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CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

sworcester@mdedge.com

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

sworcester@mdedge.com

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

sworcester@mdedge.com

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

Veterans with chronic obstructive pulmonary disease (COPD) have seen a sharp increase since 2012 in rates of non-TB mycobacteria infections, which carry a significantly higher risk of death in COPD patients, according to findings from a nationwide study.

Dr. George Kubica/CDC

For their research, published in Frontiers of Medicine, Fahim Pyarali, MD, and colleagues at the University of Miami, reviewed data from Veterans Affairs hospitals to identify non-TB mycobacteria (NTM) infections among more than 2 million COPD patients seen between 2000 and 2015. Incidence of NTM infections was 34.2 per 100,000 COPD patients in 2001, a rate that remained steady until 2012, when it began climbing sharply through 2015 to reach 70.3 per 100,000 (P = .035). Dr. Pyarali and colleagues also found that, during the study period, prevalence of NTM climbed from 93.1 infections per 100,000 population in 2001 to 277.6 per 100,000 in 2015.

Hotspots for NTM infections included Puerto Rico, which had the highest prevalence seen in the study at 370 infections per 100,000 COPD population; Florida, with 351 per 100,000; and Washington, D.C., with 309 per 100,000. Additional hotspots were identified around Lake Michigan, in coastal Louisiana, and in parts of the Southwest.

Dr. Pyarali and colleagues noted that the geographical concentration of cases near oceans and lakes was “supported by previous findings that warmer temperatures, lower dissolved oxygen, and lower pH in the soils and waters provide a major environmental source for NTM organisms;” however, the study is the first to identify Puerto Rico as having exceptionally high prevalence. The reasons for this should be extensively investigated, the investigators argued.

The mortality risk was 43% higher among NTM-infected patients than in COPD patients without an NTM diagnosis (95% confidence interval, 1.31-1.58; P less than .001), independent of other comorbidities.

Though rates of NTM infection were seen rising steeply in men and women alike, Dr. Pyarali and colleagues noted as a limitation of their study its use of an overwhelmingly male population, writing that this may obscure “the true reach of NTM disease and mortality” in the general population. The average age of NTM diagnosis remained steady throughout the study period, suggesting that rising incidence is not attributable to earlier diagnosis.

Dr. Pyarali and colleagues reported no outside sources of funding or financial conflicts of interest.

SOURCE: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.

Veterans with chronic obstructive pulmonary disease (COPD) have seen a sharp increase since 2012 in rates of non-TB mycobacteria infections, which carry a significantly higher risk of death in COPD patients, according to findings from a nationwide study.

Dr. George Kubica/CDC

For their research, published in Frontiers of Medicine, Fahim Pyarali, MD, and colleagues at the University of Miami, reviewed data from Veterans Affairs hospitals to identify non-TB mycobacteria (NTM) infections among more than 2 million COPD patients seen between 2000 and 2015. Incidence of NTM infections was 34.2 per 100,000 COPD patients in 2001, a rate that remained steady until 2012, when it began climbing sharply through 2015 to reach 70.3 per 100,000 (P = .035). Dr. Pyarali and colleagues also found that, during the study period, prevalence of NTM climbed from 93.1 infections per 100,000 population in 2001 to 277.6 per 100,000 in 2015.

Hotspots for NTM infections included Puerto Rico, which had the highest prevalence seen in the study at 370 infections per 100,000 COPD population; Florida, with 351 per 100,000; and Washington, D.C., with 309 per 100,000. Additional hotspots were identified around Lake Michigan, in coastal Louisiana, and in parts of the Southwest.

Dr. Pyarali and colleagues noted that the geographical concentration of cases near oceans and lakes was “supported by previous findings that warmer temperatures, lower dissolved oxygen, and lower pH in the soils and waters provide a major environmental source for NTM organisms;” however, the study is the first to identify Puerto Rico as having exceptionally high prevalence. The reasons for this should be extensively investigated, the investigators argued.

The mortality risk was 43% higher among NTM-infected patients than in COPD patients without an NTM diagnosis (95% confidence interval, 1.31-1.58; P less than .001), independent of other comorbidities.

Though rates of NTM infection were seen rising steeply in men and women alike, Dr. Pyarali and colleagues noted as a limitation of their study its use of an overwhelmingly male population, writing that this may obscure “the true reach of NTM disease and mortality” in the general population. The average age of NTM diagnosis remained steady throughout the study period, suggesting that rising incidence is not attributable to earlier diagnosis.

Dr. Pyarali and colleagues reported no outside sources of funding or financial conflicts of interest.

SOURCE: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.

Veterans with chronic obstructive pulmonary disease (COPD) have seen a sharp increase since 2012 in rates of non-TB mycobacteria infections, which carry a significantly higher risk of death in COPD patients, according to findings from a nationwide study.

Dr. George Kubica/CDC

For their research, published in Frontiers of Medicine, Fahim Pyarali, MD, and colleagues at the University of Miami, reviewed data from Veterans Affairs hospitals to identify non-TB mycobacteria (NTM) infections among more than 2 million COPD patients seen between 2000 and 2015. Incidence of NTM infections was 34.2 per 100,000 COPD patients in 2001, a rate that remained steady until 2012, when it began climbing sharply through 2015 to reach 70.3 per 100,000 (P = .035). Dr. Pyarali and colleagues also found that, during the study period, prevalence of NTM climbed from 93.1 infections per 100,000 population in 2001 to 277.6 per 100,000 in 2015.

Hotspots for NTM infections included Puerto Rico, which had the highest prevalence seen in the study at 370 infections per 100,000 COPD population; Florida, with 351 per 100,000; and Washington, D.C., with 309 per 100,000. Additional hotspots were identified around Lake Michigan, in coastal Louisiana, and in parts of the Southwest.

Dr. Pyarali and colleagues noted that the geographical concentration of cases near oceans and lakes was “supported by previous findings that warmer temperatures, lower dissolved oxygen, and lower pH in the soils and waters provide a major environmental source for NTM organisms;” however, the study is the first to identify Puerto Rico as having exceptionally high prevalence. The reasons for this should be extensively investigated, the investigators argued.

The mortality risk was 43% higher among NTM-infected patients than in COPD patients without an NTM diagnosis (95% confidence interval, 1.31-1.58; P less than .001), independent of other comorbidities.

Though rates of NTM infection were seen rising steeply in men and women alike, Dr. Pyarali and colleagues noted as a limitation of their study its use of an overwhelmingly male population, writing that this may obscure “the true reach of NTM disease and mortality” in the general population. The average age of NTM diagnosis remained steady throughout the study period, suggesting that rising incidence is not attributable to earlier diagnosis.

Dr. Pyarali and colleagues reported no outside sources of funding or financial conflicts of interest.

SOURCE: Pyarali F et al. Front Med. 2018 Nov 6. doi: 10.3389/fmed2018.00311.

Patients with HIV/AIDs are vulnerable to Talaromyces marneffei (T marneffei) infection, formerly penicilliosis. But in recent years more cases have been seen in patients not infected with HIV, too. Most cases originate in Southeast Asia: 10% of patients with AIDS in Hong Kong and 30% of patients in North Thailand, for example, have T marneffei infections. But patients with AIDS and penicilliosis travel, as do other immunocompromised patients. Thus, the first reported case of a patient with long-standing pulmonary sarcoidosis who developed T marneffei infection may have significance for clinicians caring for people with, or without, HIV.

Most patients with T marneffei infection have fever, weight loss, and malaise. Subcutaneous abscesses and papulelike ulcers are common (sometimes the lesions are very small). Anemia, hepatosplenomegaly, lymphadenopathy, and diarrhea also are relatively common. However, while cough is a notable symptom, pneumonia is rare—even though the organism is inhaled.

The patient in this report, a native of Cangnan County (an endemic fungal area) in Southeast China, was admitted to the hospital with a 3-week history of daily hyperpyrexia and coughing sputum. When antibiotics did not help, a fungal culture revealed why: He had T marneffei infection. The clinicians say the preexisting pulmonary sarcoidosis covered the clinical features of T marneffei and initially misled them.

After 3 months of antifungal treatment, the patient’s physical condition improved. And the lung lesions were “markedly absorbed” after 3 months. The respiratory signs and skin lesions disappeared gradually after 8 days of treatment.

T marneffei infection is fatal if untreated. Early diagnosis and treatment with antifungals can be life saving.

Source:
Yu X, Miao K, Zhou C, et al. BMC Infect Dis. 2018;18(1):390.

Patients with HIV/AIDs are vulnerable to Talaromyces marneffei (T marneffei) infection, formerly penicilliosis. But in recent years more cases have been seen in patients not infected with HIV, too. Most cases originate in Southeast Asia: 10% of patients with AIDS in Hong Kong and 30% of patients in North Thailand, for example, have T marneffei infections. But patients with AIDS and penicilliosis travel, as do other immunocompromised patients. Thus, the first reported case of a patient with long-standing pulmonary sarcoidosis who developed T marneffei infection may have significance for clinicians caring for people with, or without, HIV.

Most patients with T marneffei infection have fever, weight loss, and malaise. Subcutaneous abscesses and papulelike ulcers are common (sometimes the lesions are very small). Anemia, hepatosplenomegaly, lymphadenopathy, and diarrhea also are relatively common. However, while cough is a notable symptom, pneumonia is rare—even though the organism is inhaled.

The patient in this report, a native of Cangnan County (an endemic fungal area) in Southeast China, was admitted to the hospital with a 3-week history of daily hyperpyrexia and coughing sputum. When antibiotics did not help, a fungal culture revealed why: He had T marneffei infection. The clinicians say the preexisting pulmonary sarcoidosis covered the clinical features of T marneffei and initially misled them.

After 3 months of antifungal treatment, the patient’s physical condition improved. And the lung lesions were “markedly absorbed” after 3 months. The respiratory signs and skin lesions disappeared gradually after 8 days of treatment.

T marneffei infection is fatal if untreated. Early diagnosis and treatment with antifungals can be life saving.

Source:
Yu X, Miao K, Zhou C, et al. BMC Infect Dis. 2018;18(1):390.

Patients with HIV/AIDs are vulnerable to Talaromyces marneffei (T marneffei) infection, formerly penicilliosis. But in recent years more cases have been seen in patients not infected with HIV, too. Most cases originate in Southeast Asia: 10% of patients with AIDS in Hong Kong and 30% of patients in North Thailand, for example, have T marneffei infections. But patients with AIDS and penicilliosis travel, as do other immunocompromised patients. Thus, the first reported case of a patient with long-standing pulmonary sarcoidosis who developed T marneffei infection may have significance for clinicians caring for people with, or without, HIV.

Most patients with T marneffei infection have fever, weight loss, and malaise. Subcutaneous abscesses and papulelike ulcers are common (sometimes the lesions are very small). Anemia, hepatosplenomegaly, lymphadenopathy, and diarrhea also are relatively common. However, while cough is a notable symptom, pneumonia is rare—even though the organism is inhaled.

The patient in this report, a native of Cangnan County (an endemic fungal area) in Southeast China, was admitted to the hospital with a 3-week history of daily hyperpyrexia and coughing sputum. When antibiotics did not help, a fungal culture revealed why: He had T marneffei infection. The clinicians say the preexisting pulmonary sarcoidosis covered the clinical features of T marneffei and initially misled them.

After 3 months of antifungal treatment, the patient’s physical condition improved. And the lung lesions were “markedly absorbed” after 3 months. The respiratory signs and skin lesions disappeared gradually after 8 days of treatment.

T marneffei infection is fatal if untreated. Early diagnosis and treatment with antifungals can be life saving.

Source:
Yu X, Miao K, Zhou C, et al. BMC Infect Dis. 2018;18(1):390.

ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.

That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.

Severe asthma challenges

These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.

Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.

xavier gallego morel/fotolia.com

The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta₂-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.

It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
 

Biologics for pediatric asthma

Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.

The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.

Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.

For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV₁) and overall quality of life.

Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV₁ or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).

Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.

Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.

Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV₁. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.

Dupilumab: New kid on the block

The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.

The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.

“It could be potentially better than those currently available due to additional effect on FEV₁,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.

As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.

“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”

Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.

ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.

That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.

Severe asthma challenges

These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.

Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.

xavier gallego morel/fotolia.com

The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta₂-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.

It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
 

Biologics for pediatric asthma

Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.

The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.

Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.

For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV₁) and overall quality of life.

Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV₁ or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).

Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.

Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.

Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV₁. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.

Dupilumab: New kid on the block

The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.

The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.

“It could be potentially better than those currently available due to additional effect on FEV₁,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.

As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.

“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”

Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.

ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.

That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.

Severe asthma challenges

These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.

Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.

xavier gallego morel/fotolia.com

The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta₂-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.

It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
 

Biologics for pediatric asthma

Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.

The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.

Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.

For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV₁) and overall quality of life.

Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV₁ or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).

Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.

Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.

Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV₁. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.

Dupilumab: New kid on the block

The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.

The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.

“It could be potentially better than those currently available due to additional effect on FEV₁,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.

As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.

“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”

Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.

moodboard/thinkstockphotos

Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.

The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.

After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.

Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.

“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”

They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.

The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.

SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.

The Magnetic Resonance Imaging in Obstructive Sleep Apnea trial is an observational cohort study recruiting adults with obstructive sleep apnea undergoing surgery.

The trial will compare drug-induced sleep endoscopy and upper airway MRI in order to determine which is the better predictor of success in patients who cannot tolerate nonsurgical solutions. Upper airway MRI is a more complete evaluation during wakefulness and is cheaper than drug-induced sleep endoscopy, but no studies have thus far utilized MRI as a surgical evaluation tool.

Patients will be included if they are at least 21 years old, have moderate to severe obstructive sleep apnea, and have a body mass index less than 40 kg/m². Exclusion criteria include prior surgery for obstructive sleep apnea; known neurologic, cardiac, pulmonary, renal, or hepatic disorders; psychiatric problems except for treated depression or mild anxiety; a coexisting sleep disorder; or another contraindication to drug-induced sleep endoscopy or MRI, such as propofol allergy.

The primary outcome measure is surgical results after 6 months, which will be measured using sleep studies. Secondary outcomes include sleep-related quality of life after 6 months and daytime sleepiness after 6 months.

The estimated primary completion date is June 2020, and the estimated study completion date is July 2020. About 40 patients are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

lfranki@mdedge.com

The Magnetic Resonance Imaging in Obstructive Sleep Apnea trial is an observational cohort study recruiting adults with obstructive sleep apnea undergoing surgery.

The trial will compare drug-induced sleep endoscopy and upper airway MRI in order to determine which is the better predictor of success in patients who cannot tolerate nonsurgical solutions. Upper airway MRI is a more complete evaluation during wakefulness and is cheaper than drug-induced sleep endoscopy, but no studies have thus far utilized MRI as a surgical evaluation tool.

Patients will be included if they are at least 21 years old, have moderate to severe obstructive sleep apnea, and have a body mass index less than 40 kg/m². Exclusion criteria include prior surgery for obstructive sleep apnea; known neurologic, cardiac, pulmonary, renal, or hepatic disorders; psychiatric problems except for treated depression or mild anxiety; a coexisting sleep disorder; or another contraindication to drug-induced sleep endoscopy or MRI, such as propofol allergy.

The primary outcome measure is surgical results after 6 months, which will be measured using sleep studies. Secondary outcomes include sleep-related quality of life after 6 months and daytime sleepiness after 6 months.

The estimated primary completion date is June 2020, and the estimated study completion date is July 2020. About 40 patients are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

lfranki@mdedge.com

The Magnetic Resonance Imaging in Obstructive Sleep Apnea trial is an observational cohort study recruiting adults with obstructive sleep apnea undergoing surgery.

The trial will compare drug-induced sleep endoscopy and upper airway MRI in order to determine which is the better predictor of success in patients who cannot tolerate nonsurgical solutions. Upper airway MRI is a more complete evaluation during wakefulness and is cheaper than drug-induced sleep endoscopy, but no studies have thus far utilized MRI as a surgical evaluation tool.

Patients will be included if they are at least 21 years old, have moderate to severe obstructive sleep apnea, and have a body mass index less than 40 kg/m². Exclusion criteria include prior surgery for obstructive sleep apnea; known neurologic, cardiac, pulmonary, renal, or hepatic disorders; psychiatric problems except for treated depression or mild anxiety; a coexisting sleep disorder; or another contraindication to drug-induced sleep endoscopy or MRI, such as propofol allergy.

The primary outcome measure is surgical results after 6 months, which will be measured using sleep studies. Secondary outcomes include sleep-related quality of life after 6 months and daytime sleepiness after 6 months.

The estimated primary completion date is June 2020, and the estimated study completion date is July 2020. About 40 patients are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

lfranki@mdedge.com

People with primary central nervous system lymphoma (PCNSL) should be offered entry into clinical trials whenever possible, say the authors of the British Society for Haematology’s guidelines for the diagnosis and management of primary central nervous system diffuse large B‐cell lymphoma.

PCNSL, implicated in some 3% of all brain tumors, is complex to diagnose and treat. People with suspected PCNSL must receive quick and coordinated attention from a multidisciplinary team of neurologists, hematologist-oncologists, and ocular specialists, according to the guidelines, published in the British Journal of Haematology.

Christopher P. Fox, MD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues, stress the importance of early multidisciplinary attention, aggressive induction treatment, helping patients into trials, universal screening for eye involvement, attaining histological diagnoses in addition to imaging findings, and avoidance or discontinuation of any corticosteroids before biopsy, as even a short course of steroids can impede diagnosis.

The guidelines incorporate findings from studies published since the society’s last comprehensive PCNSL guideline was issued more than a decade ago.

Dr. Fox and his colleagues say definitive treatment for PCNSL – induction of remission followed by consolidation – should start within 2 weeks of diagnosis and that a treatment regimen should be chosen according to a patient’s physiological fitness, not age. The fittest patients, who have better organ function and fewer comorbidities, should be eligible for intensive combination immunochemotherapy incorporating high-dose methotrexate (optimally four cycles of HD-MTX, cytarabine, thiotepa, and rituximab). Those deemed unfit for this regimen should be offered induction treatment with HD-MTX, rituximab and procarbazine, the guidelines’ authors say.

If patients cannot tolerate HD-MTX, oral chemotherapy and/or whole-brain radiotherapy may be offered. Response should be assessed with contrast-enhanced magnetic resonance imaging.

Consolidation therapy should be initiated after induction for all patients with nonprogressive disease, and high-dose thiotepa-based chemotherapy with autologous stem cell transplant is the recommended first-line option for consolidation. Response to consolidation, again measured with contrast-enhanced MRI, should be carried out at between 1 and 2 months after therapy is completed, and patients should be referred for neuropsychological testing to assess cognitive function.

Patients with relapsed or refractory disease should be approached with maximum urgency – the guidelines offer an algorithm for retreatment options – and offered clinical trial entry wherever possible.

The PCNSL guideline writing process was sponsored by the British Society for Haematology, and some coauthors, including the lead author, disclosed receiving fees from pharmaceutical manufacturers Adienne or F. Hoffman-La Roche.

jensmith@mdedge.com

SOURCE: Fox et al. Br J Haematol. 2018 Nov 23 doi: 10.1111/bjh.15661.

People with primary central nervous system lymphoma (PCNSL) should be offered entry into clinical trials whenever possible, say the authors of the British Society for Haematology’s guidelines for the diagnosis and management of primary central nervous system diffuse large B‐cell lymphoma.

PCNSL, implicated in some 3% of all brain tumors, is complex to diagnose and treat. People with suspected PCNSL must receive quick and coordinated attention from a multidisciplinary team of neurologists, hematologist-oncologists, and ocular specialists, according to the guidelines, published in the British Journal of Haematology.

Christopher P. Fox, MD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues, stress the importance of early multidisciplinary attention, aggressive induction treatment, helping patients into trials, universal screening for eye involvement, attaining histological diagnoses in addition to imaging findings, and avoidance or discontinuation of any corticosteroids before biopsy, as even a short course of steroids can impede diagnosis.

The guidelines incorporate findings from studies published since the society’s last comprehensive PCNSL guideline was issued more than a decade ago.

Dr. Fox and his colleagues say definitive treatment for PCNSL – induction of remission followed by consolidation – should start within 2 weeks of diagnosis and that a treatment regimen should be chosen according to a patient’s physiological fitness, not age. The fittest patients, who have better organ function and fewer comorbidities, should be eligible for intensive combination immunochemotherapy incorporating high-dose methotrexate (optimally four cycles of HD-MTX, cytarabine, thiotepa, and rituximab). Those deemed unfit for this regimen should be offered induction treatment with HD-MTX, rituximab and procarbazine, the guidelines’ authors say.

If patients cannot tolerate HD-MTX, oral chemotherapy and/or whole-brain radiotherapy may be offered. Response should be assessed with contrast-enhanced magnetic resonance imaging.

Consolidation therapy should be initiated after induction for all patients with nonprogressive disease, and high-dose thiotepa-based chemotherapy with autologous stem cell transplant is the recommended first-line option for consolidation. Response to consolidation, again measured with contrast-enhanced MRI, should be carried out at between 1 and 2 months after therapy is completed, and patients should be referred for neuropsychological testing to assess cognitive function.

Patients with relapsed or refractory disease should be approached with maximum urgency – the guidelines offer an algorithm for retreatment options – and offered clinical trial entry wherever possible.

The PCNSL guideline writing process was sponsored by the British Society for Haematology, and some coauthors, including the lead author, disclosed receiving fees from pharmaceutical manufacturers Adienne or F. Hoffman-La Roche.

jensmith@mdedge.com

SOURCE: Fox et al. Br J Haematol. 2018 Nov 23 doi: 10.1111/bjh.15661.

People with primary central nervous system lymphoma (PCNSL) should be offered entry into clinical trials whenever possible, say the authors of the British Society for Haematology’s guidelines for the diagnosis and management of primary central nervous system diffuse large B‐cell lymphoma.

PCNSL, implicated in some 3% of all brain tumors, is complex to diagnose and treat. People with suspected PCNSL must receive quick and coordinated attention from a multidisciplinary team of neurologists, hematologist-oncologists, and ocular specialists, according to the guidelines, published in the British Journal of Haematology.

Christopher P. Fox, MD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues, stress the importance of early multidisciplinary attention, aggressive induction treatment, helping patients into trials, universal screening for eye involvement, attaining histological diagnoses in addition to imaging findings, and avoidance or discontinuation of any corticosteroids before biopsy, as even a short course of steroids can impede diagnosis.

The guidelines incorporate findings from studies published since the society’s last comprehensive PCNSL guideline was issued more than a decade ago.

Dr. Fox and his colleagues say definitive treatment for PCNSL – induction of remission followed by consolidation – should start within 2 weeks of diagnosis and that a treatment regimen should be chosen according to a patient’s physiological fitness, not age. The fittest patients, who have better organ function and fewer comorbidities, should be eligible for intensive combination immunochemotherapy incorporating high-dose methotrexate (optimally four cycles of HD-MTX, cytarabine, thiotepa, and rituximab). Those deemed unfit for this regimen should be offered induction treatment with HD-MTX, rituximab and procarbazine, the guidelines’ authors say.

If patients cannot tolerate HD-MTX, oral chemotherapy and/or whole-brain radiotherapy may be offered. Response should be assessed with contrast-enhanced magnetic resonance imaging.

Consolidation therapy should be initiated after induction for all patients with nonprogressive disease, and high-dose thiotepa-based chemotherapy with autologous stem cell transplant is the recommended first-line option for consolidation. Response to consolidation, again measured with contrast-enhanced MRI, should be carried out at between 1 and 2 months after therapy is completed, and patients should be referred for neuropsychological testing to assess cognitive function.

Patients with relapsed or refractory disease should be approached with maximum urgency – the guidelines offer an algorithm for retreatment options – and offered clinical trial entry wherever possible.

The PCNSL guideline writing process was sponsored by the British Society for Haematology, and some coauthors, including the lead author, disclosed receiving fees from pharmaceutical manufacturers Adienne or F. Hoffman-La Roche.

jensmith@mdedge.com

SOURCE: Fox et al. Br J Haematol. 2018 Nov 23 doi: 10.1111/bjh.15661.

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

Acute flaccid myelitis appears to present most commonly as asymmetric weakness after respiratory viral infection and has distinctive MRI features that could help with early diagnosis.

In a paper published in JAMA Pediatrics, researchers presented the results of a retrospective case series of 45 children who were diagnosed between 2012 and 2016 with acute flaccid myelitis, or “pseudo polio,” using the Centers for Disease Control’s case definition.

Matthew J. Elrick, MD, PhD, of Johns Hopkins University, Baltimore, and his coauthors came up with a set of reproducible and distinctive features of acute flaccid myelitis. These were the presence of a prodromal fever or viral syndrome; weakness in a lower motor neuron pattern involving one or more limbs, neck, face, and/or bulbar muscles; supportive evidence either from MRI, nerve conduction studies, or cerebrospinal fluid; and the absence of objective sensory deficits, supratentorial white matter, cortical lesions greater than 1 cm in size, encephalopathy, elevated cerebrospinal fluid without pleocytosis, or any other alternative diagnosis.

The researchers commented that, while the CDC case definition has helped with epidemiologic surveillance of acute flaccid myelitis, it may also pick up children with acute weakness caused by other conditions such as transverse myelitis, Guillain-Barré syndrome, ischemic myelopathy, and other myelopathies.

To identify clinical features that might help differentiate patients with acute flaccid myelitis, the researchers attempted to see how many alternative diagnoses were captured in the CDC case definition.

The patients in their study all presented with acute flaccid paralysis in at least one limb and with either an MRI showing a spinal cord lesion spanning one or more spinal segments but largely restricted to gray matter or pleocytosis of the cerebrospinal fluid. The researchers divided the cases into those who also met a well-defined alternative diagnosis – who they categorized as “acute flaccid myelitis with possible alternative diagnosis” (AFM-ad) – and those who were categorized as “restrictively defined AFM” (rAFM). Overall, 34 patients were classified as rAFM and 11 as AFM-ad.

Those in the rAFD group nearly all had asymmetric onset of symptoms, while those in the AFM-ad group were more likely to experience bilateral onset in their lower extremities, “reflecting the pattern of symptoms often seen in other causes of myelopathy such as transverse myelitis and ischemic injury,” the authors noted.

While both groups often presented with decreased muscle tone and reflexes, this was more likely to evolve to increased tone or hyperreflexia in the AFM-ad group. Patients with AFM-ad were also more likely to experience impaired bowel or bladder function.

On MRI, lesions were mostly or completely restricted to the spinal cord gray matter in patients with rAFM or to involve the dorsal pons. These patients did not have any supratentorial brain lesions.

Patients in the rAFM category also had lower cerebrospinal fluid protein values than those in the AFM-ad category, but this was the only cerebrospinal fluid difference between the two groups.

All patients categorized as having rAFM had an infectious prodrome – such as viral syndrome, fever, congestion, and cough – compared with 63.6% of the patients categorized as AFM-ad. The pathogen was identified in only 13 of the rAFM patients, and included 5 patients with enterovirus D68, 2 with unspecified enterovirus, 2 with rhinovirus, 2 with adenovirus, and 2 with mycoplasma. Of the three patients in the AFM-ad group whose pathogen was identified, one had an untyped rhinovirus/enterovirus and mycoplasma, one had a rhinovirus B, and one had enterovirus D68.

“These results highlight that the CDC case definition, while appropriately sensitive for epidemiologic ascertainment of possible AFM cases, also encompasses other neurologic diseases that can cause acute weakness,” the authors wrote. However, they acknowledged that acute flaccid myelitis was still poorly understood and their own definition of the disease may change as more children are diagnosed.

“We propose that the definition of rAFM presented here be used as a starting point for developing inclusion and exclusion criteria for future research studies of AFM,” they wrote.

The study was supported by Johns Hopkins University, the Bart McLean Fund for Neuroimmunology Research, and Project Restore. Two authors reported funding from private industry outside the submitted work and five reported support from or involvement with research and funding bodies.

SOURCE: Elrick MJ et al. JAMA Pediatr. 2018 Nov 30. doi: 10.1001/jamapediatrics.2018.4890.
 

The NIH and DoD are working on a new database that aims to establish the number of people in the US living with limb loss and to provide insight on their challenges and needs.

The Limb Loss and Preservation Registry, expected to be operational in 2020, will address a “significant public health knowledge gap,” said Dr. Alison Cernich, director of the National Center for Medical Rehabilitation Research. She says the information housed in the database will be vital to preventing limb loss, improving amputation surgeries, refining rehabilitation approaches, and guiding the development of devices for people who have lost limbs. Researchers will be able to sort the data by age, gender, and type of limb loss.

The National Institute of Child Health and Human Development has awarded a 5-year contract, capped at $5 million, to the Mayo Clinic to develop and launch the registry.

The NIH and DoD chose to join resources because there are not enough amputations within the DoD alone to provide a suitable sample for statistically valid conclusions, Dr. Cernich said. Moreover, data available from the DoD and the VA do not include service members who leave the military and seek care in the private sector. Cernich says the partnership between federal agencies will allow them to collect data that will “inform research and improve the lives of all citizens coping with limb loss.”

The NIH and DoD are working on a new database that aims to establish the number of people in the US living with limb loss and to provide insight on their challenges and needs.

The Limb Loss and Preservation Registry, expected to be operational in 2020, will address a “significant public health knowledge gap,” said Dr. Alison Cernich, director of the National Center for Medical Rehabilitation Research. She says the information housed in the database will be vital to preventing limb loss, improving amputation surgeries, refining rehabilitation approaches, and guiding the development of devices for people who have lost limbs. Researchers will be able to sort the data by age, gender, and type of limb loss.

The National Institute of Child Health and Human Development has awarded a 5-year contract, capped at $5 million, to the Mayo Clinic to develop and launch the registry.

The NIH and DoD chose to join resources because there are not enough amputations within the DoD alone to provide a suitable sample for statistically valid conclusions, Dr. Cernich said. Moreover, data available from the DoD and the VA do not include service members who leave the military and seek care in the private sector. Cernich says the partnership between federal agencies will allow them to collect data that will “inform research and improve the lives of all citizens coping with limb loss.”

The NIH and DoD are working on a new database that aims to establish the number of people in the US living with limb loss and to provide insight on their challenges and needs.

The Limb Loss and Preservation Registry, expected to be operational in 2020, will address a “significant public health knowledge gap,” said Dr. Alison Cernich, director of the National Center for Medical Rehabilitation Research. She says the information housed in the database will be vital to preventing limb loss, improving amputation surgeries, refining rehabilitation approaches, and guiding the development of devices for people who have lost limbs. Researchers will be able to sort the data by age, gender, and type of limb loss.

The National Institute of Child Health and Human Development has awarded a 5-year contract, capped at $5 million, to the Mayo Clinic to develop and launch the registry.

The NIH and DoD chose to join resources because there are not enough amputations within the DoD alone to provide a suitable sample for statistically valid conclusions, Dr. Cernich said. Moreover, data available from the DoD and the VA do not include service members who leave the military and seek care in the private sector. Cernich says the partnership between federal agencies will allow them to collect data that will “inform research and improve the lives of all citizens coping with limb loss.”

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.

Instances of stroke and arterial dissection in the head and neck have been reported in some multiple sclerosis patients soon after an infusion of alemtuzumab (Lemtrada), according to a safety announcement issued by the Food and Drug Administration on Nov. 29.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Since the FDA approved alemtuzumab in 2014 for relapsing forms of MS, 13 cases of ischemic and hemorrhagic stroke or arterial dissection have been reported worldwide via the FDA Adverse Event Reporting System, but “additional cases we are unaware of may have occurred,” the FDA said in the announcement.

Most of the patients who developed stroke or arterial lining tears showed symptoms within a day of taking the medication, although one patient reported symptoms three days after treatment. The drug is given via intravenous infusion and is generally reserved for patients with relapsing MS who have not responded adequately to other approved MS medications, according to the FDA.

Symptoms include sudden onset of the following: severe headache or neck pain; numbness or weakness in the arms or legs, especially on only one side of the body; confusion or trouble speaking or understanding speech; vision problems in one or both eyes; and dizziness, loss of balance, or difficulty walking.

As a result of the reports, the FDA has updated the drug label prescribing information and the patient Medication Guide to reflect these risks, and added the risk of stroke to the medication’s existing boxed warning.

Health care providers should remind patients of the potential for stroke and arterial dissection at each treatment visit and advise them to seek immediate medical attention if they experience any of the symptoms reported in previous cases. “The diagnosis is often complicated because early symptoms such as headache and neck pain are not specific,” according to the agency, but patients complaining of such symptoms should be evaluated immediately.

Alemtuzumab was also approved in May 2001 for treating B-cell chronic lymphocytic leukemia (B-CLL) under the brand name Campath. The FDA will update the Campath label to reflect the new warnings and risks.