Pharmacology

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

Researchers running the EMPA-KIDNEY trial that’s been testing the safety and efficacy of the SGLT2 inhibitor empagliflozin (Jardiance) in about 6,600 patients with chronic kidney disease (CKD) announced on March 16 that they had stopped the trial early because of positive efficacy that met the study’s prespecified threshold for early termination.

EMPA-KIDNEY is the third major trial of an agent from the sodium-glucose cotransport 2 (SGLT2) inhibitor class tested in patients with CKD to be stopped early because of positive results that met a prespecified termination rule.

HYWARDS/Getty Images

EMPA-KIDNEY enrolled a wider range of patients

EMPA-KIDNEY expands the scope of types of patients with CKD now shown to benefit from treatment with an SGLT2 inhibitor. CREDENCE tested canagliflozin only in patients with type 2 diabetes and diabetic nephropathy, and in DAPA-CKD, two-thirds of enrolled patients had type 2 diabetes, and all had CKD. In EMPA-KIDNEY, 46% of the 6,609 enrolled patients had diabetes (including a very small number with type 1 diabetes).

Another departure from prior studies of an SGLT2 inhibitor for patients selected primarily for having CKD was that in EMPA-KIDNEY, 20% of patients did not have albuminuria, and for 34%, eGFR at entry was less than 30 mL/min/1.73 m², with all enrolled patients required to have an eGFR at entry of greater than or equal to 20 mL/min/1.73 m². Average eGFR in EMPA-KIDNEY was about 38 mL/min/1.73 m². To be included in the trial, patients were not required to have albuminuria, except those whose eGFR was greater than or equal to 45 mL/min/1.73 m².

In DAPA-CKD, the minimum eGFR at entry had to be greater than or equal to 25 mL/min/1.73 m², and roughly 14% of enrolled patients had an eGFR of less than 30 mL/min/1.73 m². The average eGFR in DAPA-CKD was about 43 mL/min/1.73 m². In addition, all patients had at least microalbuminuria, with a minimum urinary albumin-to-creatinine ratio of 200. In CREDENCE, the minimum eGFR for enrollment was 30 mL/min/1.73 m², and the average eGFR was about 56 mL/min/1.73 m². All patients in CREDENCE had to have macroalbuminuria, with a urinary albumin-to-creatinine ratio of more than 300.

According to the researchers who designed EMPA-KIDNEY, the trial enrollment criteria aimed to include adults with CKD “who are frequently seen in practice but were under-represented in previous SGLT2 inhibitor trials.”

Indications for empagliflozin are expanding

The success of empagliflozin in EMPA-KIDNEY follows its positive results in both the EMPEROR-Reduced and EMPEROR-Preserved trials, which collectively proved the efficacy of the agent for patients with heart failure regardless of their left ventricular ejection fraction and regardless of whether they also had diabetes.

These results led the U.S. Food and Drug Administration to recently expand the labeled indication for empagliflozin to all patients with heart failure. Empagliflozin also has labeled indications for glycemic control in patients with type 2 diabetes and to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease.

As of today, empagliflozin has no labeled indication for treating patients with CKD. Dapagliflozin received that indication in April 2021, and canagliflozin received an indication for treating patients with type 2 diabetes, diabetic nephropathy, and albuminuria in September 2019.

EMPA-KIDNEY is sponsored by Boehringer Ingelheim and Lilly, the two companies that jointly market empagliflozin (Jardiance).

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

Older adults are more susceptible to adverse drug reactions because of changes in physiology, clearance, and reserves. Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.^1-3

Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
 

Geriatric assessment and chemotherapy-related toxic effects

A cluster randomized trial¹ at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.

The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.

The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
 

Geriatric assessment in community oncology practices

A recent study by Supriya G. Mohile, MD, and colleagues² is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.

The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
 

Geriatric assessment and oncologist-patient communication

A secondary analysis³ of data from Dr. Mohile and colleagues² evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.

In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.

Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.

References

1. Li D et al. JAMA Oncol. 2021;7:e214158.

2. Mohile SG et al. Lancet. 2021;398:1894-1904.

3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.

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

Older adults are more susceptible to adverse drug reactions because of changes in physiology, clearance, and reserves. Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.^1-3

Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
 

Geriatric assessment and chemotherapy-related toxic effects

A cluster randomized trial¹ at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.

The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.

The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
 

Geriatric assessment in community oncology practices

A recent study by Supriya G. Mohile, MD, and colleagues² is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.

The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
 

Geriatric assessment and oncologist-patient communication

A secondary analysis³ of data from Dr. Mohile and colleagues² evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.

In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.

Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.

References

1. Li D et al. JAMA Oncol. 2021;7:e214158.

2. Mohile SG et al. Lancet. 2021;398:1894-1904.

3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.

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

Older adults are more susceptible to adverse drug reactions because of changes in physiology, clearance, and reserves. Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.^1-3

Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
 

Geriatric assessment and chemotherapy-related toxic effects

A cluster randomized trial¹ at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.

The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.

The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
 

Geriatric assessment in community oncology practices

A recent study by Supriya G. Mohile, MD, and colleagues² is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.

The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
 

Geriatric assessment and oncologist-patient communication

A secondary analysis³ of data from Dr. Mohile and colleagues² evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.

In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.

Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.

References

1. Li D et al. JAMA Oncol. 2021;7:e214158.

2. Mohile SG et al. Lancet. 2021;398:1894-1904.

3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.

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

The Food and Drug Administration has approved donepezil transdermal system (Adlarity) for patients with mild, moderate, or severe Alzheimer’s disease, the manufacturer has announced.

Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.

Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.

“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.

“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.

The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

The company expects the donepezil transdermal patch to be available in early Fall 2022.

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

The Food and Drug Administration has approved donepezil transdermal system (Adlarity) for patients with mild, moderate, or severe Alzheimer’s disease, the manufacturer has announced.

Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.

Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.

“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.

“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.

The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

The company expects the donepezil transdermal patch to be available in early Fall 2022.

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

The Food and Drug Administration has approved donepezil transdermal system (Adlarity) for patients with mild, moderate, or severe Alzheimer’s disease, the manufacturer has announced.

Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.

Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.

“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.

“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.

The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

The company expects the donepezil transdermal patch to be available in early Fall 2022.

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

The PARP inhibitor olaparib (Lynparza) is now approved by the U.S. Food and Drug Administration for use in early-stage breast cancer and later-stage disease. Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.

The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.

The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.

Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.

The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.

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

The PARP inhibitor olaparib (Lynparza) is now approved by the U.S. Food and Drug Administration for use in early-stage breast cancer and later-stage disease. Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.

The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.

The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.

Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.

The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.

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

The PARP inhibitor olaparib (Lynparza) is now approved by the U.S. Food and Drug Administration for use in early-stage breast cancer and later-stage disease. Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.

The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.

The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.

Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.

The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.

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

Green tea extract (GTE) does not appear to protect against colorectal adenoma recurrence, according to a study from Germany.

Preclinical, epidemiologic, and small clinical studies have suggested that GTE and its major active component, epigallocatechin gallate (EGCG), have antineoplastic effects in the colon and rectum.

But the new study found no statistically significant difference in adenoma recurrence in people who took GTE, standardized to 150 mg EGCG, twice daily for 3 years, relative to those who took matching placebo.

However, there was a suggestion of possible benefit in men but not women, which requires further study, Thomas Seufferlein, MD, with Ulm University Hospital, Baden-Württemberg, Germany, and colleagues write.

Their study was published online in The American Journal of Gastroenterology.
 

Largest trial to date

The MIRACLE trial (Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract) included 879 adults aged 50-80 years. Participants had undergone removal of one or more histologically confirmed colorectal adenomas within 6 months prior to recruitment during colonoscopy, and there were no remaining colorectal adenomas.

There were 432 patients in the GTE group and 447 in the placebo group. Baseline characteristics were well balanced between the groups, and overall adherence to the study protocol was good.

After 3 years, adenomas were detected in 55.7% of participants in the placebo group and in 51.1% of those in the GTE group in the modified intention-to-treat population. This absolute difference of 4.6% in favor of GTE was not statistically significant.

The per protocol analysis also did not show a significant effect of GTE on new adenoma formation in the whole study population.

However, a preplanned subgroup analysis revealed a significant difference in the adenoma recurrence rate in favor of GTE in men but not women.

In men, GTE intake was associated with a significant 12.4% relative and 7.5% absolute reduction of metachronous adenomas, they report.

This potential gender-specific difference in chemoprevention “warrants further investigations,” the study team writes.

The safety profile of GTE as taken in this trial was good, with only grade 1/2 elevations in liver enzymes in the GTE group, compared with the placebo group. However, because the follow-up period was limited to 3 years, the long-term safety of GTE cannot be determined.

The researchers write that, to their knowledge, this study is the largest randomized trial to date of the effect of GTE on adenoma recurrence in a colorectal cancer screening population consisting of White patients.
 

Caveats and cautionary notes

Reached for comment, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, noted that “although the study showed no significant differences, the time horizon to show benefit may be longer than the 3-year duration of the study.”

“There are also methodologic issues with the readjustment of the target sample size, which may have led to a type II error, related to underpowering of the sample size,” said Dr. Johnson, who wasn’t involved in the study.

The researchers write that the study initially generated “great interest” and that many centers applied to participate. However, “quite a few” centers did not meet their promised recruitment targets and had to be replaced. Therefore, the statistical analysis plan had to be modified, and the number of participants had to be reduced over the course of the trial, they note.

Dr. Johnson also cautioned that while green tea is a popular drink, “there is strong evidence that green tea extract, found in many herbal and dietary supplements, is among the leading causes listed for drug-induced liver injury, including acute liver failure, urgent liver transplantation, and death.”

The study was fully funded by a grant from German Cancer Aid. The investigators and Dr. Johnson report no relevant financial relationships.

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

Green tea extract (GTE) does not appear to protect against colorectal adenoma recurrence, according to a study from Germany.

Preclinical, epidemiologic, and small clinical studies have suggested that GTE and its major active component, epigallocatechin gallate (EGCG), have antineoplastic effects in the colon and rectum.

But the new study found no statistically significant difference in adenoma recurrence in people who took GTE, standardized to 150 mg EGCG, twice daily for 3 years, relative to those who took matching placebo.

However, there was a suggestion of possible benefit in men but not women, which requires further study, Thomas Seufferlein, MD, with Ulm University Hospital, Baden-Württemberg, Germany, and colleagues write.

Their study was published online in The American Journal of Gastroenterology.
 

Largest trial to date

The MIRACLE trial (Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract) included 879 adults aged 50-80 years. Participants had undergone removal of one or more histologically confirmed colorectal adenomas within 6 months prior to recruitment during colonoscopy, and there were no remaining colorectal adenomas.

There were 432 patients in the GTE group and 447 in the placebo group. Baseline characteristics were well balanced between the groups, and overall adherence to the study protocol was good.

After 3 years, adenomas were detected in 55.7% of participants in the placebo group and in 51.1% of those in the GTE group in the modified intention-to-treat population. This absolute difference of 4.6% in favor of GTE was not statistically significant.

The per protocol analysis also did not show a significant effect of GTE on new adenoma formation in the whole study population.

However, a preplanned subgroup analysis revealed a significant difference in the adenoma recurrence rate in favor of GTE in men but not women.

In men, GTE intake was associated with a significant 12.4% relative and 7.5% absolute reduction of metachronous adenomas, they report.

This potential gender-specific difference in chemoprevention “warrants further investigations,” the study team writes.

The safety profile of GTE as taken in this trial was good, with only grade 1/2 elevations in liver enzymes in the GTE group, compared with the placebo group. However, because the follow-up period was limited to 3 years, the long-term safety of GTE cannot be determined.

The researchers write that, to their knowledge, this study is the largest randomized trial to date of the effect of GTE on adenoma recurrence in a colorectal cancer screening population consisting of White patients.
 

Caveats and cautionary notes

Reached for comment, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, noted that “although the study showed no significant differences, the time horizon to show benefit may be longer than the 3-year duration of the study.”

“There are also methodologic issues with the readjustment of the target sample size, which may have led to a type II error, related to underpowering of the sample size,” said Dr. Johnson, who wasn’t involved in the study.

The researchers write that the study initially generated “great interest” and that many centers applied to participate. However, “quite a few” centers did not meet their promised recruitment targets and had to be replaced. Therefore, the statistical analysis plan had to be modified, and the number of participants had to be reduced over the course of the trial, they note.

Dr. Johnson also cautioned that while green tea is a popular drink, “there is strong evidence that green tea extract, found in many herbal and dietary supplements, is among the leading causes listed for drug-induced liver injury, including acute liver failure, urgent liver transplantation, and death.”

The study was fully funded by a grant from German Cancer Aid. The investigators and Dr. Johnson report no relevant financial relationships.

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

Green tea extract (GTE) does not appear to protect against colorectal adenoma recurrence, according to a study from Germany.

Preclinical, epidemiologic, and small clinical studies have suggested that GTE and its major active component, epigallocatechin gallate (EGCG), have antineoplastic effects in the colon and rectum.

But the new study found no statistically significant difference in adenoma recurrence in people who took GTE, standardized to 150 mg EGCG, twice daily for 3 years, relative to those who took matching placebo.

However, there was a suggestion of possible benefit in men but not women, which requires further study, Thomas Seufferlein, MD, with Ulm University Hospital, Baden-Württemberg, Germany, and colleagues write.

Their study was published online in The American Journal of Gastroenterology.
 

Largest trial to date

The MIRACLE trial (Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract) included 879 adults aged 50-80 years. Participants had undergone removal of one or more histologically confirmed colorectal adenomas within 6 months prior to recruitment during colonoscopy, and there were no remaining colorectal adenomas.

There were 432 patients in the GTE group and 447 in the placebo group. Baseline characteristics were well balanced between the groups, and overall adherence to the study protocol was good.

After 3 years, adenomas were detected in 55.7% of participants in the placebo group and in 51.1% of those in the GTE group in the modified intention-to-treat population. This absolute difference of 4.6% in favor of GTE was not statistically significant.

The per protocol analysis also did not show a significant effect of GTE on new adenoma formation in the whole study population.

However, a preplanned subgroup analysis revealed a significant difference in the adenoma recurrence rate in favor of GTE in men but not women.

In men, GTE intake was associated with a significant 12.4% relative and 7.5% absolute reduction of metachronous adenomas, they report.

This potential gender-specific difference in chemoprevention “warrants further investigations,” the study team writes.

The safety profile of GTE as taken in this trial was good, with only grade 1/2 elevations in liver enzymes in the GTE group, compared with the placebo group. However, because the follow-up period was limited to 3 years, the long-term safety of GTE cannot be determined.

The researchers write that, to their knowledge, this study is the largest randomized trial to date of the effect of GTE on adenoma recurrence in a colorectal cancer screening population consisting of White patients.
 

Caveats and cautionary notes

Reached for comment, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, noted that “although the study showed no significant differences, the time horizon to show benefit may be longer than the 3-year duration of the study.”

“There are also methodologic issues with the readjustment of the target sample size, which may have led to a type II error, related to underpowering of the sample size,” said Dr. Johnson, who wasn’t involved in the study.

The researchers write that the study initially generated “great interest” and that many centers applied to participate. However, “quite a few” centers did not meet their promised recruitment targets and had to be replaced. Therefore, the statistical analysis plan had to be modified, and the number of participants had to be reduced over the course of the trial, they note.

Dr. Johnson also cautioned that while green tea is a popular drink, “there is strong evidence that green tea extract, found in many herbal and dietary supplements, is among the leading causes listed for drug-induced liver injury, including acute liver failure, urgent liver transplantation, and death.”

The study was fully funded by a grant from German Cancer Aid. The investigators and Dr. Johnson report no relevant financial relationships.

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

Radiofrequency ablation (RFA) is effective and long lasting in preventing esophageal adenocarcinoma, new data suggest.

Researchers, led by Paul Wolfson, MBBS, from the Wellcome/EPSRC (Engineering and Physical Sciences Research Council) Centre for Interventional & Surgical Sciences, University College London also found that most treatment relapses happen early and can be re-treated successfully.

Findings were published in a final 10-year report from the United Kingdom National Halo Radiofrequency Ablation Registry and in Gastrointestinal Endoscopy. Because RFA has been used in mainstream clinical practice only since 2005, long-term data of more than 5 years has been lacking.

Multiple studies have shown that RFA is effective in preventing esophageal cancer, but data have been lacking on how long RFA is effective in preventing esophageal adenocarcinoma in patients with dysplastic Barrett’s esophagus (BE). A significant number of patients with dysplastic BE do not initially have visible lesions. For instance, the U.S. RFA Patient Registry reported an average 2.7-year follow up of 4,982 patients, but only 1,305 had dysplasia, the authors of the U.K. report note.

“It is well-established that endoscopic treatment of dysplastic BE is initially successful in up to 90% of patients,” the authors wrote. “What is less well understood is how long that benefit lasts and if this contributes to a substantial reduction in progression to cancer.”

Researchers prospectively gathered data from 2,535 patients from 28 U.K. specialist centers who underwent RFA therapy for BE (average length 5.2cm, range 1-20 cm). Among the group, 20% had low-grade dysplasia, 54% had high-grade dysplasia, and 26% had intramucosal carcinoma.

They looked at rates of invasive cancer and analyzed data for 1,175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA, then looked at relapses and rates of return to CR-D and CR-IM after more therapy.

One year after RFA therapy, the Kaplan Meier (KM) rate of invasive cancer in the 2,535 patients was 0.5%. Ten years after starting treatment, the KM cancer rate was 4.1%, with a crude incidence rate of 0.52 per 100 patient-years. After 2 years of RFA, CR-D was 88% and CR-IM was 62.6%.

At 8 years, the KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM. Most relapses happened in the first 2 years.

“Our study confirms durable reversal of dysplasia and BE with RFA, which reduces cancer risk by more than 90% compared to historical control data of 6-19% per annum,” the authors wrote.

Despite advances in diagnosis and treatment for esophageal adenocarcinoma, there has been only small improvement in 5-year survival over the past 40 years, the authors note. Meanwhile, the incidence of continues to rise in the Western world.
 

Researchers look for minimally invasive solutions

Surgery removing the esophagus and lymph node clearance had been the standard for high-grade dysplasia, the authors wrote. It is still the intervention of choice for patients with locoregional disease, but it comes with high morbidity and mortality rates.

This has spurred researchers to look for a minimally invasive solution focused on organ preservation to treat early disease and avoid surgical side effects but also to deliver a cure, according to the authors.

Shria Kumar, MD, assistant professor in the Division of Digestive and Liver Diseases at University of Miami Miller School of Medicine, told this publication, “Endoscopic ablation of dysplasia or intramucosal cancer is a mainstay of Barrett’s treatment.”

She noted the importance of the 10-year time period as the initial studies that established ablation evaluated outcomes within 1-3 years, and more recent data shows 5-year favorable outcomes.

Citing a study from the New England Journal of Medicine, Dr. Kumar said, “The present study’s cohort developed cancer at rates similar to one of the earlier U.S.-based cohorts of Barrett’s patients, suggesting that we can draw some parallels.”

She pointed out notable characteristics in the U.K. cohort: “The majority of participants were male and Caucasian; 80% of had high-grade dysplasia or early cancer upon enrollment and long-segment Barrett’s.”

That difference is important when thinking about how this applies to a more diverse U.S. population, she said, or even patients who don’t have high-grade dysplasia or early cancer when they enroll.

“It’s also important to point out are that individuals with low-grade dysplasia were included in this U.K.-based study. There has been evidence that persons in Europe with low-grade dysplasia have higher rates of progression than persons in the U.S. with low-grade dysplasia.”

Dr. Kumar said this may be attributable to differences in the way pathologists practice in the two countries or in endoscopists’ treatment patterns. U.S. guidelines agree that ablation can be used in select persons with low-grade dysplasia, she said, but it’s an area that needs further study.

“Overall, though, this is a really important study of real-time data showing that ablation is impacting cancer rates in a positive way and that in select patients, we can really decrease the risk of invasive cancer by endoscopic eradication therapies,” Dr. Kumar said.

Two coauthors have received grants from Medtronic and Pentax Medical. The other authors have declared no relevant financial relationships. Dr. Kumar reports no relevant financial relationships.

Radiofrequency ablation (RFA) is effective and long lasting in preventing esophageal adenocarcinoma, new data suggest.

Researchers, led by Paul Wolfson, MBBS, from the Wellcome/EPSRC (Engineering and Physical Sciences Research Council) Centre for Interventional & Surgical Sciences, University College London also found that most treatment relapses happen early and can be re-treated successfully.

Findings were published in a final 10-year report from the United Kingdom National Halo Radiofrequency Ablation Registry and in Gastrointestinal Endoscopy. Because RFA has been used in mainstream clinical practice only since 2005, long-term data of more than 5 years has been lacking.

Multiple studies have shown that RFA is effective in preventing esophageal cancer, but data have been lacking on how long RFA is effective in preventing esophageal adenocarcinoma in patients with dysplastic Barrett’s esophagus (BE). A significant number of patients with dysplastic BE do not initially have visible lesions. For instance, the U.S. RFA Patient Registry reported an average 2.7-year follow up of 4,982 patients, but only 1,305 had dysplasia, the authors of the U.K. report note.

“It is well-established that endoscopic treatment of dysplastic BE is initially successful in up to 90% of patients,” the authors wrote. “What is less well understood is how long that benefit lasts and if this contributes to a substantial reduction in progression to cancer.”

Researchers prospectively gathered data from 2,535 patients from 28 U.K. specialist centers who underwent RFA therapy for BE (average length 5.2cm, range 1-20 cm). Among the group, 20% had low-grade dysplasia, 54% had high-grade dysplasia, and 26% had intramucosal carcinoma.

They looked at rates of invasive cancer and analyzed data for 1,175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA, then looked at relapses and rates of return to CR-D and CR-IM after more therapy.

One year after RFA therapy, the Kaplan Meier (KM) rate of invasive cancer in the 2,535 patients was 0.5%. Ten years after starting treatment, the KM cancer rate was 4.1%, with a crude incidence rate of 0.52 per 100 patient-years. After 2 years of RFA, CR-D was 88% and CR-IM was 62.6%.

At 8 years, the KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM. Most relapses happened in the first 2 years.

“Our study confirms durable reversal of dysplasia and BE with RFA, which reduces cancer risk by more than 90% compared to historical control data of 6-19% per annum,” the authors wrote.

Despite advances in diagnosis and treatment for esophageal adenocarcinoma, there has been only small improvement in 5-year survival over the past 40 years, the authors note. Meanwhile, the incidence of continues to rise in the Western world.
 

Researchers look for minimally invasive solutions

Surgery removing the esophagus and lymph node clearance had been the standard for high-grade dysplasia, the authors wrote. It is still the intervention of choice for patients with locoregional disease, but it comes with high morbidity and mortality rates.

This has spurred researchers to look for a minimally invasive solution focused on organ preservation to treat early disease and avoid surgical side effects but also to deliver a cure, according to the authors.

Shria Kumar, MD, assistant professor in the Division of Digestive and Liver Diseases at University of Miami Miller School of Medicine, told this publication, “Endoscopic ablation of dysplasia or intramucosal cancer is a mainstay of Barrett’s treatment.”

She noted the importance of the 10-year time period as the initial studies that established ablation evaluated outcomes within 1-3 years, and more recent data shows 5-year favorable outcomes.

Citing a study from the New England Journal of Medicine, Dr. Kumar said, “The present study’s cohort developed cancer at rates similar to one of the earlier U.S.-based cohorts of Barrett’s patients, suggesting that we can draw some parallels.”

She pointed out notable characteristics in the U.K. cohort: “The majority of participants were male and Caucasian; 80% of had high-grade dysplasia or early cancer upon enrollment and long-segment Barrett’s.”

That difference is important when thinking about how this applies to a more diverse U.S. population, she said, or even patients who don’t have high-grade dysplasia or early cancer when they enroll.

“It’s also important to point out are that individuals with low-grade dysplasia were included in this U.K.-based study. There has been evidence that persons in Europe with low-grade dysplasia have higher rates of progression than persons in the U.S. with low-grade dysplasia.”

Dr. Kumar said this may be attributable to differences in the way pathologists practice in the two countries or in endoscopists’ treatment patterns. U.S. guidelines agree that ablation can be used in select persons with low-grade dysplasia, she said, but it’s an area that needs further study.

“Overall, though, this is a really important study of real-time data showing that ablation is impacting cancer rates in a positive way and that in select patients, we can really decrease the risk of invasive cancer by endoscopic eradication therapies,” Dr. Kumar said.

Two coauthors have received grants from Medtronic and Pentax Medical. The other authors have declared no relevant financial relationships. Dr. Kumar reports no relevant financial relationships.

Radiofrequency ablation (RFA) is effective and long lasting in preventing esophageal adenocarcinoma, new data suggest.

Researchers, led by Paul Wolfson, MBBS, from the Wellcome/EPSRC (Engineering and Physical Sciences Research Council) Centre for Interventional & Surgical Sciences, University College London also found that most treatment relapses happen early and can be re-treated successfully.

Findings were published in a final 10-year report from the United Kingdom National Halo Radiofrequency Ablation Registry and in Gastrointestinal Endoscopy. Because RFA has been used in mainstream clinical practice only since 2005, long-term data of more than 5 years has been lacking.

Multiple studies have shown that RFA is effective in preventing esophageal cancer, but data have been lacking on how long RFA is effective in preventing esophageal adenocarcinoma in patients with dysplastic Barrett’s esophagus (BE). A significant number of patients with dysplastic BE do not initially have visible lesions. For instance, the U.S. RFA Patient Registry reported an average 2.7-year follow up of 4,982 patients, but only 1,305 had dysplasia, the authors of the U.K. report note.

“It is well-established that endoscopic treatment of dysplastic BE is initially successful in up to 90% of patients,” the authors wrote. “What is less well understood is how long that benefit lasts and if this contributes to a substantial reduction in progression to cancer.”

Researchers prospectively gathered data from 2,535 patients from 28 U.K. specialist centers who underwent RFA therapy for BE (average length 5.2cm, range 1-20 cm). Among the group, 20% had low-grade dysplasia, 54% had high-grade dysplasia, and 26% had intramucosal carcinoma.

They looked at rates of invasive cancer and analyzed data for 1,175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA, then looked at relapses and rates of return to CR-D and CR-IM after more therapy.

One year after RFA therapy, the Kaplan Meier (KM) rate of invasive cancer in the 2,535 patients was 0.5%. Ten years after starting treatment, the KM cancer rate was 4.1%, with a crude incidence rate of 0.52 per 100 patient-years. After 2 years of RFA, CR-D was 88% and CR-IM was 62.6%.

At 8 years, the KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM. Most relapses happened in the first 2 years.

“Our study confirms durable reversal of dysplasia and BE with RFA, which reduces cancer risk by more than 90% compared to historical control data of 6-19% per annum,” the authors wrote.

Despite advances in diagnosis and treatment for esophageal adenocarcinoma, there has been only small improvement in 5-year survival over the past 40 years, the authors note. Meanwhile, the incidence of continues to rise in the Western world.
 

Researchers look for minimally invasive solutions

Surgery removing the esophagus and lymph node clearance had been the standard for high-grade dysplasia, the authors wrote. It is still the intervention of choice for patients with locoregional disease, but it comes with high morbidity and mortality rates.

This has spurred researchers to look for a minimally invasive solution focused on organ preservation to treat early disease and avoid surgical side effects but also to deliver a cure, according to the authors.

Shria Kumar, MD, assistant professor in the Division of Digestive and Liver Diseases at University of Miami Miller School of Medicine, told this publication, “Endoscopic ablation of dysplasia or intramucosal cancer is a mainstay of Barrett’s treatment.”

She noted the importance of the 10-year time period as the initial studies that established ablation evaluated outcomes within 1-3 years, and more recent data shows 5-year favorable outcomes.

Citing a study from the New England Journal of Medicine, Dr. Kumar said, “The present study’s cohort developed cancer at rates similar to one of the earlier U.S.-based cohorts of Barrett’s patients, suggesting that we can draw some parallels.”

She pointed out notable characteristics in the U.K. cohort: “The majority of participants were male and Caucasian; 80% of had high-grade dysplasia or early cancer upon enrollment and long-segment Barrett’s.”

That difference is important when thinking about how this applies to a more diverse U.S. population, she said, or even patients who don’t have high-grade dysplasia or early cancer when they enroll.

“It’s also important to point out are that individuals with low-grade dysplasia were included in this U.K.-based study. There has been evidence that persons in Europe with low-grade dysplasia have higher rates of progression than persons in the U.S. with low-grade dysplasia.”

Dr. Kumar said this may be attributable to differences in the way pathologists practice in the two countries or in endoscopists’ treatment patterns. U.S. guidelines agree that ablation can be used in select persons with low-grade dysplasia, she said, but it’s an area that needs further study.

“Overall, though, this is a really important study of real-time data showing that ablation is impacting cancer rates in a positive way and that in select patients, we can really decrease the risk of invasive cancer by endoscopic eradication therapies,” Dr. Kumar said.

Two coauthors have received grants from Medtronic and Pentax Medical. The other authors have declared no relevant financial relationships. Dr. Kumar reports no relevant financial relationships.

The U.S. Food and Drug Administration has approved a new contact lens that elutes the antihistamine ketotifen as a treatment for ocular allergy.

“This is the world’s first and only contact lens that’s able to prevent itching associated with allergies, while at the same time providing vision correction,” said Brian Pall, DO, director of clinical science at Johnson & Johnson Vision Care, which is making the lens. “It’s certainly exciting.”

The new lens, Acuvue Theravision With Ketotifenis, is already on the market in Canada and Japan.

The lenses are daily disposable contacts indicated for the prevention of ocular itch caused by allergic conjunctivitis in people who do not have red eyes, are suitable for wearing contact lenses, and do not have more than 1.00 D of astigmatism.

Antihistamine eyedrops are contraindicated for use with contact lenses because eyedrop preservatives could interact with the lenses, and clinical trials generally exclude contact lens wearers.

Johnson & Johnson worked for over a decade to find an antihistamine that paired well with a contact lens material, finally hitting on the combination of ketotifen and etafilcon A, said Pall. The drug is integrated into the polymer during manufacturing.

In contact with the eye, the drug diffuses from the lens into the tear film and is absorbed by the ocular tissues, much like a conventional eyedrop. “The key difference is that this is a slower release,” Dr. Pall said. “Instead of a bolus of this large drop hitting the eye and then being flushed out immediately, we get a much more sustained release.”

Because the lens is kept sterilized until use, no preservatives are added to the medication. This is an advantage because preservatives cause irritation in some patients.

Ketotifen, a well-established treatment for ocular allergies, not only blocks histamine receptors but also stabilizes mast cells so that they don’t release cytokines, and it prevents inflammatory cells from rushing to the site of irritation, Dr. Pall said.

For a pair of identical clinical trials, published in 2019 in Cornea, Dr. Pall and his colleagues recruited 244 people with ocular allergies. For each trial, they divided these subjects into three groups. One group wore the ketotifen lenses in one eye and lenses without the drug in the other eye. The second group wore the ketotifen lenses in both eyes. The third wore the control lenses in both eyes.

The researchers then exposed the subjects to allergens and asked them to rate the itchiness of their eyes on a scale of 0-4 after 3 minutes, 5 minutes, and 7 minutes. Over these periods, the patients rated itchiness of the eyes with the ketotifen contact lenses a mean from 0.42-0.59; they rated the eyes with the control contacts 1.60-1.94. The differences were statistically significant (P < .001).

While about 5% of patients experienced adverse events, most of the events were not judged to be related to the contact lenses. The most common adverse event, reported by about 1% of patients, was installation site irritation. “The good news, what we’re hearing from the field, is it’s very subtle, it’s pretty mild, and it quickly dissipates,” said Dr. Pall.

The new contact lens “is promising for those who have contact lenses and the 20%-40% of the American population who have allergies,” said Leonard Bielory, MD, a professor of medicine, allergy, immunology, and ophthalmology at Hackensack Meridian School of Medicine in Nutley, N.J., who was not involved in the trial or in developing the lens.

“I have patients who wear contacts and have allergies, and they have to work around it,” he said in an interview. “I expected this 15 years ago, because this is a good idea.”

Johnson & Johnson is researching other drugs that might be delivered through contact lenses, Dr. Pall said.

The study was funded by Johnson and Johnson. Dr. Pall is an employee of Johnson & Johnson. Dr. Bielory reported no relevant financial relationships.

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

The U.S. Food and Drug Administration has approved a new contact lens that elutes the antihistamine ketotifen as a treatment for ocular allergy.

“This is the world’s first and only contact lens that’s able to prevent itching associated with allergies, while at the same time providing vision correction,” said Brian Pall, DO, director of clinical science at Johnson & Johnson Vision Care, which is making the lens. “It’s certainly exciting.”

The new lens, Acuvue Theravision With Ketotifenis, is already on the market in Canada and Japan.

The lenses are daily disposable contacts indicated for the prevention of ocular itch caused by allergic conjunctivitis in people who do not have red eyes, are suitable for wearing contact lenses, and do not have more than 1.00 D of astigmatism.

Antihistamine eyedrops are contraindicated for use with contact lenses because eyedrop preservatives could interact with the lenses, and clinical trials generally exclude contact lens wearers.

Johnson & Johnson worked for over a decade to find an antihistamine that paired well with a contact lens material, finally hitting on the combination of ketotifen and etafilcon A, said Pall. The drug is integrated into the polymer during manufacturing.

In contact with the eye, the drug diffuses from the lens into the tear film and is absorbed by the ocular tissues, much like a conventional eyedrop. “The key difference is that this is a slower release,” Dr. Pall said. “Instead of a bolus of this large drop hitting the eye and then being flushed out immediately, we get a much more sustained release.”

Because the lens is kept sterilized until use, no preservatives are added to the medication. This is an advantage because preservatives cause irritation in some patients.

Ketotifen, a well-established treatment for ocular allergies, not only blocks histamine receptors but also stabilizes mast cells so that they don’t release cytokines, and it prevents inflammatory cells from rushing to the site of irritation, Dr. Pall said.

For a pair of identical clinical trials, published in 2019 in Cornea, Dr. Pall and his colleagues recruited 244 people with ocular allergies. For each trial, they divided these subjects into three groups. One group wore the ketotifen lenses in one eye and lenses without the drug in the other eye. The second group wore the ketotifen lenses in both eyes. The third wore the control lenses in both eyes.

The researchers then exposed the subjects to allergens and asked them to rate the itchiness of their eyes on a scale of 0-4 after 3 minutes, 5 minutes, and 7 minutes. Over these periods, the patients rated itchiness of the eyes with the ketotifen contact lenses a mean from 0.42-0.59; they rated the eyes with the control contacts 1.60-1.94. The differences were statistically significant (P < .001).

While about 5% of patients experienced adverse events, most of the events were not judged to be related to the contact lenses. The most common adverse event, reported by about 1% of patients, was installation site irritation. “The good news, what we’re hearing from the field, is it’s very subtle, it’s pretty mild, and it quickly dissipates,” said Dr. Pall.

The new contact lens “is promising for those who have contact lenses and the 20%-40% of the American population who have allergies,” said Leonard Bielory, MD, a professor of medicine, allergy, immunology, and ophthalmology at Hackensack Meridian School of Medicine in Nutley, N.J., who was not involved in the trial or in developing the lens.

“I have patients who wear contacts and have allergies, and they have to work around it,” he said in an interview. “I expected this 15 years ago, because this is a good idea.”

Johnson & Johnson is researching other drugs that might be delivered through contact lenses, Dr. Pall said.

The study was funded by Johnson and Johnson. Dr. Pall is an employee of Johnson & Johnson. Dr. Bielory reported no relevant financial relationships.

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

The U.S. Food and Drug Administration has approved a new contact lens that elutes the antihistamine ketotifen as a treatment for ocular allergy.

“This is the world’s first and only contact lens that’s able to prevent itching associated with allergies, while at the same time providing vision correction,” said Brian Pall, DO, director of clinical science at Johnson & Johnson Vision Care, which is making the lens. “It’s certainly exciting.”

The new lens, Acuvue Theravision With Ketotifenis, is already on the market in Canada and Japan.

The lenses are daily disposable contacts indicated for the prevention of ocular itch caused by allergic conjunctivitis in people who do not have red eyes, are suitable for wearing contact lenses, and do not have more than 1.00 D of astigmatism.

Antihistamine eyedrops are contraindicated for use with contact lenses because eyedrop preservatives could interact with the lenses, and clinical trials generally exclude contact lens wearers.

Johnson & Johnson worked for over a decade to find an antihistamine that paired well with a contact lens material, finally hitting on the combination of ketotifen and etafilcon A, said Pall. The drug is integrated into the polymer during manufacturing.

In contact with the eye, the drug diffuses from the lens into the tear film and is absorbed by the ocular tissues, much like a conventional eyedrop. “The key difference is that this is a slower release,” Dr. Pall said. “Instead of a bolus of this large drop hitting the eye and then being flushed out immediately, we get a much more sustained release.”

Because the lens is kept sterilized until use, no preservatives are added to the medication. This is an advantage because preservatives cause irritation in some patients.

Ketotifen, a well-established treatment for ocular allergies, not only blocks histamine receptors but also stabilizes mast cells so that they don’t release cytokines, and it prevents inflammatory cells from rushing to the site of irritation, Dr. Pall said.

For a pair of identical clinical trials, published in 2019 in Cornea, Dr. Pall and his colleagues recruited 244 people with ocular allergies. For each trial, they divided these subjects into three groups. One group wore the ketotifen lenses in one eye and lenses without the drug in the other eye. The second group wore the ketotifen lenses in both eyes. The third wore the control lenses in both eyes.

The researchers then exposed the subjects to allergens and asked them to rate the itchiness of their eyes on a scale of 0-4 after 3 minutes, 5 minutes, and 7 minutes. Over these periods, the patients rated itchiness of the eyes with the ketotifen contact lenses a mean from 0.42-0.59; they rated the eyes with the control contacts 1.60-1.94. The differences were statistically significant (P < .001).

While about 5% of patients experienced adverse events, most of the events were not judged to be related to the contact lenses. The most common adverse event, reported by about 1% of patients, was installation site irritation. “The good news, what we’re hearing from the field, is it’s very subtle, it’s pretty mild, and it quickly dissipates,” said Dr. Pall.

The new contact lens “is promising for those who have contact lenses and the 20%-40% of the American population who have allergies,” said Leonard Bielory, MD, a professor of medicine, allergy, immunology, and ophthalmology at Hackensack Meridian School of Medicine in Nutley, N.J., who was not involved in the trial or in developing the lens.

“I have patients who wear contacts and have allergies, and they have to work around it,” he said in an interview. “I expected this 15 years ago, because this is a good idea.”

Johnson & Johnson is researching other drugs that might be delivered through contact lenses, Dr. Pall said.

The study was funded by Johnson and Johnson. Dr. Pall is an employee of Johnson & Johnson. Dr. Bielory reported no relevant financial relationships.

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

It’s now known that tinnitus may be an unexpected side effect of SARS-CoV-2 vaccination, and there is an urgent need to understand the precise mechanisms and best treatment for vaccine-associated tinnitus, researchers say.

As of mid-September 2021, 12,247 cases of tinnitus, or ringing in the ears, following COVID-19 vaccination had been reported to the Vaccine Adverse Event Reporting System of the U.S. Centers for Disease Control and Prevention.

“Despite several cases of tinnitus being reported following SARS-CoV-2 vaccination, the precise pathophysiology is still not clear,” write Syed Hassan Ahmed, 3rd-year MBBS student, Dow University of Health Sciences, Karachi, Pakistan, and coauthors.

The researchers review what is known and unknown about SARS-CoV-2 vaccine-associated tinnitus in an article published online Feb. 11 in Annals of Medicine and Surgery.
 

Molecular mimicry?

The researchers say cross-reactivity between anti-spike SARS-CoV-2 antibodies and otologic antigens is one possibility, based on the mechanisms behind other COVID-19 vaccine–induced disorders and the phenomenon of molecular mimicry.

“The heptapeptide resemblance between coronavirus spike glycoprotein and numerous human proteins further supports molecular mimicry as a potential mechanism behind such vaccine-induced disorders,” they write.

Anti-spike antibodies may react with antigens anywhere along the auditory pathway and fuel an inflammatory reaction, they point out.

“Therefore, understanding the phenomenon of cross-reactivity and molecular mimicry may be helpful in postulating potential treatment behind not only tinnitus but also the rare events of vaccination associated hearing loss and other otologic manifestations,” the authors say.

Genetic predispositions and associated conditions may also play a significant role in determining whether an individual develops vaccine-induced tinnitus.

Stress and anxiety following COVID vaccination may also play a role, inasmuch as anxiety-related adverse events following vaccination have been reported. Vaccine-related anxiety as a potential cause of tinnitus developing after vaccination needs to be explored, they write.
 

Jury out on best management

How best to manage COVID vaccine-associated tinnitus also remains unclear, but it starts with a well-established diagnosis, the authors say.

A well-focused and detailed history and examination are essential, with particular emphasis placed on preexisting health conditions, specifically, autoimmune diseases, such as Hashimoto thyroiditis; otologic conditions, such as sensorineural hearing loss; glaucoma; and psychological well-being. According to the review, patients often present with a history of one or more of these disorders.

“However, any such association has not yet been established and requires further investigation to be concluded as potential risk factors for vaccine-induced tinnitus,” they caution.

Routine cranial nerve examination, otoscopy, Weber test, and Rinne test, which are used for tinnitus diagnosis in general, may be helpful for confirmation of vaccine-associated tinnitus.

Owing to the significant association between tinnitus and hearing impairment, audiology should also performed, the authors say.

Although treatments for non–vaccine-induced tinnitus vary significantly, corticosteroids are the top treatment choice for SARS-CoV-2 vaccine-induced tinnitus reported in the literature.

Trials of other drug and nondrug interventions that may uniquely help with vaccine-associated tinnitus are urgently needed, the authors say.

Summing up, the reviewers say, “Although the incidence of COVID-19 vaccine-associated tinnitus is rare, there is an overwhelming need to discern the precise pathophysiology and clinical management as a better understanding of adverse events may help in encountering vaccine hesitancy and hence fostering the COVID-19 global vaccination program.

“Despite the incidence of adverse events, the benefits of the SARS-CoV-2 vaccine in reducing hospitalization and deaths continue to outweigh the rare ramifications,” they conclude.

The research had no specific funding. The authors have disclosed no relevant financial relationships.

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

It’s now known that tinnitus may be an unexpected side effect of SARS-CoV-2 vaccination, and there is an urgent need to understand the precise mechanisms and best treatment for vaccine-associated tinnitus, researchers say.

As of mid-September 2021, 12,247 cases of tinnitus, or ringing in the ears, following COVID-19 vaccination had been reported to the Vaccine Adverse Event Reporting System of the U.S. Centers for Disease Control and Prevention.

“Despite several cases of tinnitus being reported following SARS-CoV-2 vaccination, the precise pathophysiology is still not clear,” write Syed Hassan Ahmed, 3rd-year MBBS student, Dow University of Health Sciences, Karachi, Pakistan, and coauthors.

The researchers review what is known and unknown about SARS-CoV-2 vaccine-associated tinnitus in an article published online Feb. 11 in Annals of Medicine and Surgery.
 

Molecular mimicry?

The researchers say cross-reactivity between anti-spike SARS-CoV-2 antibodies and otologic antigens is one possibility, based on the mechanisms behind other COVID-19 vaccine–induced disorders and the phenomenon of molecular mimicry.

“The heptapeptide resemblance between coronavirus spike glycoprotein and numerous human proteins further supports molecular mimicry as a potential mechanism behind such vaccine-induced disorders,” they write.

Anti-spike antibodies may react with antigens anywhere along the auditory pathway and fuel an inflammatory reaction, they point out.

“Therefore, understanding the phenomenon of cross-reactivity and molecular mimicry may be helpful in postulating potential treatment behind not only tinnitus but also the rare events of vaccination associated hearing loss and other otologic manifestations,” the authors say.

Genetic predispositions and associated conditions may also play a significant role in determining whether an individual develops vaccine-induced tinnitus.

Stress and anxiety following COVID vaccination may also play a role, inasmuch as anxiety-related adverse events following vaccination have been reported. Vaccine-related anxiety as a potential cause of tinnitus developing after vaccination needs to be explored, they write.
 

Jury out on best management

How best to manage COVID vaccine-associated tinnitus also remains unclear, but it starts with a well-established diagnosis, the authors say.

A well-focused and detailed history and examination are essential, with particular emphasis placed on preexisting health conditions, specifically, autoimmune diseases, such as Hashimoto thyroiditis; otologic conditions, such as sensorineural hearing loss; glaucoma; and psychological well-being. According to the review, patients often present with a history of one or more of these disorders.

“However, any such association has not yet been established and requires further investigation to be concluded as potential risk factors for vaccine-induced tinnitus,” they caution.

Routine cranial nerve examination, otoscopy, Weber test, and Rinne test, which are used for tinnitus diagnosis in general, may be helpful for confirmation of vaccine-associated tinnitus.

Owing to the significant association between tinnitus and hearing impairment, audiology should also performed, the authors say.

Although treatments for non–vaccine-induced tinnitus vary significantly, corticosteroids are the top treatment choice for SARS-CoV-2 vaccine-induced tinnitus reported in the literature.

Trials of other drug and nondrug interventions that may uniquely help with vaccine-associated tinnitus are urgently needed, the authors say.

Summing up, the reviewers say, “Although the incidence of COVID-19 vaccine-associated tinnitus is rare, there is an overwhelming need to discern the precise pathophysiology and clinical management as a better understanding of adverse events may help in encountering vaccine hesitancy and hence fostering the COVID-19 global vaccination program.

“Despite the incidence of adverse events, the benefits of the SARS-CoV-2 vaccine in reducing hospitalization and deaths continue to outweigh the rare ramifications,” they conclude.

The research had no specific funding. The authors have disclosed no relevant financial relationships.

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

It’s now known that tinnitus may be an unexpected side effect of SARS-CoV-2 vaccination, and there is an urgent need to understand the precise mechanisms and best treatment for vaccine-associated tinnitus, researchers say.

As of mid-September 2021, 12,247 cases of tinnitus, or ringing in the ears, following COVID-19 vaccination had been reported to the Vaccine Adverse Event Reporting System of the U.S. Centers for Disease Control and Prevention.

“Despite several cases of tinnitus being reported following SARS-CoV-2 vaccination, the precise pathophysiology is still not clear,” write Syed Hassan Ahmed, 3rd-year MBBS student, Dow University of Health Sciences, Karachi, Pakistan, and coauthors.

The researchers review what is known and unknown about SARS-CoV-2 vaccine-associated tinnitus in an article published online Feb. 11 in Annals of Medicine and Surgery.
 

Molecular mimicry?

The researchers say cross-reactivity between anti-spike SARS-CoV-2 antibodies and otologic antigens is one possibility, based on the mechanisms behind other COVID-19 vaccine–induced disorders and the phenomenon of molecular mimicry.

“The heptapeptide resemblance between coronavirus spike glycoprotein and numerous human proteins further supports molecular mimicry as a potential mechanism behind such vaccine-induced disorders,” they write.

Anti-spike antibodies may react with antigens anywhere along the auditory pathway and fuel an inflammatory reaction, they point out.

“Therefore, understanding the phenomenon of cross-reactivity and molecular mimicry may be helpful in postulating potential treatment behind not only tinnitus but also the rare events of vaccination associated hearing loss and other otologic manifestations,” the authors say.

Genetic predispositions and associated conditions may also play a significant role in determining whether an individual develops vaccine-induced tinnitus.

Stress and anxiety following COVID vaccination may also play a role, inasmuch as anxiety-related adverse events following vaccination have been reported. Vaccine-related anxiety as a potential cause of tinnitus developing after vaccination needs to be explored, they write.
 

Jury out on best management

How best to manage COVID vaccine-associated tinnitus also remains unclear, but it starts with a well-established diagnosis, the authors say.

A well-focused and detailed history and examination are essential, with particular emphasis placed on preexisting health conditions, specifically, autoimmune diseases, such as Hashimoto thyroiditis; otologic conditions, such as sensorineural hearing loss; glaucoma; and psychological well-being. According to the review, patients often present with a history of one or more of these disorders.

“However, any such association has not yet been established and requires further investigation to be concluded as potential risk factors for vaccine-induced tinnitus,” they caution.

Routine cranial nerve examination, otoscopy, Weber test, and Rinne test, which are used for tinnitus diagnosis in general, may be helpful for confirmation of vaccine-associated tinnitus.

Owing to the significant association between tinnitus and hearing impairment, audiology should also performed, the authors say.

Although treatments for non–vaccine-induced tinnitus vary significantly, corticosteroids are the top treatment choice for SARS-CoV-2 vaccine-induced tinnitus reported in the literature.

Trials of other drug and nondrug interventions that may uniquely help with vaccine-associated tinnitus are urgently needed, the authors say.

Summing up, the reviewers say, “Although the incidence of COVID-19 vaccine-associated tinnitus is rare, there is an overwhelming need to discern the precise pathophysiology and clinical management as a better understanding of adverse events may help in encountering vaccine hesitancy and hence fostering the COVID-19 global vaccination program.

“Despite the incidence of adverse events, the benefits of the SARS-CoV-2 vaccine in reducing hospitalization and deaths continue to outweigh the rare ramifications,” they conclude.

The research had no specific funding. The authors have disclosed no relevant financial relationships.

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

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

The antiseptic methenamine hippurate (MH) is known to sterilize urine and has been suggested to be of use in preventing urinary tract infections (UTIs), but firm evidence has so far been lacking. Now researchers led by clinicians and scientists from Newcastle-upon-Tyne, England, have provided the ALTAR trial (Alternative to Prophylactic Antibiotics for the Treatment of Recurrent UTIs in Women).

Daily low-dose antibiotics as recommended by current guidelines for prophylactic treatment of recurrent UTI have been linked to antibiotic resistance. Using MH as an alternative could play an important role in helping to tackle the global problem of increasing antibiotic resistance, the team said.
 

Study details

They recruited 240 women aged 18 or over with recurrent UTIs requiring prophylactic treatment from eight secondary care urology and urogynecology centers in the United Kingdom from June 2016 to June 2018. Women were randomized to receive MH or daily low-dose antibiotics for 12 months, with follow up for a further 6 months beyond that.

Before trial entry the women had experienced an average of more than six UTI episodes per year. During the 12-month treatment period, in the modified intention-to-treat population, there were 90 symptomatic, antibiotic-treated UTI episodes reported over 101 person-years of follow-up in the antibiotic group, and 141 episodes over 102 person-years in the MH group.

This yielded a UTI rate of 0.89 episodes per person-year in the antibiotic group, compared with 1.38 in the MH group, an absolute difference of 0.49 episodes per person-year. In the 6-month posttreatment follow-up period, the UTI incidence rate was 1.19 episodes per person-year in the antibiotic prophylaxis group versus 1.72 in the MH group, an absolute difference of 0.53.

Before the trial, a patient and public involvement group had predefined the noninferiority margin as one episode of UTI per person-year. The small difference between the two groups was less than this, confirming noninferiority of MH to antibiotic prophylaxis in this setting. This finding was consistent across the modified intention-to-treat, strict intention-to-treat, per protocol, and modified per protocol (post hoc) analyses.

Thus the ALTAR results showed that MH was no worse than antibiotics at preventing UTIs, and MH was also associated with reduced antibiotic consumption.

The vast majority of participants were over 90% adherent with the allocated treatment. Patient satisfaction was generally high and rates of adverse events and adverse reactions generally low, and both were comparable between treatment groups. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the MH group, and most reactions were mild. In the antibiotic group there were two serious adverse reactions (severe abdominal pain and raised alanine transaminase), whereas six participants in the MH group reported an episode of febrile UTI and four were admitted to hospital because of UTI.
 

Substantial global health care problem

At least 50% and up to 80% of all women have at least one acute UTI in their lifetime, most often uncomplicated acute cystitis. About a quarter of them go on to suffer recurrent infection, defined as three or more repeat infections in the past year, or two infections in the preceding 6 months. Frequent recurrences thus represent “a substantial global health care problem,” the authors say.

Guidelines from the United Kingdom, Europe, and the United States acknowledge the need for preventive strategies and strongly recommend the use of daily, low-dose antibiotics as standard prophylactic treatment. However, the United Kingdom’s antimicrobial resistance strategy recommends a “strong focus on infection prevention,” and aims to reduce antimicrobial use in humans by 15% before 2024.

“To achieve that, exploration of nonantibiotic preventive treatments in common conditions such as UTI is essential,” the team said.

MH is one such nonantibiotic treatment. It is bactericidal and works by denaturing bacterial proteins and nucleic acids. Although previous Cochrane systematic reviews had concluded that it could be effective for preventing UTI, further large trials were needed.

“This trial adds to the evidence base for the use of MH for prophylactic treatment in adult women with recurrent UTI. Although the MH group had a 55% higher rate of UTI episodes than the antibiotics group, the absolute difference was just 0.49 UTI episodes per year, which has limited clinical consequence,” the team concluded.
 

Results could ‘support a change in practice’

In older patients, particularly, the risks of long-term antibiotic prophylaxis might outweigh the benefits, and the authors said that their results “could support a change in practice in terms of preventive treatments for recurrent UTI and provide patients and clinicians with a credible alternative to daily antibiotics, giving them the confidence to pursue strategies that avoid long-term antibiotic use.”

They acknowledged limitations of the study, including that treatment allocation was not masked, crossover between arms was allowed, and differences in antibiotics prescribed may have affected the results. In addition, data regarding long-term safety of MH are scarce.

However, they said that the trial accurately represented the broad range of women with recurrent UTI, and that its results “might encourage patients and clinicians to consider MH as a first line treatment for UTI prevention in women.”

In a linked editorial, scientists from the Institute for Evidence-Based Healthcare at Bond University in Queensland, Australia, commented: “Although the results need cautious interpretation, they align with others, and this new research increases the confidence with which MH can be offered as an option to women needing prophylaxis against recurrent urinary tract infection.”

References

Harding C et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, noninferiority trial. BMJ 2022 Mar 9;376:e068229.

Hoffmann TC et al. Methenamine hippurate for recurrent urinary tract infections. BMJ 2022 Mar 9;376:o533.

A version of this article first appeared on Medscape.co.uk.

The antiseptic methenamine hippurate (MH) is known to sterilize urine and has been suggested to be of use in preventing urinary tract infections (UTIs), but firm evidence has so far been lacking. Now researchers led by clinicians and scientists from Newcastle-upon-Tyne, England, have provided the ALTAR trial (Alternative to Prophylactic Antibiotics for the Treatment of Recurrent UTIs in Women).

Daily low-dose antibiotics as recommended by current guidelines for prophylactic treatment of recurrent UTI have been linked to antibiotic resistance. Using MH as an alternative could play an important role in helping to tackle the global problem of increasing antibiotic resistance, the team said.
 

Study details

They recruited 240 women aged 18 or over with recurrent UTIs requiring prophylactic treatment from eight secondary care urology and urogynecology centers in the United Kingdom from June 2016 to June 2018. Women were randomized to receive MH or daily low-dose antibiotics for 12 months, with follow up for a further 6 months beyond that.

Before trial entry the women had experienced an average of more than six UTI episodes per year. During the 12-month treatment period, in the modified intention-to-treat population, there were 90 symptomatic, antibiotic-treated UTI episodes reported over 101 person-years of follow-up in the antibiotic group, and 141 episodes over 102 person-years in the MH group.

This yielded a UTI rate of 0.89 episodes per person-year in the antibiotic group, compared with 1.38 in the MH group, an absolute difference of 0.49 episodes per person-year. In the 6-month posttreatment follow-up period, the UTI incidence rate was 1.19 episodes per person-year in the antibiotic prophylaxis group versus 1.72 in the MH group, an absolute difference of 0.53.

Before the trial, a patient and public involvement group had predefined the noninferiority margin as one episode of UTI per person-year. The small difference between the two groups was less than this, confirming noninferiority of MH to antibiotic prophylaxis in this setting. This finding was consistent across the modified intention-to-treat, strict intention-to-treat, per protocol, and modified per protocol (post hoc) analyses.

Thus the ALTAR results showed that MH was no worse than antibiotics at preventing UTIs, and MH was also associated with reduced antibiotic consumption.

The vast majority of participants were over 90% adherent with the allocated treatment. Patient satisfaction was generally high and rates of adverse events and adverse reactions generally low, and both were comparable between treatment groups. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the MH group, and most reactions were mild. In the antibiotic group there were two serious adverse reactions (severe abdominal pain and raised alanine transaminase), whereas six participants in the MH group reported an episode of febrile UTI and four were admitted to hospital because of UTI.
 

Substantial global health care problem

At least 50% and up to 80% of all women have at least one acute UTI in their lifetime, most often uncomplicated acute cystitis. About a quarter of them go on to suffer recurrent infection, defined as three or more repeat infections in the past year, or two infections in the preceding 6 months. Frequent recurrences thus represent “a substantial global health care problem,” the authors say.

Guidelines from the United Kingdom, Europe, and the United States acknowledge the need for preventive strategies and strongly recommend the use of daily, low-dose antibiotics as standard prophylactic treatment. However, the United Kingdom’s antimicrobial resistance strategy recommends a “strong focus on infection prevention,” and aims to reduce antimicrobial use in humans by 15% before 2024.

“To achieve that, exploration of nonantibiotic preventive treatments in common conditions such as UTI is essential,” the team said.

MH is one such nonantibiotic treatment. It is bactericidal and works by denaturing bacterial proteins and nucleic acids. Although previous Cochrane systematic reviews had concluded that it could be effective for preventing UTI, further large trials were needed.

“This trial adds to the evidence base for the use of MH for prophylactic treatment in adult women with recurrent UTI. Although the MH group had a 55% higher rate of UTI episodes than the antibiotics group, the absolute difference was just 0.49 UTI episodes per year, which has limited clinical consequence,” the team concluded.
 

Results could ‘support a change in practice’

In older patients, particularly, the risks of long-term antibiotic prophylaxis might outweigh the benefits, and the authors said that their results “could support a change in practice in terms of preventive treatments for recurrent UTI and provide patients and clinicians with a credible alternative to daily antibiotics, giving them the confidence to pursue strategies that avoid long-term antibiotic use.”

They acknowledged limitations of the study, including that treatment allocation was not masked, crossover between arms was allowed, and differences in antibiotics prescribed may have affected the results. In addition, data regarding long-term safety of MH are scarce.

However, they said that the trial accurately represented the broad range of women with recurrent UTI, and that its results “might encourage patients and clinicians to consider MH as a first line treatment for UTI prevention in women.”

In a linked editorial, scientists from the Institute for Evidence-Based Healthcare at Bond University in Queensland, Australia, commented: “Although the results need cautious interpretation, they align with others, and this new research increases the confidence with which MH can be offered as an option to women needing prophylaxis against recurrent urinary tract infection.”

References

Harding C et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, noninferiority trial. BMJ 2022 Mar 9;376:e068229.

Hoffmann TC et al. Methenamine hippurate for recurrent urinary tract infections. BMJ 2022 Mar 9;376:o533.

A version of this article first appeared on Medscape.co.uk.

The antiseptic methenamine hippurate (MH) is known to sterilize urine and has been suggested to be of use in preventing urinary tract infections (UTIs), but firm evidence has so far been lacking. Now researchers led by clinicians and scientists from Newcastle-upon-Tyne, England, have provided the ALTAR trial (Alternative to Prophylactic Antibiotics for the Treatment of Recurrent UTIs in Women).

Daily low-dose antibiotics as recommended by current guidelines for prophylactic treatment of recurrent UTI have been linked to antibiotic resistance. Using MH as an alternative could play an important role in helping to tackle the global problem of increasing antibiotic resistance, the team said.
 

Study details

They recruited 240 women aged 18 or over with recurrent UTIs requiring prophylactic treatment from eight secondary care urology and urogynecology centers in the United Kingdom from June 2016 to June 2018. Women were randomized to receive MH or daily low-dose antibiotics for 12 months, with follow up for a further 6 months beyond that.

Before trial entry the women had experienced an average of more than six UTI episodes per year. During the 12-month treatment period, in the modified intention-to-treat population, there were 90 symptomatic, antibiotic-treated UTI episodes reported over 101 person-years of follow-up in the antibiotic group, and 141 episodes over 102 person-years in the MH group.

This yielded a UTI rate of 0.89 episodes per person-year in the antibiotic group, compared with 1.38 in the MH group, an absolute difference of 0.49 episodes per person-year. In the 6-month posttreatment follow-up period, the UTI incidence rate was 1.19 episodes per person-year in the antibiotic prophylaxis group versus 1.72 in the MH group, an absolute difference of 0.53.

Before the trial, a patient and public involvement group had predefined the noninferiority margin as one episode of UTI per person-year. The small difference between the two groups was less than this, confirming noninferiority of MH to antibiotic prophylaxis in this setting. This finding was consistent across the modified intention-to-treat, strict intention-to-treat, per protocol, and modified per protocol (post hoc) analyses.

Thus the ALTAR results showed that MH was no worse than antibiotics at preventing UTIs, and MH was also associated with reduced antibiotic consumption.

The vast majority of participants were over 90% adherent with the allocated treatment. Patient satisfaction was generally high and rates of adverse events and adverse reactions generally low, and both were comparable between treatment groups. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the MH group, and most reactions were mild. In the antibiotic group there were two serious adverse reactions (severe abdominal pain and raised alanine transaminase), whereas six participants in the MH group reported an episode of febrile UTI and four were admitted to hospital because of UTI.
 

Substantial global health care problem

At least 50% and up to 80% of all women have at least one acute UTI in their lifetime, most often uncomplicated acute cystitis. About a quarter of them go on to suffer recurrent infection, defined as three or more repeat infections in the past year, or two infections in the preceding 6 months. Frequent recurrences thus represent “a substantial global health care problem,” the authors say.

Guidelines from the United Kingdom, Europe, and the United States acknowledge the need for preventive strategies and strongly recommend the use of daily, low-dose antibiotics as standard prophylactic treatment. However, the United Kingdom’s antimicrobial resistance strategy recommends a “strong focus on infection prevention,” and aims to reduce antimicrobial use in humans by 15% before 2024.

“To achieve that, exploration of nonantibiotic preventive treatments in common conditions such as UTI is essential,” the team said.

MH is one such nonantibiotic treatment. It is bactericidal and works by denaturing bacterial proteins and nucleic acids. Although previous Cochrane systematic reviews had concluded that it could be effective for preventing UTI, further large trials were needed.

“This trial adds to the evidence base for the use of MH for prophylactic treatment in adult women with recurrent UTI. Although the MH group had a 55% higher rate of UTI episodes than the antibiotics group, the absolute difference was just 0.49 UTI episodes per year, which has limited clinical consequence,” the team concluded.
 

Results could ‘support a change in practice’

In older patients, particularly, the risks of long-term antibiotic prophylaxis might outweigh the benefits, and the authors said that their results “could support a change in practice in terms of preventive treatments for recurrent UTI and provide patients and clinicians with a credible alternative to daily antibiotics, giving them the confidence to pursue strategies that avoid long-term antibiotic use.”

They acknowledged limitations of the study, including that treatment allocation was not masked, crossover between arms was allowed, and differences in antibiotics prescribed may have affected the results. In addition, data regarding long-term safety of MH are scarce.

However, they said that the trial accurately represented the broad range of women with recurrent UTI, and that its results “might encourage patients and clinicians to consider MH as a first line treatment for UTI prevention in women.”

In a linked editorial, scientists from the Institute for Evidence-Based Healthcare at Bond University in Queensland, Australia, commented: “Although the results need cautious interpretation, they align with others, and this new research increases the confidence with which MH can be offered as an option to women needing prophylaxis against recurrent urinary tract infection.”

References

Harding C et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, noninferiority trial. BMJ 2022 Mar 9;376:e068229.

Hoffmann TC et al. Methenamine hippurate for recurrent urinary tract infections. BMJ 2022 Mar 9;376:o533.

A version of this article first appeared on Medscape.co.uk.