The gepants and monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) and its receptor appear to be effective, tolerable and safe, according to several posters recently presented at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia. Information was presented on the 3 gepants being studied for US Food and Drug Administration (FDA) approval: 1 for acute care of migraine, 1 for prevention and 1 for both (though the presented data for rimegepant only covers acute care).

All drugs cause a small degree of adverse events (AEs), somewhat more than placebo. Based on the presented data, it seems that those associated with 3 times higher than normal elevation of liver enzymes, were usually not found to be the cause of that elevation. At no time was bilirubin elevated. This shows that all of these gepants appear to be effective and safe, despite the fact that some were found to have cause liver toxicity many years ago.

The first gepant study to be published was on olcegepant in 2004, in the New England Journal of Medicine. Professor Jes Olesen, MD, was the lead author of the study, which detailed the efficacy and safety of this small molecule CGRP receptor antagonist. Olcegepant was in an intravenous formulation and the plan was to convert it to a tablet, which never happened. Another company then produced telcagepant as a tablet and it was shown to be safe and effective in 2 large, multicenter, double-blind trials. Before receiving FDA approval for the acute care of migraine, it was studied on a daily basis for migraine prevention. It was found to cause some liver toxicity, so development was stopped. At that time several other gepants in development were placed on the shelf, partially for the fear of liver toxicity. The FDA is unlikely to approve a drug with significant liver toxicity, which can cause a range of symptoms including jaundice, itching, abdominal pain, fatigue, loss of appetite, nausea, vomiting, rash, and weight loss.

In the next few years we will have 4 mAbs for the prevention of migraine, and 3 gepants if all studies are positive. Below are the key takeaways from the presented posters on ubrogepant and atogepant, as information that is currently available on rimegepant.
 

Key Takeaways:

• Ubrogepant – Ailani J, Hutchinson S, Lipton R, et al.
  • Intermittent use of ubrogepant for the acute treatment of migraine over 1 year was well-tolerated with no identified safety concerns. Throughout the 1-year, Phase III study of 1254 participants, 22,454 migraine attacks were treated with 31,968 doses of ubrogepant.
  • Twenty cases of ALT/AST ≥3x ULN were reported and adjudicated by an independent panel of liver experts blinded to treatment.
  • Of the 20 cases, 17 (4 usual care, 3 ubrogepant 50-mg, and 10 ubrogepant 100-mg) were determined to be unlikely related based on plausible alternative etiology/confounding factors.
  • Just 2 cases (both ubrogepant 50-mg) were described as possibly related to study medication and 1 case (ubrogepant 100-mg) was adjudicated as probably related; however, confounding factors were noted.
  • All cases were asymptomatic with no concurrent bilirubin elevation. ALT/AST elevations resolved in those who continued dosing.
     
• Atogepant – Goadsby PJ, Dodick DW, Trugman JM, et al.
  • In a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of adults with a history of migraine, with or without aura, atogepant was well tolerated with no treatment-related serious AEs.
  • Of the 834 randomized subjects, 825 were evaluated in the safety population. Treatment-emergent AEs were reported by 480 subjects (58.2%), and for 170 (20.6%), the AEs were considered treatment-related. Seven subjects (0.8%) reported serious AEs, but none were determined as treatment related.
  • There were 10 cases of treatment-emergent ALT/AST elevations >3x the upper limit of normal, and this was balanced across the treatment dosage groups (10 mg QD, 30 mg QD, 30 mg BID, 60 mg QD, and 60 mg BID).
     
• Rimegepant – See Biogen press release for more information
  • In December 2019, Biohaven announced initial positive results from an ongoing long-term, open-label safety study for rimegepant.
  • The interim results included hepatic safety and tolerability data of rimegepant 75 mg in study participants based on a review of adverse events and regularly scheduled liver function tests.
  • A panel of external independent liver experts provided a consensus based on the Drug-Induced Liver Injury Network (DILIN) causality assessment, determining that there were no liver cases probably related to the study drug and that there were no Hy’s Law cases identified.
  • The panel also concluded that there were no liver safety signals detected and that, compared to placebo arms of other migraine treatments, there was a very low incidence of overall elevations of liver abnormalities.

The gepants and monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) and its receptor appear to be effective, tolerable and safe, according to several posters recently presented at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia. Information was presented on the 3 gepants being studied for US Food and Drug Administration (FDA) approval: 1 for acute care of migraine, 1 for prevention and 1 for both (though the presented data for rimegepant only covers acute care).

All drugs cause a small degree of adverse events (AEs), somewhat more than placebo. Based on the presented data, it seems that those associated with 3 times higher than normal elevation of liver enzymes, were usually not found to be the cause of that elevation. At no time was bilirubin elevated. This shows that all of these gepants appear to be effective and safe, despite the fact that some were found to have cause liver toxicity many years ago.

The first gepant study to be published was on olcegepant in 2004, in the New England Journal of Medicine. Professor Jes Olesen, MD, was the lead author of the study, which detailed the efficacy and safety of this small molecule CGRP receptor antagonist. Olcegepant was in an intravenous formulation and the plan was to convert it to a tablet, which never happened. Another company then produced telcagepant as a tablet and it was shown to be safe and effective in 2 large, multicenter, double-blind trials. Before receiving FDA approval for the acute care of migraine, it was studied on a daily basis for migraine prevention. It was found to cause some liver toxicity, so development was stopped. At that time several other gepants in development were placed on the shelf, partially for the fear of liver toxicity. The FDA is unlikely to approve a drug with significant liver toxicity, which can cause a range of symptoms including jaundice, itching, abdominal pain, fatigue, loss of appetite, nausea, vomiting, rash, and weight loss.

In the next few years we will have 4 mAbs for the prevention of migraine, and 3 gepants if all studies are positive. Below are the key takeaways from the presented posters on ubrogepant and atogepant, as information that is currently available on rimegepant.
 

Key Takeaways:

• Ubrogepant – Ailani J, Hutchinson S, Lipton R, et al.
  • Intermittent use of ubrogepant for the acute treatment of migraine over 1 year was well-tolerated with no identified safety concerns. Throughout the 1-year, Phase III study of 1254 participants, 22,454 migraine attacks were treated with 31,968 doses of ubrogepant.
  • Twenty cases of ALT/AST ≥3x ULN were reported and adjudicated by an independent panel of liver experts blinded to treatment.
  • Of the 20 cases, 17 (4 usual care, 3 ubrogepant 50-mg, and 10 ubrogepant 100-mg) were determined to be unlikely related based on plausible alternative etiology/confounding factors.
  • Just 2 cases (both ubrogepant 50-mg) were described as possibly related to study medication and 1 case (ubrogepant 100-mg) was adjudicated as probably related; however, confounding factors were noted.
  • All cases were asymptomatic with no concurrent bilirubin elevation. ALT/AST elevations resolved in those who continued dosing.
     
• Atogepant – Goadsby PJ, Dodick DW, Trugman JM, et al.
  • In a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of adults with a history of migraine, with or without aura, atogepant was well tolerated with no treatment-related serious AEs.
  • Of the 834 randomized subjects, 825 were evaluated in the safety population. Treatment-emergent AEs were reported by 480 subjects (58.2%), and for 170 (20.6%), the AEs were considered treatment-related. Seven subjects (0.8%) reported serious AEs, but none were determined as treatment related.
  • There were 10 cases of treatment-emergent ALT/AST elevations >3x the upper limit of normal, and this was balanced across the treatment dosage groups (10 mg QD, 30 mg QD, 30 mg BID, 60 mg QD, and 60 mg BID).
     
• Rimegepant – See Biogen press release for more information
  • In December 2019, Biohaven announced initial positive results from an ongoing long-term, open-label safety study for rimegepant.
  • The interim results included hepatic safety and tolerability data of rimegepant 75 mg in study participants based on a review of adverse events and regularly scheduled liver function tests.
  • A panel of external independent liver experts provided a consensus based on the Drug-Induced Liver Injury Network (DILIN) causality assessment, determining that there were no liver cases probably related to the study drug and that there were no Hy’s Law cases identified.
  • The panel also concluded that there were no liver safety signals detected and that, compared to placebo arms of other migraine treatments, there was a very low incidence of overall elevations of liver abnormalities.

The gepants and monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) and its receptor appear to be effective, tolerable and safe, according to several posters recently presented at the 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia. Information was presented on the 3 gepants being studied for US Food and Drug Administration (FDA) approval: 1 for acute care of migraine, 1 for prevention and 1 for both (though the presented data for rimegepant only covers acute care).

All drugs cause a small degree of adverse events (AEs), somewhat more than placebo. Based on the presented data, it seems that those associated with 3 times higher than normal elevation of liver enzymes, were usually not found to be the cause of that elevation. At no time was bilirubin elevated. This shows that all of these gepants appear to be effective and safe, despite the fact that some were found to have cause liver toxicity many years ago.

The first gepant study to be published was on olcegepant in 2004, in the New England Journal of Medicine. Professor Jes Olesen, MD, was the lead author of the study, which detailed the efficacy and safety of this small molecule CGRP receptor antagonist. Olcegepant was in an intravenous formulation and the plan was to convert it to a tablet, which never happened. Another company then produced telcagepant as a tablet and it was shown to be safe and effective in 2 large, multicenter, double-blind trials. Before receiving FDA approval for the acute care of migraine, it was studied on a daily basis for migraine prevention. It was found to cause some liver toxicity, so development was stopped. At that time several other gepants in development were placed on the shelf, partially for the fear of liver toxicity. The FDA is unlikely to approve a drug with significant liver toxicity, which can cause a range of symptoms including jaundice, itching, abdominal pain, fatigue, loss of appetite, nausea, vomiting, rash, and weight loss.

In the next few years we will have 4 mAbs for the prevention of migraine, and 3 gepants if all studies are positive. Below are the key takeaways from the presented posters on ubrogepant and atogepant, as information that is currently available on rimegepant.
 

Key Takeaways:

• Ubrogepant – Ailani J, Hutchinson S, Lipton R, et al.
  • Intermittent use of ubrogepant for the acute treatment of migraine over 1 year was well-tolerated with no identified safety concerns. Throughout the 1-year, Phase III study of 1254 participants, 22,454 migraine attacks were treated with 31,968 doses of ubrogepant.
  • Twenty cases of ALT/AST ≥3x ULN were reported and adjudicated by an independent panel of liver experts blinded to treatment.
  • Of the 20 cases, 17 (4 usual care, 3 ubrogepant 50-mg, and 10 ubrogepant 100-mg) were determined to be unlikely related based on plausible alternative etiology/confounding factors.
  • Just 2 cases (both ubrogepant 50-mg) were described as possibly related to study medication and 1 case (ubrogepant 100-mg) was adjudicated as probably related; however, confounding factors were noted.
  • All cases were asymptomatic with no concurrent bilirubin elevation. ALT/AST elevations resolved in those who continued dosing.
     
• Atogepant – Goadsby PJ, Dodick DW, Trugman JM, et al.
  • In a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of adults with a history of migraine, with or without aura, atogepant was well tolerated with no treatment-related serious AEs.
  • Of the 834 randomized subjects, 825 were evaluated in the safety population. Treatment-emergent AEs were reported by 480 subjects (58.2%), and for 170 (20.6%), the AEs were considered treatment-related. Seven subjects (0.8%) reported serious AEs, but none were determined as treatment related.
  • There were 10 cases of treatment-emergent ALT/AST elevations >3x the upper limit of normal, and this was balanced across the treatment dosage groups (10 mg QD, 30 mg QD, 30 mg BID, 60 mg QD, and 60 mg BID).
     
• Rimegepant – See Biogen press release for more information
  • In December 2019, Biohaven announced initial positive results from an ongoing long-term, open-label safety study for rimegepant.
  • The interim results included hepatic safety and tolerability data of rimegepant 75 mg in study participants based on a review of adverse events and regularly scheduled liver function tests.
  • A panel of external independent liver experts provided a consensus based on the Drug-Induced Liver Injury Network (DILIN) causality assessment, determining that there were no liver cases probably related to the study drug and that there were no Hy’s Law cases identified.
  • The panel also concluded that there were no liver safety signals detected and that, compared to placebo arms of other migraine treatments, there was a very low incidence of overall elevations of liver abnormalities.

CRYSTAL CITY, VA. – Individuals with mood disorders might have an altered microbiome, but more information is needed to understand how the microorganisms that make up the microbiome affect patients’ health, an expert said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“An increased understanding of the neurobiology of the microbiome is required so that the benefit that these microorganisms serve to human health can be fully harnessed,” said Emily G. Severance, PhD, assistant professor of pediatrics at John Hopkins University, Baltimore.

Diseases that involve the microbiome include those with a single identifiable infectious agent that produces persistent inflammation, central nervous system diseases with mucosal surface involvement, and diseases with “variable response to antibiotic and anti-inflammatory agents.”

“It’s becoming clear that [the microbiome is] integral for the modulation of the central nervous system,” which occurs through neurotransmitter production, Dr. Severance said at the meeting presented by Global Academy for Medical Education.

“We have an extensive enteric nervous system that has the very same receptors that the brain does,” she said. “If you have those receptors activated in the gut or [are] having the neurotransmitters produced in the gut, and if there’s a way for those neurotransmitters to reach the brain, that’s a very powerful mechanism to illustrate the gut-brain axis.”

In addition to neuropsychiatric diseases, the microbiome also can be involved in inflammatory gastrointestinal, systemic rheumatoid and autoimmune, chronic inflammatory lung, and periodontal diseases, as well as immune-mediated skin disorders. Mood disorders in particular have evidence for dysbiosis in low-level inflammation and leaky gut pathology, which is present in patients with depression, Dr. Severance said. “All these data suggest that there’s a viable rationale to try to harness the functional significance of the microbial community. We can do that because gut bacteria are easily accessed and can be altered through probiotics, prebiotics, diet, and fecal transplant, and in patients, Lactobacillus and Bifidobacterium combinations may improve mood, reduce anxiety, and enhance cognitive function.”

In addition, epidemiological studies show that antibiotic exposure can be a risk factor for developing mood disorders. One recent study found that anti-infective agents, particularly antibiotics, increased the risk of schizophrenia (hazard rate ratio, 2.05; 95% confidence interval, 1.77-2.38) and affective disorders (HRR, 2.59; 95% CI, 2.31-2.89), which the researchers attributed to brain inflammation, the microbiome, and environmental factors (Acta Psychiatr Scand. 2016 Nov 21. doi: 10.1111/acps.12671). In mice, other researchers found that those that received a fecal transplant with a “depression microbiota” showed symptoms of major depressive disorder, compared with mice that received a “healthy microbiota.” Those results suggest that change in microbiota can induce mood disorders (Mol Psychiatry. 2016 Apr 12. doi: 10.1038/mp.2016.44).


The evidence for probiotics is mixed, primarily because the study population in trials are so heterogeneous, but there is evidence for its efficacy in patients with mood disorders, Dr. Severance said. Probiotics have been shown to prevent rehospitalization for patients in mania. For example, one study showed reduced rehospitalization in patients with mania (8 of 33 patients) who received probiotics, compared with placebo (24 of 33 patients). Also, probiotic use was associated with fewer days of rehospitalization (Bipolar Disord. 2018 Apr 25. doi: 10. 1111/bdi.12652).

Meanwhile, a pilot study analyzing patients with irritable bowel syndrome and mild to moderate anxiety and/or depression found use of B. longum in this population reduced depression scores, but not anxiety or irritable bowel syndrome symptoms, compared with placebo (Gastroenterology. 2017 May 5. doi: 10.1053/j.gastro.2017.05.003).

Probiotic efficacy can be variable for patients with mood disorders, but the intervention is a “relatively low-risk, potentially high reward” option for these patients, Dr. Severance said. “Clinicians should inquire about patient GI conditions and overall GI health. Dietary interventions and the use of probiotics and their limitations should be discussed as supplemental therapeutic options.”

Dr. Severance reported no relevant financial disclosures.

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

CRYSTAL CITY, VA. – Individuals with mood disorders might have an altered microbiome, but more information is needed to understand how the microorganisms that make up the microbiome affect patients’ health, an expert said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“An increased understanding of the neurobiology of the microbiome is required so that the benefit that these microorganisms serve to human health can be fully harnessed,” said Emily G. Severance, PhD, assistant professor of pediatrics at John Hopkins University, Baltimore.

Diseases that involve the microbiome include those with a single identifiable infectious agent that produces persistent inflammation, central nervous system diseases with mucosal surface involvement, and diseases with “variable response to antibiotic and anti-inflammatory agents.”

“It’s becoming clear that [the microbiome is] integral for the modulation of the central nervous system,” which occurs through neurotransmitter production, Dr. Severance said at the meeting presented by Global Academy for Medical Education.

“We have an extensive enteric nervous system that has the very same receptors that the brain does,” she said. “If you have those receptors activated in the gut or [are] having the neurotransmitters produced in the gut, and if there’s a way for those neurotransmitters to reach the brain, that’s a very powerful mechanism to illustrate the gut-brain axis.”

In addition to neuropsychiatric diseases, the microbiome also can be involved in inflammatory gastrointestinal, systemic rheumatoid and autoimmune, chronic inflammatory lung, and periodontal diseases, as well as immune-mediated skin disorders. Mood disorders in particular have evidence for dysbiosis in low-level inflammation and leaky gut pathology, which is present in patients with depression, Dr. Severance said. “All these data suggest that there’s a viable rationale to try to harness the functional significance of the microbial community. We can do that because gut bacteria are easily accessed and can be altered through probiotics, prebiotics, diet, and fecal transplant, and in patients, Lactobacillus and Bifidobacterium combinations may improve mood, reduce anxiety, and enhance cognitive function.”

In addition, epidemiological studies show that antibiotic exposure can be a risk factor for developing mood disorders. One recent study found that anti-infective agents, particularly antibiotics, increased the risk of schizophrenia (hazard rate ratio, 2.05; 95% confidence interval, 1.77-2.38) and affective disorders (HRR, 2.59; 95% CI, 2.31-2.89), which the researchers attributed to brain inflammation, the microbiome, and environmental factors (Acta Psychiatr Scand. 2016 Nov 21. doi: 10.1111/acps.12671). In mice, other researchers found that those that received a fecal transplant with a “depression microbiota” showed symptoms of major depressive disorder, compared with mice that received a “healthy microbiota.” Those results suggest that change in microbiota can induce mood disorders (Mol Psychiatry. 2016 Apr 12. doi: 10.1038/mp.2016.44).


The evidence for probiotics is mixed, primarily because the study population in trials are so heterogeneous, but there is evidence for its efficacy in patients with mood disorders, Dr. Severance said. Probiotics have been shown to prevent rehospitalization for patients in mania. For example, one study showed reduced rehospitalization in patients with mania (8 of 33 patients) who received probiotics, compared with placebo (24 of 33 patients). Also, probiotic use was associated with fewer days of rehospitalization (Bipolar Disord. 2018 Apr 25. doi: 10. 1111/bdi.12652).

Meanwhile, a pilot study analyzing patients with irritable bowel syndrome and mild to moderate anxiety and/or depression found use of B. longum in this population reduced depression scores, but not anxiety or irritable bowel syndrome symptoms, compared with placebo (Gastroenterology. 2017 May 5. doi: 10.1053/j.gastro.2017.05.003).

Probiotic efficacy can be variable for patients with mood disorders, but the intervention is a “relatively low-risk, potentially high reward” option for these patients, Dr. Severance said. “Clinicians should inquire about patient GI conditions and overall GI health. Dietary interventions and the use of probiotics and their limitations should be discussed as supplemental therapeutic options.”

Dr. Severance reported no relevant financial disclosures.

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

CRYSTAL CITY, VA. – Individuals with mood disorders might have an altered microbiome, but more information is needed to understand how the microorganisms that make up the microbiome affect patients’ health, an expert said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“An increased understanding of the neurobiology of the microbiome is required so that the benefit that these microorganisms serve to human health can be fully harnessed,” said Emily G. Severance, PhD, assistant professor of pediatrics at John Hopkins University, Baltimore.

Diseases that involve the microbiome include those with a single identifiable infectious agent that produces persistent inflammation, central nervous system diseases with mucosal surface involvement, and diseases with “variable response to antibiotic and anti-inflammatory agents.”

“It’s becoming clear that [the microbiome is] integral for the modulation of the central nervous system,” which occurs through neurotransmitter production, Dr. Severance said at the meeting presented by Global Academy for Medical Education.

“We have an extensive enteric nervous system that has the very same receptors that the brain does,” she said. “If you have those receptors activated in the gut or [are] having the neurotransmitters produced in the gut, and if there’s a way for those neurotransmitters to reach the brain, that’s a very powerful mechanism to illustrate the gut-brain axis.”

In addition to neuropsychiatric diseases, the microbiome also can be involved in inflammatory gastrointestinal, systemic rheumatoid and autoimmune, chronic inflammatory lung, and periodontal diseases, as well as immune-mediated skin disorders. Mood disorders in particular have evidence for dysbiosis in low-level inflammation and leaky gut pathology, which is present in patients with depression, Dr. Severance said. “All these data suggest that there’s a viable rationale to try to harness the functional significance of the microbial community. We can do that because gut bacteria are easily accessed and can be altered through probiotics, prebiotics, diet, and fecal transplant, and in patients, Lactobacillus and Bifidobacterium combinations may improve mood, reduce anxiety, and enhance cognitive function.”

In addition, epidemiological studies show that antibiotic exposure can be a risk factor for developing mood disorders. One recent study found that anti-infective agents, particularly antibiotics, increased the risk of schizophrenia (hazard rate ratio, 2.05; 95% confidence interval, 1.77-2.38) and affective disorders (HRR, 2.59; 95% CI, 2.31-2.89), which the researchers attributed to brain inflammation, the microbiome, and environmental factors (Acta Psychiatr Scand. 2016 Nov 21. doi: 10.1111/acps.12671). In mice, other researchers found that those that received a fecal transplant with a “depression microbiota” showed symptoms of major depressive disorder, compared with mice that received a “healthy microbiota.” Those results suggest that change in microbiota can induce mood disorders (Mol Psychiatry. 2016 Apr 12. doi: 10.1038/mp.2016.44).


The evidence for probiotics is mixed, primarily because the study population in trials are so heterogeneous, but there is evidence for its efficacy in patients with mood disorders, Dr. Severance said. Probiotics have been shown to prevent rehospitalization for patients in mania. For example, one study showed reduced rehospitalization in patients with mania (8 of 33 patients) who received probiotics, compared with placebo (24 of 33 patients). Also, probiotic use was associated with fewer days of rehospitalization (Bipolar Disord. 2018 Apr 25. doi: 10. 1111/bdi.12652).

Meanwhile, a pilot study analyzing patients with irritable bowel syndrome and mild to moderate anxiety and/or depression found use of B. longum in this population reduced depression scores, but not anxiety or irritable bowel syndrome symptoms, compared with placebo (Gastroenterology. 2017 May 5. doi: 10.1053/j.gastro.2017.05.003).

Probiotic efficacy can be variable for patients with mood disorders, but the intervention is a “relatively low-risk, potentially high reward” option for these patients, Dr. Severance said. “Clinicians should inquire about patient GI conditions and overall GI health. Dietary interventions and the use of probiotics and their limitations should be discussed as supplemental therapeutic options.”

Dr. Severance reported no relevant financial disclosures.

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

AMSTERDAM – For patients with low-risk myelodysplastic syndrome (MDS) for whom erythropoietin therapy has failed, the novel telomerase inhibitor imetelstat may provide long-lasting independence from transfusion, investigators reported.

Neil Osterweil/MDedge News

Among 38 patients with low-risk MDS who had relapsed or were refractory to treatment with an erythropoiesis stimulating agent (ESA) who received imetelstat, 16 (42%) were free from the need for transfusion for at least 8 weeks, with one patient being transfusion free for up to 141 weeks, reported Pierre Fenaux, MD, of Hôpital Saint-Louis in Paris.

Patients with a generally worse prognosis “tended to respond better to imetelstat in terms of transfusion independence, which suggests that the drug is promising for higher-risk MDS,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

Imetelstat is a first-in-class telomerase inhibitor targeting cells with short telomere lengths and active telomerase, the enzyme that maintains telomere length. Higher telomerase activity and shorter telomeres are predictive of shorter overall survival in patients with MDS, Dr. Fenaux explained.

He and colleagues enrolled 38 patients, median age 71.5 years, with low-risk MDS, with an International Prognostic Scoring System (IPSS) score of low or intermediate-1, whose disease was relapsed or refractory to ESA or to erythropoietin at a dose of more than 500 mU/mL. Of this group, 24 patients had IPSS low disease, 14 had intermediate-1 disease.

The median transfusion burden was 8 units per 8 weeks (range 4-14). The majority of patients (34, or 89%) had received prior ESAs.

The patients were transfusion dependent, defined as the need for 4 or more units of red blood cells within 8 weeks over the 16 weeks prior to study entry.

No patients had the 5q deletion, and no patients had received either a hypomethylating agent or lenolidamide (Revlimid), neither of which are approved for this indication in Europe.

The patients received imetelstat 7.5 mg/kg intravenously every 4 weeks.

As noted earlier, 16 patients (42%) achieved the primary endpoint of 8-week transfusion independence, with a median duration of 85.9 weeks (range 8-141 weeks).

Eleven patients (29%) had transfusion independence lasting at least 24 weeks – a secondary endpoint – and 26 (68%) met International Working Group 2006 criteria for a HI-E (erythroid) response, with 12 of these patients having an increase in hemoglobin of 1.5 g/dL or greater lasting for at least 8 weeks, and all 26 having a reduction in transfusions of 4 or more units over 8 weeks.

There was evidence to suggest a disease-modifying effect of imetelstat, with five patients achieving a complete response (CR), and five having a marrow CR.

The most frequent adverse events were manageable and reversible grade 3 or greater cytopenias, but there were no new safety signals seen. Two patients were hospitalized for febrile neutropenia, but there were no treatment-related deaths.

Based on these results, investigators are planning a phase 3 study comparing imetelstat with placebo in a 2:1 ratio. The trial is scheduled to begin in the late summer or fall of 2019.

When asked if imetelstat might have off-target effects by inhibiting telomerase in other cells, Dr. Fenaux replied that the mechanism of action is unclear, and that its potential effects on erythropoiesis are still unknown.

Neil Osterweil/MDedge News

Briefing moderator Anton Hagenbeek, MD, of Amsterdam University Medical Center, commented on the drug’s potential for treating MDS, and asked whether investigators are considering combining it with other therapies for MDS.

“I think the first step will be to study it in high-risk MDS as a single agent before combining it, including with hypomethylating agents, et cetera,” Dr. Fenaux replied.

SOURCE: Fenaux P et al. EHA 2019, Abstract S837.

AMSTERDAM – For patients with low-risk myelodysplastic syndrome (MDS) for whom erythropoietin therapy has failed, the novel telomerase inhibitor imetelstat may provide long-lasting independence from transfusion, investigators reported.

Neil Osterweil/MDedge News

Among 38 patients with low-risk MDS who had relapsed or were refractory to treatment with an erythropoiesis stimulating agent (ESA) who received imetelstat, 16 (42%) were free from the need for transfusion for at least 8 weeks, with one patient being transfusion free for up to 141 weeks, reported Pierre Fenaux, MD, of Hôpital Saint-Louis in Paris.

Patients with a generally worse prognosis “tended to respond better to imetelstat in terms of transfusion independence, which suggests that the drug is promising for higher-risk MDS,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

Imetelstat is a first-in-class telomerase inhibitor targeting cells with short telomere lengths and active telomerase, the enzyme that maintains telomere length. Higher telomerase activity and shorter telomeres are predictive of shorter overall survival in patients with MDS, Dr. Fenaux explained.

He and colleagues enrolled 38 patients, median age 71.5 years, with low-risk MDS, with an International Prognostic Scoring System (IPSS) score of low or intermediate-1, whose disease was relapsed or refractory to ESA or to erythropoietin at a dose of more than 500 mU/mL. Of this group, 24 patients had IPSS low disease, 14 had intermediate-1 disease.

The median transfusion burden was 8 units per 8 weeks (range 4-14). The majority of patients (34, or 89%) had received prior ESAs.

The patients were transfusion dependent, defined as the need for 4 or more units of red blood cells within 8 weeks over the 16 weeks prior to study entry.

No patients had the 5q deletion, and no patients had received either a hypomethylating agent or lenolidamide (Revlimid), neither of which are approved for this indication in Europe.

The patients received imetelstat 7.5 mg/kg intravenously every 4 weeks.

As noted earlier, 16 patients (42%) achieved the primary endpoint of 8-week transfusion independence, with a median duration of 85.9 weeks (range 8-141 weeks).

Eleven patients (29%) had transfusion independence lasting at least 24 weeks – a secondary endpoint – and 26 (68%) met International Working Group 2006 criteria for a HI-E (erythroid) response, with 12 of these patients having an increase in hemoglobin of 1.5 g/dL or greater lasting for at least 8 weeks, and all 26 having a reduction in transfusions of 4 or more units over 8 weeks.

There was evidence to suggest a disease-modifying effect of imetelstat, with five patients achieving a complete response (CR), and five having a marrow CR.

The most frequent adverse events were manageable and reversible grade 3 or greater cytopenias, but there were no new safety signals seen. Two patients were hospitalized for febrile neutropenia, but there were no treatment-related deaths.

Based on these results, investigators are planning a phase 3 study comparing imetelstat with placebo in a 2:1 ratio. The trial is scheduled to begin in the late summer or fall of 2019.

When asked if imetelstat might have off-target effects by inhibiting telomerase in other cells, Dr. Fenaux replied that the mechanism of action is unclear, and that its potential effects on erythropoiesis are still unknown.

Neil Osterweil/MDedge News

Briefing moderator Anton Hagenbeek, MD, of Amsterdam University Medical Center, commented on the drug’s potential for treating MDS, and asked whether investigators are considering combining it with other therapies for MDS.

“I think the first step will be to study it in high-risk MDS as a single agent before combining it, including with hypomethylating agents, et cetera,” Dr. Fenaux replied.

SOURCE: Fenaux P et al. EHA 2019, Abstract S837.

AMSTERDAM – For patients with low-risk myelodysplastic syndrome (MDS) for whom erythropoietin therapy has failed, the novel telomerase inhibitor imetelstat may provide long-lasting independence from transfusion, investigators reported.

Neil Osterweil/MDedge News

Among 38 patients with low-risk MDS who had relapsed or were refractory to treatment with an erythropoiesis stimulating agent (ESA) who received imetelstat, 16 (42%) were free from the need for transfusion for at least 8 weeks, with one patient being transfusion free for up to 141 weeks, reported Pierre Fenaux, MD, of Hôpital Saint-Louis in Paris.

Patients with a generally worse prognosis “tended to respond better to imetelstat in terms of transfusion independence, which suggests that the drug is promising for higher-risk MDS,” he said at a briefing prior to his presentation of the data at the annual congress of the European Hematology Association.

Imetelstat is a first-in-class telomerase inhibitor targeting cells with short telomere lengths and active telomerase, the enzyme that maintains telomere length. Higher telomerase activity and shorter telomeres are predictive of shorter overall survival in patients with MDS, Dr. Fenaux explained.

He and colleagues enrolled 38 patients, median age 71.5 years, with low-risk MDS, with an International Prognostic Scoring System (IPSS) score of low or intermediate-1, whose disease was relapsed or refractory to ESA or to erythropoietin at a dose of more than 500 mU/mL. Of this group, 24 patients had IPSS low disease, 14 had intermediate-1 disease.

The median transfusion burden was 8 units per 8 weeks (range 4-14). The majority of patients (34, or 89%) had received prior ESAs.

The patients were transfusion dependent, defined as the need for 4 or more units of red blood cells within 8 weeks over the 16 weeks prior to study entry.

No patients had the 5q deletion, and no patients had received either a hypomethylating agent or lenolidamide (Revlimid), neither of which are approved for this indication in Europe.

The patients received imetelstat 7.5 mg/kg intravenously every 4 weeks.

As noted earlier, 16 patients (42%) achieved the primary endpoint of 8-week transfusion independence, with a median duration of 85.9 weeks (range 8-141 weeks).

Eleven patients (29%) had transfusion independence lasting at least 24 weeks – a secondary endpoint – and 26 (68%) met International Working Group 2006 criteria for a HI-E (erythroid) response, with 12 of these patients having an increase in hemoglobin of 1.5 g/dL or greater lasting for at least 8 weeks, and all 26 having a reduction in transfusions of 4 or more units over 8 weeks.

There was evidence to suggest a disease-modifying effect of imetelstat, with five patients achieving a complete response (CR), and five having a marrow CR.

The most frequent adverse events were manageable and reversible grade 3 or greater cytopenias, but there were no new safety signals seen. Two patients were hospitalized for febrile neutropenia, but there were no treatment-related deaths.

Based on these results, investigators are planning a phase 3 study comparing imetelstat with placebo in a 2:1 ratio. The trial is scheduled to begin in the late summer or fall of 2019.

When asked if imetelstat might have off-target effects by inhibiting telomerase in other cells, Dr. Fenaux replied that the mechanism of action is unclear, and that its potential effects on erythropoiesis are still unknown.

Neil Osterweil/MDedge News

Briefing moderator Anton Hagenbeek, MD, of Amsterdam University Medical Center, commented on the drug’s potential for treating MDS, and asked whether investigators are considering combining it with other therapies for MDS.

“I think the first step will be to study it in high-risk MDS as a single agent before combining it, including with hypomethylating agents, et cetera,” Dr. Fenaux replied.

SOURCE: Fenaux P et al. EHA 2019, Abstract S837.

Case

A 55-year-old male with a history of tobacco use disorder presents with 2 days of productive cough, fever, chills, and mild shortness of breath. T 38.4, HR 89, RR 32, BP 100/65, 02 sat 86% on room air. Exam reveals diminished breath sounds and positive egophony over the right lung base. WBC is 16,000 and BUN 22. Chest x-ray reveals right lower lobe consolidation. He is given ceftriaxone and azithromycin.

Brief overview of the issue

Community-acquired pneumonia (CAP) is the leading cause of infectious disease–related death in the United States. Mortality associated with CAP is estimated at 57,000 deaths annually and occurs largely in patients requiring hospitalization.¹ The 30-day mortality rate in patients who are hospitalized for CAP is approximately 10%-12%.² After discharge from the hospital, about 18% of patients are readmitted within 30 days.³ An excessive inflammatory cytokine response may be a major contributor to the high mortality rate in CAP and systemic corticosteroids may reduce the inflammatory response from the infection by down-regulating this proinflammatory cytokine production.

Almost all of the major decisions regarding management of CAP, including diagnostic and treatment issues, revolve around the initial assessment of severity of illness. Between 40% and 60% of patients who present to the emergency department with CAP are admitted⁴ and approximately 10% of hospitalized patients with CAP require ICU admission.⁵ Validated instruments such as CURB-65, the pneumonia severity index (PSI), and guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) may predict severity of illness but should always be supplemented with physician determination of subjective factors when determining treatment.⁵ Although there is no census definition of severe pneumonia, studies generally define the condition in the following order of preference: PSI score of IV or V followed by CURB-65 score of two or greater. If these scoring modalities were not available, the IDSA/ATS criteria was used (1 major or 3 minor). Others define severe CAP as pneumonia requiring supportive therapy within a critical care environment.
 

Overview of the data

The use of corticosteroids in addition to antibiotics in the treatment of CAP was proposed as early as the 1950s and yet only in the last decade has the body of evidence grown significantly.⁵ There is evidence that corticosteroids suppress inflammation without acutely impairing the immune response as evidenced by a rapid and sustained decrease in circulating inflammatory markers such as C-reactive protein and interleukin 6 and no effect on the anti-inflammatory interleukin 10.⁶ Within the last year, three meta-analyses, one by the Cochrane Library, one by the IDSA, and a third in the American Journal of Emergency Medicine, addressed the role of routine low dose (20-60 mg of prednisone or equivalent), short-course (3-7 days) systemic corticosteroids in hospitalized patients with CAP of varying severities.

The Cochrane meta-analysis, the largest and most recent dataset, included 13 trials with a combined 1,954 adult patients and found that corticosteroids significantly lowered mortality in hospitalized patients with severe CAP with a number needed to treat of 19.⁷ In this group with severe CAP, mortality was lowered from 13% to 8% and there were significantly fewer episodes of respiratory failure and shock with the addition of corticosteroids. No effect was seen on mortality in patients with less severe CAP. In those patients who received adjuvant corticosteroids, length of hospital stay decreased by 3 days, regardless of CAP severity.⁷

The IDSA meta-analysis was similar and included 1,506 patients from six trials.⁸ In contrast with the Cochrane study, this analysis found corticosteroids did not significantly lower mortality in patients with severe CAP but did reduce time to clinical stability and length of hospital stay by over 1 day. This study also found significantly more CAP-related, 30-day rehospitalizations (5% vs. 3%; defined as recurrent pneumonia, other infection, pleuritic pain, adverse cardiovascular event, or diarrhea) in patient with non-severe CAP treated with corticosteroids.

The study in the American Journal of Emergency Medicine involved ten trials involving more than 700 patients admitted with severe CAP and found in-hospital mortality was cut in half (RR 0.49) and length of hospital stay was reduced when patients were treated with corticosteroids in addition to standard antibiotic therapy.⁹

In 2015, two randomized clinical trials, one in the Lancet and the other in JAMA, and a meta-analysis in Annals of Internal Medicine assessed the impact of adjuvant corticosteroids in the treatment of hospitalized patients with CAP. The Lancet study of 785 patients hospitalized with CAP of any severity found shortened time to clinical stability (3.0 vs. 4.4 days) as defined by stable vital signs, improved oral intake, and normalized mental status for greater than 24 hours when oral prednisone 50 mg for 7 days was added to standard therapy.¹⁰ Patients in the treatment group were also discharged 1 day earlier compared with the placebo control group.

The study in JAMA was small, with only 100 patients at three teaching hospitals in Spain, but found that patients hospitalized with severe CAP and high inflammatory response based on elevated C-reactive protein were less likely to experience a treatment failure, defined as shock, mechanical ventilation, death, or radiographic progression, when intravenous methylprednisolone 0.5 mg/kg was added to standard antibiotic therapy.¹¹

Finally, the meta-analysis in Annals of Internal Medicine assessed 13 randomized controlled placebo trials of 1,974 patients and found that adjuvant corticosteroids in a dose of 20-60 mg of prednisone or equivalent total daily dose significantly lowered mortality in patients with severe CAP and incidence of respiratory distress syndrome, and need for mechanical ventilation in all patients hospitalized with CAP.¹²

Importantly, nearly all of the described studies showed a significantly higher incidence of hyperglycemia in patients who received corticosteroids.
 

Application of the data to our patients

The benefit of adjuvant corticosteroids is most clear in hospitalized patients with severe CAP. Recent, strong evidence supports decreased mortality, decreased time to clinical stability, and decreased length of stay in our patient, with severe CAP, if treated with 20-60 mg of prednisone or equivalent total daily dose for 3-7 days. For patients with non-severe CAP, we suggest taking a risk-benefit approach based on other comorbidities, as the risk for CAP-related rehospitalizations may be higher.

For patients with underlying lung disease, specifically COPD or reactive airway disease, we suggest a low threshold for adding corticosteroids. This approach is more anecdotal than data driven, though corticosteroids are a mainstay of treatment for COPD exacerbations and a retrospective analysis of more than 20,000 hospitalized children with CAP and wheezing revealed decreased length of stay with corticosteroid treatment.¹³ Furthermore, a number of the studies described above included patients with COPD. Our threshold rises significantly in patients with poorly controlled diabetes mellitus.
 

Bottom line

For patients hospitalized with severe community-acquired pneumonia, recent evidence supports the use of low dose, short-course, systemic corticosteroids in addition to standard therapy.

Dr. Parsons is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center in Charlottesville, Va. Dr. Miller is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center. Dr. Hoke is Associate Director of Hospital Medicine and Faculty Development at the University of Virginia.

References

1. Ramirez J et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis. 2017 Dec 1:65(11):1806-12.

2. Musher D et al. Community-acquired pneumonia: Review article. N Engl J Med. 2014 Oct 23;371:1619-28.

3. Wunderink R et al. Community-aquired pneumonia: Clinical practice. N Engl J Med. 2014 Feb 6;370:543-51.

4. Mandell L et al. Infectious Diseases Society America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44:S27-72.

5. Wagner HN et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98:197-215.

6. Polverino E et al. Systemic corticosteroids for community-acquired pneumonia: Reasons for use and lack of benefit on outcome. Respirology. 2013. Feb;18(2):263-71 (https://doi.org/10.1111/resp.12013).

7. Stern A et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13; 12:CD007720 (https://doi.org/10.1002/14651858.CD007720.pub3).

8. Briel M et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1;66:346 (https://doi.org/10.1093/cid/cix801).

9. Wu W-F et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2017 Jul 15; [e-pub] (http://dx.doi.org/10.1016/j.ajem.2017.07.050).

10. Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015 Jan 18; [e-pub ahead of print] (http://dx.doi.org/10.1016/S0140-6736[14]62447-8).

11. Torres A et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015 Feb 17; 313:677 (http://dx.doi.org/10.1001/jama.2015.88).

12. Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163:519 (http://dx.doi.org/10.7326/M15-0715).

13. Simon LH et al. Management of community-acquired pneumonia in hospitalized children. Current Treat Options Peds (2015) 1:59 (https://doi:.org/10.1007/s40746-014-0011-3).


 

Key points

• For patients hospitalized with severe CAP, recent evidence supports the use of low-dose, short-course, systemic corticosteroids in addition to standard therapy.

• Among hospitalized patients with non-severe CAP, the benefit is not well defined. Studies suggest these patients may benefit from reduced time to clinical stability and reduced length of hospital stay. However, they may be at risk for significantly more CAP-related, 30-day rehospitalizations and hyperglycemia.

• Further prospective, randomized controlled studies are needed to further delineate the patient population who will most benefit from adjunctive corticosteroids use, including dose and duration of treatment.
 

QUIZ

Which of the following is FALSE regarding community acquired pneumonia?

A. CAP is the leading cause of infectious disease related death in the United States.

B. An excessive inflammatory cytokine response may contribute to the high mortality rate in CAP.

C. Adjunctive steroid therapy has been shown to decrease mortality in all patients with CAP.

D. Hyperglycemia occurs more frequently in patients receiving steroid therapy.

E. Reasons to avoid adjunctive steroid therapy in CAP include low risk for mortality, poorly controlled diabetes, suspected viral or fungal etiology, and elevated risk for gastrointestinal bleeding.



ANSWER: C. The patient population that may benefit most from the use of adjuvant corticosteroids is poorly defined. However, in patients with severe pneumonia, the use of adjuvant steroids has been shown to decrease mortality, time to clinical stability, and length of stay.
 

Additional reading

Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6; 163:519. (http://dx.doi.org/10.7326/M15-0715).

Briel M et al. Corticosteroids in patients hospitalized with community-acquired Pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1; 66:346 (https://doi.org/10.1093/cid/cix801).

Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8).

Feldman C et al. Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials. J Thorac Dis. 2016 Mar; 8(3):E162-E171.

Wan YD et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: A systemic review and meta-analysis. Chest. 2016 Jan;149(1):209-19.
 

Case

A 55-year-old male with a history of tobacco use disorder presents with 2 days of productive cough, fever, chills, and mild shortness of breath. T 38.4, HR 89, RR 32, BP 100/65, 02 sat 86% on room air. Exam reveals diminished breath sounds and positive egophony over the right lung base. WBC is 16,000 and BUN 22. Chest x-ray reveals right lower lobe consolidation. He is given ceftriaxone and azithromycin.

Brief overview of the issue

Community-acquired pneumonia (CAP) is the leading cause of infectious disease–related death in the United States. Mortality associated with CAP is estimated at 57,000 deaths annually and occurs largely in patients requiring hospitalization.¹ The 30-day mortality rate in patients who are hospitalized for CAP is approximately 10%-12%.² After discharge from the hospital, about 18% of patients are readmitted within 30 days.³ An excessive inflammatory cytokine response may be a major contributor to the high mortality rate in CAP and systemic corticosteroids may reduce the inflammatory response from the infection by down-regulating this proinflammatory cytokine production.

Almost all of the major decisions regarding management of CAP, including diagnostic and treatment issues, revolve around the initial assessment of severity of illness. Between 40% and 60% of patients who present to the emergency department with CAP are admitted⁴ and approximately 10% of hospitalized patients with CAP require ICU admission.⁵ Validated instruments such as CURB-65, the pneumonia severity index (PSI), and guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) may predict severity of illness but should always be supplemented with physician determination of subjective factors when determining treatment.⁵ Although there is no census definition of severe pneumonia, studies generally define the condition in the following order of preference: PSI score of IV or V followed by CURB-65 score of two or greater. If these scoring modalities were not available, the IDSA/ATS criteria was used (1 major or 3 minor). Others define severe CAP as pneumonia requiring supportive therapy within a critical care environment.
 

Overview of the data

The use of corticosteroids in addition to antibiotics in the treatment of CAP was proposed as early as the 1950s and yet only in the last decade has the body of evidence grown significantly.⁵ There is evidence that corticosteroids suppress inflammation without acutely impairing the immune response as evidenced by a rapid and sustained decrease in circulating inflammatory markers such as C-reactive protein and interleukin 6 and no effect on the anti-inflammatory interleukin 10.⁶ Within the last year, three meta-analyses, one by the Cochrane Library, one by the IDSA, and a third in the American Journal of Emergency Medicine, addressed the role of routine low dose (20-60 mg of prednisone or equivalent), short-course (3-7 days) systemic corticosteroids in hospitalized patients with CAP of varying severities.

The Cochrane meta-analysis, the largest and most recent dataset, included 13 trials with a combined 1,954 adult patients and found that corticosteroids significantly lowered mortality in hospitalized patients with severe CAP with a number needed to treat of 19.⁷ In this group with severe CAP, mortality was lowered from 13% to 8% and there were significantly fewer episodes of respiratory failure and shock with the addition of corticosteroids. No effect was seen on mortality in patients with less severe CAP. In those patients who received adjuvant corticosteroids, length of hospital stay decreased by 3 days, regardless of CAP severity.⁷

The IDSA meta-analysis was similar and included 1,506 patients from six trials.⁸ In contrast with the Cochrane study, this analysis found corticosteroids did not significantly lower mortality in patients with severe CAP but did reduce time to clinical stability and length of hospital stay by over 1 day. This study also found significantly more CAP-related, 30-day rehospitalizations (5% vs. 3%; defined as recurrent pneumonia, other infection, pleuritic pain, adverse cardiovascular event, or diarrhea) in patient with non-severe CAP treated with corticosteroids.

The study in the American Journal of Emergency Medicine involved ten trials involving more than 700 patients admitted with severe CAP and found in-hospital mortality was cut in half (RR 0.49) and length of hospital stay was reduced when patients were treated with corticosteroids in addition to standard antibiotic therapy.⁹

In 2015, two randomized clinical trials, one in the Lancet and the other in JAMA, and a meta-analysis in Annals of Internal Medicine assessed the impact of adjuvant corticosteroids in the treatment of hospitalized patients with CAP. The Lancet study of 785 patients hospitalized with CAP of any severity found shortened time to clinical stability (3.0 vs. 4.4 days) as defined by stable vital signs, improved oral intake, and normalized mental status for greater than 24 hours when oral prednisone 50 mg for 7 days was added to standard therapy.¹⁰ Patients in the treatment group were also discharged 1 day earlier compared with the placebo control group.

The study in JAMA was small, with only 100 patients at three teaching hospitals in Spain, but found that patients hospitalized with severe CAP and high inflammatory response based on elevated C-reactive protein were less likely to experience a treatment failure, defined as shock, mechanical ventilation, death, or radiographic progression, when intravenous methylprednisolone 0.5 mg/kg was added to standard antibiotic therapy.¹¹

Finally, the meta-analysis in Annals of Internal Medicine assessed 13 randomized controlled placebo trials of 1,974 patients and found that adjuvant corticosteroids in a dose of 20-60 mg of prednisone or equivalent total daily dose significantly lowered mortality in patients with severe CAP and incidence of respiratory distress syndrome, and need for mechanical ventilation in all patients hospitalized with CAP.¹²

Importantly, nearly all of the described studies showed a significantly higher incidence of hyperglycemia in patients who received corticosteroids.
 

Application of the data to our patients

The benefit of adjuvant corticosteroids is most clear in hospitalized patients with severe CAP. Recent, strong evidence supports decreased mortality, decreased time to clinical stability, and decreased length of stay in our patient, with severe CAP, if treated with 20-60 mg of prednisone or equivalent total daily dose for 3-7 days. For patients with non-severe CAP, we suggest taking a risk-benefit approach based on other comorbidities, as the risk for CAP-related rehospitalizations may be higher.

For patients with underlying lung disease, specifically COPD or reactive airway disease, we suggest a low threshold for adding corticosteroids. This approach is more anecdotal than data driven, though corticosteroids are a mainstay of treatment for COPD exacerbations and a retrospective analysis of more than 20,000 hospitalized children with CAP and wheezing revealed decreased length of stay with corticosteroid treatment.¹³ Furthermore, a number of the studies described above included patients with COPD. Our threshold rises significantly in patients with poorly controlled diabetes mellitus.
 

Bottom line

For patients hospitalized with severe community-acquired pneumonia, recent evidence supports the use of low dose, short-course, systemic corticosteroids in addition to standard therapy.

Dr. Parsons is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center in Charlottesville, Va. Dr. Miller is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center. Dr. Hoke is Associate Director of Hospital Medicine and Faculty Development at the University of Virginia.

References

1. Ramirez J et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis. 2017 Dec 1:65(11):1806-12.

2. Musher D et al. Community-acquired pneumonia: Review article. N Engl J Med. 2014 Oct 23;371:1619-28.

3. Wunderink R et al. Community-aquired pneumonia: Clinical practice. N Engl J Med. 2014 Feb 6;370:543-51.

4. Mandell L et al. Infectious Diseases Society America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44:S27-72.

5. Wagner HN et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98:197-215.

6. Polverino E et al. Systemic corticosteroids for community-acquired pneumonia: Reasons for use and lack of benefit on outcome. Respirology. 2013. Feb;18(2):263-71 (https://doi.org/10.1111/resp.12013).

7. Stern A et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13; 12:CD007720 (https://doi.org/10.1002/14651858.CD007720.pub3).

8. Briel M et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1;66:346 (https://doi.org/10.1093/cid/cix801).

9. Wu W-F et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2017 Jul 15; [e-pub] (http://dx.doi.org/10.1016/j.ajem.2017.07.050).

10. Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015 Jan 18; [e-pub ahead of print] (http://dx.doi.org/10.1016/S0140-6736[14]62447-8).

11. Torres A et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015 Feb 17; 313:677 (http://dx.doi.org/10.1001/jama.2015.88).

12. Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163:519 (http://dx.doi.org/10.7326/M15-0715).

13. Simon LH et al. Management of community-acquired pneumonia in hospitalized children. Current Treat Options Peds (2015) 1:59 (https://doi:.org/10.1007/s40746-014-0011-3).


 

Key points

• For patients hospitalized with severe CAP, recent evidence supports the use of low-dose, short-course, systemic corticosteroids in addition to standard therapy.

• Among hospitalized patients with non-severe CAP, the benefit is not well defined. Studies suggest these patients may benefit from reduced time to clinical stability and reduced length of hospital stay. However, they may be at risk for significantly more CAP-related, 30-day rehospitalizations and hyperglycemia.

• Further prospective, randomized controlled studies are needed to further delineate the patient population who will most benefit from adjunctive corticosteroids use, including dose and duration of treatment.
 

QUIZ

Which of the following is FALSE regarding community acquired pneumonia?

A. CAP is the leading cause of infectious disease related death in the United States.

B. An excessive inflammatory cytokine response may contribute to the high mortality rate in CAP.

C. Adjunctive steroid therapy has been shown to decrease mortality in all patients with CAP.

D. Hyperglycemia occurs more frequently in patients receiving steroid therapy.

E. Reasons to avoid adjunctive steroid therapy in CAP include low risk for mortality, poorly controlled diabetes, suspected viral or fungal etiology, and elevated risk for gastrointestinal bleeding.



ANSWER: C. The patient population that may benefit most from the use of adjuvant corticosteroids is poorly defined. However, in patients with severe pneumonia, the use of adjuvant steroids has been shown to decrease mortality, time to clinical stability, and length of stay.
 

Additional reading

Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6; 163:519. (http://dx.doi.org/10.7326/M15-0715).

Briel M et al. Corticosteroids in patients hospitalized with community-acquired Pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1; 66:346 (https://doi.org/10.1093/cid/cix801).

Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8).

Feldman C et al. Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials. J Thorac Dis. 2016 Mar; 8(3):E162-E171.

Wan YD et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: A systemic review and meta-analysis. Chest. 2016 Jan;149(1):209-19.
 

Case

A 55-year-old male with a history of tobacco use disorder presents with 2 days of productive cough, fever, chills, and mild shortness of breath. T 38.4, HR 89, RR 32, BP 100/65, 02 sat 86% on room air. Exam reveals diminished breath sounds and positive egophony over the right lung base. WBC is 16,000 and BUN 22. Chest x-ray reveals right lower lobe consolidation. He is given ceftriaxone and azithromycin.

Brief overview of the issue

Community-acquired pneumonia (CAP) is the leading cause of infectious disease–related death in the United States. Mortality associated with CAP is estimated at 57,000 deaths annually and occurs largely in patients requiring hospitalization.¹ The 30-day mortality rate in patients who are hospitalized for CAP is approximately 10%-12%.² After discharge from the hospital, about 18% of patients are readmitted within 30 days.³ An excessive inflammatory cytokine response may be a major contributor to the high mortality rate in CAP and systemic corticosteroids may reduce the inflammatory response from the infection by down-regulating this proinflammatory cytokine production.

Almost all of the major decisions regarding management of CAP, including diagnostic and treatment issues, revolve around the initial assessment of severity of illness. Between 40% and 60% of patients who present to the emergency department with CAP are admitted⁴ and approximately 10% of hospitalized patients with CAP require ICU admission.⁵ Validated instruments such as CURB-65, the pneumonia severity index (PSI), and guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) may predict severity of illness but should always be supplemented with physician determination of subjective factors when determining treatment.⁵ Although there is no census definition of severe pneumonia, studies generally define the condition in the following order of preference: PSI score of IV or V followed by CURB-65 score of two or greater. If these scoring modalities were not available, the IDSA/ATS criteria was used (1 major or 3 minor). Others define severe CAP as pneumonia requiring supportive therapy within a critical care environment.
 

Overview of the data

The use of corticosteroids in addition to antibiotics in the treatment of CAP was proposed as early as the 1950s and yet only in the last decade has the body of evidence grown significantly.⁵ There is evidence that corticosteroids suppress inflammation without acutely impairing the immune response as evidenced by a rapid and sustained decrease in circulating inflammatory markers such as C-reactive protein and interleukin 6 and no effect on the anti-inflammatory interleukin 10.⁶ Within the last year, three meta-analyses, one by the Cochrane Library, one by the IDSA, and a third in the American Journal of Emergency Medicine, addressed the role of routine low dose (20-60 mg of prednisone or equivalent), short-course (3-7 days) systemic corticosteroids in hospitalized patients with CAP of varying severities.

The Cochrane meta-analysis, the largest and most recent dataset, included 13 trials with a combined 1,954 adult patients and found that corticosteroids significantly lowered mortality in hospitalized patients with severe CAP with a number needed to treat of 19.⁷ In this group with severe CAP, mortality was lowered from 13% to 8% and there were significantly fewer episodes of respiratory failure and shock with the addition of corticosteroids. No effect was seen on mortality in patients with less severe CAP. In those patients who received adjuvant corticosteroids, length of hospital stay decreased by 3 days, regardless of CAP severity.⁷

The IDSA meta-analysis was similar and included 1,506 patients from six trials.⁸ In contrast with the Cochrane study, this analysis found corticosteroids did not significantly lower mortality in patients with severe CAP but did reduce time to clinical stability and length of hospital stay by over 1 day. This study also found significantly more CAP-related, 30-day rehospitalizations (5% vs. 3%; defined as recurrent pneumonia, other infection, pleuritic pain, adverse cardiovascular event, or diarrhea) in patient with non-severe CAP treated with corticosteroids.

The study in the American Journal of Emergency Medicine involved ten trials involving more than 700 patients admitted with severe CAP and found in-hospital mortality was cut in half (RR 0.49) and length of hospital stay was reduced when patients were treated with corticosteroids in addition to standard antibiotic therapy.⁹

In 2015, two randomized clinical trials, one in the Lancet and the other in JAMA, and a meta-analysis in Annals of Internal Medicine assessed the impact of adjuvant corticosteroids in the treatment of hospitalized patients with CAP. The Lancet study of 785 patients hospitalized with CAP of any severity found shortened time to clinical stability (3.0 vs. 4.4 days) as defined by stable vital signs, improved oral intake, and normalized mental status for greater than 24 hours when oral prednisone 50 mg for 7 days was added to standard therapy.¹⁰ Patients in the treatment group were also discharged 1 day earlier compared with the placebo control group.

The study in JAMA was small, with only 100 patients at three teaching hospitals in Spain, but found that patients hospitalized with severe CAP and high inflammatory response based on elevated C-reactive protein were less likely to experience a treatment failure, defined as shock, mechanical ventilation, death, or radiographic progression, when intravenous methylprednisolone 0.5 mg/kg was added to standard antibiotic therapy.¹¹

Finally, the meta-analysis in Annals of Internal Medicine assessed 13 randomized controlled placebo trials of 1,974 patients and found that adjuvant corticosteroids in a dose of 20-60 mg of prednisone or equivalent total daily dose significantly lowered mortality in patients with severe CAP and incidence of respiratory distress syndrome, and need for mechanical ventilation in all patients hospitalized with CAP.¹²

Importantly, nearly all of the described studies showed a significantly higher incidence of hyperglycemia in patients who received corticosteroids.
 

Application of the data to our patients

The benefit of adjuvant corticosteroids is most clear in hospitalized patients with severe CAP. Recent, strong evidence supports decreased mortality, decreased time to clinical stability, and decreased length of stay in our patient, with severe CAP, if treated with 20-60 mg of prednisone or equivalent total daily dose for 3-7 days. For patients with non-severe CAP, we suggest taking a risk-benefit approach based on other comorbidities, as the risk for CAP-related rehospitalizations may be higher.

For patients with underlying lung disease, specifically COPD or reactive airway disease, we suggest a low threshold for adding corticosteroids. This approach is more anecdotal than data driven, though corticosteroids are a mainstay of treatment for COPD exacerbations and a retrospective analysis of more than 20,000 hospitalized children with CAP and wheezing revealed decreased length of stay with corticosteroid treatment.¹³ Furthermore, a number of the studies described above included patients with COPD. Our threshold rises significantly in patients with poorly controlled diabetes mellitus.
 

Bottom line

For patients hospitalized with severe community-acquired pneumonia, recent evidence supports the use of low dose, short-course, systemic corticosteroids in addition to standard therapy.

Dr. Parsons is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center in Charlottesville, Va. Dr. Miller is an assistant professor at the University of Virginia and a hospitalist at the University of Virginia Medical Center. Dr. Hoke is Associate Director of Hospital Medicine and Faculty Development at the University of Virginia.

References

1. Ramirez J et al. Adults hospitalized with pneumonia in the United States: Incidence, epidemiology, and mortality. Clin Infect Dis. 2017 Dec 1:65(11):1806-12.

2. Musher D et al. Community-acquired pneumonia: Review article. N Engl J Med. 2014 Oct 23;371:1619-28.

3. Wunderink R et al. Community-aquired pneumonia: Clinical practice. N Engl J Med. 2014 Feb 6;370:543-51.

4. Mandell L et al. Infectious Diseases Society America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44:S27-72.

5. Wagner HN et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98:197-215.

6. Polverino E et al. Systemic corticosteroids for community-acquired pneumonia: Reasons for use and lack of benefit on outcome. Respirology. 2013. Feb;18(2):263-71 (https://doi.org/10.1111/resp.12013).

7. Stern A et al. Corticosteroids for pneumonia. Cochrane Database Syst Rev. 2017 Dec 13; 12:CD007720 (https://doi.org/10.1002/14651858.CD007720.pub3).

8. Briel M et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1;66:346 (https://doi.org/10.1093/cid/cix801).

9. Wu W-F et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis. Am J Emerg Med. 2017 Jul 15; [e-pub] (http://dx.doi.org/10.1016/j.ajem.2017.07.050).

10. Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015 Jan 18; [e-pub ahead of print] (http://dx.doi.org/10.1016/S0140-6736[14]62447-8).

11. Torres A et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015 Feb 17; 313:677 (http://dx.doi.org/10.1001/jama.2015.88).

12. Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6;163:519 (http://dx.doi.org/10.7326/M15-0715).

13. Simon LH et al. Management of community-acquired pneumonia in hospitalized children. Current Treat Options Peds (2015) 1:59 (https://doi:.org/10.1007/s40746-014-0011-3).


 

Key points

• For patients hospitalized with severe CAP, recent evidence supports the use of low-dose, short-course, systemic corticosteroids in addition to standard therapy.

• Among hospitalized patients with non-severe CAP, the benefit is not well defined. Studies suggest these patients may benefit from reduced time to clinical stability and reduced length of hospital stay. However, they may be at risk for significantly more CAP-related, 30-day rehospitalizations and hyperglycemia.

• Further prospective, randomized controlled studies are needed to further delineate the patient population who will most benefit from adjunctive corticosteroids use, including dose and duration of treatment.
 

QUIZ

Which of the following is FALSE regarding community acquired pneumonia?

A. CAP is the leading cause of infectious disease related death in the United States.

B. An excessive inflammatory cytokine response may contribute to the high mortality rate in CAP.

C. Adjunctive steroid therapy has been shown to decrease mortality in all patients with CAP.

D. Hyperglycemia occurs more frequently in patients receiving steroid therapy.

E. Reasons to avoid adjunctive steroid therapy in CAP include low risk for mortality, poorly controlled diabetes, suspected viral or fungal etiology, and elevated risk for gastrointestinal bleeding.



ANSWER: C. The patient population that may benefit most from the use of adjuvant corticosteroids is poorly defined. However, in patients with severe pneumonia, the use of adjuvant steroids has been shown to decrease mortality, time to clinical stability, and length of stay.
 

Additional reading

Siemieniuk RAC et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med. 2015 Oct 6; 163:519. (http://dx.doi.org/10.7326/M15-0715).

Briel M et al. Corticosteroids in patients hospitalized with community-acquired Pneumonia: Systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018 Feb 1; 66:346 (https://doi.org/10.1093/cid/cix801).

Blum CA et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8).

Feldman C et al. Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials. J Thorac Dis. 2016 Mar; 8(3):E162-E171.

Wan YD et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: A systemic review and meta-analysis. Chest. 2016 Jan;149(1):209-19.
 

The combined rate of obesity and overweight among children in the Supplemental Nutrition Program for Women, Infants, and Children (WIC) decreased by 3.2% during 2010-2016, according to a study in JAMA.

Liping Pan, MD, MPH, of the Centers for Disease Control and Prevention and colleagues used data from the WIC Participant and Program Characteristics survey from 2010, 2012, 2014, and 2016 for 12,403,629 children aged 2-4 years from 50 states, Washington, D.C., and 5 territories. In addition to a –3.2% change (95% confidence interval, –3.3% to –3.2%) in adjusted prevalence difference for the combined rate of obesity and overweight seen between 2010 and 2016, the researchers found the crude prevalence decreased from 32.5% to 29.1%. A decrease was also seen for obesity alone (crude prevalence, 15.9% to 13.9%; adjusted prevalence difference, –1.9%; 95% CI, –1.9% to –1.8%).


One of the limitations of the study is that the characteristics of enrolled children might differ from those of children not enrolled in this WIC program; however, the researchers noted that they accounted for many demographic characteristics in the trend analyses.

“Reasons for the declines in obesity among young children in WIC remain undetermined but may include WIC food package revisions and local, state, and national initiatives,” they wrote.

[email protected]

SOURCE: Pan L et al. JAMA. 2019 Jun 18;321(23):2364-6.

The combined rate of obesity and overweight among children in the Supplemental Nutrition Program for Women, Infants, and Children (WIC) decreased by 3.2% during 2010-2016, according to a study in JAMA.

Liping Pan, MD, MPH, of the Centers for Disease Control and Prevention and colleagues used data from the WIC Participant and Program Characteristics survey from 2010, 2012, 2014, and 2016 for 12,403,629 children aged 2-4 years from 50 states, Washington, D.C., and 5 territories. In addition to a –3.2% change (95% confidence interval, –3.3% to –3.2%) in adjusted prevalence difference for the combined rate of obesity and overweight seen between 2010 and 2016, the researchers found the crude prevalence decreased from 32.5% to 29.1%. A decrease was also seen for obesity alone (crude prevalence, 15.9% to 13.9%; adjusted prevalence difference, –1.9%; 95% CI, –1.9% to –1.8%).


One of the limitations of the study is that the characteristics of enrolled children might differ from those of children not enrolled in this WIC program; however, the researchers noted that they accounted for many demographic characteristics in the trend analyses.

“Reasons for the declines in obesity among young children in WIC remain undetermined but may include WIC food package revisions and local, state, and national initiatives,” they wrote.

[email protected]

SOURCE: Pan L et al. JAMA. 2019 Jun 18;321(23):2364-6.

The combined rate of obesity and overweight among children in the Supplemental Nutrition Program for Women, Infants, and Children (WIC) decreased by 3.2% during 2010-2016, according to a study in JAMA.

Liping Pan, MD, MPH, of the Centers for Disease Control and Prevention and colleagues used data from the WIC Participant and Program Characteristics survey from 2010, 2012, 2014, and 2016 for 12,403,629 children aged 2-4 years from 50 states, Washington, D.C., and 5 territories. In addition to a –3.2% change (95% confidence interval, –3.3% to –3.2%) in adjusted prevalence difference for the combined rate of obesity and overweight seen between 2010 and 2016, the researchers found the crude prevalence decreased from 32.5% to 29.1%. A decrease was also seen for obesity alone (crude prevalence, 15.9% to 13.9%; adjusted prevalence difference, –1.9%; 95% CI, –1.9% to –1.8%).


One of the limitations of the study is that the characteristics of enrolled children might differ from those of children not enrolled in this WIC program; however, the researchers noted that they accounted for many demographic characteristics in the trend analyses.

“Reasons for the declines in obesity among young children in WIC remain undetermined but may include WIC food package revisions and local, state, and national initiatives,” they wrote.

[email protected]

SOURCE: Pan L et al. JAMA. 2019 Jun 18;321(23):2364-6.

Suicides in teens and young adults reached 6,241 in 2017, the highest since 2000, according to data from a review of the Centers for Disease Control and Prevention Underlying Cause of Death database.

StHelena/Getty Images

The suicide rate overall was 12 per 100,000 in 2017 for 15-19 year olds.

Although suicide rates have increased across all age groups in the United States since 2000, “adolescents are of particular concern, with increases in social media use, anxiety, depression, and self-inflicted injuries,” wrote Oren Miron of Harvard Medical School, Boston, and colleagues.

In a research letter published in JAMA, the researchers analyzed trends in teen and young adult suicides from 2000 to 2017. The combined suicide rate for males and females aged 15-19 years in 2000 was 8 per 100,000 with no significant changes until 2007, followed by an annual percentage change (APC) of 3% from 2007 to 2014 and 10% from 2014 to 2017.

When the data were broken out by gender, males aged 15-19 years showed a spike in suicides in recent years, with an increase in APC of 14% from 2015 to 2017. Of note, these young men showed a decreasing trend in APC of –2% from 2000 to 2007 before increasing.

Among females aged 15-19 years, no increase was noted until 2010, then researchers identified an APC of 8% from 2010 to 2017.

For ages 20-24 years, the combined suicide rate for males and females was 13 per 100,000 in 2000, which rose to 17 per 100,000 in 2017. The APC in the older group was 1% from 2000 to 2013 and 6% from 2013 to 2017. Increasing trends were observed for both males and females over the study period.

The study was limited by the potential inaccuracy in cause of death listed on death certificates, such as mistaking a suicide for an accidental overdose, and the increased suicide rate could reflect more accurate reporting, the researchers noted.

Nonetheless, the results support the need for more studies of contributing factors to teen and young adult suicides to help develop prevention strategies and analysis of factors that may have contributed to declines in suicide rates in the past, they said.

Coauthor Dr. Yu was supported by the Harvard Data Science Fellowship. The researchers had no relevant financial disclosures.

SOURCE: Miron O et al. JAMA. 2019 Jun 28;321:2362-4.

Suicides in teens and young adults reached 6,241 in 2017, the highest since 2000, according to data from a review of the Centers for Disease Control and Prevention Underlying Cause of Death database.

StHelena/Getty Images

The suicide rate overall was 12 per 100,000 in 2017 for 15-19 year olds.

Although suicide rates have increased across all age groups in the United States since 2000, “adolescents are of particular concern, with increases in social media use, anxiety, depression, and self-inflicted injuries,” wrote Oren Miron of Harvard Medical School, Boston, and colleagues.

In a research letter published in JAMA, the researchers analyzed trends in teen and young adult suicides from 2000 to 2017. The combined suicide rate for males and females aged 15-19 years in 2000 was 8 per 100,000 with no significant changes until 2007, followed by an annual percentage change (APC) of 3% from 2007 to 2014 and 10% from 2014 to 2017.

When the data were broken out by gender, males aged 15-19 years showed a spike in suicides in recent years, with an increase in APC of 14% from 2015 to 2017. Of note, these young men showed a decreasing trend in APC of –2% from 2000 to 2007 before increasing.

Among females aged 15-19 years, no increase was noted until 2010, then researchers identified an APC of 8% from 2010 to 2017.

For ages 20-24 years, the combined suicide rate for males and females was 13 per 100,000 in 2000, which rose to 17 per 100,000 in 2017. The APC in the older group was 1% from 2000 to 2013 and 6% from 2013 to 2017. Increasing trends were observed for both males and females over the study period.

The study was limited by the potential inaccuracy in cause of death listed on death certificates, such as mistaking a suicide for an accidental overdose, and the increased suicide rate could reflect more accurate reporting, the researchers noted.

Nonetheless, the results support the need for more studies of contributing factors to teen and young adult suicides to help develop prevention strategies and analysis of factors that may have contributed to declines in suicide rates in the past, they said.

Coauthor Dr. Yu was supported by the Harvard Data Science Fellowship. The researchers had no relevant financial disclosures.

SOURCE: Miron O et al. JAMA. 2019 Jun 28;321:2362-4.

Suicides in teens and young adults reached 6,241 in 2017, the highest since 2000, according to data from a review of the Centers for Disease Control and Prevention Underlying Cause of Death database.

StHelena/Getty Images

The suicide rate overall was 12 per 100,000 in 2017 for 15-19 year olds.

Although suicide rates have increased across all age groups in the United States since 2000, “adolescents are of particular concern, with increases in social media use, anxiety, depression, and self-inflicted injuries,” wrote Oren Miron of Harvard Medical School, Boston, and colleagues.

In a research letter published in JAMA, the researchers analyzed trends in teen and young adult suicides from 2000 to 2017. The combined suicide rate for males and females aged 15-19 years in 2000 was 8 per 100,000 with no significant changes until 2007, followed by an annual percentage change (APC) of 3% from 2007 to 2014 and 10% from 2014 to 2017.

When the data were broken out by gender, males aged 15-19 years showed a spike in suicides in recent years, with an increase in APC of 14% from 2015 to 2017. Of note, these young men showed a decreasing trend in APC of –2% from 2000 to 2007 before increasing.

Among females aged 15-19 years, no increase was noted until 2010, then researchers identified an APC of 8% from 2010 to 2017.

For ages 20-24 years, the combined suicide rate for males and females was 13 per 100,000 in 2000, which rose to 17 per 100,000 in 2017. The APC in the older group was 1% from 2000 to 2013 and 6% from 2013 to 2017. Increasing trends were observed for both males and females over the study period.

The study was limited by the potential inaccuracy in cause of death listed on death certificates, such as mistaking a suicide for an accidental overdose, and the increased suicide rate could reflect more accurate reporting, the researchers noted.

Nonetheless, the results support the need for more studies of contributing factors to teen and young adult suicides to help develop prevention strategies and analysis of factors that may have contributed to declines in suicide rates in the past, they said.

Coauthor Dr. Yu was supported by the Harvard Data Science Fellowship. The researchers had no relevant financial disclosures.

SOURCE: Miron O et al. JAMA. 2019 Jun 28;321:2362-4.

Cyclic Vomiting Syndrome and Primary Headache

Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a very high risk of developing headache, mostly migraine, later in life. This according to a longitudinal study that assessed the rate of headache in patients presenting with cyclic vomiting syndrome and benign paroxysmal torticollis during infancy and defined the main clinical features of the disorder. Researchers administered a questionnaire to the parents of pediatric patients with previous diagnosis of cyclic vomiting syndrome and/or benign paroxysmal torticollis. They found:

• 82 patients with cyclic vomiting syndrome and 33 with benign paroxysmal torticollis were included in the final analysis.
• 79% of patients with cyclic vomiting syndrome presented with headache during the follow-up with a mean age at onset of 6 years.
• 67% of patients with benign paroxysmal torticollis suffered from headache during the follow-up with a mean age at onset of 5 years.

Moavero R, et al. Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a high risk of developing primary headache: A longitudinal study. [Published online ahead of print April 13, 2019]. Cephalalgia. doi: 10.1177/0333102419844542.

Cyclic Vomiting Syndrome and Primary Headache

Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a very high risk of developing headache, mostly migraine, later in life. This according to a longitudinal study that assessed the rate of headache in patients presenting with cyclic vomiting syndrome and benign paroxysmal torticollis during infancy and defined the main clinical features of the disorder. Researchers administered a questionnaire to the parents of pediatric patients with previous diagnosis of cyclic vomiting syndrome and/or benign paroxysmal torticollis. They found:

• 82 patients with cyclic vomiting syndrome and 33 with benign paroxysmal torticollis were included in the final analysis.
• 79% of patients with cyclic vomiting syndrome presented with headache during the follow-up with a mean age at onset of 6 years.
• 67% of patients with benign paroxysmal torticollis suffered from headache during the follow-up with a mean age at onset of 5 years.

Moavero R, et al. Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a high risk of developing primary headache: A longitudinal study. [Published online ahead of print April 13, 2019]. Cephalalgia. doi: 10.1177/0333102419844542.

Cyclic Vomiting Syndrome and Primary Headache

Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a very high risk of developing headache, mostly migraine, later in life. This according to a longitudinal study that assessed the rate of headache in patients presenting with cyclic vomiting syndrome and benign paroxysmal torticollis during infancy and defined the main clinical features of the disorder. Researchers administered a questionnaire to the parents of pediatric patients with previous diagnosis of cyclic vomiting syndrome and/or benign paroxysmal torticollis. They found:

• 82 patients with cyclic vomiting syndrome and 33 with benign paroxysmal torticollis were included in the final analysis.
• 79% of patients with cyclic vomiting syndrome presented with headache during the follow-up with a mean age at onset of 6 years.
• 67% of patients with benign paroxysmal torticollis suffered from headache during the follow-up with a mean age at onset of 5 years.

Moavero R, et al. Cyclic vomiting syndrome and benign paroxysmal torticollis are associated with a high risk of developing primary headache: A longitudinal study. [Published online ahead of print April 13, 2019]. Cephalalgia. doi: 10.1177/0333102419844542.

The clinical characteristics of migraine attacks are sufficiently different in patients with and without neurocysticercosis, a new study found. Researchers investigated the characteristics of migraine attacks in patients with calcified neurocysticercosis (NCC) on brain imaging. Of 350 migraine patients, 166 had undergone brain imaging. Seventy-two patients with migraines had calcified NCC. The migraine attacks of the patients with calcification (MiC) were compared with those of 94 patients without calcification (MiNC). Among the findings:

• Side-locked headaches were seen in 48.6% of the MiC patients.
• Aura preceding the migraine attack was more common in the MiC group vs the MiNC group.
• The MiC group had fewer headache episodes per month with fewer common associated features and required fewer drugs for secondary prophylaxis.

Pradhan S, et al. Clinical characteristics of migraine in patients with calcified neurocysticercosis. [Published online ahead of print April 6, 2019]. Trans R Soc Trop Med Hyg. doi: 10.1093/trstmh/trz018.

The clinical characteristics of migraine attacks are sufficiently different in patients with and without neurocysticercosis, a new study found. Researchers investigated the characteristics of migraine attacks in patients with calcified neurocysticercosis (NCC) on brain imaging. Of 350 migraine patients, 166 had undergone brain imaging. Seventy-two patients with migraines had calcified NCC. The migraine attacks of the patients with calcification (MiC) were compared with those of 94 patients without calcification (MiNC). Among the findings:

• Side-locked headaches were seen in 48.6% of the MiC patients.
• Aura preceding the migraine attack was more common in the MiC group vs the MiNC group.
• The MiC group had fewer headache episodes per month with fewer common associated features and required fewer drugs for secondary prophylaxis.

Pradhan S, et al. Clinical characteristics of migraine in patients with calcified neurocysticercosis. [Published online ahead of print April 6, 2019]. Trans R Soc Trop Med Hyg. doi: 10.1093/trstmh/trz018.

The clinical characteristics of migraine attacks are sufficiently different in patients with and without neurocysticercosis, a new study found. Researchers investigated the characteristics of migraine attacks in patients with calcified neurocysticercosis (NCC) on brain imaging. Of 350 migraine patients, 166 had undergone brain imaging. Seventy-two patients with migraines had calcified NCC. The migraine attacks of the patients with calcification (MiC) were compared with those of 94 patients without calcification (MiNC). Among the findings:

• Side-locked headaches were seen in 48.6% of the MiC patients.
• Aura preceding the migraine attack was more common in the MiC group vs the MiNC group.
• The MiC group had fewer headache episodes per month with fewer common associated features and required fewer drugs for secondary prophylaxis.

Pradhan S, et al. Clinical characteristics of migraine in patients with calcified neurocysticercosis. [Published online ahead of print April 6, 2019]. Trans R Soc Trop Med Hyg. doi: 10.1093/trstmh/trz018.

CRYSTAL CITY, VA. – As technology advances and the population becomes older, clinicians should understand how modest age-related declines in cognition affect older adults’ ability to learn new technological skills, Philip D. Harvey, PhD, said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

©AlexRaths/thinkstockphotos.com

According to the U.S. Census Bureau, the number of adults in the United States above age 65 is slated to increase over the next several decades, and by 2030, one in five adults in the United States will be at retirement age. By 2050, “a significant number of people” in the United States are expected to be age 90, Dr. Harvey said at the meeting, presented by Global Academy for Medical Education.

“What we need to do is to understand what are the normal things that happen to people as they become 90 years of age,” said Dr. Harvey, of the department of psychiatry and behavioral sciences at the University of Miami.

Within the technology industry, significant advancements were made over the last 40 years with the advent of the personal computer in the 1980s, mobile phones in the 1990s, and wireless Internet, smartphones, and wireless devices in the 2000s. Many interactions that used to be person-to-person are now performed online, and it is feasible for a 90-year-old living today to never have encountered this technology during their careers. “Utilizing technology is a central requirement for independent living today,” Dr. Harvey said.

Most people passively adapt to these new changes in technology. However, Dr. Harvey noted that adults in their 80s and 90s who are retired can have difficulty using or learning about new technology as they age. “Human-technology interaction involves information processing, and places demands on memory and other cognitive abilities,” he said. “Age is associated with declines specifically in the kind of abilities that are required to master new technology.”

Learning about and using technology requires different elements of cognition that include different types of memory, such as working, episodic, declarative, procedural, semantic, long-term factual, and emotional. A decline in any of those kinds of memory could result in failures in forgetting, learning or recalling material, and learning new motor skills, among other problems. Crystallized intelligence is more likely to be retained over time, but fluid cognition in the form of processing speed, working and episodic memory, and the ability to solve abstract problems tend to decline over time as people age, Dr. Harvey said.

Base cognitive abilities do play a role in how crystallized and fluid cognition decline over time. For example, while vocabulary might increase as one ages, a person’s working memory, processing speed, and episodic memory decline over time. Evidence also suggests that speed training and exercise appear to improve cognition. In the ACTIVE trial, 2,832 adults with a baseline age of 73.6 years who underwent 10 cognitive training sessions to improve memory showed better cognitive scores that remained at 10-year follow-up (J Am Geriatr Soc. 13 Jan 2014. doi: 10.1111/jgs.12607).

Cyrus Raji, MD, PhD, and colleagues also explored the relationship between caloric expenditure and gray matter volume in the Cardiovascular Health Study, and found that exercise of various types improved gray matter volume and reduced the risk of dementia in people aged 65 or older. Furthermore, Dr. Raji and colleagues found, caloric expenditures, rather than intensity of exercise, may alone predict increases in gray matter volume (J Alzheimers Dis. 2016. doi: 10.3233/JAD-160057).

“If you want to improve your memory, grow your hippocampus,” Dr. Harvey said at the meeting.

Dr. Harvey reported serving as a consultant for Alkermes, Boehringer-Ingelheim, Lundbeck, Otsuka Digital Health, Sanofi, Sunovion Pharmaceuticals, Takeda, and Teva. He also reported receiving a grant from Takeda, and is the founder and CSO of i-Function.

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

CRYSTAL CITY, VA. – As technology advances and the population becomes older, clinicians should understand how modest age-related declines in cognition affect older adults’ ability to learn new technological skills, Philip D. Harvey, PhD, said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

©AlexRaths/thinkstockphotos.com

According to the U.S. Census Bureau, the number of adults in the United States above age 65 is slated to increase over the next several decades, and by 2030, one in five adults in the United States will be at retirement age. By 2050, “a significant number of people” in the United States are expected to be age 90, Dr. Harvey said at the meeting, presented by Global Academy for Medical Education.

“What we need to do is to understand what are the normal things that happen to people as they become 90 years of age,” said Dr. Harvey, of the department of psychiatry and behavioral sciences at the University of Miami.

Within the technology industry, significant advancements were made over the last 40 years with the advent of the personal computer in the 1980s, mobile phones in the 1990s, and wireless Internet, smartphones, and wireless devices in the 2000s. Many interactions that used to be person-to-person are now performed online, and it is feasible for a 90-year-old living today to never have encountered this technology during their careers. “Utilizing technology is a central requirement for independent living today,” Dr. Harvey said.

Most people passively adapt to these new changes in technology. However, Dr. Harvey noted that adults in their 80s and 90s who are retired can have difficulty using or learning about new technology as they age. “Human-technology interaction involves information processing, and places demands on memory and other cognitive abilities,” he said. “Age is associated with declines specifically in the kind of abilities that are required to master new technology.”

Learning about and using technology requires different elements of cognition that include different types of memory, such as working, episodic, declarative, procedural, semantic, long-term factual, and emotional. A decline in any of those kinds of memory could result in failures in forgetting, learning or recalling material, and learning new motor skills, among other problems. Crystallized intelligence is more likely to be retained over time, but fluid cognition in the form of processing speed, working and episodic memory, and the ability to solve abstract problems tend to decline over time as people age, Dr. Harvey said.

Base cognitive abilities do play a role in how crystallized and fluid cognition decline over time. For example, while vocabulary might increase as one ages, a person’s working memory, processing speed, and episodic memory decline over time. Evidence also suggests that speed training and exercise appear to improve cognition. In the ACTIVE trial, 2,832 adults with a baseline age of 73.6 years who underwent 10 cognitive training sessions to improve memory showed better cognitive scores that remained at 10-year follow-up (J Am Geriatr Soc. 13 Jan 2014. doi: 10.1111/jgs.12607).

Cyrus Raji, MD, PhD, and colleagues also explored the relationship between caloric expenditure and gray matter volume in the Cardiovascular Health Study, and found that exercise of various types improved gray matter volume and reduced the risk of dementia in people aged 65 or older. Furthermore, Dr. Raji and colleagues found, caloric expenditures, rather than intensity of exercise, may alone predict increases in gray matter volume (J Alzheimers Dis. 2016. doi: 10.3233/JAD-160057).

“If you want to improve your memory, grow your hippocampus,” Dr. Harvey said at the meeting.

Dr. Harvey reported serving as a consultant for Alkermes, Boehringer-Ingelheim, Lundbeck, Otsuka Digital Health, Sanofi, Sunovion Pharmaceuticals, Takeda, and Teva. He also reported receiving a grant from Takeda, and is the founder and CSO of i-Function.

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

CRYSTAL CITY, VA. – As technology advances and the population becomes older, clinicians should understand how modest age-related declines in cognition affect older adults’ ability to learn new technological skills, Philip D. Harvey, PhD, said at Focus on Neuropsychiatry presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

©AlexRaths/thinkstockphotos.com

According to the U.S. Census Bureau, the number of adults in the United States above age 65 is slated to increase over the next several decades, and by 2030, one in five adults in the United States will be at retirement age. By 2050, “a significant number of people” in the United States are expected to be age 90, Dr. Harvey said at the meeting, presented by Global Academy for Medical Education.

“What we need to do is to understand what are the normal things that happen to people as they become 90 years of age,” said Dr. Harvey, of the department of psychiatry and behavioral sciences at the University of Miami.

Within the technology industry, significant advancements were made over the last 40 years with the advent of the personal computer in the 1980s, mobile phones in the 1990s, and wireless Internet, smartphones, and wireless devices in the 2000s. Many interactions that used to be person-to-person are now performed online, and it is feasible for a 90-year-old living today to never have encountered this technology during their careers. “Utilizing technology is a central requirement for independent living today,” Dr. Harvey said.

Most people passively adapt to these new changes in technology. However, Dr. Harvey noted that adults in their 80s and 90s who are retired can have difficulty using or learning about new technology as they age. “Human-technology interaction involves information processing, and places demands on memory and other cognitive abilities,” he said. “Age is associated with declines specifically in the kind of abilities that are required to master new technology.”

Learning about and using technology requires different elements of cognition that include different types of memory, such as working, episodic, declarative, procedural, semantic, long-term factual, and emotional. A decline in any of those kinds of memory could result in failures in forgetting, learning or recalling material, and learning new motor skills, among other problems. Crystallized intelligence is more likely to be retained over time, but fluid cognition in the form of processing speed, working and episodic memory, and the ability to solve abstract problems tend to decline over time as people age, Dr. Harvey said.

Base cognitive abilities do play a role in how crystallized and fluid cognition decline over time. For example, while vocabulary might increase as one ages, a person’s working memory, processing speed, and episodic memory decline over time. Evidence also suggests that speed training and exercise appear to improve cognition. In the ACTIVE trial, 2,832 adults with a baseline age of 73.6 years who underwent 10 cognitive training sessions to improve memory showed better cognitive scores that remained at 10-year follow-up (J Am Geriatr Soc. 13 Jan 2014. doi: 10.1111/jgs.12607).

Cyrus Raji, MD, PhD, and colleagues also explored the relationship between caloric expenditure and gray matter volume in the Cardiovascular Health Study, and found that exercise of various types improved gray matter volume and reduced the risk of dementia in people aged 65 or older. Furthermore, Dr. Raji and colleagues found, caloric expenditures, rather than intensity of exercise, may alone predict increases in gray matter volume (J Alzheimers Dis. 2016. doi: 10.3233/JAD-160057).

“If you want to improve your memory, grow your hippocampus,” Dr. Harvey said at the meeting.

Dr. Harvey reported serving as a consultant for Alkermes, Boehringer-Ingelheim, Lundbeck, Otsuka Digital Health, Sanofi, Sunovion Pharmaceuticals, Takeda, and Teva. He also reported receiving a grant from Takeda, and is the founder and CSO of i-Function.

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SEATTLE – Preliminary findings from a registry questionnaire reveal that 77% of patients with multiple sclerosis (MS) are employed either full or part time, with the rest being unemployed.

“MS seems to prevent people with MS from realizing their full potential at work or home,” said study coauthor Kottil Rammohan, MD, who summarized the study results in a video interview. Dr. Rammohan is professor of clinical neurology, director of the MS center of excellence, and chief of the multiple sclerosis division at the University of Miami. The study findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) prospectively collects information about the health care economics of patients with MS and its effects on daily life. In 2017, NARCRMS established the health care economics outcomes research (HEOR) advisory group. NARCRMS developed a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire. The questionnaires were incorporated into the existing case report forms that are completed by patients at enrollment, annual, and exacerbation visits.

This analysis was based on 480 patients who had completed HEOR case report forms. Among those, 77% are employed either full or part time; however, of those 15% were underemployed, meaning they wanted to work more than their current work levels. About 13% are on disability.


“What we found was there was a significant impact at home as well,” said Dr. Rammohan. Patients reported that MS kept them from completing household chores. “MS is a disease that seems to impact not only the work environment, but also the home environment.”

When polled to determine the main reason why these MS patients are not able to function, “what we found was that it was not because of gait or immobility, it was difficulty related to fatigue,” Dr. Rammohan said. The second most common impairment was related to cognition.

“These are what we call the silent or the transparent symptoms of MS.”

Dr. Rammohan disclosed consulting fees from EMD Serono, Biogen, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech.

[email protected]

SEATTLE – Preliminary findings from a registry questionnaire reveal that 77% of patients with multiple sclerosis (MS) are employed either full or part time, with the rest being unemployed.

“MS seems to prevent people with MS from realizing their full potential at work or home,” said study coauthor Kottil Rammohan, MD, who summarized the study results in a video interview. Dr. Rammohan is professor of clinical neurology, director of the MS center of excellence, and chief of the multiple sclerosis division at the University of Miami. The study findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) prospectively collects information about the health care economics of patients with MS and its effects on daily life. In 2017, NARCRMS established the health care economics outcomes research (HEOR) advisory group. NARCRMS developed a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire. The questionnaires were incorporated into the existing case report forms that are completed by patients at enrollment, annual, and exacerbation visits.

This analysis was based on 480 patients who had completed HEOR case report forms. Among those, 77% are employed either full or part time; however, of those 15% were underemployed, meaning they wanted to work more than their current work levels. About 13% are on disability.


“What we found was there was a significant impact at home as well,” said Dr. Rammohan. Patients reported that MS kept them from completing household chores. “MS is a disease that seems to impact not only the work environment, but also the home environment.”

When polled to determine the main reason why these MS patients are not able to function, “what we found was that it was not because of gait or immobility, it was difficulty related to fatigue,” Dr. Rammohan said. The second most common impairment was related to cognition.

“These are what we call the silent or the transparent symptoms of MS.”

Dr. Rammohan disclosed consulting fees from EMD Serono, Biogen, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech.

[email protected]

SEATTLE – Preliminary findings from a registry questionnaire reveal that 77% of patients with multiple sclerosis (MS) are employed either full or part time, with the rest being unemployed.

“MS seems to prevent people with MS from realizing their full potential at work or home,” said study coauthor Kottil Rammohan, MD, who summarized the study results in a video interview. Dr. Rammohan is professor of clinical neurology, director of the MS center of excellence, and chief of the multiple sclerosis division at the University of Miami. The study findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) prospectively collects information about the health care economics of patients with MS and its effects on daily life. In 2017, NARCRMS established the health care economics outcomes research (HEOR) advisory group. NARCRMS developed a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire. The questionnaires were incorporated into the existing case report forms that are completed by patients at enrollment, annual, and exacerbation visits.

This analysis was based on 480 patients who had completed HEOR case report forms. Among those, 77% are employed either full or part time; however, of those 15% were underemployed, meaning they wanted to work more than their current work levels. About 13% are on disability.


“What we found was there was a significant impact at home as well,” said Dr. Rammohan. Patients reported that MS kept them from completing household chores. “MS is a disease that seems to impact not only the work environment, but also the home environment.”

When polled to determine the main reason why these MS patients are not able to function, “what we found was that it was not because of gait or immobility, it was difficulty related to fatigue,” Dr. Rammohan said. The second most common impairment was related to cognition.

“These are what we call the silent or the transparent symptoms of MS.”

Dr. Rammohan disclosed consulting fees from EMD Serono, Biogen, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech.

[email protected]