Clinician Reviews

The “twincretin” tirzepatide might become part of the “arsenal” against diabetic kidney disease, new research suggests. Notably, the drug significantly reduced the likelihood of macroalbuminuria, in a prespecified subanalysis of the SURPASS-4 clinical trial.

“Once-per-week tirzepatide compared to [daily] insulin glargine treatment resulted in a meaningful improvement in estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (UACR) and the risk of end stage kidney disease (ESKD) – with low risk of clinically relevant hypoglycemia in participants with type 2 diabetes at high cardiovascular risk and varying degrees of chronic kidney disease (CKD),” lead investigator Hiddo J. L. Heerspink, PhD, PharmD, summarized in an email to this news organization.

The U.S. Food and Drug Administration has just approved tirzepatide (Mounjaro, Eli Lilly) – a novel, glucose-dependent insulinotropic polypeptide (GIP) combined with a glucagonlike peptide-1 (GLP-1) receptor agonist – to treat glycemia in patients with type 2 diabetes, based on five pivotal SURPASS trials.

Dr. Heerspink presented the new findings about tirzepatide’s impact on kidney function in an oral session at the annual scientific sessions of the American Diabetes Association.

40% reduced risk of kidney function decline

The main results of SURPASS-4 were published in the Lancet in October 2021, and showed that tirzepatide appeared superior to insulin glargine in lowering hemoglobin A1c in patients with type 2 diabetes at high cardiovascular risk who were inadequately controlled on oral diabetes treatments.

Now, Dr. Heerspink has shown that patients who received tirzepatide as opposed to insulin glargine were significantly less likely to have kidney function decline that included new-onset macroalbuminuria (hazard ratio, 0.59; P < .05).

“These are very large benefits and clearly indicate the potential of tirzepatide to be a very strong kidney protective drug,” said Dr. Heerspink, from the department of clinical pharmacy and pharmacology, University Medical Center Groningen (the Netherlands).

“Based on results from the SURPASS-4 trial, tirzepatide has significant kidney-protective effects in adults with type 2 diabetes with high cardiovascular risk and largely normal kidney function,” Christine Limonte, MD, chair of the session in which the analysis was presented, agreed, in an email to this news organization.

The approximate 40% reduced risk of kidney function decline in this population “is important because it suggests that this novel agent may contribute to the growing arsenal for preventing and treating diabetic kidney disease,” added Dr. Limonte, a clinical research fellow in the division of nephrology, University of Washington, Seattle.

“Over the last several years,” she noted, “sodium glucose cotransporter-2 [SGLT2] inhibitors and GLP-1 receptor agonists have been identified as having significant kidney-protective effects in type 2 diabetes, and as such are becoming first-line agents in the treatment of diabetic kidney disease.”

Additional studies are needed, she added, to assess the impacts of tirzepatide compared to these agents (particularly GLP-1 receptor agonists, which overlap in their mechanism of action).

“With the growing number of therapeutic options for diabetic kidney disease, future research should also focus on identifying combinations of agents which benefit individuals in a ‘targeted’ manner,” according to Dr. Limonte.

“Ensuring accessibility to kidney-protective agents by promoting access to health care and reducing drug costs is essential to improving outcomes in diabetic kidney disease,” she added.

Strongest reduction seen in risk of new macroalbuminuria

One in three adults with diabetes has CKD, according to a press release issued by the ADA. Therefore, there is a need for therapies to reduce the development and progression of CKD in patients with type 2 diabetes.

The prespecified analysis of SUPRESS-4 investigated potential renoprotective effects of tirzepatide.

The trial enrolled 1,995 patients with type 2 diabetes who were at increased risk of cardiovascular disease. The patients had a mean age of 63.6 years and a mean hemoglobin A1c of 8.5%.

Most patients had normal kidney function. The mean eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was 81.3 mL/min per 1.73 m².

Few patients (17%) had moderately or severely reduced kidney function (eGFR <60 mL/min per 1.73 m²). Around a quarter of the patients (28%) had microalbuminuria (UACR 30-300 mg/g) and 8% had macroalbuminuria (UACR >300 mg/g).

The patients were randomized to receive a weekly injection of 5, 10, or 15 mg tirzepatide or a daily individualized injection of insulin glargine starting at 10 IU/day at bedtime, titrated to a fasting blood glucose <100 mg/dL, in addition to existing oral glucose-lowering agents. The primary outcomes in the subanalysis were:

• Endpoint 1: a composite of ≥40% decline in eGFR from baseline, renal death, progression to ESKD, and new-onset macroalbuminuria.
• Endpoint 2: the same as endpoint 1 excluding new-onset macroalbuminuria.

During a median follow up of 85 weeks and up to 104 weeks, patients who received tirzepatide versus insulin glargine were significantly less likely to reach endpoint 1 but not endpoint 2.

In addition, tirzepatide “very strongly” reduced the risk of new-onset macroalbuminuria, compared to insulin glargine, by approximately 60% in the complete study cohort (hazard ratio, 0.41; P < .05), Dr. Limonte noted.

Tirzepatide also reduced the risk of a >40% decline in eGFR, but this effect was not statistically significant, possibly because this outcome was underpowered. There were also too few kidney deaths and progressions to ESKD to meaningfully assess the effects of tirzepatide on these outcomes.

Therefore, Dr. Limonte noted, “it is likely that tirzepatide’s significant benefit on composite endpoint 1 was largely driven by this agent’s impact on reducing macroalbuminuria onset [explaining why a significant benefit was not seen with composite endpoint 2, which excluded new-onset macroalbuminuria].”

The study was funded by Eli Lilly. Dr. Heerspink disclosed that he is a consultant for AstraZeneca, Bayer AG, Boehringer Ingelheim, Chinook Therapeutics, CSL Behring, Gilead Sciences, Goldfinch Bio, Janssen Research & Development, Mitsubishi Tanabe Pharma, Mundipharma, and Traveere Pharmaceuticals, and has received research support from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk.

Dr. Limonte disclosed that she receives funds from the American Kidney Fund’s Clinical Scientist in Nephrology Award.

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

The “twincretin” tirzepatide might become part of the “arsenal” against diabetic kidney disease, new research suggests. Notably, the drug significantly reduced the likelihood of macroalbuminuria, in a prespecified subanalysis of the SURPASS-4 clinical trial.

“Once-per-week tirzepatide compared to [daily] insulin glargine treatment resulted in a meaningful improvement in estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (UACR) and the risk of end stage kidney disease (ESKD) – with low risk of clinically relevant hypoglycemia in participants with type 2 diabetes at high cardiovascular risk and varying degrees of chronic kidney disease (CKD),” lead investigator Hiddo J. L. Heerspink, PhD, PharmD, summarized in an email to this news organization.

The U.S. Food and Drug Administration has just approved tirzepatide (Mounjaro, Eli Lilly) – a novel, glucose-dependent insulinotropic polypeptide (GIP) combined with a glucagonlike peptide-1 (GLP-1) receptor agonist – to treat glycemia in patients with type 2 diabetes, based on five pivotal SURPASS trials.

Dr. Heerspink presented the new findings about tirzepatide’s impact on kidney function in an oral session at the annual scientific sessions of the American Diabetes Association.

40% reduced risk of kidney function decline

The main results of SURPASS-4 were published in the Lancet in October 2021, and showed that tirzepatide appeared superior to insulin glargine in lowering hemoglobin A1c in patients with type 2 diabetes at high cardiovascular risk who were inadequately controlled on oral diabetes treatments.

Now, Dr. Heerspink has shown that patients who received tirzepatide as opposed to insulin glargine were significantly less likely to have kidney function decline that included new-onset macroalbuminuria (hazard ratio, 0.59; P < .05).

“These are very large benefits and clearly indicate the potential of tirzepatide to be a very strong kidney protective drug,” said Dr. Heerspink, from the department of clinical pharmacy and pharmacology, University Medical Center Groningen (the Netherlands).

“Based on results from the SURPASS-4 trial, tirzepatide has significant kidney-protective effects in adults with type 2 diabetes with high cardiovascular risk and largely normal kidney function,” Christine Limonte, MD, chair of the session in which the analysis was presented, agreed, in an email to this news organization.

The approximate 40% reduced risk of kidney function decline in this population “is important because it suggests that this novel agent may contribute to the growing arsenal for preventing and treating diabetic kidney disease,” added Dr. Limonte, a clinical research fellow in the division of nephrology, University of Washington, Seattle.

“Over the last several years,” she noted, “sodium glucose cotransporter-2 [SGLT2] inhibitors and GLP-1 receptor agonists have been identified as having significant kidney-protective effects in type 2 diabetes, and as such are becoming first-line agents in the treatment of diabetic kidney disease.”

Additional studies are needed, she added, to assess the impacts of tirzepatide compared to these agents (particularly GLP-1 receptor agonists, which overlap in their mechanism of action).

“With the growing number of therapeutic options for diabetic kidney disease, future research should also focus on identifying combinations of agents which benefit individuals in a ‘targeted’ manner,” according to Dr. Limonte.

“Ensuring accessibility to kidney-protective agents by promoting access to health care and reducing drug costs is essential to improving outcomes in diabetic kidney disease,” she added.

Strongest reduction seen in risk of new macroalbuminuria

One in three adults with diabetes has CKD, according to a press release issued by the ADA. Therefore, there is a need for therapies to reduce the development and progression of CKD in patients with type 2 diabetes.

The prespecified analysis of SUPRESS-4 investigated potential renoprotective effects of tirzepatide.

The trial enrolled 1,995 patients with type 2 diabetes who were at increased risk of cardiovascular disease. The patients had a mean age of 63.6 years and a mean hemoglobin A1c of 8.5%.

Most patients had normal kidney function. The mean eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was 81.3 mL/min per 1.73 m².

Few patients (17%) had moderately or severely reduced kidney function (eGFR <60 mL/min per 1.73 m²). Around a quarter of the patients (28%) had microalbuminuria (UACR 30-300 mg/g) and 8% had macroalbuminuria (UACR >300 mg/g).

The patients were randomized to receive a weekly injection of 5, 10, or 15 mg tirzepatide or a daily individualized injection of insulin glargine starting at 10 IU/day at bedtime, titrated to a fasting blood glucose <100 mg/dL, in addition to existing oral glucose-lowering agents. The primary outcomes in the subanalysis were:

• Endpoint 1: a composite of ≥40% decline in eGFR from baseline, renal death, progression to ESKD, and new-onset macroalbuminuria.
• Endpoint 2: the same as endpoint 1 excluding new-onset macroalbuminuria.

During a median follow up of 85 weeks and up to 104 weeks, patients who received tirzepatide versus insulin glargine were significantly less likely to reach endpoint 1 but not endpoint 2.

In addition, tirzepatide “very strongly” reduced the risk of new-onset macroalbuminuria, compared to insulin glargine, by approximately 60% in the complete study cohort (hazard ratio, 0.41; P < .05), Dr. Limonte noted.

Tirzepatide also reduced the risk of a >40% decline in eGFR, but this effect was not statistically significant, possibly because this outcome was underpowered. There were also too few kidney deaths and progressions to ESKD to meaningfully assess the effects of tirzepatide on these outcomes.

Therefore, Dr. Limonte noted, “it is likely that tirzepatide’s significant benefit on composite endpoint 1 was largely driven by this agent’s impact on reducing macroalbuminuria onset [explaining why a significant benefit was not seen with composite endpoint 2, which excluded new-onset macroalbuminuria].”

The study was funded by Eli Lilly. Dr. Heerspink disclosed that he is a consultant for AstraZeneca, Bayer AG, Boehringer Ingelheim, Chinook Therapeutics, CSL Behring, Gilead Sciences, Goldfinch Bio, Janssen Research & Development, Mitsubishi Tanabe Pharma, Mundipharma, and Traveere Pharmaceuticals, and has received research support from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk.

Dr. Limonte disclosed that she receives funds from the American Kidney Fund’s Clinical Scientist in Nephrology Award.

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

The “twincretin” tirzepatide might become part of the “arsenal” against diabetic kidney disease, new research suggests. Notably, the drug significantly reduced the likelihood of macroalbuminuria, in a prespecified subanalysis of the SURPASS-4 clinical trial.

“Once-per-week tirzepatide compared to [daily] insulin glargine treatment resulted in a meaningful improvement in estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (UACR) and the risk of end stage kidney disease (ESKD) – with low risk of clinically relevant hypoglycemia in participants with type 2 diabetes at high cardiovascular risk and varying degrees of chronic kidney disease (CKD),” lead investigator Hiddo J. L. Heerspink, PhD, PharmD, summarized in an email to this news organization.

The U.S. Food and Drug Administration has just approved tirzepatide (Mounjaro, Eli Lilly) – a novel, glucose-dependent insulinotropic polypeptide (GIP) combined with a glucagonlike peptide-1 (GLP-1) receptor agonist – to treat glycemia in patients with type 2 diabetes, based on five pivotal SURPASS trials.

Dr. Heerspink presented the new findings about tirzepatide’s impact on kidney function in an oral session at the annual scientific sessions of the American Diabetes Association.

40% reduced risk of kidney function decline

The main results of SURPASS-4 were published in the Lancet in October 2021, and showed that tirzepatide appeared superior to insulin glargine in lowering hemoglobin A1c in patients with type 2 diabetes at high cardiovascular risk who were inadequately controlled on oral diabetes treatments.

Now, Dr. Heerspink has shown that patients who received tirzepatide as opposed to insulin glargine were significantly less likely to have kidney function decline that included new-onset macroalbuminuria (hazard ratio, 0.59; P < .05).

“These are very large benefits and clearly indicate the potential of tirzepatide to be a very strong kidney protective drug,” said Dr. Heerspink, from the department of clinical pharmacy and pharmacology, University Medical Center Groningen (the Netherlands).

“Based on results from the SURPASS-4 trial, tirzepatide has significant kidney-protective effects in adults with type 2 diabetes with high cardiovascular risk and largely normal kidney function,” Christine Limonte, MD, chair of the session in which the analysis was presented, agreed, in an email to this news organization.

The approximate 40% reduced risk of kidney function decline in this population “is important because it suggests that this novel agent may contribute to the growing arsenal for preventing and treating diabetic kidney disease,” added Dr. Limonte, a clinical research fellow in the division of nephrology, University of Washington, Seattle.

“Over the last several years,” she noted, “sodium glucose cotransporter-2 [SGLT2] inhibitors and GLP-1 receptor agonists have been identified as having significant kidney-protective effects in type 2 diabetes, and as such are becoming first-line agents in the treatment of diabetic kidney disease.”

Additional studies are needed, she added, to assess the impacts of tirzepatide compared to these agents (particularly GLP-1 receptor agonists, which overlap in their mechanism of action).

“With the growing number of therapeutic options for diabetic kidney disease, future research should also focus on identifying combinations of agents which benefit individuals in a ‘targeted’ manner,” according to Dr. Limonte.

“Ensuring accessibility to kidney-protective agents by promoting access to health care and reducing drug costs is essential to improving outcomes in diabetic kidney disease,” she added.

Strongest reduction seen in risk of new macroalbuminuria

One in three adults with diabetes has CKD, according to a press release issued by the ADA. Therefore, there is a need for therapies to reduce the development and progression of CKD in patients with type 2 diabetes.

The prespecified analysis of SUPRESS-4 investigated potential renoprotective effects of tirzepatide.

The trial enrolled 1,995 patients with type 2 diabetes who were at increased risk of cardiovascular disease. The patients had a mean age of 63.6 years and a mean hemoglobin A1c of 8.5%.

Most patients had normal kidney function. The mean eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was 81.3 mL/min per 1.73 m².

Few patients (17%) had moderately or severely reduced kidney function (eGFR <60 mL/min per 1.73 m²). Around a quarter of the patients (28%) had microalbuminuria (UACR 30-300 mg/g) and 8% had macroalbuminuria (UACR >300 mg/g).

The patients were randomized to receive a weekly injection of 5, 10, or 15 mg tirzepatide or a daily individualized injection of insulin glargine starting at 10 IU/day at bedtime, titrated to a fasting blood glucose <100 mg/dL, in addition to existing oral glucose-lowering agents. The primary outcomes in the subanalysis were:

• Endpoint 1: a composite of ≥40% decline in eGFR from baseline, renal death, progression to ESKD, and new-onset macroalbuminuria.
• Endpoint 2: the same as endpoint 1 excluding new-onset macroalbuminuria.

During a median follow up of 85 weeks and up to 104 weeks, patients who received tirzepatide versus insulin glargine were significantly less likely to reach endpoint 1 but not endpoint 2.

In addition, tirzepatide “very strongly” reduced the risk of new-onset macroalbuminuria, compared to insulin glargine, by approximately 60% in the complete study cohort (hazard ratio, 0.41; P < .05), Dr. Limonte noted.

Tirzepatide also reduced the risk of a >40% decline in eGFR, but this effect was not statistically significant, possibly because this outcome was underpowered. There were also too few kidney deaths and progressions to ESKD to meaningfully assess the effects of tirzepatide on these outcomes.

Therefore, Dr. Limonte noted, “it is likely that tirzepatide’s significant benefit on composite endpoint 1 was largely driven by this agent’s impact on reducing macroalbuminuria onset [explaining why a significant benefit was not seen with composite endpoint 2, which excluded new-onset macroalbuminuria].”

The study was funded by Eli Lilly. Dr. Heerspink disclosed that he is a consultant for AstraZeneca, Bayer AG, Boehringer Ingelheim, Chinook Therapeutics, CSL Behring, Gilead Sciences, Goldfinch Bio, Janssen Research & Development, Mitsubishi Tanabe Pharma, Mundipharma, and Traveere Pharmaceuticals, and has received research support from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk.

Dr. Limonte disclosed that she receives funds from the American Kidney Fund’s Clinical Scientist in Nephrology Award.

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

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/mcL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

“It’s meaningless to just go by some recommendation covering time since the last treatment,” study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor at Uppsala University, both in Sweden, told this news organization.

“It’s misleading and potentially harmful for patients,” Dr. Burman said.

The findings were published online  in JAMA Network Open.
 

Finding the cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/mcL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs. 2.1; P = .002).
 

Close monitoring needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/mcL, versus 51/mcL for the remainder of the cohort (P < .001).

A cutoff value of 40/mcL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible – but that they should hold off on receiving a booster until their B-cell counts reach 40/mcL.

Regarding when a clinician should re-vaccinate, “the results from our study strongly suggest that you should not do that right away or just follow some generic guideline,” Dr. Burman said.

“You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/mcL” he added.

Dr. Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.
 

Too soon for B-cell measures?

Commenting for this news organization, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the United States for treating MS.

“Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines,” said Dr. Fox, who was not involved with the research.

“Given the unknown efficacy of these extended intervals, I don’t think we’re at the point of making management recommendations based upon B-cell counts,” he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Dr. Burman reported.

“Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class,” Dr. Fox said.

“Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data,” he noted.

“At this point, we don’t know which decisions were right or wrong, but I certainly don’t think we should judge clinicians for making decisions the best they could.”

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Dr. Burman reported no relevant financial relationships. Dr. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

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

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/mcL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

“It’s meaningless to just go by some recommendation covering time since the last treatment,” study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor at Uppsala University, both in Sweden, told this news organization.

“It’s misleading and potentially harmful for patients,” Dr. Burman said.

The findings were published online  in JAMA Network Open.
 

Finding the cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/mcL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs. 2.1; P = .002).
 

Close monitoring needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/mcL, versus 51/mcL for the remainder of the cohort (P < .001).

A cutoff value of 40/mcL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible – but that they should hold off on receiving a booster until their B-cell counts reach 40/mcL.

Regarding when a clinician should re-vaccinate, “the results from our study strongly suggest that you should not do that right away or just follow some generic guideline,” Dr. Burman said.

“You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/mcL” he added.

Dr. Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.
 

Too soon for B-cell measures?

Commenting for this news organization, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the United States for treating MS.

“Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines,” said Dr. Fox, who was not involved with the research.

“Given the unknown efficacy of these extended intervals, I don’t think we’re at the point of making management recommendations based upon B-cell counts,” he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Dr. Burman reported.

“Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class,” Dr. Fox said.

“Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data,” he noted.

“At this point, we don’t know which decisions were right or wrong, but I certainly don’t think we should judge clinicians for making decisions the best they could.”

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Dr. Burman reported no relevant financial relationships. Dr. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

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

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/mcL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

“It’s meaningless to just go by some recommendation covering time since the last treatment,” study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor at Uppsala University, both in Sweden, told this news organization.

“It’s misleading and potentially harmful for patients,” Dr. Burman said.

The findings were published online  in JAMA Network Open.
 

Finding the cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/mcL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs. 2.1; P = .002).
 

Close monitoring needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/mcL, versus 51/mcL for the remainder of the cohort (P < .001).

A cutoff value of 40/mcL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible – but that they should hold off on receiving a booster until their B-cell counts reach 40/mcL.

Regarding when a clinician should re-vaccinate, “the results from our study strongly suggest that you should not do that right away or just follow some generic guideline,” Dr. Burman said.

“You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/mcL” he added.

Dr. Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.
 

Too soon for B-cell measures?

Commenting for this news organization, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the United States for treating MS.

“Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines,” said Dr. Fox, who was not involved with the research.

“Given the unknown efficacy of these extended intervals, I don’t think we’re at the point of making management recommendations based upon B-cell counts,” he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Dr. Burman reported.

“Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class,” Dr. Fox said.

“Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data,” he noted.

“At this point, we don’t know which decisions were right or wrong, but I certainly don’t think we should judge clinicians for making decisions the best they could.”

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Dr. Burman reported no relevant financial relationships. Dr. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

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

In a new risk-assessment document, the European Centre for Disease Prevention and Control summarizes what we currently know about monkeypox and recommends that European countries focus on the identification and management of the disease as well as contract tracing and prompt reporting of new cases of the virus.

Recent developments

From May 15 to May 23, in eight European Union member states (Belgium, France, Germany, Italy, the Netherlands, Portugal, Spain, and Sweden) a total of 85 cases of monkeypox were reported; they were acquired through autochthonous transmission. Current diagnosed cases of monkeypox have mainly been recorded in men who have sexual relations with other men, suggesting that transmission may occur during sexual intercourse, through infectious material coming into contact with mucosa or damaged skin, or via large respiratory droplets during prolonged face-to-face contact.

Andrea Ammon, MD, director of the ECDC, stated that “most current cases have presented with mild symptoms of the disease, and for the general population, the chance of diffusion is very low. However, the likelihood of a further spread of the virus through close contact, for example during sexual activities among people with multiple sexual partners, is considerably increased.”

Stella Kyriakides, European commissioner for health and food safety, added, “I am worried about the increase of cases of monkeypox in the EU and worldwide. We are currently monitoring the situation and, although, at the moment, the probability of it spreading to the general population is low, the situation is evolving. We should all remain alert, making sure that contact tracing and a sufficient diagnostic capacity are in place and guarantee that vaccines and antiviral drugs are available, as well as sufficient personal protective equipment [PPE] for health care professionals.”
 

Routes of transmission

Monkeypox is not easily spread among people. Person-to-person transmission occurs through close contact with infectious material, coming from skin lesions of an infected person, through air droplets in the case of prolonged face-to-face contact, and through fomites. So far, diagnosed cases suggest that transmission can occur through sexual intercourse.

The incubation period is 5-21 days, and patients are symptomatic for 2-4 weeks.

According to the ECDC, the likelihood of this infection spreading is increased among people who have more than one sexual partner. Although most current cases present with mild symptoms, monkeypox can cause severe disease in some groups (such as young children, pregnant women, and immunosuppressed people). However, the probability of severe disease cannot yet be estimated precisely.

The overall risk is considered moderate for people who have multiple sexual partners and low for the general population.
 

Clinical course

The disease initially presents with fever, myalgia, fatigue, and headache. Within 3 days of the onset of the prodromal symptoms, a centrifugal maculopapular rash appears on the site of primary infection and rapidly spreads to other parts of the body. The palms of the hands and bottoms of the feet are involved in cases where the rash has spread, which is a characteristic of the disease. Usually within 12 days, the lesions progress, simultaneously changing from macules to papules, blisters, pustules, and scabs before falling off. The lesions may have a central depression and be extremely itchy.

If the patient scratches them, a secondary bacterial infection may take hold (for which treatment with oral antihistamines is indicated). Lesions may also be present in the oral or ocular mucous membrane. Either before or at the same time as onset of the rash, patients may experience swelling of the lymph nodes, which usually is not seen with smallpox or chickenpox.

The onset of the rash is considered the start of the infectious period; however, people with prodromal symptoms may also transmit the virus.

Most cases in people present with mild or moderate symptoms. Complications seen in endemic countries include encephalitis, secondary bacterial skin infections, dehydration, conjunctivitis, keratitis, and pneumonia. The death rate ranges from 0% to 11% in endemic areas, with fatalities from the disease mostly occurring in younger children.

There is not a lot of information available on the disease in immunosuppressed individuals. In the 2017 Nigerian epidemic, patients with a concomitant HIV infection presented with more severe disease, with a greater number of skin lesions and genital ulcers, compared with HIV-negative individuals. No deaths were reported among seropositive patients. The main sequelae from the disease are usually disfiguring scars and permanent corneal lesions.
 

Treatment

No smallpox vaccines are authorized for use against monkeypox, however the third-generation smallpox vaccine Imvanex (Modified Vaccinia Ankara) has been authorized by the European Medicines Agency (EMA) for the EU market against smallpox and has demonstrated to provide protection in primates.

Old-generation smallpox vaccines have significant side effects, are no longer authorized, and should no longer be used. It is also important to note the lack of safety data for the use of Imvanex in immunocompromised people.

For this reason, National Immunization Technical Advisory Groups have been asked to develop specific guidelines for vaccination in close contacts of patients with monkeypox. The use of a smallpox vaccine for preexposure prophylaxis cannot be considered now, when taking into account the risk-benefit ratio.

In regard to treatment, tecovirimat is the only antiviral drug with an EMA-authorized indication for orthopoxvirus infection.

Brincidofovir is not authorized in the EU but has been authorized by the US Food and Drug Administration. However, availability on the European market is limited somewhat by the number of doses.

According to the ECDC, health care authorities should provide information about which groups should have priority access to treatment.

The use of antivirals for postexposure prophylaxis should be investigated further. Cidofovir is active in vitro for smallpox but has a pronounced nephrotoxicity profile that makes it unsuitable for first-line treatment.

The ECDC document also proposes an interim case definition for epidemiologic reporting. Further indications will also be provided for the management of monkeypox cases and close contacts. Those infected should remain in isolation until the scabs have fallen off and should, above all, avoid close contact with at-risk or immunosuppressed people as well as pets.

Most infected people can remain at home with supportive care.
 

Prevention

Close contacts for cases of monkeypox should monitor the development of their symptoms until 21 days have passed from their most recent exposure to the virus.

Health care workers should wear appropriate PPE (gloves, water-resistant gowns, FFP2 masks) during screening for suspected cases or when working with confirmed cases. Laboratory staff should also take precautions to avoid exposure in the workplace.

Close contacts of an infected person should not donate blood, organs, or bone marrow for at least 21 days from the last day of exposure.

Finally, the ECDC recommends increasing proactive communication of the risks to increase awareness and provide updates and indications to individuals who are at a greater risk, as well as to the general public. These messages should highlight that monkeypox is spread through close person-to-person contact, especially within the family unit, and also potentially through sexual intercourse. A balance, however, should be maintained between informing the individuals who are at greater risk and communicating that the virus is not easily spread and that the risk for the general population is low.
 

Human-to-animal transmission

A potential risk for human-to-animal transmission exists in Europe; therefore, a close collaboration is required between human and veterinary health care authorities, working together to manage domestic animals exposed to the virus and to prevent transmission of the disease to wildlife. To date, the European Food Safety Authority is not aware of any reports of animal infections (domestic or wild) within the EU.

There are still many unknown factors about this outbreak. The ECDC continues to closely monitor any developments and will update the risk assessment as soon as new data and information become available.

If human-to-animal transmission occurs and the virus spreads among animal populations, there is a risk that the disease could become an endemic in Europe. Therefore, human and veterinary health care authorities should work together closely to manage cases of domestic animals exposed to the virus and prevent transmission of the disease to wildlife.

A version of this article appeared on Medscape.com. This article was translated from Univadis Italy.

In a new risk-assessment document, the European Centre for Disease Prevention and Control summarizes what we currently know about monkeypox and recommends that European countries focus on the identification and management of the disease as well as contract tracing and prompt reporting of new cases of the virus.

Recent developments

From May 15 to May 23, in eight European Union member states (Belgium, France, Germany, Italy, the Netherlands, Portugal, Spain, and Sweden) a total of 85 cases of monkeypox were reported; they were acquired through autochthonous transmission. Current diagnosed cases of monkeypox have mainly been recorded in men who have sexual relations with other men, suggesting that transmission may occur during sexual intercourse, through infectious material coming into contact with mucosa or damaged skin, or via large respiratory droplets during prolonged face-to-face contact.

Andrea Ammon, MD, director of the ECDC, stated that “most current cases have presented with mild symptoms of the disease, and for the general population, the chance of diffusion is very low. However, the likelihood of a further spread of the virus through close contact, for example during sexual activities among people with multiple sexual partners, is considerably increased.”

Stella Kyriakides, European commissioner for health and food safety, added, “I am worried about the increase of cases of monkeypox in the EU and worldwide. We are currently monitoring the situation and, although, at the moment, the probability of it spreading to the general population is low, the situation is evolving. We should all remain alert, making sure that contact tracing and a sufficient diagnostic capacity are in place and guarantee that vaccines and antiviral drugs are available, as well as sufficient personal protective equipment [PPE] for health care professionals.”
 

Routes of transmission

Monkeypox is not easily spread among people. Person-to-person transmission occurs through close contact with infectious material, coming from skin lesions of an infected person, through air droplets in the case of prolonged face-to-face contact, and through fomites. So far, diagnosed cases suggest that transmission can occur through sexual intercourse.

The incubation period is 5-21 days, and patients are symptomatic for 2-4 weeks.

According to the ECDC, the likelihood of this infection spreading is increased among people who have more than one sexual partner. Although most current cases present with mild symptoms, monkeypox can cause severe disease in some groups (such as young children, pregnant women, and immunosuppressed people). However, the probability of severe disease cannot yet be estimated precisely.

The overall risk is considered moderate for people who have multiple sexual partners and low for the general population.
 

Clinical course

The disease initially presents with fever, myalgia, fatigue, and headache. Within 3 days of the onset of the prodromal symptoms, a centrifugal maculopapular rash appears on the site of primary infection and rapidly spreads to other parts of the body. The palms of the hands and bottoms of the feet are involved in cases where the rash has spread, which is a characteristic of the disease. Usually within 12 days, the lesions progress, simultaneously changing from macules to papules, blisters, pustules, and scabs before falling off. The lesions may have a central depression and be extremely itchy.

If the patient scratches them, a secondary bacterial infection may take hold (for which treatment with oral antihistamines is indicated). Lesions may also be present in the oral or ocular mucous membrane. Either before or at the same time as onset of the rash, patients may experience swelling of the lymph nodes, which usually is not seen with smallpox or chickenpox.

The onset of the rash is considered the start of the infectious period; however, people with prodromal symptoms may also transmit the virus.

Most cases in people present with mild or moderate symptoms. Complications seen in endemic countries include encephalitis, secondary bacterial skin infections, dehydration, conjunctivitis, keratitis, and pneumonia. The death rate ranges from 0% to 11% in endemic areas, with fatalities from the disease mostly occurring in younger children.

There is not a lot of information available on the disease in immunosuppressed individuals. In the 2017 Nigerian epidemic, patients with a concomitant HIV infection presented with more severe disease, with a greater number of skin lesions and genital ulcers, compared with HIV-negative individuals. No deaths were reported among seropositive patients. The main sequelae from the disease are usually disfiguring scars and permanent corneal lesions.
 

Treatment

No smallpox vaccines are authorized for use against monkeypox, however the third-generation smallpox vaccine Imvanex (Modified Vaccinia Ankara) has been authorized by the European Medicines Agency (EMA) for the EU market against smallpox and has demonstrated to provide protection in primates.

Old-generation smallpox vaccines have significant side effects, are no longer authorized, and should no longer be used. It is also important to note the lack of safety data for the use of Imvanex in immunocompromised people.

For this reason, National Immunization Technical Advisory Groups have been asked to develop specific guidelines for vaccination in close contacts of patients with monkeypox. The use of a smallpox vaccine for preexposure prophylaxis cannot be considered now, when taking into account the risk-benefit ratio.

In regard to treatment, tecovirimat is the only antiviral drug with an EMA-authorized indication for orthopoxvirus infection.

Brincidofovir is not authorized in the EU but has been authorized by the US Food and Drug Administration. However, availability on the European market is limited somewhat by the number of doses.

According to the ECDC, health care authorities should provide information about which groups should have priority access to treatment.

The use of antivirals for postexposure prophylaxis should be investigated further. Cidofovir is active in vitro for smallpox but has a pronounced nephrotoxicity profile that makes it unsuitable for first-line treatment.

The ECDC document also proposes an interim case definition for epidemiologic reporting. Further indications will also be provided for the management of monkeypox cases and close contacts. Those infected should remain in isolation until the scabs have fallen off and should, above all, avoid close contact with at-risk or immunosuppressed people as well as pets.

Most infected people can remain at home with supportive care.
 

Prevention

Close contacts for cases of monkeypox should monitor the development of their symptoms until 21 days have passed from their most recent exposure to the virus.

Health care workers should wear appropriate PPE (gloves, water-resistant gowns, FFP2 masks) during screening for suspected cases or when working with confirmed cases. Laboratory staff should also take precautions to avoid exposure in the workplace.

Close contacts of an infected person should not donate blood, organs, or bone marrow for at least 21 days from the last day of exposure.

Finally, the ECDC recommends increasing proactive communication of the risks to increase awareness and provide updates and indications to individuals who are at a greater risk, as well as to the general public. These messages should highlight that monkeypox is spread through close person-to-person contact, especially within the family unit, and also potentially through sexual intercourse. A balance, however, should be maintained between informing the individuals who are at greater risk and communicating that the virus is not easily spread and that the risk for the general population is low.
 

Human-to-animal transmission

A potential risk for human-to-animal transmission exists in Europe; therefore, a close collaboration is required between human and veterinary health care authorities, working together to manage domestic animals exposed to the virus and to prevent transmission of the disease to wildlife. To date, the European Food Safety Authority is not aware of any reports of animal infections (domestic or wild) within the EU.

There are still many unknown factors about this outbreak. The ECDC continues to closely monitor any developments and will update the risk assessment as soon as new data and information become available.

If human-to-animal transmission occurs and the virus spreads among animal populations, there is a risk that the disease could become an endemic in Europe. Therefore, human and veterinary health care authorities should work together closely to manage cases of domestic animals exposed to the virus and prevent transmission of the disease to wildlife.

A version of this article appeared on Medscape.com. This article was translated from Univadis Italy.

In a new risk-assessment document, the European Centre for Disease Prevention and Control summarizes what we currently know about monkeypox and recommends that European countries focus on the identification and management of the disease as well as contract tracing and prompt reporting of new cases of the virus.

Recent developments

From May 15 to May 23, in eight European Union member states (Belgium, France, Germany, Italy, the Netherlands, Portugal, Spain, and Sweden) a total of 85 cases of monkeypox were reported; they were acquired through autochthonous transmission. Current diagnosed cases of monkeypox have mainly been recorded in men who have sexual relations with other men, suggesting that transmission may occur during sexual intercourse, through infectious material coming into contact with mucosa or damaged skin, or via large respiratory droplets during prolonged face-to-face contact.

Andrea Ammon, MD, director of the ECDC, stated that “most current cases have presented with mild symptoms of the disease, and for the general population, the chance of diffusion is very low. However, the likelihood of a further spread of the virus through close contact, for example during sexual activities among people with multiple sexual partners, is considerably increased.”

Stella Kyriakides, European commissioner for health and food safety, added, “I am worried about the increase of cases of monkeypox in the EU and worldwide. We are currently monitoring the situation and, although, at the moment, the probability of it spreading to the general population is low, the situation is evolving. We should all remain alert, making sure that contact tracing and a sufficient diagnostic capacity are in place and guarantee that vaccines and antiviral drugs are available, as well as sufficient personal protective equipment [PPE] for health care professionals.”
 

Routes of transmission

Monkeypox is not easily spread among people. Person-to-person transmission occurs through close contact with infectious material, coming from skin lesions of an infected person, through air droplets in the case of prolonged face-to-face contact, and through fomites. So far, diagnosed cases suggest that transmission can occur through sexual intercourse.

The incubation period is 5-21 days, and patients are symptomatic for 2-4 weeks.

According to the ECDC, the likelihood of this infection spreading is increased among people who have more than one sexual partner. Although most current cases present with mild symptoms, monkeypox can cause severe disease in some groups (such as young children, pregnant women, and immunosuppressed people). However, the probability of severe disease cannot yet be estimated precisely.

The overall risk is considered moderate for people who have multiple sexual partners and low for the general population.
 

Clinical course

The disease initially presents with fever, myalgia, fatigue, and headache. Within 3 days of the onset of the prodromal symptoms, a centrifugal maculopapular rash appears on the site of primary infection and rapidly spreads to other parts of the body. The palms of the hands and bottoms of the feet are involved in cases where the rash has spread, which is a characteristic of the disease. Usually within 12 days, the lesions progress, simultaneously changing from macules to papules, blisters, pustules, and scabs before falling off. The lesions may have a central depression and be extremely itchy.

If the patient scratches them, a secondary bacterial infection may take hold (for which treatment with oral antihistamines is indicated). Lesions may also be present in the oral or ocular mucous membrane. Either before or at the same time as onset of the rash, patients may experience swelling of the lymph nodes, which usually is not seen with smallpox or chickenpox.

The onset of the rash is considered the start of the infectious period; however, people with prodromal symptoms may also transmit the virus.

Most cases in people present with mild or moderate symptoms. Complications seen in endemic countries include encephalitis, secondary bacterial skin infections, dehydration, conjunctivitis, keratitis, and pneumonia. The death rate ranges from 0% to 11% in endemic areas, with fatalities from the disease mostly occurring in younger children.

There is not a lot of information available on the disease in immunosuppressed individuals. In the 2017 Nigerian epidemic, patients with a concomitant HIV infection presented with more severe disease, with a greater number of skin lesions and genital ulcers, compared with HIV-negative individuals. No deaths were reported among seropositive patients. The main sequelae from the disease are usually disfiguring scars and permanent corneal lesions.
 

Treatment

No smallpox vaccines are authorized for use against monkeypox, however the third-generation smallpox vaccine Imvanex (Modified Vaccinia Ankara) has been authorized by the European Medicines Agency (EMA) for the EU market against smallpox and has demonstrated to provide protection in primates.

Old-generation smallpox vaccines have significant side effects, are no longer authorized, and should no longer be used. It is also important to note the lack of safety data for the use of Imvanex in immunocompromised people.

For this reason, National Immunization Technical Advisory Groups have been asked to develop specific guidelines for vaccination in close contacts of patients with monkeypox. The use of a smallpox vaccine for preexposure prophylaxis cannot be considered now, when taking into account the risk-benefit ratio.

In regard to treatment, tecovirimat is the only antiviral drug with an EMA-authorized indication for orthopoxvirus infection.

Brincidofovir is not authorized in the EU but has been authorized by the US Food and Drug Administration. However, availability on the European market is limited somewhat by the number of doses.

According to the ECDC, health care authorities should provide information about which groups should have priority access to treatment.

The use of antivirals for postexposure prophylaxis should be investigated further. Cidofovir is active in vitro for smallpox but has a pronounced nephrotoxicity profile that makes it unsuitable for first-line treatment.

The ECDC document also proposes an interim case definition for epidemiologic reporting. Further indications will also be provided for the management of monkeypox cases and close contacts. Those infected should remain in isolation until the scabs have fallen off and should, above all, avoid close contact with at-risk or immunosuppressed people as well as pets.

Most infected people can remain at home with supportive care.
 

Prevention

Close contacts for cases of monkeypox should monitor the development of their symptoms until 21 days have passed from their most recent exposure to the virus.

Health care workers should wear appropriate PPE (gloves, water-resistant gowns, FFP2 masks) during screening for suspected cases or when working with confirmed cases. Laboratory staff should also take precautions to avoid exposure in the workplace.

Close contacts of an infected person should not donate blood, organs, or bone marrow for at least 21 days from the last day of exposure.

Finally, the ECDC recommends increasing proactive communication of the risks to increase awareness and provide updates and indications to individuals who are at a greater risk, as well as to the general public. These messages should highlight that monkeypox is spread through close person-to-person contact, especially within the family unit, and also potentially through sexual intercourse. A balance, however, should be maintained between informing the individuals who are at greater risk and communicating that the virus is not easily spread and that the risk for the general population is low.
 

Human-to-animal transmission

A potential risk for human-to-animal transmission exists in Europe; therefore, a close collaboration is required between human and veterinary health care authorities, working together to manage domestic animals exposed to the virus and to prevent transmission of the disease to wildlife. To date, the European Food Safety Authority is not aware of any reports of animal infections (domestic or wild) within the EU.

There are still many unknown factors about this outbreak. The ECDC continues to closely monitor any developments and will update the risk assessment as soon as new data and information become available.

If human-to-animal transmission occurs and the virus spreads among animal populations, there is a risk that the disease could become an endemic in Europe. Therefore, human and veterinary health care authorities should work together closely to manage cases of domestic animals exposed to the virus and prevent transmission of the disease to wildlife.

A version of this article appeared on Medscape.com. This article was translated from Univadis Italy.

The Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA) trial was launched in order to examine the effects of treatment on children with poorly controlled allergic asthma who live in low-income urban environments in the United States, according to the National Institute of Allergy and Infectious Diseases.

Black and Hispanic children who live in these environments are at particularly high risk for asthma and are prone to attacks. These children and adolescents often have many allergies and are exposed to both high levels of indoor allergens and traffic-related pollution, which can make their asthma even more difficult to control, according to a June 2 NIAID press release.

PANDA is a multicenter, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for the reduction of asthma exacerbations in urban children and adolescents 6-17 years with T2-high exacerbation-prone asthma. Approximately 240 participants will be randomized 2:1 to one of two study arms: 1) guidelines-based asthma treatment plus dupilumab, or 2) guidelines-based asthma treatment plus placebo. The planned study treatment will continue for 1 year with an additional 3 months of follow-up following completion of study treatment, according to the study details.

In an earlier study, NIAID-supported investigators identified numerous networks of genes that are activated together and are associated with asthma attacks in minority children and adolescents living in low-income urban settings

“We need to find out how well approved asthma drugs work for disadvantaged children of color living in urban areas, and whether biological markers can help predict how the drugs affect their asthma,” NIAID director Anthony S. Fauci, MD, said in the release. “The PANDA trial is an important step toward these goals.”

Participant criteria for the study include children of either sex, ages 6-17 years, who live in prespecified urban areas. Participants must have a diagnosis of asthma and must have had at least two asthma exacerbations in the prior year (defined as a requirement for systemic corticosteroids and/or hospitalization). At the screening visit, participants must have the following requirements for asthma controller medication: For children ages 6-11 years: treatments with at least fluticasone 250 mcg dry powder inhaler (DPI) one puff twice daily or its equivalent; for children ages 12 years and older, treatment with at least fluticasone 250 mcg plus long-acting beta agonist (LABA) DPI one puff twice daily or its equivalent.
 

ClinicalTrials.gov Identifier: NCT05347771Location: The NIAID-funded Childhood Asthma in Urban Settings (CAUSE) Network is conducting the study at seven medical centers located in Aurora, Colo.; Boston; Chicago; Cincinnati; New York, and Washington, D.C.

Sponsor: NIAID, Regeneron Pharmaceuticals and Sanofi are cofunding the phase 2 trial.

Study start date: April 2022

Expected completion Date: March 31, 2025

The Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA) trial was launched in order to examine the effects of treatment on children with poorly controlled allergic asthma who live in low-income urban environments in the United States, according to the National Institute of Allergy and Infectious Diseases.

Black and Hispanic children who live in these environments are at particularly high risk for asthma and are prone to attacks. These children and adolescents often have many allergies and are exposed to both high levels of indoor allergens and traffic-related pollution, which can make their asthma even more difficult to control, according to a June 2 NIAID press release.

PANDA is a multicenter, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for the reduction of asthma exacerbations in urban children and adolescents 6-17 years with T2-high exacerbation-prone asthma. Approximately 240 participants will be randomized 2:1 to one of two study arms: 1) guidelines-based asthma treatment plus dupilumab, or 2) guidelines-based asthma treatment plus placebo. The planned study treatment will continue for 1 year with an additional 3 months of follow-up following completion of study treatment, according to the study details.

In an earlier study, NIAID-supported investigators identified numerous networks of genes that are activated together and are associated with asthma attacks in minority children and adolescents living in low-income urban settings

“We need to find out how well approved asthma drugs work for disadvantaged children of color living in urban areas, and whether biological markers can help predict how the drugs affect their asthma,” NIAID director Anthony S. Fauci, MD, said in the release. “The PANDA trial is an important step toward these goals.”

Participant criteria for the study include children of either sex, ages 6-17 years, who live in prespecified urban areas. Participants must have a diagnosis of asthma and must have had at least two asthma exacerbations in the prior year (defined as a requirement for systemic corticosteroids and/or hospitalization). At the screening visit, participants must have the following requirements for asthma controller medication: For children ages 6-11 years: treatments with at least fluticasone 250 mcg dry powder inhaler (DPI) one puff twice daily or its equivalent; for children ages 12 years and older, treatment with at least fluticasone 250 mcg plus long-acting beta agonist (LABA) DPI one puff twice daily or its equivalent.
 

ClinicalTrials.gov Identifier: NCT05347771Location: The NIAID-funded Childhood Asthma in Urban Settings (CAUSE) Network is conducting the study at seven medical centers located in Aurora, Colo.; Boston; Chicago; Cincinnati; New York, and Washington, D.C.

Sponsor: NIAID, Regeneron Pharmaceuticals and Sanofi are cofunding the phase 2 trial.

Study start date: April 2022

Expected completion Date: March 31, 2025

The Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA) trial was launched in order to examine the effects of treatment on children with poorly controlled allergic asthma who live in low-income urban environments in the United States, according to the National Institute of Allergy and Infectious Diseases.

Black and Hispanic children who live in these environments are at particularly high risk for asthma and are prone to attacks. These children and adolescents often have many allergies and are exposed to both high levels of indoor allergens and traffic-related pollution, which can make their asthma even more difficult to control, according to a June 2 NIAID press release.

PANDA is a multicenter, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for the reduction of asthma exacerbations in urban children and adolescents 6-17 years with T2-high exacerbation-prone asthma. Approximately 240 participants will be randomized 2:1 to one of two study arms: 1) guidelines-based asthma treatment plus dupilumab, or 2) guidelines-based asthma treatment plus placebo. The planned study treatment will continue for 1 year with an additional 3 months of follow-up following completion of study treatment, according to the study details.

In an earlier study, NIAID-supported investigators identified numerous networks of genes that are activated together and are associated with asthma attacks in minority children and adolescents living in low-income urban settings

“We need to find out how well approved asthma drugs work for disadvantaged children of color living in urban areas, and whether biological markers can help predict how the drugs affect their asthma,” NIAID director Anthony S. Fauci, MD, said in the release. “The PANDA trial is an important step toward these goals.”

Participant criteria for the study include children of either sex, ages 6-17 years, who live in prespecified urban areas. Participants must have a diagnosis of asthma and must have had at least two asthma exacerbations in the prior year (defined as a requirement for systemic corticosteroids and/or hospitalization). At the screening visit, participants must have the following requirements for asthma controller medication: For children ages 6-11 years: treatments with at least fluticasone 250 mcg dry powder inhaler (DPI) one puff twice daily or its equivalent; for children ages 12 years and older, treatment with at least fluticasone 250 mcg plus long-acting beta agonist (LABA) DPI one puff twice daily or its equivalent.
 

ClinicalTrials.gov Identifier: NCT05347771Location: The NIAID-funded Childhood Asthma in Urban Settings (CAUSE) Network is conducting the study at seven medical centers located in Aurora, Colo.; Boston; Chicago; Cincinnati; New York, and Washington, D.C.

Sponsor: NIAID, Regeneron Pharmaceuticals and Sanofi are cofunding the phase 2 trial.

Study start date: April 2022

Expected completion Date: March 31, 2025

Sorry, cat people and only children: Having a dog as a toddler and growing up in a large family are two things linked to a significantly lower chance of getting Crohn’s disease later in life, according to a new study.

Children who lived with a dog between the ages of 2 years and 4 years were 37% less likely to have Crohn’s disease, the study says. And those who lived with at least three other family members during the first year of life were 64% less likely to have this form of inflammatory bowel disease (IBD).

“In this study, we’re interested in environmental exposures and which ones are associated with Crohn’s disease onset,” Williams Turpin, PhD, said in a media interview May 23 at the annual Digestive Disease Week® (DDW).

Dr. Turpin and colleagues looked at other things in the environment – including living on a farm, drinking unpasteurized milk or well water, and growing up with a cat – but they did not have a significant link to a higher risk.

Two other things were associated with a slight increase in risk: having a sibling with Crohn’s disease and living with a bird at time of the study. But the number of bird owners was small; only a few people in the study had a pet bird when they enrolled.

The link to living with a dog as a toddler “was more robust,” said Dr. Turpin, a project manager at Mount Sinai Hospital in Toronto.

The study included 4,289 healthy first-degree relatives of people diagnosed with Crohn’s disease. They provided urine, blood, and stool samples and did surveys about environmental exposures at different stages of life.

Investigators followed them an average of 5.6 years, during which time 86 people got Crohn’s disease.
 

Gut instinct

Living with a dog early in life likely means more exposure to different microbes, boosting the strength of a person’s immune system against later challenges. This theory was supported in the study comparing the gut microbiome in people who did and not have a dog in the home early in life.

Dr. Turpin and colleagues genetically sequenced the gut microbiome of the people in the study and found differences in bacteria between groups.

“Our study also shows that just by living with a dog, it impacts your gut microbiome composition, which may have an impact on the immune response later in life,” Dr. Turpin said.

The researchers also looked at the health of the gut by measuring certain factors in the urine. One factor was higher in people who did not live with a dog at any point.
 

Mediated by the microbiome?

Living with a dog between the ages of 2 and 4 years and a large family size (more than three people) in the first year were significantly associated with a lower risk of Crohn’s disease onset.

It is unknown if the results apply to other populations; the researchers studied first-degree relatives of people with Crohn’s disease.

“The study needs to be replicated and validated,” Dr. Turpin said.

Future research could evaluate people who never had a dog and look for changes in their microbiome after they get one.
 

‘Well-crafted’ study

“It’s a really interesting study from a good group. It’s novel in terms of getting at what really drives environmental risk factors,” said Brigid Boland, MD, a gastroenterologist at UC San Diego Health, who was not affiliated with the study.

Autoimmune diseases are really complicated, in part because the risk of getting an autoimmune disease is low, and you’re going back in time to look at what put people at risk.

“The study was well crafted in choosing siblings and family members of people with IBD,” Dr. Boland said, agreeing with Dr. Turpin that more research is needed to understand this.

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

Sorry, cat people and only children: Having a dog as a toddler and growing up in a large family are two things linked to a significantly lower chance of getting Crohn’s disease later in life, according to a new study.

Children who lived with a dog between the ages of 2 years and 4 years were 37% less likely to have Crohn’s disease, the study says. And those who lived with at least three other family members during the first year of life were 64% less likely to have this form of inflammatory bowel disease (IBD).

“In this study, we’re interested in environmental exposures and which ones are associated with Crohn’s disease onset,” Williams Turpin, PhD, said in a media interview May 23 at the annual Digestive Disease Week® (DDW).

Dr. Turpin and colleagues looked at other things in the environment – including living on a farm, drinking unpasteurized milk or well water, and growing up with a cat – but they did not have a significant link to a higher risk.

Two other things were associated with a slight increase in risk: having a sibling with Crohn’s disease and living with a bird at time of the study. But the number of bird owners was small; only a few people in the study had a pet bird when they enrolled.

The link to living with a dog as a toddler “was more robust,” said Dr. Turpin, a project manager at Mount Sinai Hospital in Toronto.

The study included 4,289 healthy first-degree relatives of people diagnosed with Crohn’s disease. They provided urine, blood, and stool samples and did surveys about environmental exposures at different stages of life.

Investigators followed them an average of 5.6 years, during which time 86 people got Crohn’s disease.
 

Gut instinct

Living with a dog early in life likely means more exposure to different microbes, boosting the strength of a person’s immune system against later challenges. This theory was supported in the study comparing the gut microbiome in people who did and not have a dog in the home early in life.

Dr. Turpin and colleagues genetically sequenced the gut microbiome of the people in the study and found differences in bacteria between groups.

“Our study also shows that just by living with a dog, it impacts your gut microbiome composition, which may have an impact on the immune response later in life,” Dr. Turpin said.

The researchers also looked at the health of the gut by measuring certain factors in the urine. One factor was higher in people who did not live with a dog at any point.
 

Mediated by the microbiome?

Living with a dog between the ages of 2 and 4 years and a large family size (more than three people) in the first year were significantly associated with a lower risk of Crohn’s disease onset.

It is unknown if the results apply to other populations; the researchers studied first-degree relatives of people with Crohn’s disease.

“The study needs to be replicated and validated,” Dr. Turpin said.

Future research could evaluate people who never had a dog and look for changes in their microbiome after they get one.
 

‘Well-crafted’ study

“It’s a really interesting study from a good group. It’s novel in terms of getting at what really drives environmental risk factors,” said Brigid Boland, MD, a gastroenterologist at UC San Diego Health, who was not affiliated with the study.

Autoimmune diseases are really complicated, in part because the risk of getting an autoimmune disease is low, and you’re going back in time to look at what put people at risk.

“The study was well crafted in choosing siblings and family members of people with IBD,” Dr. Boland said, agreeing with Dr. Turpin that more research is needed to understand this.

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

Sorry, cat people and only children: Having a dog as a toddler and growing up in a large family are two things linked to a significantly lower chance of getting Crohn’s disease later in life, according to a new study.

Children who lived with a dog between the ages of 2 years and 4 years were 37% less likely to have Crohn’s disease, the study says. And those who lived with at least three other family members during the first year of life were 64% less likely to have this form of inflammatory bowel disease (IBD).

“In this study, we’re interested in environmental exposures and which ones are associated with Crohn’s disease onset,” Williams Turpin, PhD, said in a media interview May 23 at the annual Digestive Disease Week® (DDW).

Dr. Turpin and colleagues looked at other things in the environment – including living on a farm, drinking unpasteurized milk or well water, and growing up with a cat – but they did not have a significant link to a higher risk.

Two other things were associated with a slight increase in risk: having a sibling with Crohn’s disease and living with a bird at time of the study. But the number of bird owners was small; only a few people in the study had a pet bird when they enrolled.

The link to living with a dog as a toddler “was more robust,” said Dr. Turpin, a project manager at Mount Sinai Hospital in Toronto.

The study included 4,289 healthy first-degree relatives of people diagnosed with Crohn’s disease. They provided urine, blood, and stool samples and did surveys about environmental exposures at different stages of life.

Investigators followed them an average of 5.6 years, during which time 86 people got Crohn’s disease.
 

Gut instinct

Living with a dog early in life likely means more exposure to different microbes, boosting the strength of a person’s immune system against later challenges. This theory was supported in the study comparing the gut microbiome in people who did and not have a dog in the home early in life.

Dr. Turpin and colleagues genetically sequenced the gut microbiome of the people in the study and found differences in bacteria between groups.

“Our study also shows that just by living with a dog, it impacts your gut microbiome composition, which may have an impact on the immune response later in life,” Dr. Turpin said.

The researchers also looked at the health of the gut by measuring certain factors in the urine. One factor was higher in people who did not live with a dog at any point.
 

Mediated by the microbiome?

Living with a dog between the ages of 2 and 4 years and a large family size (more than three people) in the first year were significantly associated with a lower risk of Crohn’s disease onset.

It is unknown if the results apply to other populations; the researchers studied first-degree relatives of people with Crohn’s disease.

“The study needs to be replicated and validated,” Dr. Turpin said.

Future research could evaluate people who never had a dog and look for changes in their microbiome after they get one.
 

‘Well-crafted’ study

“It’s a really interesting study from a good group. It’s novel in terms of getting at what really drives environmental risk factors,” said Brigid Boland, MD, a gastroenterologist at UC San Diego Health, who was not affiliated with the study.

Autoimmune diseases are really complicated, in part because the risk of getting an autoimmune disease is low, and you’re going back in time to look at what put people at risk.

“The study was well crafted in choosing siblings and family members of people with IBD,” Dr. Boland said, agreeing with Dr. Turpin that more research is needed to understand this.

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

The FDA has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, which clears the way for approval and distribution in June.

Pfizer announced June 1 that it completed the application for a three-dose vaccine for kids between 6 months and 5 years old, and the FDA said it received the emergency use application.

Children in this age group – the last to be eligible for COVID-19 vaccines – could begin getting shots as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

Meanwhile, COVID-19 cases are still high – an average of 100,000 cases a day – but death numbers are about 90% lower than they were when President Joe Biden first took office, Dr. Jha said. 

The FDA’s advisory group, the Vaccines and Related Biological Products Advisory Committee, is scheduled to meet June 14 and June 15 to discuss data submitted by both Pfizer and Moderna.  

If the FDA gives them the green light, the CDC will then weigh in.

“We know that many, many parents are eager to vaccinate their youngest kids, and it’s important to do this right,” Dr. Jha said at a White House press briefing on June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

States can place their orders as early as June 3, Dr. Jha said, and there will initially be 10 million doses available. If the FDA gives emergency use authorization for the vaccines, the government will begin shipping doses to thousands of sites across the country.

“The good news is we have plenty of supply of Pfizer and Moderna vaccines,” Dr. Jha said. “We’ve asked states to distribute to their highest priority sites, serving the highest risk and hardest to reach areas.”

Pfizer’s clinical trials found that three doses of the vaccine for children 6 months to under 5 years were safe and effective and proved to be 80% effective against Omicron.

The FDA announced its meeting information with a conversation about the Moderna vaccine for ages 6-17 scheduled for June 14 and a conversation about the Pfizer and Moderna vaccines for young children scheduled for June 15.

Moderna applied for FDA authorization of its two-dose vaccine for children under age 6 on April 28. The company said the vaccine was 51% effective against infections with symptoms for children ages 6 months to 2 years and 37% effective for ages 2-5.

Pfizer’s 3-microgram dose is one-tenth of its adult dose. Moderna’s 25-microgram dose is one-quarter of its adult dose.

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

The FDA has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, which clears the way for approval and distribution in June.

Pfizer announced June 1 that it completed the application for a three-dose vaccine for kids between 6 months and 5 years old, and the FDA said it received the emergency use application.

Children in this age group – the last to be eligible for COVID-19 vaccines – could begin getting shots as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

Meanwhile, COVID-19 cases are still high – an average of 100,000 cases a day – but death numbers are about 90% lower than they were when President Joe Biden first took office, Dr. Jha said. 

The FDA’s advisory group, the Vaccines and Related Biological Products Advisory Committee, is scheduled to meet June 14 and June 15 to discuss data submitted by both Pfizer and Moderna.  

If the FDA gives them the green light, the CDC will then weigh in.

“We know that many, many parents are eager to vaccinate their youngest kids, and it’s important to do this right,” Dr. Jha said at a White House press briefing on June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

States can place their orders as early as June 3, Dr. Jha said, and there will initially be 10 million doses available. If the FDA gives emergency use authorization for the vaccines, the government will begin shipping doses to thousands of sites across the country.

“The good news is we have plenty of supply of Pfizer and Moderna vaccines,” Dr. Jha said. “We’ve asked states to distribute to their highest priority sites, serving the highest risk and hardest to reach areas.”

Pfizer’s clinical trials found that three doses of the vaccine for children 6 months to under 5 years were safe and effective and proved to be 80% effective against Omicron.

The FDA announced its meeting information with a conversation about the Moderna vaccine for ages 6-17 scheduled for June 14 and a conversation about the Pfizer and Moderna vaccines for young children scheduled for June 15.

Moderna applied for FDA authorization of its two-dose vaccine for children under age 6 on April 28. The company said the vaccine was 51% effective against infections with symptoms for children ages 6 months to 2 years and 37% effective for ages 2-5.

Pfizer’s 3-microgram dose is one-tenth of its adult dose. Moderna’s 25-microgram dose is one-quarter of its adult dose.

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

The FDA has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, which clears the way for approval and distribution in June.

Pfizer announced June 1 that it completed the application for a three-dose vaccine for kids between 6 months and 5 years old, and the FDA said it received the emergency use application.

Children in this age group – the last to be eligible for COVID-19 vaccines – could begin getting shots as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

Meanwhile, COVID-19 cases are still high – an average of 100,000 cases a day – but death numbers are about 90% lower than they were when President Joe Biden first took office, Dr. Jha said. 

The FDA’s advisory group, the Vaccines and Related Biological Products Advisory Committee, is scheduled to meet June 14 and June 15 to discuss data submitted by both Pfizer and Moderna.  

If the FDA gives them the green light, the CDC will then weigh in.

“We know that many, many parents are eager to vaccinate their youngest kids, and it’s important to do this right,” Dr. Jha said at a White House press briefing on June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

States can place their orders as early as June 3, Dr. Jha said, and there will initially be 10 million doses available. If the FDA gives emergency use authorization for the vaccines, the government will begin shipping doses to thousands of sites across the country.

“The good news is we have plenty of supply of Pfizer and Moderna vaccines,” Dr. Jha said. “We’ve asked states to distribute to their highest priority sites, serving the highest risk and hardest to reach areas.”

Pfizer’s clinical trials found that three doses of the vaccine for children 6 months to under 5 years were safe and effective and proved to be 80% effective against Omicron.

The FDA announced its meeting information with a conversation about the Moderna vaccine for ages 6-17 scheduled for June 14 and a conversation about the Pfizer and Moderna vaccines for young children scheduled for June 15.

Moderna applied for FDA authorization of its two-dose vaccine for children under age 6 on April 28. The company said the vaccine was 51% effective against infections with symptoms for children ages 6 months to 2 years and 37% effective for ages 2-5.

Pfizer’s 3-microgram dose is one-tenth of its adult dose. Moderna’s 25-microgram dose is one-quarter of its adult dose.

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

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, results of a multicenter observational study indicate.

Following two doses of either vaccine, the risk of hospital admission was 75% lower among vaccinated patients while the risk of death was 88% lower, compared with those who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients over the age of 65 or with increasing time since vaccination, the authors add. The need for oxygen and ventilation was also halved among those who had received two shots, compared with those who had not.

“The coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on the CKD (chronic kidney disease) community, particularly for individuals receiving maintenance dialysis,” Matthew Oliver, MD, University of Toronto, and Peter Blake, MD, Western University, London, Ont., write in an editorial published with the study.

“Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes,” they conclude.

The study was published in the June issue of the Clinical Journal of the American Society of Nephrology.
 

Severe outcomes observed less in patients who tested positive

The cohort included 1,323 patients on hemodialysis who tested positive on PCR testing to SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, report, Damien Ashby, MD, Hammersmith Hospital, London, and colleagues report.

Among those who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators note. Oxygen support was required by 29% of those who tested positive, and 13% died before 28 days, they added. Among those who died within 28 days of testing positive, 90% of the deaths were deemed to be caused by the virus itself.

“Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose,” Dr. Ashby and colleagues emphasize.

“And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers,” they add. Following vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy controls.

In contrast, this was not the case for the Oxford AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stress.  

They also note that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem. “This study may, therefore, be useful in reducing vaccine hesitancy, which has resulted in low uptake in some countries (for example, Australia, where almost a quarter of patients on dialysis declined),” Dr. Ashby and colleagues point out.

Although significant vulnerability in the dialysis population remains, “this population has much to gain from vaccination, regardless of age or vaccine type,” the authors underscore.
 

CKD community quick to prioritize vaccine

As the editorialists point out, leaders in the CKD community were quick – and successful – in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, 90% of the maintenance dialysis population had received two doses of a COVID-19 vaccine by September 2021 and 78% had received three doses by January 2022.

Moreover, in Ontario, “our group found that two doses of mRNA vaccine reduced the risk of infection by 69%,” Dr. Oliver and Dr. Blake point out. U.S. researchers also found that the Pfizer mRNA vaccine reduced infection risk from COVID-19 by 79% while the Moderna mRNA vaccine reduced that risk by 73%. Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-Co-V-2 virus, as the editorialists note.

However, “the VE for preventing severe outcomes is clinically more important for patients on dialysis because their risk of [morbid] events is high,” Dr. Oliver and Dr. Blake write. Indeed, their own study estimated that two doses of an mRNA vaccine reduced severe outcomes by 83%, “a greater benefit than for infection prevention,” they stress.

The editorialists caution that the SARS-CoV-2 virus continues to mutate and serology studies do show that vaccine-induced immunity does wane over time. Thus, while the COVID-19 pandemic is ever-changing, “we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population,” Dr. Oliver and Dr. Blake recommend.
 

Need to increase vaccine acceptance

Commenting on the study, Uwe K.H. Korst from Bensheim, Germany, notes that COVID-19 is a daily reminder of how fragile life is for people with CKD. “Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease,” he writes.

Thus, Mr. Korst continues to call for additional education for health care professionals, patients, and the public to increase vaccine acceptance as well as more research to better understand the virus and its long-term consequences.

“Finally, patients need to express their needs, and physicians need to listen to patients’ voices,” Mr. Korst advises.

Dr. Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter Healthcare and participating in advisory boards for Amgen and Janssen. Dr. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Dr. Ashby and Dr. Korst have reported no relevant financial relationships.

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

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, results of a multicenter observational study indicate.

Following two doses of either vaccine, the risk of hospital admission was 75% lower among vaccinated patients while the risk of death was 88% lower, compared with those who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients over the age of 65 or with increasing time since vaccination, the authors add. The need for oxygen and ventilation was also halved among those who had received two shots, compared with those who had not.

“The coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on the CKD (chronic kidney disease) community, particularly for individuals receiving maintenance dialysis,” Matthew Oliver, MD, University of Toronto, and Peter Blake, MD, Western University, London, Ont., write in an editorial published with the study.

“Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes,” they conclude.

The study was published in the June issue of the Clinical Journal of the American Society of Nephrology.
 

Severe outcomes observed less in patients who tested positive

The cohort included 1,323 patients on hemodialysis who tested positive on PCR testing to SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, report, Damien Ashby, MD, Hammersmith Hospital, London, and colleagues report.

Among those who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators note. Oxygen support was required by 29% of those who tested positive, and 13% died before 28 days, they added. Among those who died within 28 days of testing positive, 90% of the deaths were deemed to be caused by the virus itself.

“Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose,” Dr. Ashby and colleagues emphasize.

“And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers,” they add. Following vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy controls.

In contrast, this was not the case for the Oxford AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stress.  

They also note that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem. “This study may, therefore, be useful in reducing vaccine hesitancy, which has resulted in low uptake in some countries (for example, Australia, where almost a quarter of patients on dialysis declined),” Dr. Ashby and colleagues point out.

Although significant vulnerability in the dialysis population remains, “this population has much to gain from vaccination, regardless of age or vaccine type,” the authors underscore.
 

CKD community quick to prioritize vaccine

As the editorialists point out, leaders in the CKD community were quick – and successful – in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, 90% of the maintenance dialysis population had received two doses of a COVID-19 vaccine by September 2021 and 78% had received three doses by January 2022.

Moreover, in Ontario, “our group found that two doses of mRNA vaccine reduced the risk of infection by 69%,” Dr. Oliver and Dr. Blake point out. U.S. researchers also found that the Pfizer mRNA vaccine reduced infection risk from COVID-19 by 79% while the Moderna mRNA vaccine reduced that risk by 73%. Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-Co-V-2 virus, as the editorialists note.

However, “the VE for preventing severe outcomes is clinically more important for patients on dialysis because their risk of [morbid] events is high,” Dr. Oliver and Dr. Blake write. Indeed, their own study estimated that two doses of an mRNA vaccine reduced severe outcomes by 83%, “a greater benefit than for infection prevention,” they stress.

The editorialists caution that the SARS-CoV-2 virus continues to mutate and serology studies do show that vaccine-induced immunity does wane over time. Thus, while the COVID-19 pandemic is ever-changing, “we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population,” Dr. Oliver and Dr. Blake recommend.
 

Need to increase vaccine acceptance

Commenting on the study, Uwe K.H. Korst from Bensheim, Germany, notes that COVID-19 is a daily reminder of how fragile life is for people with CKD. “Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease,” he writes.

Thus, Mr. Korst continues to call for additional education for health care professionals, patients, and the public to increase vaccine acceptance as well as more research to better understand the virus and its long-term consequences.

“Finally, patients need to express their needs, and physicians need to listen to patients’ voices,” Mr. Korst advises.

Dr. Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter Healthcare and participating in advisory boards for Amgen and Janssen. Dr. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Dr. Ashby and Dr. Korst have reported no relevant financial relationships.

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

Two doses of either the Pfizer-BioNTech COVID-19 vaccine or the Oxford AstraZeneca alternative provide equal and significant protection against severe disease in patients on hemodialysis who have contracted SARS-CoV-2 infection, results of a multicenter observational study indicate.

Following two doses of either vaccine, the risk of hospital admission was 75% lower among vaccinated patients while the risk of death was 88% lower, compared with those who remained unvaccinated.

No difference was seen between the two vaccine types in terms of outcome severity, and there was no loss of protection in patients over the age of 65 or with increasing time since vaccination, the authors add. The need for oxygen and ventilation was also halved among those who had received two shots, compared with those who had not.

“The coronavirus disease 2019 (COVID-19) pandemic has had a devastating effect on the CKD (chronic kidney disease) community, particularly for individuals receiving maintenance dialysis,” Matthew Oliver, MD, University of Toronto, and Peter Blake, MD, Western University, London, Ont., write in an editorial published with the study.

“Overall, [this and other studies] show that COVID-19 vaccination in the maintenance dialysis population provides moderate protection against acquiring SARS-CoV-2 infection but is highly protective against severe outcomes,” they conclude.

The study was published in the June issue of the Clinical Journal of the American Society of Nephrology.
 

Severe outcomes observed less in patients who tested positive

The cohort included 1,323 patients on hemodialysis who tested positive on PCR testing to SARS-CoV-2 during a surveillance interval between December 2020 and September 2021, report, Damien Ashby, MD, Hammersmith Hospital, London, and colleagues report.

Among those who tested positive, 79% had not been vaccinated, 7% tested positive after their first dose of either vaccine, and 14% tested positive at least 10 days beyond their second dose.

The course of illness was mild in 61% of patients in that they did not require hospital admission, investigators note. Oxygen support was required by 29% of those who tested positive, and 13% died before 28 days, they added. Among those who died within 28 days of testing positive, 90% of the deaths were deemed to be caused by the virus itself.

“Compared with unvaccinated patients, severe COVID-19 outcomes were observed less than half as often in patients testing positive for SARS-Co-V-2 at least 10 days after the second dose,” Dr. Ashby and colleagues emphasize.

“And the protection from severe illness associated with vaccination was most obvious in patients over 65 years, in whom severe COVID-19 outcomes were reduced at least as much after vaccination as in their younger peers,” they add. Following vaccination with the Pfizer-BioNTech vaccine, antibody levels in patients on dialysis were comparable with those of healthy controls.

In contrast, this was not the case for the Oxford AstraZeneca vaccine where neutralizing titers in patients who received the vaccine were less effective against most variants. Despite its ability to produce comparable immunogenicity, the Oxford AstraZeneca vaccine was clearly associated with clinical protection against severe illness, the authors stress.  

They also note that their results are relevant to vaccine uptake in the dialysis population where vaccine hesitancy remains a problem. “This study may, therefore, be useful in reducing vaccine hesitancy, which has resulted in low uptake in some countries (for example, Australia, where almost a quarter of patients on dialysis declined),” Dr. Ashby and colleagues point out.

Although significant vulnerability in the dialysis population remains, “this population has much to gain from vaccination, regardless of age or vaccine type,” the authors underscore.
 

CKD community quick to prioritize vaccine

As the editorialists point out, leaders in the CKD community were quick – and successful – in prioritizing vaccination in the dialysis population right from the beginning of the pandemic. For example, in Ontario, 90% of the maintenance dialysis population had received two doses of a COVID-19 vaccine by September 2021 and 78% had received three doses by January 2022.

Moreover, in Ontario, “our group found that two doses of mRNA vaccine reduced the risk of infection by 69%,” Dr. Oliver and Dr. Blake point out. U.S. researchers also found that the Pfizer mRNA vaccine reduced infection risk from COVID-19 by 79% while the Moderna mRNA vaccine reduced that risk by 73%. Vaccine effectiveness (VE) in the real-world setting indicates that COVID-19 vaccines provide moderate protection against being infected with the SARS-Co-V-2 virus, as the editorialists note.

However, “the VE for preventing severe outcomes is clinically more important for patients on dialysis because their risk of [morbid] events is high,” Dr. Oliver and Dr. Blake write. Indeed, their own study estimated that two doses of an mRNA vaccine reduced severe outcomes by 83%, “a greater benefit than for infection prevention,” they stress.

The editorialists caution that the SARS-CoV-2 virus continues to mutate and serology studies do show that vaccine-induced immunity does wane over time. Thus, while the COVID-19 pandemic is ever-changing, “we should conduct [VE] studies rigorously and expeditiously to bolster the case for prioritizing vaccination in the dialysis population,” Dr. Oliver and Dr. Blake recommend.
 

Need to increase vaccine acceptance

Commenting on the study, Uwe K.H. Korst from Bensheim, Germany, notes that COVID-19 is a daily reminder of how fragile life is for people with CKD. “Daily, the virus continues its horrific and unprecedented course through immunocompromised and immunosuppressed patients with kidney disease,” he writes.

Thus, Mr. Korst continues to call for additional education for health care professionals, patients, and the public to increase vaccine acceptance as well as more research to better understand the virus and its long-term consequences.

“Finally, patients need to express their needs, and physicians need to listen to patients’ voices,” Mr. Korst advises.

Dr. Oliver is a contracted medical lead of Ontario Renal Network and owner of Oliver Medical Management for which he holds patents and has received royalties. He has also reported receiving honoraria for speaking from Baxter Healthcare and participating in advisory boards for Amgen and Janssen. Dr. Blake has reported receiving honoraria from Baxter Global for speaking engagements and serves on the editorial board for the American Journal of Nephrology. Dr. Ashby and Dr. Korst have reported no relevant financial relationships.

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

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

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

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

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

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

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

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.