mofetil/mycophenolic acid, sulfasalazine, and tacrolimus. A total of 122 patients (37%) were taking biologic DMARDs, 101 patients were taking glucocorticoids (30%), 86 patients (26%) were taking hydroxychloroquine, 41 patients (12%) were taking NSAIDs, and 18 patients (5%) were taking a Janus kinase inhibitor.

The most recent data from the registry show that 128 patients (38%) have been hospitalized for COVID-19, and 19 patients (6%) have died. Although 104 patients (31%) resolved their infections, 177 patients (53%) have a COVID-19 infection status of “unresolved,” and 53 patients (16%) have an unknown infection status.
 

EULAR registry results

As of April 21, 249 cases were in the EULAR registry, including 110 hospitalizations (44%) and 37 deaths (15%). Overall, 64% of these patients were women, and they had a median age of 60 years.

The top five diagnoses of these patients were RA (39%), psoriatic arthritis (15%), spondyloarthritis (9%), systemic lupus erythematosus (9%), and gout (5%). A total of 27% had no reported comorbidities, while lung disease occurred in 26%, hypertension in 34%, diabetes in 11%, and cardiovascular disease on 11%. The registry also reported use of any DMARD in 80%, including 62% on csDMARDs, 31% on biologics, and 2% on targeted synthetic DMARDs.

Ten authors in the Lancet Rheumatology paper reported personal and institutional relationships in the form of grants, corporate sponsorships, advisory board memberships, investigator appointments, speaker’s bureau positions, personal fees, and consultancies for a variety of pharmaceutical companies, agencies, societies, and other organizations. The other authors reported no relevant conflicts of interest.

MAUI, HAWAII – Desensitization is a powerful and effective tool in patients with certain types of hypersensitivity reactions to therapeutic monoclonal antibodies, but it’s best considered a last resort reserved for individuals with no options left other than the offending biologic, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Why so selective? Desensitization is considered a high-risk intervention. It’s typically done as an inpatient procedure involving an overnight hospital stay followed by an elaborate 12-step protocol involving administration of small quantities of the culprit biologic in ascending concentrations over a 5- to 6-hour period.

Moreover, for an intravenous agent, such as infliximab (Remicade), desensitization has to be repeated prior to giving every dose of the biologic. So it makes sense to skip desensitization and simply switch to an alternative tumor necrosis factor inhibitor or a different class of biologic unless experience has shown that the culprit monoclonal antibody is the only one that works for that patient. It’s known, for example, that infliximab has no crossreactivity with adalimumab (Humira), explained Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.
 

Defining type and severity of the hypersensitivity reaction

Dr. Postolova favors the hypersensitivity reaction classification system developed by Mariana Castells, MD, PhD, and coworkers at Brigham and Women’s Hospital, Boston.

They divide the field into immediate and delayed hypersensitivity reactions. Immediate hypersensitivity reactions arise rapidly, between minutes and a few hours. They can be categorized as infusion reactions, cytokine-release reactions, and IgE-mediated reactions. Phenotypically, infusion reactions and cytokine-release reactions are typically characterized by various combinations of chills, fever, flushing, hypertension, tachycardia, nausea, vomiting, syncope, and shortness of breath.

IgE-mediated reactions can also involve flushing and shortness of breath, and in addition itch, urticaria, and hypotension. These are anaphylactic reactions. Neither hypertension nor fever is part of the anaphylactic picture; those findings point instead to an infusion reaction or cytokine-release reaction.

Most allergists grade reaction severity on a 1-3 scale. Grade 1 reactions are considered mild and involve symptoms limited to the skin, such as flushing, or a single other organ system.

“That being said, if my patient is having a reaction with bronchospasm, I consider that a moderate, grade 2 reaction, and I stop the infusion. There’s only so much you can do for bronchospasm. It’s a very serious reaction,” Dr. Postolova observed.

Grade 2 reactions ordinarily involve two or more organ systems, but without hypotension or cyanosis. Grade 3 reactions are severe anaphylactic reactions with cardiovascular and/or neurologic compromise.

Delayed hypersensitivity reactions are of two types: serum sickness–like reactions and type IV cell-mediated mucocutaneous reactions.

Type IV reactions can range from a mild maculopapular rash to erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS (drug reaction with eosinophilia and systemic symptoms). Onset of type IV reactions can occur after 12 hours up to several weeks after exposure.

Serum sickness–like reactions typically begin 5-7 days after the infusion. These reactions are marked by evidence of immune overactivation: fever, arthralgia, arthritis, malaise, purpura, skin rash, and even renal failure.
 

Management of reactions

A patient with a grade 3 reaction who needs to continue using the culprit monoclonal antibody should be referred to an allergist for skin testing in an effort to identify an IgE-mediated reaction.

The timing of the referral for skin testing is important: The allergist wants to test roughly 4-6 weeks after the hypersensitivity reaction. Test too early and the results will be uninformative because the patient will still be anergic. On the other hand, after 7-8 weeks the patient will have lost the allergy. So there is a sweet spot.

If the patient is skin test positive – with the caveat that skin testing in this setting is not well validated – then the allergist will suggest desensitization, usually as an inpatient.

In contrast, infusion reactions can be handled in the rheumatologist’s infusion center. They are self-limited upon repeat exposure with premedication using antihistamines, NSAIDs, oral or injectable steroids, and perhaps montelukast (Singulair).

If a patient initially thought to have an infusion reaction continues to experience reactions even after the biologic is being delivered more slowly and under the protection of premedication, it’s time to consider the possibility that what’s really going on is a cytokine-release reaction or an IgE-mediated reaction. Diagnostic skin testing is in order.

For a skin test–negative patient with a suspected cytokine-release reaction, the allergist may propose a therapeutic challenge. This is reserved for patients who the allergist believe will not experience an immediate reaction, and unlike desensitization it’s not an intervention intended to induce drug tolerance. The challenge involves giving 10% of a full dose of the biologic, waiting in the allergist’s office for 30-60 minutes, then giving the other 90% of the medication, followed by an hour of in-office observation.

The solution to severe type IV delayed hypersensitivity reactions is strict medication avoidance, not desensitization, according to Dr. Postolova.
 

Top offending monoclonal antibodies

Infliximab and rituximab (Rituxan) are the most common culprits when it comes to immediate hypersensitivity reactions. About 10% of infliximab-treated patients develop these reactions. Although the reaction can occur with the first dose, the peak incidence is with the seventh infusion. Patients with anti-infliximab IgG antibodies are at 140%-300% increased risk; however, concomitant disease-modifying antirheumatic drug therapy lessens that risk.

Infusion reactions or cytokine-release reactions occur upon the first infusion of rituximab in about 25% of treated rheumatology patients and in a higher proportion of cancer patients. Most of these reactions are mild and don’t recur when the biologic is administered more slowly and with premedication. Severe recurrent reactions upon subsequent exposure are much more likely to be an IgE-mediated hypersensitivity reaction.

“Stop the medication, send the patient to your local allergist for skin testing, and they’ll use a desensitization protocol if rituximab is the best drug for your patient,” Dr. Postolova advised.

She reported having no financial conflicts regarding her presentation.

[email protected]

MAUI, HAWAII – Desensitization is a powerful and effective tool in patients with certain types of hypersensitivity reactions to therapeutic monoclonal antibodies, but it’s best considered a last resort reserved for individuals with no options left other than the offending biologic, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Why so selective? Desensitization is considered a high-risk intervention. It’s typically done as an inpatient procedure involving an overnight hospital stay followed by an elaborate 12-step protocol involving administration of small quantities of the culprit biologic in ascending concentrations over a 5- to 6-hour period.

Moreover, for an intravenous agent, such as infliximab (Remicade), desensitization has to be repeated prior to giving every dose of the biologic. So it makes sense to skip desensitization and simply switch to an alternative tumor necrosis factor inhibitor or a different class of biologic unless experience has shown that the culprit monoclonal antibody is the only one that works for that patient. It’s known, for example, that infliximab has no crossreactivity with adalimumab (Humira), explained Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.
 

Defining type and severity of the hypersensitivity reaction

Dr. Postolova favors the hypersensitivity reaction classification system developed by Mariana Castells, MD, PhD, and coworkers at Brigham and Women’s Hospital, Boston.

They divide the field into immediate and delayed hypersensitivity reactions. Immediate hypersensitivity reactions arise rapidly, between minutes and a few hours. They can be categorized as infusion reactions, cytokine-release reactions, and IgE-mediated reactions. Phenotypically, infusion reactions and cytokine-release reactions are typically characterized by various combinations of chills, fever, flushing, hypertension, tachycardia, nausea, vomiting, syncope, and shortness of breath.

IgE-mediated reactions can also involve flushing and shortness of breath, and in addition itch, urticaria, and hypotension. These are anaphylactic reactions. Neither hypertension nor fever is part of the anaphylactic picture; those findings point instead to an infusion reaction or cytokine-release reaction.

Most allergists grade reaction severity on a 1-3 scale. Grade 1 reactions are considered mild and involve symptoms limited to the skin, such as flushing, or a single other organ system.

“That being said, if my patient is having a reaction with bronchospasm, I consider that a moderate, grade 2 reaction, and I stop the infusion. There’s only so much you can do for bronchospasm. It’s a very serious reaction,” Dr. Postolova observed.

Grade 2 reactions ordinarily involve two or more organ systems, but without hypotension or cyanosis. Grade 3 reactions are severe anaphylactic reactions with cardiovascular and/or neurologic compromise.

Delayed hypersensitivity reactions are of two types: serum sickness–like reactions and type IV cell-mediated mucocutaneous reactions.

Type IV reactions can range from a mild maculopapular rash to erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS (drug reaction with eosinophilia and systemic symptoms). Onset of type IV reactions can occur after 12 hours up to several weeks after exposure.

Serum sickness–like reactions typically begin 5-7 days after the infusion. These reactions are marked by evidence of immune overactivation: fever, arthralgia, arthritis, malaise, purpura, skin rash, and even renal failure.
 

Management of reactions

A patient with a grade 3 reaction who needs to continue using the culprit monoclonal antibody should be referred to an allergist for skin testing in an effort to identify an IgE-mediated reaction.

The timing of the referral for skin testing is important: The allergist wants to test roughly 4-6 weeks after the hypersensitivity reaction. Test too early and the results will be uninformative because the patient will still be anergic. On the other hand, after 7-8 weeks the patient will have lost the allergy. So there is a sweet spot.

If the patient is skin test positive – with the caveat that skin testing in this setting is not well validated – then the allergist will suggest desensitization, usually as an inpatient.

In contrast, infusion reactions can be handled in the rheumatologist’s infusion center. They are self-limited upon repeat exposure with premedication using antihistamines, NSAIDs, oral or injectable steroids, and perhaps montelukast (Singulair).

If a patient initially thought to have an infusion reaction continues to experience reactions even after the biologic is being delivered more slowly and under the protection of premedication, it’s time to consider the possibility that what’s really going on is a cytokine-release reaction or an IgE-mediated reaction. Diagnostic skin testing is in order.

For a skin test–negative patient with a suspected cytokine-release reaction, the allergist may propose a therapeutic challenge. This is reserved for patients who the allergist believe will not experience an immediate reaction, and unlike desensitization it’s not an intervention intended to induce drug tolerance. The challenge involves giving 10% of a full dose of the biologic, waiting in the allergist’s office for 30-60 minutes, then giving the other 90% of the medication, followed by an hour of in-office observation.

The solution to severe type IV delayed hypersensitivity reactions is strict medication avoidance, not desensitization, according to Dr. Postolova.
 

Top offending monoclonal antibodies

Infliximab and rituximab (Rituxan) are the most common culprits when it comes to immediate hypersensitivity reactions. About 10% of infliximab-treated patients develop these reactions. Although the reaction can occur with the first dose, the peak incidence is with the seventh infusion. Patients with anti-infliximab IgG antibodies are at 140%-300% increased risk; however, concomitant disease-modifying antirheumatic drug therapy lessens that risk.

Infusion reactions or cytokine-release reactions occur upon the first infusion of rituximab in about 25% of treated rheumatology patients and in a higher proportion of cancer patients. Most of these reactions are mild and don’t recur when the biologic is administered more slowly and with premedication. Severe recurrent reactions upon subsequent exposure are much more likely to be an IgE-mediated hypersensitivity reaction.

“Stop the medication, send the patient to your local allergist for skin testing, and they’ll use a desensitization protocol if rituximab is the best drug for your patient,” Dr. Postolova advised.

She reported having no financial conflicts regarding her presentation.

[email protected]

MAUI, HAWAII – Desensitization is a powerful and effective tool in patients with certain types of hypersensitivity reactions to therapeutic monoclonal antibodies, but it’s best considered a last resort reserved for individuals with no options left other than the offending biologic, Anna Postolova, MD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Why so selective? Desensitization is considered a high-risk intervention. It’s typically done as an inpatient procedure involving an overnight hospital stay followed by an elaborate 12-step protocol involving administration of small quantities of the culprit biologic in ascending concentrations over a 5- to 6-hour period.

Moreover, for an intravenous agent, such as infliximab (Remicade), desensitization has to be repeated prior to giving every dose of the biologic. So it makes sense to skip desensitization and simply switch to an alternative tumor necrosis factor inhibitor or a different class of biologic unless experience has shown that the culprit monoclonal antibody is the only one that works for that patient. It’s known, for example, that infliximab has no crossreactivity with adalimumab (Humira), explained Dr. Postolova, a dual rheumatologist and allergist/immunologist at Stanford (Calif.) University.
 

Defining type and severity of the hypersensitivity reaction

Dr. Postolova favors the hypersensitivity reaction classification system developed by Mariana Castells, MD, PhD, and coworkers at Brigham and Women’s Hospital, Boston.

They divide the field into immediate and delayed hypersensitivity reactions. Immediate hypersensitivity reactions arise rapidly, between minutes and a few hours. They can be categorized as infusion reactions, cytokine-release reactions, and IgE-mediated reactions. Phenotypically, infusion reactions and cytokine-release reactions are typically characterized by various combinations of chills, fever, flushing, hypertension, tachycardia, nausea, vomiting, syncope, and shortness of breath.

IgE-mediated reactions can also involve flushing and shortness of breath, and in addition itch, urticaria, and hypotension. These are anaphylactic reactions. Neither hypertension nor fever is part of the anaphylactic picture; those findings point instead to an infusion reaction or cytokine-release reaction.

Most allergists grade reaction severity on a 1-3 scale. Grade 1 reactions are considered mild and involve symptoms limited to the skin, such as flushing, or a single other organ system.

“That being said, if my patient is having a reaction with bronchospasm, I consider that a moderate, grade 2 reaction, and I stop the infusion. There’s only so much you can do for bronchospasm. It’s a very serious reaction,” Dr. Postolova observed.

Grade 2 reactions ordinarily involve two or more organ systems, but without hypotension or cyanosis. Grade 3 reactions are severe anaphylactic reactions with cardiovascular and/or neurologic compromise.

Delayed hypersensitivity reactions are of two types: serum sickness–like reactions and type IV cell-mediated mucocutaneous reactions.

Type IV reactions can range from a mild maculopapular rash to erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS (drug reaction with eosinophilia and systemic symptoms). Onset of type IV reactions can occur after 12 hours up to several weeks after exposure.

Serum sickness–like reactions typically begin 5-7 days after the infusion. These reactions are marked by evidence of immune overactivation: fever, arthralgia, arthritis, malaise, purpura, skin rash, and even renal failure.
 

Management of reactions

A patient with a grade 3 reaction who needs to continue using the culprit monoclonal antibody should be referred to an allergist for skin testing in an effort to identify an IgE-mediated reaction.

The timing of the referral for skin testing is important: The allergist wants to test roughly 4-6 weeks after the hypersensitivity reaction. Test too early and the results will be uninformative because the patient will still be anergic. On the other hand, after 7-8 weeks the patient will have lost the allergy. So there is a sweet spot.

If the patient is skin test positive – with the caveat that skin testing in this setting is not well validated – then the allergist will suggest desensitization, usually as an inpatient.

In contrast, infusion reactions can be handled in the rheumatologist’s infusion center. They are self-limited upon repeat exposure with premedication using antihistamines, NSAIDs, oral or injectable steroids, and perhaps montelukast (Singulair).

If a patient initially thought to have an infusion reaction continues to experience reactions even after the biologic is being delivered more slowly and under the protection of premedication, it’s time to consider the possibility that what’s really going on is a cytokine-release reaction or an IgE-mediated reaction. Diagnostic skin testing is in order.

For a skin test–negative patient with a suspected cytokine-release reaction, the allergist may propose a therapeutic challenge. This is reserved for patients who the allergist believe will not experience an immediate reaction, and unlike desensitization it’s not an intervention intended to induce drug tolerance. The challenge involves giving 10% of a full dose of the biologic, waiting in the allergist’s office for 30-60 minutes, then giving the other 90% of the medication, followed by an hour of in-office observation.

The solution to severe type IV delayed hypersensitivity reactions is strict medication avoidance, not desensitization, according to Dr. Postolova.
 

Top offending monoclonal antibodies

Infliximab and rituximab (Rituxan) are the most common culprits when it comes to immediate hypersensitivity reactions. About 10% of infliximab-treated patients develop these reactions. Although the reaction can occur with the first dose, the peak incidence is with the seventh infusion. Patients with anti-infliximab IgG antibodies are at 140%-300% increased risk; however, concomitant disease-modifying antirheumatic drug therapy lessens that risk.

Infusion reactions or cytokine-release reactions occur upon the first infusion of rituximab in about 25% of treated rheumatology patients and in a higher proportion of cancer patients. Most of these reactions are mild and don’t recur when the biologic is administered more slowly and with premedication. Severe recurrent reactions upon subsequent exposure are much more likely to be an IgE-mediated hypersensitivity reaction.

“Stop the medication, send the patient to your local allergist for skin testing, and they’ll use a desensitization protocol if rituximab is the best drug for your patient,” Dr. Postolova advised.

She reported having no financial conflicts regarding her presentation.

[email protected]

The adoption of the infused biosimilar infliximab therapies Inflectra and Renflexis was slower at an academic medical center than at a neighboring Veterans Affairs Medical Center (VAMC) during the same time period in 2015-2019, according to an analysis published in Arthritis and Rheumatology.

The use of the biosimilars also was associated with cost savings at the VAMC, but not at the academic medical center, which illustrates that insufficient financial incentives can delay the adoption of biosimilars and the health care system’s realization of cost savings, according to the authors.

Medicare, which is not allowed to negotiate drug prices, is one of the largest payers for infused therapies. Medicare reimbursement for infused therapies is based on the latter’s average selling price (ASP) during the previous quarter. Institutions may negotiate purchase prices with drug manufacturers and receive Medicare reimbursement. Biosimilars generally have lower ASPs than their corresponding reference therapies, and biosimilar manufacturers may have less room to negotiate prices than reference therapy manufacturers. Consequently, a given institution might have a greater incentive to use reference products than to use biosimilars.
 

An examination of pharmacy data

The VA negotiates drug prices for all of its medical centers and has mandated that clinicians prefer biosimilars to their corresponding reference therapies, so Joshua F. Baker, MD, of the University of Pennsylvania and the Corporal Michael J. Crescenz VAMC, both in Philadelphia, and his colleagues hypothesized that the adoption of biosimilars had proceeded more quickly at a VAMC than at a nearby academic medical center.

The investigators examined pharmacy data from the University of Pennsylvania Health System (UPHS) electronic medical record and the Corporal Michael J. Crescenz VAMC to compare the frequency of prescribing biosimilars at these sites between Jan. 1, 2015, and May 31, 2019. Dr. Baker and his associates focused specifically on reference infliximab (Remicade) and the reference noninfusion therapies filgrastim (Neupogen) and pegfilgrastim (Neulasta) and on biosimilars of these therapies (infliximab-dyyb [Inflectra], infliximab-abda [Renflexis], filgrastim-sndz [Zarxio], and pegfilgrastim-jmdb [Fulphila]).

Because Medicare was the predominant payer, the researchers estimated reimbursement for reference and biosimilar infliximabs according to the Medicare Part B reimbursement policy. They defined an institution’s incentive to use a given therapy as the difference between the reimbursement and acquisition cost for that therapy. Dr. Baker and colleagues compared the incentives for UPHS with those for the VAMC.
 

VAMC saved 81% of reference product cost

The researchers identified 15,761 infusions of infliximab at UPHS and 446 at the VAMC during the study period. The proportion of infusions that used the reference product was 99% at UPHS and 62% at the VAMC. ASPs for biosimilar infliximab have been consistently lower than those for the reference product since July 2017. In December 2017, the VAMC switched to the biosimilar infliximab.

Institutional incentives based on Medicare Part B reimbursement and acquisitions costs for reference and biosimilar infliximab have been similar since 2018. In 2019, the institutional incentive favored the reference product by $49-$64 per 100-mg vial. But at the VAMC, the cost per 100-mg vial was $623.48 for the reference product and $115.58 for the biosimilar Renflexis. Purchasing the biosimilar thus yielded a savings of 81%. The current costs for the therapies are $546 and $116, respectively.

In addition, Dr. Baker and colleagues identified 46,683 orders for filgrastim or pegfilgrastim at UPHS. Approximately 90% of the orders were for either of the two reference products despite the ASP of biosimilar filgrastim being approximately 40% lower than that of its reference product. At the VAMC, about 88% of orders were for the reference products. Biosimilars became available in 2016. UPHS began using them at a modest rate, but their adoption was greater at the VAMC, which designated them as preferred products.

Tendering and a nationwide policy mandating use of biosimilars have resulted in financial savings for the VAMC, wrote Dr. Baker and colleagues. “These data suggest that, with current Medicare Part B reimbursement policy, the absence of financial incentives to encourage use of infliximab biosimilars has resulted in slower uptake of biosimilar use at institutions outside of the VA system. The implications of this are a slower reduction in costs to the health care system, since decreases in ASP over time are predicated on negotiations at the institutional level, which have been gradual and stepwise. ...

“Although some of our results may not be applicable to other geographical regions of the U.S., the comparison of two affiliated institutions in geographical proximity and with shared health care providers is a strength,” they continued. “Our findings should be replicated using national VAMC data or data from other health care systems.”

The researchers said that their findings may not apply to noninfused therapies, which are not covered under Medicare Part B, and they did not directly study the impact of pharmacy benefit managers. However, they noted that their data on filgrastim and pegfilgrastim support the hypothesis that pharmacy benefit managers receive “incentives that continue to promote the use of reference products that have higher manufacturer’s list prices, which likely will limit the uptake of both infused and injectable biosimilar therapies over time.” They said that “this finding has important implications for when noninfused biosimilars (e.g. etanercept and adalimumab) are eventually introduced to the U.S. market.”

European governments incentivize use of biosimilars

Government and institutional incentives have increased the adoption of biosimilars in Europe, wrote Guro Lovik Goll, MD, and Tore Kristian Kvien, MD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, in an accompanying editorial. Norway and Denmark have annual national tender systems in which biosimilars and reference products compete. The price of infliximab biosimilar was 39% lower than the reference product in 2014 and 69% lower in 2015. “Competition has caused dramatically lower prices both for biosimilars and also for the originator drugs competing with them,” wrote the authors.

In 2015, the government of Denmark mandated that patients on infliximab be switched to a biosimilar, and patients in Norway also have been switched to biosimilars. The use of etanercept in Norway increased by 40% from 2016 to 2019, and the use of infliximab has increased by more than threefold since 2015. “In Norway, the consequence of competition, national tenders, and availability of biosimilars have led to better access to therapy for more people in need of biologic drugs, while at the same time showing a total cost reduction of biologics for use in rheumatology, gastroenterology, and dermatology,” wrote the authors.

Health care costs $10,000 per capita in the United States, compared with $5,300 for other wealthy countries in the Organization for Economic Cooperation and Development. Low life expectancy and high infant mortality in the U.S. indicate that high costs are not associated with better outcomes. “As Americans seem to lose out on the cost-cutting potential of biosimilars, this missed opportunity is set to get even more expensive,” the authors concluded.

The U.S. Department of Veterans Affairs, the National Institutes of Health, and the American Diabetes Association contributed funding for the study. Dr. Baker reported receiving consulting fees from Bristol-Myers Squibb and Gilead, and another author reported receiving research support paid to his institution by Pfizer and UCB, as well as receiving consulting fees from nine pharmaceutical companies. Dr. Goll and Dr. Kvien both reported receiving fees for speaking and/or consulting from numerous pharmaceutical companies, including Pfizer.

[email protected]

SOURCES: Baker JF et al. Arthritis Rheumatol. 2020 Apr 6. doi: 10.1002/art.41277.

The adoption of the infused biosimilar infliximab therapies Inflectra and Renflexis was slower at an academic medical center than at a neighboring Veterans Affairs Medical Center (VAMC) during the same time period in 2015-2019, according to an analysis published in Arthritis and Rheumatology.

The use of the biosimilars also was associated with cost savings at the VAMC, but not at the academic medical center, which illustrates that insufficient financial incentives can delay the adoption of biosimilars and the health care system’s realization of cost savings, according to the authors.

Medicare, which is not allowed to negotiate drug prices, is one of the largest payers for infused therapies. Medicare reimbursement for infused therapies is based on the latter’s average selling price (ASP) during the previous quarter. Institutions may negotiate purchase prices with drug manufacturers and receive Medicare reimbursement. Biosimilars generally have lower ASPs than their corresponding reference therapies, and biosimilar manufacturers may have less room to negotiate prices than reference therapy manufacturers. Consequently, a given institution might have a greater incentive to use reference products than to use biosimilars.
 

An examination of pharmacy data

The VA negotiates drug prices for all of its medical centers and has mandated that clinicians prefer biosimilars to their corresponding reference therapies, so Joshua F. Baker, MD, of the University of Pennsylvania and the Corporal Michael J. Crescenz VAMC, both in Philadelphia, and his colleagues hypothesized that the adoption of biosimilars had proceeded more quickly at a VAMC than at a nearby academic medical center.

The investigators examined pharmacy data from the University of Pennsylvania Health System (UPHS) electronic medical record and the Corporal Michael J. Crescenz VAMC to compare the frequency of prescribing biosimilars at these sites between Jan. 1, 2015, and May 31, 2019. Dr. Baker and his associates focused specifically on reference infliximab (Remicade) and the reference noninfusion therapies filgrastim (Neupogen) and pegfilgrastim (Neulasta) and on biosimilars of these therapies (infliximab-dyyb [Inflectra], infliximab-abda [Renflexis], filgrastim-sndz [Zarxio], and pegfilgrastim-jmdb [Fulphila]).

Because Medicare was the predominant payer, the researchers estimated reimbursement for reference and biosimilar infliximabs according to the Medicare Part B reimbursement policy. They defined an institution’s incentive to use a given therapy as the difference between the reimbursement and acquisition cost for that therapy. Dr. Baker and colleagues compared the incentives for UPHS with those for the VAMC.
 

VAMC saved 81% of reference product cost

The researchers identified 15,761 infusions of infliximab at UPHS and 446 at the VAMC during the study period. The proportion of infusions that used the reference product was 99% at UPHS and 62% at the VAMC. ASPs for biosimilar infliximab have been consistently lower than those for the reference product since July 2017. In December 2017, the VAMC switched to the biosimilar infliximab.

Institutional incentives based on Medicare Part B reimbursement and acquisitions costs for reference and biosimilar infliximab have been similar since 2018. In 2019, the institutional incentive favored the reference product by $49-$64 per 100-mg vial. But at the VAMC, the cost per 100-mg vial was $623.48 for the reference product and $115.58 for the biosimilar Renflexis. Purchasing the biosimilar thus yielded a savings of 81%. The current costs for the therapies are $546 and $116, respectively.

In addition, Dr. Baker and colleagues identified 46,683 orders for filgrastim or pegfilgrastim at UPHS. Approximately 90% of the orders were for either of the two reference products despite the ASP of biosimilar filgrastim being approximately 40% lower than that of its reference product. At the VAMC, about 88% of orders were for the reference products. Biosimilars became available in 2016. UPHS began using them at a modest rate, but their adoption was greater at the VAMC, which designated them as preferred products.

Tendering and a nationwide policy mandating use of biosimilars have resulted in financial savings for the VAMC, wrote Dr. Baker and colleagues. “These data suggest that, with current Medicare Part B reimbursement policy, the absence of financial incentives to encourage use of infliximab biosimilars has resulted in slower uptake of biosimilar use at institutions outside of the VA system. The implications of this are a slower reduction in costs to the health care system, since decreases in ASP over time are predicated on negotiations at the institutional level, which have been gradual and stepwise. ...

“Although some of our results may not be applicable to other geographical regions of the U.S., the comparison of two affiliated institutions in geographical proximity and with shared health care providers is a strength,” they continued. “Our findings should be replicated using national VAMC data or data from other health care systems.”

The researchers said that their findings may not apply to noninfused therapies, which are not covered under Medicare Part B, and they did not directly study the impact of pharmacy benefit managers. However, they noted that their data on filgrastim and pegfilgrastim support the hypothesis that pharmacy benefit managers receive “incentives that continue to promote the use of reference products that have higher manufacturer’s list prices, which likely will limit the uptake of both infused and injectable biosimilar therapies over time.” They said that “this finding has important implications for when noninfused biosimilars (e.g. etanercept and adalimumab) are eventually introduced to the U.S. market.”

European governments incentivize use of biosimilars

Government and institutional incentives have increased the adoption of biosimilars in Europe, wrote Guro Lovik Goll, MD, and Tore Kristian Kvien, MD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, in an accompanying editorial. Norway and Denmark have annual national tender systems in which biosimilars and reference products compete. The price of infliximab biosimilar was 39% lower than the reference product in 2014 and 69% lower in 2015. “Competition has caused dramatically lower prices both for biosimilars and also for the originator drugs competing with them,” wrote the authors.

In 2015, the government of Denmark mandated that patients on infliximab be switched to a biosimilar, and patients in Norway also have been switched to biosimilars. The use of etanercept in Norway increased by 40% from 2016 to 2019, and the use of infliximab has increased by more than threefold since 2015. “In Norway, the consequence of competition, national tenders, and availability of biosimilars have led to better access to therapy for more people in need of biologic drugs, while at the same time showing a total cost reduction of biologics for use in rheumatology, gastroenterology, and dermatology,” wrote the authors.

Health care costs $10,000 per capita in the United States, compared with $5,300 for other wealthy countries in the Organization for Economic Cooperation and Development. Low life expectancy and high infant mortality in the U.S. indicate that high costs are not associated with better outcomes. “As Americans seem to lose out on the cost-cutting potential of biosimilars, this missed opportunity is set to get even more expensive,” the authors concluded.

The U.S. Department of Veterans Affairs, the National Institutes of Health, and the American Diabetes Association contributed funding for the study. Dr. Baker reported receiving consulting fees from Bristol-Myers Squibb and Gilead, and another author reported receiving research support paid to his institution by Pfizer and UCB, as well as receiving consulting fees from nine pharmaceutical companies. Dr. Goll and Dr. Kvien both reported receiving fees for speaking and/or consulting from numerous pharmaceutical companies, including Pfizer.

[email protected]

SOURCES: Baker JF et al. Arthritis Rheumatol. 2020 Apr 6. doi: 10.1002/art.41277.

The adoption of the infused biosimilar infliximab therapies Inflectra and Renflexis was slower at an academic medical center than at a neighboring Veterans Affairs Medical Center (VAMC) during the same time period in 2015-2019, according to an analysis published in Arthritis and Rheumatology.

The use of the biosimilars also was associated with cost savings at the VAMC, but not at the academic medical center, which illustrates that insufficient financial incentives can delay the adoption of biosimilars and the health care system’s realization of cost savings, according to the authors.

Medicare, which is not allowed to negotiate drug prices, is one of the largest payers for infused therapies. Medicare reimbursement for infused therapies is based on the latter’s average selling price (ASP) during the previous quarter. Institutions may negotiate purchase prices with drug manufacturers and receive Medicare reimbursement. Biosimilars generally have lower ASPs than their corresponding reference therapies, and biosimilar manufacturers may have less room to negotiate prices than reference therapy manufacturers. Consequently, a given institution might have a greater incentive to use reference products than to use biosimilars.
 

An examination of pharmacy data

The VA negotiates drug prices for all of its medical centers and has mandated that clinicians prefer biosimilars to their corresponding reference therapies, so Joshua F. Baker, MD, of the University of Pennsylvania and the Corporal Michael J. Crescenz VAMC, both in Philadelphia, and his colleagues hypothesized that the adoption of biosimilars had proceeded more quickly at a VAMC than at a nearby academic medical center.

The investigators examined pharmacy data from the University of Pennsylvania Health System (UPHS) electronic medical record and the Corporal Michael J. Crescenz VAMC to compare the frequency of prescribing biosimilars at these sites between Jan. 1, 2015, and May 31, 2019. Dr. Baker and his associates focused specifically on reference infliximab (Remicade) and the reference noninfusion therapies filgrastim (Neupogen) and pegfilgrastim (Neulasta) and on biosimilars of these therapies (infliximab-dyyb [Inflectra], infliximab-abda [Renflexis], filgrastim-sndz [Zarxio], and pegfilgrastim-jmdb [Fulphila]).

Because Medicare was the predominant payer, the researchers estimated reimbursement for reference and biosimilar infliximabs according to the Medicare Part B reimbursement policy. They defined an institution’s incentive to use a given therapy as the difference between the reimbursement and acquisition cost for that therapy. Dr. Baker and colleagues compared the incentives for UPHS with those for the VAMC.
 

VAMC saved 81% of reference product cost

The researchers identified 15,761 infusions of infliximab at UPHS and 446 at the VAMC during the study period. The proportion of infusions that used the reference product was 99% at UPHS and 62% at the VAMC. ASPs for biosimilar infliximab have been consistently lower than those for the reference product since July 2017. In December 2017, the VAMC switched to the biosimilar infliximab.

Institutional incentives based on Medicare Part B reimbursement and acquisitions costs for reference and biosimilar infliximab have been similar since 2018. In 2019, the institutional incentive favored the reference product by $49-$64 per 100-mg vial. But at the VAMC, the cost per 100-mg vial was $623.48 for the reference product and $115.58 for the biosimilar Renflexis. Purchasing the biosimilar thus yielded a savings of 81%. The current costs for the therapies are $546 and $116, respectively.

In addition, Dr. Baker and colleagues identified 46,683 orders for filgrastim or pegfilgrastim at UPHS. Approximately 90% of the orders were for either of the two reference products despite the ASP of biosimilar filgrastim being approximately 40% lower than that of its reference product. At the VAMC, about 88% of orders were for the reference products. Biosimilars became available in 2016. UPHS began using them at a modest rate, but their adoption was greater at the VAMC, which designated them as preferred products.

Tendering and a nationwide policy mandating use of biosimilars have resulted in financial savings for the VAMC, wrote Dr. Baker and colleagues. “These data suggest that, with current Medicare Part B reimbursement policy, the absence of financial incentives to encourage use of infliximab biosimilars has resulted in slower uptake of biosimilar use at institutions outside of the VA system. The implications of this are a slower reduction in costs to the health care system, since decreases in ASP over time are predicated on negotiations at the institutional level, which have been gradual and stepwise. ...

“Although some of our results may not be applicable to other geographical regions of the U.S., the comparison of two affiliated institutions in geographical proximity and with shared health care providers is a strength,” they continued. “Our findings should be replicated using national VAMC data or data from other health care systems.”

The researchers said that their findings may not apply to noninfused therapies, which are not covered under Medicare Part B, and they did not directly study the impact of pharmacy benefit managers. However, they noted that their data on filgrastim and pegfilgrastim support the hypothesis that pharmacy benefit managers receive “incentives that continue to promote the use of reference products that have higher manufacturer’s list prices, which likely will limit the uptake of both infused and injectable biosimilar therapies over time.” They said that “this finding has important implications for when noninfused biosimilars (e.g. etanercept and adalimumab) are eventually introduced to the U.S. market.”

European governments incentivize use of biosimilars

Government and institutional incentives have increased the adoption of biosimilars in Europe, wrote Guro Lovik Goll, MD, and Tore Kristian Kvien, MD, of the department of rheumatology at Diakonhjemmet Hospital in Oslo, in an accompanying editorial. Norway and Denmark have annual national tender systems in which biosimilars and reference products compete. The price of infliximab biosimilar was 39% lower than the reference product in 2014 and 69% lower in 2015. “Competition has caused dramatically lower prices both for biosimilars and also for the originator drugs competing with them,” wrote the authors.

In 2015, the government of Denmark mandated that patients on infliximab be switched to a biosimilar, and patients in Norway also have been switched to biosimilars. The use of etanercept in Norway increased by 40% from 2016 to 2019, and the use of infliximab has increased by more than threefold since 2015. “In Norway, the consequence of competition, national tenders, and availability of biosimilars have led to better access to therapy for more people in need of biologic drugs, while at the same time showing a total cost reduction of biologics for use in rheumatology, gastroenterology, and dermatology,” wrote the authors.

Health care costs $10,000 per capita in the United States, compared with $5,300 for other wealthy countries in the Organization for Economic Cooperation and Development. Low life expectancy and high infant mortality in the U.S. indicate that high costs are not associated with better outcomes. “As Americans seem to lose out on the cost-cutting potential of biosimilars, this missed opportunity is set to get even more expensive,” the authors concluded.

The U.S. Department of Veterans Affairs, the National Institutes of Health, and the American Diabetes Association contributed funding for the study. Dr. Baker reported receiving consulting fees from Bristol-Myers Squibb and Gilead, and another author reported receiving research support paid to his institution by Pfizer and UCB, as well as receiving consulting fees from nine pharmaceutical companies. Dr. Goll and Dr. Kvien both reported receiving fees for speaking and/or consulting from numerous pharmaceutical companies, including Pfizer.

[email protected]

SOURCES: Baker JF et al. Arthritis Rheumatol. 2020 Apr 6. doi: 10.1002/art.41277.

Count Vikram Sengupta, MD, among the slew of health care workers feeling overwhelmed by the impact that COVID-19 is having on the delivery of health care in Manhattan and its surrounding boroughs.

“Nobody in the country is suffering like New York City,” said Dr. Sengupta, chief medical officer of Thrivewell Infusion, which operates three stand-alone infusion centers in the region: a four-chair center in Crown Heights, a 10-chair center in Borough Park, Brooklyn, and an eight-chair center in Manhasset. “We have 30%-50% of all cases in the country. I’ve been reading the news, and some people think this thing is going away. We’re in great distress here. There need to be new strategies moving forward. The whole world has changed. Our whole approach to ambulatory care has changed.”

In early March 2020, when it became clear that New York hospitals would face a tidal wave of citizens infected with COVID-19, Thrivewell began to receive an influx of referrals originating from concerned patients, providers, payers, and even large integrated health care systems, all in an effort to help prevent infectious exposure through infusion in hospital-based settings. “We are trying to accommodate them as swiftly as possible,” said Dr. Sengupta, who was interviewed for this story on April 9. “There’s been a huge uptick from that standpoint. We’ve made sure that we’ve kept our facilities clean by employing standards that have been released by the CDC, as well as by the major academic centers who are dealing with this firsthand, and also with guidance from the National Infusion Center Association.”

He and his colleagues launched a pop-up infusion center in the Bronx to help offload Montefiore Medical Center, “because they’re so overwhelmed with COVID-19 patients that they need help taking care of the autoimmune patients,” Dr. Sengupta said. “That’s the role we’re playing. We’ve made our resources available to these centers in a very flexible way in order to ensure that we do the best thing we can for everybody.”

Thrivewell is also deploying a mobile infusion unit to recovered COVID-19 patients who require an infusion for their autoimmune disease, in order to minimize the risk of contamination and transmission in their stand-alone centers. The RV-sized unit, about the size of a Bloodmobile, is equipped with infusion chairs and staffed by a physician and nurse practitioner. “The objective is continuant care and reduction of cross-contamination, and also, on a broader health care systems level, to ensure that we as ambulatory infusion center providers can offload an overburdened system,” he said.

Dr. Sengupta, who has assisted on COVID-19 inpatient wards at New York University as a volunteer, is also leading a trial of a stem cell-derived therapy developed by Israel-based Pluristem Therapeutics, to treat New York–area patients severely ill from COVID-19 infection. “There are reports from Wuhan, China, in which clinicians are delivering IV mesenchymal stem cells to patients who are on mechanical ventilators, and the patients are getting better,” he said. “I have initiated a study in which we have three cohorts: One is the outpatient setting in which we are trying to treat COVID-19 patients who have hypoxia but have been turned away from overwhelmed EDs and need some therapy. We will be converting one of our infusion centers to conduct this trial. We are also going to be administering this [stem cell-derived therapy] to COVID-19 patients in ICUs, in EDs, and on med-surg floors throughout the city.”

[email protected]

Count Vikram Sengupta, MD, among the slew of health care workers feeling overwhelmed by the impact that COVID-19 is having on the delivery of health care in Manhattan and its surrounding boroughs.

“Nobody in the country is suffering like New York City,” said Dr. Sengupta, chief medical officer of Thrivewell Infusion, which operates three stand-alone infusion centers in the region: a four-chair center in Crown Heights, a 10-chair center in Borough Park, Brooklyn, and an eight-chair center in Manhasset. “We have 30%-50% of all cases in the country. I’ve been reading the news, and some people think this thing is going away. We’re in great distress here. There need to be new strategies moving forward. The whole world has changed. Our whole approach to ambulatory care has changed.”

In early March 2020, when it became clear that New York hospitals would face a tidal wave of citizens infected with COVID-19, Thrivewell began to receive an influx of referrals originating from concerned patients, providers, payers, and even large integrated health care systems, all in an effort to help prevent infectious exposure through infusion in hospital-based settings. “We are trying to accommodate them as swiftly as possible,” said Dr. Sengupta, who was interviewed for this story on April 9. “There’s been a huge uptick from that standpoint. We’ve made sure that we’ve kept our facilities clean by employing standards that have been released by the CDC, as well as by the major academic centers who are dealing with this firsthand, and also with guidance from the National Infusion Center Association.”

He and his colleagues launched a pop-up infusion center in the Bronx to help offload Montefiore Medical Center, “because they’re so overwhelmed with COVID-19 patients that they need help taking care of the autoimmune patients,” Dr. Sengupta said. “That’s the role we’re playing. We’ve made our resources available to these centers in a very flexible way in order to ensure that we do the best thing we can for everybody.”

Thrivewell is also deploying a mobile infusion unit to recovered COVID-19 patients who require an infusion for their autoimmune disease, in order to minimize the risk of contamination and transmission in their stand-alone centers. The RV-sized unit, about the size of a Bloodmobile, is equipped with infusion chairs and staffed by a physician and nurse practitioner. “The objective is continuant care and reduction of cross-contamination, and also, on a broader health care systems level, to ensure that we as ambulatory infusion center providers can offload an overburdened system,” he said.

Dr. Sengupta, who has assisted on COVID-19 inpatient wards at New York University as a volunteer, is also leading a trial of a stem cell-derived therapy developed by Israel-based Pluristem Therapeutics, to treat New York–area patients severely ill from COVID-19 infection. “There are reports from Wuhan, China, in which clinicians are delivering IV mesenchymal stem cells to patients who are on mechanical ventilators, and the patients are getting better,” he said. “I have initiated a study in which we have three cohorts: One is the outpatient setting in which we are trying to treat COVID-19 patients who have hypoxia but have been turned away from overwhelmed EDs and need some therapy. We will be converting one of our infusion centers to conduct this trial. We are also going to be administering this [stem cell-derived therapy] to COVID-19 patients in ICUs, in EDs, and on med-surg floors throughout the city.”

[email protected]

Count Vikram Sengupta, MD, among the slew of health care workers feeling overwhelmed by the impact that COVID-19 is having on the delivery of health care in Manhattan and its surrounding boroughs.

“Nobody in the country is suffering like New York City,” said Dr. Sengupta, chief medical officer of Thrivewell Infusion, which operates three stand-alone infusion centers in the region: a four-chair center in Crown Heights, a 10-chair center in Borough Park, Brooklyn, and an eight-chair center in Manhasset. “We have 30%-50% of all cases in the country. I’ve been reading the news, and some people think this thing is going away. We’re in great distress here. There need to be new strategies moving forward. The whole world has changed. Our whole approach to ambulatory care has changed.”

In early March 2020, when it became clear that New York hospitals would face a tidal wave of citizens infected with COVID-19, Thrivewell began to receive an influx of referrals originating from concerned patients, providers, payers, and even large integrated health care systems, all in an effort to help prevent infectious exposure through infusion in hospital-based settings. “We are trying to accommodate them as swiftly as possible,” said Dr. Sengupta, who was interviewed for this story on April 9. “There’s been a huge uptick from that standpoint. We’ve made sure that we’ve kept our facilities clean by employing standards that have been released by the CDC, as well as by the major academic centers who are dealing with this firsthand, and also with guidance from the National Infusion Center Association.”

He and his colleagues launched a pop-up infusion center in the Bronx to help offload Montefiore Medical Center, “because they’re so overwhelmed with COVID-19 patients that they need help taking care of the autoimmune patients,” Dr. Sengupta said. “That’s the role we’re playing. We’ve made our resources available to these centers in a very flexible way in order to ensure that we do the best thing we can for everybody.”

Thrivewell is also deploying a mobile infusion unit to recovered COVID-19 patients who require an infusion for their autoimmune disease, in order to minimize the risk of contamination and transmission in their stand-alone centers. The RV-sized unit, about the size of a Bloodmobile, is equipped with infusion chairs and staffed by a physician and nurse practitioner. “The objective is continuant care and reduction of cross-contamination, and also, on a broader health care systems level, to ensure that we as ambulatory infusion center providers can offload an overburdened system,” he said.

Dr. Sengupta, who has assisted on COVID-19 inpatient wards at New York University as a volunteer, is also leading a trial of a stem cell-derived therapy developed by Israel-based Pluristem Therapeutics, to treat New York–area patients severely ill from COVID-19 infection. “There are reports from Wuhan, China, in which clinicians are delivering IV mesenchymal stem cells to patients who are on mechanical ventilators, and the patients are getting better,” he said. “I have initiated a study in which we have three cohorts: One is the outpatient setting in which we are trying to treat COVID-19 patients who have hypoxia but have been turned away from overwhelmed EDs and need some therapy. We will be converting one of our infusion centers to conduct this trial. We are also going to be administering this [stem cell-derived therapy] to COVID-19 patients in ICUs, in EDs, and on med-surg floors throughout the city.”

[email protected]

For patients with inflammatory bowel disease or other immune-mediated inflammatory diseases, Janus kinase (JAK) inhibitors appear generally safe, though they may increase the risk of herpes zoster infection, according to a large-scale systematic review and meta-analysis.

Data from more than 66,000 patients revealed no significant links between JAK inhibitors and risks of serious infections, malignancy, or major adverse cardiovascular events, reported lead author Pablo Olivera, MD, of Centro de Educación Médica e Investigación Clínica (CEMIC) in Buenos Aires and colleagues.

“To the best of our knowledge, this is the first systematic review evaluating the risk profile of JAK inhibitors in a wide spectrum of immune-mediated inflammatory diseases,” they wrote in Gastroenterology.

The investigators drew studies from the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from 1990 to 2019 and from conference databases from 2012 to 2018. Out of 973 studies identified, 82 were included in the final analysis, of which two-thirds were randomized clinical trials. In total, 101,925 subjects were included, of whom a majority had rheumatoid arthritis (n = 86,308), followed by psoriasis (n = 9,311), inflammatory bowel disease (n = 5,987), and ankylosing spondylitis (n = 319).

Meta-analysis of JAK inhibitor usage involved 66,159 patients. Four JAK inhibitors were included: tofacitinib, filgotinib, baricitinib, and upadacitinib. The primary outcomes were the incidence rates of adverse events and serious adverse events. The investigators also estimated incidence rates of herpes zoster infection, serious infections, mortality, malignancy, and major adverse cardiovascular events. These rates were compared with those of patients who received placebo or an active comparator in clinical trials.

Analysis showed that almost 9 out of 10 patients (87.16%) who were exposed to a JAK inhibitor received tofacitinib. The investigators described high variability in treatment duration and baseline characteristics of participants. Rates of adverse events and serious adverse events also fell across a broad spectrum, from 10% to 82% and from 0% to 29%, respectively.

“Most [adverse events] were mild, and included worsening of the underlying condition, probably showing lack of efficacy,” the investigators wrote.

Rates of mortality and most adverse events were not significantly associated with JAK inhibitor exposure. In contrast, relative risk of herpes zoster infection was 57% higher in patients who received a JAK inhibitor than in those who received a placebo or comparator (RR, 1.57; 95% confidence interval, 1.01-2.37).

“Regarding the risk of herpes zoster with JAK inhibitors, the largest evidence comes from the use of tofacitinib, but it appears to be a class effect, with a clear dose-dependent effect,” the investigators wrote.

Although risks of herpes zoster may be carried across the drug class, they may not be evenly distributed given that a subgroup analysis revealed that some JAK inhibitors may bring higher risks than others; specifically, tofacitinib and baricitinib were associated with higher relative risks of herpes zoster than were upadacitinib and filgotinib.

“Although this is merely a qualitative comparison, this difference could be related to the fact that both filgotinib and upadacitinib are selective JAK1 inhibitors, whereas tofacitinib is a JAK1/JAK3 inhibitor and baricitinib a JAK1/JAK2 inhibitor,” the investigators wrote. “Further studies are needed to determine if JAK isoform selectivity affects the risk of herpes zoster.”

The investigators emphasized this need for more research. While the present findings help illuminate the safety profile of JAK inhibitors, they are clouded by various other factors, such as disease-specific considerations, a lack of real-world data, and studies that are likely too short to accurately determine risk of malignancy, the investigators wrote.

“More studies with long follow-up and in the real world setting, in different conditions, will be needed to fully elucidate the safety profile of the different JAK inhibitors,” the investigators concluded.

The investigators disclosed relationships with AbbVie, Takeda, Pfizer, and others.

SOURCE: Olivera P et al. Gastroenterology. 2020 Jan 8. doi: 10.1053/j.gastro.2020.01.001.

For patients with inflammatory bowel disease or other immune-mediated inflammatory diseases, Janus kinase (JAK) inhibitors appear generally safe, though they may increase the risk of herpes zoster infection, according to a large-scale systematic review and meta-analysis.

Data from more than 66,000 patients revealed no significant links between JAK inhibitors and risks of serious infections, malignancy, or major adverse cardiovascular events, reported lead author Pablo Olivera, MD, of Centro de Educación Médica e Investigación Clínica (CEMIC) in Buenos Aires and colleagues.

“To the best of our knowledge, this is the first systematic review evaluating the risk profile of JAK inhibitors in a wide spectrum of immune-mediated inflammatory diseases,” they wrote in Gastroenterology.

The investigators drew studies from the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from 1990 to 2019 and from conference databases from 2012 to 2018. Out of 973 studies identified, 82 were included in the final analysis, of which two-thirds were randomized clinical trials. In total, 101,925 subjects were included, of whom a majority had rheumatoid arthritis (n = 86,308), followed by psoriasis (n = 9,311), inflammatory bowel disease (n = 5,987), and ankylosing spondylitis (n = 319).

Meta-analysis of JAK inhibitor usage involved 66,159 patients. Four JAK inhibitors were included: tofacitinib, filgotinib, baricitinib, and upadacitinib. The primary outcomes were the incidence rates of adverse events and serious adverse events. The investigators also estimated incidence rates of herpes zoster infection, serious infections, mortality, malignancy, and major adverse cardiovascular events. These rates were compared with those of patients who received placebo or an active comparator in clinical trials.

Analysis showed that almost 9 out of 10 patients (87.16%) who were exposed to a JAK inhibitor received tofacitinib. The investigators described high variability in treatment duration and baseline characteristics of participants. Rates of adverse events and serious adverse events also fell across a broad spectrum, from 10% to 82% and from 0% to 29%, respectively.

“Most [adverse events] were mild, and included worsening of the underlying condition, probably showing lack of efficacy,” the investigators wrote.

Rates of mortality and most adverse events were not significantly associated with JAK inhibitor exposure. In contrast, relative risk of herpes zoster infection was 57% higher in patients who received a JAK inhibitor than in those who received a placebo or comparator (RR, 1.57; 95% confidence interval, 1.01-2.37).

“Regarding the risk of herpes zoster with JAK inhibitors, the largest evidence comes from the use of tofacitinib, but it appears to be a class effect, with a clear dose-dependent effect,” the investigators wrote.

Although risks of herpes zoster may be carried across the drug class, they may not be evenly distributed given that a subgroup analysis revealed that some JAK inhibitors may bring higher risks than others; specifically, tofacitinib and baricitinib were associated with higher relative risks of herpes zoster than were upadacitinib and filgotinib.

“Although this is merely a qualitative comparison, this difference could be related to the fact that both filgotinib and upadacitinib are selective JAK1 inhibitors, whereas tofacitinib is a JAK1/JAK3 inhibitor and baricitinib a JAK1/JAK2 inhibitor,” the investigators wrote. “Further studies are needed to determine if JAK isoform selectivity affects the risk of herpes zoster.”

The investigators emphasized this need for more research. While the present findings help illuminate the safety profile of JAK inhibitors, they are clouded by various other factors, such as disease-specific considerations, a lack of real-world data, and studies that are likely too short to accurately determine risk of malignancy, the investigators wrote.

“More studies with long follow-up and in the real world setting, in different conditions, will be needed to fully elucidate the safety profile of the different JAK inhibitors,” the investigators concluded.

The investigators disclosed relationships with AbbVie, Takeda, Pfizer, and others.

SOURCE: Olivera P et al. Gastroenterology. 2020 Jan 8. doi: 10.1053/j.gastro.2020.01.001.

For patients with inflammatory bowel disease or other immune-mediated inflammatory diseases, Janus kinase (JAK) inhibitors appear generally safe, though they may increase the risk of herpes zoster infection, according to a large-scale systematic review and meta-analysis.

Data from more than 66,000 patients revealed no significant links between JAK inhibitors and risks of serious infections, malignancy, or major adverse cardiovascular events, reported lead author Pablo Olivera, MD, of Centro de Educación Médica e Investigación Clínica (CEMIC) in Buenos Aires and colleagues.

“To the best of our knowledge, this is the first systematic review evaluating the risk profile of JAK inhibitors in a wide spectrum of immune-mediated inflammatory diseases,” they wrote in Gastroenterology.

The investigators drew studies from the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from 1990 to 2019 and from conference databases from 2012 to 2018. Out of 973 studies identified, 82 were included in the final analysis, of which two-thirds were randomized clinical trials. In total, 101,925 subjects were included, of whom a majority had rheumatoid arthritis (n = 86,308), followed by psoriasis (n = 9,311), inflammatory bowel disease (n = 5,987), and ankylosing spondylitis (n = 319).

Meta-analysis of JAK inhibitor usage involved 66,159 patients. Four JAK inhibitors were included: tofacitinib, filgotinib, baricitinib, and upadacitinib. The primary outcomes were the incidence rates of adverse events and serious adverse events. The investigators also estimated incidence rates of herpes zoster infection, serious infections, mortality, malignancy, and major adverse cardiovascular events. These rates were compared with those of patients who received placebo or an active comparator in clinical trials.

Analysis showed that almost 9 out of 10 patients (87.16%) who were exposed to a JAK inhibitor received tofacitinib. The investigators described high variability in treatment duration and baseline characteristics of participants. Rates of adverse events and serious adverse events also fell across a broad spectrum, from 10% to 82% and from 0% to 29%, respectively.

“Most [adverse events] were mild, and included worsening of the underlying condition, probably showing lack of efficacy,” the investigators wrote.

Rates of mortality and most adverse events were not significantly associated with JAK inhibitor exposure. In contrast, relative risk of herpes zoster infection was 57% higher in patients who received a JAK inhibitor than in those who received a placebo or comparator (RR, 1.57; 95% confidence interval, 1.01-2.37).

“Regarding the risk of herpes zoster with JAK inhibitors, the largest evidence comes from the use of tofacitinib, but it appears to be a class effect, with a clear dose-dependent effect,” the investigators wrote.

Although risks of herpes zoster may be carried across the drug class, they may not be evenly distributed given that a subgroup analysis revealed that some JAK inhibitors may bring higher risks than others; specifically, tofacitinib and baricitinib were associated with higher relative risks of herpes zoster than were upadacitinib and filgotinib.

“Although this is merely a qualitative comparison, this difference could be related to the fact that both filgotinib and upadacitinib are selective JAK1 inhibitors, whereas tofacitinib is a JAK1/JAK3 inhibitor and baricitinib a JAK1/JAK2 inhibitor,” the investigators wrote. “Further studies are needed to determine if JAK isoform selectivity affects the risk of herpes zoster.”

The investigators emphasized this need for more research. While the present findings help illuminate the safety profile of JAK inhibitors, they are clouded by various other factors, such as disease-specific considerations, a lack of real-world data, and studies that are likely too short to accurately determine risk of malignancy, the investigators wrote.

“More studies with long follow-up and in the real world setting, in different conditions, will be needed to fully elucidate the safety profile of the different JAK inhibitors,” the investigators concluded.

The investigators disclosed relationships with AbbVie, Takeda, Pfizer, and others.

SOURCE: Olivera P et al. Gastroenterology. 2020 Jan 8. doi: 10.1053/j.gastro.2020.01.001.