Federal Practitioner

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

Adjuvant immunotherapy with atezolizumab for patients with renal cell carcinoma who have had a nephrectomy with or without a metastasectomy, failed to improve clinical outcomes in a group of patients who are at high risk of recurrence, finds a new international study conducted across 28 countries.

The study, called IMmotion010 and published in The Lancet, was a randomized, double-blind, multicenter, phase 3 trial of 778 adult patients with renal cell carcinoma (RCC) with a clear cell or sarcomatoid component. The study failed to meet its primary endpoint which was defined as a statistically significant improvement in disease-free survival as compared with placebo.

“Our results add to an emerging body of literature around the role of adjuvant immunotherapy for renal cell carcinoma. With the longest duration of follow-up to date to our knowledge. We observed no evidence of clinical benefit in disease-free survival or overall survival with adjuvant atezolizumab in patients with high-risk localized or fully resected renal cell carcinoma,” wrote the authors who were led by Sumanta Kumar Pal, MD, of City of Hope Comprehensive Cancer Center, Duarte, Calif. “Given a growing list of trials that have not shown benefit with adjuvant immunotherapy, the results call for greater attention to patient selection with this approach.”

Dr. Pal and associates conducted the study to gain more insight into the potential role of adjuvant immunotherapy in patients with renal cell carcinoma who have undergone the standard treatment of nephrectomy with or without metastasectomy. Previous studies of anti-VEGF treatments have produced mixed results, including the large phase 3 ASSURE trial, the authors wrote. “Given these mixed results, use of adjuvant targeted therapy in renal cell carcinoma remains infrequent,” Dr. Pal and associates wrote.

However, pembrolizumab (Keytruda, Merck) a programmed death receptor-1–blocking antibody, is an immunotherapy which, in combination with axitinib, is approved as a first-line treatment for patients with advanced RCC.

Atezolizumab (Tecentriq, Genentech) is approved for treatment in urothelial carcinoma, non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), and melanoma. There are currently a number of ongoing studies that are exploring the use of atezolizumab as a treatment for renal cell carcinoma.

The study details

This new study was conducted between 2017 and 2019. It included 778 patients from 215 clinics in 28 countries who were assigned to the treatment arm (1,200 mg of IV atezolizumab (n = 390, 50%) once every 3 weeks for 16 cycles or 1 year, which ever came first – or, they were assigned to the placebo group (n = 388, 50%). The two groups were similar: average age 60-61, 72%-74% male, 78%-83% white, and 36%-37% based in North America. Most patients, (92%-93%) had clear cell cancer, and 64%-65% were at pathological disease stage T2 or T3a.

The 3-year disease-free survival rate at 36 months was 65.0% (95% confidence interval, 59.9-70.2) in the treatment group and 62.7% (95% CI, 57.5-67.9) in the placebo group. At follow-up at 44.7 months, there was no statistically significant difference in median disease-free survival between atezolizumab (57.2 months; 95% CI, 44.6 to not evaluable) and placebo (49.5 months; 95% CI, 47.4 to not evaluable).

While there were no deaths attributable to treatment, 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo experienced a serious adverse event.

“The results of IMmotion010 do not support the use of adjuvant atezolizumab for fully resected renal cell carcinoma. Future work will include exploration of clinical-based or biomarker-based subsets that might derive benefit from this approach,” the authors wrote.

The researchers acknowledge their findings contrast with those of the KEYNOTE-564 trial of adjuvant immunotherapy with pembrolizumab after nephrectomy in renal cell carcinoma. KEYNOTE-564 reported a disease-free survival benefit of over 24 months and in an analysis done at 30 months. But in KEYNOTE-564, the study comprised only 6% of patients with M1 no evidence of disease. And, it included only patients with synchronous metastases or metastases resected within 1 year of nephrectomy. In the new study, 14% of patients had M1 no evidence of disease, and it included both synchronous and metachronous disease with recurrence within 1year of surgery.

Adjuvant immunotherapy with pembrolizumab is considered optional for patients with intermediate-risk or high-risk operable clear cell renal cell carcinoma per European Society for Medical Oncology and European Association of Urology guidelines because of the lack of confirmed overall survival benefit and toxicity-related considerations associated with immunotherapy.

“These factors must be considered in the adjuvant setting as, following nephrectomy, patients are cancer free and might be cured by surgery alone. As such, additional trials are needed to clarify the role of adjuvant immunotherapy in this disease space,” the authors wrote.

What’s next? “Biomarker work is underway to determine whether tumor genomic characteristics or circulating biomarkers can identify patient populations who derive benefit from adjuvant atezolizumab,” Dr. Pal and associates wrote. “There is precedent for tissue-based adjuvant therapy selection in other diseases, such as HER2-based and endocrine receptor–based approaches in breast cancer and EGFR mutation–directed therapy in lung cancer.”

The study was funded by F Hoffmann-La Roche and Genentech. The academic authors of the study collaborated with F Hoffmann-La Roche and Genentech on all facets of the trial.

Adjuvant immunotherapy with atezolizumab for patients with renal cell carcinoma who have had a nephrectomy with or without a metastasectomy, failed to improve clinical outcomes in a group of patients who are at high risk of recurrence, finds a new international study conducted across 28 countries.

The study, called IMmotion010 and published in The Lancet, was a randomized, double-blind, multicenter, phase 3 trial of 778 adult patients with renal cell carcinoma (RCC) with a clear cell or sarcomatoid component. The study failed to meet its primary endpoint which was defined as a statistically significant improvement in disease-free survival as compared with placebo.

“Our results add to an emerging body of literature around the role of adjuvant immunotherapy for renal cell carcinoma. With the longest duration of follow-up to date to our knowledge. We observed no evidence of clinical benefit in disease-free survival or overall survival with adjuvant atezolizumab in patients with high-risk localized or fully resected renal cell carcinoma,” wrote the authors who were led by Sumanta Kumar Pal, MD, of City of Hope Comprehensive Cancer Center, Duarte, Calif. “Given a growing list of trials that have not shown benefit with adjuvant immunotherapy, the results call for greater attention to patient selection with this approach.”

Dr. Pal and associates conducted the study to gain more insight into the potential role of adjuvant immunotherapy in patients with renal cell carcinoma who have undergone the standard treatment of nephrectomy with or without metastasectomy. Previous studies of anti-VEGF treatments have produced mixed results, including the large phase 3 ASSURE trial, the authors wrote. “Given these mixed results, use of adjuvant targeted therapy in renal cell carcinoma remains infrequent,” Dr. Pal and associates wrote.

However, pembrolizumab (Keytruda, Merck) a programmed death receptor-1–blocking antibody, is an immunotherapy which, in combination with axitinib, is approved as a first-line treatment for patients with advanced RCC.

Atezolizumab (Tecentriq, Genentech) is approved for treatment in urothelial carcinoma, non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), and melanoma. There are currently a number of ongoing studies that are exploring the use of atezolizumab as a treatment for renal cell carcinoma.

The study details

This new study was conducted between 2017 and 2019. It included 778 patients from 215 clinics in 28 countries who were assigned to the treatment arm (1,200 mg of IV atezolizumab (n = 390, 50%) once every 3 weeks for 16 cycles or 1 year, which ever came first – or, they were assigned to the placebo group (n = 388, 50%). The two groups were similar: average age 60-61, 72%-74% male, 78%-83% white, and 36%-37% based in North America. Most patients, (92%-93%) had clear cell cancer, and 64%-65% were at pathological disease stage T2 or T3a.

The 3-year disease-free survival rate at 36 months was 65.0% (95% confidence interval, 59.9-70.2) in the treatment group and 62.7% (95% CI, 57.5-67.9) in the placebo group. At follow-up at 44.7 months, there was no statistically significant difference in median disease-free survival between atezolizumab (57.2 months; 95% CI, 44.6 to not evaluable) and placebo (49.5 months; 95% CI, 47.4 to not evaluable).

While there were no deaths attributable to treatment, 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo experienced a serious adverse event.

“The results of IMmotion010 do not support the use of adjuvant atezolizumab for fully resected renal cell carcinoma. Future work will include exploration of clinical-based or biomarker-based subsets that might derive benefit from this approach,” the authors wrote.

The researchers acknowledge their findings contrast with those of the KEYNOTE-564 trial of adjuvant immunotherapy with pembrolizumab after nephrectomy in renal cell carcinoma. KEYNOTE-564 reported a disease-free survival benefit of over 24 months and in an analysis done at 30 months. But in KEYNOTE-564, the study comprised only 6% of patients with M1 no evidence of disease. And, it included only patients with synchronous metastases or metastases resected within 1 year of nephrectomy. In the new study, 14% of patients had M1 no evidence of disease, and it included both synchronous and metachronous disease with recurrence within 1year of surgery.

Adjuvant immunotherapy with pembrolizumab is considered optional for patients with intermediate-risk or high-risk operable clear cell renal cell carcinoma per European Society for Medical Oncology and European Association of Urology guidelines because of the lack of confirmed overall survival benefit and toxicity-related considerations associated with immunotherapy.

“These factors must be considered in the adjuvant setting as, following nephrectomy, patients are cancer free and might be cured by surgery alone. As such, additional trials are needed to clarify the role of adjuvant immunotherapy in this disease space,” the authors wrote.

What’s next? “Biomarker work is underway to determine whether tumor genomic characteristics or circulating biomarkers can identify patient populations who derive benefit from adjuvant atezolizumab,” Dr. Pal and associates wrote. “There is precedent for tissue-based adjuvant therapy selection in other diseases, such as HER2-based and endocrine receptor–based approaches in breast cancer and EGFR mutation–directed therapy in lung cancer.”

The study was funded by F Hoffmann-La Roche and Genentech. The academic authors of the study collaborated with F Hoffmann-La Roche and Genentech on all facets of the trial.

Adjuvant immunotherapy with atezolizumab for patients with renal cell carcinoma who have had a nephrectomy with or without a metastasectomy, failed to improve clinical outcomes in a group of patients who are at high risk of recurrence, finds a new international study conducted across 28 countries.

The study, called IMmotion010 and published in The Lancet, was a randomized, double-blind, multicenter, phase 3 trial of 778 adult patients with renal cell carcinoma (RCC) with a clear cell or sarcomatoid component. The study failed to meet its primary endpoint which was defined as a statistically significant improvement in disease-free survival as compared with placebo.

“Our results add to an emerging body of literature around the role of adjuvant immunotherapy for renal cell carcinoma. With the longest duration of follow-up to date to our knowledge. We observed no evidence of clinical benefit in disease-free survival or overall survival with adjuvant atezolizumab in patients with high-risk localized or fully resected renal cell carcinoma,” wrote the authors who were led by Sumanta Kumar Pal, MD, of City of Hope Comprehensive Cancer Center, Duarte, Calif. “Given a growing list of trials that have not shown benefit with adjuvant immunotherapy, the results call for greater attention to patient selection with this approach.”

Dr. Pal and associates conducted the study to gain more insight into the potential role of adjuvant immunotherapy in patients with renal cell carcinoma who have undergone the standard treatment of nephrectomy with or without metastasectomy. Previous studies of anti-VEGF treatments have produced mixed results, including the large phase 3 ASSURE trial, the authors wrote. “Given these mixed results, use of adjuvant targeted therapy in renal cell carcinoma remains infrequent,” Dr. Pal and associates wrote.

However, pembrolizumab (Keytruda, Merck) a programmed death receptor-1–blocking antibody, is an immunotherapy which, in combination with axitinib, is approved as a first-line treatment for patients with advanced RCC.

Atezolizumab (Tecentriq, Genentech) is approved for treatment in urothelial carcinoma, non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), and melanoma. There are currently a number of ongoing studies that are exploring the use of atezolizumab as a treatment for renal cell carcinoma.

The study details

This new study was conducted between 2017 and 2019. It included 778 patients from 215 clinics in 28 countries who were assigned to the treatment arm (1,200 mg of IV atezolizumab (n = 390, 50%) once every 3 weeks for 16 cycles or 1 year, which ever came first – or, they were assigned to the placebo group (n = 388, 50%). The two groups were similar: average age 60-61, 72%-74% male, 78%-83% white, and 36%-37% based in North America. Most patients, (92%-93%) had clear cell cancer, and 64%-65% were at pathological disease stage T2 or T3a.

The 3-year disease-free survival rate at 36 months was 65.0% (95% confidence interval, 59.9-70.2) in the treatment group and 62.7% (95% CI, 57.5-67.9) in the placebo group. At follow-up at 44.7 months, there was no statistically significant difference in median disease-free survival between atezolizumab (57.2 months; 95% CI, 44.6 to not evaluable) and placebo (49.5 months; 95% CI, 47.4 to not evaluable).

While there were no deaths attributable to treatment, 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo experienced a serious adverse event.

“The results of IMmotion010 do not support the use of adjuvant atezolizumab for fully resected renal cell carcinoma. Future work will include exploration of clinical-based or biomarker-based subsets that might derive benefit from this approach,” the authors wrote.

The researchers acknowledge their findings contrast with those of the KEYNOTE-564 trial of adjuvant immunotherapy with pembrolizumab after nephrectomy in renal cell carcinoma. KEYNOTE-564 reported a disease-free survival benefit of over 24 months and in an analysis done at 30 months. But in KEYNOTE-564, the study comprised only 6% of patients with M1 no evidence of disease. And, it included only patients with synchronous metastases or metastases resected within 1 year of nephrectomy. In the new study, 14% of patients had M1 no evidence of disease, and it included both synchronous and metachronous disease with recurrence within 1year of surgery.

Adjuvant immunotherapy with pembrolizumab is considered optional for patients with intermediate-risk or high-risk operable clear cell renal cell carcinoma per European Society for Medical Oncology and European Association of Urology guidelines because of the lack of confirmed overall survival benefit and toxicity-related considerations associated with immunotherapy.

“These factors must be considered in the adjuvant setting as, following nephrectomy, patients are cancer free and might be cured by surgery alone. As such, additional trials are needed to clarify the role of adjuvant immunotherapy in this disease space,” the authors wrote.

What’s next? “Biomarker work is underway to determine whether tumor genomic characteristics or circulating biomarkers can identify patient populations who derive benefit from adjuvant atezolizumab,” Dr. Pal and associates wrote. “There is precedent for tissue-based adjuvant therapy selection in other diseases, such as HER2-based and endocrine receptor–based approaches in breast cancer and EGFR mutation–directed therapy in lung cancer.”

The study was funded by F Hoffmann-La Roche and Genentech. The academic authors of the study collaborated with F Hoffmann-La Roche and Genentech on all facets of the trial.

The patients of Jill Krapf, MD, are often too embarrassed to tell her about discomfort in their clitoris.

“I ask all of my patients about clitoral pain, and it is often the first time they have ever been asked about this,” says Dr. Krapf, the associate director of the Center for Vulvovaginal Disorders, a private clinic in Washington and New York. 

Dr. Krapf is an ob.gyn. who specializes in female sexual pain that involves the pelvis, vagina, and vulva. 

Many of the conditions Dr. Krapf treats don’t have outward symptoms that appear abnormal, but internally, there are damaged or irritated nerves that can result in hypersensitivity, unwanted arousal, or pain.

“Most recent research indicates that even a herniated disk or tear in the spine can lead to clitoral or vulvar symptoms, just like sciatica pain that shoots down the leg is related to issues in the spine,” Dr. Krapf says.

Dr. Krapf was excited to read of a new discovery: The clitoris has more than 10,000 nerve fibers – 2,000 more than previously reported in 1976 – a medical breakthrough for a part of the body that has often been neglected by the scientific field. Dr. Krapf and other doctors are hopeful that the attention to the clitoris will spark more interest and comprehensive education among people in their field. They also hope it will empower patients to seek medical help if they are having issues with their clitoris.

“Female sexual health has historically been underfunded, especially compared with male sexual health, like erectile dysfunction,” Dr. Krapf says. “Optimizing vulvar and vaginal health is not only necessary for sexual well-being.”

Blair Peters, MD, a plastic surgeon who specializes in gender-affirming care, led the study, which was presented at the Sexual Medicine Society of North America conference in October. Dr. Peters says he hopes that the new information decreases stigma that the clitoris is not worthy of the same medical attention that other organs of the body receive. 

When the clitoris doesn’t properly function, there can be harm to a person’s physical and mental health. Paying attention to discomfort in the clitoris, and seeking medical attention, can help catch and prevent some urinary and vaginal infections.  

“The fact that it took until 2022 for someone to do this work speaks to how little attention the clitoris has received,” says Dr. Peters, an assistant professor of surgery at the Oregon Health and Science University School of Medicine, Portland. 
 

What’s inside? 

Dr. Peters and his colleagues completed the study by taking clitoral nerve tissue from seven adult transgender men who had received gender-affirming genital surgery. The tissues were dyed and magnified 1,000 times under a microscope so the researchers could count nerve fibers. 

Dr. Peters says the finding is important because many surgeries take place in the groin region – like hip replacements, episiotomies during childbirth, and pelvic mesh procedures – and the revived attention to the clitoris may help health care providers know where nerves are so that injuries from medical mistakes are prevented. 

“Nerves are at risk of damage if it’s not understood where they are at all times,” he says. 

Dr. Peters hopes the new finding will help create new surgical techniques for nerve repair and offer insight for gender-affirming phalloplasty, which is the surgical construction of a penis often for transmasculine people.
 

Ownership of the body part 

When it comes to the clitoris, no one type of doctor has specialized in the sex organ.   

Urologists, gynecologists, plastic surgeons, and sex therapists all address potential problems that can arise with the clitoris and its surrounding body parts. But specialists like Dr. Krapf are few and far between.

It wasn’t until 2005 that Australian urologist Helen O’Connell found that the clitoris is filled with erectile and non-erectile tissues that are often hidden in anatomy drawings by fat and bone. And it wasn’t until the early 2000s that researchers began delving in earnest into the anatomy of the clitoris and how it functions.

And a 2018 study showed that if more doctors examined the clitoris, they could identify issues like adhesions or infections in the area, most of which can be treated without surgery.
 

A body part built for pleasure 

Randi Levinson, a sex, marriage, and family therapist in Los Angeles, sees patients who have less sensation in the clitoris or pain while having sex, many of whom have recently given birth or are going through menopause. 

Women often become embarrassed when they can’t orgasm, or have less sensation in the clitoris, but tend to avoid seeking medical advice, she says. Normalizing discussions about women’s pleasure and the vast anatomy that supports it may help some of her patients.

“The more normal it is to talk about and explore women’s pleasure, the less shame women will have when getting help when they aren’t experiencing pleasure,” Ms. Levinson says. “I have many ... clients who experience pain and discomfort with sex [after pregnancy] and no longer feel pleasure and are concerned that something is wrong with them.”

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

The patients of Jill Krapf, MD, are often too embarrassed to tell her about discomfort in their clitoris.

“I ask all of my patients about clitoral pain, and it is often the first time they have ever been asked about this,” says Dr. Krapf, the associate director of the Center for Vulvovaginal Disorders, a private clinic in Washington and New York. 

Dr. Krapf is an ob.gyn. who specializes in female sexual pain that involves the pelvis, vagina, and vulva. 

Many of the conditions Dr. Krapf treats don’t have outward symptoms that appear abnormal, but internally, there are damaged or irritated nerves that can result in hypersensitivity, unwanted arousal, or pain.

“Most recent research indicates that even a herniated disk or tear in the spine can lead to clitoral or vulvar symptoms, just like sciatica pain that shoots down the leg is related to issues in the spine,” Dr. Krapf says.

Dr. Krapf was excited to read of a new discovery: The clitoris has more than 10,000 nerve fibers – 2,000 more than previously reported in 1976 – a medical breakthrough for a part of the body that has often been neglected by the scientific field. Dr. Krapf and other doctors are hopeful that the attention to the clitoris will spark more interest and comprehensive education among people in their field. They also hope it will empower patients to seek medical help if they are having issues with their clitoris.

“Female sexual health has historically been underfunded, especially compared with male sexual health, like erectile dysfunction,” Dr. Krapf says. “Optimizing vulvar and vaginal health is not only necessary for sexual well-being.”

Blair Peters, MD, a plastic surgeon who specializes in gender-affirming care, led the study, which was presented at the Sexual Medicine Society of North America conference in October. Dr. Peters says he hopes that the new information decreases stigma that the clitoris is not worthy of the same medical attention that other organs of the body receive. 

When the clitoris doesn’t properly function, there can be harm to a person’s physical and mental health. Paying attention to discomfort in the clitoris, and seeking medical attention, can help catch and prevent some urinary and vaginal infections.  

“The fact that it took until 2022 for someone to do this work speaks to how little attention the clitoris has received,” says Dr. Peters, an assistant professor of surgery at the Oregon Health and Science University School of Medicine, Portland. 
 

What’s inside? 

Dr. Peters and his colleagues completed the study by taking clitoral nerve tissue from seven adult transgender men who had received gender-affirming genital surgery. The tissues were dyed and magnified 1,000 times under a microscope so the researchers could count nerve fibers. 

Dr. Peters says the finding is important because many surgeries take place in the groin region – like hip replacements, episiotomies during childbirth, and pelvic mesh procedures – and the revived attention to the clitoris may help health care providers know where nerves are so that injuries from medical mistakes are prevented. 

“Nerves are at risk of damage if it’s not understood where they are at all times,” he says. 

Dr. Peters hopes the new finding will help create new surgical techniques for nerve repair and offer insight for gender-affirming phalloplasty, which is the surgical construction of a penis often for transmasculine people.
 

Ownership of the body part 

When it comes to the clitoris, no one type of doctor has specialized in the sex organ.   

Urologists, gynecologists, plastic surgeons, and sex therapists all address potential problems that can arise with the clitoris and its surrounding body parts. But specialists like Dr. Krapf are few and far between.

It wasn’t until 2005 that Australian urologist Helen O’Connell found that the clitoris is filled with erectile and non-erectile tissues that are often hidden in anatomy drawings by fat and bone. And it wasn’t until the early 2000s that researchers began delving in earnest into the anatomy of the clitoris and how it functions.

And a 2018 study showed that if more doctors examined the clitoris, they could identify issues like adhesions or infections in the area, most of which can be treated without surgery.
 

A body part built for pleasure 

Randi Levinson, a sex, marriage, and family therapist in Los Angeles, sees patients who have less sensation in the clitoris or pain while having sex, many of whom have recently given birth or are going through menopause. 

Women often become embarrassed when they can’t orgasm, or have less sensation in the clitoris, but tend to avoid seeking medical advice, she says. Normalizing discussions about women’s pleasure and the vast anatomy that supports it may help some of her patients.

“The more normal it is to talk about and explore women’s pleasure, the less shame women will have when getting help when they aren’t experiencing pleasure,” Ms. Levinson says. “I have many ... clients who experience pain and discomfort with sex [after pregnancy] and no longer feel pleasure and are concerned that something is wrong with them.”

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

The patients of Jill Krapf, MD, are often too embarrassed to tell her about discomfort in their clitoris.

“I ask all of my patients about clitoral pain, and it is often the first time they have ever been asked about this,” says Dr. Krapf, the associate director of the Center for Vulvovaginal Disorders, a private clinic in Washington and New York. 

Dr. Krapf is an ob.gyn. who specializes in female sexual pain that involves the pelvis, vagina, and vulva. 

Many of the conditions Dr. Krapf treats don’t have outward symptoms that appear abnormal, but internally, there are damaged or irritated nerves that can result in hypersensitivity, unwanted arousal, or pain.

“Most recent research indicates that even a herniated disk or tear in the spine can lead to clitoral or vulvar symptoms, just like sciatica pain that shoots down the leg is related to issues in the spine,” Dr. Krapf says.

Dr. Krapf was excited to read of a new discovery: The clitoris has more than 10,000 nerve fibers – 2,000 more than previously reported in 1976 – a medical breakthrough for a part of the body that has often been neglected by the scientific field. Dr. Krapf and other doctors are hopeful that the attention to the clitoris will spark more interest and comprehensive education among people in their field. They also hope it will empower patients to seek medical help if they are having issues with their clitoris.

“Female sexual health has historically been underfunded, especially compared with male sexual health, like erectile dysfunction,” Dr. Krapf says. “Optimizing vulvar and vaginal health is not only necessary for sexual well-being.”

Blair Peters, MD, a plastic surgeon who specializes in gender-affirming care, led the study, which was presented at the Sexual Medicine Society of North America conference in October. Dr. Peters says he hopes that the new information decreases stigma that the clitoris is not worthy of the same medical attention that other organs of the body receive. 

When the clitoris doesn’t properly function, there can be harm to a person’s physical and mental health. Paying attention to discomfort in the clitoris, and seeking medical attention, can help catch and prevent some urinary and vaginal infections.  

“The fact that it took until 2022 for someone to do this work speaks to how little attention the clitoris has received,” says Dr. Peters, an assistant professor of surgery at the Oregon Health and Science University School of Medicine, Portland. 
 

What’s inside? 

Dr. Peters and his colleagues completed the study by taking clitoral nerve tissue from seven adult transgender men who had received gender-affirming genital surgery. The tissues were dyed and magnified 1,000 times under a microscope so the researchers could count nerve fibers. 

Dr. Peters says the finding is important because many surgeries take place in the groin region – like hip replacements, episiotomies during childbirth, and pelvic mesh procedures – and the revived attention to the clitoris may help health care providers know where nerves are so that injuries from medical mistakes are prevented. 

“Nerves are at risk of damage if it’s not understood where they are at all times,” he says. 

Dr. Peters hopes the new finding will help create new surgical techniques for nerve repair and offer insight for gender-affirming phalloplasty, which is the surgical construction of a penis often for transmasculine people.
 

Ownership of the body part 

When it comes to the clitoris, no one type of doctor has specialized in the sex organ.   

Urologists, gynecologists, plastic surgeons, and sex therapists all address potential problems that can arise with the clitoris and its surrounding body parts. But specialists like Dr. Krapf are few and far between.

It wasn’t until 2005 that Australian urologist Helen O’Connell found that the clitoris is filled with erectile and non-erectile tissues that are often hidden in anatomy drawings by fat and bone. And it wasn’t until the early 2000s that researchers began delving in earnest into the anatomy of the clitoris and how it functions.

And a 2018 study showed that if more doctors examined the clitoris, they could identify issues like adhesions or infections in the area, most of which can be treated without surgery.
 

A body part built for pleasure 

Randi Levinson, a sex, marriage, and family therapist in Los Angeles, sees patients who have less sensation in the clitoris or pain while having sex, many of whom have recently given birth or are going through menopause. 

Women often become embarrassed when they can’t orgasm, or have less sensation in the clitoris, but tend to avoid seeking medical advice, she says. Normalizing discussions about women’s pleasure and the vast anatomy that supports it may help some of her patients.

“The more normal it is to talk about and explore women’s pleasure, the less shame women will have when getting help when they aren’t experiencing pleasure,” Ms. Levinson says. “I have many ... clients who experience pain and discomfort with sex [after pregnancy] and no longer feel pleasure and are concerned that something is wrong with them.”

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

Shortly into the COVID-19 pandemic, Dr. Robert Califf, the commissioner of the US Food and Drug Administration, warned of a coming tsunami of chronic diseases, exacerbated by missed care during the pandemic.¹ According to a Centers for Disease Control and Prevention (CDC) survey, more than 30% of adults reported delaying or avoiding routine medical care in the first 6 months of 2020. This rate was highest in people with comorbidities.² Multiple studies demonstrated declines in hypertension care, hemoglobin A_1c testing, mammography, and colon cancer screening.^3-5 There has been a resultant increase in colon cancer complications, wounds, and amputations.^6,7 The United Kingdom is expected to have a 7.9% to 16.6% increase in future deaths due to breast and colorectal cancer (CRC).⁸ The World Health Organization estimates an excess 14.9 million people died in 2020 and 2021, either directly from or indirectly related to COVID-19.⁹

Due to the large-scale conversion from face-to-face care to telehealth modalities, COVID-19 vaccination events offered a unique opportunity to perform preventive health care that requires in-person visits, since most US adults have sought vaccination. However, vaccine events may not reach people most at risk for COVID-19 or chronic disease. Groups of Americans with lower vaccination rates were concerned about driving times and missing work to get the vaccine.¹⁰

Distance and travel time may be a particular challenge in Hawaii. Oahu is considered rural by the US Department of Veterans Affairs (VA); some communities are 80 minutes away from the VA Pacific Islands Health Care System (VAPIHCS) main facility. Oahu has approximately 150 veterans experiencing homelessness who may not have transportation to vaccine events. Additionally, VAPIHCS serves veterans that may be at higher risk of not receiving COVID-19 vaccination. Racial and ethnic minority residents have lower vaccination rates, yet are at a higher risk of COVID-19 infection and complications, and through the pandemic, this vaccination gap worsened.^11,12 More than 10% of the population of Hawaii is Native Hawaiian or Pacific Islander, and this population is at elevated risk for diabetes mellitus, hypertension, and COVID-19 mortality.^13-16

Health Fair Program

The VA provides clinical reminders in its electronic health record (EHR) that are specified by age, gender assigned at birth, and comorbidities. The clinical reminder program is intended to provide clinically relevant reminders for preventive care at the point of care. Veterans with overdue clinical reminders can be identified by name and address, allowing for the creation of health fair events that were directed towards communities with veterans with clinical reminders, including COVID-19 vaccination need. A team of health care professionals from VAPIHCS conceived of a health fair program to increase the reach of vaccine events and include preventive care in partnership with the VAPIHCS Vet Center Program, local communities, U.S.VETS, and the Hawaii Institute of Health Services (HIHS). We sought to determine which services could be offered in community settings; large vaccine events; and at homeless emergency, transitional, or permanent housing. We tracked veterans who received care in the different locations of the directed health fair.

This project was determined to be a quality improvement initiative by the VAPIHCS Office of Research and Development. It was jointly planned by the VAPIHCS pharmacy, infectious diseases, Vet Center Program, and homeless team to make the COVID-19 vaccines available to more rural and to veterans experiencing homelessness, and in response to a decline in facility face-to-face visits. Monthly meetings were held to select sites within zip codes with higher numbers of open clinical reminders and lower vaccination uptake. Informatics developed a list of clinical reminders by zip code for care performed at face-to-face visits.

Partners

The Vet Center Program, suicide prevention coordinator, and the homeless outreach team have a mandate to perform outreach events.^17,18 These services collaborate with community partners to locate sites for events. The team was able to leverage these contacts to set up sites for events. The Vet Center Program readjustment counselor and the suicide prevention coordinator provide mental health counseling. The Vet Center counsels on veteran benefits. They supplied a mobile van with WiFi, counseling and examination spaces, and refrigeration, which became the mobile clinic for the preventive care offered at events. The homeless program works with multiple community partners. They contract with HIHS and U.S.VETS to provide emergency and permanent housing for veterans. Each event is reviewed with HIHS and U.S.VETS staff for permission to be on site. The suicide prevention coordinator or the Vet Center readjustment counselor and the homeless team became regular attendees of events. The homeless team provided resources for housing or food insecurity.

Preventive Health Measures

The VA clinical reminder system supports caregivers for both preventive health care and chronic condition management.¹⁹ Clinical reminders appear as due in the EHR, and reminder reports can be run by clinical informatics to determine groups of patients who have not had a reminder completed. The following reminders were completed: vaccinations (including COVID-19), CRC screening, diabetic foot check and teaching of foot care, diabetic retinal consultations, laboratory studies (lipids, hemoglobin A_1c, microalbumin), mammogram and pap smear referrals, mental health reminders, homeless and food insecurity screening, HIV and hepatitis C testing, and blood pressure (BP) measurement. Health records were reviewed 3 months after each event to determine whether they were completed by the veteran. Additionally, we determined whether BP was controlled (< 130/80 mm Hg).

Settings

Large urban event. The first setting for the health fair was a large vaccination event near the VAPIHCS center in April 2021. Attendance was solicited by VEText, phone calls, and social media advertisements. At check-in, veterans with relevant open clinical reminders were invited to receive preventive health care during the 15-minute monitoring period after the COVID-19 vaccine. The Vet Center Program stationed the mobile van outside the vaccination event, where a physician and a clinical pharmacy specialist (CPS) did assessments, completed reminders, and entered follow-up requests for about 4 hours. A medical support assistant registered veterans who had never signed up for VA health care.

Community Settings. Nine events occurred at least monthly between March and September 2021 at 4 different sites in Oahu. Texts and phone calls were used to solicit attendance; there was no prior publicity on social media. Community events required scheduling resources; this required about 30 hours of medical staff assistant time. Seven sites were visited for about 3 hours each. A physician, pharmacy technician, and CPS conducted assessments, completed reminders, and entered follow-up requests. A medical support assistant registered veterans who had never signed up for VA health care.

Homeless veteran outreach. Five events occurred at 2 homeless veteran housing sites between August 2021 and January 2022. These sites were emergency housing sites (2 events) and transitional and permanent housing (2 events). U.S.VETS and HIHS contacted veterans living in those settings to promote the event. A physician, registered nurse, licensed practical nurse, and CPS conducted assessments, completed reminders, and entered follow-up requests. A medical support assistant registered veterans that had never signed up for VA health care. Each event lasted approximate 3 hours.

Process Quality Improvement

After the CDC changed recommendations to allow concurrent vaccination with the COVID-19 vaccine, we added other vaccinations to the events. This occurred during the course of community events. In June of 2021, there was a health advisory concerning hepatitis A among people experiencing homelessness in Oahu, so hepatitis vaccinations were added for events for veterans.²⁰

Veterans Served

The EHR was used to determine demographics, open clinical reminders, and attendance at follow-up. Simple descriptive statistics were performed in Microsoft Excel. A total of 115 veterans were seen for preventive health visits, and 404 clinical reminders were completed. Seven hundred veterans attended the large centrally located vaccine event and 43 agreed to have a preventive health visit. Thirty-eight veterans had a preventive health visit at homeless outreach events and 34 veterans had a preventive health visit at the community events. Veterans at community

Of the 166 vaccines given, 73 were for COVID-19. Besides vaccination,

Discussion

This program provided evidence that adding preventive screenings to vaccine events may help reach veterans who may have missed important preventive care due to the COVID-19 pandemic. The involvement of clinical informatics service allowed the outreach to be targeted to communities with incomplete clinical reminders. Interventions that could not be completed at the event had high levels of follow-up by veterans with important findings. The presence of a physician or nurse and a CPS allowed for point-of-care testing, as well as entering orders for medication, laboratory tests, and consultations. The attendance by representatives from the Vet Center, suicide prevention, and homeless services allowed counseling regarding benefits, and mental health follow-up. We believe that we were able to reach communities of veterans with unmet preventive needs and had higher risk of severe COVID-19, given the high numbers with open clinical reminders, the number of vaccines provided, and the high percentage of racial and ethnic minority veterans at events in the community. Our program experience provides some evidence that mobile and pop-up vaccination clinics may be beneficial for screening and managing chronic diseases, as proposed elsewhere.^21-24

Strengths of this intervention include that we were able to show a high level of follow-up for recommended medical care as well as the results of our interventions. We have found no similar articles that provide data on completion of follow-up appointments after a health fair. A prior study showed only 23% to 63% of participants at a health fair reported having a recommended follow-up discussion with doctors, but the study reported no outcome of completed cancer screenings.²⁵

Limitations

Weaknesses include the fact that health fair events may reach only healthy people, since attendees generally report better health and better health behaviors than nonattendees.^26,27 We felt this was more problematic for the large-scale urban event and that offering rural events and events in homeless housing improved the reach. Future efforts will involve the use of social media and mailings to solicit attendance. To improve follow-up, future work will include adding to the events: phlebotomy or expanded point-of-care testing; specialty care telehealth capability; cervical cancer screen self-collection; and tele-retinal services.

Conclusions

This program provided evidence that directed, preventive screening can be performed in outreach settings paired with vaccine events. These vaccination events in rural and homeless settings reached communities with demonstrable COVID-19 vaccination and other preventive care needs. This approach could be used to help veterans catch up on needed preventive care.

Acknowledgments

Veterans Affairs Pacific Islands Health Care System: Anthony Chance, LCSW; Nicholas Chang, PharmD; Andrew Dahlburg, LCSW; Wilminia G. Ellorimo-Gil, RN; Paul Guillory, RN; Wendy D. Joy; Arthur Minor, LCSW; Avalua Smith; Jessica Spurrier, RN. Veterans Health Administration Vet Center Program: Rolly O. Alvarado; Edmond G. DeGuzman; Richard T. Teel. Hawaii Institute for Human Services. U.S.VETS.

Shortly into the COVID-19 pandemic, Dr. Robert Califf, the commissioner of the US Food and Drug Administration, warned of a coming tsunami of chronic diseases, exacerbated by missed care during the pandemic.¹ According to a Centers for Disease Control and Prevention (CDC) survey, more than 30% of adults reported delaying or avoiding routine medical care in the first 6 months of 2020. This rate was highest in people with comorbidities.² Multiple studies demonstrated declines in hypertension care, hemoglobin A_1c testing, mammography, and colon cancer screening.^3-5 There has been a resultant increase in colon cancer complications, wounds, and amputations.^6,7 The United Kingdom is expected to have a 7.9% to 16.6% increase in future deaths due to breast and colorectal cancer (CRC).⁸ The World Health Organization estimates an excess 14.9 million people died in 2020 and 2021, either directly from or indirectly related to COVID-19.⁹

Due to the large-scale conversion from face-to-face care to telehealth modalities, COVID-19 vaccination events offered a unique opportunity to perform preventive health care that requires in-person visits, since most US adults have sought vaccination. However, vaccine events may not reach people most at risk for COVID-19 or chronic disease. Groups of Americans with lower vaccination rates were concerned about driving times and missing work to get the vaccine.¹⁰

Distance and travel time may be a particular challenge in Hawaii. Oahu is considered rural by the US Department of Veterans Affairs (VA); some communities are 80 minutes away from the VA Pacific Islands Health Care System (VAPIHCS) main facility. Oahu has approximately 150 veterans experiencing homelessness who may not have transportation to vaccine events. Additionally, VAPIHCS serves veterans that may be at higher risk of not receiving COVID-19 vaccination. Racial and ethnic minority residents have lower vaccination rates, yet are at a higher risk of COVID-19 infection and complications, and through the pandemic, this vaccination gap worsened.^11,12 More than 10% of the population of Hawaii is Native Hawaiian or Pacific Islander, and this population is at elevated risk for diabetes mellitus, hypertension, and COVID-19 mortality.^13-16

Health Fair Program

The VA provides clinical reminders in its electronic health record (EHR) that are specified by age, gender assigned at birth, and comorbidities. The clinical reminder program is intended to provide clinically relevant reminders for preventive care at the point of care. Veterans with overdue clinical reminders can be identified by name and address, allowing for the creation of health fair events that were directed towards communities with veterans with clinical reminders, including COVID-19 vaccination need. A team of health care professionals from VAPIHCS conceived of a health fair program to increase the reach of vaccine events and include preventive care in partnership with the VAPIHCS Vet Center Program, local communities, U.S.VETS, and the Hawaii Institute of Health Services (HIHS). We sought to determine which services could be offered in community settings; large vaccine events; and at homeless emergency, transitional, or permanent housing. We tracked veterans who received care in the different locations of the directed health fair.

This project was determined to be a quality improvement initiative by the VAPIHCS Office of Research and Development. It was jointly planned by the VAPIHCS pharmacy, infectious diseases, Vet Center Program, and homeless team to make the COVID-19 vaccines available to more rural and to veterans experiencing homelessness, and in response to a decline in facility face-to-face visits. Monthly meetings were held to select sites within zip codes with higher numbers of open clinical reminders and lower vaccination uptake. Informatics developed a list of clinical reminders by zip code for care performed at face-to-face visits.

Partners

The Vet Center Program, suicide prevention coordinator, and the homeless outreach team have a mandate to perform outreach events.^17,18 These services collaborate with community partners to locate sites for events. The team was able to leverage these contacts to set up sites for events. The Vet Center Program readjustment counselor and the suicide prevention coordinator provide mental health counseling. The Vet Center counsels on veteran benefits. They supplied a mobile van with WiFi, counseling and examination spaces, and refrigeration, which became the mobile clinic for the preventive care offered at events. The homeless program works with multiple community partners. They contract with HIHS and U.S.VETS to provide emergency and permanent housing for veterans. Each event is reviewed with HIHS and U.S.VETS staff for permission to be on site. The suicide prevention coordinator or the Vet Center readjustment counselor and the homeless team became regular attendees of events. The homeless team provided resources for housing or food insecurity.

Preventive Health Measures

The VA clinical reminder system supports caregivers for both preventive health care and chronic condition management.¹⁹ Clinical reminders appear as due in the EHR, and reminder reports can be run by clinical informatics to determine groups of patients who have not had a reminder completed. The following reminders were completed: vaccinations (including COVID-19), CRC screening, diabetic foot check and teaching of foot care, diabetic retinal consultations, laboratory studies (lipids, hemoglobin A_1c, microalbumin), mammogram and pap smear referrals, mental health reminders, homeless and food insecurity screening, HIV and hepatitis C testing, and blood pressure (BP) measurement. Health records were reviewed 3 months after each event to determine whether they were completed by the veteran. Additionally, we determined whether BP was controlled (< 130/80 mm Hg).

Settings

Large urban event. The first setting for the health fair was a large vaccination event near the VAPIHCS center in April 2021. Attendance was solicited by VEText, phone calls, and social media advertisements. At check-in, veterans with relevant open clinical reminders were invited to receive preventive health care during the 15-minute monitoring period after the COVID-19 vaccine. The Vet Center Program stationed the mobile van outside the vaccination event, where a physician and a clinical pharmacy specialist (CPS) did assessments, completed reminders, and entered follow-up requests for about 4 hours. A medical support assistant registered veterans who had never signed up for VA health care.

Community Settings. Nine events occurred at least monthly between March and September 2021 at 4 different sites in Oahu. Texts and phone calls were used to solicit attendance; there was no prior publicity on social media. Community events required scheduling resources; this required about 30 hours of medical staff assistant time. Seven sites were visited for about 3 hours each. A physician, pharmacy technician, and CPS conducted assessments, completed reminders, and entered follow-up requests. A medical support assistant registered veterans who had never signed up for VA health care.

Homeless veteran outreach. Five events occurred at 2 homeless veteran housing sites between August 2021 and January 2022. These sites were emergency housing sites (2 events) and transitional and permanent housing (2 events). U.S.VETS and HIHS contacted veterans living in those settings to promote the event. A physician, registered nurse, licensed practical nurse, and CPS conducted assessments, completed reminders, and entered follow-up requests. A medical support assistant registered veterans that had never signed up for VA health care. Each event lasted approximate 3 hours.

Process Quality Improvement

After the CDC changed recommendations to allow concurrent vaccination with the COVID-19 vaccine, we added other vaccinations to the events. This occurred during the course of community events. In June of 2021, there was a health advisory concerning hepatitis A among people experiencing homelessness in Oahu, so hepatitis vaccinations were added for events for veterans.²⁰

Veterans Served

The EHR was used to determine demographics, open clinical reminders, and attendance at follow-up. Simple descriptive statistics were performed in Microsoft Excel. A total of 115 veterans were seen for preventive health visits, and 404 clinical reminders were completed. Seven hundred veterans attended the large centrally located vaccine event and 43 agreed to have a preventive health visit. Thirty-eight veterans had a preventive health visit at homeless outreach events and 34 veterans had a preventive health visit at the community events. Veterans at community

Of the 166 vaccines given, 73 were for COVID-19. Besides vaccination,

Discussion

This program provided evidence that adding preventive screenings to vaccine events may help reach veterans who may have missed important preventive care due to the COVID-19 pandemic. The involvement of clinical informatics service allowed the outreach to be targeted to communities with incomplete clinical reminders. Interventions that could not be completed at the event had high levels of follow-up by veterans with important findings. The presence of a physician or nurse and a CPS allowed for point-of-care testing, as well as entering orders for medication, laboratory tests, and consultations. The attendance by representatives from the Vet Center, suicide prevention, and homeless services allowed counseling regarding benefits, and mental health follow-up. We believe that we were able to reach communities of veterans with unmet preventive needs and had higher risk of severe COVID-19, given the high numbers with open clinical reminders, the number of vaccines provided, and the high percentage of racial and ethnic minority veterans at events in the community. Our program experience provides some evidence that mobile and pop-up vaccination clinics may be beneficial for screening and managing chronic diseases, as proposed elsewhere.^21-24

Strengths of this intervention include that we were able to show a high level of follow-up for recommended medical care as well as the results of our interventions. We have found no similar articles that provide data on completion of follow-up appointments after a health fair. A prior study showed only 23% to 63% of participants at a health fair reported having a recommended follow-up discussion with doctors, but the study reported no outcome of completed cancer screenings.²⁵

Limitations

Weaknesses include the fact that health fair events may reach only healthy people, since attendees generally report better health and better health behaviors than nonattendees.^26,27 We felt this was more problematic for the large-scale urban event and that offering rural events and events in homeless housing improved the reach. Future efforts will involve the use of social media and mailings to solicit attendance. To improve follow-up, future work will include adding to the events: phlebotomy or expanded point-of-care testing; specialty care telehealth capability; cervical cancer screen self-collection; and tele-retinal services.

Conclusions

This program provided evidence that directed, preventive screening can be performed in outreach settings paired with vaccine events. These vaccination events in rural and homeless settings reached communities with demonstrable COVID-19 vaccination and other preventive care needs. This approach could be used to help veterans catch up on needed preventive care.

Acknowledgments

Veterans Affairs Pacific Islands Health Care System: Anthony Chance, LCSW; Nicholas Chang, PharmD; Andrew Dahlburg, LCSW; Wilminia G. Ellorimo-Gil, RN; Paul Guillory, RN; Wendy D. Joy; Arthur Minor, LCSW; Avalua Smith; Jessica Spurrier, RN. Veterans Health Administration Vet Center Program: Rolly O. Alvarado; Edmond G. DeGuzman; Richard T. Teel. Hawaii Institute for Human Services. U.S.VETS.

Shortly into the COVID-19 pandemic, Dr. Robert Califf, the commissioner of the US Food and Drug Administration, warned of a coming tsunami of chronic diseases, exacerbated by missed care during the pandemic.¹ According to a Centers for Disease Control and Prevention (CDC) survey, more than 30% of adults reported delaying or avoiding routine medical care in the first 6 months of 2020. This rate was highest in people with comorbidities.² Multiple studies demonstrated declines in hypertension care, hemoglobin A_1c testing, mammography, and colon cancer screening.^3-5 There has been a resultant increase in colon cancer complications, wounds, and amputations.^6,7 The United Kingdom is expected to have a 7.9% to 16.6% increase in future deaths due to breast and colorectal cancer (CRC).⁸ The World Health Organization estimates an excess 14.9 million people died in 2020 and 2021, either directly from or indirectly related to COVID-19.⁹

Due to the large-scale conversion from face-to-face care to telehealth modalities, COVID-19 vaccination events offered a unique opportunity to perform preventive health care that requires in-person visits, since most US adults have sought vaccination. However, vaccine events may not reach people most at risk for COVID-19 or chronic disease. Groups of Americans with lower vaccination rates were concerned about driving times and missing work to get the vaccine.¹⁰

Distance and travel time may be a particular challenge in Hawaii. Oahu is considered rural by the US Department of Veterans Affairs (VA); some communities are 80 minutes away from the VA Pacific Islands Health Care System (VAPIHCS) main facility. Oahu has approximately 150 veterans experiencing homelessness who may not have transportation to vaccine events. Additionally, VAPIHCS serves veterans that may be at higher risk of not receiving COVID-19 vaccination. Racial and ethnic minority residents have lower vaccination rates, yet are at a higher risk of COVID-19 infection and complications, and through the pandemic, this vaccination gap worsened.^11,12 More than 10% of the population of Hawaii is Native Hawaiian or Pacific Islander, and this population is at elevated risk for diabetes mellitus, hypertension, and COVID-19 mortality.^13-16

Health Fair Program

The VA provides clinical reminders in its electronic health record (EHR) that are specified by age, gender assigned at birth, and comorbidities. The clinical reminder program is intended to provide clinically relevant reminders for preventive care at the point of care. Veterans with overdue clinical reminders can be identified by name and address, allowing for the creation of health fair events that were directed towards communities with veterans with clinical reminders, including COVID-19 vaccination need. A team of health care professionals from VAPIHCS conceived of a health fair program to increase the reach of vaccine events and include preventive care in partnership with the VAPIHCS Vet Center Program, local communities, U.S.VETS, and the Hawaii Institute of Health Services (HIHS). We sought to determine which services could be offered in community settings; large vaccine events; and at homeless emergency, transitional, or permanent housing. We tracked veterans who received care in the different locations of the directed health fair.

This project was determined to be a quality improvement initiative by the VAPIHCS Office of Research and Development. It was jointly planned by the VAPIHCS pharmacy, infectious diseases, Vet Center Program, and homeless team to make the COVID-19 vaccines available to more rural and to veterans experiencing homelessness, and in response to a decline in facility face-to-face visits. Monthly meetings were held to select sites within zip codes with higher numbers of open clinical reminders and lower vaccination uptake. Informatics developed a list of clinical reminders by zip code for care performed at face-to-face visits.

Partners

The Vet Center Program, suicide prevention coordinator, and the homeless outreach team have a mandate to perform outreach events.^17,18 These services collaborate with community partners to locate sites for events. The team was able to leverage these contacts to set up sites for events. The Vet Center Program readjustment counselor and the suicide prevention coordinator provide mental health counseling. The Vet Center counsels on veteran benefits. They supplied a mobile van with WiFi, counseling and examination spaces, and refrigeration, which became the mobile clinic for the preventive care offered at events. The homeless program works with multiple community partners. They contract with HIHS and U.S.VETS to provide emergency and permanent housing for veterans. Each event is reviewed with HIHS and U.S.VETS staff for permission to be on site. The suicide prevention coordinator or the Vet Center readjustment counselor and the homeless team became regular attendees of events. The homeless team provided resources for housing or food insecurity.

Preventive Health Measures

The VA clinical reminder system supports caregivers for both preventive health care and chronic condition management.¹⁹ Clinical reminders appear as due in the EHR, and reminder reports can be run by clinical informatics to determine groups of patients who have not had a reminder completed. The following reminders were completed: vaccinations (including COVID-19), CRC screening, diabetic foot check and teaching of foot care, diabetic retinal consultations, laboratory studies (lipids, hemoglobin A_1c, microalbumin), mammogram and pap smear referrals, mental health reminders, homeless and food insecurity screening, HIV and hepatitis C testing, and blood pressure (BP) measurement. Health records were reviewed 3 months after each event to determine whether they were completed by the veteran. Additionally, we determined whether BP was controlled (< 130/80 mm Hg).

Settings

Large urban event. The first setting for the health fair was a large vaccination event near the VAPIHCS center in April 2021. Attendance was solicited by VEText, phone calls, and social media advertisements. At check-in, veterans with relevant open clinical reminders were invited to receive preventive health care during the 15-minute monitoring period after the COVID-19 vaccine. The Vet Center Program stationed the mobile van outside the vaccination event, where a physician and a clinical pharmacy specialist (CPS) did assessments, completed reminders, and entered follow-up requests for about 4 hours. A medical support assistant registered veterans who had never signed up for VA health care.

Community Settings. Nine events occurred at least monthly between March and September 2021 at 4 different sites in Oahu. Texts and phone calls were used to solicit attendance; there was no prior publicity on social media. Community events required scheduling resources; this required about 30 hours of medical staff assistant time. Seven sites were visited for about 3 hours each. A physician, pharmacy technician, and CPS conducted assessments, completed reminders, and entered follow-up requests. A medical support assistant registered veterans who had never signed up for VA health care.

Homeless veteran outreach. Five events occurred at 2 homeless veteran housing sites between August 2021 and January 2022. These sites were emergency housing sites (2 events) and transitional and permanent housing (2 events). U.S.VETS and HIHS contacted veterans living in those settings to promote the event. A physician, registered nurse, licensed practical nurse, and CPS conducted assessments, completed reminders, and entered follow-up requests. A medical support assistant registered veterans that had never signed up for VA health care. Each event lasted approximate 3 hours.

Process Quality Improvement

After the CDC changed recommendations to allow concurrent vaccination with the COVID-19 vaccine, we added other vaccinations to the events. This occurred during the course of community events. In June of 2021, there was a health advisory concerning hepatitis A among people experiencing homelessness in Oahu, so hepatitis vaccinations were added for events for veterans.²⁰

Veterans Served

The EHR was used to determine demographics, open clinical reminders, and attendance at follow-up. Simple descriptive statistics were performed in Microsoft Excel. A total of 115 veterans were seen for preventive health visits, and 404 clinical reminders were completed. Seven hundred veterans attended the large centrally located vaccine event and 43 agreed to have a preventive health visit. Thirty-eight veterans had a preventive health visit at homeless outreach events and 34 veterans had a preventive health visit at the community events. Veterans at community

Of the 166 vaccines given, 73 were for COVID-19. Besides vaccination,

Discussion

This program provided evidence that adding preventive screenings to vaccine events may help reach veterans who may have missed important preventive care due to the COVID-19 pandemic. The involvement of clinical informatics service allowed the outreach to be targeted to communities with incomplete clinical reminders. Interventions that could not be completed at the event had high levels of follow-up by veterans with important findings. The presence of a physician or nurse and a CPS allowed for point-of-care testing, as well as entering orders for medication, laboratory tests, and consultations. The attendance by representatives from the Vet Center, suicide prevention, and homeless services allowed counseling regarding benefits, and mental health follow-up. We believe that we were able to reach communities of veterans with unmet preventive needs and had higher risk of severe COVID-19, given the high numbers with open clinical reminders, the number of vaccines provided, and the high percentage of racial and ethnic minority veterans at events in the community. Our program experience provides some evidence that mobile and pop-up vaccination clinics may be beneficial for screening and managing chronic diseases, as proposed elsewhere.^21-24

Strengths of this intervention include that we were able to show a high level of follow-up for recommended medical care as well as the results of our interventions. We have found no similar articles that provide data on completion of follow-up appointments after a health fair. A prior study showed only 23% to 63% of participants at a health fair reported having a recommended follow-up discussion with doctors, but the study reported no outcome of completed cancer screenings.²⁵

Limitations

Weaknesses include the fact that health fair events may reach only healthy people, since attendees generally report better health and better health behaviors than nonattendees.^26,27 We felt this was more problematic for the large-scale urban event and that offering rural events and events in homeless housing improved the reach. Future efforts will involve the use of social media and mailings to solicit attendance. To improve follow-up, future work will include adding to the events: phlebotomy or expanded point-of-care testing; specialty care telehealth capability; cervical cancer screen self-collection; and tele-retinal services.

Conclusions

This program provided evidence that directed, preventive screening can be performed in outreach settings paired with vaccine events. These vaccination events in rural and homeless settings reached communities with demonstrable COVID-19 vaccination and other preventive care needs. This approach could be used to help veterans catch up on needed preventive care.

Acknowledgments

Veterans Affairs Pacific Islands Health Care System: Anthony Chance, LCSW; Nicholas Chang, PharmD; Andrew Dahlburg, LCSW; Wilminia G. Ellorimo-Gil, RN; Paul Guillory, RN; Wendy D. Joy; Arthur Minor, LCSW; Avalua Smith; Jessica Spurrier, RN. Veterans Health Administration Vet Center Program: Rolly O. Alvarado; Edmond G. DeGuzman; Richard T. Teel. Hawaii Institute for Human Services. U.S.VETS.

CHICAGO – Early ablation of atrial fibrillation (AFib) reduces the risk of progression, compared with antiarrhythmic therapies, according to results of a multicenter, randomized trial called PROGRESSIVE-AF.

Over 36 months of follow-up, the trial linked early ablation with a reduced risk of persistent AFib (1.9% vs. 7.4%), and in addition, those in the ablation group were less likely to have recurrent atrial tachyarrhythmias of any kind (56.5% vs. 77.2%), reported Jason G. Andrade, MD, at the American Heart Association scientific sessions.

Ted Bosworth/MDedge

Serving as a long-term extension of the EARLY-AF trial published almost 2 years ago, this trial expands evidence that progressive AFib can be attenuated, a concept that has been debated.

“Can early AFib ablation stop progression?” asked Carina Blomström-Lindqvist, MD, PhD. The invited discussant for the PROGRESSION-AF trial, Dr. Blomström-Lundqvist concluded, “here is another set of data that suggests it can.”

By another set of data, Dr. Blomström-Lindqvist was referring to a previously published multinational study called ATTEST In this study, which involved 29 sites worldwide and compared radiofrequency ablation to antiarrhythmic drug therapy, early ablation also produced a lower risk of persistent AFib at the end of 3 years (2.4% vs. 17.5%; P = .0009).

In the previously published open-label EARLY-AF trial, 303 patients with paroxysmal, untreated AFib were randomized to cryoballoon ablation or antiarrhythmic drugs. The primary endpoint was the first documented recurrence of an atrial tachyarrhythmia between 91 and 365 days. The lower rate following ablation (42.9% vs. 67.8%) represented a more than 50% reduction in risk (hazard ratio, 0.48; P < .001) relative to antiarrhythmic therapy.

In PROGRESSIVE-AF, the same 303 patients were monitored continuously for an additional 24 months with an implanted cardiac monitor programmed with an AFib-detection algorithm. The data from the monitor were obtained daily. Over the final 2 years of the study, office visits were conducted every 6 months.
 

Tachyarrhythmias represent primary endpoint

In addition to persistent AFib, defined as lasting ≥ 7 days or lasting 48 hours to 7 days but requiring cardioversion for termination, patients in PROGRESSIVE-AF were also monitored for recurrent atrial tachyarrhythmias, AFib burden, quality of life (QOL), and health care utilization, and safety.

The average age was roughly 58 years. Although more than one-third had hypertension, most had no other comorbidities. The authors emphasized that the study population overall was relatively young and healthy.

Those randomized to antiarrhythmic therapy in EARLY-AF/PROGRESSIVE-AF received commonly prescribed therapies titrated to maximally tolerated doses using standardized protocols. At the start of EARLY-AF, flecainide, taken by 65% of patients, was the most commonly used agent, followed by sotalol, propafenone, dronedarone, and amiodarone.

At the end of PROGRESSIVE-AF, the order of the most common therapies did not change relative to EARLY-AF, but only 49% of patients were taking flecainide and 31% were no longer taking any antiarrhythmic therapy.

At the end of 3 years of follow-up in EARLY-AF/PROGRESSIVE-AF, the difference in persistent AFib represented a 75% reduction in favor of early ablation (HR, 0.25; 95% confidence interval, 0.09-0.70).

In those treated with ablation relative to those treated with antiarrhythmic therapy, the lower rate of atrial tachyarrhythmia lasting more than 7 days (1.9% vs. 6.0%) represented a 70% risk reduction (HR, 0.30; 95% CI 0.10-0.93). The protection from cardioversion for atrial tachyarrhythmia lasting between 2 and 7 days in duration (0.6% vs. 4.7%) translated into an 86% relative reduction (HR, 0.14; 95% CI, 0.02-0.85).

The impact on QOL for those randomized to ablation, which was measured with both AFib-specific and generic measures, was meaningful to patients, according to Dr. Andrade, director of the Cardiac Electrophysiology Laboratory, Vancouver General Hospital.

For example, the mean difference in the AF Quality of Life Survey (AFEQT), was 8.0 at 1 year and 7.4 at 3 years in favor of ablation. A change of 5 points in this score is considered to be a clinically meaningful difference, according to Dr. Andrade.

Numerically, the relative risk of emergency room visits and cardioversion were lower in the ablation group, but the differences did not reach statistical significance. However, the lower hazard ratio for hospitalization was significant (HR, 0.31; 95% CI, 0.15-0.66), supporting a reduction in consumption of health care resources.
 

Ablation found safer than drugs

The rate of adverse events of any kind (11.0% vs. 23.5%) and serious adverse events (4.5% vs. 10.1%) were lower in the ablation group.

There were no differences in major adverse cardiovascular events observed in this period of follow-up, but Dr. Andrade pointed out that follow-up was not long enough to expect differences in these events.

Impressed by the magnitude of the reduction in persistent AFib in a population of relatively young and healthy patients considered to be at a low risk of AFib progression, Dr. Blomström-Lindqvist, a professor of cardiology at the Institution of Medical Science, Uppsala, Sweden, indicated that the data support early ablation as a means to reduce risk of this outcome.

However, she did caution that progressive AFib was observed in a relatively small proportion of patients managed with antiarrhythmic therapy at 3 years, an outcome relevant when discussing treatment options with patients.

The results were published in New England Journal of Medicine simultaneously with Dr. Andrade’s presentation.

Dr. Andrade reports financial relationships with Bayer, Bayliss, Biosense, Bristol-Myers Squibb, Medtronic and Servier. The trial, funded largely by the Canadian government and Canadian professional societies, received additional funding from Bayliss and Medtronic. Dr. Blomström-Lundqvist reports financial relationships with Bayer, Boston Scientific, Cathprint, Medtronic, and Sanofi.

CHICAGO – Early ablation of atrial fibrillation (AFib) reduces the risk of progression, compared with antiarrhythmic therapies, according to results of a multicenter, randomized trial called PROGRESSIVE-AF.

Over 36 months of follow-up, the trial linked early ablation with a reduced risk of persistent AFib (1.9% vs. 7.4%), and in addition, those in the ablation group were less likely to have recurrent atrial tachyarrhythmias of any kind (56.5% vs. 77.2%), reported Jason G. Andrade, MD, at the American Heart Association scientific sessions.

Ted Bosworth/MDedge

Serving as a long-term extension of the EARLY-AF trial published almost 2 years ago, this trial expands evidence that progressive AFib can be attenuated, a concept that has been debated.

“Can early AFib ablation stop progression?” asked Carina Blomström-Lindqvist, MD, PhD. The invited discussant for the PROGRESSION-AF trial, Dr. Blomström-Lundqvist concluded, “here is another set of data that suggests it can.”

By another set of data, Dr. Blomström-Lindqvist was referring to a previously published multinational study called ATTEST In this study, which involved 29 sites worldwide and compared radiofrequency ablation to antiarrhythmic drug therapy, early ablation also produced a lower risk of persistent AFib at the end of 3 years (2.4% vs. 17.5%; P = .0009).

In the previously published open-label EARLY-AF trial, 303 patients with paroxysmal, untreated AFib were randomized to cryoballoon ablation or antiarrhythmic drugs. The primary endpoint was the first documented recurrence of an atrial tachyarrhythmia between 91 and 365 days. The lower rate following ablation (42.9% vs. 67.8%) represented a more than 50% reduction in risk (hazard ratio, 0.48; P < .001) relative to antiarrhythmic therapy.

In PROGRESSIVE-AF, the same 303 patients were monitored continuously for an additional 24 months with an implanted cardiac monitor programmed with an AFib-detection algorithm. The data from the monitor were obtained daily. Over the final 2 years of the study, office visits were conducted every 6 months.
 

Tachyarrhythmias represent primary endpoint

In addition to persistent AFib, defined as lasting ≥ 7 days or lasting 48 hours to 7 days but requiring cardioversion for termination, patients in PROGRESSIVE-AF were also monitored for recurrent atrial tachyarrhythmias, AFib burden, quality of life (QOL), and health care utilization, and safety.

The average age was roughly 58 years. Although more than one-third had hypertension, most had no other comorbidities. The authors emphasized that the study population overall was relatively young and healthy.

Those randomized to antiarrhythmic therapy in EARLY-AF/PROGRESSIVE-AF received commonly prescribed therapies titrated to maximally tolerated doses using standardized protocols. At the start of EARLY-AF, flecainide, taken by 65% of patients, was the most commonly used agent, followed by sotalol, propafenone, dronedarone, and amiodarone.

At the end of PROGRESSIVE-AF, the order of the most common therapies did not change relative to EARLY-AF, but only 49% of patients were taking flecainide and 31% were no longer taking any antiarrhythmic therapy.

At the end of 3 years of follow-up in EARLY-AF/PROGRESSIVE-AF, the difference in persistent AFib represented a 75% reduction in favor of early ablation (HR, 0.25; 95% confidence interval, 0.09-0.70).

In those treated with ablation relative to those treated with antiarrhythmic therapy, the lower rate of atrial tachyarrhythmia lasting more than 7 days (1.9% vs. 6.0%) represented a 70% risk reduction (HR, 0.30; 95% CI 0.10-0.93). The protection from cardioversion for atrial tachyarrhythmia lasting between 2 and 7 days in duration (0.6% vs. 4.7%) translated into an 86% relative reduction (HR, 0.14; 95% CI, 0.02-0.85).

The impact on QOL for those randomized to ablation, which was measured with both AFib-specific and generic measures, was meaningful to patients, according to Dr. Andrade, director of the Cardiac Electrophysiology Laboratory, Vancouver General Hospital.

For example, the mean difference in the AF Quality of Life Survey (AFEQT), was 8.0 at 1 year and 7.4 at 3 years in favor of ablation. A change of 5 points in this score is considered to be a clinically meaningful difference, according to Dr. Andrade.

Numerically, the relative risk of emergency room visits and cardioversion were lower in the ablation group, but the differences did not reach statistical significance. However, the lower hazard ratio for hospitalization was significant (HR, 0.31; 95% CI, 0.15-0.66), supporting a reduction in consumption of health care resources.
 

Ablation found safer than drugs

The rate of adverse events of any kind (11.0% vs. 23.5%) and serious adverse events (4.5% vs. 10.1%) were lower in the ablation group.

There were no differences in major adverse cardiovascular events observed in this period of follow-up, but Dr. Andrade pointed out that follow-up was not long enough to expect differences in these events.

Impressed by the magnitude of the reduction in persistent AFib in a population of relatively young and healthy patients considered to be at a low risk of AFib progression, Dr. Blomström-Lindqvist, a professor of cardiology at the Institution of Medical Science, Uppsala, Sweden, indicated that the data support early ablation as a means to reduce risk of this outcome.

However, she did caution that progressive AFib was observed in a relatively small proportion of patients managed with antiarrhythmic therapy at 3 years, an outcome relevant when discussing treatment options with patients.

The results were published in New England Journal of Medicine simultaneously with Dr. Andrade’s presentation.

Dr. Andrade reports financial relationships with Bayer, Bayliss, Biosense, Bristol-Myers Squibb, Medtronic and Servier. The trial, funded largely by the Canadian government and Canadian professional societies, received additional funding from Bayliss and Medtronic. Dr. Blomström-Lundqvist reports financial relationships with Bayer, Boston Scientific, Cathprint, Medtronic, and Sanofi.

CHICAGO – Early ablation of atrial fibrillation (AFib) reduces the risk of progression, compared with antiarrhythmic therapies, according to results of a multicenter, randomized trial called PROGRESSIVE-AF.

Over 36 months of follow-up, the trial linked early ablation with a reduced risk of persistent AFib (1.9% vs. 7.4%), and in addition, those in the ablation group were less likely to have recurrent atrial tachyarrhythmias of any kind (56.5% vs. 77.2%), reported Jason G. Andrade, MD, at the American Heart Association scientific sessions.

Ted Bosworth/MDedge

Serving as a long-term extension of the EARLY-AF trial published almost 2 years ago, this trial expands evidence that progressive AFib can be attenuated, a concept that has been debated.

“Can early AFib ablation stop progression?” asked Carina Blomström-Lindqvist, MD, PhD. The invited discussant for the PROGRESSION-AF trial, Dr. Blomström-Lundqvist concluded, “here is another set of data that suggests it can.”

By another set of data, Dr. Blomström-Lindqvist was referring to a previously published multinational study called ATTEST In this study, which involved 29 sites worldwide and compared radiofrequency ablation to antiarrhythmic drug therapy, early ablation also produced a lower risk of persistent AFib at the end of 3 years (2.4% vs. 17.5%; P = .0009).

In the previously published open-label EARLY-AF trial, 303 patients with paroxysmal, untreated AFib were randomized to cryoballoon ablation or antiarrhythmic drugs. The primary endpoint was the first documented recurrence of an atrial tachyarrhythmia between 91 and 365 days. The lower rate following ablation (42.9% vs. 67.8%) represented a more than 50% reduction in risk (hazard ratio, 0.48; P < .001) relative to antiarrhythmic therapy.

In PROGRESSIVE-AF, the same 303 patients were monitored continuously for an additional 24 months with an implanted cardiac monitor programmed with an AFib-detection algorithm. The data from the monitor were obtained daily. Over the final 2 years of the study, office visits were conducted every 6 months.
 

Tachyarrhythmias represent primary endpoint

In addition to persistent AFib, defined as lasting ≥ 7 days or lasting 48 hours to 7 days but requiring cardioversion for termination, patients in PROGRESSIVE-AF were also monitored for recurrent atrial tachyarrhythmias, AFib burden, quality of life (QOL), and health care utilization, and safety.

The average age was roughly 58 years. Although more than one-third had hypertension, most had no other comorbidities. The authors emphasized that the study population overall was relatively young and healthy.

Those randomized to antiarrhythmic therapy in EARLY-AF/PROGRESSIVE-AF received commonly prescribed therapies titrated to maximally tolerated doses using standardized protocols. At the start of EARLY-AF, flecainide, taken by 65% of patients, was the most commonly used agent, followed by sotalol, propafenone, dronedarone, and amiodarone.

At the end of PROGRESSIVE-AF, the order of the most common therapies did not change relative to EARLY-AF, but only 49% of patients were taking flecainide and 31% were no longer taking any antiarrhythmic therapy.

At the end of 3 years of follow-up in EARLY-AF/PROGRESSIVE-AF, the difference in persistent AFib represented a 75% reduction in favor of early ablation (HR, 0.25; 95% confidence interval, 0.09-0.70).

In those treated with ablation relative to those treated with antiarrhythmic therapy, the lower rate of atrial tachyarrhythmia lasting more than 7 days (1.9% vs. 6.0%) represented a 70% risk reduction (HR, 0.30; 95% CI 0.10-0.93). The protection from cardioversion for atrial tachyarrhythmia lasting between 2 and 7 days in duration (0.6% vs. 4.7%) translated into an 86% relative reduction (HR, 0.14; 95% CI, 0.02-0.85).

The impact on QOL for those randomized to ablation, which was measured with both AFib-specific and generic measures, was meaningful to patients, according to Dr. Andrade, director of the Cardiac Electrophysiology Laboratory, Vancouver General Hospital.

For example, the mean difference in the AF Quality of Life Survey (AFEQT), was 8.0 at 1 year and 7.4 at 3 years in favor of ablation. A change of 5 points in this score is considered to be a clinically meaningful difference, according to Dr. Andrade.

Numerically, the relative risk of emergency room visits and cardioversion were lower in the ablation group, but the differences did not reach statistical significance. However, the lower hazard ratio for hospitalization was significant (HR, 0.31; 95% CI, 0.15-0.66), supporting a reduction in consumption of health care resources.
 

Ablation found safer than drugs

The rate of adverse events of any kind (11.0% vs. 23.5%) and serious adverse events (4.5% vs. 10.1%) were lower in the ablation group.

There were no differences in major adverse cardiovascular events observed in this period of follow-up, but Dr. Andrade pointed out that follow-up was not long enough to expect differences in these events.

Impressed by the magnitude of the reduction in persistent AFib in a population of relatively young and healthy patients considered to be at a low risk of AFib progression, Dr. Blomström-Lindqvist, a professor of cardiology at the Institution of Medical Science, Uppsala, Sweden, indicated that the data support early ablation as a means to reduce risk of this outcome.

However, she did caution that progressive AFib was observed in a relatively small proportion of patients managed with antiarrhythmic therapy at 3 years, an outcome relevant when discussing treatment options with patients.

The results were published in New England Journal of Medicine simultaneously with Dr. Andrade’s presentation.

Dr. Andrade reports financial relationships with Bayer, Bayliss, Biosense, Bristol-Myers Squibb, Medtronic and Servier. The trial, funded largely by the Canadian government and Canadian professional societies, received additional funding from Bayliss and Medtronic. Dr. Blomström-Lundqvist reports financial relationships with Bayer, Boston Scientific, Cathprint, Medtronic, and Sanofi.

U.S. mortality for alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased at “alarming” rates during the COVID-19 pandemic, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

Between 2019 and 2021, ALD-related deaths increased by 17.6% and NAFLD-related deaths increased by 14.5%, Yee Hui Yeo, MD, a resident physician and hepatology-focused investigator at Cedars-Sinai Medical Center in Los Angeles, said at a preconference press briefing.

“Even before the pandemic, the mortality rates for these two diseases have been increasing, with NAFLD having an even steeper increasing trend,” he said. “During the pandemic, these two diseases had a significant surge.”
 

Recent U.S. liver disease death rates

Dr. Yeo and colleagues analyzed data from the Center for Disease Control and Prevention’s National Vital Statistic System to estimate the age-standardized mortality rates (ASMR) of liver disease between 2010 and 2021, including ALD, NAFLD, hepatitis B, and hepatitis C. Using prediction modeling analyses based on trends from 2010 to 2019, they predicted mortality rates for 2020-2021 and compared them with the observed rates to quantify the differences related to the pandemic.

Between 2010 and 2021, there were about 626,000 chronic liver disease–related deaths, including about 343,000 ALD-related deaths, 204,000 hepatitis C–related deaths, 58,000 NAFLD-related deaths, and 21,000 hepatitis B–related deaths.

For ALD-related deaths, the annual percentage change was 3.5% for 2010-2019 and 17.6% for 2019-2021. The observed ASMR in 2020 was significantly higher than predicted, at 15.7 deaths per 100,000 people versus 13.0 predicted from the 2010-2019 rate. The trend continued in 2021, with 17.4 deaths per 100,000 people versus 13.4 in the previous decade.

The highest numbers of ALD-related deaths during the COVID-19 pandemic occurred in Alaska, Montana, Wyoming, Colorado, New Mexico, and South Dakota.

For NAFLD-related deaths, the annual percentage change was 7.6% for 2010-2014, 11.8% for 2014-2019, and 14.5% for 2019-2021. The observed ASMR was also higher than predicted, at 3.1 deaths per 100,000 people versus 2.6 in 2020, as well as 3.4 versus 2.8 in 2021.

The highest numbers of NAFLD-related deaths during the COVID-19 pandemic occurred in Oklahoma, Indiana, Kentucky, Tennessee, and West Virginia.
 

Hepatitis B and C gains lost in pandemic

In contrast, the annual percentage change in was –1.9% for hepatitis B and –2.8% for hepatitis C. After new treatment for hepatitis C emerged in 2013-2014, mortality rates were –7.8% for 2014-2019, Dr. Yeo noted.

“However, during the pandemic, we saw that this decrease has become a nonsignificant change,” he said. “That means our progress of the past 5 or 6 years has already stopped during the pandemic.”

By race and ethnicity, the increase in ALD-related mortality was most pronounced in non-Hispanic White, non-Hispanic Black, and Alaska Native/American Indian populations, Dr. Yeo said. Alaska Natives and American Indians had the highest annual percentage change, at 18%, followed by non-Hispanic Whites at 11.7% and non-Hispanic Blacks at 10.8%. There were no significant differences in race and ethnicity for NAFLD-related deaths, although all groups had major increases in recent years.
 

Biggest rise in young adults

By age, the increase in ALD-related mortality was particularly severe for ages 25-44, with an annual percentage change of 34.6% in 2019-2021, as compared with 13.7% for ages 45-64 and 12.6% for ages 65 and older.

For NAFLD-related deaths, another major increase was observed among ages 25-44, with an annual percentage change of 28.1% for 2019-2021, as compared with 12% for ages 65 and older and 7.4% for ages 45-64.

By sex, the ASMR increase in NAFLD-related mortality was steady throughout 2010-2021 for both men and women. In contrast, ALD-related death increased sharply between 2019 and 2021, with an annual percentage change of 19.1% for women and 16.7% for men.

“The increasing trend in mortality rates for ALD and NAFLD has been quite alarming, with disparities in age, race, and ethnicity,” Dr. Yeo said.

The study received no funding support. Some authors disclosed research funding, advisory board roles, and consulting fees with various pharmaceutical companies.

U.S. mortality for alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased at “alarming” rates during the COVID-19 pandemic, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

Between 2019 and 2021, ALD-related deaths increased by 17.6% and NAFLD-related deaths increased by 14.5%, Yee Hui Yeo, MD, a resident physician and hepatology-focused investigator at Cedars-Sinai Medical Center in Los Angeles, said at a preconference press briefing.

“Even before the pandemic, the mortality rates for these two diseases have been increasing, with NAFLD having an even steeper increasing trend,” he said. “During the pandemic, these two diseases had a significant surge.”
 

Recent U.S. liver disease death rates

Dr. Yeo and colleagues analyzed data from the Center for Disease Control and Prevention’s National Vital Statistic System to estimate the age-standardized mortality rates (ASMR) of liver disease between 2010 and 2021, including ALD, NAFLD, hepatitis B, and hepatitis C. Using prediction modeling analyses based on trends from 2010 to 2019, they predicted mortality rates for 2020-2021 and compared them with the observed rates to quantify the differences related to the pandemic.

Between 2010 and 2021, there were about 626,000 chronic liver disease–related deaths, including about 343,000 ALD-related deaths, 204,000 hepatitis C–related deaths, 58,000 NAFLD-related deaths, and 21,000 hepatitis B–related deaths.

For ALD-related deaths, the annual percentage change was 3.5% for 2010-2019 and 17.6% for 2019-2021. The observed ASMR in 2020 was significantly higher than predicted, at 15.7 deaths per 100,000 people versus 13.0 predicted from the 2010-2019 rate. The trend continued in 2021, with 17.4 deaths per 100,000 people versus 13.4 in the previous decade.

The highest numbers of ALD-related deaths during the COVID-19 pandemic occurred in Alaska, Montana, Wyoming, Colorado, New Mexico, and South Dakota.

For NAFLD-related deaths, the annual percentage change was 7.6% for 2010-2014, 11.8% for 2014-2019, and 14.5% for 2019-2021. The observed ASMR was also higher than predicted, at 3.1 deaths per 100,000 people versus 2.6 in 2020, as well as 3.4 versus 2.8 in 2021.

The highest numbers of NAFLD-related deaths during the COVID-19 pandemic occurred in Oklahoma, Indiana, Kentucky, Tennessee, and West Virginia.
 

Hepatitis B and C gains lost in pandemic

In contrast, the annual percentage change in was –1.9% for hepatitis B and –2.8% for hepatitis C. After new treatment for hepatitis C emerged in 2013-2014, mortality rates were –7.8% for 2014-2019, Dr. Yeo noted.

“However, during the pandemic, we saw that this decrease has become a nonsignificant change,” he said. “That means our progress of the past 5 or 6 years has already stopped during the pandemic.”

By race and ethnicity, the increase in ALD-related mortality was most pronounced in non-Hispanic White, non-Hispanic Black, and Alaska Native/American Indian populations, Dr. Yeo said. Alaska Natives and American Indians had the highest annual percentage change, at 18%, followed by non-Hispanic Whites at 11.7% and non-Hispanic Blacks at 10.8%. There were no significant differences in race and ethnicity for NAFLD-related deaths, although all groups had major increases in recent years.
 

Biggest rise in young adults

By age, the increase in ALD-related mortality was particularly severe for ages 25-44, with an annual percentage change of 34.6% in 2019-2021, as compared with 13.7% for ages 45-64 and 12.6% for ages 65 and older.

For NAFLD-related deaths, another major increase was observed among ages 25-44, with an annual percentage change of 28.1% for 2019-2021, as compared with 12% for ages 65 and older and 7.4% for ages 45-64.

By sex, the ASMR increase in NAFLD-related mortality was steady throughout 2010-2021 for both men and women. In contrast, ALD-related death increased sharply between 2019 and 2021, with an annual percentage change of 19.1% for women and 16.7% for men.

“The increasing trend in mortality rates for ALD and NAFLD has been quite alarming, with disparities in age, race, and ethnicity,” Dr. Yeo said.

The study received no funding support. Some authors disclosed research funding, advisory board roles, and consulting fees with various pharmaceutical companies.

U.S. mortality for alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased at “alarming” rates during the COVID-19 pandemic, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

Between 2019 and 2021, ALD-related deaths increased by 17.6% and NAFLD-related deaths increased by 14.5%, Yee Hui Yeo, MD, a resident physician and hepatology-focused investigator at Cedars-Sinai Medical Center in Los Angeles, said at a preconference press briefing.

“Even before the pandemic, the mortality rates for these two diseases have been increasing, with NAFLD having an even steeper increasing trend,” he said. “During the pandemic, these two diseases had a significant surge.”
 

Recent U.S. liver disease death rates

Dr. Yeo and colleagues analyzed data from the Center for Disease Control and Prevention’s National Vital Statistic System to estimate the age-standardized mortality rates (ASMR) of liver disease between 2010 and 2021, including ALD, NAFLD, hepatitis B, and hepatitis C. Using prediction modeling analyses based on trends from 2010 to 2019, they predicted mortality rates for 2020-2021 and compared them with the observed rates to quantify the differences related to the pandemic.

Between 2010 and 2021, there were about 626,000 chronic liver disease–related deaths, including about 343,000 ALD-related deaths, 204,000 hepatitis C–related deaths, 58,000 NAFLD-related deaths, and 21,000 hepatitis B–related deaths.

For ALD-related deaths, the annual percentage change was 3.5% for 2010-2019 and 17.6% for 2019-2021. The observed ASMR in 2020 was significantly higher than predicted, at 15.7 deaths per 100,000 people versus 13.0 predicted from the 2010-2019 rate. The trend continued in 2021, with 17.4 deaths per 100,000 people versus 13.4 in the previous decade.

The highest numbers of ALD-related deaths during the COVID-19 pandemic occurred in Alaska, Montana, Wyoming, Colorado, New Mexico, and South Dakota.

For NAFLD-related deaths, the annual percentage change was 7.6% for 2010-2014, 11.8% for 2014-2019, and 14.5% for 2019-2021. The observed ASMR was also higher than predicted, at 3.1 deaths per 100,000 people versus 2.6 in 2020, as well as 3.4 versus 2.8 in 2021.

The highest numbers of NAFLD-related deaths during the COVID-19 pandemic occurred in Oklahoma, Indiana, Kentucky, Tennessee, and West Virginia.
 

Hepatitis B and C gains lost in pandemic

In contrast, the annual percentage change in was –1.9% for hepatitis B and –2.8% for hepatitis C. After new treatment for hepatitis C emerged in 2013-2014, mortality rates were –7.8% for 2014-2019, Dr. Yeo noted.

“However, during the pandemic, we saw that this decrease has become a nonsignificant change,” he said. “That means our progress of the past 5 or 6 years has already stopped during the pandemic.”

By race and ethnicity, the increase in ALD-related mortality was most pronounced in non-Hispanic White, non-Hispanic Black, and Alaska Native/American Indian populations, Dr. Yeo said. Alaska Natives and American Indians had the highest annual percentage change, at 18%, followed by non-Hispanic Whites at 11.7% and non-Hispanic Blacks at 10.8%. There were no significant differences in race and ethnicity for NAFLD-related deaths, although all groups had major increases in recent years.
 

Biggest rise in young adults

By age, the increase in ALD-related mortality was particularly severe for ages 25-44, with an annual percentage change of 34.6% in 2019-2021, as compared with 13.7% for ages 45-64 and 12.6% for ages 65 and older.

For NAFLD-related deaths, another major increase was observed among ages 25-44, with an annual percentage change of 28.1% for 2019-2021, as compared with 12% for ages 65 and older and 7.4% for ages 45-64.

By sex, the ASMR increase in NAFLD-related mortality was steady throughout 2010-2021 for both men and women. In contrast, ALD-related death increased sharply between 2019 and 2021, with an annual percentage change of 19.1% for women and 16.7% for men.

“The increasing trend in mortality rates for ALD and NAFLD has been quite alarming, with disparities in age, race, and ethnicity,” Dr. Yeo said.

The study received no funding support. Some authors disclosed research funding, advisory board roles, and consulting fees with various pharmaceutical companies.

Monkeypox, though often mild, may be severe and even fatal in immunocompromised individuals, particularly those with untreated AIDS, according to a Centers for Disease Control and Prevention study in Morbidity and Mortality Weekly Report.

The study described a group of patients recently treated for severe monkeypox. The majority were Black, HIV positive, and not receiving treatment. Many were also facing homelessness.

The authors urged HIV testing for all sexually active individuals with suspected monkeypox. Early or prolonged monkeypox treatment may be necessary, they concluded.

Coauthor John T. Brooks, MD, called the study “a real call to action.”

“If we want to reduce cases of severe monkeypox, we need to reduce the number of persons with HIV who are undiagnosed and not treated,” said Dr. Brooks, a medical epidemiologist who is chief medical officer of CDC›s multinational monkeypox response. Dr. Brooks also leads the epidemiology research team in CDC’s division of HIV/AIDS prevention.

The article reflects long-existing health disparities, noted Richard Silvera, MD, MPH, CPH, who is associate program director of the infectious diseases fellowship and assistant professor of medicine (infectious diseases) at the Icahn School of Medicine at Mount Sinai, New York. He was not involved with the study.

“These patients really have not been served by the health care system,” Dr. Silvera said. “Monkeypox is just really taking advantage of that.”
 

How severe monkeypox can manifest

The authors reported on 57 adults hospitalized with severe monkeypox between Aug. 10 and Sept. 10, 2022, for whose care the providers sought CDC consultation.

The vast majority (95%) were men, their median age was 34 years, and 68% were Black. Nearly one in four were homeless (23%).

Overall, 47 (82%) were HIV positive, of whom just 4 had been receiving antiretroviral therapy (ART). Of 43 for whom CD4 counts were known, 71% had fewer than 50 CD4 cells/mm3.

Clinical signs included severe skin lesions in all patients and severe mucosal lesions in 68%. Other affected organ systems included lungs (21%), eyes (21%), and central nervous system (7%).

Treatments included oral or intravenous tecovirimat (93% and 65%, respectively), vaccinia immune globulin intravenous (VIGIV, 51%), and cidofovir (23%).

Nearly 1 in 3 patients (30%) received care in an ICU; 12 died (21%). Monkeypox was considered the cause or a contributing factor in five of the deaths and not a factor in one death; the remaining six deaths are under investigation.
 

Case studies

The report included details of three representative cases of the CDC consultations.

One was a Hispanic man in his 20s with a fever of 102.8° F, a rash including eschars, oral lesions, neck mass, and cervical lymphadenopathy. He had tested positive for monkeypox as an outpatient and upon admission was found to be HIV positive, with a CD4 count of 79 cells/mm³. He experienced a severe and ultimately fatal clinical course that included intubation, refractory hypotension, seizures, renal failure, and cardiac arrest. An autopsy revealed diffuse organ necrosis plus orthopoxvirus and cytomegalovirus.

The second was a Black man in his 30s with untreated AIDS and diffuse rash. He was tested and treated for gonorrhea, chlamydia, and syphilis before phimosis and urinary retention led to admission and a monkeypox diagnosis 4 weeks after his rash began. He was discharged with oral tecovirimat, but his skin lesions developed necrosis and he was readmitted twice, each time with new lesions. His clinical course included methicillin-resistant Staphylococcus aureus bacteremia, atrial fibrillation, eye and ear involvement, a suprapubic catheter, and progressive necrosis of his lesions. As of the CDC report, he was receiving ART and intravenous tecovirimat.

The third patient, a White man in his 40s with untreated AIDS, presented with diffuse rash. He was promptly diagnosed with monkeypox and admitted for pain control. He was discharged with oral tecovirimat and ART, but homelessness and food insecurity jeopardized the absorption of his tecovirimat (which depends on a full fatty meal), and the lesions worsened. Despite readmission and aggressive medical treatment, the patient required finger debridement and a toe amputation. After discharge, he was again readmitted for lesions and pain and, at report publication, remained hospitalized, taking oral tecovirimat and ART.

The patients in the study may not be typical of severe monkeypox cases, wrote the authors reported. Deaths after the study period were not counted.
 

Fewer cases, some severe

As of Nov. 7, the CDC has confirmed 28,709 monkeypox cases. These have trended downward since August. Most people with recent diagnoses are men who are gay, bisexual, same gender loving, or who have sex with men, and most are Black, according to Brooks.

Dr. Brooks urges clinicians to report suspected monkeypox cases – especially severe ones – to their health departments.

“We don’t have a good bead on exactly how many severe cases there are in the States because of complexities in our surveillance systems,” Dr. Brooks said.

For patients with suspected or confirmed monkeypox, Brooks recommends testing for sexually transmitted infections, including HIV if status is unknown. Patients with HIV should receive prompt ART. For those at risk for severe disease, the authors recommend early treatment for suspected monkeypox, even before results are back. Some patients may benefit from tecovirimat courses lasting beyond 14 days, plus additional antivirals (cidofovir or brincidofovir) and/or VIGIV.

“With severe cases, clinicians may want to consider the value of more than one drug to attack the virus at different stages of its replication cycle,” Dr. Brooks said.
 

Inequities matter

The authors called on providers to engage communities burdened by HIV and to ensure access to not only monkeypox vaccination, diagnosis, and treatment but also sustained HIV care.

Dr. Silvera added that providers need to tailor care plans to patients’ social determinants of health. For example, he explained, inpatient care for monkeypox could be appropriate for some patients facing homelessness and food insecurity – even if they are able to take tecovirimat orally.

He recommends tapping others’ expertise: “Our social work colleagues are well versed in this.”

“I don’t think these clinicians failed these patients. ... I think everyone made all the right choices medically,” Dr. Silvera added. “I think that the system failed these patients – and we as clinicians are part of those systems. So we also have the power to change those systems. And I think we just need to start opening our eyes to that and [start] to work together towards that goal to take better care of our patients.”

Dr. Brooks reported no relevant financial disclosures.

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

Monkeypox, though often mild, may be severe and even fatal in immunocompromised individuals, particularly those with untreated AIDS, according to a Centers for Disease Control and Prevention study in Morbidity and Mortality Weekly Report.

The study described a group of patients recently treated for severe monkeypox. The majority were Black, HIV positive, and not receiving treatment. Many were also facing homelessness.

The authors urged HIV testing for all sexually active individuals with suspected monkeypox. Early or prolonged monkeypox treatment may be necessary, they concluded.

Coauthor John T. Brooks, MD, called the study “a real call to action.”

“If we want to reduce cases of severe monkeypox, we need to reduce the number of persons with HIV who are undiagnosed and not treated,” said Dr. Brooks, a medical epidemiologist who is chief medical officer of CDC›s multinational monkeypox response. Dr. Brooks also leads the epidemiology research team in CDC’s division of HIV/AIDS prevention.

The article reflects long-existing health disparities, noted Richard Silvera, MD, MPH, CPH, who is associate program director of the infectious diseases fellowship and assistant professor of medicine (infectious diseases) at the Icahn School of Medicine at Mount Sinai, New York. He was not involved with the study.

“These patients really have not been served by the health care system,” Dr. Silvera said. “Monkeypox is just really taking advantage of that.”
 

How severe monkeypox can manifest

The authors reported on 57 adults hospitalized with severe monkeypox between Aug. 10 and Sept. 10, 2022, for whose care the providers sought CDC consultation.

The vast majority (95%) were men, their median age was 34 years, and 68% were Black. Nearly one in four were homeless (23%).

Overall, 47 (82%) were HIV positive, of whom just 4 had been receiving antiretroviral therapy (ART). Of 43 for whom CD4 counts were known, 71% had fewer than 50 CD4 cells/mm3.

Clinical signs included severe skin lesions in all patients and severe mucosal lesions in 68%. Other affected organ systems included lungs (21%), eyes (21%), and central nervous system (7%).

Treatments included oral or intravenous tecovirimat (93% and 65%, respectively), vaccinia immune globulin intravenous (VIGIV, 51%), and cidofovir (23%).

Nearly 1 in 3 patients (30%) received care in an ICU; 12 died (21%). Monkeypox was considered the cause or a contributing factor in five of the deaths and not a factor in one death; the remaining six deaths are under investigation.
 

Case studies

The report included details of three representative cases of the CDC consultations.

One was a Hispanic man in his 20s with a fever of 102.8° F, a rash including eschars, oral lesions, neck mass, and cervical lymphadenopathy. He had tested positive for monkeypox as an outpatient and upon admission was found to be HIV positive, with a CD4 count of 79 cells/mm³. He experienced a severe and ultimately fatal clinical course that included intubation, refractory hypotension, seizures, renal failure, and cardiac arrest. An autopsy revealed diffuse organ necrosis plus orthopoxvirus and cytomegalovirus.

The second was a Black man in his 30s with untreated AIDS and diffuse rash. He was tested and treated for gonorrhea, chlamydia, and syphilis before phimosis and urinary retention led to admission and a monkeypox diagnosis 4 weeks after his rash began. He was discharged with oral tecovirimat, but his skin lesions developed necrosis and he was readmitted twice, each time with new lesions. His clinical course included methicillin-resistant Staphylococcus aureus bacteremia, atrial fibrillation, eye and ear involvement, a suprapubic catheter, and progressive necrosis of his lesions. As of the CDC report, he was receiving ART and intravenous tecovirimat.

The third patient, a White man in his 40s with untreated AIDS, presented with diffuse rash. He was promptly diagnosed with monkeypox and admitted for pain control. He was discharged with oral tecovirimat and ART, but homelessness and food insecurity jeopardized the absorption of his tecovirimat (which depends on a full fatty meal), and the lesions worsened. Despite readmission and aggressive medical treatment, the patient required finger debridement and a toe amputation. After discharge, he was again readmitted for lesions and pain and, at report publication, remained hospitalized, taking oral tecovirimat and ART.

The patients in the study may not be typical of severe monkeypox cases, wrote the authors reported. Deaths after the study period were not counted.
 

Fewer cases, some severe

As of Nov. 7, the CDC has confirmed 28,709 monkeypox cases. These have trended downward since August. Most people with recent diagnoses are men who are gay, bisexual, same gender loving, or who have sex with men, and most are Black, according to Brooks.

Dr. Brooks urges clinicians to report suspected monkeypox cases – especially severe ones – to their health departments.

“We don’t have a good bead on exactly how many severe cases there are in the States because of complexities in our surveillance systems,” Dr. Brooks said.

For patients with suspected or confirmed monkeypox, Brooks recommends testing for sexually transmitted infections, including HIV if status is unknown. Patients with HIV should receive prompt ART. For those at risk for severe disease, the authors recommend early treatment for suspected monkeypox, even before results are back. Some patients may benefit from tecovirimat courses lasting beyond 14 days, plus additional antivirals (cidofovir or brincidofovir) and/or VIGIV.

“With severe cases, clinicians may want to consider the value of more than one drug to attack the virus at different stages of its replication cycle,” Dr. Brooks said.
 

Inequities matter

The authors called on providers to engage communities burdened by HIV and to ensure access to not only monkeypox vaccination, diagnosis, and treatment but also sustained HIV care.

Dr. Silvera added that providers need to tailor care plans to patients’ social determinants of health. For example, he explained, inpatient care for monkeypox could be appropriate for some patients facing homelessness and food insecurity – even if they are able to take tecovirimat orally.

He recommends tapping others’ expertise: “Our social work colleagues are well versed in this.”

“I don’t think these clinicians failed these patients. ... I think everyone made all the right choices medically,” Dr. Silvera added. “I think that the system failed these patients – and we as clinicians are part of those systems. So we also have the power to change those systems. And I think we just need to start opening our eyes to that and [start] to work together towards that goal to take better care of our patients.”

Dr. Brooks reported no relevant financial disclosures.

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

Monkeypox, though often mild, may be severe and even fatal in immunocompromised individuals, particularly those with untreated AIDS, according to a Centers for Disease Control and Prevention study in Morbidity and Mortality Weekly Report.

The study described a group of patients recently treated for severe monkeypox. The majority were Black, HIV positive, and not receiving treatment. Many were also facing homelessness.

The authors urged HIV testing for all sexually active individuals with suspected monkeypox. Early or prolonged monkeypox treatment may be necessary, they concluded.

Coauthor John T. Brooks, MD, called the study “a real call to action.”

“If we want to reduce cases of severe monkeypox, we need to reduce the number of persons with HIV who are undiagnosed and not treated,” said Dr. Brooks, a medical epidemiologist who is chief medical officer of CDC›s multinational monkeypox response. Dr. Brooks also leads the epidemiology research team in CDC’s division of HIV/AIDS prevention.

The article reflects long-existing health disparities, noted Richard Silvera, MD, MPH, CPH, who is associate program director of the infectious diseases fellowship and assistant professor of medicine (infectious diseases) at the Icahn School of Medicine at Mount Sinai, New York. He was not involved with the study.

“These patients really have not been served by the health care system,” Dr. Silvera said. “Monkeypox is just really taking advantage of that.”
 

How severe monkeypox can manifest

The authors reported on 57 adults hospitalized with severe monkeypox between Aug. 10 and Sept. 10, 2022, for whose care the providers sought CDC consultation.

The vast majority (95%) were men, their median age was 34 years, and 68% were Black. Nearly one in four were homeless (23%).

Overall, 47 (82%) were HIV positive, of whom just 4 had been receiving antiretroviral therapy (ART). Of 43 for whom CD4 counts were known, 71% had fewer than 50 CD4 cells/mm3.

Clinical signs included severe skin lesions in all patients and severe mucosal lesions in 68%. Other affected organ systems included lungs (21%), eyes (21%), and central nervous system (7%).

Treatments included oral or intravenous tecovirimat (93% and 65%, respectively), vaccinia immune globulin intravenous (VIGIV, 51%), and cidofovir (23%).

Nearly 1 in 3 patients (30%) received care in an ICU; 12 died (21%). Monkeypox was considered the cause or a contributing factor in five of the deaths and not a factor in one death; the remaining six deaths are under investigation.
 

Case studies

The report included details of three representative cases of the CDC consultations.

One was a Hispanic man in his 20s with a fever of 102.8° F, a rash including eschars, oral lesions, neck mass, and cervical lymphadenopathy. He had tested positive for monkeypox as an outpatient and upon admission was found to be HIV positive, with a CD4 count of 79 cells/mm³. He experienced a severe and ultimately fatal clinical course that included intubation, refractory hypotension, seizures, renal failure, and cardiac arrest. An autopsy revealed diffuse organ necrosis plus orthopoxvirus and cytomegalovirus.

The second was a Black man in his 30s with untreated AIDS and diffuse rash. He was tested and treated for gonorrhea, chlamydia, and syphilis before phimosis and urinary retention led to admission and a monkeypox diagnosis 4 weeks after his rash began. He was discharged with oral tecovirimat, but his skin lesions developed necrosis and he was readmitted twice, each time with new lesions. His clinical course included methicillin-resistant Staphylococcus aureus bacteremia, atrial fibrillation, eye and ear involvement, a suprapubic catheter, and progressive necrosis of his lesions. As of the CDC report, he was receiving ART and intravenous tecovirimat.

The third patient, a White man in his 40s with untreated AIDS, presented with diffuse rash. He was promptly diagnosed with monkeypox and admitted for pain control. He was discharged with oral tecovirimat and ART, but homelessness and food insecurity jeopardized the absorption of his tecovirimat (which depends on a full fatty meal), and the lesions worsened. Despite readmission and aggressive medical treatment, the patient required finger debridement and a toe amputation. After discharge, he was again readmitted for lesions and pain and, at report publication, remained hospitalized, taking oral tecovirimat and ART.

The patients in the study may not be typical of severe monkeypox cases, wrote the authors reported. Deaths after the study period were not counted.
 

Fewer cases, some severe

As of Nov. 7, the CDC has confirmed 28,709 monkeypox cases. These have trended downward since August. Most people with recent diagnoses are men who are gay, bisexual, same gender loving, or who have sex with men, and most are Black, according to Brooks.

Dr. Brooks urges clinicians to report suspected monkeypox cases – especially severe ones – to their health departments.

“We don’t have a good bead on exactly how many severe cases there are in the States because of complexities in our surveillance systems,” Dr. Brooks said.

For patients with suspected or confirmed monkeypox, Brooks recommends testing for sexually transmitted infections, including HIV if status is unknown. Patients with HIV should receive prompt ART. For those at risk for severe disease, the authors recommend early treatment for suspected monkeypox, even before results are back. Some patients may benefit from tecovirimat courses lasting beyond 14 days, plus additional antivirals (cidofovir or brincidofovir) and/or VIGIV.

“With severe cases, clinicians may want to consider the value of more than one drug to attack the virus at different stages of its replication cycle,” Dr. Brooks said.
 

Inequities matter

The authors called on providers to engage communities burdened by HIV and to ensure access to not only monkeypox vaccination, diagnosis, and treatment but also sustained HIV care.

Dr. Silvera added that providers need to tailor care plans to patients’ social determinants of health. For example, he explained, inpatient care for monkeypox could be appropriate for some patients facing homelessness and food insecurity – even if they are able to take tecovirimat orally.

He recommends tapping others’ expertise: “Our social work colleagues are well versed in this.”

“I don’t think these clinicians failed these patients. ... I think everyone made all the right choices medically,” Dr. Silvera added. “I think that the system failed these patients – and we as clinicians are part of those systems. So we also have the power to change those systems. And I think we just need to start opening our eyes to that and [start] to work together towards that goal to take better care of our patients.”

Dr. Brooks reported no relevant financial disclosures.

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

SAN DIEGO – Weight loss with tirzepatide was fairly uniform across different body mass index ranges, ages, and number of obesity-related comorbidities in patients with overweight/obesity without type 2 diabetes.

These were the main findings in a session about tirzepatide – the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist – for obesity, presented at the annual meeting of the Obesity Society.

In May, tirzepatide (Mounjaro), a once-weekly subcutaneous injection, was approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes based on the SURPASS clinical trials.

Then in June, at the American Diabetes Association 2022 annual meeting, researchers reported “unprecedented” weight loss with tirzepatide in patients without type 2 diabetes, in the phase 3 SURMOUNT-1 clinical trial.

In early October, the FDA granted fast track status (expedited review) to tirzepatide for use as an antiobesity drug.

Now these new analyses from SURMOUNT-1 show that “regardless of BMI, regardless of age, regardless of number of obesity-related complications, there was a clear dose-related weight loss that was pretty consistent across groups,” Session Chair Patrick M. O’Neil, PhD, who was not involved with this research, summarized.

“The absolute levels of these weight losses are higher than we’ve seen thus far with [antiobesity] medications,” added Dr. O’Neil, professor of psychiatry and behavioral sciences and director of the Weight Management Center at the Medical University of South Carolina, Charleston.

“Semaglutide took things up one big notch, and this is up a little notch above that,” he said in an interview.

“I’m a psychologist. It should be remembered that in all cases, the FDA approvals are predicated to using [drugs] as an adjunct to diet and exercise change as well,” he stressed.

“I don’t think people should expect that any medication that is currently available will have a lasting effect when it’s no longer taken,” he continued.

“We don’t expect any of these [antiobesity] medications to be making any permanent physiological changes,” Dr. O’Neil added, but patients could “use this medication to help themselves make some long-lasting behavioral changes, so that when they come off the medication, hopefully they’ll be able to continue these new patterns.

“Clearly the medications are having a significant impact,” he emphasized.
 

BMI, age, comorbidity subgroups, and overall QoL in SURMOUNT-1

SURMOUNT-1 compared the efficacy and safety of tirzepatide 5, 10, and 15 mg subcutaneous once-weekly to placebo, as an adjunct to a reduced-calorie diet and increased physical activity. The study included 2,539 adults without type 2 diabetes who had obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one obesity-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).

Age subgroups

Robert F. Kushner, MD, of Northwestern University, Chicago, noted that “Excessive lean mass loss is a clinical concern in elderly individuals being treated for obesity,” so it’s important to know if weight loss with tirzepatide differs by age.

The researchers performed a post hoc analysis in patients who had dual-energy x-ray absorptiometry (DXA) readings at baseline and week 72 (oral abstract 109).

The three age groups in the current analysis were < 50 years old (99 patients), ≥ 50 to < 65 years old (41 patients), and ≥ 65 years old (20 patients). Overall, 63% of patients were age < 50 years, 31% were age 50 to < 65 years, and 6% were ≥ 65 years.

At 72 weeks, patients taking 5, 10, and 15 mg/week tirzepatide lost 21.5%, 20.8%, and 22% of their initial body weight, respectively.

“Tirzepatide significantly lowered total body mass versus placebo regardless of age subgroups,” and it “consistently lowered fat mass, lean mass, fat-mass-to-lean-mass ratio, and visceral fat mass across age subgroups,” Dr. Kushner reported.
 

BMI subgroups

Louis J. Aronne, MD, Weill Cornell Medicine, New York, presented findings from a prespecified analysis of BMI subgroups (oral abstract 110).

The four BMI subgroups were:

• ≥ 27 to < 30 kg/m² (overweight), mean initial weight 178 pounds, mean weight reduction 29-30 pounds
• ≥ 30 to < 35 kg/m² (class 1 obesity), mean initial weight 198 pounds, mean weight reduction 33-43 pounds
• 35 to < 40 kg/m² (class 2 obesity), mean initial weight 228 pounds, mean reduction 34-56 pounds
• 40 kg/m² (class 3 obesity), mean initial weight 280 pounds, mean weight reduction 44-64 pounds

Patients with an initial BMI of ≥ 35 to < 40 kg/m² who received the 15-mg/week dose of tirzepatide had the greatest weight loss, at 24.5%, which is approximately what is seen with bariatric surgeries such as sleeve gastrectomy (25%).

The proportion of patients reaching ≥ 5% weight reduction was approximately 90% in all weight categories. “These numbers are unprecedented,” said Dr. Aronne.

In addition, overall, 73%-90% of patients receiving the 5- to 15-mg doses of tirzepatide achieved ≥ 10% body weight reduction, and “something we never thought we would see” is that 50%-78% of the patients receiving the drug lost 15% or more of their body weight.

In reply to an audience question, Dr. Aronne said it would take further study to determine who would respond well to tirzepatide.

And in reply to another question about whether it would make sense to treat to a target of a normal BMI, he said: “I think we are getting there.”

Patients in the 27- to 30-kg/m² BMI category lost about the same amount of weight at a 5-mg dose as at a higher dose, suggesting they should stick to the lower dose, which would likely also have fewer side effects, he noted.
 

Number of comorbidities

Comorbidities in SURMOUNT-1 included hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, osteoarthritis, anxiety/depression, polycystic ovary syndrome, nonalcoholic fatty liver disease, and asthma/chronic obstructive pulmonary disease. Of the patients with no comorbidities, 32.6% had prediabetes (oral abstract 111).

Sriram Machineni, MD, University of North Carolina at Chapel Hill, noted that obesity is associated with a significantly increased risk of clustering of at least two obesity-related complications, but little is known about how this affects outcomes. 

The patients in SURMOUNT-1 were classified into three groups based on number of comorbidities:

• Zero comorbidities, 37% of patients: baseline mean age of 39, mean duration of obesity of 12 years, 29% men
• One comorbidity, 27% of patients: baseline mean age of 44, mean duration of obesity of 14 years, 31% men
• Two or more comorbidities, 36% of patients: baseline mean age of 52, duration of obesity 17 years, 37% men

Regardless of the number of comorbidities, all doses of tirzepatide resulted in a greater reduction in body weight compared with placebo.
 

Quality of life

Jiat Ling Poon, MD, an employee of Eli Lilly, presented findings from patient-reported replies to questionnaires including Impact of Weight on Quality of Life–Lite (IWQOL-Lite), which assesses physical and psychosocial health, and the Short Form–36 Health Survey, which assesses physical functioning, bodily pain, vitality, role-emotional, role-physical, general health, social functioning, and mental health (oral abstract 112).

Tirzepatide at all doses resulted in significantly greater improvements in patient-reported outcomes compared with placebo.

Meanwhile, the phase 3 SURMOUNT-2 clinical trial of tirzepatide for weight loss in patients with type 2 diabetes is projected to be completed in April 2023.  

The studies were funded by Eli Lilly.

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


SAN DIEGO – Weight loss with tirzepatide was fairly uniform across different body mass index ranges, ages, and number of obesity-related comorbidities in patients with overweight/obesity without type 2 diabetes.

These were the main findings in a session about tirzepatide – the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist – for obesity, presented at the annual meeting of the Obesity Society.

In May, tirzepatide (Mounjaro), a once-weekly subcutaneous injection, was approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes based on the SURPASS clinical trials.

Then in June, at the American Diabetes Association 2022 annual meeting, researchers reported “unprecedented” weight loss with tirzepatide in patients without type 2 diabetes, in the phase 3 SURMOUNT-1 clinical trial.

In early October, the FDA granted fast track status (expedited review) to tirzepatide for use as an antiobesity drug.

Now these new analyses from SURMOUNT-1 show that “regardless of BMI, regardless of age, regardless of number of obesity-related complications, there was a clear dose-related weight loss that was pretty consistent across groups,” Session Chair Patrick M. O’Neil, PhD, who was not involved with this research, summarized.

“The absolute levels of these weight losses are higher than we’ve seen thus far with [antiobesity] medications,” added Dr. O’Neil, professor of psychiatry and behavioral sciences and director of the Weight Management Center at the Medical University of South Carolina, Charleston.

“Semaglutide took things up one big notch, and this is up a little notch above that,” he said in an interview.

“I’m a psychologist. It should be remembered that in all cases, the FDA approvals are predicated to using [drugs] as an adjunct to diet and exercise change as well,” he stressed.

“I don’t think people should expect that any medication that is currently available will have a lasting effect when it’s no longer taken,” he continued.

“We don’t expect any of these [antiobesity] medications to be making any permanent physiological changes,” Dr. O’Neil added, but patients could “use this medication to help themselves make some long-lasting behavioral changes, so that when they come off the medication, hopefully they’ll be able to continue these new patterns.

“Clearly the medications are having a significant impact,” he emphasized.
 

BMI, age, comorbidity subgroups, and overall QoL in SURMOUNT-1

SURMOUNT-1 compared the efficacy and safety of tirzepatide 5, 10, and 15 mg subcutaneous once-weekly to placebo, as an adjunct to a reduced-calorie diet and increased physical activity. The study included 2,539 adults without type 2 diabetes who had obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one obesity-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).

Age subgroups

Robert F. Kushner, MD, of Northwestern University, Chicago, noted that “Excessive lean mass loss is a clinical concern in elderly individuals being treated for obesity,” so it’s important to know if weight loss with tirzepatide differs by age.

The researchers performed a post hoc analysis in patients who had dual-energy x-ray absorptiometry (DXA) readings at baseline and week 72 (oral abstract 109).

The three age groups in the current analysis were < 50 years old (99 patients), ≥ 50 to < 65 years old (41 patients), and ≥ 65 years old (20 patients). Overall, 63% of patients were age < 50 years, 31% were age 50 to < 65 years, and 6% were ≥ 65 years.

At 72 weeks, patients taking 5, 10, and 15 mg/week tirzepatide lost 21.5%, 20.8%, and 22% of their initial body weight, respectively.

“Tirzepatide significantly lowered total body mass versus placebo regardless of age subgroups,” and it “consistently lowered fat mass, lean mass, fat-mass-to-lean-mass ratio, and visceral fat mass across age subgroups,” Dr. Kushner reported.
 

BMI subgroups

Louis J. Aronne, MD, Weill Cornell Medicine, New York, presented findings from a prespecified analysis of BMI subgroups (oral abstract 110).

The four BMI subgroups were:

• ≥ 27 to < 30 kg/m² (overweight), mean initial weight 178 pounds, mean weight reduction 29-30 pounds
• ≥ 30 to < 35 kg/m² (class 1 obesity), mean initial weight 198 pounds, mean weight reduction 33-43 pounds
• 35 to < 40 kg/m² (class 2 obesity), mean initial weight 228 pounds, mean reduction 34-56 pounds
• 40 kg/m² (class 3 obesity), mean initial weight 280 pounds, mean weight reduction 44-64 pounds

Patients with an initial BMI of ≥ 35 to < 40 kg/m² who received the 15-mg/week dose of tirzepatide had the greatest weight loss, at 24.5%, which is approximately what is seen with bariatric surgeries such as sleeve gastrectomy (25%).

The proportion of patients reaching ≥ 5% weight reduction was approximately 90% in all weight categories. “These numbers are unprecedented,” said Dr. Aronne.

In addition, overall, 73%-90% of patients receiving the 5- to 15-mg doses of tirzepatide achieved ≥ 10% body weight reduction, and “something we never thought we would see” is that 50%-78% of the patients receiving the drug lost 15% or more of their body weight.

In reply to an audience question, Dr. Aronne said it would take further study to determine who would respond well to tirzepatide.

And in reply to another question about whether it would make sense to treat to a target of a normal BMI, he said: “I think we are getting there.”

Patients in the 27- to 30-kg/m² BMI category lost about the same amount of weight at a 5-mg dose as at a higher dose, suggesting they should stick to the lower dose, which would likely also have fewer side effects, he noted.
 

Number of comorbidities

Comorbidities in SURMOUNT-1 included hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, osteoarthritis, anxiety/depression, polycystic ovary syndrome, nonalcoholic fatty liver disease, and asthma/chronic obstructive pulmonary disease. Of the patients with no comorbidities, 32.6% had prediabetes (oral abstract 111).

Sriram Machineni, MD, University of North Carolina at Chapel Hill, noted that obesity is associated with a significantly increased risk of clustering of at least two obesity-related complications, but little is known about how this affects outcomes. 

The patients in SURMOUNT-1 were classified into three groups based on number of comorbidities:

• Zero comorbidities, 37% of patients: baseline mean age of 39, mean duration of obesity of 12 years, 29% men
• One comorbidity, 27% of patients: baseline mean age of 44, mean duration of obesity of 14 years, 31% men
• Two or more comorbidities, 36% of patients: baseline mean age of 52, duration of obesity 17 years, 37% men

Regardless of the number of comorbidities, all doses of tirzepatide resulted in a greater reduction in body weight compared with placebo.
 

Quality of life

Jiat Ling Poon, MD, an employee of Eli Lilly, presented findings from patient-reported replies to questionnaires including Impact of Weight on Quality of Life–Lite (IWQOL-Lite), which assesses physical and psychosocial health, and the Short Form–36 Health Survey, which assesses physical functioning, bodily pain, vitality, role-emotional, role-physical, general health, social functioning, and mental health (oral abstract 112).

Tirzepatide at all doses resulted in significantly greater improvements in patient-reported outcomes compared with placebo.

Meanwhile, the phase 3 SURMOUNT-2 clinical trial of tirzepatide for weight loss in patients with type 2 diabetes is projected to be completed in April 2023.  

The studies were funded by Eli Lilly.

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


SAN DIEGO – Weight loss with tirzepatide was fairly uniform across different body mass index ranges, ages, and number of obesity-related comorbidities in patients with overweight/obesity without type 2 diabetes.

These were the main findings in a session about tirzepatide – the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist – for obesity, presented at the annual meeting of the Obesity Society.

In May, tirzepatide (Mounjaro), a once-weekly subcutaneous injection, was approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes based on the SURPASS clinical trials.

Then in June, at the American Diabetes Association 2022 annual meeting, researchers reported “unprecedented” weight loss with tirzepatide in patients without type 2 diabetes, in the phase 3 SURMOUNT-1 clinical trial.

In early October, the FDA granted fast track status (expedited review) to tirzepatide for use as an antiobesity drug.

Now these new analyses from SURMOUNT-1 show that “regardless of BMI, regardless of age, regardless of number of obesity-related complications, there was a clear dose-related weight loss that was pretty consistent across groups,” Session Chair Patrick M. O’Neil, PhD, who was not involved with this research, summarized.

“The absolute levels of these weight losses are higher than we’ve seen thus far with [antiobesity] medications,” added Dr. O’Neil, professor of psychiatry and behavioral sciences and director of the Weight Management Center at the Medical University of South Carolina, Charleston.

“Semaglutide took things up one big notch, and this is up a little notch above that,” he said in an interview.

“I’m a psychologist. It should be remembered that in all cases, the FDA approvals are predicated to using [drugs] as an adjunct to diet and exercise change as well,” he stressed.

“I don’t think people should expect that any medication that is currently available will have a lasting effect when it’s no longer taken,” he continued.

“We don’t expect any of these [antiobesity] medications to be making any permanent physiological changes,” Dr. O’Neil added, but patients could “use this medication to help themselves make some long-lasting behavioral changes, so that when they come off the medication, hopefully they’ll be able to continue these new patterns.

“Clearly the medications are having a significant impact,” he emphasized.
 

BMI, age, comorbidity subgroups, and overall QoL in SURMOUNT-1

SURMOUNT-1 compared the efficacy and safety of tirzepatide 5, 10, and 15 mg subcutaneous once-weekly to placebo, as an adjunct to a reduced-calorie diet and increased physical activity. The study included 2,539 adults without type 2 diabetes who had obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one obesity-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).

Age subgroups

Robert F. Kushner, MD, of Northwestern University, Chicago, noted that “Excessive lean mass loss is a clinical concern in elderly individuals being treated for obesity,” so it’s important to know if weight loss with tirzepatide differs by age.

The researchers performed a post hoc analysis in patients who had dual-energy x-ray absorptiometry (DXA) readings at baseline and week 72 (oral abstract 109).

The three age groups in the current analysis were < 50 years old (99 patients), ≥ 50 to < 65 years old (41 patients), and ≥ 65 years old (20 patients). Overall, 63% of patients were age < 50 years, 31% were age 50 to < 65 years, and 6% were ≥ 65 years.

At 72 weeks, patients taking 5, 10, and 15 mg/week tirzepatide lost 21.5%, 20.8%, and 22% of their initial body weight, respectively.

“Tirzepatide significantly lowered total body mass versus placebo regardless of age subgroups,” and it “consistently lowered fat mass, lean mass, fat-mass-to-lean-mass ratio, and visceral fat mass across age subgroups,” Dr. Kushner reported.
 

BMI subgroups

Louis J. Aronne, MD, Weill Cornell Medicine, New York, presented findings from a prespecified analysis of BMI subgroups (oral abstract 110).

The four BMI subgroups were:

• ≥ 27 to < 30 kg/m² (overweight), mean initial weight 178 pounds, mean weight reduction 29-30 pounds
• ≥ 30 to < 35 kg/m² (class 1 obesity), mean initial weight 198 pounds, mean weight reduction 33-43 pounds
• 35 to < 40 kg/m² (class 2 obesity), mean initial weight 228 pounds, mean reduction 34-56 pounds
• 40 kg/m² (class 3 obesity), mean initial weight 280 pounds, mean weight reduction 44-64 pounds

Patients with an initial BMI of ≥ 35 to < 40 kg/m² who received the 15-mg/week dose of tirzepatide had the greatest weight loss, at 24.5%, which is approximately what is seen with bariatric surgeries such as sleeve gastrectomy (25%).

The proportion of patients reaching ≥ 5% weight reduction was approximately 90% in all weight categories. “These numbers are unprecedented,” said Dr. Aronne.

In addition, overall, 73%-90% of patients receiving the 5- to 15-mg doses of tirzepatide achieved ≥ 10% body weight reduction, and “something we never thought we would see” is that 50%-78% of the patients receiving the drug lost 15% or more of their body weight.

In reply to an audience question, Dr. Aronne said it would take further study to determine who would respond well to tirzepatide.

And in reply to another question about whether it would make sense to treat to a target of a normal BMI, he said: “I think we are getting there.”

Patients in the 27- to 30-kg/m² BMI category lost about the same amount of weight at a 5-mg dose as at a higher dose, suggesting they should stick to the lower dose, which would likely also have fewer side effects, he noted.
 

Number of comorbidities

Comorbidities in SURMOUNT-1 included hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, osteoarthritis, anxiety/depression, polycystic ovary syndrome, nonalcoholic fatty liver disease, and asthma/chronic obstructive pulmonary disease. Of the patients with no comorbidities, 32.6% had prediabetes (oral abstract 111).

Sriram Machineni, MD, University of North Carolina at Chapel Hill, noted that obesity is associated with a significantly increased risk of clustering of at least two obesity-related complications, but little is known about how this affects outcomes. 

The patients in SURMOUNT-1 were classified into three groups based on number of comorbidities:

• Zero comorbidities, 37% of patients: baseline mean age of 39, mean duration of obesity of 12 years, 29% men
• One comorbidity, 27% of patients: baseline mean age of 44, mean duration of obesity of 14 years, 31% men
• Two or more comorbidities, 36% of patients: baseline mean age of 52, duration of obesity 17 years, 37% men

Regardless of the number of comorbidities, all doses of tirzepatide resulted in a greater reduction in body weight compared with placebo.
 

Quality of life

Jiat Ling Poon, MD, an employee of Eli Lilly, presented findings from patient-reported replies to questionnaires including Impact of Weight on Quality of Life–Lite (IWQOL-Lite), which assesses physical and psychosocial health, and the Short Form–36 Health Survey, which assesses physical functioning, bodily pain, vitality, role-emotional, role-physical, general health, social functioning, and mental health (oral abstract 112).

Tirzepatide at all doses resulted in significantly greater improvements in patient-reported outcomes compared with placebo.

Meanwhile, the phase 3 SURMOUNT-2 clinical trial of tirzepatide for weight loss in patients with type 2 diabetes is projected to be completed in April 2023.  

The studies were funded by Eli Lilly.

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