Lupus & Connective Tissue Diseases

MILAN – Skin manifestations of the vasculitides can point the way to an accurate diagnosis and provide clues about disease severity, Robert Micheletti, MD, said at the World Congress of Dermatology.

In granulomatous vasculitis, histiocytes and giant cells can play a significant role, explained Dr. Micheletti, director of the cutaneous vasculitis clinic at the University of Pennsylvania, Philadelphia. The condition may be secondary to an autoimmune disease such as lupus erythematosus or RA; a granulomatous disease such as Crohn’s disease or sarcoidosis; infections such as tuberculosis, a fungal disease, or herpes or zoster viruses, or lymphoma, Dr. Micheletti said.

However, a primary systemic vasculitis such as granulomatosis with polyangiitis (GPA; formerly known as Wegener’s polyangiitis) or eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss vasculitis), giant cell arteritis, or Takayasu arteritis may also be responsible, he said. Occasionally, the culprit can also be a drug-induced vasculitis.

The physical examination gives clues to the size of involved vessels, which in turn helps to classify the vasculitis, Dr. Micheletti said.

When vasculitis affects small vessels, the skin findings will be palpable purpura, urticarial papules, vesicles, and petechiae, he said, adding that “The small vessel involvement accounts for the small size of the lesions, and complement cascade and inflammation account for the palpability of the lesions and the symptomatology.” As red blood cells extravasate from the affected vessels, nonblanching purpura develop, and gravity’s effect on the deposition of immune complex material dictates how lesions are distributed.

“Manifestations more typical of medium vessel vasculitis include subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis,” he said. “If such lesions are seen, suspect medium-vessel vasculitis or vasculitis overlapping small and medium vessels.” Cutaneous or systemic polyarteritis nodosa, antineutrophilic cytoplasmic autoantibody (ANCA)–associated vasculitis, and cryoglobulinemic vasculitis are examples, he added.

The particularities of renal manifestations of vasculitis also offer clues to the vessels involved. When a vasculitis patient has glomerulonephritis, suspect small-vessel involvement, Dr. Micheletti said. However, vasculitis affecting medium-sized vessels will cause renovascular hypertension and, potentially renal arterial aneurysms.

Nerves are typically spared in small-vessel vasculitis, while wrist or foot drop can be seen in mononeuritis multiplex.

Recently, the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) looked at more than 6,800 patients at over 130 sites around the world, proposing new classification criteria for ANCA-associated vasculitis (AAV) and large-vessel vasculitis. The study found that skin findings are common in AAV, with 30%-50% of cases presenting initially with skin lesions. Petechiae and/or purpura are the most common of the skin manifestations, he said. By contrast, for EGPA, allergic and nonspecific findings were the most common findings.

Although skin biopsy can confirm the diagnosis in up to 94% of AAV cases, it’s underutilized and performed in less than half (24%-44%) of cases, Dr. Micheletti said. The study’s findings “demonstrate the importance of a good skin exam, as well as its utility for diagnosis” of vasculitis, he said.

An additional finding form the DCVAS study was that skin lesions can give clues to severity of vasculitis: “Among 1,184 patients with ANCA-associated vasculitis, those with cutaneous involvement were more likely to have systemic manifestations of disease, more likely to have such severe manifestations as glomerulonephritis, alveolar hemorrhage, and mononeuritis,” said Dr. Micheletti, with a hazard ratio of 2.0 among those individuals who had EGPA or GPA.

“Skin findings have diagnostic and, potentially, prognostic importance,” he said. “Use the physician exam and your clinical acumen to your advantage,” but always confirm vasculitis with a biopsy. “Clinicopathologic correlation is key.” A simple urinalysis will screen for renal involvement, and is of “paramount importance,” he added.

Dr. Micheletti reported that he had no relevant disclosures.

[email protected]

MILAN – Skin manifestations of the vasculitides can point the way to an accurate diagnosis and provide clues about disease severity, Robert Micheletti, MD, said at the World Congress of Dermatology.

In granulomatous vasculitis, histiocytes and giant cells can play a significant role, explained Dr. Micheletti, director of the cutaneous vasculitis clinic at the University of Pennsylvania, Philadelphia. The condition may be secondary to an autoimmune disease such as lupus erythematosus or RA; a granulomatous disease such as Crohn’s disease or sarcoidosis; infections such as tuberculosis, a fungal disease, or herpes or zoster viruses, or lymphoma, Dr. Micheletti said.

However, a primary systemic vasculitis such as granulomatosis with polyangiitis (GPA; formerly known as Wegener’s polyangiitis) or eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss vasculitis), giant cell arteritis, or Takayasu arteritis may also be responsible, he said. Occasionally, the culprit can also be a drug-induced vasculitis.

The physical examination gives clues to the size of involved vessels, which in turn helps to classify the vasculitis, Dr. Micheletti said.

When vasculitis affects small vessels, the skin findings will be palpable purpura, urticarial papules, vesicles, and petechiae, he said, adding that “The small vessel involvement accounts for the small size of the lesions, and complement cascade and inflammation account for the palpability of the lesions and the symptomatology.” As red blood cells extravasate from the affected vessels, nonblanching purpura develop, and gravity’s effect on the deposition of immune complex material dictates how lesions are distributed.

“Manifestations more typical of medium vessel vasculitis include subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis,” he said. “If such lesions are seen, suspect medium-vessel vasculitis or vasculitis overlapping small and medium vessels.” Cutaneous or systemic polyarteritis nodosa, antineutrophilic cytoplasmic autoantibody (ANCA)–associated vasculitis, and cryoglobulinemic vasculitis are examples, he added.

The particularities of renal manifestations of vasculitis also offer clues to the vessels involved. When a vasculitis patient has glomerulonephritis, suspect small-vessel involvement, Dr. Micheletti said. However, vasculitis affecting medium-sized vessels will cause renovascular hypertension and, potentially renal arterial aneurysms.

Nerves are typically spared in small-vessel vasculitis, while wrist or foot drop can be seen in mononeuritis multiplex.

Recently, the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) looked at more than 6,800 patients at over 130 sites around the world, proposing new classification criteria for ANCA-associated vasculitis (AAV) and large-vessel vasculitis. The study found that skin findings are common in AAV, with 30%-50% of cases presenting initially with skin lesions. Petechiae and/or purpura are the most common of the skin manifestations, he said. By contrast, for EGPA, allergic and nonspecific findings were the most common findings.

Although skin biopsy can confirm the diagnosis in up to 94% of AAV cases, it’s underutilized and performed in less than half (24%-44%) of cases, Dr. Micheletti said. The study’s findings “demonstrate the importance of a good skin exam, as well as its utility for diagnosis” of vasculitis, he said.

An additional finding form the DCVAS study was that skin lesions can give clues to severity of vasculitis: “Among 1,184 patients with ANCA-associated vasculitis, those with cutaneous involvement were more likely to have systemic manifestations of disease, more likely to have such severe manifestations as glomerulonephritis, alveolar hemorrhage, and mononeuritis,” said Dr. Micheletti, with a hazard ratio of 2.0 among those individuals who had EGPA or GPA.

“Skin findings have diagnostic and, potentially, prognostic importance,” he said. “Use the physician exam and your clinical acumen to your advantage,” but always confirm vasculitis with a biopsy. “Clinicopathologic correlation is key.” A simple urinalysis will screen for renal involvement, and is of “paramount importance,” he added.

Dr. Micheletti reported that he had no relevant disclosures.

[email protected]

MILAN – Skin manifestations of the vasculitides can point the way to an accurate diagnosis and provide clues about disease severity, Robert Micheletti, MD, said at the World Congress of Dermatology.

In granulomatous vasculitis, histiocytes and giant cells can play a significant role, explained Dr. Micheletti, director of the cutaneous vasculitis clinic at the University of Pennsylvania, Philadelphia. The condition may be secondary to an autoimmune disease such as lupus erythematosus or RA; a granulomatous disease such as Crohn’s disease or sarcoidosis; infections such as tuberculosis, a fungal disease, or herpes or zoster viruses, or lymphoma, Dr. Micheletti said.

However, a primary systemic vasculitis such as granulomatosis with polyangiitis (GPA; formerly known as Wegener’s polyangiitis) or eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss vasculitis), giant cell arteritis, or Takayasu arteritis may also be responsible, he said. Occasionally, the culprit can also be a drug-induced vasculitis.

The physical examination gives clues to the size of involved vessels, which in turn helps to classify the vasculitis, Dr. Micheletti said.

When vasculitis affects small vessels, the skin findings will be palpable purpura, urticarial papules, vesicles, and petechiae, he said, adding that “The small vessel involvement accounts for the small size of the lesions, and complement cascade and inflammation account for the palpability of the lesions and the symptomatology.” As red blood cells extravasate from the affected vessels, nonblanching purpura develop, and gravity’s effect on the deposition of immune complex material dictates how lesions are distributed.

“Manifestations more typical of medium vessel vasculitis include subcutaneous nodules, livedo reticularis, retiform purpura, larger hemorrhagic bullae, and more significant ulceration and necrosis,” he said. “If such lesions are seen, suspect medium-vessel vasculitis or vasculitis overlapping small and medium vessels.” Cutaneous or systemic polyarteritis nodosa, antineutrophilic cytoplasmic autoantibody (ANCA)–associated vasculitis, and cryoglobulinemic vasculitis are examples, he added.

The particularities of renal manifestations of vasculitis also offer clues to the vessels involved. When a vasculitis patient has glomerulonephritis, suspect small-vessel involvement, Dr. Micheletti said. However, vasculitis affecting medium-sized vessels will cause renovascular hypertension and, potentially renal arterial aneurysms.

Nerves are typically spared in small-vessel vasculitis, while wrist or foot drop can be seen in mononeuritis multiplex.

Recently, the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) looked at more than 6,800 patients at over 130 sites around the world, proposing new classification criteria for ANCA-associated vasculitis (AAV) and large-vessel vasculitis. The study found that skin findings are common in AAV, with 30%-50% of cases presenting initially with skin lesions. Petechiae and/or purpura are the most common of the skin manifestations, he said. By contrast, for EGPA, allergic and nonspecific findings were the most common findings.

Although skin biopsy can confirm the diagnosis in up to 94% of AAV cases, it’s underutilized and performed in less than half (24%-44%) of cases, Dr. Micheletti said. The study’s findings “demonstrate the importance of a good skin exam, as well as its utility for diagnosis” of vasculitis, he said.

An additional finding form the DCVAS study was that skin lesions can give clues to severity of vasculitis: “Among 1,184 patients with ANCA-associated vasculitis, those with cutaneous involvement were more likely to have systemic manifestations of disease, more likely to have such severe manifestations as glomerulonephritis, alveolar hemorrhage, and mononeuritis,” said Dr. Micheletti, with a hazard ratio of 2.0 among those individuals who had EGPA or GPA.

“Skin findings have diagnostic and, potentially, prognostic importance,” he said. “Use the physician exam and your clinical acumen to your advantage,” but always confirm vasculitis with a biopsy. “Clinicopathologic correlation is key.” A simple urinalysis will screen for renal involvement, and is of “paramount importance,” he added.

Dr. Micheletti reported that he had no relevant disclosures.

[email protected]

Vaccination status should be reviewed annually for patients with autoimmune inflammatory rheumatic diseases, according to updated recommendations from the European League Against Rheumatism.

luiscar/Thinkstock

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at increased risk for infections, and vaccination has been shown to reduce risk by “potentially translating into a lower rate of hospital admissions due to infections, emergency room visits, and the rate of invasive infectious diseases,” wrote Victoria Furer, MD, of Tel Aviv Sourasky Medical Center, and members of the task force that updated the recommendations, which were published in Annals of the Rheumatic Diseases.

However, AIIRD patients often go unvaccinated because of a lack of awareness or concerns about vaccine safety and efficacy, they said (Ann Rheum Dis. 2019 Aug 14. doi: 10.1136/annrheumdis-2019-215882).

The task force consisted of 21 experts, including patients, rheumatologists, immunologists, an infectious disease specialist, and health professionals in rheumatology representing eight countries. They evaluated data from four systematic literature reviews and developed nine recommendations based on six key principles.

“For each recommendation, the level of evidence for the incidence/prevalence of vaccine preventable infection in AIIRD, and efficacy/immunogenicity/safety of vaccination were stated, when available, followed by the strength of recommendation and the level of agreement,” the task force wrote.

These overarching principles start with an annual assessment of vaccination status by the AIIRD patient’s rheumatology team. Other principles include explanation of an individualized vaccination program to the patient as a foundation for joint decision-making, vaccinating patients during quiescent disease periods, vaccinating in advance of planned immunosuppression when possible, considering non-live vaccines for AIIRD patients also treated with systemic glucocorticoids and DMARDs, and considering live-attenuated vaccines with caution.

Several of the nine recommendations developed by the task force are modified from the previous recommendations issued in 2011. The task force made its recommendations with an eye toward optimizing individual risk stratification and avoiding “unnecessary” vaccination in AIIRD patients with low risk of infection as part of the update process. A notable change from the 2011 guidelines is the recommendation of both influenza and pneumococcal vaccinations for the majority of patients with AIIRD as opposed to all patients to emphasize the importance of individualized risk assessment, the task force noted.

The recommendations state that influenza vaccination and pneumococcal vaccination should be “strongly considered” for patients with AIIRD, and patients also should receive tetanus toxoid vaccination according to recommendations for the general population. However, clinicians should consider passive immunization for patients treated with B-cell depleting therapy, the task force wrote.

AIIRD patients at risk for hepatitis A and B should receive vaccinations for those diseases, with boosters or passive immunization if indicated, and high-risk patients may consider herpes zoster vaccination, according to the recommendations.

In addition, AIIRD patients – especially patients with systemic lupus erythematosus – should receive human papilloma virus vaccination according to recommendations for the general population, but AIIRD patients should avoid yellow fever vaccination, the task force stated. However, for AIIRD patients traveling to areas of yellow fever risk, “withholding immunosuppressive therapy to allow a safe vaccination or measuring serology in previously exposed patients may be considered.”

Finally, mothers treated with biologics during the second half of pregnancy should avoid live-attenuated vaccines for their newborns, and immunocompetent household members of AIIRD patients should be encouraged to follow national guidelines for routine vaccination with the exception of the oral polio vaccine, the task force concluded.

Vaccination status should be reviewed annually for patients with autoimmune inflammatory rheumatic diseases, according to updated recommendations from the European League Against Rheumatism.

luiscar/Thinkstock

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at increased risk for infections, and vaccination has been shown to reduce risk by “potentially translating into a lower rate of hospital admissions due to infections, emergency room visits, and the rate of invasive infectious diseases,” wrote Victoria Furer, MD, of Tel Aviv Sourasky Medical Center, and members of the task force that updated the recommendations, which were published in Annals of the Rheumatic Diseases.

However, AIIRD patients often go unvaccinated because of a lack of awareness or concerns about vaccine safety and efficacy, they said (Ann Rheum Dis. 2019 Aug 14. doi: 10.1136/annrheumdis-2019-215882).

The task force consisted of 21 experts, including patients, rheumatologists, immunologists, an infectious disease specialist, and health professionals in rheumatology representing eight countries. They evaluated data from four systematic literature reviews and developed nine recommendations based on six key principles.

“For each recommendation, the level of evidence for the incidence/prevalence of vaccine preventable infection in AIIRD, and efficacy/immunogenicity/safety of vaccination were stated, when available, followed by the strength of recommendation and the level of agreement,” the task force wrote.

These overarching principles start with an annual assessment of vaccination status by the AIIRD patient’s rheumatology team. Other principles include explanation of an individualized vaccination program to the patient as a foundation for joint decision-making, vaccinating patients during quiescent disease periods, vaccinating in advance of planned immunosuppression when possible, considering non-live vaccines for AIIRD patients also treated with systemic glucocorticoids and DMARDs, and considering live-attenuated vaccines with caution.

Several of the nine recommendations developed by the task force are modified from the previous recommendations issued in 2011. The task force made its recommendations with an eye toward optimizing individual risk stratification and avoiding “unnecessary” vaccination in AIIRD patients with low risk of infection as part of the update process. A notable change from the 2011 guidelines is the recommendation of both influenza and pneumococcal vaccinations for the majority of patients with AIIRD as opposed to all patients to emphasize the importance of individualized risk assessment, the task force noted.

The recommendations state that influenza vaccination and pneumococcal vaccination should be “strongly considered” for patients with AIIRD, and patients also should receive tetanus toxoid vaccination according to recommendations for the general population. However, clinicians should consider passive immunization for patients treated with B-cell depleting therapy, the task force wrote.

AIIRD patients at risk for hepatitis A and B should receive vaccinations for those diseases, with boosters or passive immunization if indicated, and high-risk patients may consider herpes zoster vaccination, according to the recommendations.

In addition, AIIRD patients – especially patients with systemic lupus erythematosus – should receive human papilloma virus vaccination according to recommendations for the general population, but AIIRD patients should avoid yellow fever vaccination, the task force stated. However, for AIIRD patients traveling to areas of yellow fever risk, “withholding immunosuppressive therapy to allow a safe vaccination or measuring serology in previously exposed patients may be considered.”

Finally, mothers treated with biologics during the second half of pregnancy should avoid live-attenuated vaccines for their newborns, and immunocompetent household members of AIIRD patients should be encouraged to follow national guidelines for routine vaccination with the exception of the oral polio vaccine, the task force concluded.

Vaccination status should be reviewed annually for patients with autoimmune inflammatory rheumatic diseases, according to updated recommendations from the European League Against Rheumatism.

luiscar/Thinkstock

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at increased risk for infections, and vaccination has been shown to reduce risk by “potentially translating into a lower rate of hospital admissions due to infections, emergency room visits, and the rate of invasive infectious diseases,” wrote Victoria Furer, MD, of Tel Aviv Sourasky Medical Center, and members of the task force that updated the recommendations, which were published in Annals of the Rheumatic Diseases.

However, AIIRD patients often go unvaccinated because of a lack of awareness or concerns about vaccine safety and efficacy, they said (Ann Rheum Dis. 2019 Aug 14. doi: 10.1136/annrheumdis-2019-215882).

The task force consisted of 21 experts, including patients, rheumatologists, immunologists, an infectious disease specialist, and health professionals in rheumatology representing eight countries. They evaluated data from four systematic literature reviews and developed nine recommendations based on six key principles.

“For each recommendation, the level of evidence for the incidence/prevalence of vaccine preventable infection in AIIRD, and efficacy/immunogenicity/safety of vaccination were stated, when available, followed by the strength of recommendation and the level of agreement,” the task force wrote.

These overarching principles start with an annual assessment of vaccination status by the AIIRD patient’s rheumatology team. Other principles include explanation of an individualized vaccination program to the patient as a foundation for joint decision-making, vaccinating patients during quiescent disease periods, vaccinating in advance of planned immunosuppression when possible, considering non-live vaccines for AIIRD patients also treated with systemic glucocorticoids and DMARDs, and considering live-attenuated vaccines with caution.

Several of the nine recommendations developed by the task force are modified from the previous recommendations issued in 2011. The task force made its recommendations with an eye toward optimizing individual risk stratification and avoiding “unnecessary” vaccination in AIIRD patients with low risk of infection as part of the update process. A notable change from the 2011 guidelines is the recommendation of both influenza and pneumococcal vaccinations for the majority of patients with AIIRD as opposed to all patients to emphasize the importance of individualized risk assessment, the task force noted.

The recommendations state that influenza vaccination and pneumococcal vaccination should be “strongly considered” for patients with AIIRD, and patients also should receive tetanus toxoid vaccination according to recommendations for the general population. However, clinicians should consider passive immunization for patients treated with B-cell depleting therapy, the task force wrote.

AIIRD patients at risk for hepatitis A and B should receive vaccinations for those diseases, with boosters or passive immunization if indicated, and high-risk patients may consider herpes zoster vaccination, according to the recommendations.

In addition, AIIRD patients – especially patients with systemic lupus erythematosus – should receive human papilloma virus vaccination according to recommendations for the general population, but AIIRD patients should avoid yellow fever vaccination, the task force stated. However, for AIIRD patients traveling to areas of yellow fever risk, “withholding immunosuppressive therapy to allow a safe vaccination or measuring serology in previously exposed patients may be considered.”

Finally, mothers treated with biologics during the second half of pregnancy should avoid live-attenuated vaccines for their newborns, and immunocompetent household members of AIIRD patients should be encouraged to follow national guidelines for routine vaccination with the exception of the oral polio vaccine, the task force concluded.

Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.

According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.

Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).

The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.

The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.

Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.

These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.

[email protected]

SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.

Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.

According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.

Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).

The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.

The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.

Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.

These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.

[email protected]

SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.

Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.

According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.

Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).

The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.

The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.

Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.

These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.

[email protected]

SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.

LAKE BUENA VISTA, FLA. – Patient Reported Outcomes Measurement Information System (PROMIS) tools developed by the National Institutes of Health provide particularly useful information for managing rheumatology patients, according to Jeffrey Curtis, MD.

Courtesy UAB Photo

The PROMIS tools – which like most patient-reported outcome (PRO) measurement tools are designed to evaluate and monitor physical, mental, and social health – can be used both for the general population and for individuals living with chronic conditions, Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham (UAB), said at the annual meeting of the Florida Society of Rheumatology.

The tools take a deeper dive into various symptoms and their effects; for instance, with respect to physical health, they measure fatigue, physical function, sleep disturbance, pain intensity, and pain interference – the extent to which pain “messes your patient’s life up,” explained Dr. Curtis, who also is codirector of the UAB Pharmacoepidemiology and Pharmacoeconomics Unit.

Additional physical health domains that PROs measure include dyspnea, gastrointestinal symptoms, pain behavior, pain quality, sexual function, and sleep-related impairment.

These are “things that, honestly, we don’t talk about much as a field, but absolutely affect patients with autoimmune diseases,” he said. “You know, sexual function – that doesn’t come up in my practice spontaneously very often, but there are ways you can quantify that, and for many patients that’s actually a big deal.”

The domains measured by PROMIS tools for mental health look at anxiety and depression, but also delve into alcohol use, anger, cognitive function, life satisfaction, self-efficacy for managing chronic conditions, substance use, and more. The domains for social health address ability to participate in social roles and activities, as well as companionship, satisfaction with social roles and activity, social isolation, and social support.

“You can’t go on a hike with friends [and] be far from a bathroom, because you have bad arthritis and you have Crohn’s disease. Well, that’s kind of an important thing that may or may not come up in your discussions about inflammatory arthritis associated with [inflammatory bowel disease],” he said.

Another example is a patient who is embarrassed attending social functions or wearing a swimsuit because of really bad psoriasis.

“These are the kinds of things that I’m suggesting you and I probably want to measure if we’re providing holistic care to rheumatology patients,” Dr. Curtis said.

The PROMIS tools provide a simple, user-friendly means for doing so in English, Spanish, and many other languages, he noted.

All the scales use the same 1-100 scoring range, which simplifies measurements. They are available for free by download and can be printed or used electronically for use in the office, at home, on the web, and via smartphone.

The NIH developed the PROMIS tools several years ago and validated them for multiple chronic disease populations, Dr. Curtis said, adding that the tools include multiple individual domains and overall “profiles” of varying lengths.

Most are fixed-length scales that are between 4 and 10 questions and can be completed within 30-60 seconds per scale, so several scales can be completed within 5-10 minutes.

However, some scales are longer and provide greater detail.

“The nice thing is that if you ask a few more questions you can get more precise information – there’s more of a floor and ceiling. You can detect people who do really well. You can distinguish between the marathon runners and the 5K-ers and the people who can walk 2 miles but aren’t going to run a race,” he explained.

Further, the PROMIS tools, like the 36-item Short Form Health Survey (SF-36), are benchmarked against the U.S. adult population, allowing for assessment of how a specific drug or treatment “impacts your arthritis patient on a scale that would also be relevant for somebody who doesn’t have arthritis, they have diabetes.”

The metrics and scales are the same, and that can be helpful when trying to get a payer to pay for a particular drug, he said.

“None of these are rheumatology specific; this puts PROs into a language that can help rheumatology contend for the value of the care that we provide on a scale that would be relevant for any other chronic illness, even for nonrheumatology patients,” he explained.

In addition, minimally important differences (group mean change of about 2-3 units) and minimally clinical important differences for individuals (5 units) have been established.

“So we know what the numbers mean, and this is true for all of the scales,” he said.

PROMIS tools also include computer-adaptive testing (CAT) versions, which helps to personalize the scales to provide more precise information for a given patient and eliminate irrelevant information.

Of note, PROMIS health measures are among the data that can be tracked on a smartphone using Arthritis Power, an arthritis research registry developed with the help of a recent infrastructure grant awarded to the Center for Education and Research and Therapeutics of Musculoskeletal Disorders at UAB, Dr. Curtis said.


The measures were also shown in the AWARE study to track closely with other measures, including the Clinical Disease Activity Index (CDAI), and with patient improvement on therapy.

“So these PROMIS scores are tracking with things that you and I are familiar with ... and it looks like these scores are faithfully tracking, over time, patients getting better on therapies that we would expect them to,” he said. “I think this is additional validation – not just from the National Institutes of Health and a decade of research by lots of different groups, but in our own field – that these actually correlate with disease activity ... and that when you start an effective therapy like a [tumor necrosis factor inhibitor] they’re going to improve as you would anticipate.”

Dr. Curtis reported funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.

[email protected]

LAKE BUENA VISTA, FLA. – Patient Reported Outcomes Measurement Information System (PROMIS) tools developed by the National Institutes of Health provide particularly useful information for managing rheumatology patients, according to Jeffrey Curtis, MD.

Courtesy UAB Photo

The PROMIS tools – which like most patient-reported outcome (PRO) measurement tools are designed to evaluate and monitor physical, mental, and social health – can be used both for the general population and for individuals living with chronic conditions, Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham (UAB), said at the annual meeting of the Florida Society of Rheumatology.

The tools take a deeper dive into various symptoms and their effects; for instance, with respect to physical health, they measure fatigue, physical function, sleep disturbance, pain intensity, and pain interference – the extent to which pain “messes your patient’s life up,” explained Dr. Curtis, who also is codirector of the UAB Pharmacoepidemiology and Pharmacoeconomics Unit.

Additional physical health domains that PROs measure include dyspnea, gastrointestinal symptoms, pain behavior, pain quality, sexual function, and sleep-related impairment.

These are “things that, honestly, we don’t talk about much as a field, but absolutely affect patients with autoimmune diseases,” he said. “You know, sexual function – that doesn’t come up in my practice spontaneously very often, but there are ways you can quantify that, and for many patients that’s actually a big deal.”

The domains measured by PROMIS tools for mental health look at anxiety and depression, but also delve into alcohol use, anger, cognitive function, life satisfaction, self-efficacy for managing chronic conditions, substance use, and more. The domains for social health address ability to participate in social roles and activities, as well as companionship, satisfaction with social roles and activity, social isolation, and social support.

“You can’t go on a hike with friends [and] be far from a bathroom, because you have bad arthritis and you have Crohn’s disease. Well, that’s kind of an important thing that may or may not come up in your discussions about inflammatory arthritis associated with [inflammatory bowel disease],” he said.

Another example is a patient who is embarrassed attending social functions or wearing a swimsuit because of really bad psoriasis.

“These are the kinds of things that I’m suggesting you and I probably want to measure if we’re providing holistic care to rheumatology patients,” Dr. Curtis said.

The PROMIS tools provide a simple, user-friendly means for doing so in English, Spanish, and many other languages, he noted.

All the scales use the same 1-100 scoring range, which simplifies measurements. They are available for free by download and can be printed or used electronically for use in the office, at home, on the web, and via smartphone.

The NIH developed the PROMIS tools several years ago and validated them for multiple chronic disease populations, Dr. Curtis said, adding that the tools include multiple individual domains and overall “profiles” of varying lengths.

Most are fixed-length scales that are between 4 and 10 questions and can be completed within 30-60 seconds per scale, so several scales can be completed within 5-10 minutes.

However, some scales are longer and provide greater detail.

“The nice thing is that if you ask a few more questions you can get more precise information – there’s more of a floor and ceiling. You can detect people who do really well. You can distinguish between the marathon runners and the 5K-ers and the people who can walk 2 miles but aren’t going to run a race,” he explained.

Further, the PROMIS tools, like the 36-item Short Form Health Survey (SF-36), are benchmarked against the U.S. adult population, allowing for assessment of how a specific drug or treatment “impacts your arthritis patient on a scale that would also be relevant for somebody who doesn’t have arthritis, they have diabetes.”

The metrics and scales are the same, and that can be helpful when trying to get a payer to pay for a particular drug, he said.

“None of these are rheumatology specific; this puts PROs into a language that can help rheumatology contend for the value of the care that we provide on a scale that would be relevant for any other chronic illness, even for nonrheumatology patients,” he explained.

In addition, minimally important differences (group mean change of about 2-3 units) and minimally clinical important differences for individuals (5 units) have been established.

“So we know what the numbers mean, and this is true for all of the scales,” he said.

PROMIS tools also include computer-adaptive testing (CAT) versions, which helps to personalize the scales to provide more precise information for a given patient and eliminate irrelevant information.

Of note, PROMIS health measures are among the data that can be tracked on a smartphone using Arthritis Power, an arthritis research registry developed with the help of a recent infrastructure grant awarded to the Center for Education and Research and Therapeutics of Musculoskeletal Disorders at UAB, Dr. Curtis said.


The measures were also shown in the AWARE study to track closely with other measures, including the Clinical Disease Activity Index (CDAI), and with patient improvement on therapy.

“So these PROMIS scores are tracking with things that you and I are familiar with ... and it looks like these scores are faithfully tracking, over time, patients getting better on therapies that we would expect them to,” he said. “I think this is additional validation – not just from the National Institutes of Health and a decade of research by lots of different groups, but in our own field – that these actually correlate with disease activity ... and that when you start an effective therapy like a [tumor necrosis factor inhibitor] they’re going to improve as you would anticipate.”

Dr. Curtis reported funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.

[email protected]

LAKE BUENA VISTA, FLA. – Patient Reported Outcomes Measurement Information System (PROMIS) tools developed by the National Institutes of Health provide particularly useful information for managing rheumatology patients, according to Jeffrey Curtis, MD.

Courtesy UAB Photo

The PROMIS tools – which like most patient-reported outcome (PRO) measurement tools are designed to evaluate and monitor physical, mental, and social health – can be used both for the general population and for individuals living with chronic conditions, Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham (UAB), said at the annual meeting of the Florida Society of Rheumatology.

The tools take a deeper dive into various symptoms and their effects; for instance, with respect to physical health, they measure fatigue, physical function, sleep disturbance, pain intensity, and pain interference – the extent to which pain “messes your patient’s life up,” explained Dr. Curtis, who also is codirector of the UAB Pharmacoepidemiology and Pharmacoeconomics Unit.

Additional physical health domains that PROs measure include dyspnea, gastrointestinal symptoms, pain behavior, pain quality, sexual function, and sleep-related impairment.

These are “things that, honestly, we don’t talk about much as a field, but absolutely affect patients with autoimmune diseases,” he said. “You know, sexual function – that doesn’t come up in my practice spontaneously very often, but there are ways you can quantify that, and for many patients that’s actually a big deal.”

The domains measured by PROMIS tools for mental health look at anxiety and depression, but also delve into alcohol use, anger, cognitive function, life satisfaction, self-efficacy for managing chronic conditions, substance use, and more. The domains for social health address ability to participate in social roles and activities, as well as companionship, satisfaction with social roles and activity, social isolation, and social support.

“You can’t go on a hike with friends [and] be far from a bathroom, because you have bad arthritis and you have Crohn’s disease. Well, that’s kind of an important thing that may or may not come up in your discussions about inflammatory arthritis associated with [inflammatory bowel disease],” he said.

Another example is a patient who is embarrassed attending social functions or wearing a swimsuit because of really bad psoriasis.

“These are the kinds of things that I’m suggesting you and I probably want to measure if we’re providing holistic care to rheumatology patients,” Dr. Curtis said.

The PROMIS tools provide a simple, user-friendly means for doing so in English, Spanish, and many other languages, he noted.

All the scales use the same 1-100 scoring range, which simplifies measurements. They are available for free by download and can be printed or used electronically for use in the office, at home, on the web, and via smartphone.

The NIH developed the PROMIS tools several years ago and validated them for multiple chronic disease populations, Dr. Curtis said, adding that the tools include multiple individual domains and overall “profiles” of varying lengths.

Most are fixed-length scales that are between 4 and 10 questions and can be completed within 30-60 seconds per scale, so several scales can be completed within 5-10 minutes.

However, some scales are longer and provide greater detail.

“The nice thing is that if you ask a few more questions you can get more precise information – there’s more of a floor and ceiling. You can detect people who do really well. You can distinguish between the marathon runners and the 5K-ers and the people who can walk 2 miles but aren’t going to run a race,” he explained.

Further, the PROMIS tools, like the 36-item Short Form Health Survey (SF-36), are benchmarked against the U.S. adult population, allowing for assessment of how a specific drug or treatment “impacts your arthritis patient on a scale that would also be relevant for somebody who doesn’t have arthritis, they have diabetes.”

The metrics and scales are the same, and that can be helpful when trying to get a payer to pay for a particular drug, he said.

“None of these are rheumatology specific; this puts PROs into a language that can help rheumatology contend for the value of the care that we provide on a scale that would be relevant for any other chronic illness, even for nonrheumatology patients,” he explained.

In addition, minimally important differences (group mean change of about 2-3 units) and minimally clinical important differences for individuals (5 units) have been established.

“So we know what the numbers mean, and this is true for all of the scales,” he said.

PROMIS tools also include computer-adaptive testing (CAT) versions, which helps to personalize the scales to provide more precise information for a given patient and eliminate irrelevant information.

Of note, PROMIS health measures are among the data that can be tracked on a smartphone using Arthritis Power, an arthritis research registry developed with the help of a recent infrastructure grant awarded to the Center for Education and Research and Therapeutics of Musculoskeletal Disorders at UAB, Dr. Curtis said.


The measures were also shown in the AWARE study to track closely with other measures, including the Clinical Disease Activity Index (CDAI), and with patient improvement on therapy.

“So these PROMIS scores are tracking with things that you and I are familiar with ... and it looks like these scores are faithfully tracking, over time, patients getting better on therapies that we would expect them to,” he said. “I think this is additional validation – not just from the National Institutes of Health and a decade of research by lots of different groups, but in our own field – that these actually correlate with disease activity ... and that when you start an effective therapy like a [tumor necrosis factor inhibitor] they’re going to improve as you would anticipate.”

Dr. Curtis reported funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.

[email protected]

Although giant cell arteritis (GCA) had been established in previous studies as more common in white populations, a new study in JAMA Ophthalmology with a larger sample of black patients found similar incidence rates between black and white individuals.

Nephron/Wikimedia Commons

To determine the incidence of biopsy-proven GCA (BP-GCA) in a racially diverse cohort, Anna M. Gruener of Nottingham (England) University Hospitals NHS Trust and coauthors analyzed the medical records of more than 10 years of patients who underwent temporal artery biopsy at Johns Hopkins Wilmer Eye Institute in Baltimore. Of the 586 patients in the study, 167 (28.5%) were black, 382 (65.2%) were white, and 37 (6.3%) were other or unknown. The mean age was 70.5 years.

Of the 573 patients who were aged 50 years and older, 92 (16.1%) had a positive biopsy for BP-GCA; 14 were black (8.4% of all black patients), 75 were white (19.6% of all white patients), and 3 were other or unknown. The population-adjusted, age- and sex-standardized incidence rates per 100,000 were 3.1 (95% confidence interval, 1.0-5.2) for black patients and 3.6 (95% CI, 2.5-4.7) for white patients.

Overall, BP-GCA occurred more frequently in women than in men (incidence rate ratio, 1.9; 95% CI, 1.1-3.4; P = .03) but at similar levels in white and black patients (IRR, 1.2; 95% CI, 0.6-2.4; P = .66).

In an accompanying editorial, Michael K. Yoon, MD, and Joseph F. Rizzo III, MD, of Harvard Medical School, Boston, praised the researchers for conducting their study in a population with a large percentage of black patients, a noted weakness of earlier studies in this area (JAMA Ophthalmol. 2019 Aug 8. doi: 10.1001/jamaophthalmol.2019.2933). That said, the two doctors also recognized the limitations of the work done by Gruener et al., including relying on U.S. Census data to calculate adjusted incidence rates instead of local racial distribution and also the potentially problematic choice to count patients with healed arteritis as having BP-GCA.


Still, Dr. Yoon and Dr. Rizzo commended Gruener et al. for questioning previous findings on GCA rates. “Although the authors’ methods are imperfect,” they wrote, “the studies that had previously established a low incidence of GCA in black patients were also flawed in design.”

The study had no outside funding source, and no conflicts of interest were reported.

SOURCE: Gruener AM et al. JAMA Ophthalmol. 2019 Aug 8. doi: 10.1001/jamaophthalmol.2019.2919.

Although giant cell arteritis (GCA) had been established in previous studies as more common in white populations, a new study in JAMA Ophthalmology with a larger sample of black patients found similar incidence rates between black and white individuals.

Nephron/Wikimedia Commons

To determine the incidence of biopsy-proven GCA (BP-GCA) in a racially diverse cohort, Anna M. Gruener of Nottingham (England) University Hospitals NHS Trust and coauthors analyzed the medical records of more than 10 years of patients who underwent temporal artery biopsy at Johns Hopkins Wilmer Eye Institute in Baltimore. Of the 586 patients in the study, 167 (28.5%) were black, 382 (65.2%) were white, and 37 (6.3%) were other or unknown. The mean age was 70.5 years.

Of the 573 patients who were aged 50 years and older, 92 (16.1%) had a positive biopsy for BP-GCA; 14 were black (8.4% of all black patients), 75 were white (19.6% of all white patients), and 3 were other or unknown. The population-adjusted, age- and sex-standardized incidence rates per 100,000 were 3.1 (95% confidence interval, 1.0-5.2) for black patients and 3.6 (95% CI, 2.5-4.7) for white patients.

Overall, BP-GCA occurred more frequently in women than in men (incidence rate ratio, 1.9; 95% CI, 1.1-3.4; P = .03) but at similar levels in white and black patients (IRR, 1.2; 95% CI, 0.6-2.4; P = .66).

In an accompanying editorial, Michael K. Yoon, MD, and Joseph F. Rizzo III, MD, of Harvard Medical School, Boston, praised the researchers for conducting their study in a population with a large percentage of black patients, a noted weakness of earlier studies in this area (JAMA Ophthalmol. 2019 Aug 8. doi: 10.1001/jamaophthalmol.2019.2933). That said, the two doctors also recognized the limitations of the work done by Gruener et al., including relying on U.S. Census data to calculate adjusted incidence rates instead of local racial distribution and also the potentially problematic choice to count patients with healed arteritis as having BP-GCA.


Still, Dr. Yoon and Dr. Rizzo commended Gruener et al. for questioning previous findings on GCA rates. “Although the authors’ methods are imperfect,” they wrote, “the studies that had previously established a low incidence of GCA in black patients were also flawed in design.”

The study had no outside funding source, and no conflicts of interest were reported.

SOURCE: Gruener AM et al. JAMA Ophthalmol. 2019 Aug 8. doi: 10.1001/jamaophthalmol.2019.2919.

Although giant cell arteritis (GCA) had been established in previous studies as more common in white populations, a new study in JAMA Ophthalmology with a larger sample of black patients found similar incidence rates between black and white individuals.

Nephron/Wikimedia Commons

To determine the incidence of biopsy-proven GCA (BP-GCA) in a racially diverse cohort, Anna M. Gruener of Nottingham (England) University Hospitals NHS Trust and coauthors analyzed the medical records of more than 10 years of patients who underwent temporal artery biopsy at Johns Hopkins Wilmer Eye Institute in Baltimore. Of the 586 patients in the study, 167 (28.5%) were black, 382 (65.2%) were white, and 37 (6.3%) were other or unknown. The mean age was 70.5 years.

Of the 573 patients who were aged 50 years and older, 92 (16.1%) had a positive biopsy for BP-GCA; 14 were black (8.4% of all black patients), 75 were white (19.6% of all white patients), and 3 were other or unknown. The population-adjusted, age- and sex-standardized incidence rates per 100,000 were 3.1 (95% confidence interval, 1.0-5.2) for black patients and 3.6 (95% CI, 2.5-4.7) for white patients.

Overall, BP-GCA occurred more frequently in women than in men (incidence rate ratio, 1.9; 95% CI, 1.1-3.4; P = .03) but at similar levels in white and black patients (IRR, 1.2; 95% CI, 0.6-2.4; P = .66).

In an accompanying editorial, Michael K. Yoon, MD, and Joseph F. Rizzo III, MD, of Harvard Medical School, Boston, praised the researchers for conducting their study in a population with a large percentage of black patients, a noted weakness of earlier studies in this area (JAMA Ophthalmol. 2019 Aug 8. doi: 10.1001/jamaophthalmol.2019.2933). That said, the two doctors also recognized the limitations of the work done by Gruener et al., including relying on U.S. Census data to calculate adjusted incidence rates instead of local racial distribution and also the potentially problematic choice to count patients with healed arteritis as having BP-GCA.


Still, Dr. Yoon and Dr. Rizzo commended Gruener et al. for questioning previous findings on GCA rates. “Although the authors’ methods are imperfect,” they wrote, “the studies that had previously established a low incidence of GCA in black patients were also flawed in design.”

The study had no outside funding source, and no conflicts of interest were reported.

SOURCE: Gruener AM et al. JAMA Ophthalmol. 2019 Aug 8. doi: 10.1001/jamaophthalmol.2019.2919.

The heterogeneity of lupus and the subsequent lack of a clear disease definition have been identified by an international group of experts as the primary barriers hindering timely diagnosis, improved treatment options, and appropriate access to care.

A report published in Lupus Science & Medicine titled “Global Consensus Building and Prioritization of Fundamental Lupus Challenges: The ALPHA Project” describes the results of a first-ever global consensus on key barriers to advances in lupus care, including a lack of validated biomarkers and flawed clinical trial design.

A lack of access to medical professionals familiar with lupus, challenges in managing lupus because of social determinants, and lack of treatment adherence were also considered to be barriers to improving the outcomes of people living with lupus.

First author Susan Manzi, MD, codirector of the Lupus Center of Excellence at Allegheny Health Network, Pittsburgh, and her colleagues said that, in contrast to other autoimmune diseases such as rheumatoid arthritis and psoriasis, the field of lupus has struggled with establishing a clear pathway for lupus drug development because of “persistent challenges in understanding the biology of the disease, defining clinical trial entry criteria and end points, developing instruments to measure changes in clinical activity, and controlling background medications.”

The authors noted that the intention of the Addressing Lupus Pillars for Health Advancement (ALPHA) Project was to build on the work of other initiatives, including some that were international in scope or were still ongoing.

“The ALPHA project was founded as the first step in an ongoing commitment to identify, prioritize, and implement strategies to address the most pressing challenges that limit progress in lupus across the continuum,” they wrote. In a joint initiative, the Lupus Foundation of America (LFA) and the Tufts Center for the Study of Drug Development (Tufts CSDD) set up a Global Advisory Committee (GAC) that included 13 lupus experts from the United States, Australia, United Kingdom, Germany, and South Korea to guide and oversee the study. Members had extensive knowledge of the disease, with specific expertise in rheumatology, dermatology, immunology, nephrology, and pediatrics.

Next, in-depth interviews were conducted with 17 experts who were well respected in the lupus scientific and care communities and represented all stakeholders. Using information garnered from these interviews, the LFA, Tufts CSDD, and GAC collaborated to develop a survey that included 23 questions addressing attitudes and perceptions about lupus as well as the prioritization of the most pressing challenges to improving diagnosis, care, treatment, and research.

The online survey was sent to 366 candidates, from whom the researchers received 127 completed responses. Of these, 82 (65%) were clinician-researcher-scientists and 14 (11%) worked in industry/biotechnology, 13 (10%) were researcher-scientists, and 12 (9%) were clinicians; 5% marked “other.”

The research team used a weighting system to prioritize barriers ranked by respondents, whereby higher ratings represented the challenges of highest impact (a score of 9 was highest rating, with 1 the lowest).

Survey respondents ranked the following as the top barriers to improving outcomes in lupus:
 

• A lack of diagnostic, predictive, and prognostic biomarkers for lupus (weighted prioritization score of 7.294) and lack of biomarkers to predict drug response in clinical trials (weighted prioritization score of 6.614).
• Flawed clinical trial design (weighted prioritization score of 6.370).
• Lack of access to clinicians familiar with lupus (weighted prioritization score of 6.873), and limited awareness of lupus among nonexpert medical professionals (weighted prioritization score of 5.800).
• Barriers to effective management of lupus because of social determinants of care in predominantly lower socioeconomic status areas (weighted prioritization score of 6.937).
• A lack of treatment adherence (weighted prioritization score of 6.717).

“A strong consensus built throughout the study, as themes and insights gathered from the in-depth interviews were highly consistent with those collected in the survey,” the researchers noted.

They said it was not surprising that the development of biomarkers had received a high ranking, as advances in this area would help accelerate drug development and precision medicine as well as more practical aspects of clinical care.

The research team acknowledged that substantial funds would be needed to address the top priorities identified in the study, and some of the issues may be more easily addressed than others.

“In the past decade, the overall funding landscape for lupus has been on a decline, particularly through the National Institutes of Health – the largest public funder of lupus research in the world – during a time in which arguably, lupus research has been prolific,” they wrote.

They concluded that comprehensive measures were needed to transform the lupus research and health care landscape.

“Lupus experts must convene to determine feasible and coordinated approaches for addressing long-standing barriers across the global lupus community,” they stressed.

The next part of the project will involve an international stakeholder meeting to develop a global road map of specific recommendations to address identified barriers, which “may include multipronged strategies using regulatory and advocacy approaches, scientific consensus building, communication efforts, among other possible tactics,” they added.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development (a business of Merck KGaA) and through additional support by GlaxoSmithKline. Many authors of the report had financial connections to the pharmaceutical industry.

SOURCE: Manzi S et al. Lupus Sci Med. 2019;6:e000342. doi: 10.1136/lupus-2019-000342.

The heterogeneity of lupus and the subsequent lack of a clear disease definition have been identified by an international group of experts as the primary barriers hindering timely diagnosis, improved treatment options, and appropriate access to care.

A report published in Lupus Science & Medicine titled “Global Consensus Building and Prioritization of Fundamental Lupus Challenges: The ALPHA Project” describes the results of a first-ever global consensus on key barriers to advances in lupus care, including a lack of validated biomarkers and flawed clinical trial design.

A lack of access to medical professionals familiar with lupus, challenges in managing lupus because of social determinants, and lack of treatment adherence were also considered to be barriers to improving the outcomes of people living with lupus.

First author Susan Manzi, MD, codirector of the Lupus Center of Excellence at Allegheny Health Network, Pittsburgh, and her colleagues said that, in contrast to other autoimmune diseases such as rheumatoid arthritis and psoriasis, the field of lupus has struggled with establishing a clear pathway for lupus drug development because of “persistent challenges in understanding the biology of the disease, defining clinical trial entry criteria and end points, developing instruments to measure changes in clinical activity, and controlling background medications.”

The authors noted that the intention of the Addressing Lupus Pillars for Health Advancement (ALPHA) Project was to build on the work of other initiatives, including some that were international in scope or were still ongoing.

“The ALPHA project was founded as the first step in an ongoing commitment to identify, prioritize, and implement strategies to address the most pressing challenges that limit progress in lupus across the continuum,” they wrote. In a joint initiative, the Lupus Foundation of America (LFA) and the Tufts Center for the Study of Drug Development (Tufts CSDD) set up a Global Advisory Committee (GAC) that included 13 lupus experts from the United States, Australia, United Kingdom, Germany, and South Korea to guide and oversee the study. Members had extensive knowledge of the disease, with specific expertise in rheumatology, dermatology, immunology, nephrology, and pediatrics.

Next, in-depth interviews were conducted with 17 experts who were well respected in the lupus scientific and care communities and represented all stakeholders. Using information garnered from these interviews, the LFA, Tufts CSDD, and GAC collaborated to develop a survey that included 23 questions addressing attitudes and perceptions about lupus as well as the prioritization of the most pressing challenges to improving diagnosis, care, treatment, and research.

The online survey was sent to 366 candidates, from whom the researchers received 127 completed responses. Of these, 82 (65%) were clinician-researcher-scientists and 14 (11%) worked in industry/biotechnology, 13 (10%) were researcher-scientists, and 12 (9%) were clinicians; 5% marked “other.”

The research team used a weighting system to prioritize barriers ranked by respondents, whereby higher ratings represented the challenges of highest impact (a score of 9 was highest rating, with 1 the lowest).

Survey respondents ranked the following as the top barriers to improving outcomes in lupus:
 

• A lack of diagnostic, predictive, and prognostic biomarkers for lupus (weighted prioritization score of 7.294) and lack of biomarkers to predict drug response in clinical trials (weighted prioritization score of 6.614).
• Flawed clinical trial design (weighted prioritization score of 6.370).
• Lack of access to clinicians familiar with lupus (weighted prioritization score of 6.873), and limited awareness of lupus among nonexpert medical professionals (weighted prioritization score of 5.800).
• Barriers to effective management of lupus because of social determinants of care in predominantly lower socioeconomic status areas (weighted prioritization score of 6.937).
• A lack of treatment adherence (weighted prioritization score of 6.717).

“A strong consensus built throughout the study, as themes and insights gathered from the in-depth interviews were highly consistent with those collected in the survey,” the researchers noted.

They said it was not surprising that the development of biomarkers had received a high ranking, as advances in this area would help accelerate drug development and precision medicine as well as more practical aspects of clinical care.

The research team acknowledged that substantial funds would be needed to address the top priorities identified in the study, and some of the issues may be more easily addressed than others.

“In the past decade, the overall funding landscape for lupus has been on a decline, particularly through the National Institutes of Health – the largest public funder of lupus research in the world – during a time in which arguably, lupus research has been prolific,” they wrote.

They concluded that comprehensive measures were needed to transform the lupus research and health care landscape.

“Lupus experts must convene to determine feasible and coordinated approaches for addressing long-standing barriers across the global lupus community,” they stressed.

The next part of the project will involve an international stakeholder meeting to develop a global road map of specific recommendations to address identified barriers, which “may include multipronged strategies using regulatory and advocacy approaches, scientific consensus building, communication efforts, among other possible tactics,” they added.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development (a business of Merck KGaA) and through additional support by GlaxoSmithKline. Many authors of the report had financial connections to the pharmaceutical industry.

SOURCE: Manzi S et al. Lupus Sci Med. 2019;6:e000342. doi: 10.1136/lupus-2019-000342.

The heterogeneity of lupus and the subsequent lack of a clear disease definition have been identified by an international group of experts as the primary barriers hindering timely diagnosis, improved treatment options, and appropriate access to care.

A report published in Lupus Science & Medicine titled “Global Consensus Building and Prioritization of Fundamental Lupus Challenges: The ALPHA Project” describes the results of a first-ever global consensus on key barriers to advances in lupus care, including a lack of validated biomarkers and flawed clinical trial design.

A lack of access to medical professionals familiar with lupus, challenges in managing lupus because of social determinants, and lack of treatment adherence were also considered to be barriers to improving the outcomes of people living with lupus.

First author Susan Manzi, MD, codirector of the Lupus Center of Excellence at Allegheny Health Network, Pittsburgh, and her colleagues said that, in contrast to other autoimmune diseases such as rheumatoid arthritis and psoriasis, the field of lupus has struggled with establishing a clear pathway for lupus drug development because of “persistent challenges in understanding the biology of the disease, defining clinical trial entry criteria and end points, developing instruments to measure changes in clinical activity, and controlling background medications.”

The authors noted that the intention of the Addressing Lupus Pillars for Health Advancement (ALPHA) Project was to build on the work of other initiatives, including some that were international in scope or were still ongoing.

“The ALPHA project was founded as the first step in an ongoing commitment to identify, prioritize, and implement strategies to address the most pressing challenges that limit progress in lupus across the continuum,” they wrote. In a joint initiative, the Lupus Foundation of America (LFA) and the Tufts Center for the Study of Drug Development (Tufts CSDD) set up a Global Advisory Committee (GAC) that included 13 lupus experts from the United States, Australia, United Kingdom, Germany, and South Korea to guide and oversee the study. Members had extensive knowledge of the disease, with specific expertise in rheumatology, dermatology, immunology, nephrology, and pediatrics.

Next, in-depth interviews were conducted with 17 experts who were well respected in the lupus scientific and care communities and represented all stakeholders. Using information garnered from these interviews, the LFA, Tufts CSDD, and GAC collaborated to develop a survey that included 23 questions addressing attitudes and perceptions about lupus as well as the prioritization of the most pressing challenges to improving diagnosis, care, treatment, and research.

The online survey was sent to 366 candidates, from whom the researchers received 127 completed responses. Of these, 82 (65%) were clinician-researcher-scientists and 14 (11%) worked in industry/biotechnology, 13 (10%) were researcher-scientists, and 12 (9%) were clinicians; 5% marked “other.”

The research team used a weighting system to prioritize barriers ranked by respondents, whereby higher ratings represented the challenges of highest impact (a score of 9 was highest rating, with 1 the lowest).

Survey respondents ranked the following as the top barriers to improving outcomes in lupus:
 

• A lack of diagnostic, predictive, and prognostic biomarkers for lupus (weighted prioritization score of 7.294) and lack of biomarkers to predict drug response in clinical trials (weighted prioritization score of 6.614).
• Flawed clinical trial design (weighted prioritization score of 6.370).
• Lack of access to clinicians familiar with lupus (weighted prioritization score of 6.873), and limited awareness of lupus among nonexpert medical professionals (weighted prioritization score of 5.800).
• Barriers to effective management of lupus because of social determinants of care in predominantly lower socioeconomic status areas (weighted prioritization score of 6.937).
• A lack of treatment adherence (weighted prioritization score of 6.717).

“A strong consensus built throughout the study, as themes and insights gathered from the in-depth interviews were highly consistent with those collected in the survey,” the researchers noted.

They said it was not surprising that the development of biomarkers had received a high ranking, as advances in this area would help accelerate drug development and precision medicine as well as more practical aspects of clinical care.

The research team acknowledged that substantial funds would be needed to address the top priorities identified in the study, and some of the issues may be more easily addressed than others.

“In the past decade, the overall funding landscape for lupus has been on a decline, particularly through the National Institutes of Health – the largest public funder of lupus research in the world – during a time in which arguably, lupus research has been prolific,” they wrote.

They concluded that comprehensive measures were needed to transform the lupus research and health care landscape.

“Lupus experts must convene to determine feasible and coordinated approaches for addressing long-standing barriers across the global lupus community,” they stressed.

The next part of the project will involve an international stakeholder meeting to develop a global road map of specific recommendations to address identified barriers, which “may include multipronged strategies using regulatory and advocacy approaches, scientific consensus building, communication efforts, among other possible tactics,” they added.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development (a business of Merck KGaA) and through additional support by GlaxoSmithKline. Many authors of the report had financial connections to the pharmaceutical industry.

SOURCE: Manzi S et al. Lupus Sci Med. 2019;6:e000342. doi: 10.1136/lupus-2019-000342.

MILAN – A novel synthetic cannabinoid helped reduce the severity of dermatomyositis and improved patient-reported outcomes in early clinical trials, according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.

Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.

Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.

In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.

Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.

However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.

Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.

Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.

“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.

Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.

[email protected]

MILAN – A novel synthetic cannabinoid helped reduce the severity of dermatomyositis and improved patient-reported outcomes in early clinical trials, according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.

Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.

Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.

In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.

Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.

However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.

Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.

Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.

“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.

Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.

[email protected]

MILAN – A novel synthetic cannabinoid helped reduce the severity of dermatomyositis and improved patient-reported outcomes in early clinical trials, according to Victoria Werth, MD, who presented early-stage findings at the World Congress of Dermatology.

Lenabasum – previously known as anabasum – is a synthetic cannabinoid that binds to the CB2 receptor present on a variety of cells, including lymphocytes, explained Dr. Werth, professor of medicine at the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Administration Hospital. The nonpsychoactive compound’s mechanism of action helps prevent tissue thickening and fibrosis. In addition to its potential for dermatomyositis treatment, it is also being investigated as a treatment for cystic fibrosis, scleroderma, and lupus.

Dr. Werth added that earlier in vitro work with peripheral blood mononuclear cells of patients with dermatomyositis showed that lenabasum markedly suppressed the cells’ secretion of tumor necrosis factor–alpha, interferon-alpha, and interferon-beta (J Invest Dermatol. 2017 Nov;137[11]:2445-7). A randomized, placebo-controlled trial tested lenabasum, known in the trial as JBT-101, in 22 patients with skin-predominant myositis. The study was structured so patients took a half dose of lenabasum for 1 month, followed by 2 months of taking a full dose, and finally 1 month with no lenabasum dosing. Compared with placebo, scores on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) were significantly improved with full dosing of lenabasum (P = .02), Dr. Werth said.

In this 16-week trial, the mean change in CDASI score dropped for participants in both the lenabasum and placebo groups for the first 4 weeks. After that, however, those taking lenabasum saw an improvement of about 8 points from baseline CDASI score at 8 weeks, while those taking placebo had a decline of 3 points (P = .05). The differences remained significant at trial’s end.

Patient-reported outcomes for pain were significantly better with lenabasum, with patients on lenabasum recording a decrease on the Patient-Reported Outcomes Measurement Information System–29 pain interference scale, while patients on placebo reported an increase in pain by the end of the study period (P = .026). Scores on two other patient-reported dermatomyositis scales were numerically improved for patients taking lenabasum, but the differences from the patients on placebo were not statistically significant, Dr. Werth said.

However, patients in the initial clinical trial were given the opportunity to continue in a long-term extension arm, and that group has seen the clinician-rated CDASI scores continue to fall, with a mean decrease of 22 points from baseline (about 12 further points from the mean for those on lenabasum in the initial trial) at the 68-week mark, she added.

Itch scores continued to drop as well, with a reduction of 3.7 points on the 5-D Itch scale by 68 weeks; at 16 weeks, the reduction for the lenabasum arm had been 1.3 points.

Skin samples taken from trial participants showed many fewer CD4 cells in those taking lenabasum, compared with placebo at week 12 of the initial study. Interferon-beta and -gamma levels also dropped in those taking lenabasum, but not in the placebo arm.

“Lenabasum has effects on cytokine signatures and inflammatory cells correlating with response to therapy,” Dr. Werth said, adding that the findings gave support for a planned global phase 3 clinical trial of lenabasum in dermatomyositis.

Dr. Werth reported receiving grants from Pfizer and Corbus, and consulting fees from Pfizer, Janssen, Neovacs, Idera Pharmaceuticals, Octapharma, CSL Behring, and Corbus Pharmaceuticals. The study was funded by Corbus, the National Institutes of Health, and the University of Pennsylvania.

[email protected]

LAKE BUENA VISTA, FLA. – When it comes to lupus nephritis, the guidelines – and prevailing wisdom – don’t always get it quite right, according to Michelle A. Petri, MD.

Mitchel L. Zoler/MDedge News

During an update at the annual meeting of the Florida Society of Rheumatology, she outlined five key components of lupus nephritis treatment, and the status of the evidence for each.

Antihypertensive therapy

Antihypertensive therapy isn’t just for hypertension in patients with lupus nephritis – it’s for reducing proteinuria and preventing renal fibrosis, said Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.

“I get a lot of push-back on this,” she added, explaining that other physicians often will stop the treatment as she prescribed it, because they believe it’s unnecessary.

She described a case involving a 33-year-old African American man with blood pressure of 132/86 mm Hg and grade 3+ ankle edema. Laboratory tests were remarkable for hematocrit (33.4%), white blood cell count (3.1), erythrocyte sedimentation rate (67 mm/hr) and urinalysis (2+ protein by dipstick, 3 red cells/high-power field, no casts). Additionally, 24-hour urine protein showed 400 mg of microalbumin, and he had a positive antinuclear antibody test, positive anti–double stranded DNA, and low complement.

“I’m going to argue really strenuously that he has to be on an ACE inhibitor or an ARB [angiotensin receptor blocker],” she said, explaining that even before an immunosuppressant therapy is started, optimizing ACE inhibitor or ARB therapy can reduce proteinuria by 50%.

The “sweet spot” for blood pressure in these patients is between 110 and 129, she said.

“You don’t want it too low, because you might hurt renal perfusion, but you sure don’t want it above 130,” she said.

The problem is that many physicians think 110 or 112 is too low.

“Not for a lupus nephritis patient,” she said. “It’s really where we want to be.”

ACE inhibitors and ARBs are preferable for reaching this goal, she said, noting that calcium channel blockers have been linked with shorter time to renal failure.

Hydroxychloroquine

Everyone with lupus nephritis should be on hydroxychloroquine, Dr. Petri argued.

“It improves renal outcomes,” she said. “It more than triples the chance that a patient will have a complete renal response.”

Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) are in agreement on this, she said.

Even the renal guidelines for lupus nephritis now include hydroxychloroquine as mandatory, she added, noting that it is not necessary to check glucose-6-phosphate dehydrogenase (G6PD) before starting treatment.

In fact, a recent study showed that only 2 of 11 patients with G6PD deficiency had episodes of hemolysis, and those episodes did not occur during hydroxychloroquine therapy. The authors concluded that the routine measurement of G6PD levels and withholding therapy among African American patients with G6PD deficiency is not supported, she said (Arthritis Care Res. 2018;70[3]:481-5).

“Of course, if your patient has renal insufficiency you’re going to have to reduce the dose in half,” she noted.
 

Vitamin D

Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.

In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).

“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
 

Mycophenolate mofetil

The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.

Left untreated, he would be in end-stage renal disease within a year, she said.

“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.

This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.

“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”

In this case, however, the best induction therapy is mycophenolate mofetil, she said.

“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”

In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.

After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”

“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.

“So we really need something that’s much more successful.”
 

Steroids

How much prednisone should lupus nephritis patients get?

As little as possible, according to Dr. Petri.

“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”

She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.

“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.

“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.

EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”

“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”

Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).

“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”

Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.

“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.

“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).

Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).

Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.

[email protected]

LAKE BUENA VISTA, FLA. – When it comes to lupus nephritis, the guidelines – and prevailing wisdom – don’t always get it quite right, according to Michelle A. Petri, MD.

Mitchel L. Zoler/MDedge News

During an update at the annual meeting of the Florida Society of Rheumatology, she outlined five key components of lupus nephritis treatment, and the status of the evidence for each.

Antihypertensive therapy

Antihypertensive therapy isn’t just for hypertension in patients with lupus nephritis – it’s for reducing proteinuria and preventing renal fibrosis, said Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.

“I get a lot of push-back on this,” she added, explaining that other physicians often will stop the treatment as she prescribed it, because they believe it’s unnecessary.

She described a case involving a 33-year-old African American man with blood pressure of 132/86 mm Hg and grade 3+ ankle edema. Laboratory tests were remarkable for hematocrit (33.4%), white blood cell count (3.1), erythrocyte sedimentation rate (67 mm/hr) and urinalysis (2+ protein by dipstick, 3 red cells/high-power field, no casts). Additionally, 24-hour urine protein showed 400 mg of microalbumin, and he had a positive antinuclear antibody test, positive anti–double stranded DNA, and low complement.

“I’m going to argue really strenuously that he has to be on an ACE inhibitor or an ARB [angiotensin receptor blocker],” she said, explaining that even before an immunosuppressant therapy is started, optimizing ACE inhibitor or ARB therapy can reduce proteinuria by 50%.

The “sweet spot” for blood pressure in these patients is between 110 and 129, she said.

“You don’t want it too low, because you might hurt renal perfusion, but you sure don’t want it above 130,” she said.

The problem is that many physicians think 110 or 112 is too low.

“Not for a lupus nephritis patient,” she said. “It’s really where we want to be.”

ACE inhibitors and ARBs are preferable for reaching this goal, she said, noting that calcium channel blockers have been linked with shorter time to renal failure.

Hydroxychloroquine

Everyone with lupus nephritis should be on hydroxychloroquine, Dr. Petri argued.

“It improves renal outcomes,” she said. “It more than triples the chance that a patient will have a complete renal response.”

Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) are in agreement on this, she said.

Even the renal guidelines for lupus nephritis now include hydroxychloroquine as mandatory, she added, noting that it is not necessary to check glucose-6-phosphate dehydrogenase (G6PD) before starting treatment.

In fact, a recent study showed that only 2 of 11 patients with G6PD deficiency had episodes of hemolysis, and those episodes did not occur during hydroxychloroquine therapy. The authors concluded that the routine measurement of G6PD levels and withholding therapy among African American patients with G6PD deficiency is not supported, she said (Arthritis Care Res. 2018;70[3]:481-5).

“Of course, if your patient has renal insufficiency you’re going to have to reduce the dose in half,” she noted.
 

Vitamin D

Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.

In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).

“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
 

Mycophenolate mofetil

The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.

Left untreated, he would be in end-stage renal disease within a year, she said.

“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.

This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.

“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”

In this case, however, the best induction therapy is mycophenolate mofetil, she said.

“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”

In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.

After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”

“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.

“So we really need something that’s much more successful.”
 

Steroids

How much prednisone should lupus nephritis patients get?

As little as possible, according to Dr. Petri.

“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”

She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.

“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.

“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.

EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”

“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”

Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).

“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”

Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.

“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.

“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).

Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).

Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.

[email protected]

LAKE BUENA VISTA, FLA. – When it comes to lupus nephritis, the guidelines – and prevailing wisdom – don’t always get it quite right, according to Michelle A. Petri, MD.

Mitchel L. Zoler/MDedge News

During an update at the annual meeting of the Florida Society of Rheumatology, she outlined five key components of lupus nephritis treatment, and the status of the evidence for each.

Antihypertensive therapy

Antihypertensive therapy isn’t just for hypertension in patients with lupus nephritis – it’s for reducing proteinuria and preventing renal fibrosis, said Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.

“I get a lot of push-back on this,” she added, explaining that other physicians often will stop the treatment as she prescribed it, because they believe it’s unnecessary.

She described a case involving a 33-year-old African American man with blood pressure of 132/86 mm Hg and grade 3+ ankle edema. Laboratory tests were remarkable for hematocrit (33.4%), white blood cell count (3.1), erythrocyte sedimentation rate (67 mm/hr) and urinalysis (2+ protein by dipstick, 3 red cells/high-power field, no casts). Additionally, 24-hour urine protein showed 400 mg of microalbumin, and he had a positive antinuclear antibody test, positive anti–double stranded DNA, and low complement.

“I’m going to argue really strenuously that he has to be on an ACE inhibitor or an ARB [angiotensin receptor blocker],” she said, explaining that even before an immunosuppressant therapy is started, optimizing ACE inhibitor or ARB therapy can reduce proteinuria by 50%.

The “sweet spot” for blood pressure in these patients is between 110 and 129, she said.

“You don’t want it too low, because you might hurt renal perfusion, but you sure don’t want it above 130,” she said.

The problem is that many physicians think 110 or 112 is too low.

“Not for a lupus nephritis patient,” she said. “It’s really where we want to be.”

ACE inhibitors and ARBs are preferable for reaching this goal, she said, noting that calcium channel blockers have been linked with shorter time to renal failure.

Hydroxychloroquine

Everyone with lupus nephritis should be on hydroxychloroquine, Dr. Petri argued.

“It improves renal outcomes,” she said. “It more than triples the chance that a patient will have a complete renal response.”

Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) are in agreement on this, she said.

Even the renal guidelines for lupus nephritis now include hydroxychloroquine as mandatory, she added, noting that it is not necessary to check glucose-6-phosphate dehydrogenase (G6PD) before starting treatment.

In fact, a recent study showed that only 2 of 11 patients with G6PD deficiency had episodes of hemolysis, and those episodes did not occur during hydroxychloroquine therapy. The authors concluded that the routine measurement of G6PD levels and withholding therapy among African American patients with G6PD deficiency is not supported, she said (Arthritis Care Res. 2018;70[3]:481-5).

“Of course, if your patient has renal insufficiency you’re going to have to reduce the dose in half,” she noted.
 

Vitamin D

Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.

In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).

“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
 

Mycophenolate mofetil

The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.

Left untreated, he would be in end-stage renal disease within a year, she said.

“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.

This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.

“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”

In this case, however, the best induction therapy is mycophenolate mofetil, she said.

“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”

In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.

After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”

“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.

“So we really need something that’s much more successful.”
 

Steroids

How much prednisone should lupus nephritis patients get?

As little as possible, according to Dr. Petri.

“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”

She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.

“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.

“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.

EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”

“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”

Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).

“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”

Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.

“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.

“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).

Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).

Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.

[email protected]

LAKE BUENA VISTA, FLA. – “Crude and uninformed.”

That’s how Leonard H. Calabrese, DO, described the general approach to managing immune-related adverse events (irAEs) in cancer patients treated with checkpoint inhibitor therapy.

Rheumatologists have the expertise to change that, he said during a presentation at the annual meeting of the Florida Society of Rheumatology.

“The therapy is where it’s at – this is where rheumatologists come into play,” said Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic.

According to relevant guidelines, such as those recently developed by the American Society of Clinical Oncology/National Comprehensive Cancer Network and the Society for the Immunotherapy of Cancer, irAEs are graded on a severity-based scale. Grade 1 events are mild and generally require observation; grade 2 events may include arthralgias and myalgias that are typically treated with symptomatic therapy; grade 3 events involve more serious conditions and may require hospitalization; and grade 4 events are life-threatening and may require targeted therapies.

“Grade 3 – these would be people with profound polyarthritis, vasculitis, myositis – rely heavily on glucocorticoids, and if patients don’t tolerate glucocorticoids or don’t respond to tapering doses, consider the use of [disease-modifying antirheumatic drugs],” he said, noting that the guidelines are vaguely written and refer to both conventional and biologic DMARDs.

“This is all anecdotal at the present time; this is a story to be discovered as we move along,” he explained.

A recommendation for the use of targeted therapies, such as tumor necrosis factor inhibitors, anti-interleukin (IL)-6, and antimetabolites, in patients with the most advanced disease is similarly vague and just represents “the beginning of the beginning,” he said.

The “crude and uninformed” nature of the current approach to irAEs, as he described it, is related to a failure to consider the immunopathogenesis of specific conditions.

“The oncologists, who have done such an incredible job with this – learning about derm[atitis] and colitis that respond to steroids and infliximab, immediately extrapolated that steroids and infliximab are for everything,” he said. “They give it for pneumonitis, they give it for [central nervous system] disease, they give it for everything.”

However, there’s no pathophysiologic basis for doing so, and not surprisingly, some patients don’t respond.

“Here we are sitting on this amazing armamentarium of targeted therapies and only now just starting to ask the questions: ‘Do they offer benefit for these irAEs? Do they offer risk? Will they blunt the antitumoral response of this?’ ” he said.

A “Personal View” published in Lancet Oncology in January 2019 was among the first from the oncology arena to pose these questions (20[1]:PE54-64. doi: 10.1016/S1470-2045[18]30828-3).

“It said, ‘well maybe we should look at the immunopathogenesis of each of these diseases and then pick the therapy – if it’s IL-17 mediated, we’ve got drugs for that; if it’s IL-1 mediated, we’ve got drugs for that; if it’s interferon-mediated, we can deal with that,’ ” he said. “The problem is we don’t yet have detailed immunopathogenic knowledge of these diseases, but it’s coming.”

Data needed to define best treatments

Data also are emerging to define the roles of various targeted therapies for treating irAEs, but most of the evidence remains anecdotal, he said.

For example, anecdotal reports suggest that rituximab has some efficacy in cytopenias, arthritis, and myositis, and a case report suggests that secukinumab and other IL-17 inhibitors may have benefit in psoriasis and inflammatory bowel disease with tumoral progression, he said.

A reasonable question has been whether attacking T cells might be worthwhile given that “these things are all T-cell mediated,” but until very recently, “no one has had the temerity to actually do this,” he said.

However, two cases reported in the June 13 issue of the New England Journal of Medicine described “very successful” treatment of checkpoint inhibitor-associated myocarditis. One case described the use of alemtuzumab in a 71-year-old woman being treated with first-line pembrolizumab for stage IV melanoma, and another case involved the use of abatacept for severe, glucocorticoid-refractory myocarditis in a 66-year-old woman who had been treated with nivolumab for metastatic lung cancer (2019;380:2375-6 and 2377-79).Dr. Calabrese urged rheumatologists who are interested in addressing the treatment of irAEs to “get involved.”

“People need good rheumatologists, and I will tell you that whoever your oncologists are who you refer patients to for cancer – they’re seeing this and they need help,” he said. “Particularly outside of these big major centers, just having someone to lean on is very important.”

Keep in mind, however, that triage is very important, he said, stressing that patients with irAEs “actually need to be seen.”

Between three and five new irAE patients are being seen each week at the Cleveland Clinic, he noted.
 

Need for multidisciplinary collaboration

Collaboration was the focus of an article in the June 2019 issue of the Journal of the National Comprehensive Cancer Network, which looked at the value of a virtual “multidisciplinary toxicity team” for managing cancer irAEs. The investigators found that such an approach was feasible, used by oncology providers, and effective for facilitating toxicity identification and management.

A number of other recent studies have attempted to assess confidence and knowledge of rheumatologists and others with respect to the treatment of irAEs in cancer patients, and the findings highlight the need for education at the oncologist, specialist, generalist, and advanced practitioner level, Dr. Calabrese said, adding that the findings also highlight a need for assistance from “big pharma, which makes these drugs,” in supporting this type of education.

The need for “novel venues for such educational interchange” also was the topic of a study on a new Cleveland Clinic irAE tumor board that he and his colleagues presented at the 2018 annual meeting of the American College of Rheumatology.

The study showed that the tumor board, which is now “one of the most popular conferences at the clinic,” has educational value for participants, and “may increase skill and confidence in patient management.”

“We just present case after case of new things. Last week was autoimmune lipodystrophy from checkpoint inhibitors,” he said, noting that the rheumatologists and oncologists at the clinic co-chair the events.

In another 2018 article, he and coauthor Xavier Mariette, MD, further highlighted the “evolving role of the rheumatologist” in managing cancer treatment–related irAEs.

“We think that rheumatologists have a lot to offer here,” he said. “We understand these drugs better than all of these guys, and as we gain more knowledge in this field, we have guidance, and counsel, and experience to add to this.”

He encouraged rheumatologists to “stay tuned on this, follow this along,” adding that their help is needed.

“It’s really simple – talk to your oncologists and say, ‘Hey, what are you doing with these patients?’ – and I think you’ll have something new, exciting, and invigorating.”

Dr. Calabrese reported serving as a consultant and/or speaker for Bristol-Myers Squibb, Genentech, AbbVie, Pfizer, Crescendo Bioscience, UCB, Janssen, Gilead, Sanofi-Regeneron, Novartis, AstraZeneca, and Amgen.

[email protected]

LAKE BUENA VISTA, FLA. – “Crude and uninformed.”

That’s how Leonard H. Calabrese, DO, described the general approach to managing immune-related adverse events (irAEs) in cancer patients treated with checkpoint inhibitor therapy.

Rheumatologists have the expertise to change that, he said during a presentation at the annual meeting of the Florida Society of Rheumatology.

“The therapy is where it’s at – this is where rheumatologists come into play,” said Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic.

According to relevant guidelines, such as those recently developed by the American Society of Clinical Oncology/National Comprehensive Cancer Network and the Society for the Immunotherapy of Cancer, irAEs are graded on a severity-based scale. Grade 1 events are mild and generally require observation; grade 2 events may include arthralgias and myalgias that are typically treated with symptomatic therapy; grade 3 events involve more serious conditions and may require hospitalization; and grade 4 events are life-threatening and may require targeted therapies.

“Grade 3 – these would be people with profound polyarthritis, vasculitis, myositis – rely heavily on glucocorticoids, and if patients don’t tolerate glucocorticoids or don’t respond to tapering doses, consider the use of [disease-modifying antirheumatic drugs],” he said, noting that the guidelines are vaguely written and refer to both conventional and biologic DMARDs.

“This is all anecdotal at the present time; this is a story to be discovered as we move along,” he explained.

A recommendation for the use of targeted therapies, such as tumor necrosis factor inhibitors, anti-interleukin (IL)-6, and antimetabolites, in patients with the most advanced disease is similarly vague and just represents “the beginning of the beginning,” he said.

The “crude and uninformed” nature of the current approach to irAEs, as he described it, is related to a failure to consider the immunopathogenesis of specific conditions.

“The oncologists, who have done such an incredible job with this – learning about derm[atitis] and colitis that respond to steroids and infliximab, immediately extrapolated that steroids and infliximab are for everything,” he said. “They give it for pneumonitis, they give it for [central nervous system] disease, they give it for everything.”

However, there’s no pathophysiologic basis for doing so, and not surprisingly, some patients don’t respond.

“Here we are sitting on this amazing armamentarium of targeted therapies and only now just starting to ask the questions: ‘Do they offer benefit for these irAEs? Do they offer risk? Will they blunt the antitumoral response of this?’ ” he said.

A “Personal View” published in Lancet Oncology in January 2019 was among the first from the oncology arena to pose these questions (20[1]:PE54-64. doi: 10.1016/S1470-2045[18]30828-3).

“It said, ‘well maybe we should look at the immunopathogenesis of each of these diseases and then pick the therapy – if it’s IL-17 mediated, we’ve got drugs for that; if it’s IL-1 mediated, we’ve got drugs for that; if it’s interferon-mediated, we can deal with that,’ ” he said. “The problem is we don’t yet have detailed immunopathogenic knowledge of these diseases, but it’s coming.”

Data needed to define best treatments

Data also are emerging to define the roles of various targeted therapies for treating irAEs, but most of the evidence remains anecdotal, he said.

For example, anecdotal reports suggest that rituximab has some efficacy in cytopenias, arthritis, and myositis, and a case report suggests that secukinumab and other IL-17 inhibitors may have benefit in psoriasis and inflammatory bowel disease with tumoral progression, he said.

A reasonable question has been whether attacking T cells might be worthwhile given that “these things are all T-cell mediated,” but until very recently, “no one has had the temerity to actually do this,” he said.

However, two cases reported in the June 13 issue of the New England Journal of Medicine described “very successful” treatment of checkpoint inhibitor-associated myocarditis. One case described the use of alemtuzumab in a 71-year-old woman being treated with first-line pembrolizumab for stage IV melanoma, and another case involved the use of abatacept for severe, glucocorticoid-refractory myocarditis in a 66-year-old woman who had been treated with nivolumab for metastatic lung cancer (2019;380:2375-6 and 2377-79).Dr. Calabrese urged rheumatologists who are interested in addressing the treatment of irAEs to “get involved.”

“People need good rheumatologists, and I will tell you that whoever your oncologists are who you refer patients to for cancer – they’re seeing this and they need help,” he said. “Particularly outside of these big major centers, just having someone to lean on is very important.”

Keep in mind, however, that triage is very important, he said, stressing that patients with irAEs “actually need to be seen.”

Between three and five new irAE patients are being seen each week at the Cleveland Clinic, he noted.
 

Need for multidisciplinary collaboration

Collaboration was the focus of an article in the June 2019 issue of the Journal of the National Comprehensive Cancer Network, which looked at the value of a virtual “multidisciplinary toxicity team” for managing cancer irAEs. The investigators found that such an approach was feasible, used by oncology providers, and effective for facilitating toxicity identification and management.

A number of other recent studies have attempted to assess confidence and knowledge of rheumatologists and others with respect to the treatment of irAEs in cancer patients, and the findings highlight the need for education at the oncologist, specialist, generalist, and advanced practitioner level, Dr. Calabrese said, adding that the findings also highlight a need for assistance from “big pharma, which makes these drugs,” in supporting this type of education.

The need for “novel venues for such educational interchange” also was the topic of a study on a new Cleveland Clinic irAE tumor board that he and his colleagues presented at the 2018 annual meeting of the American College of Rheumatology.

The study showed that the tumor board, which is now “one of the most popular conferences at the clinic,” has educational value for participants, and “may increase skill and confidence in patient management.”

“We just present case after case of new things. Last week was autoimmune lipodystrophy from checkpoint inhibitors,” he said, noting that the rheumatologists and oncologists at the clinic co-chair the events.

In another 2018 article, he and coauthor Xavier Mariette, MD, further highlighted the “evolving role of the rheumatologist” in managing cancer treatment–related irAEs.

“We think that rheumatologists have a lot to offer here,” he said. “We understand these drugs better than all of these guys, and as we gain more knowledge in this field, we have guidance, and counsel, and experience to add to this.”

He encouraged rheumatologists to “stay tuned on this, follow this along,” adding that their help is needed.

“It’s really simple – talk to your oncologists and say, ‘Hey, what are you doing with these patients?’ – and I think you’ll have something new, exciting, and invigorating.”

Dr. Calabrese reported serving as a consultant and/or speaker for Bristol-Myers Squibb, Genentech, AbbVie, Pfizer, Crescendo Bioscience, UCB, Janssen, Gilead, Sanofi-Regeneron, Novartis, AstraZeneca, and Amgen.

[email protected]

LAKE BUENA VISTA, FLA. – “Crude and uninformed.”

That’s how Leonard H. Calabrese, DO, described the general approach to managing immune-related adverse events (irAEs) in cancer patients treated with checkpoint inhibitor therapy.

Rheumatologists have the expertise to change that, he said during a presentation at the annual meeting of the Florida Society of Rheumatology.

“The therapy is where it’s at – this is where rheumatologists come into play,” said Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic.

According to relevant guidelines, such as those recently developed by the American Society of Clinical Oncology/National Comprehensive Cancer Network and the Society for the Immunotherapy of Cancer, irAEs are graded on a severity-based scale. Grade 1 events are mild and generally require observation; grade 2 events may include arthralgias and myalgias that are typically treated with symptomatic therapy; grade 3 events involve more serious conditions and may require hospitalization; and grade 4 events are life-threatening and may require targeted therapies.

“Grade 3 – these would be people with profound polyarthritis, vasculitis, myositis – rely heavily on glucocorticoids, and if patients don’t tolerate glucocorticoids or don’t respond to tapering doses, consider the use of [disease-modifying antirheumatic drugs],” he said, noting that the guidelines are vaguely written and refer to both conventional and biologic DMARDs.

“This is all anecdotal at the present time; this is a story to be discovered as we move along,” he explained.

A recommendation for the use of targeted therapies, such as tumor necrosis factor inhibitors, anti-interleukin (IL)-6, and antimetabolites, in patients with the most advanced disease is similarly vague and just represents “the beginning of the beginning,” he said.

The “crude and uninformed” nature of the current approach to irAEs, as he described it, is related to a failure to consider the immunopathogenesis of specific conditions.

“The oncologists, who have done such an incredible job with this – learning about derm[atitis] and colitis that respond to steroids and infliximab, immediately extrapolated that steroids and infliximab are for everything,” he said. “They give it for pneumonitis, they give it for [central nervous system] disease, they give it for everything.”

However, there’s no pathophysiologic basis for doing so, and not surprisingly, some patients don’t respond.

“Here we are sitting on this amazing armamentarium of targeted therapies and only now just starting to ask the questions: ‘Do they offer benefit for these irAEs? Do they offer risk? Will they blunt the antitumoral response of this?’ ” he said.

A “Personal View” published in Lancet Oncology in January 2019 was among the first from the oncology arena to pose these questions (20[1]:PE54-64. doi: 10.1016/S1470-2045[18]30828-3).

“It said, ‘well maybe we should look at the immunopathogenesis of each of these diseases and then pick the therapy – if it’s IL-17 mediated, we’ve got drugs for that; if it’s IL-1 mediated, we’ve got drugs for that; if it’s interferon-mediated, we can deal with that,’ ” he said. “The problem is we don’t yet have detailed immunopathogenic knowledge of these diseases, but it’s coming.”

Data needed to define best treatments

Data also are emerging to define the roles of various targeted therapies for treating irAEs, but most of the evidence remains anecdotal, he said.

For example, anecdotal reports suggest that rituximab has some efficacy in cytopenias, arthritis, and myositis, and a case report suggests that secukinumab and other IL-17 inhibitors may have benefit in psoriasis and inflammatory bowel disease with tumoral progression, he said.

A reasonable question has been whether attacking T cells might be worthwhile given that “these things are all T-cell mediated,” but until very recently, “no one has had the temerity to actually do this,” he said.

However, two cases reported in the June 13 issue of the New England Journal of Medicine described “very successful” treatment of checkpoint inhibitor-associated myocarditis. One case described the use of alemtuzumab in a 71-year-old woman being treated with first-line pembrolizumab for stage IV melanoma, and another case involved the use of abatacept for severe, glucocorticoid-refractory myocarditis in a 66-year-old woman who had been treated with nivolumab for metastatic lung cancer (2019;380:2375-6 and 2377-79).Dr. Calabrese urged rheumatologists who are interested in addressing the treatment of irAEs to “get involved.”

“People need good rheumatologists, and I will tell you that whoever your oncologists are who you refer patients to for cancer – they’re seeing this and they need help,” he said. “Particularly outside of these big major centers, just having someone to lean on is very important.”

Keep in mind, however, that triage is very important, he said, stressing that patients with irAEs “actually need to be seen.”

Between three and five new irAE patients are being seen each week at the Cleveland Clinic, he noted.
 

Need for multidisciplinary collaboration

Collaboration was the focus of an article in the June 2019 issue of the Journal of the National Comprehensive Cancer Network, which looked at the value of a virtual “multidisciplinary toxicity team” for managing cancer irAEs. The investigators found that such an approach was feasible, used by oncology providers, and effective for facilitating toxicity identification and management.

A number of other recent studies have attempted to assess confidence and knowledge of rheumatologists and others with respect to the treatment of irAEs in cancer patients, and the findings highlight the need for education at the oncologist, specialist, generalist, and advanced practitioner level, Dr. Calabrese said, adding that the findings also highlight a need for assistance from “big pharma, which makes these drugs,” in supporting this type of education.

The need for “novel venues for such educational interchange” also was the topic of a study on a new Cleveland Clinic irAE tumor board that he and his colleagues presented at the 2018 annual meeting of the American College of Rheumatology.

The study showed that the tumor board, which is now “one of the most popular conferences at the clinic,” has educational value for participants, and “may increase skill and confidence in patient management.”

“We just present case after case of new things. Last week was autoimmune lipodystrophy from checkpoint inhibitors,” he said, noting that the rheumatologists and oncologists at the clinic co-chair the events.

In another 2018 article, he and coauthor Xavier Mariette, MD, further highlighted the “evolving role of the rheumatologist” in managing cancer treatment–related irAEs.

“We think that rheumatologists have a lot to offer here,” he said. “We understand these drugs better than all of these guys, and as we gain more knowledge in this field, we have guidance, and counsel, and experience to add to this.”

He encouraged rheumatologists to “stay tuned on this, follow this along,” adding that their help is needed.

“It’s really simple – talk to your oncologists and say, ‘Hey, what are you doing with these patients?’ – and I think you’ll have something new, exciting, and invigorating.”

Dr. Calabrese reported serving as a consultant and/or speaker for Bristol-Myers Squibb, Genentech, AbbVie, Pfizer, Crescendo Bioscience, UCB, Janssen, Gilead, Sanofi-Regeneron, Novartis, AstraZeneca, and Amgen.

[email protected]

The Food and Drug Administration Arthritis Advisory Committee recommended approval of nintedanib for the treatment of interstitial lung disease in patients with systemic sclerosis by a 10-7 vote on July 25, 2019. If the FDA acts in accord with the panel’s recommendation, it would make nintedanib (Ofev) the first drug to receive marketing approval for this indication.

Nintedanib has had FDA approval for treating idiopathic pulmonary fibrosis since 2014, and the manufacturer, Boehringer Ingelheim, designed the current pivotal trial with 576 patients to broaden the indication to patients with a different but similar fibrotic lung disease, interstitial lung disease (ILD), that is a common and eventually lethal complication of systemic sclerosis. The results of the pivotal study, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) trial, recently appeared in print and showed that patients randomized to receive 150 mg of nintedanib orally twice daily had an average 41-mL cut in the rate of loss of forced vital capacity (FVC) during 52 weeks on treatment, compared with those randomized to placebo. This was a 44% relative reduction in rate of FVC loss that was statistically significant for the study’s primary endpoint (N Engl J Med. 2019 June 27;380[26]:2518-28).

Votes in favor of FDA approval for many on the panel seemed to stem from a combination of the fact that nintedanib met the pivotal trial’s primary endpoint; which had been developed in consultation with the FDA, as well as the absence of any new safety signals when compared with prior experience using the drug; the lack of any treatment specifically recognized as beneficial to systemic sclerosis patients who develop the terminal complication of ILD; and the challenge of running a second trial in an orphan disease with an estimated U.S. prevalence of no more than 100,000 patients. Several committee members who voted in favor of nintedanib’s approval also voiced concern that the case in favor of its benefit/risk balance was not open and shut.

“I have a fair amount of apprehension,” admitted the committee’s chair, Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School, Boston. “I support the needs of patients, but we don’t want to give them false hope. We need to be able to say who will benefit, and the single study [SENSCIS] results don’t tell us how to use the drug. I want to understand which patient subgroups benefit.” He suggested that the FDA mandate further data collection through postmarketing studies.

Comments from panel members who voted against recommending approval generally focused on what was generally agreed to be a very modest treatment effect with a 41-mL average difference in FVC decline that has marginal clinical meaningfulness. Although the SENSCIS results met the study’s primary endpoint it was neutral for all prespecified secondary endpoints, including a measure of quality of life, although many on the panel agreed that a good measure of quality of life in the target patient population is lacking. Some sensitivity analyses run by FDA staffers also failed to confirm the primary result. Fewer questions arose about safety, although some panelists expressed concern about gastrointestinal effects, especially diarrhea, that seemed to link with treatment, as well as a signal for an increased incidence of pneumonia among patients on nintedanib. The data also showed a possible signal of reduced efficacy among patients who also received treatment with the immunosuppressive agent mycophenolate mofetil, often used off label to treat systemic sclerosis patients with ILD. However, a statistician involved in the discussion warned against overinterpreting this or other subgroup analyses.

Dr. Solomon has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer.

[email protected]

The Food and Drug Administration Arthritis Advisory Committee recommended approval of nintedanib for the treatment of interstitial lung disease in patients with systemic sclerosis by a 10-7 vote on July 25, 2019. If the FDA acts in accord with the panel’s recommendation, it would make nintedanib (Ofev) the first drug to receive marketing approval for this indication.

Nintedanib has had FDA approval for treating idiopathic pulmonary fibrosis since 2014, and the manufacturer, Boehringer Ingelheim, designed the current pivotal trial with 576 patients to broaden the indication to patients with a different but similar fibrotic lung disease, interstitial lung disease (ILD), that is a common and eventually lethal complication of systemic sclerosis. The results of the pivotal study, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) trial, recently appeared in print and showed that patients randomized to receive 150 mg of nintedanib orally twice daily had an average 41-mL cut in the rate of loss of forced vital capacity (FVC) during 52 weeks on treatment, compared with those randomized to placebo. This was a 44% relative reduction in rate of FVC loss that was statistically significant for the study’s primary endpoint (N Engl J Med. 2019 June 27;380[26]:2518-28).

Votes in favor of FDA approval for many on the panel seemed to stem from a combination of the fact that nintedanib met the pivotal trial’s primary endpoint; which had been developed in consultation with the FDA, as well as the absence of any new safety signals when compared with prior experience using the drug; the lack of any treatment specifically recognized as beneficial to systemic sclerosis patients who develop the terminal complication of ILD; and the challenge of running a second trial in an orphan disease with an estimated U.S. prevalence of no more than 100,000 patients. Several committee members who voted in favor of nintedanib’s approval also voiced concern that the case in favor of its benefit/risk balance was not open and shut.

“I have a fair amount of apprehension,” admitted the committee’s chair, Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School, Boston. “I support the needs of patients, but we don’t want to give them false hope. We need to be able to say who will benefit, and the single study [SENSCIS] results don’t tell us how to use the drug. I want to understand which patient subgroups benefit.” He suggested that the FDA mandate further data collection through postmarketing studies.

Comments from panel members who voted against recommending approval generally focused on what was generally agreed to be a very modest treatment effect with a 41-mL average difference in FVC decline that has marginal clinical meaningfulness. Although the SENSCIS results met the study’s primary endpoint it was neutral for all prespecified secondary endpoints, including a measure of quality of life, although many on the panel agreed that a good measure of quality of life in the target patient population is lacking. Some sensitivity analyses run by FDA staffers also failed to confirm the primary result. Fewer questions arose about safety, although some panelists expressed concern about gastrointestinal effects, especially diarrhea, that seemed to link with treatment, as well as a signal for an increased incidence of pneumonia among patients on nintedanib. The data also showed a possible signal of reduced efficacy among patients who also received treatment with the immunosuppressive agent mycophenolate mofetil, often used off label to treat systemic sclerosis patients with ILD. However, a statistician involved in the discussion warned against overinterpreting this or other subgroup analyses.

Dr. Solomon has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer.

[email protected]

The Food and Drug Administration Arthritis Advisory Committee recommended approval of nintedanib for the treatment of interstitial lung disease in patients with systemic sclerosis by a 10-7 vote on July 25, 2019. If the FDA acts in accord with the panel’s recommendation, it would make nintedanib (Ofev) the first drug to receive marketing approval for this indication.

Nintedanib has had FDA approval for treating idiopathic pulmonary fibrosis since 2014, and the manufacturer, Boehringer Ingelheim, designed the current pivotal trial with 576 patients to broaden the indication to patients with a different but similar fibrotic lung disease, interstitial lung disease (ILD), that is a common and eventually lethal complication of systemic sclerosis. The results of the pivotal study, the SENSCIS (Safety and Efficacy of Nintedanib in Systemic Sclerosis) trial, recently appeared in print and showed that patients randomized to receive 150 mg of nintedanib orally twice daily had an average 41-mL cut in the rate of loss of forced vital capacity (FVC) during 52 weeks on treatment, compared with those randomized to placebo. This was a 44% relative reduction in rate of FVC loss that was statistically significant for the study’s primary endpoint (N Engl J Med. 2019 June 27;380[26]:2518-28).

Votes in favor of FDA approval for many on the panel seemed to stem from a combination of the fact that nintedanib met the pivotal trial’s primary endpoint; which had been developed in consultation with the FDA, as well as the absence of any new safety signals when compared with prior experience using the drug; the lack of any treatment specifically recognized as beneficial to systemic sclerosis patients who develop the terminal complication of ILD; and the challenge of running a second trial in an orphan disease with an estimated U.S. prevalence of no more than 100,000 patients. Several committee members who voted in favor of nintedanib’s approval also voiced concern that the case in favor of its benefit/risk balance was not open and shut.

“I have a fair amount of apprehension,” admitted the committee’s chair, Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School, Boston. “I support the needs of patients, but we don’t want to give them false hope. We need to be able to say who will benefit, and the single study [SENSCIS] results don’t tell us how to use the drug. I want to understand which patient subgroups benefit.” He suggested that the FDA mandate further data collection through postmarketing studies.

Comments from panel members who voted against recommending approval generally focused on what was generally agreed to be a very modest treatment effect with a 41-mL average difference in FVC decline that has marginal clinical meaningfulness. Although the SENSCIS results met the study’s primary endpoint it was neutral for all prespecified secondary endpoints, including a measure of quality of life, although many on the panel agreed that a good measure of quality of life in the target patient population is lacking. Some sensitivity analyses run by FDA staffers also failed to confirm the primary result. Fewer questions arose about safety, although some panelists expressed concern about gastrointestinal effects, especially diarrhea, that seemed to link with treatment, as well as a signal for an increased incidence of pneumonia among patients on nintedanib. The data also showed a possible signal of reduced efficacy among patients who also received treatment with the immunosuppressive agent mycophenolate mofetil, often used off label to treat systemic sclerosis patients with ILD. However, a statistician involved in the discussion warned against overinterpreting this or other subgroup analyses.

Dr. Solomon has received research support from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer.

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