Lupus & Connective Tissue Diseases

Fully 48% of patients with autoimmune rheumatic diseases who developed persistent hypogammaglobulinemia after initiating treatment with immunomodulatory agents harbored gene variants associated with inborn errors of immunity, according to the findings of a single-center study published in Annals of the Rheumatic Diseases.

The results raise the possibility of a shared genetic etiology between “primary” and “secondary” hypogammaglobulinemia and suggest that some cases of autoimmune rheumatic disease may result from inborn errors of immunity. “In other words, a rheumatologist may be treating the rheumatic manifestations of a primary immunodeficiency disorder,” the study’s lead author, Georgios Sogkas, MD, PhD, said in an interview.

‘Striking’ findings suggest a future in personalized medicine

Experts who were not involved in the study called the results noteworthy. “The fact that half of patients with rheumatic disease who developed secondary hypogammaglobulinemia were found to have a functionally relevant mutation in a known PID gene is striking, albeit purely circumstantial given the absence of any functional or mechanistic data,” said Michael J. Ombrello, MD, principal investigator and head of the translational genetics and genomics unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study.

The findings, if they are validated by additional studies, might help clinicians personalize medicine by avoiding hypogammaglobulinemia-inducing immunomodulatory regimens in genetically predisposed patients, or by targeting Janus kinase (JAK) inhibitor therapy for patients with STAT3 gain-of-function variants, or PI3K delta inhibitors for patients with variants leading to hyperactivation of the PI3Kdelta gene, Dr. Sogkas said.

Dr. Ombrello agreed: “Whether the hypogammaglobulinemia is classified as primary or secondary, the presence of these genetic variants in half of patients with hypogammaglobulinemia suggests an opportunity to improve clinical care. Although far off at this point, one can imagine a day where genetic data allows a rheumatologist to identify new-onset rheumatic disease patients carrying PID gene mutations and cater their therapy and monitoring accordingly.”

If further research validates these findings, they would add to a growing body of support for incorporating expanded or universal exome or genome sequencing in the care of medically complex patients, such as those with rheumatic diseases, Dr. Ombrello said. However, he cautioned that the investigators could have “overstated” the relationship in their study between secondary hypogammaglobulinemia and immunomodulatory treatment. The fact that a small group of study participants (about 7%) developed hypogammaglobulinemia after initiating immunomodulatory therapy does not confirm a causal relationship, he emphasized. Common variable immune deficiency (CVID) can develop in adults as late as the fifth and sixth decade of life, he noted, making it “not implausible that a small number of rheumatic disease patients would develop CVID while under the care of a rheumatologist. Would these patients have developed hypogammaglobulinemia even without treatment with immunomodulators, purely related to their genetic mutations? If so, they would be better classified as having primary immune deficiency, although that distinction is largely one of semantics.”

‘Rheumatologists are obliged to step up’

Interestingly, only 23% of the patients with hypogammaglobulinemia in the study had a clinically significant history of infections even though only 9% were receiving prophylactic antibiotics. Such findings highlight the complexity of PIDs, according to experts. “A long generation ago, we thought of immunodeficiencies as infections. Now we see them as autoimmune diseases, inflammatory diseases, allergic diseases – the spectrum continues to enlarge,” said Leonard H. Calabrese, DO, the RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, who was not involved in the study.

Dr. Calabrese noted that more than 450 monogenic variants have been linked to inborn errors of immunity. “Because these [PIDs] can mimic autoinflammatory presentations, rheumatologists are obliged to step up and gain a greater understanding, to be able to recognize and diagnose them and sort them out.”

Future goals should include quantifying the prevalence of genetic variants underlying hypogammaglobulinemia among patients with rheumatic diseases, and better characterizing outcomes and phenotypes of patients harboring variants linked to inborn errors of immunity, Dr. Sogkas said. “Whether these patients actually have a different disease than what they are being treated for, I can’t tell from this paper, and that’s an important question for the future,” added Dr. Calabrese. “I also do wonder about the effects of different drugs,” he said, noting that many patients with PID-associated autosomal gene variants developed persistent secondary hypogammaglobulinemia after initiating methotrexate. “It makes me wonder whether some of these genes have a specific interaction with methotrexate,” he said. “That could be a biomarker for drug toxicity.”

Study funders included the German Research Foundation, the German multiorgan Autoimmunity Network, Hannover Medical School, the Rosemarie-Germscheid Foundation, the German Academic Exchange Service, HBRS, the Center for Infection Biology, and the German Center for Infection Research. The investigators reported having no competing interests.

SOURCE: Sogkas G et al. Ann Rheum Dis. 2020 Oct 12. doi: 10.1136/annrheumdis-2020-218280.

Fully 48% of patients with autoimmune rheumatic diseases who developed persistent hypogammaglobulinemia after initiating treatment with immunomodulatory agents harbored gene variants associated with inborn errors of immunity, according to the findings of a single-center study published in Annals of the Rheumatic Diseases.

The results raise the possibility of a shared genetic etiology between “primary” and “secondary” hypogammaglobulinemia and suggest that some cases of autoimmune rheumatic disease may result from inborn errors of immunity. “In other words, a rheumatologist may be treating the rheumatic manifestations of a primary immunodeficiency disorder,” the study’s lead author, Georgios Sogkas, MD, PhD, said in an interview.

‘Striking’ findings suggest a future in personalized medicine

Experts who were not involved in the study called the results noteworthy. “The fact that half of patients with rheumatic disease who developed secondary hypogammaglobulinemia were found to have a functionally relevant mutation in a known PID gene is striking, albeit purely circumstantial given the absence of any functional or mechanistic data,” said Michael J. Ombrello, MD, principal investigator and head of the translational genetics and genomics unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study.

The findings, if they are validated by additional studies, might help clinicians personalize medicine by avoiding hypogammaglobulinemia-inducing immunomodulatory regimens in genetically predisposed patients, or by targeting Janus kinase (JAK) inhibitor therapy for patients with STAT3 gain-of-function variants, or PI3K delta inhibitors for patients with variants leading to hyperactivation of the PI3Kdelta gene, Dr. Sogkas said.

Dr. Ombrello agreed: “Whether the hypogammaglobulinemia is classified as primary or secondary, the presence of these genetic variants in half of patients with hypogammaglobulinemia suggests an opportunity to improve clinical care. Although far off at this point, one can imagine a day where genetic data allows a rheumatologist to identify new-onset rheumatic disease patients carrying PID gene mutations and cater their therapy and monitoring accordingly.”

If further research validates these findings, they would add to a growing body of support for incorporating expanded or universal exome or genome sequencing in the care of medically complex patients, such as those with rheumatic diseases, Dr. Ombrello said. However, he cautioned that the investigators could have “overstated” the relationship in their study between secondary hypogammaglobulinemia and immunomodulatory treatment. The fact that a small group of study participants (about 7%) developed hypogammaglobulinemia after initiating immunomodulatory therapy does not confirm a causal relationship, he emphasized. Common variable immune deficiency (CVID) can develop in adults as late as the fifth and sixth decade of life, he noted, making it “not implausible that a small number of rheumatic disease patients would develop CVID while under the care of a rheumatologist. Would these patients have developed hypogammaglobulinemia even without treatment with immunomodulators, purely related to their genetic mutations? If so, they would be better classified as having primary immune deficiency, although that distinction is largely one of semantics.”

‘Rheumatologists are obliged to step up’

Interestingly, only 23% of the patients with hypogammaglobulinemia in the study had a clinically significant history of infections even though only 9% were receiving prophylactic antibiotics. Such findings highlight the complexity of PIDs, according to experts. “A long generation ago, we thought of immunodeficiencies as infections. Now we see them as autoimmune diseases, inflammatory diseases, allergic diseases – the spectrum continues to enlarge,” said Leonard H. Calabrese, DO, the RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, who was not involved in the study.

Dr. Calabrese noted that more than 450 monogenic variants have been linked to inborn errors of immunity. “Because these [PIDs] can mimic autoinflammatory presentations, rheumatologists are obliged to step up and gain a greater understanding, to be able to recognize and diagnose them and sort them out.”

Future goals should include quantifying the prevalence of genetic variants underlying hypogammaglobulinemia among patients with rheumatic diseases, and better characterizing outcomes and phenotypes of patients harboring variants linked to inborn errors of immunity, Dr. Sogkas said. “Whether these patients actually have a different disease than what they are being treated for, I can’t tell from this paper, and that’s an important question for the future,” added Dr. Calabrese. “I also do wonder about the effects of different drugs,” he said, noting that many patients with PID-associated autosomal gene variants developed persistent secondary hypogammaglobulinemia after initiating methotrexate. “It makes me wonder whether some of these genes have a specific interaction with methotrexate,” he said. “That could be a biomarker for drug toxicity.”

Study funders included the German Research Foundation, the German multiorgan Autoimmunity Network, Hannover Medical School, the Rosemarie-Germscheid Foundation, the German Academic Exchange Service, HBRS, the Center for Infection Biology, and the German Center for Infection Research. The investigators reported having no competing interests.

SOURCE: Sogkas G et al. Ann Rheum Dis. 2020 Oct 12. doi: 10.1136/annrheumdis-2020-218280.

Fully 48% of patients with autoimmune rheumatic diseases who developed persistent hypogammaglobulinemia after initiating treatment with immunomodulatory agents harbored gene variants associated with inborn errors of immunity, according to the findings of a single-center study published in Annals of the Rheumatic Diseases.

The results raise the possibility of a shared genetic etiology between “primary” and “secondary” hypogammaglobulinemia and suggest that some cases of autoimmune rheumatic disease may result from inborn errors of immunity. “In other words, a rheumatologist may be treating the rheumatic manifestations of a primary immunodeficiency disorder,” the study’s lead author, Georgios Sogkas, MD, PhD, said in an interview.

‘Striking’ findings suggest a future in personalized medicine

Experts who were not involved in the study called the results noteworthy. “The fact that half of patients with rheumatic disease who developed secondary hypogammaglobulinemia were found to have a functionally relevant mutation in a known PID gene is striking, albeit purely circumstantial given the absence of any functional or mechanistic data,” said Michael J. Ombrello, MD, principal investigator and head of the translational genetics and genomics unit at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study.

The findings, if they are validated by additional studies, might help clinicians personalize medicine by avoiding hypogammaglobulinemia-inducing immunomodulatory regimens in genetically predisposed patients, or by targeting Janus kinase (JAK) inhibitor therapy for patients with STAT3 gain-of-function variants, or PI3K delta inhibitors for patients with variants leading to hyperactivation of the PI3Kdelta gene, Dr. Sogkas said.

Dr. Ombrello agreed: “Whether the hypogammaglobulinemia is classified as primary or secondary, the presence of these genetic variants in half of patients with hypogammaglobulinemia suggests an opportunity to improve clinical care. Although far off at this point, one can imagine a day where genetic data allows a rheumatologist to identify new-onset rheumatic disease patients carrying PID gene mutations and cater their therapy and monitoring accordingly.”

If further research validates these findings, they would add to a growing body of support for incorporating expanded or universal exome or genome sequencing in the care of medically complex patients, such as those with rheumatic diseases, Dr. Ombrello said. However, he cautioned that the investigators could have “overstated” the relationship in their study between secondary hypogammaglobulinemia and immunomodulatory treatment. The fact that a small group of study participants (about 7%) developed hypogammaglobulinemia after initiating immunomodulatory therapy does not confirm a causal relationship, he emphasized. Common variable immune deficiency (CVID) can develop in adults as late as the fifth and sixth decade of life, he noted, making it “not implausible that a small number of rheumatic disease patients would develop CVID while under the care of a rheumatologist. Would these patients have developed hypogammaglobulinemia even without treatment with immunomodulators, purely related to their genetic mutations? If so, they would be better classified as having primary immune deficiency, although that distinction is largely one of semantics.”

‘Rheumatologists are obliged to step up’

Interestingly, only 23% of the patients with hypogammaglobulinemia in the study had a clinically significant history of infections even though only 9% were receiving prophylactic antibiotics. Such findings highlight the complexity of PIDs, according to experts. “A long generation ago, we thought of immunodeficiencies as infections. Now we see them as autoimmune diseases, inflammatory diseases, allergic diseases – the spectrum continues to enlarge,” said Leonard H. Calabrese, DO, the RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, who was not involved in the study.

Dr. Calabrese noted that more than 450 monogenic variants have been linked to inborn errors of immunity. “Because these [PIDs] can mimic autoinflammatory presentations, rheumatologists are obliged to step up and gain a greater understanding, to be able to recognize and diagnose them and sort them out.”

Future goals should include quantifying the prevalence of genetic variants underlying hypogammaglobulinemia among patients with rheumatic diseases, and better characterizing outcomes and phenotypes of patients harboring variants linked to inborn errors of immunity, Dr. Sogkas said. “Whether these patients actually have a different disease than what they are being treated for, I can’t tell from this paper, and that’s an important question for the future,” added Dr. Calabrese. “I also do wonder about the effects of different drugs,” he said, noting that many patients with PID-associated autosomal gene variants developed persistent secondary hypogammaglobulinemia after initiating methotrexate. “It makes me wonder whether some of these genes have a specific interaction with methotrexate,” he said. “That could be a biomarker for drug toxicity.”

Study funders included the German Research Foundation, the German multiorgan Autoimmunity Network, Hannover Medical School, the Rosemarie-Germscheid Foundation, the German Academic Exchange Service, HBRS, the Center for Infection Biology, and the German Center for Infection Research. The investigators reported having no competing interests.

SOURCE: Sogkas G et al. Ann Rheum Dis. 2020 Oct 12. doi: 10.1136/annrheumdis-2020-218280.

Selexipag (Uptravi) does not change the level of daily activity of patients with pulmonary arterial hypertension (PAH), results from the phase 4 TRACE trial suggest.

“We had no preconceived idea if this drug would improve exercise capacity,” said Luke Howard, MD, of Imperial College Healthcare NHS Trust in London. It was clear, however, that 6-minute walk tests conducted a few times a year “don’t paint a picture of what daily life is like for patients on selexipag.”

The oral prostacyclin IP receptor agonist is prescribed to slow the progression of PAH and reduce hospital admissions, but there are no studies that show whether it improves quality of life.

Dr. Howard and his team turned to wearable technology to “capture a snapshot of everyday life,” he explained during his presentation at the annual meeting of the American College of Chest Physicians (CHEST 2020), held virtually this year.

The primary concern of the investigators was to get TRACE participants – all with PAH – to wear a wrist device; they did not encourage patients to become more active. “We wanted a true picture of the impact of the drug itself,” he noted.

After 24 months of daily tracking, “there was no benefit to increased daily activity for patients taking this drug,” Dr. Howard said in an interview. “That was a bit deflating.”

The daily activity of TRACE participants was “slightly more elevated” in the selexipag group than in the placebo group. “We saw some numerical drops in activity in the placebo group, and a trend that might make a difference over a longer, bigger study, but not in a statically significant way,” he reported.

In the randomized, blinded trial – the first to track the activity of PAH patients – 53 participants received selexipag and 55 received placebo. All 108 wore a wrist accelerometer (GT9X Link) that counted the number of steps taken each day, providing an indication of daily activity.

Device compliance – the mean number of days in which the device was worn for at least 7 hours during a 14-day predrug period – was similar in the selexipag and placebo groups (13.2 vs 13.0 days).

“We wanted to make sure we had people who were stable and weren’t enrolled in a rehabilitation program; we didn’t want any competing influences,” Dr. Howard explained. All in all, the participants were in pretty good shape. “There was a low risk of a bad outcome.”

The primary endpoint was change in activity from baseline to week 24. The secondary endpoints were PAH-SYMPACT health quality-of-life tests and 6-minute walk distance.
 

Similar activity levels in both groups

As expected in a population in which the majority of patients meet the criteria for WHO functional class II PAH, all participants had low PAH-SYMPACT domain scores throughout the trial.

All adverse events were “consistent with the known profile” of selexipag, and there were no deaths, Dr. Howard reported.

“We did not show any significant benefit to taking the drug,” he said, but the drug is marketed for the prevention of disease progression, and this finding “doesn’t change that.”
 

Pulmonary rehabilitation

“Pulmonary rehabilitation is one of the most vital management issues with chronic lung disease,” Riddhi Upadhyay, MD, of Carle Foundation Hospital in Urbana, Ill., said during her CHEST 2020 presentation on improving PAH rehabilitation referral rates.

“We know it improves exercise capacity, lung function, and decreases total hospital stays and recurrent hospital admission,” she explained. And studies have shown that PAH rehabilitation “also reduces frailty and improves quality of life.”

In their study, Dr. Upadhyay and colleagues showed that when pulmonary rehabilitation is added to the discharge order set, referrals increase by 60%.

They attribute their success to “recognizing the benefits of pulmonary rehab and understanding where interventions are required.”

An encouraging takeaway from the TRACE data is that it established that daily activity can be tracked in this patient population. “We think we might need to encourage these patients to get active, maybe combine the drug with a formal rehabilitation program; that might increase motivation,” Dr. Howard said.

“People don’t necessarily do more just because they can,” he noted.

Dr. Howard has received consulting fees from Actelion.
 

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

Selexipag (Uptravi) does not change the level of daily activity of patients with pulmonary arterial hypertension (PAH), results from the phase 4 TRACE trial suggest.

“We had no preconceived idea if this drug would improve exercise capacity,” said Luke Howard, MD, of Imperial College Healthcare NHS Trust in London. It was clear, however, that 6-minute walk tests conducted a few times a year “don’t paint a picture of what daily life is like for patients on selexipag.”

The oral prostacyclin IP receptor agonist is prescribed to slow the progression of PAH and reduce hospital admissions, but there are no studies that show whether it improves quality of life.

Dr. Howard and his team turned to wearable technology to “capture a snapshot of everyday life,” he explained during his presentation at the annual meeting of the American College of Chest Physicians (CHEST 2020), held virtually this year.

The primary concern of the investigators was to get TRACE participants – all with PAH – to wear a wrist device; they did not encourage patients to become more active. “We wanted a true picture of the impact of the drug itself,” he noted.

After 24 months of daily tracking, “there was no benefit to increased daily activity for patients taking this drug,” Dr. Howard said in an interview. “That was a bit deflating.”

The daily activity of TRACE participants was “slightly more elevated” in the selexipag group than in the placebo group. “We saw some numerical drops in activity in the placebo group, and a trend that might make a difference over a longer, bigger study, but not in a statically significant way,” he reported.

In the randomized, blinded trial – the first to track the activity of PAH patients – 53 participants received selexipag and 55 received placebo. All 108 wore a wrist accelerometer (GT9X Link) that counted the number of steps taken each day, providing an indication of daily activity.

Device compliance – the mean number of days in which the device was worn for at least 7 hours during a 14-day predrug period – was similar in the selexipag and placebo groups (13.2 vs 13.0 days).

“We wanted to make sure we had people who were stable and weren’t enrolled in a rehabilitation program; we didn’t want any competing influences,” Dr. Howard explained. All in all, the participants were in pretty good shape. “There was a low risk of a bad outcome.”

The primary endpoint was change in activity from baseline to week 24. The secondary endpoints were PAH-SYMPACT health quality-of-life tests and 6-minute walk distance.
 

Similar activity levels in both groups

As expected in a population in which the majority of patients meet the criteria for WHO functional class II PAH, all participants had low PAH-SYMPACT domain scores throughout the trial.

All adverse events were “consistent with the known profile” of selexipag, and there were no deaths, Dr. Howard reported.

“We did not show any significant benefit to taking the drug,” he said, but the drug is marketed for the prevention of disease progression, and this finding “doesn’t change that.”
 

Pulmonary rehabilitation

“Pulmonary rehabilitation is one of the most vital management issues with chronic lung disease,” Riddhi Upadhyay, MD, of Carle Foundation Hospital in Urbana, Ill., said during her CHEST 2020 presentation on improving PAH rehabilitation referral rates.

“We know it improves exercise capacity, lung function, and decreases total hospital stays and recurrent hospital admission,” she explained. And studies have shown that PAH rehabilitation “also reduces frailty and improves quality of life.”

In their study, Dr. Upadhyay and colleagues showed that when pulmonary rehabilitation is added to the discharge order set, referrals increase by 60%.

They attribute their success to “recognizing the benefits of pulmonary rehab and understanding where interventions are required.”

An encouraging takeaway from the TRACE data is that it established that daily activity can be tracked in this patient population. “We think we might need to encourage these patients to get active, maybe combine the drug with a formal rehabilitation program; that might increase motivation,” Dr. Howard said.

“People don’t necessarily do more just because they can,” he noted.

Dr. Howard has received consulting fees from Actelion.
 

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

Selexipag (Uptravi) does not change the level of daily activity of patients with pulmonary arterial hypertension (PAH), results from the phase 4 TRACE trial suggest.

“We had no preconceived idea if this drug would improve exercise capacity,” said Luke Howard, MD, of Imperial College Healthcare NHS Trust in London. It was clear, however, that 6-minute walk tests conducted a few times a year “don’t paint a picture of what daily life is like for patients on selexipag.”

The oral prostacyclin IP receptor agonist is prescribed to slow the progression of PAH and reduce hospital admissions, but there are no studies that show whether it improves quality of life.

Dr. Howard and his team turned to wearable technology to “capture a snapshot of everyday life,” he explained during his presentation at the annual meeting of the American College of Chest Physicians (CHEST 2020), held virtually this year.

The primary concern of the investigators was to get TRACE participants – all with PAH – to wear a wrist device; they did not encourage patients to become more active. “We wanted a true picture of the impact of the drug itself,” he noted.

After 24 months of daily tracking, “there was no benefit to increased daily activity for patients taking this drug,” Dr. Howard said in an interview. “That was a bit deflating.”

The daily activity of TRACE participants was “slightly more elevated” in the selexipag group than in the placebo group. “We saw some numerical drops in activity in the placebo group, and a trend that might make a difference over a longer, bigger study, but not in a statically significant way,” he reported.

In the randomized, blinded trial – the first to track the activity of PAH patients – 53 participants received selexipag and 55 received placebo. All 108 wore a wrist accelerometer (GT9X Link) that counted the number of steps taken each day, providing an indication of daily activity.

Device compliance – the mean number of days in which the device was worn for at least 7 hours during a 14-day predrug period – was similar in the selexipag and placebo groups (13.2 vs 13.0 days).

“We wanted to make sure we had people who were stable and weren’t enrolled in a rehabilitation program; we didn’t want any competing influences,” Dr. Howard explained. All in all, the participants were in pretty good shape. “There was a low risk of a bad outcome.”

The primary endpoint was change in activity from baseline to week 24. The secondary endpoints were PAH-SYMPACT health quality-of-life tests and 6-minute walk distance.
 

Similar activity levels in both groups

As expected in a population in which the majority of patients meet the criteria for WHO functional class II PAH, all participants had low PAH-SYMPACT domain scores throughout the trial.

All adverse events were “consistent with the known profile” of selexipag, and there were no deaths, Dr. Howard reported.

“We did not show any significant benefit to taking the drug,” he said, but the drug is marketed for the prevention of disease progression, and this finding “doesn’t change that.”
 

Pulmonary rehabilitation

“Pulmonary rehabilitation is one of the most vital management issues with chronic lung disease,” Riddhi Upadhyay, MD, of Carle Foundation Hospital in Urbana, Ill., said during her CHEST 2020 presentation on improving PAH rehabilitation referral rates.

“We know it improves exercise capacity, lung function, and decreases total hospital stays and recurrent hospital admission,” she explained. And studies have shown that PAH rehabilitation “also reduces frailty and improves quality of life.”

In their study, Dr. Upadhyay and colleagues showed that when pulmonary rehabilitation is added to the discharge order set, referrals increase by 60%.

They attribute their success to “recognizing the benefits of pulmonary rehab and understanding where interventions are required.”

An encouraging takeaway from the TRACE data is that it established that daily activity can be tracked in this patient population. “We think we might need to encourage these patients to get active, maybe combine the drug with a formal rehabilitation program; that might increase motivation,” Dr. Howard said.

“People don’t necessarily do more just because they can,” he noted.

Dr. Howard has received consulting fees from Actelion.
 

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

Patients with systemic sclerosis have variable disease progression but often experience debilitating fatigue, pain, and digestive issues – and they’re extremely concerned about progressive organ damage, according to those who spoke at and provided input at a public meeting on patient-focused drug development for the disease.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The virtual meeting was part of the Food and Drug Administration’s Patient-Focused Drug Development (PFDD) initiative, which began in 2012 and aims to provide a systematic way for patients’ experiences, needs, and priorities to be “captured and meaningfully incorporated” into drug development and evaluation.
 

Patients rate their most impactful symptoms

Dinesh Khanna, MBBS, MSc, a rheumatologist who directs a scleroderma research program at the University of Michigan, Ann Arbor, attended the meeting after giving an opening presentation on the disease to FDA officials, patients, and other participants. In a later interview, he said that patients’ ratings of their most impactful symptoms was especially striking.

Raynaud’s phenomenon, digestive symptoms, and fatigue were the top three answers to a poll question that asked patients what symptom had the most significant impact on daily life, he noted, “and none of these are being [strongly] addressed right now [in clinical trials] apart from Raynaud’s phenomenon, for which there are some trials ongoing.”

He and other researchers are “struggling with what outcomes measures to use [in their studies],” said Dr. Khanna, the Frederick G.L. Huetwell Professor of Rheumatology at the University. “My takeaway from the meeting as a clinical trialist is that we should be paying close attention to the symptoms that patients tell us are the most important. We should be including these in our trial designs as secondary endpoints, if not primary endpoints. We have not done that [thus far], really.”

Approximately 200,000 patients in the United States have scleroderma, and approximately 75,000-80,000 of these patients have systemic scleroderma, or systemic sclerosis, Dr. Khanna said in his opening presentation. Each year, he estimates, about 6,000 new diagnoses of systemic sclerosis are made.

More than 200 people – patients, FDA officials, and others – participated in the PFDD meeting. Patients participated in one of two panels – one focused on health effects and daily impacts, and the other on treatments – or submitted input electronically. All were invited to answer poll questions.

Raj Nair, MD, one of eight FDA leaders attending the meeting, noted in closing remarks that the pain experienced by patients with systemic sclerosis includes severe pain from Raynaud’s phenomenon and pain caused by digital ulcers and by calcinosis. “We heard about how paralyzing the pain from calcinosis is, and that there are very few options for alleviating this pain,” said Dr. Nair, of the division of rheumatology and transplant medicine.

Another takeaway, he said, is that the “fatigue can be severe and debilitating, leading to days where it is impossible to get out of bed,” and that digestive symptoms can also be severe. “Reflux,” he noted, “requires significant medical intervention.”
 

Patients describe their experiences

Rosemary Lyons, diagnosed with scleroderma 35 years ago, explained that while her skin is no longer hardened, she is overly sensitive to fabrics and skin care products and has difficulty with sleeping and eating. She moved away from family in the Northeast to live in the South where the climate is warmer, but even on a 90-degree night she needs a blanket and two comforters to curb the cold and attempt to sleep.

Impaired gastrointestinal motility has made food her “biggest problem” for the past 10 years, and because of GI symptoms, she can eat only one meal a day. She also experiences fainting, brain fog, and severe fatigue. On a good day, Ms. Lyons noted, she sometimes opts to do some house chores “knowing that I’ll have 1-3 days of recovery.”

Another patient, Amy Harding, said that 22 years after her scleroderma diagnosis, “the calcinosis I get in my fingers, elbows, toes, and ears tops all the prior symptoms.” The skin tightening and digital ulcers that she experienced in the first 10 years have tapered off, and while Raynaud’s symptoms and heartburn have worsened, they are at least partly manageable with medications, unlike the pain from calcinosis.
 

Treating symptoms vs. disease may be key in risk-benefit analysis

In questions after patient presentations, FDA officials probed for more perspective on issues such as how fatigue should be assessed, the differences between fatigue and brain fog, the impact of calcinosis on functioning, and how much risk patients would be willing to assume from treatments that have side effects and that may or may not modulate the disease and slow disease progression.

Most patients said in response to an FDA poll question that they definitely (almost 40%) or possibly (almost 50%) would be willing to try a hypothetical new self-injectable medication if it were shown to reduce their most impactful symptoms but had side effects.

“I think what [we’ve been hearing] today is that whether we’re working on the symptoms or the disease itself is [the key]” to patients’ risk-benefit analysis, said meeting moderator Capt. Robyn Bent, RN, MS, of the U.S. Public Health Service, and director of the PFDD.

Anita Devine, diagnosed 13 years ago with systemic sclerosis, was one of several panel members who said she would accept more bothersome treatment side effects and risks “if the gain was control of disease progression and overall quality of life ... and organ preservation.” Ms. Devine, who has needed kidney dialysis and multiple hand surgeries, noted that she previously took anti-neoplastic and anti-inflammatory agents “to try to stem the course of my disease, but unfortunately the disease did not abate.”

Treatments for systemic sclerosis include vasodilators, immunosuppressive medications, antifibrotic therapies, and stem cell transplants, Dr. Khanna said in his opening remarks.

Trials of drugs for scleroderma have focused on early disease that may be amenable to treatment, with the exception of trials for pulmonary arterial hypertension, which affects some patients with systemic sclerosis. There are multiple FDA-approved drugs for pulmonary arterial hypertension and more trials are underway.

Outcomes such as pain and fatigue are included in many of the trials currently underway, but they tend to be lower-level secondary outcomes measures that cannot be incorporated into drug labeling or are more “exploratory in nature,” Dr. Khanna said in the interview.

Dr. Khanna disclosed that he is the chief medical officer (an equity position) for CiVi Biopharma/Eicos Sciences Inc., which is developing a drug for Raynaud’s, and serves as a consultant and grant recipient for numerous companies that make or are developing drugs for systemic sclerosis.

The FDA will accept patient comments until Dec. 15, 2020, at which time comments will be compiled into a summary report, Ms. Bent said.

Patients with systemic sclerosis have variable disease progression but often experience debilitating fatigue, pain, and digestive issues – and they’re extremely concerned about progressive organ damage, according to those who spoke at and provided input at a public meeting on patient-focused drug development for the disease.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The virtual meeting was part of the Food and Drug Administration’s Patient-Focused Drug Development (PFDD) initiative, which began in 2012 and aims to provide a systematic way for patients’ experiences, needs, and priorities to be “captured and meaningfully incorporated” into drug development and evaluation.
 

Patients rate their most impactful symptoms

Dinesh Khanna, MBBS, MSc, a rheumatologist who directs a scleroderma research program at the University of Michigan, Ann Arbor, attended the meeting after giving an opening presentation on the disease to FDA officials, patients, and other participants. In a later interview, he said that patients’ ratings of their most impactful symptoms was especially striking.

Raynaud’s phenomenon, digestive symptoms, and fatigue were the top three answers to a poll question that asked patients what symptom had the most significant impact on daily life, he noted, “and none of these are being [strongly] addressed right now [in clinical trials] apart from Raynaud’s phenomenon, for which there are some trials ongoing.”

He and other researchers are “struggling with what outcomes measures to use [in their studies],” said Dr. Khanna, the Frederick G.L. Huetwell Professor of Rheumatology at the University. “My takeaway from the meeting as a clinical trialist is that we should be paying close attention to the symptoms that patients tell us are the most important. We should be including these in our trial designs as secondary endpoints, if not primary endpoints. We have not done that [thus far], really.”

Approximately 200,000 patients in the United States have scleroderma, and approximately 75,000-80,000 of these patients have systemic scleroderma, or systemic sclerosis, Dr. Khanna said in his opening presentation. Each year, he estimates, about 6,000 new diagnoses of systemic sclerosis are made.

More than 200 people – patients, FDA officials, and others – participated in the PFDD meeting. Patients participated in one of two panels – one focused on health effects and daily impacts, and the other on treatments – or submitted input electronically. All were invited to answer poll questions.

Raj Nair, MD, one of eight FDA leaders attending the meeting, noted in closing remarks that the pain experienced by patients with systemic sclerosis includes severe pain from Raynaud’s phenomenon and pain caused by digital ulcers and by calcinosis. “We heard about how paralyzing the pain from calcinosis is, and that there are very few options for alleviating this pain,” said Dr. Nair, of the division of rheumatology and transplant medicine.

Another takeaway, he said, is that the “fatigue can be severe and debilitating, leading to days where it is impossible to get out of bed,” and that digestive symptoms can also be severe. “Reflux,” he noted, “requires significant medical intervention.”
 

Patients describe their experiences

Rosemary Lyons, diagnosed with scleroderma 35 years ago, explained that while her skin is no longer hardened, she is overly sensitive to fabrics and skin care products and has difficulty with sleeping and eating. She moved away from family in the Northeast to live in the South where the climate is warmer, but even on a 90-degree night she needs a blanket and two comforters to curb the cold and attempt to sleep.

Impaired gastrointestinal motility has made food her “biggest problem” for the past 10 years, and because of GI symptoms, she can eat only one meal a day. She also experiences fainting, brain fog, and severe fatigue. On a good day, Ms. Lyons noted, she sometimes opts to do some house chores “knowing that I’ll have 1-3 days of recovery.”

Another patient, Amy Harding, said that 22 years after her scleroderma diagnosis, “the calcinosis I get in my fingers, elbows, toes, and ears tops all the prior symptoms.” The skin tightening and digital ulcers that she experienced in the first 10 years have tapered off, and while Raynaud’s symptoms and heartburn have worsened, they are at least partly manageable with medications, unlike the pain from calcinosis.
 

Treating symptoms vs. disease may be key in risk-benefit analysis

In questions after patient presentations, FDA officials probed for more perspective on issues such as how fatigue should be assessed, the differences between fatigue and brain fog, the impact of calcinosis on functioning, and how much risk patients would be willing to assume from treatments that have side effects and that may or may not modulate the disease and slow disease progression.

Most patients said in response to an FDA poll question that they definitely (almost 40%) or possibly (almost 50%) would be willing to try a hypothetical new self-injectable medication if it were shown to reduce their most impactful symptoms but had side effects.

“I think what [we’ve been hearing] today is that whether we’re working on the symptoms or the disease itself is [the key]” to patients’ risk-benefit analysis, said meeting moderator Capt. Robyn Bent, RN, MS, of the U.S. Public Health Service, and director of the PFDD.

Anita Devine, diagnosed 13 years ago with systemic sclerosis, was one of several panel members who said she would accept more bothersome treatment side effects and risks “if the gain was control of disease progression and overall quality of life ... and organ preservation.” Ms. Devine, who has needed kidney dialysis and multiple hand surgeries, noted that she previously took anti-neoplastic and anti-inflammatory agents “to try to stem the course of my disease, but unfortunately the disease did not abate.”

Treatments for systemic sclerosis include vasodilators, immunosuppressive medications, antifibrotic therapies, and stem cell transplants, Dr. Khanna said in his opening remarks.

Trials of drugs for scleroderma have focused on early disease that may be amenable to treatment, with the exception of trials for pulmonary arterial hypertension, which affects some patients with systemic sclerosis. There are multiple FDA-approved drugs for pulmonary arterial hypertension and more trials are underway.

Outcomes such as pain and fatigue are included in many of the trials currently underway, but they tend to be lower-level secondary outcomes measures that cannot be incorporated into drug labeling or are more “exploratory in nature,” Dr. Khanna said in the interview.

Dr. Khanna disclosed that he is the chief medical officer (an equity position) for CiVi Biopharma/Eicos Sciences Inc., which is developing a drug for Raynaud’s, and serves as a consultant and grant recipient for numerous companies that make or are developing drugs for systemic sclerosis.

The FDA will accept patient comments until Dec. 15, 2020, at which time comments will be compiled into a summary report, Ms. Bent said.

Patients with systemic sclerosis have variable disease progression but often experience debilitating fatigue, pain, and digestive issues – and they’re extremely concerned about progressive organ damage, according to those who spoke at and provided input at a public meeting on patient-focused drug development for the disease.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The virtual meeting was part of the Food and Drug Administration’s Patient-Focused Drug Development (PFDD) initiative, which began in 2012 and aims to provide a systematic way for patients’ experiences, needs, and priorities to be “captured and meaningfully incorporated” into drug development and evaluation.
 

Patients rate their most impactful symptoms

Dinesh Khanna, MBBS, MSc, a rheumatologist who directs a scleroderma research program at the University of Michigan, Ann Arbor, attended the meeting after giving an opening presentation on the disease to FDA officials, patients, and other participants. In a later interview, he said that patients’ ratings of their most impactful symptoms was especially striking.

Raynaud’s phenomenon, digestive symptoms, and fatigue were the top three answers to a poll question that asked patients what symptom had the most significant impact on daily life, he noted, “and none of these are being [strongly] addressed right now [in clinical trials] apart from Raynaud’s phenomenon, for which there are some trials ongoing.”

He and other researchers are “struggling with what outcomes measures to use [in their studies],” said Dr. Khanna, the Frederick G.L. Huetwell Professor of Rheumatology at the University. “My takeaway from the meeting as a clinical trialist is that we should be paying close attention to the symptoms that patients tell us are the most important. We should be including these in our trial designs as secondary endpoints, if not primary endpoints. We have not done that [thus far], really.”

Approximately 200,000 patients in the United States have scleroderma, and approximately 75,000-80,000 of these patients have systemic scleroderma, or systemic sclerosis, Dr. Khanna said in his opening presentation. Each year, he estimates, about 6,000 new diagnoses of systemic sclerosis are made.

More than 200 people – patients, FDA officials, and others – participated in the PFDD meeting. Patients participated in one of two panels – one focused on health effects and daily impacts, and the other on treatments – or submitted input electronically. All were invited to answer poll questions.

Raj Nair, MD, one of eight FDA leaders attending the meeting, noted in closing remarks that the pain experienced by patients with systemic sclerosis includes severe pain from Raynaud’s phenomenon and pain caused by digital ulcers and by calcinosis. “We heard about how paralyzing the pain from calcinosis is, and that there are very few options for alleviating this pain,” said Dr. Nair, of the division of rheumatology and transplant medicine.

Another takeaway, he said, is that the “fatigue can be severe and debilitating, leading to days where it is impossible to get out of bed,” and that digestive symptoms can also be severe. “Reflux,” he noted, “requires significant medical intervention.”
 

Patients describe their experiences

Rosemary Lyons, diagnosed with scleroderma 35 years ago, explained that while her skin is no longer hardened, she is overly sensitive to fabrics and skin care products and has difficulty with sleeping and eating. She moved away from family in the Northeast to live in the South where the climate is warmer, but even on a 90-degree night she needs a blanket and two comforters to curb the cold and attempt to sleep.

Impaired gastrointestinal motility has made food her “biggest problem” for the past 10 years, and because of GI symptoms, she can eat only one meal a day. She also experiences fainting, brain fog, and severe fatigue. On a good day, Ms. Lyons noted, she sometimes opts to do some house chores “knowing that I’ll have 1-3 days of recovery.”

Another patient, Amy Harding, said that 22 years after her scleroderma diagnosis, “the calcinosis I get in my fingers, elbows, toes, and ears tops all the prior symptoms.” The skin tightening and digital ulcers that she experienced in the first 10 years have tapered off, and while Raynaud’s symptoms and heartburn have worsened, they are at least partly manageable with medications, unlike the pain from calcinosis.
 

Treating symptoms vs. disease may be key in risk-benefit analysis

In questions after patient presentations, FDA officials probed for more perspective on issues such as how fatigue should be assessed, the differences between fatigue and brain fog, the impact of calcinosis on functioning, and how much risk patients would be willing to assume from treatments that have side effects and that may or may not modulate the disease and slow disease progression.

Most patients said in response to an FDA poll question that they definitely (almost 40%) or possibly (almost 50%) would be willing to try a hypothetical new self-injectable medication if it were shown to reduce their most impactful symptoms but had side effects.

“I think what [we’ve been hearing] today is that whether we’re working on the symptoms or the disease itself is [the key]” to patients’ risk-benefit analysis, said meeting moderator Capt. Robyn Bent, RN, MS, of the U.S. Public Health Service, and director of the PFDD.

Anita Devine, diagnosed 13 years ago with systemic sclerosis, was one of several panel members who said she would accept more bothersome treatment side effects and risks “if the gain was control of disease progression and overall quality of life ... and organ preservation.” Ms. Devine, who has needed kidney dialysis and multiple hand surgeries, noted that she previously took anti-neoplastic and anti-inflammatory agents “to try to stem the course of my disease, but unfortunately the disease did not abate.”

Treatments for systemic sclerosis include vasodilators, immunosuppressive medications, antifibrotic therapies, and stem cell transplants, Dr. Khanna said in his opening remarks.

Trials of drugs for scleroderma have focused on early disease that may be amenable to treatment, with the exception of trials for pulmonary arterial hypertension, which affects some patients with systemic sclerosis. There are multiple FDA-approved drugs for pulmonary arterial hypertension and more trials are underway.

Outcomes such as pain and fatigue are included in many of the trials currently underway, but they tend to be lower-level secondary outcomes measures that cannot be incorporated into drug labeling or are more “exploratory in nature,” Dr. Khanna said in the interview.

Dr. Khanna disclosed that he is the chief medical officer (an equity position) for CiVi Biopharma/Eicos Sciences Inc., which is developing a drug for Raynaud’s, and serves as a consultant and grant recipient for numerous companies that make or are developing drugs for systemic sclerosis.

The FDA will accept patient comments until Dec. 15, 2020, at which time comments will be compiled into a summary report, Ms. Bent said.

A new study of immunoglobulin levels in adult patients with systemic lupus erythematosus (SLE) has found that acquired low levels of IgA are associated with a higher risk of infection.

To the knowledge of first author Ibrahim Almaghlouth, MD, of the division of rheumatology at the University of Toronto, and colleagues, “this is the first dedicated study to examine the relationship between acquired low immunoglobulins and infection risk in adult patients with SLE.” But as to whether there may be a “protective role for immunoglobulins and the potential effect of immunoglobulin replacement in a setting of recurrent or severe infection among SLE patients requires further study.”

To determine if the risk of infection was tied to acquired low immunoglobulin levels, the researchers launched a retrospective analysis of data from a prospective cohort study of adult SLE patients from a Toronto lupus cohort that was established in 1970. The study was published in Rheumatology.

A total of 448 patients with at least two low immunoglobulin tests were matched with 656 SLE patients with no low immunoglobulins according to enrollment decade. The average age of the low-immunoglobulin group was 41.8 years, compared with 39.3 years in the control group. Average disease duration was 11.2 years in the low-immunoglobulin group and 7.6 years in the control group.

Of the patients in the low-immunoglobulin group, 221 had consecutive low tests and 227 had nonconsecutive low tests. Overall, 98 of those patients had low IgG, 251 patients had low IgM, and 51 patients had low IgA. Only 48 patients had overlapping low levels, including 5 with all three.

Average levels among the low-immunoglobulin group at baseline were 11.5 (standard deviation, 6.1) g/L of IgG, 0.8 (1.1) g/L of IgM, and 2.4 (1.6) g/L of IgA, while average levels among the control group were 16.3 (6.4) g/L of IgG, 1.8 (1.2) g/L of IgM, and 3.2 (1.5) g/L of IgA. In the primary analysis, after adjustment using propensity scoring, there were 97 infections: 47 in the low-immunoglobulin group and 50 in the control group. The most common types were respiratory and urinary tract infections, and the rate of infection was higher in patients with low IgA. The IgA level associated with risk of infection was less than 0.75 g/L.

After Cox regression analysis, the only variable that significantly increased infection risk was a low IgA level (hazard ratio, 3.19; 95% confidence interval, 1.17-8.71), not a low IgG level (HR, 1.87; 95% CI, 0.77-4.54) or low IgM level (HR, 0.63; 95% CI, 0.34-1.17). In regard to recovery among the low-immunoglobulin group, 11 patients (2.5%) recovered from low immunoglobulins within in the first year, followed by 36 (8.2%) in the second year, 44 (10.1%) in the third year, and 80 (18.4%) in the fourth year. All told, 60% (263) of patients with acquired hypogammaglobulinemia recovered over a 4-year period.

Is there clinical relevance to low IgA?

“I don’t see us using this clinically immediately,” Karen Costenbader, MD, a rheumatologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said in an interview. “We do test immunoglobulins often, especially in patients who’ve had biologic therapy. Will we start thinking about their IgA levels? It’s not clear, and the researchers leave it up in the air as to what this means, beyond them being at high risk.”

That said, she added, “IgA levels are interesting, especially in a time of COVID, because they’re associated with mucosal immunity. Is this subset of patients going to be at particularly high risk for the coronavirus?”

She also noted that, though immunoglobulin replacement has been helpful in her patients, it’s an expensive therapy to recommend for low IgA levels without knowing exactly what is causing these deficiencies. “My question is, would it be useful to follow these levels in lupus patients, even we don’t know what to do about them?” she asked. “We know there are a lot of risk factors for infections, so is the IgA going to be useful above and beyond that, and then what can we do about it?”

The authors acknowledged their study’s potential limitations, including low infection rates and yearly measurements of immunoglobulin levels, which could’ve led to misclassifying a lab error as true low immunoglobulin. They also highlighted its strengths, including using various methods to reduce selection and confounding bias while also reporting consistent results after examining multiple definitions of low immunoglobulins and outcomes.

The study received no specific funding, and the authors reported no potential conflicts of interest.

SOURCE: Almaghlouth I et al. Rheumatology. 2020 Oct 2. doi: 10.1093/rheumatology/keaa641.

A new study of immunoglobulin levels in adult patients with systemic lupus erythematosus (SLE) has found that acquired low levels of IgA are associated with a higher risk of infection.

To the knowledge of first author Ibrahim Almaghlouth, MD, of the division of rheumatology at the University of Toronto, and colleagues, “this is the first dedicated study to examine the relationship between acquired low immunoglobulins and infection risk in adult patients with SLE.” But as to whether there may be a “protective role for immunoglobulins and the potential effect of immunoglobulin replacement in a setting of recurrent or severe infection among SLE patients requires further study.”

To determine if the risk of infection was tied to acquired low immunoglobulin levels, the researchers launched a retrospective analysis of data from a prospective cohort study of adult SLE patients from a Toronto lupus cohort that was established in 1970. The study was published in Rheumatology.

A total of 448 patients with at least two low immunoglobulin tests were matched with 656 SLE patients with no low immunoglobulins according to enrollment decade. The average age of the low-immunoglobulin group was 41.8 years, compared with 39.3 years in the control group. Average disease duration was 11.2 years in the low-immunoglobulin group and 7.6 years in the control group.

Of the patients in the low-immunoglobulin group, 221 had consecutive low tests and 227 had nonconsecutive low tests. Overall, 98 of those patients had low IgG, 251 patients had low IgM, and 51 patients had low IgA. Only 48 patients had overlapping low levels, including 5 with all three.

Average levels among the low-immunoglobulin group at baseline were 11.5 (standard deviation, 6.1) g/L of IgG, 0.8 (1.1) g/L of IgM, and 2.4 (1.6) g/L of IgA, while average levels among the control group were 16.3 (6.4) g/L of IgG, 1.8 (1.2) g/L of IgM, and 3.2 (1.5) g/L of IgA. In the primary analysis, after adjustment using propensity scoring, there were 97 infections: 47 in the low-immunoglobulin group and 50 in the control group. The most common types were respiratory and urinary tract infections, and the rate of infection was higher in patients with low IgA. The IgA level associated with risk of infection was less than 0.75 g/L.

After Cox regression analysis, the only variable that significantly increased infection risk was a low IgA level (hazard ratio, 3.19; 95% confidence interval, 1.17-8.71), not a low IgG level (HR, 1.87; 95% CI, 0.77-4.54) or low IgM level (HR, 0.63; 95% CI, 0.34-1.17). In regard to recovery among the low-immunoglobulin group, 11 patients (2.5%) recovered from low immunoglobulins within in the first year, followed by 36 (8.2%) in the second year, 44 (10.1%) in the third year, and 80 (18.4%) in the fourth year. All told, 60% (263) of patients with acquired hypogammaglobulinemia recovered over a 4-year period.

Is there clinical relevance to low IgA?

“I don’t see us using this clinically immediately,” Karen Costenbader, MD, a rheumatologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said in an interview. “We do test immunoglobulins often, especially in patients who’ve had biologic therapy. Will we start thinking about their IgA levels? It’s not clear, and the researchers leave it up in the air as to what this means, beyond them being at high risk.”

That said, she added, “IgA levels are interesting, especially in a time of COVID, because they’re associated with mucosal immunity. Is this subset of patients going to be at particularly high risk for the coronavirus?”

She also noted that, though immunoglobulin replacement has been helpful in her patients, it’s an expensive therapy to recommend for low IgA levels without knowing exactly what is causing these deficiencies. “My question is, would it be useful to follow these levels in lupus patients, even we don’t know what to do about them?” she asked. “We know there are a lot of risk factors for infections, so is the IgA going to be useful above and beyond that, and then what can we do about it?”

The authors acknowledged their study’s potential limitations, including low infection rates and yearly measurements of immunoglobulin levels, which could’ve led to misclassifying a lab error as true low immunoglobulin. They also highlighted its strengths, including using various methods to reduce selection and confounding bias while also reporting consistent results after examining multiple definitions of low immunoglobulins and outcomes.

The study received no specific funding, and the authors reported no potential conflicts of interest.

SOURCE: Almaghlouth I et al. Rheumatology. 2020 Oct 2. doi: 10.1093/rheumatology/keaa641.

A new study of immunoglobulin levels in adult patients with systemic lupus erythematosus (SLE) has found that acquired low levels of IgA are associated with a higher risk of infection.

To the knowledge of first author Ibrahim Almaghlouth, MD, of the division of rheumatology at the University of Toronto, and colleagues, “this is the first dedicated study to examine the relationship between acquired low immunoglobulins and infection risk in adult patients with SLE.” But as to whether there may be a “protective role for immunoglobulins and the potential effect of immunoglobulin replacement in a setting of recurrent or severe infection among SLE patients requires further study.”

To determine if the risk of infection was tied to acquired low immunoglobulin levels, the researchers launched a retrospective analysis of data from a prospective cohort study of adult SLE patients from a Toronto lupus cohort that was established in 1970. The study was published in Rheumatology.

A total of 448 patients with at least two low immunoglobulin tests were matched with 656 SLE patients with no low immunoglobulins according to enrollment decade. The average age of the low-immunoglobulin group was 41.8 years, compared with 39.3 years in the control group. Average disease duration was 11.2 years in the low-immunoglobulin group and 7.6 years in the control group.

Of the patients in the low-immunoglobulin group, 221 had consecutive low tests and 227 had nonconsecutive low tests. Overall, 98 of those patients had low IgG, 251 patients had low IgM, and 51 patients had low IgA. Only 48 patients had overlapping low levels, including 5 with all three.

Average levels among the low-immunoglobulin group at baseline were 11.5 (standard deviation, 6.1) g/L of IgG, 0.8 (1.1) g/L of IgM, and 2.4 (1.6) g/L of IgA, while average levels among the control group were 16.3 (6.4) g/L of IgG, 1.8 (1.2) g/L of IgM, and 3.2 (1.5) g/L of IgA. In the primary analysis, after adjustment using propensity scoring, there were 97 infections: 47 in the low-immunoglobulin group and 50 in the control group. The most common types were respiratory and urinary tract infections, and the rate of infection was higher in patients with low IgA. The IgA level associated with risk of infection was less than 0.75 g/L.

After Cox regression analysis, the only variable that significantly increased infection risk was a low IgA level (hazard ratio, 3.19; 95% confidence interval, 1.17-8.71), not a low IgG level (HR, 1.87; 95% CI, 0.77-4.54) or low IgM level (HR, 0.63; 95% CI, 0.34-1.17). In regard to recovery among the low-immunoglobulin group, 11 patients (2.5%) recovered from low immunoglobulins within in the first year, followed by 36 (8.2%) in the second year, 44 (10.1%) in the third year, and 80 (18.4%) in the fourth year. All told, 60% (263) of patients with acquired hypogammaglobulinemia recovered over a 4-year period.

Is there clinical relevance to low IgA?

“I don’t see us using this clinically immediately,” Karen Costenbader, MD, a rheumatologist at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, said in an interview. “We do test immunoglobulins often, especially in patients who’ve had biologic therapy. Will we start thinking about their IgA levels? It’s not clear, and the researchers leave it up in the air as to what this means, beyond them being at high risk.”

That said, she added, “IgA levels are interesting, especially in a time of COVID, because they’re associated with mucosal immunity. Is this subset of patients going to be at particularly high risk for the coronavirus?”

She also noted that, though immunoglobulin replacement has been helpful in her patients, it’s an expensive therapy to recommend for low IgA levels without knowing exactly what is causing these deficiencies. “My question is, would it be useful to follow these levels in lupus patients, even we don’t know what to do about them?” she asked. “We know there are a lot of risk factors for infections, so is the IgA going to be useful above and beyond that, and then what can we do about it?”

The authors acknowledged their study’s potential limitations, including low infection rates and yearly measurements of immunoglobulin levels, which could’ve led to misclassifying a lab error as true low immunoglobulin. They also highlighted its strengths, including using various methods to reduce selection and confounding bias while also reporting consistent results after examining multiple definitions of low immunoglobulins and outcomes.

The study received no specific funding, and the authors reported no potential conflicts of interest.

SOURCE: Almaghlouth I et al. Rheumatology. 2020 Oct 2. doi: 10.1093/rheumatology/keaa641.

The 2019 systemic lupus erythematosus (SLE) classification criteria jointly developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) proved significantly better at detecting true positive cases of the disease in children and young adults than did the 1997 ACR criteria, according to results from a single-center, retrospective study.

However, the 2019 criteria, which were developed using cohorts of adult patients with SLE, were statistically no better than the 1997 ACR criteria at identifying those without the disease, first author Najla Aljaberi, MBBS, of the Cincinnati Children’s Hospital Medical Center, and colleagues reported in Arthritis Care & Research.

The 2019 criteria were especially good at correctly classifying SLE in non-White youths, but the two sets of criteria performed equally well among male and female youths with SLE and across age groups.

“Our study confirms superior sensitivity of the new criteria over the 1997-ACR criteria in youths with SLE. The difference in sensitivity estimates between the two criteria sets (2019-EULAR/ACR vs. 1997-ACR) may be explained by a higher weight being assigned to immunologic criteria, less strict hematologic criteria (not requiring >2 occurrences), and the inclusion of subjective features of arthritis. Notably, our estimates of the sensitivity of the 2019-EULAR/ACR criteria were similar to those reported from a Brazilian pediatric study by Fonseca et al. (87.7%) that also used physician diagnosis as reference standard,” the researchers wrote.

Dr. Aljaberi and colleagues reviewed electronic medical records of 112 patients with SLE aged 2-21 years and 105 controls aged 1-19 years at Cincinnati Children’s Hospital Medical Center during 2008-2019. Patients identified in the records at the center were considered to have SLE based on ICD-10 codes assigned by experienced pediatric rheumatologists. The control patients included 69 (66%) with juvenile dermatomyositis and 36 with juvenile scleroderma/systemic sclerosis, based on corresponding ICD-10 codes.

Among the SLE cases, 57% were White and 81% were female, while Whites represented 83% and females 71% of control patients. Young adults aged 18-21 years represented a minority of SLE cases (18%) and controls (7%).

The 2019 criteria had significantly higher sensitivity than did the 1997 criteria (85% vs. 72%, respectively; P = .023) but similar specificity (83% vs. 87%; P = .456). A total of 17 out of the 112 SLE cases failed to meet the 2019 criteria, 13 (76%) of whom were White. Overall, 31 SLE cases did not meet the 1997 criteria, but 15 of those fulfilled the 2019 criteria. While there was no statistically significant difference in the sensitivity of the 2019 criteria between non-White and White cases (92% vs. 80%, respectively; P = .08), the difference in sensitivity was significant with the 1997 criteria (83% vs. 64%; P < .02).

The 2019 criteria had similar sensitivity in males and females (86% vs. 81%, respectively), as well as specificity (81% vs. 87%). The 1997 criteria also provided similar sensitivity between males and females (71% vs. 76%) as well as specificity (85% vs. 90%).

In only four instances did SLE cases meet 2019 criteria before ICD-10 diagnosis of SLE, whereas in the other 108 cases the ICD-10 diagnosis coincided with reaching the threshold for meeting 2019 criteria.

There was no funding secured for the study, and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Aljaberi N et al. Arthritis Care Res. 2020 Aug 25. doi: 10.1002/acr.24430.

The 2019 systemic lupus erythematosus (SLE) classification criteria jointly developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) proved significantly better at detecting true positive cases of the disease in children and young adults than did the 1997 ACR criteria, according to results from a single-center, retrospective study.

However, the 2019 criteria, which were developed using cohorts of adult patients with SLE, were statistically no better than the 1997 ACR criteria at identifying those without the disease, first author Najla Aljaberi, MBBS, of the Cincinnati Children’s Hospital Medical Center, and colleagues reported in Arthritis Care & Research.

The 2019 criteria were especially good at correctly classifying SLE in non-White youths, but the two sets of criteria performed equally well among male and female youths with SLE and across age groups.

“Our study confirms superior sensitivity of the new criteria over the 1997-ACR criteria in youths with SLE. The difference in sensitivity estimates between the two criteria sets (2019-EULAR/ACR vs. 1997-ACR) may be explained by a higher weight being assigned to immunologic criteria, less strict hematologic criteria (not requiring >2 occurrences), and the inclusion of subjective features of arthritis. Notably, our estimates of the sensitivity of the 2019-EULAR/ACR criteria were similar to those reported from a Brazilian pediatric study by Fonseca et al. (87.7%) that also used physician diagnosis as reference standard,” the researchers wrote.

Dr. Aljaberi and colleagues reviewed electronic medical records of 112 patients with SLE aged 2-21 years and 105 controls aged 1-19 years at Cincinnati Children’s Hospital Medical Center during 2008-2019. Patients identified in the records at the center were considered to have SLE based on ICD-10 codes assigned by experienced pediatric rheumatologists. The control patients included 69 (66%) with juvenile dermatomyositis and 36 with juvenile scleroderma/systemic sclerosis, based on corresponding ICD-10 codes.

Among the SLE cases, 57% were White and 81% were female, while Whites represented 83% and females 71% of control patients. Young adults aged 18-21 years represented a minority of SLE cases (18%) and controls (7%).

The 2019 criteria had significantly higher sensitivity than did the 1997 criteria (85% vs. 72%, respectively; P = .023) but similar specificity (83% vs. 87%; P = .456). A total of 17 out of the 112 SLE cases failed to meet the 2019 criteria, 13 (76%) of whom were White. Overall, 31 SLE cases did not meet the 1997 criteria, but 15 of those fulfilled the 2019 criteria. While there was no statistically significant difference in the sensitivity of the 2019 criteria between non-White and White cases (92% vs. 80%, respectively; P = .08), the difference in sensitivity was significant with the 1997 criteria (83% vs. 64%; P < .02).

The 2019 criteria had similar sensitivity in males and females (86% vs. 81%, respectively), as well as specificity (81% vs. 87%). The 1997 criteria also provided similar sensitivity between males and females (71% vs. 76%) as well as specificity (85% vs. 90%).

In only four instances did SLE cases meet 2019 criteria before ICD-10 diagnosis of SLE, whereas in the other 108 cases the ICD-10 diagnosis coincided with reaching the threshold for meeting 2019 criteria.

There was no funding secured for the study, and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Aljaberi N et al. Arthritis Care Res. 2020 Aug 25. doi: 10.1002/acr.24430.

The 2019 systemic lupus erythematosus (SLE) classification criteria jointly developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) proved significantly better at detecting true positive cases of the disease in children and young adults than did the 1997 ACR criteria, according to results from a single-center, retrospective study.

However, the 2019 criteria, which were developed using cohorts of adult patients with SLE, were statistically no better than the 1997 ACR criteria at identifying those without the disease, first author Najla Aljaberi, MBBS, of the Cincinnati Children’s Hospital Medical Center, and colleagues reported in Arthritis Care & Research.

The 2019 criteria were especially good at correctly classifying SLE in non-White youths, but the two sets of criteria performed equally well among male and female youths with SLE and across age groups.

“Our study confirms superior sensitivity of the new criteria over the 1997-ACR criteria in youths with SLE. The difference in sensitivity estimates between the two criteria sets (2019-EULAR/ACR vs. 1997-ACR) may be explained by a higher weight being assigned to immunologic criteria, less strict hematologic criteria (not requiring >2 occurrences), and the inclusion of subjective features of arthritis. Notably, our estimates of the sensitivity of the 2019-EULAR/ACR criteria were similar to those reported from a Brazilian pediatric study by Fonseca et al. (87.7%) that also used physician diagnosis as reference standard,” the researchers wrote.

Dr. Aljaberi and colleagues reviewed electronic medical records of 112 patients with SLE aged 2-21 years and 105 controls aged 1-19 years at Cincinnati Children’s Hospital Medical Center during 2008-2019. Patients identified in the records at the center were considered to have SLE based on ICD-10 codes assigned by experienced pediatric rheumatologists. The control patients included 69 (66%) with juvenile dermatomyositis and 36 with juvenile scleroderma/systemic sclerosis, based on corresponding ICD-10 codes.

Among the SLE cases, 57% were White and 81% were female, while Whites represented 83% and females 71% of control patients. Young adults aged 18-21 years represented a minority of SLE cases (18%) and controls (7%).

The 2019 criteria had significantly higher sensitivity than did the 1997 criteria (85% vs. 72%, respectively; P = .023) but similar specificity (83% vs. 87%; P = .456). A total of 17 out of the 112 SLE cases failed to meet the 2019 criteria, 13 (76%) of whom were White. Overall, 31 SLE cases did not meet the 1997 criteria, but 15 of those fulfilled the 2019 criteria. While there was no statistically significant difference in the sensitivity of the 2019 criteria between non-White and White cases (92% vs. 80%, respectively; P = .08), the difference in sensitivity was significant with the 1997 criteria (83% vs. 64%; P < .02).

The 2019 criteria had similar sensitivity in males and females (86% vs. 81%, respectively), as well as specificity (81% vs. 87%). The 1997 criteria also provided similar sensitivity between males and females (71% vs. 76%) as well as specificity (85% vs. 90%).

In only four instances did SLE cases meet 2019 criteria before ICD-10 diagnosis of SLE, whereas in the other 108 cases the ICD-10 diagnosis coincided with reaching the threshold for meeting 2019 criteria.

There was no funding secured for the study, and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Aljaberi N et al. Arthritis Care Res. 2020 Aug 25. doi: 10.1002/acr.24430.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

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

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

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

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

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

Low-dose aspirin may be considered for the primary prevention of cardiovascular disease (CVD) in patients with autoimmune systemic rheumatic diseases who are at particularly high risk because of their individual cardiovascular risk profile, according to authors of a new review article in the journal Rheumatology who acknowledge the controversial nature of the issue, because while significant cardiovascular benefit from aspirin for secondary prevention is well established, it has not been for primary prevention.

Secondary prevention with daily, low-dose aspirin is part of aggressive, comprehensive risk modification in patients who have experienced an MI or stroke or are considered at high risk for CVD. But when it comes to primary prevention of the onset of disease, the authors, led by Serena Fasano, MD, PhD, of the rheumatology unit at the University of Campania, Naples, Italy, acknowledged the contradictory positions of international guidelines and uncertainty over balancing benefit versus harm – including risk of mortality in the context of excess bleeding. They called for “robust data” from high-quality randomized, controlled trials for subgroups of patients with specific rheumatologic diseases in order to better answer the question of aspirin for primary prevention.

“This review is devoted to reporting the present knowledge on the effectiveness of low-dose [aspirin] in primary CV prevention in a number of autoimmune systemic rheumatic diseases, not a systematic review or meta-analysis,” the authors stated. “We are not claiming to have covered more than a selection of the literature for each disease. Available data are not high-quality data and do not provide firm conclusions.”

The authors focused primarily on accelerated, rather than spontaneous, atherosclerosis or buildup of plaque in artery walls, implicated in ischemic heart diseases such as MI and ischemic cerebrovascular diseases such as stroke. They looked at its association with autoimmune rheumatic diseases, primarily systemic lupus erythematosus (SLE) and RA, but also including antiphospholipid syndrome, systemic sclerosis, mixed connective tissue disease, dermatomyositis/polymyositis, primary Sjögren’s syndrome, and systemic vasculitis.

They shared results from a review of 167 patients with SLE consecutively admitted to their tertiary medical center who had not previously experienced a cardiovascular event and who were prescribed low-dose (100 mg) aspirin on their first visit and followed for 8 years. The cardiovascular event-free rate was higher in the aspirin group and no excess bleeding was noted, although this may be attributable to a younger patient population and routine use of proton pump inhibitors. Subsequently, hydroxychloroquine was added to the aspirin treatment and was associated with further reduction in cardiovascular events.

The research group also conducted a retrospective analysis of 746 patients with RA consecutively admitted to four tertiary medical centers who hadn’t experienced a cardiovascular event previously. Incidence of cardiovascular events was significantly lower in aspirin-treated patients.
 

Individualized aspirin prescribing with cardiologist comanagement

There may be a modest benefit of using low-dose aspirin on a long-term basis, but that benefit needs to be offset by the risk of bleeds, said M. Elaine Husni, MD, MPH, vice chair of rheumatology and director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic. It’s important to remind clinicians of cardiovascular risk, she said. “But the message for rheumatologists is it needs to be prescribed on an individual basis, rather than based on diagnosis of a rheumatic condition – at least until we have better evidence.”

Dr. Husni recommended keeping an open mind regarding individual approaches – for example, low-dose aspirin plus statins. A composite approach to prevention likely is called for, including attention to lifestyle issues such as smoking cessation, exercise, and weight loss. “That kind of complexity in decision-making highlights the need for comanagement with a cardiologist,” she said. “I’m a big believer in comanagement. At my multidisciplinary medical center, I am able to pick up the phone and talk to a cardiologist with whom our group has a relationship.” If physicians don’t have that kind of relationship with a cardiology group, she suggested reaching out to establish one.

The review paper could give some guidance to rheumatologists for use on an individual case, Michael Nurmohamed, MD, PhD, of the Amsterdam Rheumatology and Immunology Center in the Netherlands commented in an interview. “However, firm recommendations cannot be given as proper investigations are still lacking, as acknowledged by the authors. In addition, the review paper itself has some methodological constraints. Although this is a narrative review, the search strategy should have been specified, and a quality assessment of the individual studies is lacking.”

There is no doubt that the CVD burden in RA and other rheumatologic conditions is substantially increased in comparison to the general population, Dr. Nurmohamed said. That has been assessed by several well-designed, prospective, controlled studies. Other relatively frequent inflammatory arthropathies, including ankylosing spondylitis and psoriatic arthritis, also pose cardiovascular risk.

“Aspirin cannot be recommended for primary CVD prevention in inflammatory arthropathies due to the absence of adequate studies. That’s why the EULAR [European League Against Rheumatism] guidelines did not recommend its use,” he said. Currently, a EULAR task force is developing evidence-based guidelines for primary CVD prevention in the diseases discussed by Fasano et al., where the use of aspirin will be reassessed. “As these guidelines will consider the methodological quality of the underlying studies, they will enable a more refined use of aspirin in daily clinical practice.”

Primary prevention of CVD using aspirin is not currently the standard of care in taking care of patients with rheumatologic disease in the Netherlands, Ronald F. van Vollenhoven, MD, PhD, Dr. Nurmohamed’s colleague and director of the Amsterdam Rheumatology and Immunology Center and the chair of the department of rheumatology and clinical immunology at the Amsterdam University Medical Center, said in an interview.

“One reason may be the limited data, as highlighted in the review by Dr. Fasano and colleagues. However, another consideration is the problem of polypharmacy. Rheumatic diseases usually require chronic treatment, sometimes with multiple medications. This makes it even more of a concern to add an additional medication, even a relatively innocuous one such as low-dose aspirin,” he said.

Dr. Husni, Dr. Nurmohamed, and Dr. van Vollenhoven reported having no relevant disclosures. The authors of the review article had no relevant disclosures.

SOURCE: Fasano S et al. Rheumatology. 2020 Aug 25. doi: 10.1093/rheumatology/keaa335.

Low-dose aspirin may be considered for the primary prevention of cardiovascular disease (CVD) in patients with autoimmune systemic rheumatic diseases who are at particularly high risk because of their individual cardiovascular risk profile, according to authors of a new review article in the journal Rheumatology who acknowledge the controversial nature of the issue, because while significant cardiovascular benefit from aspirin for secondary prevention is well established, it has not been for primary prevention.

Secondary prevention with daily, low-dose aspirin is part of aggressive, comprehensive risk modification in patients who have experienced an MI or stroke or are considered at high risk for CVD. But when it comes to primary prevention of the onset of disease, the authors, led by Serena Fasano, MD, PhD, of the rheumatology unit at the University of Campania, Naples, Italy, acknowledged the contradictory positions of international guidelines and uncertainty over balancing benefit versus harm – including risk of mortality in the context of excess bleeding. They called for “robust data” from high-quality randomized, controlled trials for subgroups of patients with specific rheumatologic diseases in order to better answer the question of aspirin for primary prevention.

“This review is devoted to reporting the present knowledge on the effectiveness of low-dose [aspirin] in primary CV prevention in a number of autoimmune systemic rheumatic diseases, not a systematic review or meta-analysis,” the authors stated. “We are not claiming to have covered more than a selection of the literature for each disease. Available data are not high-quality data and do not provide firm conclusions.”

The authors focused primarily on accelerated, rather than spontaneous, atherosclerosis or buildup of plaque in artery walls, implicated in ischemic heart diseases such as MI and ischemic cerebrovascular diseases such as stroke. They looked at its association with autoimmune rheumatic diseases, primarily systemic lupus erythematosus (SLE) and RA, but also including antiphospholipid syndrome, systemic sclerosis, mixed connective tissue disease, dermatomyositis/polymyositis, primary Sjögren’s syndrome, and systemic vasculitis.

They shared results from a review of 167 patients with SLE consecutively admitted to their tertiary medical center who had not previously experienced a cardiovascular event and who were prescribed low-dose (100 mg) aspirin on their first visit and followed for 8 years. The cardiovascular event-free rate was higher in the aspirin group and no excess bleeding was noted, although this may be attributable to a younger patient population and routine use of proton pump inhibitors. Subsequently, hydroxychloroquine was added to the aspirin treatment and was associated with further reduction in cardiovascular events.

The research group also conducted a retrospective analysis of 746 patients with RA consecutively admitted to four tertiary medical centers who hadn’t experienced a cardiovascular event previously. Incidence of cardiovascular events was significantly lower in aspirin-treated patients.
 

Individualized aspirin prescribing with cardiologist comanagement

There may be a modest benefit of using low-dose aspirin on a long-term basis, but that benefit needs to be offset by the risk of bleeds, said M. Elaine Husni, MD, MPH, vice chair of rheumatology and director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic. It’s important to remind clinicians of cardiovascular risk, she said. “But the message for rheumatologists is it needs to be prescribed on an individual basis, rather than based on diagnosis of a rheumatic condition – at least until we have better evidence.”

Dr. Husni recommended keeping an open mind regarding individual approaches – for example, low-dose aspirin plus statins. A composite approach to prevention likely is called for, including attention to lifestyle issues such as smoking cessation, exercise, and weight loss. “That kind of complexity in decision-making highlights the need for comanagement with a cardiologist,” she said. “I’m a big believer in comanagement. At my multidisciplinary medical center, I am able to pick up the phone and talk to a cardiologist with whom our group has a relationship.” If physicians don’t have that kind of relationship with a cardiology group, she suggested reaching out to establish one.

The review paper could give some guidance to rheumatologists for use on an individual case, Michael Nurmohamed, MD, PhD, of the Amsterdam Rheumatology and Immunology Center in the Netherlands commented in an interview. “However, firm recommendations cannot be given as proper investigations are still lacking, as acknowledged by the authors. In addition, the review paper itself has some methodological constraints. Although this is a narrative review, the search strategy should have been specified, and a quality assessment of the individual studies is lacking.”

There is no doubt that the CVD burden in RA and other rheumatologic conditions is substantially increased in comparison to the general population, Dr. Nurmohamed said. That has been assessed by several well-designed, prospective, controlled studies. Other relatively frequent inflammatory arthropathies, including ankylosing spondylitis and psoriatic arthritis, also pose cardiovascular risk.

“Aspirin cannot be recommended for primary CVD prevention in inflammatory arthropathies due to the absence of adequate studies. That’s why the EULAR [European League Against Rheumatism] guidelines did not recommend its use,” he said. Currently, a EULAR task force is developing evidence-based guidelines for primary CVD prevention in the diseases discussed by Fasano et al., where the use of aspirin will be reassessed. “As these guidelines will consider the methodological quality of the underlying studies, they will enable a more refined use of aspirin in daily clinical practice.”

Primary prevention of CVD using aspirin is not currently the standard of care in taking care of patients with rheumatologic disease in the Netherlands, Ronald F. van Vollenhoven, MD, PhD, Dr. Nurmohamed’s colleague and director of the Amsterdam Rheumatology and Immunology Center and the chair of the department of rheumatology and clinical immunology at the Amsterdam University Medical Center, said in an interview.

“One reason may be the limited data, as highlighted in the review by Dr. Fasano and colleagues. However, another consideration is the problem of polypharmacy. Rheumatic diseases usually require chronic treatment, sometimes with multiple medications. This makes it even more of a concern to add an additional medication, even a relatively innocuous one such as low-dose aspirin,” he said.

Dr. Husni, Dr. Nurmohamed, and Dr. van Vollenhoven reported having no relevant disclosures. The authors of the review article had no relevant disclosures.

SOURCE: Fasano S et al. Rheumatology. 2020 Aug 25. doi: 10.1093/rheumatology/keaa335.

Low-dose aspirin may be considered for the primary prevention of cardiovascular disease (CVD) in patients with autoimmune systemic rheumatic diseases who are at particularly high risk because of their individual cardiovascular risk profile, according to authors of a new review article in the journal Rheumatology who acknowledge the controversial nature of the issue, because while significant cardiovascular benefit from aspirin for secondary prevention is well established, it has not been for primary prevention.

Secondary prevention with daily, low-dose aspirin is part of aggressive, comprehensive risk modification in patients who have experienced an MI or stroke or are considered at high risk for CVD. But when it comes to primary prevention of the onset of disease, the authors, led by Serena Fasano, MD, PhD, of the rheumatology unit at the University of Campania, Naples, Italy, acknowledged the contradictory positions of international guidelines and uncertainty over balancing benefit versus harm – including risk of mortality in the context of excess bleeding. They called for “robust data” from high-quality randomized, controlled trials for subgroups of patients with specific rheumatologic diseases in order to better answer the question of aspirin for primary prevention.

“This review is devoted to reporting the present knowledge on the effectiveness of low-dose [aspirin] in primary CV prevention in a number of autoimmune systemic rheumatic diseases, not a systematic review or meta-analysis,” the authors stated. “We are not claiming to have covered more than a selection of the literature for each disease. Available data are not high-quality data and do not provide firm conclusions.”

The authors focused primarily on accelerated, rather than spontaneous, atherosclerosis or buildup of plaque in artery walls, implicated in ischemic heart diseases such as MI and ischemic cerebrovascular diseases such as stroke. They looked at its association with autoimmune rheumatic diseases, primarily systemic lupus erythematosus (SLE) and RA, but also including antiphospholipid syndrome, systemic sclerosis, mixed connective tissue disease, dermatomyositis/polymyositis, primary Sjögren’s syndrome, and systemic vasculitis.

They shared results from a review of 167 patients with SLE consecutively admitted to their tertiary medical center who had not previously experienced a cardiovascular event and who were prescribed low-dose (100 mg) aspirin on their first visit and followed for 8 years. The cardiovascular event-free rate was higher in the aspirin group and no excess bleeding was noted, although this may be attributable to a younger patient population and routine use of proton pump inhibitors. Subsequently, hydroxychloroquine was added to the aspirin treatment and was associated with further reduction in cardiovascular events.

The research group also conducted a retrospective analysis of 746 patients with RA consecutively admitted to four tertiary medical centers who hadn’t experienced a cardiovascular event previously. Incidence of cardiovascular events was significantly lower in aspirin-treated patients.
 

Individualized aspirin prescribing with cardiologist comanagement

There may be a modest benefit of using low-dose aspirin on a long-term basis, but that benefit needs to be offset by the risk of bleeds, said M. Elaine Husni, MD, MPH, vice chair of rheumatology and director of the Arthritis and Musculoskeletal Center at the Cleveland Clinic. It’s important to remind clinicians of cardiovascular risk, she said. “But the message for rheumatologists is it needs to be prescribed on an individual basis, rather than based on diagnosis of a rheumatic condition – at least until we have better evidence.”

Dr. Husni recommended keeping an open mind regarding individual approaches – for example, low-dose aspirin plus statins. A composite approach to prevention likely is called for, including attention to lifestyle issues such as smoking cessation, exercise, and weight loss. “That kind of complexity in decision-making highlights the need for comanagement with a cardiologist,” she said. “I’m a big believer in comanagement. At my multidisciplinary medical center, I am able to pick up the phone and talk to a cardiologist with whom our group has a relationship.” If physicians don’t have that kind of relationship with a cardiology group, she suggested reaching out to establish one.

The review paper could give some guidance to rheumatologists for use on an individual case, Michael Nurmohamed, MD, PhD, of the Amsterdam Rheumatology and Immunology Center in the Netherlands commented in an interview. “However, firm recommendations cannot be given as proper investigations are still lacking, as acknowledged by the authors. In addition, the review paper itself has some methodological constraints. Although this is a narrative review, the search strategy should have been specified, and a quality assessment of the individual studies is lacking.”

There is no doubt that the CVD burden in RA and other rheumatologic conditions is substantially increased in comparison to the general population, Dr. Nurmohamed said. That has been assessed by several well-designed, prospective, controlled studies. Other relatively frequent inflammatory arthropathies, including ankylosing spondylitis and psoriatic arthritis, also pose cardiovascular risk.

“Aspirin cannot be recommended for primary CVD prevention in inflammatory arthropathies due to the absence of adequate studies. That’s why the EULAR [European League Against Rheumatism] guidelines did not recommend its use,” he said. Currently, a EULAR task force is developing evidence-based guidelines for primary CVD prevention in the diseases discussed by Fasano et al., where the use of aspirin will be reassessed. “As these guidelines will consider the methodological quality of the underlying studies, they will enable a more refined use of aspirin in daily clinical practice.”

Primary prevention of CVD using aspirin is not currently the standard of care in taking care of patients with rheumatologic disease in the Netherlands, Ronald F. van Vollenhoven, MD, PhD, Dr. Nurmohamed’s colleague and director of the Amsterdam Rheumatology and Immunology Center and the chair of the department of rheumatology and clinical immunology at the Amsterdam University Medical Center, said in an interview.

“One reason may be the limited data, as highlighted in the review by Dr. Fasano and colleagues. However, another consideration is the problem of polypharmacy. Rheumatic diseases usually require chronic treatment, sometimes with multiple medications. This makes it even more of a concern to add an additional medication, even a relatively innocuous one such as low-dose aspirin,” he said.

Dr. Husni, Dr. Nurmohamed, and Dr. van Vollenhoven reported having no relevant disclosures. The authors of the review article had no relevant disclosures.

SOURCE: Fasano S et al. Rheumatology. 2020 Aug 25. doi: 10.1093/rheumatology/keaa335.

Systemic lupus erythematosus remains a treatment challenge, but a variety of drugs in the pipeline are set to target type I interferons, cytokines, and B cells, according to Richard Furie, MD, chief of the division of rheumatology at Northwell Health and professor of medicine at Hofstra University, Hempstead, N.Y.

Sara Freeman/MDedge News

In general, when treating patients with systemic lupus erythematosus (SLE), “we just don’t see satisfactory response rates,” Dr. Furie said in an online presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“I think the greatest unmet need is in lupus nephritis,” he said. The data show that not even one-third of patients are adequately responding to standard of care treatment. “We need to do better in lupus nephritis but also for those patients with moderate-severe manifestations outside the kidney.”

Patients with SLE have elevated levels of interferon-alpha, Dr. Furie noted. Data from recent studies show that interferon inhibitors can reduce clinical activity in SLE patients, he said.

“About two-thirds to three-quarters of lupus patients have evidence of interferon pathway activation,” he said. There are three types of interferons, and five subtypes of type I interferon, and all five subtypes of type I interferon bind to the same receptor, which is an important strategy for drug development.

In particular, recent phase 2 and 3 trials have focused on targeting type I interferons with anifrolumab, which blocks all five subtypes.

Dr. Furie cited “very robust results” from a phase 2 study. Results of two phase 3 trials of anifrolumab led to a split decision, but the totality of the data collected across the phase 2 and 3 studies points to a drug that is effective for patients with SLE. The two phase 3 studies were published in Lancet Rheumatology and the New England Journal of Medicine.

Dr. Furie also identified recent studies of baricitinib (Olumiant), which has the ability to target several different cytokines. A phase 2 study in 2018 showed a significant difference in SLE Responder Index between lupus patients who received 4 mg of baricitinib or placebo, and a phase 3 study is underway, he said.

For lupus nephritis, Dr. Furie cited the BLISS-LN trial, a 104-week, randomized trial of patients with active lupus nephritis. The group of patients who received belimumab (Benlysta), a monoclonal antibody that targets B-cell activating factor, in addition to standard therapy had significant improvements in renal responses, compared with standard therapy alone (43.0% vs. 32.3%). The outcome measure was Primary Efficacy Renal Response, defined as urinary protein/creatinine ratio <0.7, eGFR ≥60 mL/min per 1.73 m², confirmation on consecutive visits, and required tapering of background glucocorticoids.

Although belimumab was approved for SLE in 2011, the BLISS-LN study focused on SLE patients with active kidney disease. “Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys represented a compelling therapeutic approach to lupus nephritis,” he explained.

Voclosporin, distinct from cyclosporine, has also been studied in lupus nephritis, Dr. Furie said. Voclosporin offers several benefits over cyclosporine, including greater potency and a lower drug and metabolite load, as well as a more consistent pharmacokinetic and pharmacodynamic relationship, he said. In the phase 3 AURORA study, presented at this year’s EULAR congress, 40% of patients with lupus nephritis met the primary endpoint of a renal response at 52 weeks, compared with 22.5% of placebo patients.

Looking ahead to the treatment of SLE in 2021, “I feel very strongly that voclosporin will be approved for lupus nephritis,” he said. He also predicted that the use of belimumab will be officially extended for lupus nephritis and that anifrolumab will receive an approval for SLE patients.

In addition, the future may witness the increased use of biomarkers and development of more individualized therapy. These breakthroughs will yield better outcomes for all lupus patients, he said.

Dr. Furie disclosed relationships with GlaxoSmithKline, Genentech/Roche, Aurinia Pharmaceuticals, AstraZeneca/MedImmune, and Eli Lilly. Global Academy for Medical Education and this news organization are owned by the same parent company.

Systemic lupus erythematosus remains a treatment challenge, but a variety of drugs in the pipeline are set to target type I interferons, cytokines, and B cells, according to Richard Furie, MD, chief of the division of rheumatology at Northwell Health and professor of medicine at Hofstra University, Hempstead, N.Y.

Sara Freeman/MDedge News

In general, when treating patients with systemic lupus erythematosus (SLE), “we just don’t see satisfactory response rates,” Dr. Furie said in an online presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“I think the greatest unmet need is in lupus nephritis,” he said. The data show that not even one-third of patients are adequately responding to standard of care treatment. “We need to do better in lupus nephritis but also for those patients with moderate-severe manifestations outside the kidney.”

Patients with SLE have elevated levels of interferon-alpha, Dr. Furie noted. Data from recent studies show that interferon inhibitors can reduce clinical activity in SLE patients, he said.

“About two-thirds to three-quarters of lupus patients have evidence of interferon pathway activation,” he said. There are three types of interferons, and five subtypes of type I interferon, and all five subtypes of type I interferon bind to the same receptor, which is an important strategy for drug development.

In particular, recent phase 2 and 3 trials have focused on targeting type I interferons with anifrolumab, which blocks all five subtypes.

Dr. Furie cited “very robust results” from a phase 2 study. Results of two phase 3 trials of anifrolumab led to a split decision, but the totality of the data collected across the phase 2 and 3 studies points to a drug that is effective for patients with SLE. The two phase 3 studies were published in Lancet Rheumatology and the New England Journal of Medicine.

Dr. Furie also identified recent studies of baricitinib (Olumiant), which has the ability to target several different cytokines. A phase 2 study in 2018 showed a significant difference in SLE Responder Index between lupus patients who received 4 mg of baricitinib or placebo, and a phase 3 study is underway, he said.

For lupus nephritis, Dr. Furie cited the BLISS-LN trial, a 104-week, randomized trial of patients with active lupus nephritis. The group of patients who received belimumab (Benlysta), a monoclonal antibody that targets B-cell activating factor, in addition to standard therapy had significant improvements in renal responses, compared with standard therapy alone (43.0% vs. 32.3%). The outcome measure was Primary Efficacy Renal Response, defined as urinary protein/creatinine ratio <0.7, eGFR ≥60 mL/min per 1.73 m², confirmation on consecutive visits, and required tapering of background glucocorticoids.

Although belimumab was approved for SLE in 2011, the BLISS-LN study focused on SLE patients with active kidney disease. “Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys represented a compelling therapeutic approach to lupus nephritis,” he explained.

Voclosporin, distinct from cyclosporine, has also been studied in lupus nephritis, Dr. Furie said. Voclosporin offers several benefits over cyclosporine, including greater potency and a lower drug and metabolite load, as well as a more consistent pharmacokinetic and pharmacodynamic relationship, he said. In the phase 3 AURORA study, presented at this year’s EULAR congress, 40% of patients with lupus nephritis met the primary endpoint of a renal response at 52 weeks, compared with 22.5% of placebo patients.

Looking ahead to the treatment of SLE in 2021, “I feel very strongly that voclosporin will be approved for lupus nephritis,” he said. He also predicted that the use of belimumab will be officially extended for lupus nephritis and that anifrolumab will receive an approval for SLE patients.

In addition, the future may witness the increased use of biomarkers and development of more individualized therapy. These breakthroughs will yield better outcomes for all lupus patients, he said.

Dr. Furie disclosed relationships with GlaxoSmithKline, Genentech/Roche, Aurinia Pharmaceuticals, AstraZeneca/MedImmune, and Eli Lilly. Global Academy for Medical Education and this news organization are owned by the same parent company.

Systemic lupus erythematosus remains a treatment challenge, but a variety of drugs in the pipeline are set to target type I interferons, cytokines, and B cells, according to Richard Furie, MD, chief of the division of rheumatology at Northwell Health and professor of medicine at Hofstra University, Hempstead, N.Y.

Sara Freeman/MDedge News

In general, when treating patients with systemic lupus erythematosus (SLE), “we just don’t see satisfactory response rates,” Dr. Furie said in an online presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“I think the greatest unmet need is in lupus nephritis,” he said. The data show that not even one-third of patients are adequately responding to standard of care treatment. “We need to do better in lupus nephritis but also for those patients with moderate-severe manifestations outside the kidney.”

Patients with SLE have elevated levels of interferon-alpha, Dr. Furie noted. Data from recent studies show that interferon inhibitors can reduce clinical activity in SLE patients, he said.

“About two-thirds to three-quarters of lupus patients have evidence of interferon pathway activation,” he said. There are three types of interferons, and five subtypes of type I interferon, and all five subtypes of type I interferon bind to the same receptor, which is an important strategy for drug development.

In particular, recent phase 2 and 3 trials have focused on targeting type I interferons with anifrolumab, which blocks all five subtypes.

Dr. Furie cited “very robust results” from a phase 2 study. Results of two phase 3 trials of anifrolumab led to a split decision, but the totality of the data collected across the phase 2 and 3 studies points to a drug that is effective for patients with SLE. The two phase 3 studies were published in Lancet Rheumatology and the New England Journal of Medicine.

Dr. Furie also identified recent studies of baricitinib (Olumiant), which has the ability to target several different cytokines. A phase 2 study in 2018 showed a significant difference in SLE Responder Index between lupus patients who received 4 mg of baricitinib or placebo, and a phase 3 study is underway, he said.

For lupus nephritis, Dr. Furie cited the BLISS-LN trial, a 104-week, randomized trial of patients with active lupus nephritis. The group of patients who received belimumab (Benlysta), a monoclonal antibody that targets B-cell activating factor, in addition to standard therapy had significant improvements in renal responses, compared with standard therapy alone (43.0% vs. 32.3%). The outcome measure was Primary Efficacy Renal Response, defined as urinary protein/creatinine ratio <0.7, eGFR ≥60 mL/min per 1.73 m², confirmation on consecutive visits, and required tapering of background glucocorticoids.

Although belimumab was approved for SLE in 2011, the BLISS-LN study focused on SLE patients with active kidney disease. “Neutralizing B-cell activating factor and down-regulating autoreactive B-cell function in kidneys represented a compelling therapeutic approach to lupus nephritis,” he explained.

Voclosporin, distinct from cyclosporine, has also been studied in lupus nephritis, Dr. Furie said. Voclosporin offers several benefits over cyclosporine, including greater potency and a lower drug and metabolite load, as well as a more consistent pharmacokinetic and pharmacodynamic relationship, he said. In the phase 3 AURORA study, presented at this year’s EULAR congress, 40% of patients with lupus nephritis met the primary endpoint of a renal response at 52 weeks, compared with 22.5% of placebo patients.

Looking ahead to the treatment of SLE in 2021, “I feel very strongly that voclosporin will be approved for lupus nephritis,” he said. He also predicted that the use of belimumab will be officially extended for lupus nephritis and that anifrolumab will receive an approval for SLE patients.

In addition, the future may witness the increased use of biomarkers and development of more individualized therapy. These breakthroughs will yield better outcomes for all lupus patients, he said.

Dr. Furie disclosed relationships with GlaxoSmithKline, Genentech/Roche, Aurinia Pharmaceuticals, AstraZeneca/MedImmune, and Eli Lilly. Global Academy for Medical Education and this news organization are owned by the same parent company.

A new study has found that late-onset neutropenia is a notably common and occasionally serious occurrence in rituximab-treated patients with autoimmune diseases.

“The literature on late-onset neutropenia – or LON – has, to date, been limited in size and scope,” first author Reza Zonozi, MD, of Massachusetts General Hospital in Boston, said in an interview. “At the Vasculitis and Glomerulonephritis Center at Mass General, we’ve seen a number of cases of LON. Even though most are incidental and can be self-limiting, some can be severe and associated with sepsis. As such, we’ve come to appreciate it as one of the more concerning side effects of rituximab.

“Our hope was to offer a practical analysis of LON, how often it happens, and what it looks like,” he added, “as well as to share our approach to its management.” Their findings were published in Arthritis & Rheumatology.

To investigate the incidence, clinical features and outcomes of LON, the researchers launched a study of 738 adult patients with autoimmune diseases who were being treated with rituximab-induced continuous B-cell depletion. For the purposes of this study, LON was defined as an unexplained absolute neutrophil count of less than 1,000 cells/mcL during the period of B-cell depletion. Regarding disease type, 529 of the patients had antineutrophil cytoplasmic antibody–associated vasculitis (AAV), 73 had membranous nephropathy (MN), 59 had minimal change disease or focal segmental glomerulosclerosis (MCD/FSGS), 24 had lupus nephritis, and 53 had another autoimmune disease. Their average age was 58, and 53% were female.

All patients received a median of eight doses of rituximab – most commonly administered as one 1,000-mg IV dose every 4-6 months – and were in a state of B-cell depletion for a median of 2.5 years. Two months of low-dose daily oral cyclophosphamide was also used concurrently in 70% (n = 515) of patients. Glucocorticoids were used in 95% (n = 698) of patients.

During follow-up, 107 episodes of LON occurred in 71 patients. At 1, 2, and 5 years of continuous B-cell depletion, the incidence of LON was 6.6% (95% confidence interval, 5.0%-8.7%), 7.9% (95% CI, 6.1%-10.2%), and 13.5% (95% CI, 10.4%-17.4%), respectively. The first year following treatment initiation saw a much higher incidence rate of 7.2 per 100 person-years (95% CI, 5.4-9.6), compared with the rate thereafter of 1.5 per 100 person-years (95% CI, 1.0-2.3). LON occurred at a median of 4.1 months (interquartile range, 1.6-23.1) after the first rituximab infusion. The most common treatment for a LON episode was filgrastim.

Of the 107 episodes, 63 (59%) were asymptomatic. No infections were identified in asymptomatic episodes, while infections were identified in all symptomatic episodes. The most common symptom was a fever, and all 30 patients with LON and fever were hospitalized for management of febrile neutropenia. Four of the episodes included gingival soreness, and eight were complicated by sepsis. All the sepsis cases were resolved with standard therapy. One patient died with multiple relapsing LON.

Of the 71 patients with LON, 9 were not rechallenged with rituximab. A total of four of those patients had second LON episodes. Of the 62 patients who were rechallenged, 13 had second LON episodes over a median follow-up period of 2.4 years. The cumulative incidence of recurrent LON at 1, 2, and 5 years after rechallenge was 11.5% (95% CI, 5.6%-22.6%), 23.4% (95% CI, 13.8%-38.2%), and 30.4% (95% CI, 16.9%-50.9%), respectively.

Percentagewise, LON occurred significantly more often in patients with lupus nephritis (25%) than in patients with AAV (10.4%), MN (8.2%), or other diseases (7.6%) (P = .03). LON did not occur in any of the patients with MCD/FSGS. After multivariable analysis, lupus nephritis was associated with higher odds of developing LON (adjusted hazard ratio, 2.96; 95% CI, 1.10-8.01). A multivariable model also found that patients treated with cyclophosphamide and rituximab had higher odds of developing LON, compared with patients who did not receive cyclophosphamide (aHR, 1.98; 95% CI, 1.06-3.71).

 

Still more to learn about what leads to LON

“In large part, these findings quantify what our experience has been with LON in clinical practice,” Dr. Zonozi said. “It is indeed common, it’s often incidental, and most cases are reversible and respond well to treatment. But it can be associated with severe infections, including sepsis, and warrants close monitoring.”

In an interview, Md Yuzaiful Md Yusof, MBChB, PhD, observed that this incidence rate was notably higher than what he’d seen previously. Dr. Md Yusof presented at EULAR Congress 2015 on rituximab and LON, finding that 23 patients (2.5%) from a cohort of 912 developed rituximab-associated neutropenia.

“Most of our cases were in patients with rheumatoid arthritis,” he added, “so it may just be a difference in cohorts.”

Regardless, he applauded additional research in this area, noting that “the etiology of rituximab-associated LON is still unclear. The reasons behind this occurrence need investigating, particularly in regard to severe neutropenia cases. If we can find the predictors of those, it will be extremely helpful for the future of treatment.”

Dr. Zonozi agreed that “more investigation is needed to accurately define the mechanism of LON, which remains unknown. This will likely lead to more targeted strategies to both prevent and treat it.”

The authors acknowledged their study’s limitations, including being a single-center study that relied on retrospective data collection. They also acknowledged that, because the center is a nephrology-based practice, there was a low number of certain diseases like RA, opening up the possibility that “rates of LON are different” in those patients.

Two authors’ work on the study was funded by grants from the National Institutes of Health. The authors disclosed no potential conflicts of interest.

SOURCE: Zonozi R et al. Arthritis Rheumatol. 2020 Sep 6. doi: 10.1002/art.41501.

A new study has found that late-onset neutropenia is a notably common and occasionally serious occurrence in rituximab-treated patients with autoimmune diseases.

“The literature on late-onset neutropenia – or LON – has, to date, been limited in size and scope,” first author Reza Zonozi, MD, of Massachusetts General Hospital in Boston, said in an interview. “At the Vasculitis and Glomerulonephritis Center at Mass General, we’ve seen a number of cases of LON. Even though most are incidental and can be self-limiting, some can be severe and associated with sepsis. As such, we’ve come to appreciate it as one of the more concerning side effects of rituximab.

“Our hope was to offer a practical analysis of LON, how often it happens, and what it looks like,” he added, “as well as to share our approach to its management.” Their findings were published in Arthritis & Rheumatology.

To investigate the incidence, clinical features and outcomes of LON, the researchers launched a study of 738 adult patients with autoimmune diseases who were being treated with rituximab-induced continuous B-cell depletion. For the purposes of this study, LON was defined as an unexplained absolute neutrophil count of less than 1,000 cells/mcL during the period of B-cell depletion. Regarding disease type, 529 of the patients had antineutrophil cytoplasmic antibody–associated vasculitis (AAV), 73 had membranous nephropathy (MN), 59 had minimal change disease or focal segmental glomerulosclerosis (MCD/FSGS), 24 had lupus nephritis, and 53 had another autoimmune disease. Their average age was 58, and 53% were female.

All patients received a median of eight doses of rituximab – most commonly administered as one 1,000-mg IV dose every 4-6 months – and were in a state of B-cell depletion for a median of 2.5 years. Two months of low-dose daily oral cyclophosphamide was also used concurrently in 70% (n = 515) of patients. Glucocorticoids were used in 95% (n = 698) of patients.

During follow-up, 107 episodes of LON occurred in 71 patients. At 1, 2, and 5 years of continuous B-cell depletion, the incidence of LON was 6.6% (95% confidence interval, 5.0%-8.7%), 7.9% (95% CI, 6.1%-10.2%), and 13.5% (95% CI, 10.4%-17.4%), respectively. The first year following treatment initiation saw a much higher incidence rate of 7.2 per 100 person-years (95% CI, 5.4-9.6), compared with the rate thereafter of 1.5 per 100 person-years (95% CI, 1.0-2.3). LON occurred at a median of 4.1 months (interquartile range, 1.6-23.1) after the first rituximab infusion. The most common treatment for a LON episode was filgrastim.

Of the 107 episodes, 63 (59%) were asymptomatic. No infections were identified in asymptomatic episodes, while infections were identified in all symptomatic episodes. The most common symptom was a fever, and all 30 patients with LON and fever were hospitalized for management of febrile neutropenia. Four of the episodes included gingival soreness, and eight were complicated by sepsis. All the sepsis cases were resolved with standard therapy. One patient died with multiple relapsing LON.

Of the 71 patients with LON, 9 were not rechallenged with rituximab. A total of four of those patients had second LON episodes. Of the 62 patients who were rechallenged, 13 had second LON episodes over a median follow-up period of 2.4 years. The cumulative incidence of recurrent LON at 1, 2, and 5 years after rechallenge was 11.5% (95% CI, 5.6%-22.6%), 23.4% (95% CI, 13.8%-38.2%), and 30.4% (95% CI, 16.9%-50.9%), respectively.

Percentagewise, LON occurred significantly more often in patients with lupus nephritis (25%) than in patients with AAV (10.4%), MN (8.2%), or other diseases (7.6%) (P = .03). LON did not occur in any of the patients with MCD/FSGS. After multivariable analysis, lupus nephritis was associated with higher odds of developing LON (adjusted hazard ratio, 2.96; 95% CI, 1.10-8.01). A multivariable model also found that patients treated with cyclophosphamide and rituximab had higher odds of developing LON, compared with patients who did not receive cyclophosphamide (aHR, 1.98; 95% CI, 1.06-3.71).

 

Still more to learn about what leads to LON

“In large part, these findings quantify what our experience has been with LON in clinical practice,” Dr. Zonozi said. “It is indeed common, it’s often incidental, and most cases are reversible and respond well to treatment. But it can be associated with severe infections, including sepsis, and warrants close monitoring.”

In an interview, Md Yuzaiful Md Yusof, MBChB, PhD, observed that this incidence rate was notably higher than what he’d seen previously. Dr. Md Yusof presented at EULAR Congress 2015 on rituximab and LON, finding that 23 patients (2.5%) from a cohort of 912 developed rituximab-associated neutropenia.

“Most of our cases were in patients with rheumatoid arthritis,” he added, “so it may just be a difference in cohorts.”

Regardless, he applauded additional research in this area, noting that “the etiology of rituximab-associated LON is still unclear. The reasons behind this occurrence need investigating, particularly in regard to severe neutropenia cases. If we can find the predictors of those, it will be extremely helpful for the future of treatment.”

Dr. Zonozi agreed that “more investigation is needed to accurately define the mechanism of LON, which remains unknown. This will likely lead to more targeted strategies to both prevent and treat it.”

The authors acknowledged their study’s limitations, including being a single-center study that relied on retrospective data collection. They also acknowledged that, because the center is a nephrology-based practice, there was a low number of certain diseases like RA, opening up the possibility that “rates of LON are different” in those patients.

Two authors’ work on the study was funded by grants from the National Institutes of Health. The authors disclosed no potential conflicts of interest.

SOURCE: Zonozi R et al. Arthritis Rheumatol. 2020 Sep 6. doi: 10.1002/art.41501.

A new study has found that late-onset neutropenia is a notably common and occasionally serious occurrence in rituximab-treated patients with autoimmune diseases.

“The literature on late-onset neutropenia – or LON – has, to date, been limited in size and scope,” first author Reza Zonozi, MD, of Massachusetts General Hospital in Boston, said in an interview. “At the Vasculitis and Glomerulonephritis Center at Mass General, we’ve seen a number of cases of LON. Even though most are incidental and can be self-limiting, some can be severe and associated with sepsis. As such, we’ve come to appreciate it as one of the more concerning side effects of rituximab.

“Our hope was to offer a practical analysis of LON, how often it happens, and what it looks like,” he added, “as well as to share our approach to its management.” Their findings were published in Arthritis & Rheumatology.

To investigate the incidence, clinical features and outcomes of LON, the researchers launched a study of 738 adult patients with autoimmune diseases who were being treated with rituximab-induced continuous B-cell depletion. For the purposes of this study, LON was defined as an unexplained absolute neutrophil count of less than 1,000 cells/mcL during the period of B-cell depletion. Regarding disease type, 529 of the patients had antineutrophil cytoplasmic antibody–associated vasculitis (AAV), 73 had membranous nephropathy (MN), 59 had minimal change disease or focal segmental glomerulosclerosis (MCD/FSGS), 24 had lupus nephritis, and 53 had another autoimmune disease. Their average age was 58, and 53% were female.

All patients received a median of eight doses of rituximab – most commonly administered as one 1,000-mg IV dose every 4-6 months – and were in a state of B-cell depletion for a median of 2.5 years. Two months of low-dose daily oral cyclophosphamide was also used concurrently in 70% (n = 515) of patients. Glucocorticoids were used in 95% (n = 698) of patients.

During follow-up, 107 episodes of LON occurred in 71 patients. At 1, 2, and 5 years of continuous B-cell depletion, the incidence of LON was 6.6% (95% confidence interval, 5.0%-8.7%), 7.9% (95% CI, 6.1%-10.2%), and 13.5% (95% CI, 10.4%-17.4%), respectively. The first year following treatment initiation saw a much higher incidence rate of 7.2 per 100 person-years (95% CI, 5.4-9.6), compared with the rate thereafter of 1.5 per 100 person-years (95% CI, 1.0-2.3). LON occurred at a median of 4.1 months (interquartile range, 1.6-23.1) after the first rituximab infusion. The most common treatment for a LON episode was filgrastim.

Of the 107 episodes, 63 (59%) were asymptomatic. No infections were identified in asymptomatic episodes, while infections were identified in all symptomatic episodes. The most common symptom was a fever, and all 30 patients with LON and fever were hospitalized for management of febrile neutropenia. Four of the episodes included gingival soreness, and eight were complicated by sepsis. All the sepsis cases were resolved with standard therapy. One patient died with multiple relapsing LON.

Of the 71 patients with LON, 9 were not rechallenged with rituximab. A total of four of those patients had second LON episodes. Of the 62 patients who were rechallenged, 13 had second LON episodes over a median follow-up period of 2.4 years. The cumulative incidence of recurrent LON at 1, 2, and 5 years after rechallenge was 11.5% (95% CI, 5.6%-22.6%), 23.4% (95% CI, 13.8%-38.2%), and 30.4% (95% CI, 16.9%-50.9%), respectively.

Percentagewise, LON occurred significantly more often in patients with lupus nephritis (25%) than in patients with AAV (10.4%), MN (8.2%), or other diseases (7.6%) (P = .03). LON did not occur in any of the patients with MCD/FSGS. After multivariable analysis, lupus nephritis was associated with higher odds of developing LON (adjusted hazard ratio, 2.96; 95% CI, 1.10-8.01). A multivariable model also found that patients treated with cyclophosphamide and rituximab had higher odds of developing LON, compared with patients who did not receive cyclophosphamide (aHR, 1.98; 95% CI, 1.06-3.71).

 

Still more to learn about what leads to LON

“In large part, these findings quantify what our experience has been with LON in clinical practice,” Dr. Zonozi said. “It is indeed common, it’s often incidental, and most cases are reversible and respond well to treatment. But it can be associated with severe infections, including sepsis, and warrants close monitoring.”

In an interview, Md Yuzaiful Md Yusof, MBChB, PhD, observed that this incidence rate was notably higher than what he’d seen previously. Dr. Md Yusof presented at EULAR Congress 2015 on rituximab and LON, finding that 23 patients (2.5%) from a cohort of 912 developed rituximab-associated neutropenia.

“Most of our cases were in patients with rheumatoid arthritis,” he added, “so it may just be a difference in cohorts.”

Regardless, he applauded additional research in this area, noting that “the etiology of rituximab-associated LON is still unclear. The reasons behind this occurrence need investigating, particularly in regard to severe neutropenia cases. If we can find the predictors of those, it will be extremely helpful for the future of treatment.”

Dr. Zonozi agreed that “more investigation is needed to accurately define the mechanism of LON, which remains unknown. This will likely lead to more targeted strategies to both prevent and treat it.”

The authors acknowledged their study’s limitations, including being a single-center study that relied on retrospective data collection. They also acknowledged that, because the center is a nephrology-based practice, there was a low number of certain diseases like RA, opening up the possibility that “rates of LON are different” in those patients.

Two authors’ work on the study was funded by grants from the National Institutes of Health. The authors disclosed no potential conflicts of interest.

SOURCE: Zonozi R et al. Arthritis Rheumatol. 2020 Sep 6. doi: 10.1002/art.41501.

A nurse-led intervention aimed at reducing hospital readmission rates for systemic lupus erythematosus (SLE) is feasible but the jury is out as to whether it can achieve its primary goal, a study has found.

Copyright Kimberly Pack/Thinkstock

A paper published in Arthritis Care & Research presents the outcomes of a retrospective study using electronic health records that looked at the effect of a quality improvement initiative at the University of Colorado Hospital on readmission rates in two cohorts of 48 and 56 individuals with SLE.

Emily Bowers, MD, of the department of rheumatology at the University of Colorado at Denver, Aurora, and coauthors wrote that hospital readmission rates for SLE are as high as 36% for 30-day readmission. They are significantly higher than for other common chronic diseases such as heart failure, COPD, and diabetes. Readmission for SLE is associated with young age, ethnic or racial diversity, public health insurance, multiorgan involvement, and other comorbidities.

The intervention involved first alerting clinic nurses via the patient’s electronic medical record when the patient was discharged from hospital. The nurses would then call the patient within 48 hours to answer any questions and review their discharge information, and then consult with a rheumatologist on on-call if needed. This call was documented in the patient’s medical record.

In the preintervention cohort, there were 59 hospitalizations among 48 patients, 29% of which were followed by readmission within 30 days; 53% of these readmissions were lupus related. In the cohort that followed introduction of the intervention, there were 73 hospitalizations among 56 individuals, and 19% were followed by readmission within 30 days, 29% of which were lupus related.

After accounting for gender, age, race, and insurance type, the researchers calculated that there was an 89% higher odds of readmission in the nonintervention group than in the intervention group, but the difference was not statistically significant.

The authors noted that although the results were not statistically significant, the low cost of the intervention – requiring around 30 minutes of nursing time – meant even small reductions in the number of emergency department or hospital admissions would make it a cost-effective approach.

“Telephone outreach is an excellent method of providing additional support to patients, assessing clinical needs, reinforcing education about SLE, medications, and common complications such as drug side effects and infections, and allows for patients to ask pertinent questions to RN providers with expertise in the management of lupus,” the authors wrote.

The nurses also recorded qualitative information about the calls, which picked up some patient issues that could be addressed. For example, a patient was discharged with the wrong amount of prednisone, which the nurse was able to fix by adjusting the order and sending it to the pharmacy. Two other patients were confused by their medication instructions and were taking the medication incorrectly; the nurse arranged for the patients to come in for educational session. In another case, the nurse was able to arrange an infusion for the patient, and for one patient with concerns about infection, the nurse was able to advise that person on symptoms and how to seek care.

“To increase implementation of the intervention, we have discussed creating a discharge order set, which would include an automatic EMR message to the nurses,” the authors wrote. “Future studies should explore alternative ways of communicating with our patients after discharge, such as the use of text messaging, messaging through the patient portal in the EMR, or telehealth.”

The authors had no financial disclosures, and there was no outside financial support for the study.

SOURCE: Bowers E et al. Arthritis Care Res. 2020 Aug 29. doi: 10.1002/acr.24435.

A nurse-led intervention aimed at reducing hospital readmission rates for systemic lupus erythematosus (SLE) is feasible but the jury is out as to whether it can achieve its primary goal, a study has found.

Copyright Kimberly Pack/Thinkstock

A paper published in Arthritis Care & Research presents the outcomes of a retrospective study using electronic health records that looked at the effect of a quality improvement initiative at the University of Colorado Hospital on readmission rates in two cohorts of 48 and 56 individuals with SLE.

Emily Bowers, MD, of the department of rheumatology at the University of Colorado at Denver, Aurora, and coauthors wrote that hospital readmission rates for SLE are as high as 36% for 30-day readmission. They are significantly higher than for other common chronic diseases such as heart failure, COPD, and diabetes. Readmission for SLE is associated with young age, ethnic or racial diversity, public health insurance, multiorgan involvement, and other comorbidities.

The intervention involved first alerting clinic nurses via the patient’s electronic medical record when the patient was discharged from hospital. The nurses would then call the patient within 48 hours to answer any questions and review their discharge information, and then consult with a rheumatologist on on-call if needed. This call was documented in the patient’s medical record.

In the preintervention cohort, there were 59 hospitalizations among 48 patients, 29% of which were followed by readmission within 30 days; 53% of these readmissions were lupus related. In the cohort that followed introduction of the intervention, there were 73 hospitalizations among 56 individuals, and 19% were followed by readmission within 30 days, 29% of which were lupus related.

After accounting for gender, age, race, and insurance type, the researchers calculated that there was an 89% higher odds of readmission in the nonintervention group than in the intervention group, but the difference was not statistically significant.

The authors noted that although the results were not statistically significant, the low cost of the intervention – requiring around 30 minutes of nursing time – meant even small reductions in the number of emergency department or hospital admissions would make it a cost-effective approach.

“Telephone outreach is an excellent method of providing additional support to patients, assessing clinical needs, reinforcing education about SLE, medications, and common complications such as drug side effects and infections, and allows for patients to ask pertinent questions to RN providers with expertise in the management of lupus,” the authors wrote.

The nurses also recorded qualitative information about the calls, which picked up some patient issues that could be addressed. For example, a patient was discharged with the wrong amount of prednisone, which the nurse was able to fix by adjusting the order and sending it to the pharmacy. Two other patients were confused by their medication instructions and were taking the medication incorrectly; the nurse arranged for the patients to come in for educational session. In another case, the nurse was able to arrange an infusion for the patient, and for one patient with concerns about infection, the nurse was able to advise that person on symptoms and how to seek care.

“To increase implementation of the intervention, we have discussed creating a discharge order set, which would include an automatic EMR message to the nurses,” the authors wrote. “Future studies should explore alternative ways of communicating with our patients after discharge, such as the use of text messaging, messaging through the patient portal in the EMR, or telehealth.”

The authors had no financial disclosures, and there was no outside financial support for the study.

SOURCE: Bowers E et al. Arthritis Care Res. 2020 Aug 29. doi: 10.1002/acr.24435.

A nurse-led intervention aimed at reducing hospital readmission rates for systemic lupus erythematosus (SLE) is feasible but the jury is out as to whether it can achieve its primary goal, a study has found.

Copyright Kimberly Pack/Thinkstock

A paper published in Arthritis Care & Research presents the outcomes of a retrospective study using electronic health records that looked at the effect of a quality improvement initiative at the University of Colorado Hospital on readmission rates in two cohorts of 48 and 56 individuals with SLE.

Emily Bowers, MD, of the department of rheumatology at the University of Colorado at Denver, Aurora, and coauthors wrote that hospital readmission rates for SLE are as high as 36% for 30-day readmission. They are significantly higher than for other common chronic diseases such as heart failure, COPD, and diabetes. Readmission for SLE is associated with young age, ethnic or racial diversity, public health insurance, multiorgan involvement, and other comorbidities.

The intervention involved first alerting clinic nurses via the patient’s electronic medical record when the patient was discharged from hospital. The nurses would then call the patient within 48 hours to answer any questions and review their discharge information, and then consult with a rheumatologist on on-call if needed. This call was documented in the patient’s medical record.

In the preintervention cohort, there were 59 hospitalizations among 48 patients, 29% of which were followed by readmission within 30 days; 53% of these readmissions were lupus related. In the cohort that followed introduction of the intervention, there were 73 hospitalizations among 56 individuals, and 19% were followed by readmission within 30 days, 29% of which were lupus related.

After accounting for gender, age, race, and insurance type, the researchers calculated that there was an 89% higher odds of readmission in the nonintervention group than in the intervention group, but the difference was not statistically significant.

The authors noted that although the results were not statistically significant, the low cost of the intervention – requiring around 30 minutes of nursing time – meant even small reductions in the number of emergency department or hospital admissions would make it a cost-effective approach.

“Telephone outreach is an excellent method of providing additional support to patients, assessing clinical needs, reinforcing education about SLE, medications, and common complications such as drug side effects and infections, and allows for patients to ask pertinent questions to RN providers with expertise in the management of lupus,” the authors wrote.

The nurses also recorded qualitative information about the calls, which picked up some patient issues that could be addressed. For example, a patient was discharged with the wrong amount of prednisone, which the nurse was able to fix by adjusting the order and sending it to the pharmacy. Two other patients were confused by their medication instructions and were taking the medication incorrectly; the nurse arranged for the patients to come in for educational session. In another case, the nurse was able to arrange an infusion for the patient, and for one patient with concerns about infection, the nurse was able to advise that person on symptoms and how to seek care.

“To increase implementation of the intervention, we have discussed creating a discharge order set, which would include an automatic EMR message to the nurses,” the authors wrote. “Future studies should explore alternative ways of communicating with our patients after discharge, such as the use of text messaging, messaging through the patient portal in the EMR, or telehealth.”

The authors had no financial disclosures, and there was no outside financial support for the study.

SOURCE: Bowers E et al. Arthritis Care Res. 2020 Aug 29. doi: 10.1002/acr.24435.