Pulmonology

Interstitial lung disease (ILD) is a frequent complication of systemic autoimmune rheumatic diseases (SARDs) associated with considerable morbidity and mortality.¹ The risk of ILD, however, is higher in a subset of SARDs—rheumatoid arthritis (RA), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), mixed connective tissue disease (MCTD), and Sjögren’s disease (SjD). Prior to this year, guidelines for ILD screening, monitoring, and treatment in this high-risk population did not exist. Accordingly, the American College of Rheumatology (ACR) and American College of Chest Physicians (CHEST) jointly endorsed the recent publication of two separate guidelines detailing recommendations for (1) screening and monitoring and (2) treatment of ILD in adults with SARDs.^2,3 These guidelines mark the first of their kind, aiming to promote multidisciplinary collaboration and comprehensive, standardized care. Below, we summarize the major highlights from these guidelines.

 

Screening and monitoring

For patients with SARD, who should be screened for ILD and how?

The prevalence of ILD is not equally distributed amongst those with SARDs, and the heterogeneity poses a challenge when creating guidelines applicable to all.⁴ The ACR/CHEST guidelines focus on recommendations for those with SARDs at highest risk of ILD (RA, SSc, IIM, MCTD, and SjD), while excluding pediatric SARDs, sarcoidosis, interstitial pneumonia with autoimmune features, vasculitides, systemic lupus erythematosus, and unclassifiable ILD.^2,3 As the guidelines’ recommendations are all conditional and based on low-quality evidence, an individualized ILD screening approach should be implemented for patients with SARDs with regard to risk. 

For patients with these high-risk SARDs, screening for ILD with pulmonary function testing (PFT) and high-resolution chest tomography (HRCT) is conditionally recommended at the time of diagnosis. This recommendation was founded on observational studies showing PFTs have low sensitivity and high specificity while HRCT has high sensitivity and low specificity for detection of ILD. The combination was also favored, as it provides complementary information on functional impact (PFTs) and radiologic pattern (HRCT). 

The guideline committee conditionally recommended against several routine tests due to poor performance—chest radiography, six-minute walk distance, ambulatory desaturation testing, and bronchoscopy. There was a strong recommendation against pursuing surgical lung biopsy due to high-quality evidence for harm and low-quality evidence for benefit. If initial screening is negative, repeat screening is left to the discretion of the treating physician; nevertheless, for patients with high-risk features, yearly rescreening should be considered through shared decision-making. 



How should patients with SARD-ILD be monitored?

Disease monitoring following a SARD-ILD diagnosis is important. PFTs and HRCT were conditionally recommended over PFTs alone; however, the consensus was that HRCT should be less frequent than PFTs. Ambulatory desaturation monitoring was also conditionally recommended. The committee conditionally recommended against chest radiography, six-minute walk distance, and bronchoscopy for screening. 

The frequency of monitoring should be guided by patient symptoms, risk profile, and treatment response due to substantial clinical variation. For this reason, the committee made suggestions only to steer clinicians. For patients with IIM-ILD and SSc-ILD, more frequent PFT monitoring was suggested given the high risk of early, aggressive disease. For all SARD-ILDs, more frequent PFT monitoring was suggested early after diagnosis; less frequent testing should be considered for those with stable disease. No suggestion regarding the frequency of monitoring with HRCT was made; however, HRCT may be useful as a complementary test to PFTs in situations of uncertainty.

 

Treatment

First-line treatment

What are considerations when using glucocorticoids in patients with SARD-ILD?

The decision to treat SARD-ILD should incorporate patient symptoms, disease activity, risk of progression, and goals of care. For almost all SARD-ILDs, short-term glucocorticoids (ie, <3 months) are considered first-line treatment. The exception is SSc-ILD, for which there is a strong recommendation against glucocorticoids as first-line therapy due to concern for precipitating scleroderma renal crisis. Similarly, glucocorticoids should be used cautiously in those patients with MCTD and SSc features or IIM-ILD with SSc antibodies, though they are not strictly contraindicated. 

 

What are the recommended options for a steroid-sparing approach?

An important goal in the treatment of SARD-ILD is tapering off glucocorticoids to avoid toxicity. Steroid-sparing is used for those requiring long-term immunosuppression. Considerations when choosing steroid-sparing agents include contraindications, side-effect profile, and effect on active extrapulmonary symptoms. 

The committee conditionally recommended a hierarchy of first-line steroid-sparing agents via a voting consensus. Mycophenolate was conditionally recommended as the preferred agent in all SARD-ILDs for several reasons: (1) positive outcomes in trials of SSc-ILD, (2) additional limited data in other SARDs, (3) favorable side-effect profile, and (4) physicians’ familiarity. Multiple other first-line agents were recommended by disease type. These are summarized in Figure 1.



Progression on first-line treatment

What are considerations for patients with progression despite first-line ILD treatment?

The goal of first-line treatment is to improve or stabilize lung function and symptoms. Unfortunately, some patients with SARD-ILD will progress despite appropriate first-line therapy. Progression of ILD was defined using criteria from the INBUILD trial—a decline in FVC >10% predicted or a FVC decline between 5% and 10% accompanied by worsening respiratory symptoms or radiologic fibrosis within a 24-month period.⁵ When progression is diagnosed, the goal is to add on or switch to an agent based on patient-specific factors or preferences. 

Short-term steroids may have a role, particularly if a patient is experiencing an acute exacerbation; however, long-term steroid therapy (at least three to six months) is not recommended. For those who are on full-dose, first-line therapy but still progressing, addition of an alternative agent should be considered. In some instances, addition of an antifibrotic agent is recommended. If progression continues despite multiple agents, referral for lung transplantation should be discussed. 



What are some of the management options for patients with rapidly progressive ILD?

Rapidly progressive (RP)-ILD is considered when a patient exhibits rapid progression in supplemental oxygen needs within days to weeks without an alternative cause. First-line treatment is typically pulse IV methylprednisolone in addition to one to two other immunosuppressive medications; nonsteroidal immunosuppressive options include rituximab, cyclophosphamide, IV immunoglobulin, tacrolimus, mycophenolate, or Janus kinase inhibitors. The guidelines conditionally recommend double or triple therapy for most patients with SARD and RP-ILD (combination of steroids and one or two of the listed agents). For patients with confirmed or suspected anti-melanoma differentiation-associated gene 5 (MDA-5) RP-ILD, triple therapy is conditionally recommended (steroids and two additional agents) due to substantial risk of death. Of note, for patients with SSc and RP-ILD, there is no consensus on whether corticosteroids should be used. Treatment selection ultimately depends on disease severity, concern for infection, and suspected or confirmed MDA-5 RP-ILD. Finally, the committee recommended early referral for lung transplantation for patients whose disease progresses while on optimal medical treatment.

 

Conclusion

SARDs represent a diverse group of rheumatologic diseases associated with high risk of ILD. The ACR/CHEST guidelines are a first attempt to provide clinicians with evidence-based recommendations for screening, monitoring, and treatment of SARD-ILD. They represent an essential tool for management of SARD-ILD . The studies utilized to create them were mostly observational, and none had examined the relationship between disease screening, monitoring, and patient-centered outcomes. As a result, the recommendations are largely conditional. Additional studies are needed to examine the impact of surveillance in different populations, determine risk factors for RP-ILD in patients with SARD, and further investigate the most effective treatments.



Dr. Castellanos and Dr. Esposito are with the Division of Pulmonary and Critical Care, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Dr. Zhao is with the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.



References

1. Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet. 2012;380(9842):689-698.

2. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1070-1082. 

3. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1051-1069. 

4. Jeganathan N, Sathananthan M. Connective tissue disease-related interstitial lung disease: prevalence, patterns, predictors, prognosis, and treatment. Lung. 2020;198(5):735-759.

5. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727.

Interstitial lung disease (ILD) is a frequent complication of systemic autoimmune rheumatic diseases (SARDs) associated with considerable morbidity and mortality.¹ The risk of ILD, however, is higher in a subset of SARDs—rheumatoid arthritis (RA), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), mixed connective tissue disease (MCTD), and Sjögren’s disease (SjD). Prior to this year, guidelines for ILD screening, monitoring, and treatment in this high-risk population did not exist. Accordingly, the American College of Rheumatology (ACR) and American College of Chest Physicians (CHEST) jointly endorsed the recent publication of two separate guidelines detailing recommendations for (1) screening and monitoring and (2) treatment of ILD in adults with SARDs.^2,3 These guidelines mark the first of their kind, aiming to promote multidisciplinary collaboration and comprehensive, standardized care. Below, we summarize the major highlights from these guidelines.

 

Screening and monitoring

For patients with SARD, who should be screened for ILD and how?

The prevalence of ILD is not equally distributed amongst those with SARDs, and the heterogeneity poses a challenge when creating guidelines applicable to all.⁴ The ACR/CHEST guidelines focus on recommendations for those with SARDs at highest risk of ILD (RA, SSc, IIM, MCTD, and SjD), while excluding pediatric SARDs, sarcoidosis, interstitial pneumonia with autoimmune features, vasculitides, systemic lupus erythematosus, and unclassifiable ILD.^2,3 As the guidelines’ recommendations are all conditional and based on low-quality evidence, an individualized ILD screening approach should be implemented for patients with SARDs with regard to risk. 

For patients with these high-risk SARDs, screening for ILD with pulmonary function testing (PFT) and high-resolution chest tomography (HRCT) is conditionally recommended at the time of diagnosis. This recommendation was founded on observational studies showing PFTs have low sensitivity and high specificity while HRCT has high sensitivity and low specificity for detection of ILD. The combination was also favored, as it provides complementary information on functional impact (PFTs) and radiologic pattern (HRCT). 

The guideline committee conditionally recommended against several routine tests due to poor performance—chest radiography, six-minute walk distance, ambulatory desaturation testing, and bronchoscopy. There was a strong recommendation against pursuing surgical lung biopsy due to high-quality evidence for harm and low-quality evidence for benefit. If initial screening is negative, repeat screening is left to the discretion of the treating physician; nevertheless, for patients with high-risk features, yearly rescreening should be considered through shared decision-making. 



How should patients with SARD-ILD be monitored?

Disease monitoring following a SARD-ILD diagnosis is important. PFTs and HRCT were conditionally recommended over PFTs alone; however, the consensus was that HRCT should be less frequent than PFTs. Ambulatory desaturation monitoring was also conditionally recommended. The committee conditionally recommended against chest radiography, six-minute walk distance, and bronchoscopy for screening. 

The frequency of monitoring should be guided by patient symptoms, risk profile, and treatment response due to substantial clinical variation. For this reason, the committee made suggestions only to steer clinicians. For patients with IIM-ILD and SSc-ILD, more frequent PFT monitoring was suggested given the high risk of early, aggressive disease. For all SARD-ILDs, more frequent PFT monitoring was suggested early after diagnosis; less frequent testing should be considered for those with stable disease. No suggestion regarding the frequency of monitoring with HRCT was made; however, HRCT may be useful as a complementary test to PFTs in situations of uncertainty.

 

Treatment

First-line treatment

What are considerations when using glucocorticoids in patients with SARD-ILD?

The decision to treat SARD-ILD should incorporate patient symptoms, disease activity, risk of progression, and goals of care. For almost all SARD-ILDs, short-term glucocorticoids (ie, <3 months) are considered first-line treatment. The exception is SSc-ILD, for which there is a strong recommendation against glucocorticoids as first-line therapy due to concern for precipitating scleroderma renal crisis. Similarly, glucocorticoids should be used cautiously in those patients with MCTD and SSc features or IIM-ILD with SSc antibodies, though they are not strictly contraindicated. 

 

What are the recommended options for a steroid-sparing approach?

An important goal in the treatment of SARD-ILD is tapering off glucocorticoids to avoid toxicity. Steroid-sparing is used for those requiring long-term immunosuppression. Considerations when choosing steroid-sparing agents include contraindications, side-effect profile, and effect on active extrapulmonary symptoms. 

The committee conditionally recommended a hierarchy of first-line steroid-sparing agents via a voting consensus. Mycophenolate was conditionally recommended as the preferred agent in all SARD-ILDs for several reasons: (1) positive outcomes in trials of SSc-ILD, (2) additional limited data in other SARDs, (3) favorable side-effect profile, and (4) physicians’ familiarity. Multiple other first-line agents were recommended by disease type. These are summarized in Figure 1.



Progression on first-line treatment

What are considerations for patients with progression despite first-line ILD treatment?

The goal of first-line treatment is to improve or stabilize lung function and symptoms. Unfortunately, some patients with SARD-ILD will progress despite appropriate first-line therapy. Progression of ILD was defined using criteria from the INBUILD trial—a decline in FVC >10% predicted or a FVC decline between 5% and 10% accompanied by worsening respiratory symptoms or radiologic fibrosis within a 24-month period.⁵ When progression is diagnosed, the goal is to add on or switch to an agent based on patient-specific factors or preferences. 

Short-term steroids may have a role, particularly if a patient is experiencing an acute exacerbation; however, long-term steroid therapy (at least three to six months) is not recommended. For those who are on full-dose, first-line therapy but still progressing, addition of an alternative agent should be considered. In some instances, addition of an antifibrotic agent is recommended. If progression continues despite multiple agents, referral for lung transplantation should be discussed. 



What are some of the management options for patients with rapidly progressive ILD?

Rapidly progressive (RP)-ILD is considered when a patient exhibits rapid progression in supplemental oxygen needs within days to weeks without an alternative cause. First-line treatment is typically pulse IV methylprednisolone in addition to one to two other immunosuppressive medications; nonsteroidal immunosuppressive options include rituximab, cyclophosphamide, IV immunoglobulin, tacrolimus, mycophenolate, or Janus kinase inhibitors. The guidelines conditionally recommend double or triple therapy for most patients with SARD and RP-ILD (combination of steroids and one or two of the listed agents). For patients with confirmed or suspected anti-melanoma differentiation-associated gene 5 (MDA-5) RP-ILD, triple therapy is conditionally recommended (steroids and two additional agents) due to substantial risk of death. Of note, for patients with SSc and RP-ILD, there is no consensus on whether corticosteroids should be used. Treatment selection ultimately depends on disease severity, concern for infection, and suspected or confirmed MDA-5 RP-ILD. Finally, the committee recommended early referral for lung transplantation for patients whose disease progresses while on optimal medical treatment.

 

Conclusion

SARDs represent a diverse group of rheumatologic diseases associated with high risk of ILD. The ACR/CHEST guidelines are a first attempt to provide clinicians with evidence-based recommendations for screening, monitoring, and treatment of SARD-ILD. They represent an essential tool for management of SARD-ILD . The studies utilized to create them were mostly observational, and none had examined the relationship between disease screening, monitoring, and patient-centered outcomes. As a result, the recommendations are largely conditional. Additional studies are needed to examine the impact of surveillance in different populations, determine risk factors for RP-ILD in patients with SARD, and further investigate the most effective treatments.



Dr. Castellanos and Dr. Esposito are with the Division of Pulmonary and Critical Care, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Dr. Zhao is with the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.



References

1. Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet. 2012;380(9842):689-698.

2. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1070-1082. 

3. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1051-1069. 

4. Jeganathan N, Sathananthan M. Connective tissue disease-related interstitial lung disease: prevalence, patterns, predictors, prognosis, and treatment. Lung. 2020;198(5):735-759.

5. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727.

Interstitial lung disease (ILD) is a frequent complication of systemic autoimmune rheumatic diseases (SARDs) associated with considerable morbidity and mortality.¹ The risk of ILD, however, is higher in a subset of SARDs—rheumatoid arthritis (RA), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), mixed connective tissue disease (MCTD), and Sjögren’s disease (SjD). Prior to this year, guidelines for ILD screening, monitoring, and treatment in this high-risk population did not exist. Accordingly, the American College of Rheumatology (ACR) and American College of Chest Physicians (CHEST) jointly endorsed the recent publication of two separate guidelines detailing recommendations for (1) screening and monitoring and (2) treatment of ILD in adults with SARDs.^2,3 These guidelines mark the first of their kind, aiming to promote multidisciplinary collaboration and comprehensive, standardized care. Below, we summarize the major highlights from these guidelines.

 

Screening and monitoring

For patients with SARD, who should be screened for ILD and how?

The prevalence of ILD is not equally distributed amongst those with SARDs, and the heterogeneity poses a challenge when creating guidelines applicable to all.⁴ The ACR/CHEST guidelines focus on recommendations for those with SARDs at highest risk of ILD (RA, SSc, IIM, MCTD, and SjD), while excluding pediatric SARDs, sarcoidosis, interstitial pneumonia with autoimmune features, vasculitides, systemic lupus erythematosus, and unclassifiable ILD.^2,3 As the guidelines’ recommendations are all conditional and based on low-quality evidence, an individualized ILD screening approach should be implemented for patients with SARDs with regard to risk. 

For patients with these high-risk SARDs, screening for ILD with pulmonary function testing (PFT) and high-resolution chest tomography (HRCT) is conditionally recommended at the time of diagnosis. This recommendation was founded on observational studies showing PFTs have low sensitivity and high specificity while HRCT has high sensitivity and low specificity for detection of ILD. The combination was also favored, as it provides complementary information on functional impact (PFTs) and radiologic pattern (HRCT). 

The guideline committee conditionally recommended against several routine tests due to poor performance—chest radiography, six-minute walk distance, ambulatory desaturation testing, and bronchoscopy. There was a strong recommendation against pursuing surgical lung biopsy due to high-quality evidence for harm and low-quality evidence for benefit. If initial screening is negative, repeat screening is left to the discretion of the treating physician; nevertheless, for patients with high-risk features, yearly rescreening should be considered through shared decision-making. 



How should patients with SARD-ILD be monitored?

Disease monitoring following a SARD-ILD diagnosis is important. PFTs and HRCT were conditionally recommended over PFTs alone; however, the consensus was that HRCT should be less frequent than PFTs. Ambulatory desaturation monitoring was also conditionally recommended. The committee conditionally recommended against chest radiography, six-minute walk distance, and bronchoscopy for screening. 

The frequency of monitoring should be guided by patient symptoms, risk profile, and treatment response due to substantial clinical variation. For this reason, the committee made suggestions only to steer clinicians. For patients with IIM-ILD and SSc-ILD, more frequent PFT monitoring was suggested given the high risk of early, aggressive disease. For all SARD-ILDs, more frequent PFT monitoring was suggested early after diagnosis; less frequent testing should be considered for those with stable disease. No suggestion regarding the frequency of monitoring with HRCT was made; however, HRCT may be useful as a complementary test to PFTs in situations of uncertainty.

 

Treatment

First-line treatment

What are considerations when using glucocorticoids in patients with SARD-ILD?

The decision to treat SARD-ILD should incorporate patient symptoms, disease activity, risk of progression, and goals of care. For almost all SARD-ILDs, short-term glucocorticoids (ie, <3 months) are considered first-line treatment. The exception is SSc-ILD, for which there is a strong recommendation against glucocorticoids as first-line therapy due to concern for precipitating scleroderma renal crisis. Similarly, glucocorticoids should be used cautiously in those patients with MCTD and SSc features or IIM-ILD with SSc antibodies, though they are not strictly contraindicated. 

 

What are the recommended options for a steroid-sparing approach?

An important goal in the treatment of SARD-ILD is tapering off glucocorticoids to avoid toxicity. Steroid-sparing is used for those requiring long-term immunosuppression. Considerations when choosing steroid-sparing agents include contraindications, side-effect profile, and effect on active extrapulmonary symptoms. 

The committee conditionally recommended a hierarchy of first-line steroid-sparing agents via a voting consensus. Mycophenolate was conditionally recommended as the preferred agent in all SARD-ILDs for several reasons: (1) positive outcomes in trials of SSc-ILD, (2) additional limited data in other SARDs, (3) favorable side-effect profile, and (4) physicians’ familiarity. Multiple other first-line agents were recommended by disease type. These are summarized in Figure 1.



Progression on first-line treatment

What are considerations for patients with progression despite first-line ILD treatment?

The goal of first-line treatment is to improve or stabilize lung function and symptoms. Unfortunately, some patients with SARD-ILD will progress despite appropriate first-line therapy. Progression of ILD was defined using criteria from the INBUILD trial—a decline in FVC >10% predicted or a FVC decline between 5% and 10% accompanied by worsening respiratory symptoms or radiologic fibrosis within a 24-month period.⁵ When progression is diagnosed, the goal is to add on or switch to an agent based on patient-specific factors or preferences. 

Short-term steroids may have a role, particularly if a patient is experiencing an acute exacerbation; however, long-term steroid therapy (at least three to six months) is not recommended. For those who are on full-dose, first-line therapy but still progressing, addition of an alternative agent should be considered. In some instances, addition of an antifibrotic agent is recommended. If progression continues despite multiple agents, referral for lung transplantation should be discussed. 



What are some of the management options for patients with rapidly progressive ILD?

Rapidly progressive (RP)-ILD is considered when a patient exhibits rapid progression in supplemental oxygen needs within days to weeks without an alternative cause. First-line treatment is typically pulse IV methylprednisolone in addition to one to two other immunosuppressive medications; nonsteroidal immunosuppressive options include rituximab, cyclophosphamide, IV immunoglobulin, tacrolimus, mycophenolate, or Janus kinase inhibitors. The guidelines conditionally recommend double or triple therapy for most patients with SARD and RP-ILD (combination of steroids and one or two of the listed agents). For patients with confirmed or suspected anti-melanoma differentiation-associated gene 5 (MDA-5) RP-ILD, triple therapy is conditionally recommended (steroids and two additional agents) due to substantial risk of death. Of note, for patients with SSc and RP-ILD, there is no consensus on whether corticosteroids should be used. Treatment selection ultimately depends on disease severity, concern for infection, and suspected or confirmed MDA-5 RP-ILD. Finally, the committee recommended early referral for lung transplantation for patients whose disease progresses while on optimal medical treatment.

 

Conclusion

SARDs represent a diverse group of rheumatologic diseases associated with high risk of ILD. The ACR/CHEST guidelines are a first attempt to provide clinicians with evidence-based recommendations for screening, monitoring, and treatment of SARD-ILD. They represent an essential tool for management of SARD-ILD . The studies utilized to create them were mostly observational, and none had examined the relationship between disease screening, monitoring, and patient-centered outcomes. As a result, the recommendations are largely conditional. Additional studies are needed to examine the impact of surveillance in different populations, determine risk factors for RP-ILD in patients with SARD, and further investigate the most effective treatments.



Dr. Castellanos and Dr. Esposito are with the Division of Pulmonary and Critical Care, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL. Dr. Zhao is with the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.



References

1. Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet. 2012;380(9842):689-698.

2. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1070-1082. 

3. Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Care Res. 2024;76(8):1051-1069. 

4. Jeganathan N, Sathananthan M. Connective tissue disease-related interstitial lung disease: prevalence, patterns, predictors, prognosis, and treatment. Lung. 2020;198(5):735-759.

5. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727.

The Food and Drug Administration (FDA) has granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus) as an intravenous infusion for the treatment of certain adults with non–small cell lung cancer (NSCLC) or pancreatic adenocarcinoma.

Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.

The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.

Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.

“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”

The agent is expected to be available for use in the “coming weeks,” according to Merus.

“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”

Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.

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

The Food and Drug Administration (FDA) has granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus) as an intravenous infusion for the treatment of certain adults with non–small cell lung cancer (NSCLC) or pancreatic adenocarcinoma.

Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.

The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.

Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.

“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”

The agent is expected to be available for use in the “coming weeks,” according to Merus.

“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”

Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.

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

The Food and Drug Administration (FDA) has granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus) as an intravenous infusion for the treatment of certain adults with non–small cell lung cancer (NSCLC) or pancreatic adenocarcinoma.

Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.

The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.

Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.

“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”

The agent is expected to be available for use in the “coming weeks,” according to Merus.

“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”

Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.

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

Six times as many cases of pertussis were reported in the United States for the week ending November 16, 2024, as the same week in 2023, according to new data from the Centers for Disease Control and Prevention (CDC).

The numbers reflect a return to prepandemic trends, but overall, pertussis cases for 2024 so far have surpassed those seen prior to the pandemic in 2019, according to the CDC.

Of the 434 cases reported for the week ending November 16, 2024, a majority (109) occurred in the East North Central region, mostly in Ohio (93). Another 70 cases occurred in the West North Central region, with 32 cases and 37 cases in Missouri and Nebraska, respectively.

None of the 75 cases in the Middle Atlantic region occurred in New Jersey or New York City; 38 were reported elsewhere in New York, and 37 in Pennsylvania. The South Atlantic region reported 55 cases, including 29 in Florida. The East South Central and West South Central regions reported 11 and 20 cases, respectively. The Mountain and Pacific regions reported 31 (20 in Arizona) and 47 (20 in Washington State) cases, respectively.

The CDC tracks pertussis cases through a national surveillance system, but many cases are likely unrecognized and unreported, according to the CDC.

Although vaccines for pertussis (whooping cough) provide protection, their effectiveness decreases over time, and the CDC expects rates to increase in vaccinated and unvaccinated populations as case levels rebound with the lifting of pandemic mitigation strategies such as masking and remote learning.

Recent CDC data reported by Medscape Medical News showed an association between lower vaccination rates and 2024’s uptick in pertussis cases.

 

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

Six times as many cases of pertussis were reported in the United States for the week ending November 16, 2024, as the same week in 2023, according to new data from the Centers for Disease Control and Prevention (CDC).

The numbers reflect a return to prepandemic trends, but overall, pertussis cases for 2024 so far have surpassed those seen prior to the pandemic in 2019, according to the CDC.

Of the 434 cases reported for the week ending November 16, 2024, a majority (109) occurred in the East North Central region, mostly in Ohio (93). Another 70 cases occurred in the West North Central region, with 32 cases and 37 cases in Missouri and Nebraska, respectively.

None of the 75 cases in the Middle Atlantic region occurred in New Jersey or New York City; 38 were reported elsewhere in New York, and 37 in Pennsylvania. The South Atlantic region reported 55 cases, including 29 in Florida. The East South Central and West South Central regions reported 11 and 20 cases, respectively. The Mountain and Pacific regions reported 31 (20 in Arizona) and 47 (20 in Washington State) cases, respectively.

The CDC tracks pertussis cases through a national surveillance system, but many cases are likely unrecognized and unreported, according to the CDC.

Although vaccines for pertussis (whooping cough) provide protection, their effectiveness decreases over time, and the CDC expects rates to increase in vaccinated and unvaccinated populations as case levels rebound with the lifting of pandemic mitigation strategies such as masking and remote learning.

Recent CDC data reported by Medscape Medical News showed an association between lower vaccination rates and 2024’s uptick in pertussis cases.

 

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

Six times as many cases of pertussis were reported in the United States for the week ending November 16, 2024, as the same week in 2023, according to new data from the Centers for Disease Control and Prevention (CDC).

The numbers reflect a return to prepandemic trends, but overall, pertussis cases for 2024 so far have surpassed those seen prior to the pandemic in 2019, according to the CDC.

Of the 434 cases reported for the week ending November 16, 2024, a majority (109) occurred in the East North Central region, mostly in Ohio (93). Another 70 cases occurred in the West North Central region, with 32 cases and 37 cases in Missouri and Nebraska, respectively.

None of the 75 cases in the Middle Atlantic region occurred in New Jersey or New York City; 38 were reported elsewhere in New York, and 37 in Pennsylvania. The South Atlantic region reported 55 cases, including 29 in Florida. The East South Central and West South Central regions reported 11 and 20 cases, respectively. The Mountain and Pacific regions reported 31 (20 in Arizona) and 47 (20 in Washington State) cases, respectively.

The CDC tracks pertussis cases through a national surveillance system, but many cases are likely unrecognized and unreported, according to the CDC.

Although vaccines for pertussis (whooping cough) provide protection, their effectiveness decreases over time, and the CDC expects rates to increase in vaccinated and unvaccinated populations as case levels rebound with the lifting of pandemic mitigation strategies such as masking and remote learning.

Recent CDC data reported by Medscape Medical News showed an association between lower vaccination rates and 2024’s uptick in pertussis cases.

 

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

TOPLINE:

Administering the Bacillus Calmette-Guérin (BCG) vaccine during the active phase of COVID-19 may help protect against the development of long COVID.

METHODOLOGY:

• A phase 3 clinical trial initiated in early 2020 investigated the effect of the BCG vaccine injected during active infection on COVID-19 progression in adults with mild or moderate COVID-19. The current study summarizes the 6- and 12-month follow-up data with a focus on long-COVID symptoms.
• Patients who tested positive for severe acute respiratory syndrome coronavirus 2 were randomly assigned to receive either 0.1 mL of intradermal BCG (n = 191) or 0.9% saline placebo (n = 202) within 14 days of symptom onset and were followed up at 7, 14, 21, and 45 days and at 6 and 12 months postinjection.
• Overall, 157 BCG (median age, 40 years; 54.1% women) and 142 placebo (median age, 41 years; 65.5% women) recipients completed the 6-month follow-up, and 97 BCG (median age, 37 years; 49.5% women) and 95 placebo (median age, 40 years; 67.4% women) recipients completed the 12-month follow-up.
• The researchers primarily assessed the effect of the BCG vaccine on the development of the symptoms of long COVID at 6 and 12 months.

TAKEAWAY:

• Hearing problems were less frequent among BCG recipients at 6 months compared with those who received placebo (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P = .044).
• At 12 months, participants who received the BCG vaccine exhibited fewer issues with sleeping (P = .027), concentration (P = .009), memory (P = .009), and vision (P = .022) along with a lower long-COVID score (one-sided Wilcoxon test, P = .002) than those who received placebo.
• At 6 months, BCG demonstrated a sex-specific paradoxical effect on hair loss, decreasing it in men (P = .031), while causing a slight, though statistically nonsignificant, increase in women.
• Male sex was the strongest predictive factor for long COVID, cognitive dysfunction, and cardiopulmonary scores at both follow-up assessments.

IN PRACTICE:

“[The study] findings suggest that BCG immunotherapy for an existing ailment may be superior to prophylaxis in healthy individuals,” the authors wrote.

SOURCE:

The study was led by Mehrsa Jalalizadeh and Keini Buosi, UroScience, State University of Campinas, Unicamp, São Paulo, Brazil. It was published online on November 19, 2024, in the Journal of Internal Medicine.

LIMITATIONS:

Previous mycobacterial exposure was not tested among the study participants. A notable loss to follow-up, particularly at 12 months, may have introduced bias into the results.

DISCLOSURES:

The study was supported by the Coordination for the Improvement of Higher Education Personnel, Federal Government of Brazil, the General Coordination of the National Immunization Program, Ministry of Health (Brazil), and the National Council for Scientific and Technological Development-Research Productivity. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Administering the Bacillus Calmette-Guérin (BCG) vaccine during the active phase of COVID-19 may help protect against the development of long COVID.

METHODOLOGY:

• A phase 3 clinical trial initiated in early 2020 investigated the effect of the BCG vaccine injected during active infection on COVID-19 progression in adults with mild or moderate COVID-19. The current study summarizes the 6- and 12-month follow-up data with a focus on long-COVID symptoms.
• Patients who tested positive for severe acute respiratory syndrome coronavirus 2 were randomly assigned to receive either 0.1 mL of intradermal BCG (n = 191) or 0.9% saline placebo (n = 202) within 14 days of symptom onset and were followed up at 7, 14, 21, and 45 days and at 6 and 12 months postinjection.
• Overall, 157 BCG (median age, 40 years; 54.1% women) and 142 placebo (median age, 41 years; 65.5% women) recipients completed the 6-month follow-up, and 97 BCG (median age, 37 years; 49.5% women) and 95 placebo (median age, 40 years; 67.4% women) recipients completed the 12-month follow-up.
• The researchers primarily assessed the effect of the BCG vaccine on the development of the symptoms of long COVID at 6 and 12 months.

TAKEAWAY:

• Hearing problems were less frequent among BCG recipients at 6 months compared with those who received placebo (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P = .044).
• At 12 months, participants who received the BCG vaccine exhibited fewer issues with sleeping (P = .027), concentration (P = .009), memory (P = .009), and vision (P = .022) along with a lower long-COVID score (one-sided Wilcoxon test, P = .002) than those who received placebo.
• At 6 months, BCG demonstrated a sex-specific paradoxical effect on hair loss, decreasing it in men (P = .031), while causing a slight, though statistically nonsignificant, increase in women.
• Male sex was the strongest predictive factor for long COVID, cognitive dysfunction, and cardiopulmonary scores at both follow-up assessments.

IN PRACTICE:

“[The study] findings suggest that BCG immunotherapy for an existing ailment may be superior to prophylaxis in healthy individuals,” the authors wrote.

SOURCE:

The study was led by Mehrsa Jalalizadeh and Keini Buosi, UroScience, State University of Campinas, Unicamp, São Paulo, Brazil. It was published online on November 19, 2024, in the Journal of Internal Medicine.

LIMITATIONS:

Previous mycobacterial exposure was not tested among the study participants. A notable loss to follow-up, particularly at 12 months, may have introduced bias into the results.

DISCLOSURES:

The study was supported by the Coordination for the Improvement of Higher Education Personnel, Federal Government of Brazil, the General Coordination of the National Immunization Program, Ministry of Health (Brazil), and the National Council for Scientific and Technological Development-Research Productivity. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Administering the Bacillus Calmette-Guérin (BCG) vaccine during the active phase of COVID-19 may help protect against the development of long COVID.

METHODOLOGY:

• A phase 3 clinical trial initiated in early 2020 investigated the effect of the BCG vaccine injected during active infection on COVID-19 progression in adults with mild or moderate COVID-19. The current study summarizes the 6- and 12-month follow-up data with a focus on long-COVID symptoms.
• Patients who tested positive for severe acute respiratory syndrome coronavirus 2 were randomly assigned to receive either 0.1 mL of intradermal BCG (n = 191) or 0.9% saline placebo (n = 202) within 14 days of symptom onset and were followed up at 7, 14, 21, and 45 days and at 6 and 12 months postinjection.
• Overall, 157 BCG (median age, 40 years; 54.1% women) and 142 placebo (median age, 41 years; 65.5% women) recipients completed the 6-month follow-up, and 97 BCG (median age, 37 years; 49.5% women) and 95 placebo (median age, 40 years; 67.4% women) recipients completed the 12-month follow-up.
• The researchers primarily assessed the effect of the BCG vaccine on the development of the symptoms of long COVID at 6 and 12 months.

TAKEAWAY:

• Hearing problems were less frequent among BCG recipients at 6 months compared with those who received placebo (odds ratio [OR], 0.26; 95% CI, 0.045-1.0; P = .044).
• At 12 months, participants who received the BCG vaccine exhibited fewer issues with sleeping (P = .027), concentration (P = .009), memory (P = .009), and vision (P = .022) along with a lower long-COVID score (one-sided Wilcoxon test, P = .002) than those who received placebo.
• At 6 months, BCG demonstrated a sex-specific paradoxical effect on hair loss, decreasing it in men (P = .031), while causing a slight, though statistically nonsignificant, increase in women.
• Male sex was the strongest predictive factor for long COVID, cognitive dysfunction, and cardiopulmonary scores at both follow-up assessments.

IN PRACTICE:

“[The study] findings suggest that BCG immunotherapy for an existing ailment may be superior to prophylaxis in healthy individuals,” the authors wrote.

SOURCE:

The study was led by Mehrsa Jalalizadeh and Keini Buosi, UroScience, State University of Campinas, Unicamp, São Paulo, Brazil. It was published online on November 19, 2024, in the Journal of Internal Medicine.

LIMITATIONS:

Previous mycobacterial exposure was not tested among the study participants. A notable loss to follow-up, particularly at 12 months, may have introduced bias into the results.

DISCLOSURES:

The study was supported by the Coordination for the Improvement of Higher Education Personnel, Federal Government of Brazil, the General Coordination of the National Immunization Program, Ministry of Health (Brazil), and the National Council for Scientific and Technological Development-Research Productivity. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

This news organization recently spoke with the Centers for Disease Control and Prevention’s (CDC) Lisa Grohskopf, MD, MPH, Influenza Division, National Center for Immunization and Respiratory Diseases, about what providers need to know regarding recommendations for influenza vaccination in the United States.

Text has been edited for length. 

 

Are there any updates to this season’s influenza vaccine or vaccine recommendations?

Yes, we have updates to both the vaccine and the vaccine recommendations this year. Typically we have some changes each year, and this year there are two main changes in the recommendations. One relates to the composition of the vaccine for this season, and the other is a new recommendation for adult solid organ transplant recipients. 

We typically have changes in the vaccine composition each season. For most seasons, one or more parts of the vaccine will change, but this year is a little different in that all of the vaccines available in the US for the 2024-2025 season are going to be three-virus, or trivalent, vaccines. They are going to be formulated to protect against three viruses: an influenza A(H1N1) virus, an influenza A(H3N2) virus, and an influenza B/Victoria lineage virus. 

The reason for this change is that since the 2013-2014 season through the 2023-2024 season, we had quadrivalent vaccines that were available in the US that contained four viruses. Those vaccines contained a second influenza B virus from the Yamagata lineage (B viruses come from two main lineages).

The reason for the change to trivalent vaccines this season is that influenza B/Yamagata viruses have not been detected in global surveillance since March 2020, and so their inclusion is no longer warranted. So this season, all of the vaccines available in the US are going to be trivalent.

In addition to that change, we have an update in the influenza A(H3N2) component of the vaccine compared with last season.

The second change concerning adult solid organ transplant recipients is that Advisory Committee on Immunization Practices (ACIP) now recommends that solid organ transplant recipients aged 18-64 years can receive as acceptable options either the high-dose inactivated vaccine or the adjuvanted inactivated vaccine without a preference over other age appropriate, inactivated, or recombinant vaccines.

Those vaccines are both formulated with features intended to make them more immunogenic — ie, promote a stronger immune response — and there are data for immunogenicity that suggest they could be more immunogenic in that population.

 

Who needs an influenza vaccine this season?

That recommendation is the same as it’s been for a number of years, which is that everybody aged 6 months or older is recommended to get a flu vaccine, with some rare exceptions, mainly concerning contraindications to vaccination. 

Contraindications are detailed in the ACIP flu statement each year, and they’re relatively uncommon conditions overall, so most people are recommended, if they’re in that age group 6 months and up, to get an annual flu vaccine.

Are there groups for whom influenza vaccination is especially important?

Yes. While influenza vaccination is recommended for everybody in that age group 6 months and up — and in truth, we can never really predict who’s going to get severely ill — some people are more likely to be at risk of having serious illness or hospitalization. Those people include adults aged 65 years or older; young children; people with certain chronic health conditions such as heart disease, lung disease, and diabetes; and people from some racial and ethnic groups.

 

Are there any specific influenza vaccination recommendations for these groups or others? 

Not for most people. In general, we have a number of different influenza vaccines each season; this year we have a total of nine brands. In general, there’s no preferential recommendation for one vaccine or type of vaccine for specific groups of people, with one exception: For people aged 65 years or older, there’s a preferential recommendation for three specific vaccines — the high-dose inactivated vaccine, Fluzone High-Dose; the recombinant vaccine, Flublok; and the adjuvanted inactivated vaccine, FLUAD. 

Among those three, there’s no preference for any one of them over the other two; they’re all preferred vaccines for this age group, if available. If none of those three vaccines are available at the time that somebody aged 65 or older is there to get vaccinated, people in this age group should get any other age-appropriate influenza vaccine that is available.

 

When should people get vaccinated if they haven’t already?

CDC and ACIP recommend vaccination for most people, ideally by the end of October. But for those who missed the end of October, it is absolutely not too late. Providers should continue to encourage vaccination and people should get their vaccines as long as flu viruses are circulating. 

The timing of the onset and the peak and the end of the flu season vary a bit from year to year. We often start to see generally activity begin to increase in the US in the fall, which is the reason for the end of October recommendation; however, flu activity doesn’t tend to peak in the US until after October. We’re talking December, January, or later, so getting vaccinated after October can still provide important protection during the peak of the season.

There does seem to be a tendency for people to think, OK, I haven’t gotten the vaccine yet, and there probably isn’t a lot of reason to do it now. But really, it’s definitely not too late, and that’s something we like to encourage people to think about, particularly as we move into December and January — it’s not too late if you missed October. 

Influenza vaccination is also available in so many places. You don’t necessarily have to go to a healthcare provider’s office; there are many retail chains which offer influenza vaccines.

 

Is influenza spreading right now? Are activity levels increasing?

Overall influenza activity currently is low nationally, although there’s starting to be some slight increases in the pediatric age groups and, of course, we do anticipate that it will increase in the coming weeks and months.

When we get vaccinated, the protection isn’t instantaneous. The immune system needs a bit of time to react to the vaccine and to develop antibodies. That can take about 2 weeks. Even with that, now is still absolutely not too late to get a vaccine. Neither is December, for that matter. As long as the flu viruses are circulating where you are, it is still worth getting vaccinated.

 

What was influenza vaccination coverage like last season?

It’s a little bit early to tell for the current season, but one of the things that we do know is that since the COVID-19 pandemic, coverage has dropped compared with before the COVID-19 pandemic. Before COVID-19, influenza vaccination coverage had been slowly increasing in most groups, but it has decreased since then, and those downturns in coverage haven’t recovered to prepandemic levels. For example, during 2023-2024, about half of children and adults received a flu vaccine. 

What can providers do to encourage influenza vaccination in their patients?

We know that a healthcare provider’s strong recommendation for flu vaccination is a really major factor in whether or not patients get a flu vaccine, and is more effective in increasing acceptance of vaccination than just about any other factor. 

There’s a method from CDC called SHARE, which is a helpful way to help make a strong recommendation and provide information to help patients make an informed decision about whether or not they want to be vaccinated.

To implement SHARE, it’s an acronym with five parts. S is for Share the reasons why the flu vaccine is right for that patient. H is for Highlight positive experiences with flu vaccination, either personal or in practice. A is for Address patient concerns and questions about the flu vaccine, including things such as side effects, safety, and effectiveness. R is Remind patients that vaccination protects them and their loved ones from serious illness and related complications. E is Explain the potential complications and consequences of getting influenza, including serious health effects, time lost from family, work, and school, and potential financial costs.

Additional resources are accessible on CDC’s influenza resources page, including brochures, posters, and fact sheets that can help providers in encouraging and reminding people to get vaccinated.

A version of this article appeared on Medscape.com.

This news organization recently spoke with the Centers for Disease Control and Prevention’s (CDC) Lisa Grohskopf, MD, MPH, Influenza Division, National Center for Immunization and Respiratory Diseases, about what providers need to know regarding recommendations for influenza vaccination in the United States.

Text has been edited for length. 

 

Are there any updates to this season’s influenza vaccine or vaccine recommendations?

Yes, we have updates to both the vaccine and the vaccine recommendations this year. Typically we have some changes each year, and this year there are two main changes in the recommendations. One relates to the composition of the vaccine for this season, and the other is a new recommendation for adult solid organ transplant recipients. 

We typically have changes in the vaccine composition each season. For most seasons, one or more parts of the vaccine will change, but this year is a little different in that all of the vaccines available in the US for the 2024-2025 season are going to be three-virus, or trivalent, vaccines. They are going to be formulated to protect against three viruses: an influenza A(H1N1) virus, an influenza A(H3N2) virus, and an influenza B/Victoria lineage virus. 

The reason for this change is that since the 2013-2014 season through the 2023-2024 season, we had quadrivalent vaccines that were available in the US that contained four viruses. Those vaccines contained a second influenza B virus from the Yamagata lineage (B viruses come from two main lineages).

The reason for the change to trivalent vaccines this season is that influenza B/Yamagata viruses have not been detected in global surveillance since March 2020, and so their inclusion is no longer warranted. So this season, all of the vaccines available in the US are going to be trivalent.

In addition to that change, we have an update in the influenza A(H3N2) component of the vaccine compared with last season.

The second change concerning adult solid organ transplant recipients is that Advisory Committee on Immunization Practices (ACIP) now recommends that solid organ transplant recipients aged 18-64 years can receive as acceptable options either the high-dose inactivated vaccine or the adjuvanted inactivated vaccine without a preference over other age appropriate, inactivated, or recombinant vaccines.

Those vaccines are both formulated with features intended to make them more immunogenic — ie, promote a stronger immune response — and there are data for immunogenicity that suggest they could be more immunogenic in that population.

 

Who needs an influenza vaccine this season?

That recommendation is the same as it’s been for a number of years, which is that everybody aged 6 months or older is recommended to get a flu vaccine, with some rare exceptions, mainly concerning contraindications to vaccination. 

Contraindications are detailed in the ACIP flu statement each year, and they’re relatively uncommon conditions overall, so most people are recommended, if they’re in that age group 6 months and up, to get an annual flu vaccine.

Are there groups for whom influenza vaccination is especially important?

Yes. While influenza vaccination is recommended for everybody in that age group 6 months and up — and in truth, we can never really predict who’s going to get severely ill — some people are more likely to be at risk of having serious illness or hospitalization. Those people include adults aged 65 years or older; young children; people with certain chronic health conditions such as heart disease, lung disease, and diabetes; and people from some racial and ethnic groups.

 

Are there any specific influenza vaccination recommendations for these groups or others? 

Not for most people. In general, we have a number of different influenza vaccines each season; this year we have a total of nine brands. In general, there’s no preferential recommendation for one vaccine or type of vaccine for specific groups of people, with one exception: For people aged 65 years or older, there’s a preferential recommendation for three specific vaccines — the high-dose inactivated vaccine, Fluzone High-Dose; the recombinant vaccine, Flublok; and the adjuvanted inactivated vaccine, FLUAD. 

Among those three, there’s no preference for any one of them over the other two; they’re all preferred vaccines for this age group, if available. If none of those three vaccines are available at the time that somebody aged 65 or older is there to get vaccinated, people in this age group should get any other age-appropriate influenza vaccine that is available.

 

When should people get vaccinated if they haven’t already?

CDC and ACIP recommend vaccination for most people, ideally by the end of October. But for those who missed the end of October, it is absolutely not too late. Providers should continue to encourage vaccination and people should get their vaccines as long as flu viruses are circulating. 

The timing of the onset and the peak and the end of the flu season vary a bit from year to year. We often start to see generally activity begin to increase in the US in the fall, which is the reason for the end of October recommendation; however, flu activity doesn’t tend to peak in the US until after October. We’re talking December, January, or later, so getting vaccinated after October can still provide important protection during the peak of the season.

There does seem to be a tendency for people to think, OK, I haven’t gotten the vaccine yet, and there probably isn’t a lot of reason to do it now. But really, it’s definitely not too late, and that’s something we like to encourage people to think about, particularly as we move into December and January — it’s not too late if you missed October. 

Influenza vaccination is also available in so many places. You don’t necessarily have to go to a healthcare provider’s office; there are many retail chains which offer influenza vaccines.

 

Is influenza spreading right now? Are activity levels increasing?

Overall influenza activity currently is low nationally, although there’s starting to be some slight increases in the pediatric age groups and, of course, we do anticipate that it will increase in the coming weeks and months.

When we get vaccinated, the protection isn’t instantaneous. The immune system needs a bit of time to react to the vaccine and to develop antibodies. That can take about 2 weeks. Even with that, now is still absolutely not too late to get a vaccine. Neither is December, for that matter. As long as the flu viruses are circulating where you are, it is still worth getting vaccinated.

 

What was influenza vaccination coverage like last season?

It’s a little bit early to tell for the current season, but one of the things that we do know is that since the COVID-19 pandemic, coverage has dropped compared with before the COVID-19 pandemic. Before COVID-19, influenza vaccination coverage had been slowly increasing in most groups, but it has decreased since then, and those downturns in coverage haven’t recovered to prepandemic levels. For example, during 2023-2024, about half of children and adults received a flu vaccine. 

What can providers do to encourage influenza vaccination in their patients?

We know that a healthcare provider’s strong recommendation for flu vaccination is a really major factor in whether or not patients get a flu vaccine, and is more effective in increasing acceptance of vaccination than just about any other factor. 

There’s a method from CDC called SHARE, which is a helpful way to help make a strong recommendation and provide information to help patients make an informed decision about whether or not they want to be vaccinated.

To implement SHARE, it’s an acronym with five parts. S is for Share the reasons why the flu vaccine is right for that patient. H is for Highlight positive experiences with flu vaccination, either personal or in practice. A is for Address patient concerns and questions about the flu vaccine, including things such as side effects, safety, and effectiveness. R is Remind patients that vaccination protects them and their loved ones from serious illness and related complications. E is Explain the potential complications and consequences of getting influenza, including serious health effects, time lost from family, work, and school, and potential financial costs.

Additional resources are accessible on CDC’s influenza resources page, including brochures, posters, and fact sheets that can help providers in encouraging and reminding people to get vaccinated.

A version of this article appeared on Medscape.com.

This news organization recently spoke with the Centers for Disease Control and Prevention’s (CDC) Lisa Grohskopf, MD, MPH, Influenza Division, National Center for Immunization and Respiratory Diseases, about what providers need to know regarding recommendations for influenza vaccination in the United States.

Text has been edited for length. 

 

Are there any updates to this season’s influenza vaccine or vaccine recommendations?

Yes, we have updates to both the vaccine and the vaccine recommendations this year. Typically we have some changes each year, and this year there are two main changes in the recommendations. One relates to the composition of the vaccine for this season, and the other is a new recommendation for adult solid organ transplant recipients. 

We typically have changes in the vaccine composition each season. For most seasons, one or more parts of the vaccine will change, but this year is a little different in that all of the vaccines available in the US for the 2024-2025 season are going to be three-virus, or trivalent, vaccines. They are going to be formulated to protect against three viruses: an influenza A(H1N1) virus, an influenza A(H3N2) virus, and an influenza B/Victoria lineage virus. 

The reason for this change is that since the 2013-2014 season through the 2023-2024 season, we had quadrivalent vaccines that were available in the US that contained four viruses. Those vaccines contained a second influenza B virus from the Yamagata lineage (B viruses come from two main lineages).

The reason for the change to trivalent vaccines this season is that influenza B/Yamagata viruses have not been detected in global surveillance since March 2020, and so their inclusion is no longer warranted. So this season, all of the vaccines available in the US are going to be trivalent.

In addition to that change, we have an update in the influenza A(H3N2) component of the vaccine compared with last season.

The second change concerning adult solid organ transplant recipients is that Advisory Committee on Immunization Practices (ACIP) now recommends that solid organ transplant recipients aged 18-64 years can receive as acceptable options either the high-dose inactivated vaccine or the adjuvanted inactivated vaccine without a preference over other age appropriate, inactivated, or recombinant vaccines.

Those vaccines are both formulated with features intended to make them more immunogenic — ie, promote a stronger immune response — and there are data for immunogenicity that suggest they could be more immunogenic in that population.

 

Who needs an influenza vaccine this season?

That recommendation is the same as it’s been for a number of years, which is that everybody aged 6 months or older is recommended to get a flu vaccine, with some rare exceptions, mainly concerning contraindications to vaccination. 

Contraindications are detailed in the ACIP flu statement each year, and they’re relatively uncommon conditions overall, so most people are recommended, if they’re in that age group 6 months and up, to get an annual flu vaccine.

Are there groups for whom influenza vaccination is especially important?

Yes. While influenza vaccination is recommended for everybody in that age group 6 months and up — and in truth, we can never really predict who’s going to get severely ill — some people are more likely to be at risk of having serious illness or hospitalization. Those people include adults aged 65 years or older; young children; people with certain chronic health conditions such as heart disease, lung disease, and diabetes; and people from some racial and ethnic groups.

 

Are there any specific influenza vaccination recommendations for these groups or others? 

Not for most people. In general, we have a number of different influenza vaccines each season; this year we have a total of nine brands. In general, there’s no preferential recommendation for one vaccine or type of vaccine for specific groups of people, with one exception: For people aged 65 years or older, there’s a preferential recommendation for three specific vaccines — the high-dose inactivated vaccine, Fluzone High-Dose; the recombinant vaccine, Flublok; and the adjuvanted inactivated vaccine, FLUAD. 

Among those three, there’s no preference for any one of them over the other two; they’re all preferred vaccines for this age group, if available. If none of those three vaccines are available at the time that somebody aged 65 or older is there to get vaccinated, people in this age group should get any other age-appropriate influenza vaccine that is available.

 

When should people get vaccinated if they haven’t already?

CDC and ACIP recommend vaccination for most people, ideally by the end of October. But for those who missed the end of October, it is absolutely not too late. Providers should continue to encourage vaccination and people should get their vaccines as long as flu viruses are circulating. 

The timing of the onset and the peak and the end of the flu season vary a bit from year to year. We often start to see generally activity begin to increase in the US in the fall, which is the reason for the end of October recommendation; however, flu activity doesn’t tend to peak in the US until after October. We’re talking December, January, or later, so getting vaccinated after October can still provide important protection during the peak of the season.

There does seem to be a tendency for people to think, OK, I haven’t gotten the vaccine yet, and there probably isn’t a lot of reason to do it now. But really, it’s definitely not too late, and that’s something we like to encourage people to think about, particularly as we move into December and January — it’s not too late if you missed October. 

Influenza vaccination is also available in so many places. You don’t necessarily have to go to a healthcare provider’s office; there are many retail chains which offer influenza vaccines.

 

Is influenza spreading right now? Are activity levels increasing?

Overall influenza activity currently is low nationally, although there’s starting to be some slight increases in the pediatric age groups and, of course, we do anticipate that it will increase in the coming weeks and months.

When we get vaccinated, the protection isn’t instantaneous. The immune system needs a bit of time to react to the vaccine and to develop antibodies. That can take about 2 weeks. Even with that, now is still absolutely not too late to get a vaccine. Neither is December, for that matter. As long as the flu viruses are circulating where you are, it is still worth getting vaccinated.

 

What was influenza vaccination coverage like last season?

It’s a little bit early to tell for the current season, but one of the things that we do know is that since the COVID-19 pandemic, coverage has dropped compared with before the COVID-19 pandemic. Before COVID-19, influenza vaccination coverage had been slowly increasing in most groups, but it has decreased since then, and those downturns in coverage haven’t recovered to prepandemic levels. For example, during 2023-2024, about half of children and adults received a flu vaccine. 

What can providers do to encourage influenza vaccination in their patients?

We know that a healthcare provider’s strong recommendation for flu vaccination is a really major factor in whether or not patients get a flu vaccine, and is more effective in increasing acceptance of vaccination than just about any other factor. 

There’s a method from CDC called SHARE, which is a helpful way to help make a strong recommendation and provide information to help patients make an informed decision about whether or not they want to be vaccinated.

To implement SHARE, it’s an acronym with five parts. S is for Share the reasons why the flu vaccine is right for that patient. H is for Highlight positive experiences with flu vaccination, either personal or in practice. A is for Address patient concerns and questions about the flu vaccine, including things such as side effects, safety, and effectiveness. R is Remind patients that vaccination protects them and their loved ones from serious illness and related complications. E is Explain the potential complications and consequences of getting influenza, including serious health effects, time lost from family, work, and school, and potential financial costs.

Additional resources are accessible on CDC’s influenza resources page, including brochures, posters, and fact sheets that can help providers in encouraging and reminding people to get vaccinated.

A version of this article appeared on Medscape.com.

Now that Canada has confirmed its first human case of highly pathogenic avian influenza (HPAI) linked to H5N1, virologists and infectious disease experts are urging caution around surveillance, infection control, and the potential for spread among mammals and humans.

The patient, a teenager in British Columbia, was hospitalized on November 8 and remains in critical condition with acute respiratory distress as of this writing. Public health officials at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, confirmed that the virus strain is related to the ones circulating among poultry in British Columbia.

So far, the case appears to be isolated, and no additional infections have been detected among the teen’s family, friends, or healthcare workers. But Canadian and American scientists who have studied the genetic sequence of the virus have found mutations that could make it easier to infect humans. Even if this strain remains contained after the teen’s case resolves, the mere fact that mutations have occurred could be a cause for concern about future strains.

“HPAI is one of those diseases that scientists, public health specialists, animal health specialists, and physicians have been watching closely for 20 years due to its epidemic and pandemic potential, including impacts to agriculture, food security, and financial security,” Isaac Bogoch, MD, associate professor of medicine at the University of Toronto and infectious disease specialist with the University Health Network, Toronto, Ontario, Canada, said in an interview.

“The last couple of years have been notable in that the H5N1 outbreak among wild birds and migratory birds has been larger, and the spillover to dairy cows and humans in the US is obviously concerning,” he said. “As we see more viral reassortment and more mammals are impacted, the more opportunities there are for this to go awry.”

 

Current H5N1 Outlook

Canadian public health officials and virologists are still unsure how the teen in British Columbia became infected, Bogoch said. The case has prompted concern due to the disease severity and need for hospitalization, while other cases across North America have remained mild.

The United States has reported 53 human cases as of November 21, according to the Centers for Disease Control and Prevention. In all but one case, the infections occurred among dairy or poultry workers, primarily in California, Colorado, and Washington. In all these cases, patients have reported mild symptoms, including mild respiratory issues and conjunctivitis. None have been hospitalized.

In Canada, the teen was infected with a strain of the virus circulating in wild birds. This strain has also been found in poultry outbreaks in British Columbia and Washington during the past month. So far, the risk for infection remains low for the public, according to the Public Health Agency of Canada.

“This detection was picked up via hospital-based influenza surveillance, confirming that human influenza surveillance in British Columbia and Canada is effective at detecting avian influenza A (H5N1),” Theresa Tam, MD, Canada’s chief public health officer, said in a statement. “We must continue to remain vigilant in our efforts to prevent the spread of avian influenza between animals and to humans.”

For now, Canadian virologists are watching developments closely and urging caution among those who encounter wild or migratory birds but not recommending major changes overall.

“The fact that we have a first human case in Canada is not at all surprising, given what is happening in the US and Europe, as well as what is happening in domestic bird flocks in British Columbia,” said Brian Ward, MD, professor of medicine at McGill University, researcher with McGill’s JD MacLean Centre for Tropical Diseases, and co-director of McGill’s Vaccine Study Centre, Montreal, Quebec, Canada.

“Millions of migratory waterfowl are flying over Canada right now, many of which may be carrying or infected with the virus,” he said. “The bottom line is that increasing evidence of mammal-to-mammal spread among dairy cows, elephant seals, and mink and ermine farms is worrisome, but we don’t need to sound the sirens yet.”

 

Future Outbreak Measures

Looking ahead, though, the developing situation feels more threatening than benign, given the ongoing spread among dairy cattle in the United States, said Bogoch. “It’s difficult to get the genie back in the bottle. I had hoped to see the cases slow down this year, but we just haven’t seen that.”

The fact that surveillance measures such as wastewater sampling have been scaled back in some areas of Canada is cause for concern, Bogoch added.

“We have great foundations for surveillance and action; we just need to make sure they are supported adequately, that groups communicate (across too many silos), and that there are quick responses,” said Scott Weese, DVM, professor of pathobiology at the Ontario Veterinary College and director of the University of Guelph’s Centre for Public Health and Zoonoses in Ontario.

“With cattle in the US, I think it’s highlighted what can happen if the initial response is not very aggressive. There could have been a lot more proactive response to H5N1 in dairy cattle, but there are so many competing interests and unwillingness to take necessary steps that the virus continues to spread,” he said. “Hopefully we’ve learned from that. However, as is often the case, the science is sometimes the easy part. Getting people to take the required actions is the challenge.”

On a personal level, masks and social distancing work well against influenza virus, including both seasonal and avian strains, said Ward. On a broader level, healthcare providers can monitor patients and support testing, where appropriate.

“The most important thing for people to know is that there is going to be another pandemic. It might or might not be due to a variant of H5N1, but it will come at some time,” said Allison McGeer, MD, professor of laboratory medicine and pathobiology at the University of Toronto and an infectious disease specialist with the Sinai Health System, Toronto.

Healthcare providers should follow ongoing updates to public health guidance, support surveillance where possible, and work with hospital leadership and infection control officials to ensure that pandemic plans are in place, she said.

“They may not be needed in the next few months, but they will be needed,” McGeer said. “We know a lot more about influenza than we did about SARS-CoV-2, so we have more tools to mitigate the impact, but we need to have them ready and know how to use them effectively.”

A version of this article appeared on Medscape.com.

Now that Canada has confirmed its first human case of highly pathogenic avian influenza (HPAI) linked to H5N1, virologists and infectious disease experts are urging caution around surveillance, infection control, and the potential for spread among mammals and humans.

The patient, a teenager in British Columbia, was hospitalized on November 8 and remains in critical condition with acute respiratory distress as of this writing. Public health officials at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, confirmed that the virus strain is related to the ones circulating among poultry in British Columbia.

So far, the case appears to be isolated, and no additional infections have been detected among the teen’s family, friends, or healthcare workers. But Canadian and American scientists who have studied the genetic sequence of the virus have found mutations that could make it easier to infect humans. Even if this strain remains contained after the teen’s case resolves, the mere fact that mutations have occurred could be a cause for concern about future strains.

“HPAI is one of those diseases that scientists, public health specialists, animal health specialists, and physicians have been watching closely for 20 years due to its epidemic and pandemic potential, including impacts to agriculture, food security, and financial security,” Isaac Bogoch, MD, associate professor of medicine at the University of Toronto and infectious disease specialist with the University Health Network, Toronto, Ontario, Canada, said in an interview.

“The last couple of years have been notable in that the H5N1 outbreak among wild birds and migratory birds has been larger, and the spillover to dairy cows and humans in the US is obviously concerning,” he said. “As we see more viral reassortment and more mammals are impacted, the more opportunities there are for this to go awry.”

 

Current H5N1 Outlook

Canadian public health officials and virologists are still unsure how the teen in British Columbia became infected, Bogoch said. The case has prompted concern due to the disease severity and need for hospitalization, while other cases across North America have remained mild.

The United States has reported 53 human cases as of November 21, according to the Centers for Disease Control and Prevention. In all but one case, the infections occurred among dairy or poultry workers, primarily in California, Colorado, and Washington. In all these cases, patients have reported mild symptoms, including mild respiratory issues and conjunctivitis. None have been hospitalized.

In Canada, the teen was infected with a strain of the virus circulating in wild birds. This strain has also been found in poultry outbreaks in British Columbia and Washington during the past month. So far, the risk for infection remains low for the public, according to the Public Health Agency of Canada.

“This detection was picked up via hospital-based influenza surveillance, confirming that human influenza surveillance in British Columbia and Canada is effective at detecting avian influenza A (H5N1),” Theresa Tam, MD, Canada’s chief public health officer, said in a statement. “We must continue to remain vigilant in our efforts to prevent the spread of avian influenza between animals and to humans.”

For now, Canadian virologists are watching developments closely and urging caution among those who encounter wild or migratory birds but not recommending major changes overall.

“The fact that we have a first human case in Canada is not at all surprising, given what is happening in the US and Europe, as well as what is happening in domestic bird flocks in British Columbia,” said Brian Ward, MD, professor of medicine at McGill University, researcher with McGill’s JD MacLean Centre for Tropical Diseases, and co-director of McGill’s Vaccine Study Centre, Montreal, Quebec, Canada.

“Millions of migratory waterfowl are flying over Canada right now, many of which may be carrying or infected with the virus,” he said. “The bottom line is that increasing evidence of mammal-to-mammal spread among dairy cows, elephant seals, and mink and ermine farms is worrisome, but we don’t need to sound the sirens yet.”

 

Future Outbreak Measures

Looking ahead, though, the developing situation feels more threatening than benign, given the ongoing spread among dairy cattle in the United States, said Bogoch. “It’s difficult to get the genie back in the bottle. I had hoped to see the cases slow down this year, but we just haven’t seen that.”

The fact that surveillance measures such as wastewater sampling have been scaled back in some areas of Canada is cause for concern, Bogoch added.

“We have great foundations for surveillance and action; we just need to make sure they are supported adequately, that groups communicate (across too many silos), and that there are quick responses,” said Scott Weese, DVM, professor of pathobiology at the Ontario Veterinary College and director of the University of Guelph’s Centre for Public Health and Zoonoses in Ontario.

“With cattle in the US, I think it’s highlighted what can happen if the initial response is not very aggressive. There could have been a lot more proactive response to H5N1 in dairy cattle, but there are so many competing interests and unwillingness to take necessary steps that the virus continues to spread,” he said. “Hopefully we’ve learned from that. However, as is often the case, the science is sometimes the easy part. Getting people to take the required actions is the challenge.”

On a personal level, masks and social distancing work well against influenza virus, including both seasonal and avian strains, said Ward. On a broader level, healthcare providers can monitor patients and support testing, where appropriate.

“The most important thing for people to know is that there is going to be another pandemic. It might or might not be due to a variant of H5N1, but it will come at some time,” said Allison McGeer, MD, professor of laboratory medicine and pathobiology at the University of Toronto and an infectious disease specialist with the Sinai Health System, Toronto.

Healthcare providers should follow ongoing updates to public health guidance, support surveillance where possible, and work with hospital leadership and infection control officials to ensure that pandemic plans are in place, she said.

“They may not be needed in the next few months, but they will be needed,” McGeer said. “We know a lot more about influenza than we did about SARS-CoV-2, so we have more tools to mitigate the impact, but we need to have them ready and know how to use them effectively.”

A version of this article appeared on Medscape.com.

Now that Canada has confirmed its first human case of highly pathogenic avian influenza (HPAI) linked to H5N1, virologists and infectious disease experts are urging caution around surveillance, infection control, and the potential for spread among mammals and humans.

The patient, a teenager in British Columbia, was hospitalized on November 8 and remains in critical condition with acute respiratory distress as of this writing. Public health officials at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, confirmed that the virus strain is related to the ones circulating among poultry in British Columbia.

So far, the case appears to be isolated, and no additional infections have been detected among the teen’s family, friends, or healthcare workers. But Canadian and American scientists who have studied the genetic sequence of the virus have found mutations that could make it easier to infect humans. Even if this strain remains contained after the teen’s case resolves, the mere fact that mutations have occurred could be a cause for concern about future strains.

“HPAI is one of those diseases that scientists, public health specialists, animal health specialists, and physicians have been watching closely for 20 years due to its epidemic and pandemic potential, including impacts to agriculture, food security, and financial security,” Isaac Bogoch, MD, associate professor of medicine at the University of Toronto and infectious disease specialist with the University Health Network, Toronto, Ontario, Canada, said in an interview.

“The last couple of years have been notable in that the H5N1 outbreak among wild birds and migratory birds has been larger, and the spillover to dairy cows and humans in the US is obviously concerning,” he said. “As we see more viral reassortment and more mammals are impacted, the more opportunities there are for this to go awry.”

 

Current H5N1 Outlook

Canadian public health officials and virologists are still unsure how the teen in British Columbia became infected, Bogoch said. The case has prompted concern due to the disease severity and need for hospitalization, while other cases across North America have remained mild.

The United States has reported 53 human cases as of November 21, according to the Centers for Disease Control and Prevention. In all but one case, the infections occurred among dairy or poultry workers, primarily in California, Colorado, and Washington. In all these cases, patients have reported mild symptoms, including mild respiratory issues and conjunctivitis. None have been hospitalized.

In Canada, the teen was infected with a strain of the virus circulating in wild birds. This strain has also been found in poultry outbreaks in British Columbia and Washington during the past month. So far, the risk for infection remains low for the public, according to the Public Health Agency of Canada.

“This detection was picked up via hospital-based influenza surveillance, confirming that human influenza surveillance in British Columbia and Canada is effective at detecting avian influenza A (H5N1),” Theresa Tam, MD, Canada’s chief public health officer, said in a statement. “We must continue to remain vigilant in our efforts to prevent the spread of avian influenza between animals and to humans.”

For now, Canadian virologists are watching developments closely and urging caution among those who encounter wild or migratory birds but not recommending major changes overall.

“The fact that we have a first human case in Canada is not at all surprising, given what is happening in the US and Europe, as well as what is happening in domestic bird flocks in British Columbia,” said Brian Ward, MD, professor of medicine at McGill University, researcher with McGill’s JD MacLean Centre for Tropical Diseases, and co-director of McGill’s Vaccine Study Centre, Montreal, Quebec, Canada.

“Millions of migratory waterfowl are flying over Canada right now, many of which may be carrying or infected with the virus,” he said. “The bottom line is that increasing evidence of mammal-to-mammal spread among dairy cows, elephant seals, and mink and ermine farms is worrisome, but we don’t need to sound the sirens yet.”

 

Future Outbreak Measures

Looking ahead, though, the developing situation feels more threatening than benign, given the ongoing spread among dairy cattle in the United States, said Bogoch. “It’s difficult to get the genie back in the bottle. I had hoped to see the cases slow down this year, but we just haven’t seen that.”

The fact that surveillance measures such as wastewater sampling have been scaled back in some areas of Canada is cause for concern, Bogoch added.

“We have great foundations for surveillance and action; we just need to make sure they are supported adequately, that groups communicate (across too many silos), and that there are quick responses,” said Scott Weese, DVM, professor of pathobiology at the Ontario Veterinary College and director of the University of Guelph’s Centre for Public Health and Zoonoses in Ontario.

“With cattle in the US, I think it’s highlighted what can happen if the initial response is not very aggressive. There could have been a lot more proactive response to H5N1 in dairy cattle, but there are so many competing interests and unwillingness to take necessary steps that the virus continues to spread,” he said. “Hopefully we’ve learned from that. However, as is often the case, the science is sometimes the easy part. Getting people to take the required actions is the challenge.”

On a personal level, masks and social distancing work well against influenza virus, including both seasonal and avian strains, said Ward. On a broader level, healthcare providers can monitor patients and support testing, where appropriate.

“The most important thing for people to know is that there is going to be another pandemic. It might or might not be due to a variant of H5N1, but it will come at some time,” said Allison McGeer, MD, professor of laboratory medicine and pathobiology at the University of Toronto and an infectious disease specialist with the Sinai Health System, Toronto.

Healthcare providers should follow ongoing updates to public health guidance, support surveillance where possible, and work with hospital leadership and infection control officials to ensure that pandemic plans are in place, she said.

“They may not be needed in the next few months, but they will be needed,” McGeer said. “We know a lot more about influenza than we did about SARS-CoV-2, so we have more tools to mitigate the impact, but we need to have them ready and know how to use them effectively.”

A version of this article appeared on Medscape.com.

TOPLINE:

Home spirometry shows potential for early detection of pulmonary function decline in patients with systemic sclerosis–associated interstitial lung disease (SSc-ILD). It shows good cross-sectional correlation with hospital tests, along with 60% sensitivity and 87% specificity for detecting progressive ILD.

METHODOLOGY:

• Researchers conducted a prospective, observational study to examine the validity of home spirometry for detecting a decline in pulmonary function in patients with SSc-ILD.
• They included 43 patients aged 18 years or older with SSc-ILD from two tertiary referral centers in the Netherlands who received treatment with immunosuppressives for a maximum duration of 8 weeks prior to baseline.
• All participants were required to take weekly home spirometry measurements using a handheld spirometer for 1 year, with 35 completing 6 months of follow-up and 31 completing 12 months.
• Pulmonary function tests were conducted in the hospital at baseline and semiannual visits.
• The primary outcome was the κ (kappa statistic) agreement between home and hospital measurements after 1 year to detect a decline in forced vital capacity (FVC) of 5% or more; the sensitivity and specificity of home spirometry were also evaluated to detect an absolute decline in FVC%, using hospital tests as the gold standard.

TAKEAWAY:

• Home spirometry showed a fair agreement with the pulmonary function tests conducted at the hospital (κ, 0.40; 95% CI, 0.01-0.79).
• Home spirometry showed a sensitivity of 60% and specificity of 87% in detecting a decline in FVC% predicted of 5% or more.
• The intraclass correlation coefficient between home and hospital FVC measurements was moderate to high, with values of 0.85 at baseline, 0.84 at 6 months, and 0.72 at 12 months (P < .0001 for all).
• However, the longitudinal agreement between home and hospital measurements was lower with a correlation coefficient of 0.55.

IN PRACTICE:

“These findings suggest that home spirometry is both feasible and moderately accurate in patients with systemic sclerosis–associated ILD. However, where home spirometry fell short was the low sensitivity in detecting a decline in FVC% predicted,” experts wrote in an accompanying editorial.

“The results of this study support further evaluation of the implementation of home spirometry in addition to regular healthcare management but do not endorse relying solely on home monitoring to detect a decline in pulmonary function,” study authors wrote.

SOURCE:

The study was led by Arthiha Velauthapillai, MD, Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands, and was published online November 8, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study might have been underpowered because of inaccuracies in initial assumptions, with a lower-than-anticipated prevalence of progressive ILD and a higher dropout rate. The study included only Dutch patients, which may have limited the generalizability of its findings to other settings with lower internet access or literacy rates.

DISCLOSURES:

This study was partly supported by grants from Galapagos and Boehringer Ingelheim. Some authors received grants or consulting or speaker fees from Boehringer Ingelheim, AstraZeneca, and other pharmaceutical companies.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Home spirometry shows potential for early detection of pulmonary function decline in patients with systemic sclerosis–associated interstitial lung disease (SSc-ILD). It shows good cross-sectional correlation with hospital tests, along with 60% sensitivity and 87% specificity for detecting progressive ILD.

METHODOLOGY:

• Researchers conducted a prospective, observational study to examine the validity of home spirometry for detecting a decline in pulmonary function in patients with SSc-ILD.
• They included 43 patients aged 18 years or older with SSc-ILD from two tertiary referral centers in the Netherlands who received treatment with immunosuppressives for a maximum duration of 8 weeks prior to baseline.
• All participants were required to take weekly home spirometry measurements using a handheld spirometer for 1 year, with 35 completing 6 months of follow-up and 31 completing 12 months.
• Pulmonary function tests were conducted in the hospital at baseline and semiannual visits.
• The primary outcome was the κ (kappa statistic) agreement between home and hospital measurements after 1 year to detect a decline in forced vital capacity (FVC) of 5% or more; the sensitivity and specificity of home spirometry were also evaluated to detect an absolute decline in FVC%, using hospital tests as the gold standard.

TAKEAWAY:

• Home spirometry showed a fair agreement with the pulmonary function tests conducted at the hospital (κ, 0.40; 95% CI, 0.01-0.79).
• Home spirometry showed a sensitivity of 60% and specificity of 87% in detecting a decline in FVC% predicted of 5% or more.
• The intraclass correlation coefficient between home and hospital FVC measurements was moderate to high, with values of 0.85 at baseline, 0.84 at 6 months, and 0.72 at 12 months (P < .0001 for all).
• However, the longitudinal agreement between home and hospital measurements was lower with a correlation coefficient of 0.55.

IN PRACTICE:

“These findings suggest that home spirometry is both feasible and moderately accurate in patients with systemic sclerosis–associated ILD. However, where home spirometry fell short was the low sensitivity in detecting a decline in FVC% predicted,” experts wrote in an accompanying editorial.

“The results of this study support further evaluation of the implementation of home spirometry in addition to regular healthcare management but do not endorse relying solely on home monitoring to detect a decline in pulmonary function,” study authors wrote.

SOURCE:

The study was led by Arthiha Velauthapillai, MD, Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands, and was published online November 8, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study might have been underpowered because of inaccuracies in initial assumptions, with a lower-than-anticipated prevalence of progressive ILD and a higher dropout rate. The study included only Dutch patients, which may have limited the generalizability of its findings to other settings with lower internet access or literacy rates.

DISCLOSURES:

This study was partly supported by grants from Galapagos and Boehringer Ingelheim. Some authors received grants or consulting or speaker fees from Boehringer Ingelheim, AstraZeneca, and other pharmaceutical companies.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Home spirometry shows potential for early detection of pulmonary function decline in patients with systemic sclerosis–associated interstitial lung disease (SSc-ILD). It shows good cross-sectional correlation with hospital tests, along with 60% sensitivity and 87% specificity for detecting progressive ILD.

METHODOLOGY:

• Researchers conducted a prospective, observational study to examine the validity of home spirometry for detecting a decline in pulmonary function in patients with SSc-ILD.
• They included 43 patients aged 18 years or older with SSc-ILD from two tertiary referral centers in the Netherlands who received treatment with immunosuppressives for a maximum duration of 8 weeks prior to baseline.
• All participants were required to take weekly home spirometry measurements using a handheld spirometer for 1 year, with 35 completing 6 months of follow-up and 31 completing 12 months.
• Pulmonary function tests were conducted in the hospital at baseline and semiannual visits.
• The primary outcome was the κ (kappa statistic) agreement between home and hospital measurements after 1 year to detect a decline in forced vital capacity (FVC) of 5% or more; the sensitivity and specificity of home spirometry were also evaluated to detect an absolute decline in FVC%, using hospital tests as the gold standard.

TAKEAWAY:

• Home spirometry showed a fair agreement with the pulmonary function tests conducted at the hospital (κ, 0.40; 95% CI, 0.01-0.79).
• Home spirometry showed a sensitivity of 60% and specificity of 87% in detecting a decline in FVC% predicted of 5% or more.
• The intraclass correlation coefficient between home and hospital FVC measurements was moderate to high, with values of 0.85 at baseline, 0.84 at 6 months, and 0.72 at 12 months (P < .0001 for all).
• However, the longitudinal agreement between home and hospital measurements was lower with a correlation coefficient of 0.55.

IN PRACTICE:

“These findings suggest that home spirometry is both feasible and moderately accurate in patients with systemic sclerosis–associated ILD. However, where home spirometry fell short was the low sensitivity in detecting a decline in FVC% predicted,” experts wrote in an accompanying editorial.

“The results of this study support further evaluation of the implementation of home spirometry in addition to regular healthcare management but do not endorse relying solely on home monitoring to detect a decline in pulmonary function,” study authors wrote.

SOURCE:

The study was led by Arthiha Velauthapillai, MD, Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands, and was published online November 8, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study might have been underpowered because of inaccuracies in initial assumptions, with a lower-than-anticipated prevalence of progressive ILD and a higher dropout rate. The study included only Dutch patients, which may have limited the generalizability of its findings to other settings with lower internet access or literacy rates.

DISCLOSURES:

This study was partly supported by grants from Galapagos and Boehringer Ingelheim. Some authors received grants or consulting or speaker fees from Boehringer Ingelheim, AstraZeneca, and other pharmaceutical companies.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Exposure to fine particulate matter (PM_2.5) during pregnancy is associated with an increased risk for spontaneous preterm birth, with peak vulnerability in the second trimester. Lower socioeconomic status, limited green space exposure, and extreme heat amplify this risk, whereas living around more trees provides protective effects.

METHODOLOGY:

• The researchers conducted a population-based retrospective cohort study to examine the associations of exposures to total PM_2.5 and five constituents (black carbon, nitrate, organic matter, and sulfate) during pregnancy with spontaneous preterm birth.
• They included 409,037 singleton live births from the Kaiser Permanente Southern California health care system between 2008 and 2018, with mothers having a mean age of 30.3 years at delivery (51% Hispanic).
• Daily total PM_2.5 concentrations and monthly data on the constituents in California were obtained; mean exposures during the entire pregnancy and in each trimester were calculated.
• Spontaneous preterm births were identified through the evaluation of preterm labor visits and were defined as a delivery occurring before 37 weeks following the onset of spontaneous labor, without pregnancy complications, and within 7 days of the last preterm labor visit.
• The analysis also examined the effect of factors such as race and ethnicity, education, median household income, exposure to green spaces, wildfire smoke, and temperature.

TAKEAWAY:

• Each 2.76 µg/m³ increase in total PM_2.5 exposure during pregnancy raised the risk for spontaneous preterm birth by 15% (P < .001), with black carbon showing the highest risk (adjusted odds ratio [aOR], 1.15; 95% CI, 1.12-1.18; P < .001).
• Exposure to PM_2.5 during the second trimester showed the highest association with spontaneous preterm birth (aOR, 1.10; P < .001), followed by that during the third (aOR, 1.09; P < .001) and first (aOR, 1.07; P < .001) trimesters.
• Individuals with lower education levels showed a higher risk for spontaneous preterm birth than those with more than 4 years of college education (P = .003).
• Exposure to extreme heat (P < .001) and lower exposure to total green space (P = .003) increased the risk for spontaneous preterm abortion.

IN PRACTICE:

“Targeted and preventive public health interventions among these subpopulations with high risk may be critical for minimizing the burden of spontaneous preterm birth,” the authors wrote.

SOURCE:

The study was led by Anqi Jiao of the program in public health at the Department of Environmental and Occupational Health at the University of California, Irvine. It was published online in JAMA Network Open.

LIMITATIONS:

According to the authors, exposure misclassification was inevitable as individual exposure to PM_2.5 was estimated according to census tract-level data without considering personal activity patterns. Only five major PM_2.5 constituents were measured due to data availability. Additionally, street-view green space data were considered spatial snapshots, which cannot capture temporal variations, possibly leading to exposure misclassification and biased associations in either direction.

DISCLOSURES:

The study was supported by the National Institute of Environmental Health Sciences and the California Air Resources Board. One author reported receiving research funding from pharmaceutical and biopharmaceutical companies, which was paid to the institute. Another author reported receiving grants from a medical technology company outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Exposure to fine particulate matter (PM_2.5) during pregnancy is associated with an increased risk for spontaneous preterm birth, with peak vulnerability in the second trimester. Lower socioeconomic status, limited green space exposure, and extreme heat amplify this risk, whereas living around more trees provides protective effects.

METHODOLOGY:

• The researchers conducted a population-based retrospective cohort study to examine the associations of exposures to total PM_2.5 and five constituents (black carbon, nitrate, organic matter, and sulfate) during pregnancy with spontaneous preterm birth.
• They included 409,037 singleton live births from the Kaiser Permanente Southern California health care system between 2008 and 2018, with mothers having a mean age of 30.3 years at delivery (51% Hispanic).
• Daily total PM_2.5 concentrations and monthly data on the constituents in California were obtained; mean exposures during the entire pregnancy and in each trimester were calculated.
• Spontaneous preterm births were identified through the evaluation of preterm labor visits and were defined as a delivery occurring before 37 weeks following the onset of spontaneous labor, without pregnancy complications, and within 7 days of the last preterm labor visit.
• The analysis also examined the effect of factors such as race and ethnicity, education, median household income, exposure to green spaces, wildfire smoke, and temperature.

TAKEAWAY:

• Each 2.76 µg/m³ increase in total PM_2.5 exposure during pregnancy raised the risk for spontaneous preterm birth by 15% (P < .001), with black carbon showing the highest risk (adjusted odds ratio [aOR], 1.15; 95% CI, 1.12-1.18; P < .001).
• Exposure to PM_2.5 during the second trimester showed the highest association with spontaneous preterm birth (aOR, 1.10; P < .001), followed by that during the third (aOR, 1.09; P < .001) and first (aOR, 1.07; P < .001) trimesters.
• Individuals with lower education levels showed a higher risk for spontaneous preterm birth than those with more than 4 years of college education (P = .003).
• Exposure to extreme heat (P < .001) and lower exposure to total green space (P = .003) increased the risk for spontaneous preterm abortion.

IN PRACTICE:

“Targeted and preventive public health interventions among these subpopulations with high risk may be critical for minimizing the burden of spontaneous preterm birth,” the authors wrote.

SOURCE:

The study was led by Anqi Jiao of the program in public health at the Department of Environmental and Occupational Health at the University of California, Irvine. It was published online in JAMA Network Open.

LIMITATIONS:

According to the authors, exposure misclassification was inevitable as individual exposure to PM_2.5 was estimated according to census tract-level data without considering personal activity patterns. Only five major PM_2.5 constituents were measured due to data availability. Additionally, street-view green space data were considered spatial snapshots, which cannot capture temporal variations, possibly leading to exposure misclassification and biased associations in either direction.

DISCLOSURES:

The study was supported by the National Institute of Environmental Health Sciences and the California Air Resources Board. One author reported receiving research funding from pharmaceutical and biopharmaceutical companies, which was paid to the institute. Another author reported receiving grants from a medical technology company outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Exposure to fine particulate matter (PM_2.5) during pregnancy is associated with an increased risk for spontaneous preterm birth, with peak vulnerability in the second trimester. Lower socioeconomic status, limited green space exposure, and extreme heat amplify this risk, whereas living around more trees provides protective effects.

METHODOLOGY:

• The researchers conducted a population-based retrospective cohort study to examine the associations of exposures to total PM_2.5 and five constituents (black carbon, nitrate, organic matter, and sulfate) during pregnancy with spontaneous preterm birth.
• They included 409,037 singleton live births from the Kaiser Permanente Southern California health care system between 2008 and 2018, with mothers having a mean age of 30.3 years at delivery (51% Hispanic).
• Daily total PM_2.5 concentrations and monthly data on the constituents in California were obtained; mean exposures during the entire pregnancy and in each trimester were calculated.
• Spontaneous preterm births were identified through the evaluation of preterm labor visits and were defined as a delivery occurring before 37 weeks following the onset of spontaneous labor, without pregnancy complications, and within 7 days of the last preterm labor visit.
• The analysis also examined the effect of factors such as race and ethnicity, education, median household income, exposure to green spaces, wildfire smoke, and temperature.

TAKEAWAY:

• Each 2.76 µg/m³ increase in total PM_2.5 exposure during pregnancy raised the risk for spontaneous preterm birth by 15% (P < .001), with black carbon showing the highest risk (adjusted odds ratio [aOR], 1.15; 95% CI, 1.12-1.18; P < .001).
• Exposure to PM_2.5 during the second trimester showed the highest association with spontaneous preterm birth (aOR, 1.10; P < .001), followed by that during the third (aOR, 1.09; P < .001) and first (aOR, 1.07; P < .001) trimesters.
• Individuals with lower education levels showed a higher risk for spontaneous preterm birth than those with more than 4 years of college education (P = .003).
• Exposure to extreme heat (P < .001) and lower exposure to total green space (P = .003) increased the risk for spontaneous preterm abortion.

IN PRACTICE:

“Targeted and preventive public health interventions among these subpopulations with high risk may be critical for minimizing the burden of spontaneous preterm birth,” the authors wrote.

SOURCE:

The study was led by Anqi Jiao of the program in public health at the Department of Environmental and Occupational Health at the University of California, Irvine. It was published online in JAMA Network Open.

LIMITATIONS:

According to the authors, exposure misclassification was inevitable as individual exposure to PM_2.5 was estimated according to census tract-level data without considering personal activity patterns. Only five major PM_2.5 constituents were measured due to data availability. Additionally, street-view green space data were considered spatial snapshots, which cannot capture temporal variations, possibly leading to exposure misclassification and biased associations in either direction.

DISCLOSURES:

The study was supported by the National Institute of Environmental Health Sciences and the California Air Resources Board. One author reported receiving research funding from pharmaceutical and biopharmaceutical companies, which was paid to the institute. Another author reported receiving grants from a medical technology company outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

WASHINGTON — Patients with granulomatosis with polyangiitis (GPA) completely tapered off prednisone have a more than fourfold risk of relapse by 6 months, compared with those tapered to 5 mg/day of prednisone; however, this benefit was only seen in patients not on rituximab, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“For patients treated with rituximab, fully tapering off glucocorticoids is reasonable to consider as the first approach,” said Peter Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, during his presentation of the findings.

Although a low dose of glucocorticoids can prevent some minor relapses in patients on other treatment regimens such as methotrexate or azathioprine, “fully tapering off prednisone presents relatively little risk of major relapse, and that major relapse can be treated rather quickly,” Merkel added.

The Assessment of Prednisone in Remission (TAPIR) trial enrolled 143 patients with GPA who were in remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis [BVAS/WG] of 0) within 1 year of treatment to induce remission for active disease and who were taking 5-10 mg of prednisone per day. After all patients tapered to 5 mg/day of prednisone, 71 patients completely tapered off prednisone over 4 weeks and remained off glucocorticoids until month 6. The remaining patients maintained a 5-mg/day dose over the study period. Placement in either treatment group was randomized, and patients continued other immunosuppressive therapy during the study.

Researchers evaluated the rate of relapse by 6 months, defined as a physician’s decision to increase the dose of glucocorticoids to treat GPA, in both groups.

Across all participants, the median age was 58 years, and 52% of patients were male. Most patients were White, and 47% of all patients were prescribed rituximab. 

At 6 months, 15.5% of participants who completely tapered off prednisone experienced a relapse of GPA, compared with 4.2% of those taking low-dose prednisone. Time to relapse was also shorter in the 0-mg prednisone group (P = .026), and relapses occurred continually over 6 months, Merkel said.

When stratified by rituximab use, relapse rates at 6 months between the 5-mg and 0-mg prednisone groups in patients taking rituximab showed no difference. Among patients not taking rituximab, those who completely stopped prednisone were nine and a half times as likely to experience relapse as those in the low-dose group. 

Despite these differences in relapse rates, “surprisingly, there were no differences in patient-reported outcomes [such as pain interference, physical function, and fatigue],” Merkel said. 

Across all patients, all but one relapse was characterized as minor. There were five serious adverse events and 10 infections in the 0-mg group versus one adverse event and 4 infections in the 5-mg group, but these differences were not statistically significant. 

In patients who relapsed, musculoskeletal and ear, nose, and throat manifestations of GPA were most common, and these are “the kind of stuff we see that is helped by low-dose glucocorticoids,” Merkel said.

It’s a good sign that for patients who were completely weaned off glucocorticoids, nearly all relapses were minor, Galina Marder, MD, a rheumatologist and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said in an interview. She was not involved with the research. 

The study “can reinforce the message [of] trying to get them off steroids completely [when possible],” she said.

The findings also provide insight for future clinical trials, Merkel noted. For patients taking non–rituximab-based regimens, completely tapering off glucocorticoids or maintaining a low dose can affect study outcomes.

“[These data are] even more important for clinical trials because they are [reinforcing] the fact that you can have a diminishing signal if you allow some patients to stay on 5 mg prednisone” when GPA flares are the primary outcome, Marder added.

The Vasculitis Clinical Research Consortium received funding for this research through grants from the National Institutes of Health. Merkel has disclosed financial relationships with AbbVie/Abbott, Amgen, argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, ChemoCentryx, CSL Behring, Dynacure, Eicos, Electra, EMD Serono, Forbius, Genentech/Roche, Genzyme/Sanofi, GSK, HI-Bio, Inmagene, InflaRx, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sanofi, Sparrow, Takeda, Talaris, UpToDate, and Visterra. Marder consults for Amgen and Boehringer Ingelheim.

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

WASHINGTON — Patients with granulomatosis with polyangiitis (GPA) completely tapered off prednisone have a more than fourfold risk of relapse by 6 months, compared with those tapered to 5 mg/day of prednisone; however, this benefit was only seen in patients not on rituximab, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“For patients treated with rituximab, fully tapering off glucocorticoids is reasonable to consider as the first approach,” said Peter Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, during his presentation of the findings.

Although a low dose of glucocorticoids can prevent some minor relapses in patients on other treatment regimens such as methotrexate or azathioprine, “fully tapering off prednisone presents relatively little risk of major relapse, and that major relapse can be treated rather quickly,” Merkel added.

The Assessment of Prednisone in Remission (TAPIR) trial enrolled 143 patients with GPA who were in remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis [BVAS/WG] of 0) within 1 year of treatment to induce remission for active disease and who were taking 5-10 mg of prednisone per day. After all patients tapered to 5 mg/day of prednisone, 71 patients completely tapered off prednisone over 4 weeks and remained off glucocorticoids until month 6. The remaining patients maintained a 5-mg/day dose over the study period. Placement in either treatment group was randomized, and patients continued other immunosuppressive therapy during the study.

Researchers evaluated the rate of relapse by 6 months, defined as a physician’s decision to increase the dose of glucocorticoids to treat GPA, in both groups.

Across all participants, the median age was 58 years, and 52% of patients were male. Most patients were White, and 47% of all patients were prescribed rituximab. 

At 6 months, 15.5% of participants who completely tapered off prednisone experienced a relapse of GPA, compared with 4.2% of those taking low-dose prednisone. Time to relapse was also shorter in the 0-mg prednisone group (P = .026), and relapses occurred continually over 6 months, Merkel said.

When stratified by rituximab use, relapse rates at 6 months between the 5-mg and 0-mg prednisone groups in patients taking rituximab showed no difference. Among patients not taking rituximab, those who completely stopped prednisone were nine and a half times as likely to experience relapse as those in the low-dose group. 

Despite these differences in relapse rates, “surprisingly, there were no differences in patient-reported outcomes [such as pain interference, physical function, and fatigue],” Merkel said. 

Across all patients, all but one relapse was characterized as minor. There were five serious adverse events and 10 infections in the 0-mg group versus one adverse event and 4 infections in the 5-mg group, but these differences were not statistically significant. 

In patients who relapsed, musculoskeletal and ear, nose, and throat manifestations of GPA were most common, and these are “the kind of stuff we see that is helped by low-dose glucocorticoids,” Merkel said.

It’s a good sign that for patients who were completely weaned off glucocorticoids, nearly all relapses were minor, Galina Marder, MD, a rheumatologist and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said in an interview. She was not involved with the research. 

The study “can reinforce the message [of] trying to get them off steroids completely [when possible],” she said.

The findings also provide insight for future clinical trials, Merkel noted. For patients taking non–rituximab-based regimens, completely tapering off glucocorticoids or maintaining a low dose can affect study outcomes.

“[These data are] even more important for clinical trials because they are [reinforcing] the fact that you can have a diminishing signal if you allow some patients to stay on 5 mg prednisone” when GPA flares are the primary outcome, Marder added.

The Vasculitis Clinical Research Consortium received funding for this research through grants from the National Institutes of Health. Merkel has disclosed financial relationships with AbbVie/Abbott, Amgen, argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, ChemoCentryx, CSL Behring, Dynacure, Eicos, Electra, EMD Serono, Forbius, Genentech/Roche, Genzyme/Sanofi, GSK, HI-Bio, Inmagene, InflaRx, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sanofi, Sparrow, Takeda, Talaris, UpToDate, and Visterra. Marder consults for Amgen and Boehringer Ingelheim.

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

WASHINGTON — Patients with granulomatosis with polyangiitis (GPA) completely tapered off prednisone have a more than fourfold risk of relapse by 6 months, compared with those tapered to 5 mg/day of prednisone; however, this benefit was only seen in patients not on rituximab, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“For patients treated with rituximab, fully tapering off glucocorticoids is reasonable to consider as the first approach,” said Peter Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, during his presentation of the findings.

Although a low dose of glucocorticoids can prevent some minor relapses in patients on other treatment regimens such as methotrexate or azathioprine, “fully tapering off prednisone presents relatively little risk of major relapse, and that major relapse can be treated rather quickly,” Merkel added.

The Assessment of Prednisone in Remission (TAPIR) trial enrolled 143 patients with GPA who were in remission (defined as a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis [BVAS/WG] of 0) within 1 year of treatment to induce remission for active disease and who were taking 5-10 mg of prednisone per day. After all patients tapered to 5 mg/day of prednisone, 71 patients completely tapered off prednisone over 4 weeks and remained off glucocorticoids until month 6. The remaining patients maintained a 5-mg/day dose over the study period. Placement in either treatment group was randomized, and patients continued other immunosuppressive therapy during the study.

Researchers evaluated the rate of relapse by 6 months, defined as a physician’s decision to increase the dose of glucocorticoids to treat GPA, in both groups.

Across all participants, the median age was 58 years, and 52% of patients were male. Most patients were White, and 47% of all patients were prescribed rituximab. 

At 6 months, 15.5% of participants who completely tapered off prednisone experienced a relapse of GPA, compared with 4.2% of those taking low-dose prednisone. Time to relapse was also shorter in the 0-mg prednisone group (P = .026), and relapses occurred continually over 6 months, Merkel said.

When stratified by rituximab use, relapse rates at 6 months between the 5-mg and 0-mg prednisone groups in patients taking rituximab showed no difference. Among patients not taking rituximab, those who completely stopped prednisone were nine and a half times as likely to experience relapse as those in the low-dose group. 

Despite these differences in relapse rates, “surprisingly, there were no differences in patient-reported outcomes [such as pain interference, physical function, and fatigue],” Merkel said. 

Across all patients, all but one relapse was characterized as minor. There were five serious adverse events and 10 infections in the 0-mg group versus one adverse event and 4 infections in the 5-mg group, but these differences were not statistically significant. 

In patients who relapsed, musculoskeletal and ear, nose, and throat manifestations of GPA were most common, and these are “the kind of stuff we see that is helped by low-dose glucocorticoids,” Merkel said.

It’s a good sign that for patients who were completely weaned off glucocorticoids, nearly all relapses were minor, Galina Marder, MD, a rheumatologist and associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, said in an interview. She was not involved with the research. 

The study “can reinforce the message [of] trying to get them off steroids completely [when possible],” she said.

The findings also provide insight for future clinical trials, Merkel noted. For patients taking non–rituximab-based regimens, completely tapering off glucocorticoids or maintaining a low dose can affect study outcomes.

“[These data are] even more important for clinical trials because they are [reinforcing] the fact that you can have a diminishing signal if you allow some patients to stay on 5 mg prednisone” when GPA flares are the primary outcome, Marder added.

The Vasculitis Clinical Research Consortium received funding for this research through grants from the National Institutes of Health. Merkel has disclosed financial relationships with AbbVie/Abbott, Amgen, argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, ChemoCentryx, CSL Behring, Dynacure, Eicos, Electra, EMD Serono, Forbius, Genentech/Roche, Genzyme/Sanofi, GSK, HI-Bio, Inmagene, InflaRx, Janssen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sanofi, Sparrow, Takeda, Talaris, UpToDate, and Visterra. Marder consults for Amgen and Boehringer Ingelheim.

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

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

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

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

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

WASHINGTON — The B cell–depleting agent inebilizumab (Uplizna) dramatically reduced the risk of flares and increased year-long remission of IgG4-related disease (RD), new research has found.

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial of 135 adults with active IgG4-RD, treatment with inebilizumab resulted in a significant 87% reduction in flare risk and nearly fivefold greater likelihood of flare-free remission at 1 year. The results were published online November 14 in The New England Journal of Medicine and were presented at the annual meeting of the American College of Rheumatology (ACR).

The drug’s manufacturer, Amgen, released top-line results of the trial, called MITIGATE, in June 2024.

 

Until now, the mainstay of management for the chronic multiorgan disease IgG4-RD has been glucocorticoids, which can cause numerous adverse effects. “It is hoped that inebilizumab can be used as an important steroid-sparing medication in this disease to reduce steroid toxicity,” lead author John H. Stone, MD, professor of medicine at Harvard Medical School, Boston, Massachusetts, said in an interview, noting that it may not entirely eliminate the need for steroid treatment, but for many, it appears to work after the remission induction period as a monotherapy without steroids. 

Asked to comment, Leonard H. Calabrese, DO, head of the Section of Clinical Immunology and manager of the Clinical Immunology Clinic at the Cleveland Clinic, Ohio, said: “There has been anecdotal or observational evidence for some effect with other immunosuppressive agents, including rituximab, but no robust clinical trial until this study. This clearly has demonstrated efficacy by reducing the risk of flares. And most importantly, putting people into remission means no active disease in any given organ. ... This gives us another tool in the toolbox to attack B cell–directed diseases, and I think it really makes a lot of sense.”

Calabrese cautioned, though, that “this is a disease that extends over many years. This is just a 1-year study. Label extensions will be important.”

 

And several questions remain, Calabrese noted: “How long do patients need to remain on drug? What will happen when the drug is stopped? Can they be retreated? These are the natural questions that arise in any sentinel study like this. But this is extremely encouraging. And I think it’s great for patients. I also think it’s a clarion call to increase awareness about this disease since there’s now strong evidence of effective treatment.” 

 

Underrecognized, Often Misdiagnosed as Cancer

Indeed, IgG4-RD, a chronic, relapsing, autoimmune, fibro-inflammatory multiorgan disease, was only first described in Japan in 2003. Since then, it has been reported all over the world yet remains vastly underrecognized. It is often misdiagnosed as cancer because it produces lesions in multiple organs. It received an ICD-10 code only about a year ago. A previous study estimated a prevalence of about 5.3 persons per 100,000 but that is likely to be a three- to fourfold underestimate, said Stone, who is also executive chairman of the IgG4ward! Foundation. 

“Nobody had heard of the disease until about 20 years ago. ... And there are many people in the world who have still not heard of it despite the fact that it is a multiorgan autoimmune disease and is probably as common, or more common, than many other diseases that rheumatologists spend a lot of time thinking about, such as scleroderma.”

While knowledge about the disease is increasing in rheumatology circles, it’s less well-recognized among many of the specialties where patients present, depending on the location of their lesions. These include gastroenterology, ophthalmology, pulmonary medicine, neurology, and nephrology. “All would be likely to see this disease,” Stone said. 

The disease can be mistaken for tumors in many of those locations and even as metastatic cancer, he noted, adding that “any time a patient has a mass lesion in a typical organ, the pancreas, the major salivary glands, the lungs, or the kidneys, this should be on the differential diagnosis.” 

The diagnosis of IgG4-RD is a clinical one, involving “quadrangulation between clinical features, serological findings, IgG4 levels in the blood, radiology studies, and then pathology biopsies when those are available,” Stone said. 

Calabrese characterized the current situation as “we’re all blind men on the elephant. To the neurologist or the neurosurgeon, it’s a mass in the brain. It could present to the ophthalmologist as an [eye] tumor. It can be thyroid gland failure, pulmonary disease, retroperitoneal fibrosis, hepatobiliary disease, and beyond. So, whoever sees that patient, there’s often a long lag time in recognizing it.”

And interestingly, Stone noted that unlike other autoimmune diseases, IgG4-RD primarily affects middle-aged men rather than younger-to-middle-aged women. And when IgG4-RD is diagnosed, glucocorticoid treatment can be particularly toxic when the pancreas is involved, heightening the risk for hyperglycemia and potentially causing diabetes. 

 

Dramatic Improvement in Flares, Remission Achievement

MITIGATE is a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in which 135 adults (mean age 58.2 years, 88 men) with active IgG4-RD were randomized 1:1 to receive 300-mg intravenous infusions of inebilizumab or placebo on days 1 and 15, and again at week 26. At baseline, 62 (45.9%) participants had newly diagnosed IgG4-RD and 73 (54.1%) had recurrent disease. 

Both groups received identical glucocorticoid tapers. Overall, 127 (94.1%) completed the 52 weeks of treatment. 

By 52 weeks, only seven patients in the inebilizumab group (10%) had experienced disease flares vs 40 (60%) in the placebo group, a significant difference with a hazard ratio of 0.13 (P < .001). 

The percentage of participants achieving flare-free, treatment-free complete remission was 59 with inebilizumab (57%), compared with just 15 (22%) in the placebo group (odds ratio [OR], 4.68; P < .001). And for flare-free, glucocorticoid-free complete remission, those proportions were 40 (59%) vs 15 (22%), respectively (OR, 4.96; P < .001). 

Excluding the 8-week glucocorticoid taper period, mean total glucocorticoid use was 1264.2 mg less in the inebilizumab than the placebo group, a significant reduction. Overall, 61 participants (90%) were able to entirely discontinue glucocorticoids during the trial, compared with just 25 (37%) in the placebo group. 

Adverse events of grade 3 or higher occurred in 12 participants (18%) in the inebilizumab group and 8 (12%) in the placebo group; serious adverse events occurred in 12 (18%) and 6 (9%), respectively. However, no serious adverse event occurred in more than one participant, and there were no deaths. Adverse events led to withdrawal from the trial in six patients (9%) in the inebilizumab group and three patients (4%) in the placebo group. 

Adverse events that occurred in more than 10% of participants in the inebilizumab group were COVID-19 in 16 participants (24%), lymphopenia in 11 (16%), and urinary tract infection in 8 (12%). 

Importantly, Stone noted, B-cell depletion can reduce responses to vaccines, so patients should receive all recommended vaccinations, including COVID-19, influenza, respiratory syncytial virus, and others, prior to initiating therapy. 

Uplizna (inebilizumab-cdon) was approved by the Food and Drug Administration (FDA) for the treatment of neuromyelitis optica spectrum disorder in 2020. In October 2024, the FDA granted Amgen breakthrough therapy designation for use in IgG4-RD. The company is also developing the drug for use in myasthenia gravis.

The study was funded by Amgen. Stone has reported being a consultant for Amgen, Zenas, Argenx, Bristol Myers Squibb, Novartis, Sanofi, and Horizon Pharma. Calabrese has reported being a consultant and/or speaker for Amgen, AstraZeneca, Jansen, Sanofi, and UCB.

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