Guselkumab induction therapy appears to improve key clinical, histologic, and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC) at week 12, according to findings presented at the annual meeting of the American College of Gastroenterology.

The efficacy of the 200-mg dose and the 400-mg dose was comparable, said David Rubin, MD, a gastroenterologist at the University of Chicago Medicine Inflammatory Bowel Disease Center. Outcomes improved in all patients, with or without a history of inadequate response or intolerance to advanced therapy.

Guselkumab, an interleukin-12 p19 subunit antagonist, is currently being investigated in inflammatory bowel disease.

The QUASAR Induction Study 1 (NCT04033445) is a phase 2b, randomized, double-blind, placebo-controlled study that evaluates guselkumab as induction therapy in patients with moderately to severely active UC. Inclusion criteria specify a demonstrated inadequate response or intolerance to conventional therapy, such as thiopurines or corticosteroids, or to advanced therapy, such as tumor necrosis factor–alpha antagonists, vedolizumab, or tofacitinib. The study didn’t include patients exposed to ustekinumab.

Study participants were age 18 and older with moderately to severely active UC, defined as a modified Mayo score of 5-9 with a Mayo rectal bleeding subscore of 1 or greater and a Mayo endoscopy subscore of 2 or greater at baseline. The groups were randomized 1:1:1 to receive 400 mg of IV guselkumab, 200 mg of guselkumab, or placebo at weeks 0, 4, and 8.

At week 12, the research team looked for several key endpoints. Clinical response was defined as a modified Mayo score decrease of 30% or more and a drop in 2 or more points, with either a 1-point decrease or more in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission was defined as a stool frequency subscore of 0 or 1 that hadn’t increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

In addition, symptomatic remission was defined as a stool subscore of 0 or 1 that hadn’t increased from baseline and rectal bleeding subscore of 0.

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic normalization was an endoscopy subscore of 0.

Notably, the research team looked at histoendoscopic mucosal improvement, which includes a combination of endoscopic improvement and histologic improvement (neutrophil infiltration in less than 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue, according to the Geboes grading system).

Among the 313 total patients, 47% had a history of inadequate response or intolerance to advanced therapy, and about half of these patients had prior inadequate response or intolerance to two or more advanced therapy classes.

At baseline, about 90% of patients had an endoscopic subscore of 3 (severe). More than half had extensive UC, and the average UC duration was 9 years. About 20% overall had extraintestinal manifestations present, which were noted in 33% of the 400 mg guselkumab treatment arm.

At week 12, clinical response was achieved by a higher proportion of patients treated with guselkumab versus placebo, at 50.5% versus 25.5% for patients with prior inadequate response or intolerance to advanced therapy and 70.3% versus 29.6% for those without prior inadequate response or intolerance to advanced therapy, the authors reported in the abstract.

Compared with placebo, higher proportions of patients treated with guselkumab achieved clinical, endoscopic, and histologic outcomes in both groups with or without inadequate response or intolerance to advanced therapy. Generally, those without a history of inadequate response had higher response rates across all endpoints.

Overall, both the 200-mg and 400-mg doses of guselkumab were statistically superior to the placebo across all endpoints for both groups (with or without inadequate response or intolerance). Although the efficacy was comparable for the two doses, the 400-mg dose was associated with greater histoendoscopic mucosal improvement in both groups.

“It’s of interest to think about how we position and sequence our therapies with this additional data,” Dr. Rubin said.

The study was sponsored by Janssen Research & Development. Several authors are employees for and have stock options with Johnson & Johnson and Janssen. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Janssen.

Guselkumab induction therapy appears to improve key clinical, histologic, and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC) at week 12, according to findings presented at the annual meeting of the American College of Gastroenterology.

The efficacy of the 200-mg dose and the 400-mg dose was comparable, said David Rubin, MD, a gastroenterologist at the University of Chicago Medicine Inflammatory Bowel Disease Center. Outcomes improved in all patients, with or without a history of inadequate response or intolerance to advanced therapy.

Guselkumab, an interleukin-12 p19 subunit antagonist, is currently being investigated in inflammatory bowel disease.

The QUASAR Induction Study 1 (NCT04033445) is a phase 2b, randomized, double-blind, placebo-controlled study that evaluates guselkumab as induction therapy in patients with moderately to severely active UC. Inclusion criteria specify a demonstrated inadequate response or intolerance to conventional therapy, such as thiopurines or corticosteroids, or to advanced therapy, such as tumor necrosis factor–alpha antagonists, vedolizumab, or tofacitinib. The study didn’t include patients exposed to ustekinumab.

Study participants were age 18 and older with moderately to severely active UC, defined as a modified Mayo score of 5-9 with a Mayo rectal bleeding subscore of 1 or greater and a Mayo endoscopy subscore of 2 or greater at baseline. The groups were randomized 1:1:1 to receive 400 mg of IV guselkumab, 200 mg of guselkumab, or placebo at weeks 0, 4, and 8.

At week 12, the research team looked for several key endpoints. Clinical response was defined as a modified Mayo score decrease of 30% or more and a drop in 2 or more points, with either a 1-point decrease or more in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission was defined as a stool frequency subscore of 0 or 1 that hadn’t increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

In addition, symptomatic remission was defined as a stool subscore of 0 or 1 that hadn’t increased from baseline and rectal bleeding subscore of 0.

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic normalization was an endoscopy subscore of 0.

Notably, the research team looked at histoendoscopic mucosal improvement, which includes a combination of endoscopic improvement and histologic improvement (neutrophil infiltration in less than 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue, according to the Geboes grading system).

Among the 313 total patients, 47% had a history of inadequate response or intolerance to advanced therapy, and about half of these patients had prior inadequate response or intolerance to two or more advanced therapy classes.

At baseline, about 90% of patients had an endoscopic subscore of 3 (severe). More than half had extensive UC, and the average UC duration was 9 years. About 20% overall had extraintestinal manifestations present, which were noted in 33% of the 400 mg guselkumab treatment arm.

At week 12, clinical response was achieved by a higher proportion of patients treated with guselkumab versus placebo, at 50.5% versus 25.5% for patients with prior inadequate response or intolerance to advanced therapy and 70.3% versus 29.6% for those without prior inadequate response or intolerance to advanced therapy, the authors reported in the abstract.

Compared with placebo, higher proportions of patients treated with guselkumab achieved clinical, endoscopic, and histologic outcomes in both groups with or without inadequate response or intolerance to advanced therapy. Generally, those without a history of inadequate response had higher response rates across all endpoints.

Overall, both the 200-mg and 400-mg doses of guselkumab were statistically superior to the placebo across all endpoints for both groups (with or without inadequate response or intolerance). Although the efficacy was comparable for the two doses, the 400-mg dose was associated with greater histoendoscopic mucosal improvement in both groups.

“It’s of interest to think about how we position and sequence our therapies with this additional data,” Dr. Rubin said.

The study was sponsored by Janssen Research & Development. Several authors are employees for and have stock options with Johnson & Johnson and Janssen. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Janssen.

Guselkumab induction therapy appears to improve key clinical, histologic, and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC) at week 12, according to findings presented at the annual meeting of the American College of Gastroenterology.

The efficacy of the 200-mg dose and the 400-mg dose was comparable, said David Rubin, MD, a gastroenterologist at the University of Chicago Medicine Inflammatory Bowel Disease Center. Outcomes improved in all patients, with or without a history of inadequate response or intolerance to advanced therapy.

Guselkumab, an interleukin-12 p19 subunit antagonist, is currently being investigated in inflammatory bowel disease.

The QUASAR Induction Study 1 (NCT04033445) is a phase 2b, randomized, double-blind, placebo-controlled study that evaluates guselkumab as induction therapy in patients with moderately to severely active UC. Inclusion criteria specify a demonstrated inadequate response or intolerance to conventional therapy, such as thiopurines or corticosteroids, or to advanced therapy, such as tumor necrosis factor–alpha antagonists, vedolizumab, or tofacitinib. The study didn’t include patients exposed to ustekinumab.

Study participants were age 18 and older with moderately to severely active UC, defined as a modified Mayo score of 5-9 with a Mayo rectal bleeding subscore of 1 or greater and a Mayo endoscopy subscore of 2 or greater at baseline. The groups were randomized 1:1:1 to receive 400 mg of IV guselkumab, 200 mg of guselkumab, or placebo at weeks 0, 4, and 8.

At week 12, the research team looked for several key endpoints. Clinical response was defined as a modified Mayo score decrease of 30% or more and a drop in 2 or more points, with either a 1-point decrease or more in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.

Clinical remission was defined as a stool frequency subscore of 0 or 1 that hadn’t increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.

In addition, symptomatic remission was defined as a stool subscore of 0 or 1 that hadn’t increased from baseline and rectal bleeding subscore of 0.

Endoscopic improvement was defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Endoscopic normalization was an endoscopy subscore of 0.

Notably, the research team looked at histoendoscopic mucosal improvement, which includes a combination of endoscopic improvement and histologic improvement (neutrophil infiltration in less than 5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue, according to the Geboes grading system).

Among the 313 total patients, 47% had a history of inadequate response or intolerance to advanced therapy, and about half of these patients had prior inadequate response or intolerance to two or more advanced therapy classes.

At baseline, about 90% of patients had an endoscopic subscore of 3 (severe). More than half had extensive UC, and the average UC duration was 9 years. About 20% overall had extraintestinal manifestations present, which were noted in 33% of the 400 mg guselkumab treatment arm.

At week 12, clinical response was achieved by a higher proportion of patients treated with guselkumab versus placebo, at 50.5% versus 25.5% for patients with prior inadequate response or intolerance to advanced therapy and 70.3% versus 29.6% for those without prior inadequate response or intolerance to advanced therapy, the authors reported in the abstract.

Compared with placebo, higher proportions of patients treated with guselkumab achieved clinical, endoscopic, and histologic outcomes in both groups with or without inadequate response or intolerance to advanced therapy. Generally, those without a history of inadequate response had higher response rates across all endpoints.

Overall, both the 200-mg and 400-mg doses of guselkumab were statistically superior to the placebo across all endpoints for both groups (with or without inadequate response or intolerance). Although the efficacy was comparable for the two doses, the 400-mg dose was associated with greater histoendoscopic mucosal improvement in both groups.

“It’s of interest to think about how we position and sequence our therapies with this additional data,” Dr. Rubin said.

The study was sponsored by Janssen Research & Development. Several authors are employees for and have stock options with Johnson & Johnson and Janssen. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Janssen.

Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.

The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.

In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).

“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”

EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.

Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
 

Study population difficult to treat

In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.

Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.

On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.

Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.

Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.

The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
 

Pooled parts A and B findings

Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.

Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.

In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.

Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.

“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.

Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.

The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.

In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).

“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”

EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.

Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
 

Study population difficult to treat

In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.

Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.

On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.

Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.

Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.

The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
 

Pooled parts A and B findings

Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.

Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.

In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.

Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.

“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.

Dupilumab appears to improve clinical, symptomatic, histologic, and endoscopic aspects of eosinophilic esophagitis (EoE) up to 24 weeks, according to findings presented at the annual meeting of the American College of Gastroenterology.

The drug was also well tolerated, demonstrating consistency with the known dupilumab safety profile, said Evan S. Dellon, MD, a gastroenterologist at the University of North Carolina at Chapel Hill.

In May, the Food and Drug Administration approved dupilumab (Dupixent) for the treatment of EoE in adults and adolescents who are 12 years and older and weigh at least 40 kg (about 88 pounds), based on safety and efficacy data previously presented by Dr. Dellon and colleagues as part of the phase 3 LIBERTY-EoE-TREET study (NCT03633617).

“Dupilumab is now the only medication FDA approved to treat EoE in the U.S.,” Dr. Dellon said. “The findings here are that the pooled efficacy and safety data for parts A and B of the phase 3 trial are consistent with the results of the individual parts of the study that were previously reported, and which led to the drug being approved for EoE.”

EoE is a chronic, progressive, type 2 inflammatory disease of the esophagus, which can lead to symptoms of esophageal dysfunction that affect quality of life. Current treatment options often lack specificity, present adherence challenges, and provide suboptimal long-term disease control, Dr. Dellon said.

Dupilumab, a fully human monoclonal antibody manufactured by Regeneron Pharmaceuticals, blocks the shared receptor component for interleukin-4 and IL-13, which are central drivers of type 2 inflammation in EoE.
 

Study population difficult to treat

In the three-part, double-blind, placebo-controlled, phase 3 study, dupilumab was administered to 122 patients as 300-mg weekly doses through subcutaneous injection. In parts A and B, dupilumab demonstrated statistically significant and clinically meaningful improvement in adults and adolescents up to 24 weeks. In patients from part A who continued to an extended active treatment period called part C, efficacy was sustained to week 52.

Participants were included if they had EoE that hadn’t responded to high-dose proton pump inhibitors, had baseline esophageal biopsies with a peak intraepithelial eosinophilic count of 15 eosinophils per high-power field (eos/HPF) or higher in two or more esophageal regions, had a history of an average of two or more episodes of dysphagia per week in the 4 weeks prior to screening, had four or more episodes of dysphagia in the 2 weeks prior to randomization with two or more episodes that required liquids or medical attention, and had a baseline Dysphagia Symptom Questionnaire (DSQ) score of 10 or higher.

On the other hand, participants were excluded if they initiated or changed a food-elimination diet regimen or reintroduced a previously eliminated food group in the 6 weeks before screening, had other causes of esophageal eosinophilia, had a history of other inflammatory diseases such as Crohn’s disease or ulcerative colitis, or were treated with swallowed topical corticosteroids within 8 weeks prior to baseline.

Dr. Dellon and colleagues focused on co–primary endpoints: The proportion of patients who achieved peak esophageal intraepithelial eosinophil count of 6 eos/HPF or less, and the absolute change in DSQ score from baseline to week 24.

Key secondary endpoints included percentage change in eos/HPF, absolute change in EoE-Endoscopic Reference Score (EREFS), absolute change in EoE-Histologic Scoring System (EoE-HSS) grade score, and EoE-HSS stage score. Other secondary endpoints included percentage change in DSQ score and proportion of patients achieving less than 15 eos/HPF.

The baseline demographics and clinical characteristics were similar between the treatment and placebo groups. Importantly, about 70% had been treated with topical corticosteroids, and about 40% had a history of esophageal dilation, Dr. Dellon said. The DSQ scores, peak eosinophil counts, and EREFS scores were high, indicating an inflamed, symptomatic, and difficult-to-treat population.
 

Pooled parts A and B findings

Overall, dupilumab reduced peak esophageal intraepithelial eosinophil counts at week 24. In the dupilumab group, 59% of patients were down to 6 eos/HPF or less, compared with 5.9% in the placebo group. In a secondary endpoint, 77% of dupilumab patients were down to 15 eos/HPF, compared with 7.6% in the placebo group. The dupilumab group saw an 80% drop in baseline change, compared with 1.5% in the placebo group.

Dupilumab also reduced dysphagia symptoms and improved endoscopic features of EoE at week 24. The absolute change in DSQ score was –23.21 in the dupilumab group, compared with –12.69 in the placebo group. The percent change in DSQ score was –65.5% in the dupilumab group, compared with –38.2% in the placebo group. The absolute change in EREFS score was –3.95 in the dupilumab group, compared with –0.41 in the placebo group.

In addition, dupilumab reduced histologic scores at week 24. The absolute change in EoE-HSS grade score was –0.82 in the dupilumab group, compared with –0.1 in the placebo group. The absolute change in EoE-HSS stage score was –0.79 in the dupilumab group, compared with –0.09 in the placebo group.

Dupilumab demonstrated an acceptable safety profile, and no new safety signals were noted, Dr. Dellon said. The most common adverse events was injection-site reaction at 37.5% in the dupilumab group and 33.3% in the placebo group. The severe adverse events were not related to the medication.

“If patients have EoE, dupilumab might be an option for treatment. However, it’s important to realize that, in the phase 3 study, all patients were PPI nonresponders, most had been treated with topical steroids [and many were not responsive], and many had prior esophageal dilation,” Dr. Dellon said. “We don’t have a lot of data in more mild EoE patients, and insurances are currently requiring a series of authorization before patients might be able to get this medication. It’s best to talk to their doctor about whether the medication is a good fit for not.”

The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Three of the authors are employees for and have stock options with Regeneron or Sanofi. The other authors reported consultant roles, advisory roles, and research support from numerous pharmaceutical companies, including Regeneron and Sanofi.

When Katie Couric shared the news of her breast cancer diagnosis, the former co-host of NBC’s “Today” show said she considered this new health challenge to be a teachable moment to encourage people to get needed cancer screenings.

“Please get your annual mammogram,” she wrote on her website in September. “But just as importantly, please find out if you need additional screening.”

In the essay, Couric, 65, explained that because she tends to have dense breast tissue, she gets an ultrasound test in addition to a mammogram when screening for breast cancer. A breast ultrasound, sometimes called a sonogram, uses sound waves to take images of the breast tissue. It can sometimes identify malignancies that are hard to spot on a mammogram in women whose breasts are dense – that is, having a high proportion of fibrous tissue and glands vs. fatty tissue.

Ms. Couric, who famously underwent a colonoscopy on live television after her first husband died of colon cancer and who lost her sister to pancreatic cancer, has long pushed for cancer screening and better detection options.

Breast cancer experts applauded Ms. Couric for drawing attention to breast density as a risk factor for cancer. But some were less comfortable with her advocacy for supplemental screening.

“We don’t have evidence that auxiliary screening reduces breast cancer mortality or improves quality of life,” said Dr. Carol Mangione, a professor of medicine and public health at the University of California, Los Angeles, who chairs the U.S. Preventive Services Task Force, a group of medical experts who make recommendations for preventive services after weighing their benefits and harms.

Ms. Couric’s office did not respond to requests for comment.

In addition to an annual mammogram, some women with dense breasts get a breast ultrasound or MRI to help identify cancerous cells missed by the mammogram. Dense fibrous tissue appears white on a mammogram and makes it harder to see cancers, which also appear white. Fatty breast tissue, which appears dark on the mammogram, doesn’t obscure breast malignancies.

As digital breast tomosynthesis, or 3-D mammography, has become more widely available, a growing number of women are getting that screening test rather than the standard 2-D mammography. The 3-D mammography has been found to reduce the number of false-positive results and identify more cancers in some women with dense breasts, though the impact on mortality is unknown.

The task force gives an “I” rating to supplemental screening for women with dense breasts whose mammogram results don’t indicate a problem. That means the current evidence is “insufficient” to assess whether the benefits outweigh the harms of the extra screening. (The task force is updating its recommendation for breast cancer screening, including supplemental screening for women with dense breasts.)

One key harm that researchers are concerned about, besides the possible extra cost, is the chance of a false-positive result. Supplemental imaging in women who aren’t at high risk for breast cancer may identify potential trouble spots, which can lead to follow-up testing such as breast biopsies that are invasive and raise cancer fears for many patients. But research has found that very often these results turn out to be false alarms.

If 1,000 women with dense breasts get an ultrasound after a negative mammogram, the ultrasound will identify two to three cancers, studies show. But the extra imaging will also identify up to 117 potential problems that lead to recall visits and tests but are ultimately determined to be false positives.

“On the one hand, we want to do everything we can to improve detection,” said Dr. Sharon Mass, an ob.gyn. in Morristown, N.J., and the former chair of the American College of Obstetricians and Gynecologists’ New Jersey section. “But on the other hand, there are lots of costs and emotional distress” associated with false-positive results.

The professional group doesn’t recommend supplemental screening for women with dense breasts who don’t have any additional risk factors for cancer.

Many other professional groups take a similar position.

“We recommend having a conversation with a health care provider, and for patients to understand whether their breasts are dense,” Dr. Mass said. “But we do not recommend everyone get tested.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

When Katie Couric shared the news of her breast cancer diagnosis, the former co-host of NBC’s “Today” show said she considered this new health challenge to be a teachable moment to encourage people to get needed cancer screenings.

“Please get your annual mammogram,” she wrote on her website in September. “But just as importantly, please find out if you need additional screening.”

In the essay, Couric, 65, explained that because she tends to have dense breast tissue, she gets an ultrasound test in addition to a mammogram when screening for breast cancer. A breast ultrasound, sometimes called a sonogram, uses sound waves to take images of the breast tissue. It can sometimes identify malignancies that are hard to spot on a mammogram in women whose breasts are dense – that is, having a high proportion of fibrous tissue and glands vs. fatty tissue.

Ms. Couric, who famously underwent a colonoscopy on live television after her first husband died of colon cancer and who lost her sister to pancreatic cancer, has long pushed for cancer screening and better detection options.

Breast cancer experts applauded Ms. Couric for drawing attention to breast density as a risk factor for cancer. But some were less comfortable with her advocacy for supplemental screening.

“We don’t have evidence that auxiliary screening reduces breast cancer mortality or improves quality of life,” said Dr. Carol Mangione, a professor of medicine and public health at the University of California, Los Angeles, who chairs the U.S. Preventive Services Task Force, a group of medical experts who make recommendations for preventive services after weighing their benefits and harms.

Ms. Couric’s office did not respond to requests for comment.

In addition to an annual mammogram, some women with dense breasts get a breast ultrasound or MRI to help identify cancerous cells missed by the mammogram. Dense fibrous tissue appears white on a mammogram and makes it harder to see cancers, which also appear white. Fatty breast tissue, which appears dark on the mammogram, doesn’t obscure breast malignancies.

As digital breast tomosynthesis, or 3-D mammography, has become more widely available, a growing number of women are getting that screening test rather than the standard 2-D mammography. The 3-D mammography has been found to reduce the number of false-positive results and identify more cancers in some women with dense breasts, though the impact on mortality is unknown.

The task force gives an “I” rating to supplemental screening for women with dense breasts whose mammogram results don’t indicate a problem. That means the current evidence is “insufficient” to assess whether the benefits outweigh the harms of the extra screening. (The task force is updating its recommendation for breast cancer screening, including supplemental screening for women with dense breasts.)

One key harm that researchers are concerned about, besides the possible extra cost, is the chance of a false-positive result. Supplemental imaging in women who aren’t at high risk for breast cancer may identify potential trouble spots, which can lead to follow-up testing such as breast biopsies that are invasive and raise cancer fears for many patients. But research has found that very often these results turn out to be false alarms.

If 1,000 women with dense breasts get an ultrasound after a negative mammogram, the ultrasound will identify two to three cancers, studies show. But the extra imaging will also identify up to 117 potential problems that lead to recall visits and tests but are ultimately determined to be false positives.

“On the one hand, we want to do everything we can to improve detection,” said Dr. Sharon Mass, an ob.gyn. in Morristown, N.J., and the former chair of the American College of Obstetricians and Gynecologists’ New Jersey section. “But on the other hand, there are lots of costs and emotional distress” associated with false-positive results.

The professional group doesn’t recommend supplemental screening for women with dense breasts who don’t have any additional risk factors for cancer.

Many other professional groups take a similar position.

“We recommend having a conversation with a health care provider, and for patients to understand whether their breasts are dense,” Dr. Mass said. “But we do not recommend everyone get tested.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

When Katie Couric shared the news of her breast cancer diagnosis, the former co-host of NBC’s “Today” show said she considered this new health challenge to be a teachable moment to encourage people to get needed cancer screenings.

“Please get your annual mammogram,” she wrote on her website in September. “But just as importantly, please find out if you need additional screening.”

In the essay, Couric, 65, explained that because she tends to have dense breast tissue, she gets an ultrasound test in addition to a mammogram when screening for breast cancer. A breast ultrasound, sometimes called a sonogram, uses sound waves to take images of the breast tissue. It can sometimes identify malignancies that are hard to spot on a mammogram in women whose breasts are dense – that is, having a high proportion of fibrous tissue and glands vs. fatty tissue.

Ms. Couric, who famously underwent a colonoscopy on live television after her first husband died of colon cancer and who lost her sister to pancreatic cancer, has long pushed for cancer screening and better detection options.

Breast cancer experts applauded Ms. Couric for drawing attention to breast density as a risk factor for cancer. But some were less comfortable with her advocacy for supplemental screening.

“We don’t have evidence that auxiliary screening reduces breast cancer mortality or improves quality of life,” said Dr. Carol Mangione, a professor of medicine and public health at the University of California, Los Angeles, who chairs the U.S. Preventive Services Task Force, a group of medical experts who make recommendations for preventive services after weighing their benefits and harms.

Ms. Couric’s office did not respond to requests for comment.

In addition to an annual mammogram, some women with dense breasts get a breast ultrasound or MRI to help identify cancerous cells missed by the mammogram. Dense fibrous tissue appears white on a mammogram and makes it harder to see cancers, which also appear white. Fatty breast tissue, which appears dark on the mammogram, doesn’t obscure breast malignancies.

As digital breast tomosynthesis, or 3-D mammography, has become more widely available, a growing number of women are getting that screening test rather than the standard 2-D mammography. The 3-D mammography has been found to reduce the number of false-positive results and identify more cancers in some women with dense breasts, though the impact on mortality is unknown.

The task force gives an “I” rating to supplemental screening for women with dense breasts whose mammogram results don’t indicate a problem. That means the current evidence is “insufficient” to assess whether the benefits outweigh the harms of the extra screening. (The task force is updating its recommendation for breast cancer screening, including supplemental screening for women with dense breasts.)

One key harm that researchers are concerned about, besides the possible extra cost, is the chance of a false-positive result. Supplemental imaging in women who aren’t at high risk for breast cancer may identify potential trouble spots, which can lead to follow-up testing such as breast biopsies that are invasive and raise cancer fears for many patients. But research has found that very often these results turn out to be false alarms.

If 1,000 women with dense breasts get an ultrasound after a negative mammogram, the ultrasound will identify two to three cancers, studies show. But the extra imaging will also identify up to 117 potential problems that lead to recall visits and tests but are ultimately determined to be false positives.

“On the one hand, we want to do everything we can to improve detection,” said Dr. Sharon Mass, an ob.gyn. in Morristown, N.J., and the former chair of the American College of Obstetricians and Gynecologists’ New Jersey section. “But on the other hand, there are lots of costs and emotional distress” associated with false-positive results.

The professional group doesn’t recommend supplemental screening for women with dense breasts who don’t have any additional risk factors for cancer.

Many other professional groups take a similar position.

“We recommend having a conversation with a health care provider, and for patients to understand whether their breasts are dense,” Dr. Mass said. “But we do not recommend everyone get tested.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months [95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months (95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months (95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Orimo and colleagues addressed the use of liver resection in patients with more than one HCC in the liver. Patients with no or Child-Pugh A/B cirrhosis were included in this single-center retrospective study of 1088 patients who underwent hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stage 0 (n = 88), A (n = 750), or B (n = 250) HCC, with stages A and B subcategorized into A1 (single nodule 2-5 cm or ≤ 3 nodules ≤ 3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥ 10 cm), B1 (2-3 nodules > 3 cm), and B2 (≥ 4 nodules). The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (P < .0001). Significant differences in overall survival (OS) were found between stages A1 and A2 (P = .0118), A2 and A3 (P = .0013), and B1 and B2 (P = .0050), but not between stages A3 and B1 (P = .4742). In stage B1 patients, Child-Pugh B cirrhosis was the only independent prognostic factor for OS. The authors concluded that hepatectomy is beneficial in patients with three or fewer hepatocellular carcinomas and either no or Child-Pugh class A cirrhosis, with the long-term results being comparable to those in patients who underwent a resection of a single HCC. Therefore, resection of up to three HCC is safe and should be considered in clinically appropriate patients.

Many patients with multifocal HCC are not eligible for liver-directed therapies. The standard of care for first-line systemic therapy is the combination of atezolizumab and bevacizumab, as reported in the IMbrave150 clinical trial. Fulgenzi and colleagues published the results of a multicenter prospective observational study, AB-Real, that included 433 patients who received atezolizumab and bevacizumab in routine clinical practice. The investigators confirmed the efficacy of the combination and found that portal vein tumor thrombosis and worse albumin-bilirubin grade were independent prognostic factors for poor OS and were associated with an increased risk for hemorrhagic events. In addition, the authors reported that the overall response rate (ORR) predicted better outcomes, including longer OS. Therefore, atezolizumab and bevacizumab remains a safe and effective first-line treatment for many patients with unresectable HCC.

Finally, Finn and colleagues reported the results of an open-label, noncomparative cohort of the REACH-2 study of ramucirumab in 47 patients with advanced HCC and an alpha-fetoprotein (AFP) level ≥ 400 ng/mL. These patients had previously received one to two lines of systemic therapy, excluding sorafenib or chemotherapy. Lenvatinib was the most common prior systemic therapy (n = 20; 43%). Others included immune checkpoint inhibitor (CPI) monotherapies (n = 11), CPI/antiangiogenic therapy (n = 14), or dual CPI therapy (n = 5). The ORR was 10.6% (95% CI 1.8-19.5) and disease control rate was 46.8% (95% CI 32.5-61.1), with a median duration of response of 8.3 months (95% CI 2.4 to not reached). The grade 3 or more adverse event rate was 57%, with hypertension (11%) being the most common, allowing the authors to conclude that ramucirumab offers clinically significant efficacy with no new safety signals in this setting. Therefore, ramucirumab remains as a safe and effective later-line treatment option for patients with unresectable HCC and an AFP ≥ 400 ng/mL.

Oral immunotherapy (OIT) for food allergy can help prevent anaphylaxis after accidental encounters with an allergen, but the treatment rarely cures the allergy, it has risks, and it requires long-term planning and shared decision-making by patients, their families, and their allergists, according to a new review.

In OIT, a patient who is allergic to a specific food consumes increasing amounts of the allergen over time to reduce their risk for allergic reaction.

“OIT is an elective, usually noncurative procedure with inherent risks that require families to function as amateur medical professionals. Preparing them for this role is essential to protect patients and ensure the long-term success of this life-changing procedure,” lead author Douglas P. Mack, MD, MSc, a pediatric allergy, asthma, and immunology specialist at McMaster University in Hamilton, Ont., and colleagues write in Clinical & Experimental Allergy.
 

From strict avoidance to desensitization

Food allergy treatment has traditionally involved avoiding accidental exposure that may lead to anaphylaxis and providing rescue medication. In recent years, OIT “has been recommended by several guidelines as a primary option,” Dr. Mack and coauthors write. And with the “approval by European and USA regulators of [peanut allergen powder] Palforzia [Aimmune Therapeutics], there are now commercial and noncommercial forms of OIT available for use in several countries.”

They advise physicians to take a proactive, educational, supportive approach to patients and their families throughout the therapy.

“Ultimately, the decision to pursue OIT or continue avoidance strategies remains the responsibility of the family and the patients,” they write. “Some families may not be prepared for the role that they have to play in actively managing their child’s food allergy treatment.”
 

Strategies to overcome OIT challenges

Reviewing the literature about OIT for food allergy, the authors suggest various strategies physicians can use to help OIT patients and their families prepare for and overcome common treatment-related challenges.

Two experts welcome the report

Rita Kachru, MD, a specialist in allergy and immunology and a codirector of the food allergy program at UCLA Health in Los Angeles, called this “an excellent report about a wonderful, individualized option in food allergy management.

“The authors did an excellent job delineating OIT terminology, outlining the goals, risks, and benefits of OIT, noting that it’s not a cure, and emphasizing the crucial importance of discussions with each family throughout the process,” Dr. Kachru, who was not involved in developing the report, told this news organization.

“I thoroughly agree with their assessment,” she added. “The more you do OIT research and clinical care, the more you realize the pitfalls, the benefits, and the importance of patient goals and family dynamics. Discussing the goals, risks, benefits, and alternatives to OIT in detail with the family is crucial so they fully understand the process.”

Basil M. Kahwash, MD, an allergy, pulmonary, and critical care medicine specialist at Vanderbilt University Medical Center in Nashville, Tenn., said that providers in the immunology community have been discussing OIT for years and that he welcomes the well-written report that summarizes the evidence.  

“It’s important to periodically summarize the evidence, as well as the consensus expert opinion about the evidence, so we may better inform our colleagues and patients,” said Dr. Kahwash, who was not involved in developing the report. “The authors are well-known experts in our field who have experience with OIT and with reviewing the evidence of food allergy.

“OIT can be a fantastic option for some patients, especially those who are very highly motivated and understand the process from start to finish. But OIT is not the best option for every child, and it’s not much of an option for adults,” he explained. “Patients need to be chosen carefully and understand the level of motivation required to safely follow through with the treatment.

“The report will hopefully affect patient care positively and allow patients to understand the limitations around OIT when they consider their candidacy for it,” he added. “In most cases, OIT patients will still need to avoid the allergen, but if a small amount accidentally gets into their food, they probably won’t have a very severe reaction to it.”

Dr. Kahwash would like to see data on patients who have seen long-term remission with OIT.

“Clearly, some patients benefit from OIT. What differentiates patients who benefit from OIT from those who do not?” he asked. “In the future, we need to consider possible biomarkers of patients who are and who aren’t good candidates for OIT.  

“Regardless of OIT’s limitations, the potential for desensitization rather than strict avoidance represents a big step in the evolution of food allergy treatment,” Dr. Kahwash noted.

No funding details were provided. Dr. Mack and three coauthors report financial relationships with Aimmune. Aimmune Therapeutics is the manufacturer of Palforzia OIT (AR101 powder provided in capsules and sachets). Most coauthors also report financial relationships with other pharmaceutical companies. The full list can be found with the original article. Dr. Kachru was an investigator in the PALISADES clinical trial of AR101. Dr. Kahwash reports no relevant financial relationships.

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

Oral immunotherapy (OIT) for food allergy can help prevent anaphylaxis after accidental encounters with an allergen, but the treatment rarely cures the allergy, it has risks, and it requires long-term planning and shared decision-making by patients, their families, and their allergists, according to a new review.

In OIT, a patient who is allergic to a specific food consumes increasing amounts of the allergen over time to reduce their risk for allergic reaction.

“OIT is an elective, usually noncurative procedure with inherent risks that require families to function as amateur medical professionals. Preparing them for this role is essential to protect patients and ensure the long-term success of this life-changing procedure,” lead author Douglas P. Mack, MD, MSc, a pediatric allergy, asthma, and immunology specialist at McMaster University in Hamilton, Ont., and colleagues write in Clinical & Experimental Allergy.
 

From strict avoidance to desensitization

Food allergy treatment has traditionally involved avoiding accidental exposure that may lead to anaphylaxis and providing rescue medication. In recent years, OIT “has been recommended by several guidelines as a primary option,” Dr. Mack and coauthors write. And with the “approval by European and USA regulators of [peanut allergen powder] Palforzia [Aimmune Therapeutics], there are now commercial and noncommercial forms of OIT available for use in several countries.”

They advise physicians to take a proactive, educational, supportive approach to patients and their families throughout the therapy.

“Ultimately, the decision to pursue OIT or continue avoidance strategies remains the responsibility of the family and the patients,” they write. “Some families may not be prepared for the role that they have to play in actively managing their child’s food allergy treatment.”
 

Strategies to overcome OIT challenges

Reviewing the literature about OIT for food allergy, the authors suggest various strategies physicians can use to help OIT patients and their families prepare for and overcome common treatment-related challenges.

Two experts welcome the report

Rita Kachru, MD, a specialist in allergy and immunology and a codirector of the food allergy program at UCLA Health in Los Angeles, called this “an excellent report about a wonderful, individualized option in food allergy management.

“The authors did an excellent job delineating OIT terminology, outlining the goals, risks, and benefits of OIT, noting that it’s not a cure, and emphasizing the crucial importance of discussions with each family throughout the process,” Dr. Kachru, who was not involved in developing the report, told this news organization.

“I thoroughly agree with their assessment,” she added. “The more you do OIT research and clinical care, the more you realize the pitfalls, the benefits, and the importance of patient goals and family dynamics. Discussing the goals, risks, benefits, and alternatives to OIT in detail with the family is crucial so they fully understand the process.”

Basil M. Kahwash, MD, an allergy, pulmonary, and critical care medicine specialist at Vanderbilt University Medical Center in Nashville, Tenn., said that providers in the immunology community have been discussing OIT for years and that he welcomes the well-written report that summarizes the evidence.  

“It’s important to periodically summarize the evidence, as well as the consensus expert opinion about the evidence, so we may better inform our colleagues and patients,” said Dr. Kahwash, who was not involved in developing the report. “The authors are well-known experts in our field who have experience with OIT and with reviewing the evidence of food allergy.

“OIT can be a fantastic option for some patients, especially those who are very highly motivated and understand the process from start to finish. But OIT is not the best option for every child, and it’s not much of an option for adults,” he explained. “Patients need to be chosen carefully and understand the level of motivation required to safely follow through with the treatment.

“The report will hopefully affect patient care positively and allow patients to understand the limitations around OIT when they consider their candidacy for it,” he added. “In most cases, OIT patients will still need to avoid the allergen, but if a small amount accidentally gets into their food, they probably won’t have a very severe reaction to it.”

Dr. Kahwash would like to see data on patients who have seen long-term remission with OIT.

“Clearly, some patients benefit from OIT. What differentiates patients who benefit from OIT from those who do not?” he asked. “In the future, we need to consider possible biomarkers of patients who are and who aren’t good candidates for OIT.  

“Regardless of OIT’s limitations, the potential for desensitization rather than strict avoidance represents a big step in the evolution of food allergy treatment,” Dr. Kahwash noted.

No funding details were provided. Dr. Mack and three coauthors report financial relationships with Aimmune. Aimmune Therapeutics is the manufacturer of Palforzia OIT (AR101 powder provided in capsules and sachets). Most coauthors also report financial relationships with other pharmaceutical companies. The full list can be found with the original article. Dr. Kachru was an investigator in the PALISADES clinical trial of AR101. Dr. Kahwash reports no relevant financial relationships.

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

Oral immunotherapy (OIT) for food allergy can help prevent anaphylaxis after accidental encounters with an allergen, but the treatment rarely cures the allergy, it has risks, and it requires long-term planning and shared decision-making by patients, their families, and their allergists, according to a new review.

In OIT, a patient who is allergic to a specific food consumes increasing amounts of the allergen over time to reduce their risk for allergic reaction.

“OIT is an elective, usually noncurative procedure with inherent risks that require families to function as amateur medical professionals. Preparing them for this role is essential to protect patients and ensure the long-term success of this life-changing procedure,” lead author Douglas P. Mack, MD, MSc, a pediatric allergy, asthma, and immunology specialist at McMaster University in Hamilton, Ont., and colleagues write in Clinical & Experimental Allergy.
 

From strict avoidance to desensitization

Food allergy treatment has traditionally involved avoiding accidental exposure that may lead to anaphylaxis and providing rescue medication. In recent years, OIT “has been recommended by several guidelines as a primary option,” Dr. Mack and coauthors write. And with the “approval by European and USA regulators of [peanut allergen powder] Palforzia [Aimmune Therapeutics], there are now commercial and noncommercial forms of OIT available for use in several countries.”

They advise physicians to take a proactive, educational, supportive approach to patients and their families throughout the therapy.

“Ultimately, the decision to pursue OIT or continue avoidance strategies remains the responsibility of the family and the patients,” they write. “Some families may not be prepared for the role that they have to play in actively managing their child’s food allergy treatment.”
 

Strategies to overcome OIT challenges

Reviewing the literature about OIT for food allergy, the authors suggest various strategies physicians can use to help OIT patients and their families prepare for and overcome common treatment-related challenges.

Two experts welcome the report

Rita Kachru, MD, a specialist in allergy and immunology and a codirector of the food allergy program at UCLA Health in Los Angeles, called this “an excellent report about a wonderful, individualized option in food allergy management.

“The authors did an excellent job delineating OIT terminology, outlining the goals, risks, and benefits of OIT, noting that it’s not a cure, and emphasizing the crucial importance of discussions with each family throughout the process,” Dr. Kachru, who was not involved in developing the report, told this news organization.

“I thoroughly agree with their assessment,” she added. “The more you do OIT research and clinical care, the more you realize the pitfalls, the benefits, and the importance of patient goals and family dynamics. Discussing the goals, risks, benefits, and alternatives to OIT in detail with the family is crucial so they fully understand the process.”

Basil M. Kahwash, MD, an allergy, pulmonary, and critical care medicine specialist at Vanderbilt University Medical Center in Nashville, Tenn., said that providers in the immunology community have been discussing OIT for years and that he welcomes the well-written report that summarizes the evidence.  

“It’s important to periodically summarize the evidence, as well as the consensus expert opinion about the evidence, so we may better inform our colleagues and patients,” said Dr. Kahwash, who was not involved in developing the report. “The authors are well-known experts in our field who have experience with OIT and with reviewing the evidence of food allergy.

“OIT can be a fantastic option for some patients, especially those who are very highly motivated and understand the process from start to finish. But OIT is not the best option for every child, and it’s not much of an option for adults,” he explained. “Patients need to be chosen carefully and understand the level of motivation required to safely follow through with the treatment.

“The report will hopefully affect patient care positively and allow patients to understand the limitations around OIT when they consider their candidacy for it,” he added. “In most cases, OIT patients will still need to avoid the allergen, but if a small amount accidentally gets into their food, they probably won’t have a very severe reaction to it.”

Dr. Kahwash would like to see data on patients who have seen long-term remission with OIT.

“Clearly, some patients benefit from OIT. What differentiates patients who benefit from OIT from those who do not?” he asked. “In the future, we need to consider possible biomarkers of patients who are and who aren’t good candidates for OIT.  

“Regardless of OIT’s limitations, the potential for desensitization rather than strict avoidance represents a big step in the evolution of food allergy treatment,” Dr. Kahwash noted.

No funding details were provided. Dr. Mack and three coauthors report financial relationships with Aimmune. Aimmune Therapeutics is the manufacturer of Palforzia OIT (AR101 powder provided in capsules and sachets). Most coauthors also report financial relationships with other pharmaceutical companies. The full list can be found with the original article. Dr. Kachru was an investigator in the PALISADES clinical trial of AR101. Dr. Kahwash reports no relevant financial relationships.

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

Taking call is one of the more challenging - and annoying - aspects of the job for many physicians. Calls may wake them up in the middle of the night and can interfere with their at-home activities. In Medscape’s Employed Physicians Report, 37% of respondents said they have from 1 to 5 hours of call per month; 19% said they have 6 to 10 hours; and 12% have 11 hours or more.

“Even if you don’t have to come in to the ED, you can get calls in the middle of the night, and you may get paid very little, if anything,” said Robert Bitterman MD, JD, an emergency physician and attorney in Harbor Springs, Mich.

And responding to the calls is not optional. Dr. Bitterman said if on-call physicians don’t perform their duties, they could lose their hospital privileges, be fined by the federal government, or be sued for malpractice.

On-call activities are regulated by the federal Emergency Medical Treatment and Active Labor Act (EMTALA). Dr. Bitterman said it’s rare for the federal government to prosecute on-call physicians for violating EMTALA. Instead, it’s more likely that the hospital will be fined for EMTALA violations committed by on-call physicians.

However, the hospital passes the on-call obligation on to individual physicians through medical staff bylaws. Physicians who violate the bylaws may have their privileges restricted or removed, Dr. Bitterman said. Physicians could also be sued for malpractice, even if they never treated the patient, he added.
 

After-hours call duty in physicians’ practices

A very different type of call duty is having to respond to calls from one’s own patients after regular hours. Unlike doctors on ED call, who usually deal with patients they have never met, these physicians deal with their established patients or those of a colleague in their practice.

Courts have established that physicians have to provide an answering service or other means for their patients to contact them after hours, and the doctor must respond to these calls in a timely manner.

In a 2015 Louisiana ruling, a cardiologist was found liable for malpractice because he didn’t respond to an after-hours call from his patient. The patient tried several times to contact the cardiologist but got no reply.

Physicians may also be responsible if their answering service does not send critical messages to them immediately, if it fails to make appropriate documentation, or if it sends inaccurate data to the doctor.
 

Cases when on-call doctors didn’t respond

The Office of the Inspector General (OIG) of the U.S. Health and Human Services Administration oversees federal EMTALA violations and regularly reports them.

In 2018, the OIG fined a hospital in Waterloo, Iowa, $90,000 when an on-call cardiologist failed to implant a pacemaker for an ED patient. According to the OIG’s report, the patient arrived at the hospital with heart problems. Reached by phone, the cardiologist directed the ED physician to begin transcutaneous pacing but asked that the patient be transferred to another hospital for placement of the pacemaker. The patient died after transfer.

The OIG found that the original cardiologist could have placed the pacemaker, but, as often happens, it only fined the hospital, not the on-call physician for the EMTALA violation.

EMTALA requires that hospitals provide on-call specialists to assist emergency physicians with care of patients who arrive in the ED. In specialties for which there are few doctors to choose from, the on-call specialist may be on duty every third night and every third weekend. This can be daunting, especially for specialists who’ve had a grueling day of work.

Occasionally, on-call physicians, fearful they could make a medical error, request that the patient be transferred to another hospital for treatment. This is what a neurosurgeon who was on call at a Topeka, Kan., hospital did in 2001. Transferred to another hospital, the patient underwent an operation but lost sensation in his lower extremities. The patient sued the on-call neurosurgeon for negligence.

During the trial, the on-call neurosurgeon testified that he was “feeling run-down because he had been an on-call physician every third night for more than 10 years.” He also said this was the first time he had refused to see a patient because of fatigue, and he had decided that the patient “would be better off at a trauma center that had a trauma team and a fresher surgeon.”

The neurosurgeon successfully defended the malpractice suit, but Dr. Bitterman said he might have lost had there not been some unusual circumstances in the case. The court ruled that the hospital had not clearly defined the duties of on-call physicians, and the lawsuit didn’t cite the neurosurgeon’s EMTALA duty.
 

On-call duties defined by EMTALA

EMTALA sets the overall rules for on-call duties, which each hospital is expected to fine-tune on the basis of its own particular circumstances. Here are some of those rules, issued by the Centers for Medicare & Medicaid Services and the OIG.

Only an individual physician can be on call. The hospital’s on-call schedule cannot name a physician practice.

Call applies to all ED patients. Physicians cannot limit their on-call responsibilities to their own patients, to patients in their insurance network, or to paying patients.

There may be some gaps in the call schedule. The OIG is not specific as to how many gaps are allowed, said Nick Healey, an attorney in Cheyenne, Wyo., who has written about on-call duties. Among other things, adequate coverage depends on the number of available physicians and the demand for their services. Mr. Healey added that states may require more extensive availability of on-call physicians at high-level trauma centers.

Hospitals must have made arrangements for transfer. Whenever there is a gap in the schedule, hospitals need to have a designated hospital to send the patient to. Hospitals that unnecessarily transfer patients will be penalized.

The ED physician calls the shots. The emergency physician handling the case decides if the on-call doctor has to come in and treat the patient firsthand.

The on-call physician may delegate the work to others. On-call physicians may designate a nurse practitioner or physician assistant, but the on-call physician is ultimately responsible. The ED doctor may require the physician to come in anyway, according to Todd B. Taylor, MD, an emergency physician in Phoenix, who has written about on-call duties. Dr. Bitterman noted that the physician may designate a colleague to take their call, but the substitute has to have privileges at the hospital.

Physicians may do their own work while on call. Physicians can perform elective surgery while on call, provided they have made arrangements if they then become unavailable for duty, Dr. Taylor said. He added that physicians can also have simultaneous call at other hospitals, provided they make arrangements.
 

The hospital fine-tunes call obligations

The hospital is expected to further define the federal rules. For instance, the CMS says physicians should respond to calls within a “reasonable period of time” and requires hospitals to specify response times, which may be 15-30 minutes for responding to phone calls and traveling to the ED, Dr. Bitterman said.

The CMS says older physicians can be exempted from call. The hospital determines the age at which physicians can be exempted. “Hospitals typically exempt physicians over age 65 or 70, or when they have certain medical conditions,” said Lowell Brown, a Los Angeles attorney who deals with on-call duties.

The hospital also sets the call schedule, which may result in uncovered periods in specialties in which there are few physicians to draw from, according to Mr. Healey. He said many hospitals still use a simple rule of thumb, even though it has been dismissed by the CMS. Under this so-called “rule of three,” hospitals that have three doctors or fewer in a specialty do not have to provide constant call coverage.

On-call rules are part of the medical staff bylaws, and they have to be approved by the medical staff. This may require delicate negotiations between the staff’s leadership and administrators, Dr. Bitterman said.

It is often up to the emergency physician on duty to enforce the hospital’s on-call rules, Dr. Taylor said. “If the ED physician is having trouble, he or she may contact the on-call physician’s department chairman or, if necessary, the chief of the medical staff and ask that person to deal with the physician,” Dr. Taylor said.

The ED physician has to determine whether the patient needs to be transferred to another hospital. Dr. Taylor said the ED physician must fill out a transfer form and obtain consent from the receiving hospital.

If a patient has to be transferred because an on-call physician failed to appear, the originating hospital has to report this to the CMS, and the physician and the hospital can be cited for an inappropriate transfer and fined, Mr. Brown said. “The possibility of being identified in this way should be a powerful incentive to accept call duty,” he added.
 

Malpractice exposure of on-call physicians

When on-call doctors provide medical advice regarding an ED patient, that advice may be subject to malpractice litigation, Dr. Taylor said. “Even if you only give the ED doctor advice over the phone, that may establish a patient-physician relationship and a duty that patient can cite in a malpractice case,” he noted.

Refusing to take call may also be grounds for a malpractice lawsuit, Dr. Bitterman said. Refusing to see a patient would not be considered medical negligence, he continued, because no medical decision is made. Rather, it involves general negligence, which occurs when physicians fail to carry out duties expected of them.

Dr. Bitterman cited a 2006 malpractice judgment in which an on-call neurosurgeon in Missouri was found to be generally negligent. The neurosurgeon had arranged for a colleague in his practice to take his call, but the colleague did not have privileges at the hospital.

A patient with a brain bleed came in and the substitute was on duty. The patient had to be transferred to another hospital, where the patient died. The court ordered that the on-call doctor and the originating hospital had to split a fine of $400,800.
 

On-call physicians can be charged with abandonment

Dr. Bitterman said that if on-call physicians do not provide expected follow-up treatment for an ED patient, they could be charged with abandonment, which is a matter of state law and involves filing a malpractice lawsuit.

Abandonment involves unilaterally terminating the patient relationship without providing notice. There must be an established relationship, which, in the case of call, is formed when the doctor comes to the ED to examine or admit the patient, Dr. Bitterman said. He added that the on-call doctor’s obligation applies only to the medical condition the patient came in for.

Even when an on-call doctor does not see a patient, a relationship can be established if the hospital requires its on-call doctors to make follow-up visits for ED patients, Dr. Taylor said. At some hospitals, he said, on-call doctors have blanket agreements to provide follow-up care in return for not having to arrive in the middle of the night during the ED visit.

Dr. Taylor gave an example of the on-call doctor’s obligation: “The ED doctor puts a splint on the patient’s ankle fracture, and the orthopedic surgeon on call agrees to follow up with the patient within the next few days. If the orthopedic surgeon refuses to follow up without making a reasonable accommodation, it may become an issue of patient abandonment.”
 

Now everyone has a good grasp of the rules

Fifteen years ago, many doctors were in open revolt against on-call duties, but they are more accepting now and understand the rules better, Mr. Healey said.

“Many hospitals have begun paying some specialists for call and designating hospitalists and surgicalists to do at least some of the work that used to be expected of on-call doctors,” he said.

According to Dr. Taylor, today’s on-call doctors often have less to do than in the past. “For example,” he said, “the hospitalist may admit an orthopedic patient at night, and then the orthopedic surgeon does the operation the next day. We’ve had EMTALA for 36 years now, and hospitals and doctors know how call works.”

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

Taking call is one of the more challenging - and annoying - aspects of the job for many physicians. Calls may wake them up in the middle of the night and can interfere with their at-home activities. In Medscape’s Employed Physicians Report, 37% of respondents said they have from 1 to 5 hours of call per month; 19% said they have 6 to 10 hours; and 12% have 11 hours or more.

“Even if you don’t have to come in to the ED, you can get calls in the middle of the night, and you may get paid very little, if anything,” said Robert Bitterman MD, JD, an emergency physician and attorney in Harbor Springs, Mich.

And responding to the calls is not optional. Dr. Bitterman said if on-call physicians don’t perform their duties, they could lose their hospital privileges, be fined by the federal government, or be sued for malpractice.

On-call activities are regulated by the federal Emergency Medical Treatment and Active Labor Act (EMTALA). Dr. Bitterman said it’s rare for the federal government to prosecute on-call physicians for violating EMTALA. Instead, it’s more likely that the hospital will be fined for EMTALA violations committed by on-call physicians.

However, the hospital passes the on-call obligation on to individual physicians through medical staff bylaws. Physicians who violate the bylaws may have their privileges restricted or removed, Dr. Bitterman said. Physicians could also be sued for malpractice, even if they never treated the patient, he added.
 

After-hours call duty in physicians’ practices

A very different type of call duty is having to respond to calls from one’s own patients after regular hours. Unlike doctors on ED call, who usually deal with patients they have never met, these physicians deal with their established patients or those of a colleague in their practice.

Courts have established that physicians have to provide an answering service or other means for their patients to contact them after hours, and the doctor must respond to these calls in a timely manner.

In a 2015 Louisiana ruling, a cardiologist was found liable for malpractice because he didn’t respond to an after-hours call from his patient. The patient tried several times to contact the cardiologist but got no reply.

Physicians may also be responsible if their answering service does not send critical messages to them immediately, if it fails to make appropriate documentation, or if it sends inaccurate data to the doctor.
 

Cases when on-call doctors didn’t respond

The Office of the Inspector General (OIG) of the U.S. Health and Human Services Administration oversees federal EMTALA violations and regularly reports them.

In 2018, the OIG fined a hospital in Waterloo, Iowa, $90,000 when an on-call cardiologist failed to implant a pacemaker for an ED patient. According to the OIG’s report, the patient arrived at the hospital with heart problems. Reached by phone, the cardiologist directed the ED physician to begin transcutaneous pacing but asked that the patient be transferred to another hospital for placement of the pacemaker. The patient died after transfer.

The OIG found that the original cardiologist could have placed the pacemaker, but, as often happens, it only fined the hospital, not the on-call physician for the EMTALA violation.

EMTALA requires that hospitals provide on-call specialists to assist emergency physicians with care of patients who arrive in the ED. In specialties for which there are few doctors to choose from, the on-call specialist may be on duty every third night and every third weekend. This can be daunting, especially for specialists who’ve had a grueling day of work.

Occasionally, on-call physicians, fearful they could make a medical error, request that the patient be transferred to another hospital for treatment. This is what a neurosurgeon who was on call at a Topeka, Kan., hospital did in 2001. Transferred to another hospital, the patient underwent an operation but lost sensation in his lower extremities. The patient sued the on-call neurosurgeon for negligence.

During the trial, the on-call neurosurgeon testified that he was “feeling run-down because he had been an on-call physician every third night for more than 10 years.” He also said this was the first time he had refused to see a patient because of fatigue, and he had decided that the patient “would be better off at a trauma center that had a trauma team and a fresher surgeon.”

The neurosurgeon successfully defended the malpractice suit, but Dr. Bitterman said he might have lost had there not been some unusual circumstances in the case. The court ruled that the hospital had not clearly defined the duties of on-call physicians, and the lawsuit didn’t cite the neurosurgeon’s EMTALA duty.
 

On-call duties defined by EMTALA

EMTALA sets the overall rules for on-call duties, which each hospital is expected to fine-tune on the basis of its own particular circumstances. Here are some of those rules, issued by the Centers for Medicare & Medicaid Services and the OIG.

Only an individual physician can be on call. The hospital’s on-call schedule cannot name a physician practice.

Call applies to all ED patients. Physicians cannot limit their on-call responsibilities to their own patients, to patients in their insurance network, or to paying patients.

There may be some gaps in the call schedule. The OIG is not specific as to how many gaps are allowed, said Nick Healey, an attorney in Cheyenne, Wyo., who has written about on-call duties. Among other things, adequate coverage depends on the number of available physicians and the demand for their services. Mr. Healey added that states may require more extensive availability of on-call physicians at high-level trauma centers.

Hospitals must have made arrangements for transfer. Whenever there is a gap in the schedule, hospitals need to have a designated hospital to send the patient to. Hospitals that unnecessarily transfer patients will be penalized.

The ED physician calls the shots. The emergency physician handling the case decides if the on-call doctor has to come in and treat the patient firsthand.

The on-call physician may delegate the work to others. On-call physicians may designate a nurse practitioner or physician assistant, but the on-call physician is ultimately responsible. The ED doctor may require the physician to come in anyway, according to Todd B. Taylor, MD, an emergency physician in Phoenix, who has written about on-call duties. Dr. Bitterman noted that the physician may designate a colleague to take their call, but the substitute has to have privileges at the hospital.

Physicians may do their own work while on call. Physicians can perform elective surgery while on call, provided they have made arrangements if they then become unavailable for duty, Dr. Taylor said. He added that physicians can also have simultaneous call at other hospitals, provided they make arrangements.
 

The hospital fine-tunes call obligations

The hospital is expected to further define the federal rules. For instance, the CMS says physicians should respond to calls within a “reasonable period of time” and requires hospitals to specify response times, which may be 15-30 minutes for responding to phone calls and traveling to the ED, Dr. Bitterman said.

The CMS says older physicians can be exempted from call. The hospital determines the age at which physicians can be exempted. “Hospitals typically exempt physicians over age 65 or 70, or when they have certain medical conditions,” said Lowell Brown, a Los Angeles attorney who deals with on-call duties.

The hospital also sets the call schedule, which may result in uncovered periods in specialties in which there are few physicians to draw from, according to Mr. Healey. He said many hospitals still use a simple rule of thumb, even though it has been dismissed by the CMS. Under this so-called “rule of three,” hospitals that have three doctors or fewer in a specialty do not have to provide constant call coverage.

On-call rules are part of the medical staff bylaws, and they have to be approved by the medical staff. This may require delicate negotiations between the staff’s leadership and administrators, Dr. Bitterman said.

It is often up to the emergency physician on duty to enforce the hospital’s on-call rules, Dr. Taylor said. “If the ED physician is having trouble, he or she may contact the on-call physician’s department chairman or, if necessary, the chief of the medical staff and ask that person to deal with the physician,” Dr. Taylor said.

The ED physician has to determine whether the patient needs to be transferred to another hospital. Dr. Taylor said the ED physician must fill out a transfer form and obtain consent from the receiving hospital.

If a patient has to be transferred because an on-call physician failed to appear, the originating hospital has to report this to the CMS, and the physician and the hospital can be cited for an inappropriate transfer and fined, Mr. Brown said. “The possibility of being identified in this way should be a powerful incentive to accept call duty,” he added.
 

Malpractice exposure of on-call physicians

When on-call doctors provide medical advice regarding an ED patient, that advice may be subject to malpractice litigation, Dr. Taylor said. “Even if you only give the ED doctor advice over the phone, that may establish a patient-physician relationship and a duty that patient can cite in a malpractice case,” he noted.

Refusing to take call may also be grounds for a malpractice lawsuit, Dr. Bitterman said. Refusing to see a patient would not be considered medical negligence, he continued, because no medical decision is made. Rather, it involves general negligence, which occurs when physicians fail to carry out duties expected of them.

Dr. Bitterman cited a 2006 malpractice judgment in which an on-call neurosurgeon in Missouri was found to be generally negligent. The neurosurgeon had arranged for a colleague in his practice to take his call, but the colleague did not have privileges at the hospital.

A patient with a brain bleed came in and the substitute was on duty. The patient had to be transferred to another hospital, where the patient died. The court ordered that the on-call doctor and the originating hospital had to split a fine of $400,800.
 

On-call physicians can be charged with abandonment

Dr. Bitterman said that if on-call physicians do not provide expected follow-up treatment for an ED patient, they could be charged with abandonment, which is a matter of state law and involves filing a malpractice lawsuit.

Abandonment involves unilaterally terminating the patient relationship without providing notice. There must be an established relationship, which, in the case of call, is formed when the doctor comes to the ED to examine or admit the patient, Dr. Bitterman said. He added that the on-call doctor’s obligation applies only to the medical condition the patient came in for.

Even when an on-call doctor does not see a patient, a relationship can be established if the hospital requires its on-call doctors to make follow-up visits for ED patients, Dr. Taylor said. At some hospitals, he said, on-call doctors have blanket agreements to provide follow-up care in return for not having to arrive in the middle of the night during the ED visit.

Dr. Taylor gave an example of the on-call doctor’s obligation: “The ED doctor puts a splint on the patient’s ankle fracture, and the orthopedic surgeon on call agrees to follow up with the patient within the next few days. If the orthopedic surgeon refuses to follow up without making a reasonable accommodation, it may become an issue of patient abandonment.”
 

Now everyone has a good grasp of the rules

Fifteen years ago, many doctors were in open revolt against on-call duties, but they are more accepting now and understand the rules better, Mr. Healey said.

“Many hospitals have begun paying some specialists for call and designating hospitalists and surgicalists to do at least some of the work that used to be expected of on-call doctors,” he said.

According to Dr. Taylor, today’s on-call doctors often have less to do than in the past. “For example,” he said, “the hospitalist may admit an orthopedic patient at night, and then the orthopedic surgeon does the operation the next day. We’ve had EMTALA for 36 years now, and hospitals and doctors know how call works.”

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

Taking call is one of the more challenging - and annoying - aspects of the job for many physicians. Calls may wake them up in the middle of the night and can interfere with their at-home activities. In Medscape’s Employed Physicians Report, 37% of respondents said they have from 1 to 5 hours of call per month; 19% said they have 6 to 10 hours; and 12% have 11 hours or more.

“Even if you don’t have to come in to the ED, you can get calls in the middle of the night, and you may get paid very little, if anything,” said Robert Bitterman MD, JD, an emergency physician and attorney in Harbor Springs, Mich.

And responding to the calls is not optional. Dr. Bitterman said if on-call physicians don’t perform their duties, they could lose their hospital privileges, be fined by the federal government, or be sued for malpractice.

On-call activities are regulated by the federal Emergency Medical Treatment and Active Labor Act (EMTALA). Dr. Bitterman said it’s rare for the federal government to prosecute on-call physicians for violating EMTALA. Instead, it’s more likely that the hospital will be fined for EMTALA violations committed by on-call physicians.

However, the hospital passes the on-call obligation on to individual physicians through medical staff bylaws. Physicians who violate the bylaws may have their privileges restricted or removed, Dr. Bitterman said. Physicians could also be sued for malpractice, even if they never treated the patient, he added.
 

After-hours call duty in physicians’ practices

A very different type of call duty is having to respond to calls from one’s own patients after regular hours. Unlike doctors on ED call, who usually deal with patients they have never met, these physicians deal with their established patients or those of a colleague in their practice.

Courts have established that physicians have to provide an answering service or other means for their patients to contact them after hours, and the doctor must respond to these calls in a timely manner.

In a 2015 Louisiana ruling, a cardiologist was found liable for malpractice because he didn’t respond to an after-hours call from his patient. The patient tried several times to contact the cardiologist but got no reply.

Physicians may also be responsible if their answering service does not send critical messages to them immediately, if it fails to make appropriate documentation, or if it sends inaccurate data to the doctor.
 

Cases when on-call doctors didn’t respond

The Office of the Inspector General (OIG) of the U.S. Health and Human Services Administration oversees federal EMTALA violations and regularly reports them.

In 2018, the OIG fined a hospital in Waterloo, Iowa, $90,000 when an on-call cardiologist failed to implant a pacemaker for an ED patient. According to the OIG’s report, the patient arrived at the hospital with heart problems. Reached by phone, the cardiologist directed the ED physician to begin transcutaneous pacing but asked that the patient be transferred to another hospital for placement of the pacemaker. The patient died after transfer.

The OIG found that the original cardiologist could have placed the pacemaker, but, as often happens, it only fined the hospital, not the on-call physician for the EMTALA violation.

EMTALA requires that hospitals provide on-call specialists to assist emergency physicians with care of patients who arrive in the ED. In specialties for which there are few doctors to choose from, the on-call specialist may be on duty every third night and every third weekend. This can be daunting, especially for specialists who’ve had a grueling day of work.

Occasionally, on-call physicians, fearful they could make a medical error, request that the patient be transferred to another hospital for treatment. This is what a neurosurgeon who was on call at a Topeka, Kan., hospital did in 2001. Transferred to another hospital, the patient underwent an operation but lost sensation in his lower extremities. The patient sued the on-call neurosurgeon for negligence.

During the trial, the on-call neurosurgeon testified that he was “feeling run-down because he had been an on-call physician every third night for more than 10 years.” He also said this was the first time he had refused to see a patient because of fatigue, and he had decided that the patient “would be better off at a trauma center that had a trauma team and a fresher surgeon.”

The neurosurgeon successfully defended the malpractice suit, but Dr. Bitterman said he might have lost had there not been some unusual circumstances in the case. The court ruled that the hospital had not clearly defined the duties of on-call physicians, and the lawsuit didn’t cite the neurosurgeon’s EMTALA duty.
 

On-call duties defined by EMTALA

EMTALA sets the overall rules for on-call duties, which each hospital is expected to fine-tune on the basis of its own particular circumstances. Here are some of those rules, issued by the Centers for Medicare & Medicaid Services and the OIG.

Only an individual physician can be on call. The hospital’s on-call schedule cannot name a physician practice.

Call applies to all ED patients. Physicians cannot limit their on-call responsibilities to their own patients, to patients in their insurance network, or to paying patients.

There may be some gaps in the call schedule. The OIG is not specific as to how many gaps are allowed, said Nick Healey, an attorney in Cheyenne, Wyo., who has written about on-call duties. Among other things, adequate coverage depends on the number of available physicians and the demand for their services. Mr. Healey added that states may require more extensive availability of on-call physicians at high-level trauma centers.

Hospitals must have made arrangements for transfer. Whenever there is a gap in the schedule, hospitals need to have a designated hospital to send the patient to. Hospitals that unnecessarily transfer patients will be penalized.

The ED physician calls the shots. The emergency physician handling the case decides if the on-call doctor has to come in and treat the patient firsthand.

The on-call physician may delegate the work to others. On-call physicians may designate a nurse practitioner or physician assistant, but the on-call physician is ultimately responsible. The ED doctor may require the physician to come in anyway, according to Todd B. Taylor, MD, an emergency physician in Phoenix, who has written about on-call duties. Dr. Bitterman noted that the physician may designate a colleague to take their call, but the substitute has to have privileges at the hospital.

Physicians may do their own work while on call. Physicians can perform elective surgery while on call, provided they have made arrangements if they then become unavailable for duty, Dr. Taylor said. He added that physicians can also have simultaneous call at other hospitals, provided they make arrangements.
 

The hospital fine-tunes call obligations

The hospital is expected to further define the federal rules. For instance, the CMS says physicians should respond to calls within a “reasonable period of time” and requires hospitals to specify response times, which may be 15-30 minutes for responding to phone calls and traveling to the ED, Dr. Bitterman said.

The CMS says older physicians can be exempted from call. The hospital determines the age at which physicians can be exempted. “Hospitals typically exempt physicians over age 65 or 70, or when they have certain medical conditions,” said Lowell Brown, a Los Angeles attorney who deals with on-call duties.

The hospital also sets the call schedule, which may result in uncovered periods in specialties in which there are few physicians to draw from, according to Mr. Healey. He said many hospitals still use a simple rule of thumb, even though it has been dismissed by the CMS. Under this so-called “rule of three,” hospitals that have three doctors or fewer in a specialty do not have to provide constant call coverage.

On-call rules are part of the medical staff bylaws, and they have to be approved by the medical staff. This may require delicate negotiations between the staff’s leadership and administrators, Dr. Bitterman said.

It is often up to the emergency physician on duty to enforce the hospital’s on-call rules, Dr. Taylor said. “If the ED physician is having trouble, he or she may contact the on-call physician’s department chairman or, if necessary, the chief of the medical staff and ask that person to deal with the physician,” Dr. Taylor said.

The ED physician has to determine whether the patient needs to be transferred to another hospital. Dr. Taylor said the ED physician must fill out a transfer form and obtain consent from the receiving hospital.

If a patient has to be transferred because an on-call physician failed to appear, the originating hospital has to report this to the CMS, and the physician and the hospital can be cited for an inappropriate transfer and fined, Mr. Brown said. “The possibility of being identified in this way should be a powerful incentive to accept call duty,” he added.
 

Malpractice exposure of on-call physicians

When on-call doctors provide medical advice regarding an ED patient, that advice may be subject to malpractice litigation, Dr. Taylor said. “Even if you only give the ED doctor advice over the phone, that may establish a patient-physician relationship and a duty that patient can cite in a malpractice case,” he noted.

Refusing to take call may also be grounds for a malpractice lawsuit, Dr. Bitterman said. Refusing to see a patient would not be considered medical negligence, he continued, because no medical decision is made. Rather, it involves general negligence, which occurs when physicians fail to carry out duties expected of them.

Dr. Bitterman cited a 2006 malpractice judgment in which an on-call neurosurgeon in Missouri was found to be generally negligent. The neurosurgeon had arranged for a colleague in his practice to take his call, but the colleague did not have privileges at the hospital.

A patient with a brain bleed came in and the substitute was on duty. The patient had to be transferred to another hospital, where the patient died. The court ordered that the on-call doctor and the originating hospital had to split a fine of $400,800.
 

On-call physicians can be charged with abandonment

Dr. Bitterman said that if on-call physicians do not provide expected follow-up treatment for an ED patient, they could be charged with abandonment, which is a matter of state law and involves filing a malpractice lawsuit.

Abandonment involves unilaterally terminating the patient relationship without providing notice. There must be an established relationship, which, in the case of call, is formed when the doctor comes to the ED to examine or admit the patient, Dr. Bitterman said. He added that the on-call doctor’s obligation applies only to the medical condition the patient came in for.

Even when an on-call doctor does not see a patient, a relationship can be established if the hospital requires its on-call doctors to make follow-up visits for ED patients, Dr. Taylor said. At some hospitals, he said, on-call doctors have blanket agreements to provide follow-up care in return for not having to arrive in the middle of the night during the ED visit.

Dr. Taylor gave an example of the on-call doctor’s obligation: “The ED doctor puts a splint on the patient’s ankle fracture, and the orthopedic surgeon on call agrees to follow up with the patient within the next few days. If the orthopedic surgeon refuses to follow up without making a reasonable accommodation, it may become an issue of patient abandonment.”
 

Now everyone has a good grasp of the rules

Fifteen years ago, many doctors were in open revolt against on-call duties, but they are more accepting now and understand the rules better, Mr. Healey said.

“Many hospitals have begun paying some specialists for call and designating hospitalists and surgicalists to do at least some of the work that used to be expected of on-call doctors,” he said.

According to Dr. Taylor, today’s on-call doctors often have less to do than in the past. “For example,” he said, “the hospitalist may admit an orthopedic patient at night, and then the orthopedic surgeon does the operation the next day. We’ve had EMTALA for 36 years now, and hospitals and doctors know how call works.”

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

Patients with acute ischemic stroke presenting late at the hospital can be selected for endovascular thrombectomy by the presence of collateral flow on CT angiography (CTA), a new study shows.

The MR CLEAN-LATE trial found that patients selected for thrombectomy in this way had a greater chance of a better functional outcome than patients who did not receive endovascular therapy.

The study was presented at the 14th World Stroke Congress in Singapore by study investigator Susanne Olthuis, MD, of Maastricht (the Netherlands) University Medical Center.

Patients in the intervention group were more likely to show a benefit on the primary endpoint of modified Rankin Scale (mRS) score at 90 days with a significant common odds ratio of 1.68, a finding that received applause from attendees of the plenary WSC session at which the study was presented.

“This means that patients treated with endovascular therapy in this trial had about a 1.7 times higher chance of achieving a better functional outcome at 90 days,” Dr. Olthuis said.

“Selection based on collateral flow identifies an additional group of patients eligible for late-window endovascular therapy in addition to those eligible based on perfusion and clinical criteria,” Dr. Olthuis concluded.

“We recommend implementation of collateral selection in routine clinical practice as it is time efficient. The CTA is already available, and it involves a low-complexity assessment. The only distinction that needs to be made is whether or not there are any collaterals visible on CTA. If collaterals are absent or there is any doubt, then CT perfusion [CTP] imaging can still be used,” she added.

Co–principal investigator Wim H. van Zwam, MD, interventional radiologist at Maastricht, said in a comment:“My take-home message is that now in the late window we can select patients based on the presence of collaterals on CT angiography, which makes selection easier and faster and more widely available.

“If any collaterals are seen – and that is easily done just by looking at the CTA scan – then the patient can be selected for endovascular treatment,” Dr. van Zwam added. “We don’t need to wait for calculations of core and penumbra volumes from the CTP scan. There will also be additional patients who can benefit from endovascular therapy who do not fulfill the CTP criteria but do have visible collaterals.”

Explaining the background to the study, Dr. Olthuis noted that endovascular thrombectomy for large vessel occlusion stroke is safe and effective if performed within 6 hours and the effect then diminishes over time. In the original trial of endovascular treatment, MR CLEAN, patients with higher collateral grades had more treatment benefit, leading to the hypothesis that the assessment of collateral blood flow could help identify patients who would still benefit in the late time window.

The current MR CLEAN-LATE trial therefore set out to compare safety and efficacy of endovascular therapy in patients with acute ischemic stroke in the anterior circulation presenting within 6-24 hours from symptom onset with patients selected based on the presence of collateral flow on CTA.

At the time the trial was starting, the DAWN and DEFUSE 3 trials reported showing benefit of endovascular therapy in patients presenting in the late window who had been selected for endovascular treatment based on a combination of perfusion imaging and clinical criteria, so patients who fitted these criteria were also excluded from MR CLEAN-LATE as they would now be eligible for endovascular therapy under the latest clinical guidelines. 

But the study continued, as “we believed collateral selection may still be able to identify an additional group of patients that may benefit from endovascular therapy in the late window,” Dr. Olthuis said.

The trial randomly assigned 502 such patients with a National Institutes of Health Stroke Scale (NIHSS) score of at least 2 and with collateral flow grades of 1-3 to receive endovascular therapy (intervention) or control.

Safety data showed a slightly but nonsignificantly higher mortality rate at 90 days in the control group (30%) versus 24% in the intervention group.

The rate of symptomatic intracranial hemorrhage was higher in the intervention group (6.7%) versus 1.6% in the control group, but Dr. Olthuis pointed out that the rate of sICH in the intervention group was similar to that in the endovascular groups of the DAWN and DEFUSE 3 trials.

The primary endpoint – mRS score at 90 days – showed a shift toward better outcome in the intervention group, with an adjusted common OR of 1.68 (95% confidence interval, 1.21-2.33).

The median mRS score in the intervention group was 3 (95% CI, 2-5) versus 4 (95% CI, 2-6) in the control group.

Secondary outcomes also showed benefits for the intervention group for the endpoints of mRS score 0-1 versus 2-6 (OR, 1.63); mRS 0-2 versus 3-6 (OR 1.54); and mRS 0-3 versus 4-6 (OR, 1.74).

In addition, NIHSS score was reduced by 17% at 24 hours and by 27% by 5-7 days or discharge in the intervention group. Recanalization at 24 hours was also improved in the intervention group (81% vs. 52%) and infarct size was reduced by 32%.

Dr. Olthuis explained that collateral grade was defined as the amount of collateral flow in the affected hemisphere as a percentage of the contralateral site, with grade 0 correlating to an absence of collaterals (and these were the only patients excluded).

Grade 1 included patients with 50% or less collaterals, grade 2 more than 50%, and grade 3 excellent collaterals – around 100%. “We included grade 1, 2 and 3, and subgroup analysis suggested no treatment interactions between different collateral grades in the patients included,” she said.

Dr. van Zwam noted that there has been evidence from other studies suggesting that the presence of collateral flow could be used to select patients for late thrombectomy, but MR CLEAN-LATE is the first randomized trial to show this and provides confirmation that this strategy is valid.

“Our results show that patients can be selected with just standard CT angiography imaging and that CT perfusion is not necessary. This will make it easier and faster to select patients especially for centers in low-resource areas who do not yet have CT perfusion imaging,” he commented.

“But even in centers where CT perfusion imaging is performed, these results should mean that we do not have to wait to analyze these results before going ahead with thrombectomy. It will also give us an additional tool, as some patients do not meet the criteria on perfusion imaging but still have identifiable collaterals and thus would now qualify for endovascular thrombectomy,” he added.
 

Could collateral assessment replace CT perfusion?

Commenting on the MR CLEAN-LATE trial, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the WSC scientific committee, said it was an “excellent study.”

“This study does not rely on advanced imaging (e.g., mismatch) and criteria can easily be interpreted on CT/CTA. If the study is published and all details are available this study may substantially ease endovascular therapy in the late time window,” Dr. Kiechl told this news organization.

Also commenting, Urs Fischer, MD, chairman of the department of neurology at the University Hospital Basel (Switzerland), who was not involved with MR CLEAN-LATE, said: “This is another study that has nicely shown that endovascular therapy in patients in the later time window is highly effective.”

Dr. Fischer said he was not surprised by the results. 

“I was expecting the trial to be positive,” he said. “What we can say is that endovascular therapy in patients with proximal vessel occlusion is a very effective intervention – probably one of the most important interventions in the history of medicine – and now we have another subgroup to whom we can offer this therapy. So, this is an important study that will improve the outcome of many further patients.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, who was a MR CLEAN-LATE investigator, agreed that the trial has the potential to increase number of patients who can be treated with endovascular therapy.

But both Dr. Roos and Dr. Fischer were not convinced that collateral assessment would replace CT perfusion as the first-line choice in selecting patients for endovascular treatment.

“We need to see what kind of patients were included in the trial and what kind of perfusion imaging characteristics they had, to see how they compare with patients selected by perfusion imaging,” Dr. Roos noted. “I think CT perfusion is here. But if the data shows that collateral score is better able to identify patients for endovascular treatment than CT perfusion, then this has the potential to change practice. But that needs to be shown.”

All patients screened for the MR CLEAN-LATE trial also received CT perfusion imaging as part of the standard imaging protocol, and many were selected for endovascular therapy directly on this basis, so would not have entered the trial. The researchers plan to analyze these results and to compare how the two approaches differ.

MR CLEAN-LATE is an investigator-driven study, funded by the Dutch Heart Foundation, the Brain Foundation Netherlands, and Medtronic. The study was designed and conducted, analyzed, and interpreted by the investigators independently of all sponsors. Dr. Olthuis reported no relevant financial relationships.

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

Patients with acute ischemic stroke presenting late at the hospital can be selected for endovascular thrombectomy by the presence of collateral flow on CT angiography (CTA), a new study shows.

The MR CLEAN-LATE trial found that patients selected for thrombectomy in this way had a greater chance of a better functional outcome than patients who did not receive endovascular therapy.

The study was presented at the 14th World Stroke Congress in Singapore by study investigator Susanne Olthuis, MD, of Maastricht (the Netherlands) University Medical Center.

Patients in the intervention group were more likely to show a benefit on the primary endpoint of modified Rankin Scale (mRS) score at 90 days with a significant common odds ratio of 1.68, a finding that received applause from attendees of the plenary WSC session at which the study was presented.

“This means that patients treated with endovascular therapy in this trial had about a 1.7 times higher chance of achieving a better functional outcome at 90 days,” Dr. Olthuis said.

“Selection based on collateral flow identifies an additional group of patients eligible for late-window endovascular therapy in addition to those eligible based on perfusion and clinical criteria,” Dr. Olthuis concluded.

“We recommend implementation of collateral selection in routine clinical practice as it is time efficient. The CTA is already available, and it involves a low-complexity assessment. The only distinction that needs to be made is whether or not there are any collaterals visible on CTA. If collaterals are absent or there is any doubt, then CT perfusion [CTP] imaging can still be used,” she added.

Co–principal investigator Wim H. van Zwam, MD, interventional radiologist at Maastricht, said in a comment:“My take-home message is that now in the late window we can select patients based on the presence of collaterals on CT angiography, which makes selection easier and faster and more widely available.

“If any collaterals are seen – and that is easily done just by looking at the CTA scan – then the patient can be selected for endovascular treatment,” Dr. van Zwam added. “We don’t need to wait for calculations of core and penumbra volumes from the CTP scan. There will also be additional patients who can benefit from endovascular therapy who do not fulfill the CTP criteria but do have visible collaterals.”

Explaining the background to the study, Dr. Olthuis noted that endovascular thrombectomy for large vessel occlusion stroke is safe and effective if performed within 6 hours and the effect then diminishes over time. In the original trial of endovascular treatment, MR CLEAN, patients with higher collateral grades had more treatment benefit, leading to the hypothesis that the assessment of collateral blood flow could help identify patients who would still benefit in the late time window.

The current MR CLEAN-LATE trial therefore set out to compare safety and efficacy of endovascular therapy in patients with acute ischemic stroke in the anterior circulation presenting within 6-24 hours from symptom onset with patients selected based on the presence of collateral flow on CTA.

At the time the trial was starting, the DAWN and DEFUSE 3 trials reported showing benefit of endovascular therapy in patients presenting in the late window who had been selected for endovascular treatment based on a combination of perfusion imaging and clinical criteria, so patients who fitted these criteria were also excluded from MR CLEAN-LATE as they would now be eligible for endovascular therapy under the latest clinical guidelines. 

But the study continued, as “we believed collateral selection may still be able to identify an additional group of patients that may benefit from endovascular therapy in the late window,” Dr. Olthuis said.

The trial randomly assigned 502 such patients with a National Institutes of Health Stroke Scale (NIHSS) score of at least 2 and with collateral flow grades of 1-3 to receive endovascular therapy (intervention) or control.

Safety data showed a slightly but nonsignificantly higher mortality rate at 90 days in the control group (30%) versus 24% in the intervention group.

The rate of symptomatic intracranial hemorrhage was higher in the intervention group (6.7%) versus 1.6% in the control group, but Dr. Olthuis pointed out that the rate of sICH in the intervention group was similar to that in the endovascular groups of the DAWN and DEFUSE 3 trials.

The primary endpoint – mRS score at 90 days – showed a shift toward better outcome in the intervention group, with an adjusted common OR of 1.68 (95% confidence interval, 1.21-2.33).

The median mRS score in the intervention group was 3 (95% CI, 2-5) versus 4 (95% CI, 2-6) in the control group.

Secondary outcomes also showed benefits for the intervention group for the endpoints of mRS score 0-1 versus 2-6 (OR, 1.63); mRS 0-2 versus 3-6 (OR 1.54); and mRS 0-3 versus 4-6 (OR, 1.74).

In addition, NIHSS score was reduced by 17% at 24 hours and by 27% by 5-7 days or discharge in the intervention group. Recanalization at 24 hours was also improved in the intervention group (81% vs. 52%) and infarct size was reduced by 32%.

Dr. Olthuis explained that collateral grade was defined as the amount of collateral flow in the affected hemisphere as a percentage of the contralateral site, with grade 0 correlating to an absence of collaterals (and these were the only patients excluded).

Grade 1 included patients with 50% or less collaterals, grade 2 more than 50%, and grade 3 excellent collaterals – around 100%. “We included grade 1, 2 and 3, and subgroup analysis suggested no treatment interactions between different collateral grades in the patients included,” she said.

Dr. van Zwam noted that there has been evidence from other studies suggesting that the presence of collateral flow could be used to select patients for late thrombectomy, but MR CLEAN-LATE is the first randomized trial to show this and provides confirmation that this strategy is valid.

“Our results show that patients can be selected with just standard CT angiography imaging and that CT perfusion is not necessary. This will make it easier and faster to select patients especially for centers in low-resource areas who do not yet have CT perfusion imaging,” he commented.

“But even in centers where CT perfusion imaging is performed, these results should mean that we do not have to wait to analyze these results before going ahead with thrombectomy. It will also give us an additional tool, as some patients do not meet the criteria on perfusion imaging but still have identifiable collaterals and thus would now qualify for endovascular thrombectomy,” he added.
 

Could collateral assessment replace CT perfusion?

Commenting on the MR CLEAN-LATE trial, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the WSC scientific committee, said it was an “excellent study.”

“This study does not rely on advanced imaging (e.g., mismatch) and criteria can easily be interpreted on CT/CTA. If the study is published and all details are available this study may substantially ease endovascular therapy in the late time window,” Dr. Kiechl told this news organization.

Also commenting, Urs Fischer, MD, chairman of the department of neurology at the University Hospital Basel (Switzerland), who was not involved with MR CLEAN-LATE, said: “This is another study that has nicely shown that endovascular therapy in patients in the later time window is highly effective.”

Dr. Fischer said he was not surprised by the results. 

“I was expecting the trial to be positive,” he said. “What we can say is that endovascular therapy in patients with proximal vessel occlusion is a very effective intervention – probably one of the most important interventions in the history of medicine – and now we have another subgroup to whom we can offer this therapy. So, this is an important study that will improve the outcome of many further patients.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, who was a MR CLEAN-LATE investigator, agreed that the trial has the potential to increase number of patients who can be treated with endovascular therapy.

But both Dr. Roos and Dr. Fischer were not convinced that collateral assessment would replace CT perfusion as the first-line choice in selecting patients for endovascular treatment.

“We need to see what kind of patients were included in the trial and what kind of perfusion imaging characteristics they had, to see how they compare with patients selected by perfusion imaging,” Dr. Roos noted. “I think CT perfusion is here. But if the data shows that collateral score is better able to identify patients for endovascular treatment than CT perfusion, then this has the potential to change practice. But that needs to be shown.”

All patients screened for the MR CLEAN-LATE trial also received CT perfusion imaging as part of the standard imaging protocol, and many were selected for endovascular therapy directly on this basis, so would not have entered the trial. The researchers plan to analyze these results and to compare how the two approaches differ.

MR CLEAN-LATE is an investigator-driven study, funded by the Dutch Heart Foundation, the Brain Foundation Netherlands, and Medtronic. The study was designed and conducted, analyzed, and interpreted by the investigators independently of all sponsors. Dr. Olthuis reported no relevant financial relationships.

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

Patients with acute ischemic stroke presenting late at the hospital can be selected for endovascular thrombectomy by the presence of collateral flow on CT angiography (CTA), a new study shows.

The MR CLEAN-LATE trial found that patients selected for thrombectomy in this way had a greater chance of a better functional outcome than patients who did not receive endovascular therapy.

The study was presented at the 14th World Stroke Congress in Singapore by study investigator Susanne Olthuis, MD, of Maastricht (the Netherlands) University Medical Center.

Patients in the intervention group were more likely to show a benefit on the primary endpoint of modified Rankin Scale (mRS) score at 90 days with a significant common odds ratio of 1.68, a finding that received applause from attendees of the plenary WSC session at which the study was presented.

“This means that patients treated with endovascular therapy in this trial had about a 1.7 times higher chance of achieving a better functional outcome at 90 days,” Dr. Olthuis said.

“Selection based on collateral flow identifies an additional group of patients eligible for late-window endovascular therapy in addition to those eligible based on perfusion and clinical criteria,” Dr. Olthuis concluded.

“We recommend implementation of collateral selection in routine clinical practice as it is time efficient. The CTA is already available, and it involves a low-complexity assessment. The only distinction that needs to be made is whether or not there are any collaterals visible on CTA. If collaterals are absent or there is any doubt, then CT perfusion [CTP] imaging can still be used,” she added.

Co–principal investigator Wim H. van Zwam, MD, interventional radiologist at Maastricht, said in a comment:“My take-home message is that now in the late window we can select patients based on the presence of collaterals on CT angiography, which makes selection easier and faster and more widely available.

“If any collaterals are seen – and that is easily done just by looking at the CTA scan – then the patient can be selected for endovascular treatment,” Dr. van Zwam added. “We don’t need to wait for calculations of core and penumbra volumes from the CTP scan. There will also be additional patients who can benefit from endovascular therapy who do not fulfill the CTP criteria but do have visible collaterals.”

Explaining the background to the study, Dr. Olthuis noted that endovascular thrombectomy for large vessel occlusion stroke is safe and effective if performed within 6 hours and the effect then diminishes over time. In the original trial of endovascular treatment, MR CLEAN, patients with higher collateral grades had more treatment benefit, leading to the hypothesis that the assessment of collateral blood flow could help identify patients who would still benefit in the late time window.

The current MR CLEAN-LATE trial therefore set out to compare safety and efficacy of endovascular therapy in patients with acute ischemic stroke in the anterior circulation presenting within 6-24 hours from symptom onset with patients selected based on the presence of collateral flow on CTA.

At the time the trial was starting, the DAWN and DEFUSE 3 trials reported showing benefit of endovascular therapy in patients presenting in the late window who had been selected for endovascular treatment based on a combination of perfusion imaging and clinical criteria, so patients who fitted these criteria were also excluded from MR CLEAN-LATE as they would now be eligible for endovascular therapy under the latest clinical guidelines. 

But the study continued, as “we believed collateral selection may still be able to identify an additional group of patients that may benefit from endovascular therapy in the late window,” Dr. Olthuis said.

The trial randomly assigned 502 such patients with a National Institutes of Health Stroke Scale (NIHSS) score of at least 2 and with collateral flow grades of 1-3 to receive endovascular therapy (intervention) or control.

Safety data showed a slightly but nonsignificantly higher mortality rate at 90 days in the control group (30%) versus 24% in the intervention group.

The rate of symptomatic intracranial hemorrhage was higher in the intervention group (6.7%) versus 1.6% in the control group, but Dr. Olthuis pointed out that the rate of sICH in the intervention group was similar to that in the endovascular groups of the DAWN and DEFUSE 3 trials.

The primary endpoint – mRS score at 90 days – showed a shift toward better outcome in the intervention group, with an adjusted common OR of 1.68 (95% confidence interval, 1.21-2.33).

The median mRS score in the intervention group was 3 (95% CI, 2-5) versus 4 (95% CI, 2-6) in the control group.

Secondary outcomes also showed benefits for the intervention group for the endpoints of mRS score 0-1 versus 2-6 (OR, 1.63); mRS 0-2 versus 3-6 (OR 1.54); and mRS 0-3 versus 4-6 (OR, 1.74).

In addition, NIHSS score was reduced by 17% at 24 hours and by 27% by 5-7 days or discharge in the intervention group. Recanalization at 24 hours was also improved in the intervention group (81% vs. 52%) and infarct size was reduced by 32%.

Dr. Olthuis explained that collateral grade was defined as the amount of collateral flow in the affected hemisphere as a percentage of the contralateral site, with grade 0 correlating to an absence of collaterals (and these were the only patients excluded).

Grade 1 included patients with 50% or less collaterals, grade 2 more than 50%, and grade 3 excellent collaterals – around 100%. “We included grade 1, 2 and 3, and subgroup analysis suggested no treatment interactions between different collateral grades in the patients included,” she said.

Dr. van Zwam noted that there has been evidence from other studies suggesting that the presence of collateral flow could be used to select patients for late thrombectomy, but MR CLEAN-LATE is the first randomized trial to show this and provides confirmation that this strategy is valid.

“Our results show that patients can be selected with just standard CT angiography imaging and that CT perfusion is not necessary. This will make it easier and faster to select patients especially for centers in low-resource areas who do not yet have CT perfusion imaging,” he commented.

“But even in centers where CT perfusion imaging is performed, these results should mean that we do not have to wait to analyze these results before going ahead with thrombectomy. It will also give us an additional tool, as some patients do not meet the criteria on perfusion imaging but still have identifiable collaterals and thus would now qualify for endovascular thrombectomy,” he added.
 

Could collateral assessment replace CT perfusion?

Commenting on the MR CLEAN-LATE trial, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the WSC scientific committee, said it was an “excellent study.”

“This study does not rely on advanced imaging (e.g., mismatch) and criteria can easily be interpreted on CT/CTA. If the study is published and all details are available this study may substantially ease endovascular therapy in the late time window,” Dr. Kiechl told this news organization.

Also commenting, Urs Fischer, MD, chairman of the department of neurology at the University Hospital Basel (Switzerland), who was not involved with MR CLEAN-LATE, said: “This is another study that has nicely shown that endovascular therapy in patients in the later time window is highly effective.”

Dr. Fischer said he was not surprised by the results. 

“I was expecting the trial to be positive,” he said. “What we can say is that endovascular therapy in patients with proximal vessel occlusion is a very effective intervention – probably one of the most important interventions in the history of medicine – and now we have another subgroup to whom we can offer this therapy. So, this is an important study that will improve the outcome of many further patients.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, who was a MR CLEAN-LATE investigator, agreed that the trial has the potential to increase number of patients who can be treated with endovascular therapy.

But both Dr. Roos and Dr. Fischer were not convinced that collateral assessment would replace CT perfusion as the first-line choice in selecting patients for endovascular treatment.

“We need to see what kind of patients were included in the trial and what kind of perfusion imaging characteristics they had, to see how they compare with patients selected by perfusion imaging,” Dr. Roos noted. “I think CT perfusion is here. But if the data shows that collateral score is better able to identify patients for endovascular treatment than CT perfusion, then this has the potential to change practice. But that needs to be shown.”

All patients screened for the MR CLEAN-LATE trial also received CT perfusion imaging as part of the standard imaging protocol, and many were selected for endovascular therapy directly on this basis, so would not have entered the trial. The researchers plan to analyze these results and to compare how the two approaches differ.

MR CLEAN-LATE is an investigator-driven study, funded by the Dutch Heart Foundation, the Brain Foundation Netherlands, and Medtronic. The study was designed and conducted, analyzed, and interpreted by the investigators independently of all sponsors. Dr. Olthuis reported no relevant financial relationships.

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

MONTREAL – Patients hospitalized with severe COVID-19 and no prior history of thyroid dysfunction show signs of thyroiditis that, although asymptomatic, continue to persist for up to a year after infection, according to research that adds to evidence on the complex involvement of the thyroid in COVID-19.

“To our knowledge these findings are novel,” first author Ilaria Muller, MD, PhD, an assistant professor in endocrinology in the department of clinical sciences and community health, University of Milan, told this news organization.

“Little has been written about the long-term follow-up of thyroid function after severe COVID-19 disease, and we have followed patients up to 1 year after infection.”

The effects are seen in about 10%-15% of patients, and “[while] the thyroid dysfunction is transient, ultrasound areas of thyroiditis may persist after 1 year, even if they progressively shrink,” said Dr. Muller, who presented the findings at the American Thyroid Association annual meeting.
 

Immunological scars? Clinical implications unclear

The nature and implications of the persistent thyroiditis areas are uncertain, Dr. Muller noted. “These areas of thyroiditis are likely a sort of ‘immunologic scar’ of the previous SARS-CoV-2 infection,” she explained. “We still don’t know if there are clinical implications, even if they seem unlikely.”

Of note, increases in autoimmune processes or a higher incidence of thyroid dysfunction after COVID-19 have not been observed, and the shrinkage of the areas of thyroiditis over time is encouraging, she said.

The reasons why some patients develop atypical thyroiditis and others don’t are also unclear, with Dr. Muller’s team investigating further. Importantly, similar effects have been associated with other severe infections, not just COVID-19. “It is well known that in classic subacute thyroiditis due to other viral infections, the areas of thyroiditis persist for months, so this phenomenon might not be unique to COVID-19,” she explained.

Commenting on the story, Jeffrey R. Garber, MD, also noted that such thyroiditis areas stemming from other types of infection may persist – but go unnoticed.

“Resolution is the clinical rule, [and] we generally do not restudy in detail those who clinically recover,” he said in an interview. “However, there is evidence of impaired thyroid reserve in those who recover from viral thyroiditis due to other sources.”

“Thyroid symptoms are often not specific, so ‘atypical’ [cases] are common, [and] resolution with restoring thyroid status to normal is mixed,” noted Dr. Garber, an associate professor of medicine at Harvard Medical School and chief of the division of endocrinology at Atrius Health, Boston.

In terms of clinical practice, while such issues should be kept in mind when evaluating abnormal thyroid tests during severe COVID-19, “it is not a call for routinely checking it in the absence of clinical suspicion,” he observed.
 

Study details

Dr. Muller and her team previously observed that patients hospitalized in intensive care with COVID-19 often had low or suppressed serum thyroid-stimulating hormone (TSH) levels, with and without elevated free thyroxine (FT₄) concentrations, suggestive of thyrotoxicosis.

Upon investigating those cases, they found, as in their previous study reported by this news organization, that a painless, atypical thyroiditis occurs with nonthyroidal illness syndrome among patients hospitalized with severe COVID-19. The atypical thyroiditis was slightly more common in men and was associated with lymphopenia.

To further investigate those cases and follow patients up to 1 year, the team conducted a longitudinal study of 183 patients hospitalized with severe COVID-19 in Italy. The patients, who had no known prior history of thyroid dysfunction, were assessed for serum thyroid function, autoantibodies, and inflammatory markers.

At baseline, 10% of the patients were found to have thyrotoxicosis, and ultrasound performed within 2-3 months postinfection on 65 patients showed that 18 (28%) had areas of thyroiditis.

Importantly, 60% of those patients with the areas of thyroiditis had low TSH levels, while 25% had normal TSH levels (P = .034).

In addition, those showing the presence of thyroiditis on ultrasound at 23 months were more likely to have elevated serum concentrations of FT₄ (P = .018) and higher levels of interleukin-26 (P = .016), compared with those with normal ultrasound readings.

In a longitudinal analysis further following patients post infection, among 15 patients who were evaluated at 6 months, most, 13 (87%), still had areas of thyroiditis, and 6 of 12 (50%) had thyroiditis areas that, though reduced in size, still persisted even at 12 months.

In terms of thyroid uptake, at 3 months, 14 of 17 patients (82%) had diffused or focal areas of a reduction of uptake. After 6 months, there was a recovery, with a median of 28% of thyroid uptake recovered, however, 67% of patients still had some focal or diffused reduction in thyroid uptake.

Of note, the indications of thyroiditis on imaging persisted even though patients’ TSH levels had quickly normalized at the end of infection and remained normal up to 1 year of follow-up.

The patients showed no apparent development of thyroglobulin antibody, thyroid peroxidase antibodies, or TSH receptor antibodies.

A further fine needle aspiration analysis of eight patients with atypical thyroiditis at 3 months after infection showed that those patients had tissue resident memory T cells (CD4+/CD8+/CD103+/CD69+) within the thyroid, but not in the blood as expected.

Additional assessments at 8 months after infection showed those tissue resident memory T cells continued to be present on imaging.

The results showed “SARS-CoV-2–specific T cells were enriched within the thyroid compared with the blood, many with a tissue resident phenotype,” Dr. Muller explained.

The findings are notable in that “such an in-depth characterization of areas of thyroiditis triggered by SARS-CoV-2 infection combining ultrasound, scintigraphy, and immunological phenotyping has not been performed so far,” she said.

“In particular, SARS-CoV-2–specific tissue-resident memory T lymphocytes have not been described before in the thyroid gland.”

Dr. Muller and Dr. Garber have reported no relevant financial relationships.

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

MONTREAL – Patients hospitalized with severe COVID-19 and no prior history of thyroid dysfunction show signs of thyroiditis that, although asymptomatic, continue to persist for up to a year after infection, according to research that adds to evidence on the complex involvement of the thyroid in COVID-19.

“To our knowledge these findings are novel,” first author Ilaria Muller, MD, PhD, an assistant professor in endocrinology in the department of clinical sciences and community health, University of Milan, told this news organization.

“Little has been written about the long-term follow-up of thyroid function after severe COVID-19 disease, and we have followed patients up to 1 year after infection.”

The effects are seen in about 10%-15% of patients, and “[while] the thyroid dysfunction is transient, ultrasound areas of thyroiditis may persist after 1 year, even if they progressively shrink,” said Dr. Muller, who presented the findings at the American Thyroid Association annual meeting.
 

Immunological scars? Clinical implications unclear

The nature and implications of the persistent thyroiditis areas are uncertain, Dr. Muller noted. “These areas of thyroiditis are likely a sort of ‘immunologic scar’ of the previous SARS-CoV-2 infection,” she explained. “We still don’t know if there are clinical implications, even if they seem unlikely.”

Of note, increases in autoimmune processes or a higher incidence of thyroid dysfunction after COVID-19 have not been observed, and the shrinkage of the areas of thyroiditis over time is encouraging, she said.

The reasons why some patients develop atypical thyroiditis and others don’t are also unclear, with Dr. Muller’s team investigating further. Importantly, similar effects have been associated with other severe infections, not just COVID-19. “It is well known that in classic subacute thyroiditis due to other viral infections, the areas of thyroiditis persist for months, so this phenomenon might not be unique to COVID-19,” she explained.

Commenting on the story, Jeffrey R. Garber, MD, also noted that such thyroiditis areas stemming from other types of infection may persist – but go unnoticed.

“Resolution is the clinical rule, [and] we generally do not restudy in detail those who clinically recover,” he said in an interview. “However, there is evidence of impaired thyroid reserve in those who recover from viral thyroiditis due to other sources.”

“Thyroid symptoms are often not specific, so ‘atypical’ [cases] are common, [and] resolution with restoring thyroid status to normal is mixed,” noted Dr. Garber, an associate professor of medicine at Harvard Medical School and chief of the division of endocrinology at Atrius Health, Boston.

In terms of clinical practice, while such issues should be kept in mind when evaluating abnormal thyroid tests during severe COVID-19, “it is not a call for routinely checking it in the absence of clinical suspicion,” he observed.
 

Study details

Dr. Muller and her team previously observed that patients hospitalized in intensive care with COVID-19 often had low or suppressed serum thyroid-stimulating hormone (TSH) levels, with and without elevated free thyroxine (FT₄) concentrations, suggestive of thyrotoxicosis.

Upon investigating those cases, they found, as in their previous study reported by this news organization, that a painless, atypical thyroiditis occurs with nonthyroidal illness syndrome among patients hospitalized with severe COVID-19. The atypical thyroiditis was slightly more common in men and was associated with lymphopenia.

To further investigate those cases and follow patients up to 1 year, the team conducted a longitudinal study of 183 patients hospitalized with severe COVID-19 in Italy. The patients, who had no known prior history of thyroid dysfunction, were assessed for serum thyroid function, autoantibodies, and inflammatory markers.

At baseline, 10% of the patients were found to have thyrotoxicosis, and ultrasound performed within 2-3 months postinfection on 65 patients showed that 18 (28%) had areas of thyroiditis.

Importantly, 60% of those patients with the areas of thyroiditis had low TSH levels, while 25% had normal TSH levels (P = .034).

In addition, those showing the presence of thyroiditis on ultrasound at 23 months were more likely to have elevated serum concentrations of FT₄ (P = .018) and higher levels of interleukin-26 (P = .016), compared with those with normal ultrasound readings.

In a longitudinal analysis further following patients post infection, among 15 patients who were evaluated at 6 months, most, 13 (87%), still had areas of thyroiditis, and 6 of 12 (50%) had thyroiditis areas that, though reduced in size, still persisted even at 12 months.

In terms of thyroid uptake, at 3 months, 14 of 17 patients (82%) had diffused or focal areas of a reduction of uptake. After 6 months, there was a recovery, with a median of 28% of thyroid uptake recovered, however, 67% of patients still had some focal or diffused reduction in thyroid uptake.

Of note, the indications of thyroiditis on imaging persisted even though patients’ TSH levels had quickly normalized at the end of infection and remained normal up to 1 year of follow-up.

The patients showed no apparent development of thyroglobulin antibody, thyroid peroxidase antibodies, or TSH receptor antibodies.

A further fine needle aspiration analysis of eight patients with atypical thyroiditis at 3 months after infection showed that those patients had tissue resident memory T cells (CD4+/CD8+/CD103+/CD69+) within the thyroid, but not in the blood as expected.

Additional assessments at 8 months after infection showed those tissue resident memory T cells continued to be present on imaging.

The results showed “SARS-CoV-2–specific T cells were enriched within the thyroid compared with the blood, many with a tissue resident phenotype,” Dr. Muller explained.

The findings are notable in that “such an in-depth characterization of areas of thyroiditis triggered by SARS-CoV-2 infection combining ultrasound, scintigraphy, and immunological phenotyping has not been performed so far,” she said.

“In particular, SARS-CoV-2–specific tissue-resident memory T lymphocytes have not been described before in the thyroid gland.”

Dr. Muller and Dr. Garber have reported no relevant financial relationships.

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

MONTREAL – Patients hospitalized with severe COVID-19 and no prior history of thyroid dysfunction show signs of thyroiditis that, although asymptomatic, continue to persist for up to a year after infection, according to research that adds to evidence on the complex involvement of the thyroid in COVID-19.

“To our knowledge these findings are novel,” first author Ilaria Muller, MD, PhD, an assistant professor in endocrinology in the department of clinical sciences and community health, University of Milan, told this news organization.

“Little has been written about the long-term follow-up of thyroid function after severe COVID-19 disease, and we have followed patients up to 1 year after infection.”

The effects are seen in about 10%-15% of patients, and “[while] the thyroid dysfunction is transient, ultrasound areas of thyroiditis may persist after 1 year, even if they progressively shrink,” said Dr. Muller, who presented the findings at the American Thyroid Association annual meeting.
 

Immunological scars? Clinical implications unclear

The nature and implications of the persistent thyroiditis areas are uncertain, Dr. Muller noted. “These areas of thyroiditis are likely a sort of ‘immunologic scar’ of the previous SARS-CoV-2 infection,” she explained. “We still don’t know if there are clinical implications, even if they seem unlikely.”

Of note, increases in autoimmune processes or a higher incidence of thyroid dysfunction after COVID-19 have not been observed, and the shrinkage of the areas of thyroiditis over time is encouraging, she said.

The reasons why some patients develop atypical thyroiditis and others don’t are also unclear, with Dr. Muller’s team investigating further. Importantly, similar effects have been associated with other severe infections, not just COVID-19. “It is well known that in classic subacute thyroiditis due to other viral infections, the areas of thyroiditis persist for months, so this phenomenon might not be unique to COVID-19,” she explained.

Commenting on the story, Jeffrey R. Garber, MD, also noted that such thyroiditis areas stemming from other types of infection may persist – but go unnoticed.

“Resolution is the clinical rule, [and] we generally do not restudy in detail those who clinically recover,” he said in an interview. “However, there is evidence of impaired thyroid reserve in those who recover from viral thyroiditis due to other sources.”

“Thyroid symptoms are often not specific, so ‘atypical’ [cases] are common, [and] resolution with restoring thyroid status to normal is mixed,” noted Dr. Garber, an associate professor of medicine at Harvard Medical School and chief of the division of endocrinology at Atrius Health, Boston.

In terms of clinical practice, while such issues should be kept in mind when evaluating abnormal thyroid tests during severe COVID-19, “it is not a call for routinely checking it in the absence of clinical suspicion,” he observed.
 

Study details

Dr. Muller and her team previously observed that patients hospitalized in intensive care with COVID-19 often had low or suppressed serum thyroid-stimulating hormone (TSH) levels, with and without elevated free thyroxine (FT₄) concentrations, suggestive of thyrotoxicosis.

Upon investigating those cases, they found, as in their previous study reported by this news organization, that a painless, atypical thyroiditis occurs with nonthyroidal illness syndrome among patients hospitalized with severe COVID-19. The atypical thyroiditis was slightly more common in men and was associated with lymphopenia.

To further investigate those cases and follow patients up to 1 year, the team conducted a longitudinal study of 183 patients hospitalized with severe COVID-19 in Italy. The patients, who had no known prior history of thyroid dysfunction, were assessed for serum thyroid function, autoantibodies, and inflammatory markers.

At baseline, 10% of the patients were found to have thyrotoxicosis, and ultrasound performed within 2-3 months postinfection on 65 patients showed that 18 (28%) had areas of thyroiditis.

Importantly, 60% of those patients with the areas of thyroiditis had low TSH levels, while 25% had normal TSH levels (P = .034).

In addition, those showing the presence of thyroiditis on ultrasound at 23 months were more likely to have elevated serum concentrations of FT₄ (P = .018) and higher levels of interleukin-26 (P = .016), compared with those with normal ultrasound readings.

In a longitudinal analysis further following patients post infection, among 15 patients who were evaluated at 6 months, most, 13 (87%), still had areas of thyroiditis, and 6 of 12 (50%) had thyroiditis areas that, though reduced in size, still persisted even at 12 months.

In terms of thyroid uptake, at 3 months, 14 of 17 patients (82%) had diffused or focal areas of a reduction of uptake. After 6 months, there was a recovery, with a median of 28% of thyroid uptake recovered, however, 67% of patients still had some focal or diffused reduction in thyroid uptake.

Of note, the indications of thyroiditis on imaging persisted even though patients’ TSH levels had quickly normalized at the end of infection and remained normal up to 1 year of follow-up.

The patients showed no apparent development of thyroglobulin antibody, thyroid peroxidase antibodies, or TSH receptor antibodies.

A further fine needle aspiration analysis of eight patients with atypical thyroiditis at 3 months after infection showed that those patients had tissue resident memory T cells (CD4+/CD8+/CD103+/CD69+) within the thyroid, but not in the blood as expected.

Additional assessments at 8 months after infection showed those tissue resident memory T cells continued to be present on imaging.

The results showed “SARS-CoV-2–specific T cells were enriched within the thyroid compared with the blood, many with a tissue resident phenotype,” Dr. Muller explained.

The findings are notable in that “such an in-depth characterization of areas of thyroiditis triggered by SARS-CoV-2 infection combining ultrasound, scintigraphy, and immunological phenotyping has not been performed so far,” she said.

“In particular, SARS-CoV-2–specific tissue-resident memory T lymphocytes have not been described before in the thyroid gland.”

Dr. Muller and Dr. Garber have reported no relevant financial relationships.

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

Dimethyl fumarate could delay – or even prevent – clinical symptoms in patients with radiologically isolated syndrome (RIS), the earliest detected preclinical phase of multiple sclerosis (MS). Researchers found that dimethyl fumarate reduced the risk of a first acute or progressive event related to CNS demyelination by more than 80%, compared with placebo.

Patients with RIS have incidental MRI abnormalities typical of MS but have no symptoms of the disease. The condition is usually detected when a patient seeks treatment for another issue, such as migraines or head trauma.

The study is the first randomized clinical trial to examine efficacy of a disease-modifying therapy in delaying symptoms in RIS. “It really supports the concept of the benefit of early treatment intervention within this given MS disease spectrum,” lead investigator Darin Okuda, MD, professor of neurology at the University of Texas Southwestern Medical Center in Dallas, told delegates attending the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
 

Topic of debate

RIS was first identified by Dr. Okuda in 2008. Increased use of brain imaging led to the detection of patients with incidental white-matter pathology in the central nervous system on MRI. Some of the findings were nonspecific, but others were highly suggestive of demyelinating pathology based on their location and morphology in the central nervous system.

Although the prevalence of RIS is unknown, incidentally discovered white matter lesions resembling demyelination occur in an estimated 0.1%-0.7% of the general population. Up to half of patients with RIS experience a first clinical MS event within 10 years.

Diagnostic criteria and whether to treat patients with RIS prophylactically has long been a topic of debate among neurologists and radiologists.

Researchers conducted the multicenter, randomized, double-blinded, placebo-controlled ARISE study in 2016, recruiting 87 patients with RIS. The majority of participants were women, and most were diagnosed in their early 40s.

Patients received oral dimethyl fumarate at 240 mg twice daily or placebo and were followed for 96 weeks (1 year, 10 months). Clinical assessments were completed at baseline, at weeks 48 and 96, and at the time of the first clinical event. MRI scans were performed only at the beginning and end of the study.

Those who received dimethyl fumarate had a significantly lower risk of experiencing a first clinical demyelinating event during the study period (adjusted hazard ratio, 0.07; P = .005).

After adjusting for the number of gadolinium-enhancing lesions at baseline, there was a significant reduction in the number of new or newly enlarged T2-weighted hyperintense lesions, a secondary endpoint, in the dimethyl fumarate group, compared with those on placebo (HR, 0.20; P = .042).

“In the future we’d like to see further studies performed to assess the impact on disability outcome measures following treatment for a meaningful amount of time,” Dr. Okuda said.
 

‘Striking’ findings

Barbara Giesser, MD, a neurologist at Pacific Neuroscience Institute in Santa Monica, Calif., called the results “striking,” but noted that questions remain.

“Up until this study we haven’t had anything like it to guide us in determining whether we should treat RIS or not,” she said. “Obviously, larger studies are needed, but I think this is a very important and well-done study.”

In addition to the small sample size, Dr. Giesser noted that the study lacked data on the presence of risk factors that are known to increase RIS patients’ risk of developing MS, such as evidence of spinal cord lesions. That issue was also raised during discussion of the paper in Amsterdam.

“I don’t think this means you should treat everybody with RIS necessarily,” Dr. Giesser said. “But I think it suggests that in people with RIS, particularly if they do have risk factors, you could consider treatment with dimethyl fumarate.”

The study was funded by Biogen. Dr. Okuda has received support from Biogen and EMD Serono/Merck; and consulting fees from Alexion, Biogen, EMD Serono, Genzyme, Novartis, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, Celgene/Bristol Myers Squibb, Genentech, Janssen Pharmaceuticals, and Osmotica Pharmaceuticals. Dr. Giesser reports no relevant financial relationships.

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

Dimethyl fumarate could delay – or even prevent – clinical symptoms in patients with radiologically isolated syndrome (RIS), the earliest detected preclinical phase of multiple sclerosis (MS). Researchers found that dimethyl fumarate reduced the risk of a first acute or progressive event related to CNS demyelination by more than 80%, compared with placebo.

Patients with RIS have incidental MRI abnormalities typical of MS but have no symptoms of the disease. The condition is usually detected when a patient seeks treatment for another issue, such as migraines or head trauma.

The study is the first randomized clinical trial to examine efficacy of a disease-modifying therapy in delaying symptoms in RIS. “It really supports the concept of the benefit of early treatment intervention within this given MS disease spectrum,” lead investigator Darin Okuda, MD, professor of neurology at the University of Texas Southwestern Medical Center in Dallas, told delegates attending the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
 

Topic of debate

RIS was first identified by Dr. Okuda in 2008. Increased use of brain imaging led to the detection of patients with incidental white-matter pathology in the central nervous system on MRI. Some of the findings were nonspecific, but others were highly suggestive of demyelinating pathology based on their location and morphology in the central nervous system.

Although the prevalence of RIS is unknown, incidentally discovered white matter lesions resembling demyelination occur in an estimated 0.1%-0.7% of the general population. Up to half of patients with RIS experience a first clinical MS event within 10 years.

Diagnostic criteria and whether to treat patients with RIS prophylactically has long been a topic of debate among neurologists and radiologists.

Researchers conducted the multicenter, randomized, double-blinded, placebo-controlled ARISE study in 2016, recruiting 87 patients with RIS. The majority of participants were women, and most were diagnosed in their early 40s.

Patients received oral dimethyl fumarate at 240 mg twice daily or placebo and were followed for 96 weeks (1 year, 10 months). Clinical assessments were completed at baseline, at weeks 48 and 96, and at the time of the first clinical event. MRI scans were performed only at the beginning and end of the study.

Those who received dimethyl fumarate had a significantly lower risk of experiencing a first clinical demyelinating event during the study period (adjusted hazard ratio, 0.07; P = .005).

After adjusting for the number of gadolinium-enhancing lesions at baseline, there was a significant reduction in the number of new or newly enlarged T2-weighted hyperintense lesions, a secondary endpoint, in the dimethyl fumarate group, compared with those on placebo (HR, 0.20; P = .042).

“In the future we’d like to see further studies performed to assess the impact on disability outcome measures following treatment for a meaningful amount of time,” Dr. Okuda said.
 

‘Striking’ findings

Barbara Giesser, MD, a neurologist at Pacific Neuroscience Institute in Santa Monica, Calif., called the results “striking,” but noted that questions remain.

“Up until this study we haven’t had anything like it to guide us in determining whether we should treat RIS or not,” she said. “Obviously, larger studies are needed, but I think this is a very important and well-done study.”

In addition to the small sample size, Dr. Giesser noted that the study lacked data on the presence of risk factors that are known to increase RIS patients’ risk of developing MS, such as evidence of spinal cord lesions. That issue was also raised during discussion of the paper in Amsterdam.

“I don’t think this means you should treat everybody with RIS necessarily,” Dr. Giesser said. “But I think it suggests that in people with RIS, particularly if they do have risk factors, you could consider treatment with dimethyl fumarate.”

The study was funded by Biogen. Dr. Okuda has received support from Biogen and EMD Serono/Merck; and consulting fees from Alexion, Biogen, EMD Serono, Genzyme, Novartis, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, Celgene/Bristol Myers Squibb, Genentech, Janssen Pharmaceuticals, and Osmotica Pharmaceuticals. Dr. Giesser reports no relevant financial relationships.

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

Dimethyl fumarate could delay – or even prevent – clinical symptoms in patients with radiologically isolated syndrome (RIS), the earliest detected preclinical phase of multiple sclerosis (MS). Researchers found that dimethyl fumarate reduced the risk of a first acute or progressive event related to CNS demyelination by more than 80%, compared with placebo.

Patients with RIS have incidental MRI abnormalities typical of MS but have no symptoms of the disease. The condition is usually detected when a patient seeks treatment for another issue, such as migraines or head trauma.

The study is the first randomized clinical trial to examine efficacy of a disease-modifying therapy in delaying symptoms in RIS. “It really supports the concept of the benefit of early treatment intervention within this given MS disease spectrum,” lead investigator Darin Okuda, MD, professor of neurology at the University of Texas Southwestern Medical Center in Dallas, told delegates attending the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
 

Topic of debate

RIS was first identified by Dr. Okuda in 2008. Increased use of brain imaging led to the detection of patients with incidental white-matter pathology in the central nervous system on MRI. Some of the findings were nonspecific, but others were highly suggestive of demyelinating pathology based on their location and morphology in the central nervous system.

Although the prevalence of RIS is unknown, incidentally discovered white matter lesions resembling demyelination occur in an estimated 0.1%-0.7% of the general population. Up to half of patients with RIS experience a first clinical MS event within 10 years.

Diagnostic criteria and whether to treat patients with RIS prophylactically has long been a topic of debate among neurologists and radiologists.

Researchers conducted the multicenter, randomized, double-blinded, placebo-controlled ARISE study in 2016, recruiting 87 patients with RIS. The majority of participants were women, and most were diagnosed in their early 40s.

Patients received oral dimethyl fumarate at 240 mg twice daily or placebo and were followed for 96 weeks (1 year, 10 months). Clinical assessments were completed at baseline, at weeks 48 and 96, and at the time of the first clinical event. MRI scans were performed only at the beginning and end of the study.

Those who received dimethyl fumarate had a significantly lower risk of experiencing a first clinical demyelinating event during the study period (adjusted hazard ratio, 0.07; P = .005).

After adjusting for the number of gadolinium-enhancing lesions at baseline, there was a significant reduction in the number of new or newly enlarged T2-weighted hyperintense lesions, a secondary endpoint, in the dimethyl fumarate group, compared with those on placebo (HR, 0.20; P = .042).

“In the future we’d like to see further studies performed to assess the impact on disability outcome measures following treatment for a meaningful amount of time,” Dr. Okuda said.
 

‘Striking’ findings

Barbara Giesser, MD, a neurologist at Pacific Neuroscience Institute in Santa Monica, Calif., called the results “striking,” but noted that questions remain.

“Up until this study we haven’t had anything like it to guide us in determining whether we should treat RIS or not,” she said. “Obviously, larger studies are needed, but I think this is a very important and well-done study.”

In addition to the small sample size, Dr. Giesser noted that the study lacked data on the presence of risk factors that are known to increase RIS patients’ risk of developing MS, such as evidence of spinal cord lesions. That issue was also raised during discussion of the paper in Amsterdam.

“I don’t think this means you should treat everybody with RIS necessarily,” Dr. Giesser said. “But I think it suggests that in people with RIS, particularly if they do have risk factors, you could consider treatment with dimethyl fumarate.”

The study was funded by Biogen. Dr. Okuda has received support from Biogen and EMD Serono/Merck; and consulting fees from Alexion, Biogen, EMD Serono, Genzyme, Novartis, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, Celgene/Bristol Myers Squibb, Genentech, Janssen Pharmaceuticals, and Osmotica Pharmaceuticals. Dr. Giesser reports no relevant financial relationships.

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