Lupus & Connective Tissue Diseases

Patients with systemic lupus erythematosus (SLE) who received transcutaneous auricular vagus nerve stimulation (taVNS) had a clinically significant reduction in musculoskeletal pain when compared with those who received sham stimulation during a brief pilot trial.

“Our study population included individuals with significant pain and exemplifies the unmet need for adequate control of pain and fatigue in SLE. Importantly, this was a double-blind, sham-controlled study and neither the subject nor assessor was aware of a subject’s intervention. Objective outcomes, that is, tender and swollen joint counts, were also significantly reduced in subjects receiving taVNS, compared with those receiving [sham stimulation]. The stimulation was well tolerated with no adverse events attributed to the intervention, and, clinical benefits continued after taVNS was stopped,” first author Cynthia Aranow, MD, and her colleagues at the Feinstein Institutes for Medical Research in Manhasset, N.Y., wrote in Annals of the Rheumatic Diseases.

Stimulation of the vagus nerve can be achieved through the ear via its auricular branch, which innervates the cymba concha in the outer ear. Past pilot studies of implanted VNS devices lasting 6 weeks to 6 months in patients with Crohn’s disease or rheumatoid arthritis have shown improvements in measures of disease activity as well as objective markers of inflammation, and a more recent trial testing a transcutaneous devices’s effect in patients with Sjögren’s syndrome found significant reductions in fatigue over a 26-day period, the investigators noted.

In the taVNS device study, the researchers recruited 18 patients with SLE who had musculoskeletal pain rated as 4 or higher on a 10-cm visual analog scale and randomized them in a 2:1 ratio to receive taVNS once per day for 5 minutes for 4 consecutive days versus sham stimulation. Patients were allowed to be on stable doses of disease-modifying antirheumatic drugs, biologics, and/or prednisone ≤ 10 mg/day, with no change of dose within 28 days prior to baseline. The study excluded patients who used tobacco or an anticholinergic medication and those with a diagnosis of fibromyalgia.

The 12 patients who received actual taVNS had a significantly greater reduction in their pain, compared with 6 sham-treated patients (–5.00 vs. 0.10; P = .049), with 10 of 12 and 1 of 6 having a clinical response (a reduction of at least 1.58 on a 10-cm visual analog scale from baseline to day 5). Stimulation-treated patients also reported significantly greater reductions in fatigue, with 10 of 12 achieving a meaningful reduction, defined as a 4-point improvement on the Functional Assessment of Chronic Illness Therapy Fatigue Subscale; none of the sham-treated patients experienced meaningful improvement of fatigue. The patients who received taVNS had resolution of all swollen and tender joints, compared with 5.3% of tender and 9.1% of swollen joints in sham-treated patients. Ex vivo lipopolysaccharide stimulation of whole-blood samples from taVNS-treated patients, however, showed no reductions of inflammatory mediators or chemokines in tests on day 5 and day 12.

The investigators reported that there were no adverse events attributed to taVNS, including no reports of headache, lightheadedness, tinnitus, ear irritation, or changes to the external skin of the outer ear.

The study was supported by a grant from the John and Marcia Goldman Foundation. One author reported a financial relationship with Set Point Medical and My String, and three authors reported having a provisional patent application titled “Auricular stimulation device, system and methods of use.”

[email protected]

SOURCE: Aranow C et al. Ann Rheum Dis. 2020 Nov 3. doi: 10.1136/annrheumdis-2020-217872.

Patients with systemic lupus erythematosus (SLE) who received transcutaneous auricular vagus nerve stimulation (taVNS) had a clinically significant reduction in musculoskeletal pain when compared with those who received sham stimulation during a brief pilot trial.

“Our study population included individuals with significant pain and exemplifies the unmet need for adequate control of pain and fatigue in SLE. Importantly, this was a double-blind, sham-controlled study and neither the subject nor assessor was aware of a subject’s intervention. Objective outcomes, that is, tender and swollen joint counts, were also significantly reduced in subjects receiving taVNS, compared with those receiving [sham stimulation]. The stimulation was well tolerated with no adverse events attributed to the intervention, and, clinical benefits continued after taVNS was stopped,” first author Cynthia Aranow, MD, and her colleagues at the Feinstein Institutes for Medical Research in Manhasset, N.Y., wrote in Annals of the Rheumatic Diseases.

Stimulation of the vagus nerve can be achieved through the ear via its auricular branch, which innervates the cymba concha in the outer ear. Past pilot studies of implanted VNS devices lasting 6 weeks to 6 months in patients with Crohn’s disease or rheumatoid arthritis have shown improvements in measures of disease activity as well as objective markers of inflammation, and a more recent trial testing a transcutaneous devices’s effect in patients with Sjögren’s syndrome found significant reductions in fatigue over a 26-day period, the investigators noted.

In the taVNS device study, the researchers recruited 18 patients with SLE who had musculoskeletal pain rated as 4 or higher on a 10-cm visual analog scale and randomized them in a 2:1 ratio to receive taVNS once per day for 5 minutes for 4 consecutive days versus sham stimulation. Patients were allowed to be on stable doses of disease-modifying antirheumatic drugs, biologics, and/or prednisone ≤ 10 mg/day, with no change of dose within 28 days prior to baseline. The study excluded patients who used tobacco or an anticholinergic medication and those with a diagnosis of fibromyalgia.

The 12 patients who received actual taVNS had a significantly greater reduction in their pain, compared with 6 sham-treated patients (–5.00 vs. 0.10; P = .049), with 10 of 12 and 1 of 6 having a clinical response (a reduction of at least 1.58 on a 10-cm visual analog scale from baseline to day 5). Stimulation-treated patients also reported significantly greater reductions in fatigue, with 10 of 12 achieving a meaningful reduction, defined as a 4-point improvement on the Functional Assessment of Chronic Illness Therapy Fatigue Subscale; none of the sham-treated patients experienced meaningful improvement of fatigue. The patients who received taVNS had resolution of all swollen and tender joints, compared with 5.3% of tender and 9.1% of swollen joints in sham-treated patients. Ex vivo lipopolysaccharide stimulation of whole-blood samples from taVNS-treated patients, however, showed no reductions of inflammatory mediators or chemokines in tests on day 5 and day 12.

The investigators reported that there were no adverse events attributed to taVNS, including no reports of headache, lightheadedness, tinnitus, ear irritation, or changes to the external skin of the outer ear.

The study was supported by a grant from the John and Marcia Goldman Foundation. One author reported a financial relationship with Set Point Medical and My String, and three authors reported having a provisional patent application titled “Auricular stimulation device, system and methods of use.”

[email protected]

SOURCE: Aranow C et al. Ann Rheum Dis. 2020 Nov 3. doi: 10.1136/annrheumdis-2020-217872.

Patients with systemic lupus erythematosus (SLE) who received transcutaneous auricular vagus nerve stimulation (taVNS) had a clinically significant reduction in musculoskeletal pain when compared with those who received sham stimulation during a brief pilot trial.

“Our study population included individuals with significant pain and exemplifies the unmet need for adequate control of pain and fatigue in SLE. Importantly, this was a double-blind, sham-controlled study and neither the subject nor assessor was aware of a subject’s intervention. Objective outcomes, that is, tender and swollen joint counts, were also significantly reduced in subjects receiving taVNS, compared with those receiving [sham stimulation]. The stimulation was well tolerated with no adverse events attributed to the intervention, and, clinical benefits continued after taVNS was stopped,” first author Cynthia Aranow, MD, and her colleagues at the Feinstein Institutes for Medical Research in Manhasset, N.Y., wrote in Annals of the Rheumatic Diseases.

Stimulation of the vagus nerve can be achieved through the ear via its auricular branch, which innervates the cymba concha in the outer ear. Past pilot studies of implanted VNS devices lasting 6 weeks to 6 months in patients with Crohn’s disease or rheumatoid arthritis have shown improvements in measures of disease activity as well as objective markers of inflammation, and a more recent trial testing a transcutaneous devices’s effect in patients with Sjögren’s syndrome found significant reductions in fatigue over a 26-day period, the investigators noted.

In the taVNS device study, the researchers recruited 18 patients with SLE who had musculoskeletal pain rated as 4 or higher on a 10-cm visual analog scale and randomized them in a 2:1 ratio to receive taVNS once per day for 5 minutes for 4 consecutive days versus sham stimulation. Patients were allowed to be on stable doses of disease-modifying antirheumatic drugs, biologics, and/or prednisone ≤ 10 mg/day, with no change of dose within 28 days prior to baseline. The study excluded patients who used tobacco or an anticholinergic medication and those with a diagnosis of fibromyalgia.

The 12 patients who received actual taVNS had a significantly greater reduction in their pain, compared with 6 sham-treated patients (–5.00 vs. 0.10; P = .049), with 10 of 12 and 1 of 6 having a clinical response (a reduction of at least 1.58 on a 10-cm visual analog scale from baseline to day 5). Stimulation-treated patients also reported significantly greater reductions in fatigue, with 10 of 12 achieving a meaningful reduction, defined as a 4-point improvement on the Functional Assessment of Chronic Illness Therapy Fatigue Subscale; none of the sham-treated patients experienced meaningful improvement of fatigue. The patients who received taVNS had resolution of all swollen and tender joints, compared with 5.3% of tender and 9.1% of swollen joints in sham-treated patients. Ex vivo lipopolysaccharide stimulation of whole-blood samples from taVNS-treated patients, however, showed no reductions of inflammatory mediators or chemokines in tests on day 5 and day 12.

The investigators reported that there were no adverse events attributed to taVNS, including no reports of headache, lightheadedness, tinnitus, ear irritation, or changes to the external skin of the outer ear.

The study was supported by a grant from the John and Marcia Goldman Foundation. One author reported a financial relationship with Set Point Medical and My String, and three authors reported having a provisional patent application titled “Auricular stimulation device, system and methods of use.”

[email protected]

SOURCE: Aranow C et al. Ann Rheum Dis. 2020 Nov 3. doi: 10.1136/annrheumdis-2020-217872.

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

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

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

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

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

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

Abatacept’s safety as well as indicators of its potential efficacy in the treatment of patients with early diffuse cutaneous systemic sclerosis (dcSSc) were reinforced by newly reported results from the 6-month, open-label extension of the phase 2 ASSET trial.

“Exploratory outcome measures during the open-label extension, including the composite ACR CRISS [American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis] score, indicate that abatacept [Orencia] might promote overall global improvement in these participants,” Lorinda Chung, MD, of Stanford (Calif.) University, and colleagues wrote in the Lancet Rheumatology.

To continue to determine the safety and efficacy of abatacept as a treatment for dcSSc, the researchers launched the open-label extension of the randomized, double-blind ASSET trial. After patients in ASSET completed 12 months of treatment with either 125 mg weekly of subcutaneous abatacept or placebo, they were invited to join the extension period. ASSET’s primary endpoint was the change in modified Rodnan Skin Score (mRSS) from baseline to 12 months.

Of the 88 patients who began the ASSET trial – half of which were assigned to the abatacept group and the other half to the placebo group – 33 and 34 transitioned to weekly open-label treatment with 125 mg of abatacept, respectively. In the trial’s primary endpoint at 12 months, mean improvement in mRSS with abatacept was –6.6 (standard deviation, 6.4), compared to –3.7 (SD, 7.6) with placebo.

All told, 32 patients in each group completed 18 months of treatment. Patients who received abatacept in both periods had even more improvement in mRSS score (–9.8 [SD, 8.1]), as did patients who received placebo and then abatacept (–6.3 [SD, 9.3]). After 12 months, 68% of patients (23 of 34) in the abatacept group had a 5-unit or greater improvement in mRSS, compared with 50% of patients (19 of 38) in the placebo group. After 18 months, that percentage went up to 72% (23 of 32) among patients who took abatacept in both periods and 65% (20 of 31) for those who received it only in the extension.

Although the median ACR CRISS score was significantly greater at 12 months with abatacept, compared with placebo, both groups improved during the open-label period. After 12 months, an ACR CRISS score of 0.60 or higher was achieved by 55% (18 of 33) of the abatacept group and 36% (13 of 36) of the placebo group. In the extension, those percentages leapt to 66% (19 of 29) and 50% (13 of 26), respectively.

Throughout the double-blind phase, adverse events – including infectious events, serious events, and those that led to study withdrawal – were more frequent with placebo than with abatacept. During the extension period, although adverse events occurred slightly more among 18-month abatacept users, they ultimately occurred in fewer participants than in the double-blind phase.

Time to push forward with additional studies on abatacept

The results fortified by this open-label extension from Dr. Chung and colleagues should lay the groundwork for a phase 3 study on treatment with abatacept, wrote Francesco Del Galdo, MD, PhD, of the University of Leeds (England), in an accompanying editorial.

Along with clinically important improvements in several key measures, Dr. Del Galdo restated the value of abatacept’s “very benign” safety profile over the 18-month study period. However, he also acknowledged the “absence of concurrent immunosuppression” in the ASSET trial, noting that there is not yet a record of combination therapy safety across the board.

Beyond safety, he wondered if perhaps the time has passed for a placebo arm in dcSSc patients. He noted that participants in the initial placebo group were more likely to have “clinically relevant worsening of disease that required escape treatment,” which could make it ethically and analytically difficult to justify placebo.

The authors acknowledged the extension’s limitations, including the possibility that the survivors of the 12-month trial who joined the extension were more responsive to treatment or suffered from less severe disease. In addition, they noted that the study “was not powered for formal statistical comparison of the two treatment arms,” meaning all open-label results are considered exploratory. Finally, the number of participants in the extension period was small and likely contributed to low rates of adverse events, such as infection.

The trial was funded by Bristol-Myers Squibb, which markets abatacept, and the National Institutes of Health. The authors reported numerous potential conflicts of interest, including receiving grants, clinical trial support, and personal fees from various organizations and pharmaceutical companies, as well as serving on the advisory boards for such companies. Dr. Del Galdo reported receiving consultancy fees and research grants from several pharmaceutical companies.

SOURCE: Chung L et al. Lancet Rheumatol. 2020 Oct 19. doi: 10.1016/S2665-9913(20)30237-X.

Abatacept’s safety as well as indicators of its potential efficacy in the treatment of patients with early diffuse cutaneous systemic sclerosis (dcSSc) were reinforced by newly reported results from the 6-month, open-label extension of the phase 2 ASSET trial.

“Exploratory outcome measures during the open-label extension, including the composite ACR CRISS [American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis] score, indicate that abatacept [Orencia] might promote overall global improvement in these participants,” Lorinda Chung, MD, of Stanford (Calif.) University, and colleagues wrote in the Lancet Rheumatology.

To continue to determine the safety and efficacy of abatacept as a treatment for dcSSc, the researchers launched the open-label extension of the randomized, double-blind ASSET trial. After patients in ASSET completed 12 months of treatment with either 125 mg weekly of subcutaneous abatacept or placebo, they were invited to join the extension period. ASSET’s primary endpoint was the change in modified Rodnan Skin Score (mRSS) from baseline to 12 months.

Of the 88 patients who began the ASSET trial – half of which were assigned to the abatacept group and the other half to the placebo group – 33 and 34 transitioned to weekly open-label treatment with 125 mg of abatacept, respectively. In the trial’s primary endpoint at 12 months, mean improvement in mRSS with abatacept was –6.6 (standard deviation, 6.4), compared to –3.7 (SD, 7.6) with placebo.

All told, 32 patients in each group completed 18 months of treatment. Patients who received abatacept in both periods had even more improvement in mRSS score (–9.8 [SD, 8.1]), as did patients who received placebo and then abatacept (–6.3 [SD, 9.3]). After 12 months, 68% of patients (23 of 34) in the abatacept group had a 5-unit or greater improvement in mRSS, compared with 50% of patients (19 of 38) in the placebo group. After 18 months, that percentage went up to 72% (23 of 32) among patients who took abatacept in both periods and 65% (20 of 31) for those who received it only in the extension.

Although the median ACR CRISS score was significantly greater at 12 months with abatacept, compared with placebo, both groups improved during the open-label period. After 12 months, an ACR CRISS score of 0.60 or higher was achieved by 55% (18 of 33) of the abatacept group and 36% (13 of 36) of the placebo group. In the extension, those percentages leapt to 66% (19 of 29) and 50% (13 of 26), respectively.

Throughout the double-blind phase, adverse events – including infectious events, serious events, and those that led to study withdrawal – were more frequent with placebo than with abatacept. During the extension period, although adverse events occurred slightly more among 18-month abatacept users, they ultimately occurred in fewer participants than in the double-blind phase.

Time to push forward with additional studies on abatacept

The results fortified by this open-label extension from Dr. Chung and colleagues should lay the groundwork for a phase 3 study on treatment with abatacept, wrote Francesco Del Galdo, MD, PhD, of the University of Leeds (England), in an accompanying editorial.

Along with clinically important improvements in several key measures, Dr. Del Galdo restated the value of abatacept’s “very benign” safety profile over the 18-month study period. However, he also acknowledged the “absence of concurrent immunosuppression” in the ASSET trial, noting that there is not yet a record of combination therapy safety across the board.

Beyond safety, he wondered if perhaps the time has passed for a placebo arm in dcSSc patients. He noted that participants in the initial placebo group were more likely to have “clinically relevant worsening of disease that required escape treatment,” which could make it ethically and analytically difficult to justify placebo.

The authors acknowledged the extension’s limitations, including the possibility that the survivors of the 12-month trial who joined the extension were more responsive to treatment or suffered from less severe disease. In addition, they noted that the study “was not powered for formal statistical comparison of the two treatment arms,” meaning all open-label results are considered exploratory. Finally, the number of participants in the extension period was small and likely contributed to low rates of adverse events, such as infection.

The trial was funded by Bristol-Myers Squibb, which markets abatacept, and the National Institutes of Health. The authors reported numerous potential conflicts of interest, including receiving grants, clinical trial support, and personal fees from various organizations and pharmaceutical companies, as well as serving on the advisory boards for such companies. Dr. Del Galdo reported receiving consultancy fees and research grants from several pharmaceutical companies.

SOURCE: Chung L et al. Lancet Rheumatol. 2020 Oct 19. doi: 10.1016/S2665-9913(20)30237-X.

Abatacept’s safety as well as indicators of its potential efficacy in the treatment of patients with early diffuse cutaneous systemic sclerosis (dcSSc) were reinforced by newly reported results from the 6-month, open-label extension of the phase 2 ASSET trial.

“Exploratory outcome measures during the open-label extension, including the composite ACR CRISS [American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis] score, indicate that abatacept [Orencia] might promote overall global improvement in these participants,” Lorinda Chung, MD, of Stanford (Calif.) University, and colleagues wrote in the Lancet Rheumatology.

To continue to determine the safety and efficacy of abatacept as a treatment for dcSSc, the researchers launched the open-label extension of the randomized, double-blind ASSET trial. After patients in ASSET completed 12 months of treatment with either 125 mg weekly of subcutaneous abatacept or placebo, they were invited to join the extension period. ASSET’s primary endpoint was the change in modified Rodnan Skin Score (mRSS) from baseline to 12 months.

Of the 88 patients who began the ASSET trial – half of which were assigned to the abatacept group and the other half to the placebo group – 33 and 34 transitioned to weekly open-label treatment with 125 mg of abatacept, respectively. In the trial’s primary endpoint at 12 months, mean improvement in mRSS with abatacept was –6.6 (standard deviation, 6.4), compared to –3.7 (SD, 7.6) with placebo.

All told, 32 patients in each group completed 18 months of treatment. Patients who received abatacept in both periods had even more improvement in mRSS score (–9.8 [SD, 8.1]), as did patients who received placebo and then abatacept (–6.3 [SD, 9.3]). After 12 months, 68% of patients (23 of 34) in the abatacept group had a 5-unit or greater improvement in mRSS, compared with 50% of patients (19 of 38) in the placebo group. After 18 months, that percentage went up to 72% (23 of 32) among patients who took abatacept in both periods and 65% (20 of 31) for those who received it only in the extension.

Although the median ACR CRISS score was significantly greater at 12 months with abatacept, compared with placebo, both groups improved during the open-label period. After 12 months, an ACR CRISS score of 0.60 or higher was achieved by 55% (18 of 33) of the abatacept group and 36% (13 of 36) of the placebo group. In the extension, those percentages leapt to 66% (19 of 29) and 50% (13 of 26), respectively.

Throughout the double-blind phase, adverse events – including infectious events, serious events, and those that led to study withdrawal – were more frequent with placebo than with abatacept. During the extension period, although adverse events occurred slightly more among 18-month abatacept users, they ultimately occurred in fewer participants than in the double-blind phase.

Time to push forward with additional studies on abatacept

The results fortified by this open-label extension from Dr. Chung and colleagues should lay the groundwork for a phase 3 study on treatment with abatacept, wrote Francesco Del Galdo, MD, PhD, of the University of Leeds (England), in an accompanying editorial.

Along with clinically important improvements in several key measures, Dr. Del Galdo restated the value of abatacept’s “very benign” safety profile over the 18-month study period. However, he also acknowledged the “absence of concurrent immunosuppression” in the ASSET trial, noting that there is not yet a record of combination therapy safety across the board.

Beyond safety, he wondered if perhaps the time has passed for a placebo arm in dcSSc patients. He noted that participants in the initial placebo group were more likely to have “clinically relevant worsening of disease that required escape treatment,” which could make it ethically and analytically difficult to justify placebo.

The authors acknowledged the extension’s limitations, including the possibility that the survivors of the 12-month trial who joined the extension were more responsive to treatment or suffered from less severe disease. In addition, they noted that the study “was not powered for formal statistical comparison of the two treatment arms,” meaning all open-label results are considered exploratory. Finally, the number of participants in the extension period was small and likely contributed to low rates of adverse events, such as infection.

The trial was funded by Bristol-Myers Squibb, which markets abatacept, and the National Institutes of Health. The authors reported numerous potential conflicts of interest, including receiving grants, clinical trial support, and personal fees from various organizations and pharmaceutical companies, as well as serving on the advisory boards for such companies. Dr. Del Galdo reported receiving consultancy fees and research grants from several pharmaceutical companies.

SOURCE: Chung L et al. Lancet Rheumatol. 2020 Oct 19. doi: 10.1016/S2665-9913(20)30237-X.

In patients with intermediate-risk pulmonary arterial hypertension (PAH) who are not at treatment goal on standard therapy, switching to riociguat is a promising strategy across a broad range of patient subgroups, an investigator said at the annual meeting of the American College of Chest Physicians, held virtually this year.

Patients switching to riociguat in the REPLACE study more frequently met the primary efficacy endpoint, compared with patients who remained on a phosphodiesterase-5 (PDE5) inhibitor, said Marius M. Hoeper, MD, of the Clinic for Respiratory Medicine at Hannover (Germany) Medical School.

That clinical benefit of switching to riociguat, a soluble guanylate cyclase (sGC) stimulator, was relatively consistent across patient subgroups including age, sex, PAH subtype, according to Dr. Hoeper.

“At the end of the day, we believe that switching from a PDE5 inhibitor to riociguat can benefit patients with PAH at intermediate risk and may serve as a new strategic option for treatment escalation,” he said in a live virtual presentation of the study results.

About 40% of patients switching to riociguat met the primary endpoint of clinical improvement in absence of clinical worsening versus just 20% of patients who stayed on a PDE5 inhibitor, according to top-line results of the phase 4 REPLACE study, which were reported Sept. 7 at the annual meeting of the European Respiratory Society.

Results of REPLACE presented at the CHEST meeting show a benefit across most patient subgroups, including PAH subtype and whether patients came from monotherapy or combination treatment to riociguat. Some groups did not appear to respond quite as well to switching, including elderly patients, patients with a 6-minute walk distance (6MWD) of less than 320 meters at baseline, and patients switching from tadalafil as opposed to sildenafil. However, these findings were not statistically significant and may have been chance findings, according to Dr. Hoeper.

These results of REPLACE suggest the efficacy of riociguat “across the board” for intermediate-risk PAH patients with inadequate response to standard therapy, said Vijay Balasubramanian, MD, FCCP, clinical professor of medicine at the University of California San Francisco, Fresno.

Based on REPLACE results, switching from a PDE5 inhibitor to riociguat is now a “strong potential option” beyond adding a third drug such as selexipag or an inhaled prostacyclin to usual treatment with a PDE5 inhibitor plus an endothelin receptor antagonist, Dr. Balasubramanian said in an interview.

“We now have an evidence-based option where you can stay on a two-drug regimen and see whether the switch would work just as well,” said Dr. Balasubramanian, vice chair of the Pulmonary Vascular Disease Steering Committee for the American College of Chest Physicians.

REPLACE is a randomized phase 4 study including 226 patients with PAH considered to be at intermediate risk according to World Health Organization functional class III or 6MWD of 165-440 meters. The composite primary endpoint was defined as no clinical worsening (death, disease progression, or hospitalization for worsening PAH) plus clinical improvement on at least two measures including an improvement in 6MWD, achieving WHO functional class I/II, or a decrease in N-terminal pro-brain natriuretic peptide (NT-proBNP).

The primary endpoint of REPLACE was met, showing that 45 patients (41%) who switched to riociguat had clinical improvement without clinical worsening versus 22 patient (20%) who stayed on the PDE5 inhibitor (odds ratio, 2.78; 95% confidence interval, 1.53-5.06; P = .0007), Dr. Hoeper reported.

The benefit appeared consistent across PAH subgroups, according to Dr. Hoeper. In patients with idiopathic, heritable, or drug- and toxin-induced PAH, the primary endpoint favored riociguat over PDE5 inhibitor, at 45% and 23%, respectively. Similarly, a higher proportion of patients with PAH associated with congenital heart disease or portal hypertension achieved the primary endpoint (46% vs. 8%), as did patients with PAH associated with connective tissue disease (25% vs. 16%).

Adverse events were seen in 71% of riociguat-treated patients and 66% of PDE5 inhibitor–treated patients, according to Dr. Hoeper, who said severe adverse events were more frequent with PDE5-inhibitor treatment, at 17% versus 7% for riociguat. There were three clinical worsening events in the PDE5 inhibitor group leading to death, while a fourth patient died in safety follow-up, according to the reported results, whereas there were no deaths reported with riociguat.

The REPLACE study was cofunded by Bayer AG and Merck Sharpe & Dohme, a subsidiary of Merck & Co. Dr. Hoeper reported receiving fees for consultations or lectures from Acceleron, Actelion, Bayer AG, Janssen, MSD, and Pfizer.

SOURCE: Hoeper MM. CHEST 2020, Abstract A2156-A2159.

In patients with intermediate-risk pulmonary arterial hypertension (PAH) who are not at treatment goal on standard therapy, switching to riociguat is a promising strategy across a broad range of patient subgroups, an investigator said at the annual meeting of the American College of Chest Physicians, held virtually this year.

Patients switching to riociguat in the REPLACE study more frequently met the primary efficacy endpoint, compared with patients who remained on a phosphodiesterase-5 (PDE5) inhibitor, said Marius M. Hoeper, MD, of the Clinic for Respiratory Medicine at Hannover (Germany) Medical School.

That clinical benefit of switching to riociguat, a soluble guanylate cyclase (sGC) stimulator, was relatively consistent across patient subgroups including age, sex, PAH subtype, according to Dr. Hoeper.

“At the end of the day, we believe that switching from a PDE5 inhibitor to riociguat can benefit patients with PAH at intermediate risk and may serve as a new strategic option for treatment escalation,” he said in a live virtual presentation of the study results.

About 40% of patients switching to riociguat met the primary endpoint of clinical improvement in absence of clinical worsening versus just 20% of patients who stayed on a PDE5 inhibitor, according to top-line results of the phase 4 REPLACE study, which were reported Sept. 7 at the annual meeting of the European Respiratory Society.

Results of REPLACE presented at the CHEST meeting show a benefit across most patient subgroups, including PAH subtype and whether patients came from monotherapy or combination treatment to riociguat. Some groups did not appear to respond quite as well to switching, including elderly patients, patients with a 6-minute walk distance (6MWD) of less than 320 meters at baseline, and patients switching from tadalafil as opposed to sildenafil. However, these findings were not statistically significant and may have been chance findings, according to Dr. Hoeper.

These results of REPLACE suggest the efficacy of riociguat “across the board” for intermediate-risk PAH patients with inadequate response to standard therapy, said Vijay Balasubramanian, MD, FCCP, clinical professor of medicine at the University of California San Francisco, Fresno.

Based on REPLACE results, switching from a PDE5 inhibitor to riociguat is now a “strong potential option” beyond adding a third drug such as selexipag or an inhaled prostacyclin to usual treatment with a PDE5 inhibitor plus an endothelin receptor antagonist, Dr. Balasubramanian said in an interview.

“We now have an evidence-based option where you can stay on a two-drug regimen and see whether the switch would work just as well,” said Dr. Balasubramanian, vice chair of the Pulmonary Vascular Disease Steering Committee for the American College of Chest Physicians.

REPLACE is a randomized phase 4 study including 226 patients with PAH considered to be at intermediate risk according to World Health Organization functional class III or 6MWD of 165-440 meters. The composite primary endpoint was defined as no clinical worsening (death, disease progression, or hospitalization for worsening PAH) plus clinical improvement on at least two measures including an improvement in 6MWD, achieving WHO functional class I/II, or a decrease in N-terminal pro-brain natriuretic peptide (NT-proBNP).

The primary endpoint of REPLACE was met, showing that 45 patients (41%) who switched to riociguat had clinical improvement without clinical worsening versus 22 patient (20%) who stayed on the PDE5 inhibitor (odds ratio, 2.78; 95% confidence interval, 1.53-5.06; P = .0007), Dr. Hoeper reported.

The benefit appeared consistent across PAH subgroups, according to Dr. Hoeper. In patients with idiopathic, heritable, or drug- and toxin-induced PAH, the primary endpoint favored riociguat over PDE5 inhibitor, at 45% and 23%, respectively. Similarly, a higher proportion of patients with PAH associated with congenital heart disease or portal hypertension achieved the primary endpoint (46% vs. 8%), as did patients with PAH associated with connective tissue disease (25% vs. 16%).

Adverse events were seen in 71% of riociguat-treated patients and 66% of PDE5 inhibitor–treated patients, according to Dr. Hoeper, who said severe adverse events were more frequent with PDE5-inhibitor treatment, at 17% versus 7% for riociguat. There were three clinical worsening events in the PDE5 inhibitor group leading to death, while a fourth patient died in safety follow-up, according to the reported results, whereas there were no deaths reported with riociguat.

The REPLACE study was cofunded by Bayer AG and Merck Sharpe & Dohme, a subsidiary of Merck & Co. Dr. Hoeper reported receiving fees for consultations or lectures from Acceleron, Actelion, Bayer AG, Janssen, MSD, and Pfizer.

SOURCE: Hoeper MM. CHEST 2020, Abstract A2156-A2159.

In patients with intermediate-risk pulmonary arterial hypertension (PAH) who are not at treatment goal on standard therapy, switching to riociguat is a promising strategy across a broad range of patient subgroups, an investigator said at the annual meeting of the American College of Chest Physicians, held virtually this year.

Patients switching to riociguat in the REPLACE study more frequently met the primary efficacy endpoint, compared with patients who remained on a phosphodiesterase-5 (PDE5) inhibitor, said Marius M. Hoeper, MD, of the Clinic for Respiratory Medicine at Hannover (Germany) Medical School.

That clinical benefit of switching to riociguat, a soluble guanylate cyclase (sGC) stimulator, was relatively consistent across patient subgroups including age, sex, PAH subtype, according to Dr. Hoeper.

“At the end of the day, we believe that switching from a PDE5 inhibitor to riociguat can benefit patients with PAH at intermediate risk and may serve as a new strategic option for treatment escalation,” he said in a live virtual presentation of the study results.

About 40% of patients switching to riociguat met the primary endpoint of clinical improvement in absence of clinical worsening versus just 20% of patients who stayed on a PDE5 inhibitor, according to top-line results of the phase 4 REPLACE study, which were reported Sept. 7 at the annual meeting of the European Respiratory Society.

Results of REPLACE presented at the CHEST meeting show a benefit across most patient subgroups, including PAH subtype and whether patients came from monotherapy or combination treatment to riociguat. Some groups did not appear to respond quite as well to switching, including elderly patients, patients with a 6-minute walk distance (6MWD) of less than 320 meters at baseline, and patients switching from tadalafil as opposed to sildenafil. However, these findings were not statistically significant and may have been chance findings, according to Dr. Hoeper.

These results of REPLACE suggest the efficacy of riociguat “across the board” for intermediate-risk PAH patients with inadequate response to standard therapy, said Vijay Balasubramanian, MD, FCCP, clinical professor of medicine at the University of California San Francisco, Fresno.

Based on REPLACE results, switching from a PDE5 inhibitor to riociguat is now a “strong potential option” beyond adding a third drug such as selexipag or an inhaled prostacyclin to usual treatment with a PDE5 inhibitor plus an endothelin receptor antagonist, Dr. Balasubramanian said in an interview.

“We now have an evidence-based option where you can stay on a two-drug regimen and see whether the switch would work just as well,” said Dr. Balasubramanian, vice chair of the Pulmonary Vascular Disease Steering Committee for the American College of Chest Physicians.

REPLACE is a randomized phase 4 study including 226 patients with PAH considered to be at intermediate risk according to World Health Organization functional class III or 6MWD of 165-440 meters. The composite primary endpoint was defined as no clinical worsening (death, disease progression, or hospitalization for worsening PAH) plus clinical improvement on at least two measures including an improvement in 6MWD, achieving WHO functional class I/II, or a decrease in N-terminal pro-brain natriuretic peptide (NT-proBNP).

The primary endpoint of REPLACE was met, showing that 45 patients (41%) who switched to riociguat had clinical improvement without clinical worsening versus 22 patient (20%) who stayed on the PDE5 inhibitor (odds ratio, 2.78; 95% confidence interval, 1.53-5.06; P = .0007), Dr. Hoeper reported.

The benefit appeared consistent across PAH subgroups, according to Dr. Hoeper. In patients with idiopathic, heritable, or drug- and toxin-induced PAH, the primary endpoint favored riociguat over PDE5 inhibitor, at 45% and 23%, respectively. Similarly, a higher proportion of patients with PAH associated with congenital heart disease or portal hypertension achieved the primary endpoint (46% vs. 8%), as did patients with PAH associated with connective tissue disease (25% vs. 16%).

Adverse events were seen in 71% of riociguat-treated patients and 66% of PDE5 inhibitor–treated patients, according to Dr. Hoeper, who said severe adverse events were more frequent with PDE5-inhibitor treatment, at 17% versus 7% for riociguat. There were three clinical worsening events in the PDE5 inhibitor group leading to death, while a fourth patient died in safety follow-up, according to the reported results, whereas there were no deaths reported with riociguat.

The REPLACE study was cofunded by Bayer AG and Merck Sharpe & Dohme, a subsidiary of Merck & Co. Dr. Hoeper reported receiving fees for consultations or lectures from Acceleron, Actelion, Bayer AG, Janssen, MSD, and Pfizer.

SOURCE: Hoeper MM. CHEST 2020, Abstract A2156-A2159.

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.