Pharmacology

Background

Due to risk for infusion-related reactions (IRR), administration of iron dextran requires an initial test dose with an extended monitoring period and subsequent doses given as a slow infusion over 2-3 hours. Safe use of a 60-minute iron dextran infusion protocol has been demonstrated previously at fully staffed academic teaching institutions. This study sought to determine the impact on patient safety and infusion clinic efficiency after implementing a 60-minute iron dextran administration protocol at a small, rural facility utilizing a decentralized clinical model.

Methods

This single-site, prospective, interventional study was conducted at a rural level 1C Veterans Affairs secondary care facility. The Hematology/Oncology clinic staffing includes one onsite clinical pharmacy practitioner (CPP) and advanced practice nurse. Remote providers complete patient encounters through video and telehealth modalities. A 60-minute iron dextran infusion service line agreement was designed by the Hematology/Oncology CPP and approved by the facility prior to data collection. The protocol included administration of a test dose and 15-minute monitoring period for treatment naïve patients. Pre-medications were allowed at the discretion of the ordering providers. All patients who received iron dextran between May 31, 2024 and April 14, 2025 per protocol were included in data analysis and results were stratified by treatment naïve and pre-treated patients. Outcomes included the proportion of patients experiencing any grade of IRR based on the Common Criteria for Adverse Events Version 5.0, and the average duration of administration. Descriptive statistics were used for safety and efficiency outcomes.

Results

Eighty patients received 103 iron dextran infusions and were included for analysis. Pre-medications were administered for 16 of the 103 (15.5%) included infusions. Two patients experienced grade 1 IRR (nausea) on 4 occasions (3.8%) which quickly resolved with intravenous ondansetron, and full iron dextran doses were received. The mean infusion time was 94 minutes in the treatment naïve cohort vs 71 minutes in the pre-treated cohort.

Conclusions

This study suggests a Hematology/ Oncology CPP developed iron dextran 60-minute infusion protocol may be safely and efficiently administered for qualifying patients in a decentralized, rural healthcare setting.

Background

Due to risk for infusion-related reactions (IRR), administration of iron dextran requires an initial test dose with an extended monitoring period and subsequent doses given as a slow infusion over 2-3 hours. Safe use of a 60-minute iron dextran infusion protocol has been demonstrated previously at fully staffed academic teaching institutions. This study sought to determine the impact on patient safety and infusion clinic efficiency after implementing a 60-minute iron dextran administration protocol at a small, rural facility utilizing a decentralized clinical model.

Methods

This single-site, prospective, interventional study was conducted at a rural level 1C Veterans Affairs secondary care facility. The Hematology/Oncology clinic staffing includes one onsite clinical pharmacy practitioner (CPP) and advanced practice nurse. Remote providers complete patient encounters through video and telehealth modalities. A 60-minute iron dextran infusion service line agreement was designed by the Hematology/Oncology CPP and approved by the facility prior to data collection. The protocol included administration of a test dose and 15-minute monitoring period for treatment naïve patients. Pre-medications were allowed at the discretion of the ordering providers. All patients who received iron dextran between May 31, 2024 and April 14, 2025 per protocol were included in data analysis and results were stratified by treatment naïve and pre-treated patients. Outcomes included the proportion of patients experiencing any grade of IRR based on the Common Criteria for Adverse Events Version 5.0, and the average duration of administration. Descriptive statistics were used for safety and efficiency outcomes.

Results

Eighty patients received 103 iron dextran infusions and were included for analysis. Pre-medications were administered for 16 of the 103 (15.5%) included infusions. Two patients experienced grade 1 IRR (nausea) on 4 occasions (3.8%) which quickly resolved with intravenous ondansetron, and full iron dextran doses were received. The mean infusion time was 94 minutes in the treatment naïve cohort vs 71 minutes in the pre-treated cohort.

Conclusions

This study suggests a Hematology/ Oncology CPP developed iron dextran 60-minute infusion protocol may be safely and efficiently administered for qualifying patients in a decentralized, rural healthcare setting.

Background

Due to risk for infusion-related reactions (IRR), administration of iron dextran requires an initial test dose with an extended monitoring period and subsequent doses given as a slow infusion over 2-3 hours. Safe use of a 60-minute iron dextran infusion protocol has been demonstrated previously at fully staffed academic teaching institutions. This study sought to determine the impact on patient safety and infusion clinic efficiency after implementing a 60-minute iron dextran administration protocol at a small, rural facility utilizing a decentralized clinical model.

Methods

This single-site, prospective, interventional study was conducted at a rural level 1C Veterans Affairs secondary care facility. The Hematology/Oncology clinic staffing includes one onsite clinical pharmacy practitioner (CPP) and advanced practice nurse. Remote providers complete patient encounters through video and telehealth modalities. A 60-minute iron dextran infusion service line agreement was designed by the Hematology/Oncology CPP and approved by the facility prior to data collection. The protocol included administration of a test dose and 15-minute monitoring period for treatment naïve patients. Pre-medications were allowed at the discretion of the ordering providers. All patients who received iron dextran between May 31, 2024 and April 14, 2025 per protocol were included in data analysis and results were stratified by treatment naïve and pre-treated patients. Outcomes included the proportion of patients experiencing any grade of IRR based on the Common Criteria for Adverse Events Version 5.0, and the average duration of administration. Descriptive statistics were used for safety and efficiency outcomes.

Results

Eighty patients received 103 iron dextran infusions and were included for analysis. Pre-medications were administered for 16 of the 103 (15.5%) included infusions. Two patients experienced grade 1 IRR (nausea) on 4 occasions (3.8%) which quickly resolved with intravenous ondansetron, and full iron dextran doses were received. The mean infusion time was 94 minutes in the treatment naïve cohort vs 71 minutes in the pre-treated cohort.

Conclusions

This study suggests a Hematology/ Oncology CPP developed iron dextran 60-minute infusion protocol may be safely and efficiently administered for qualifying patients in a decentralized, rural healthcare setting.

Purpose/Background

Oncology clinical pharmacist practitioners (CPP) play a critical role in optimizing drug therapy, managing side effects, and ensuring medication adherence. As a specialized clinical area, specific training is needed to ensure quality of care. Oncology pharmacy training programs are commercially available but pose a financial burden and are not specific to the Veterans Health Administration (VHA). A comprehensive, virtual Oncology Bootcamp series was implemented to upskill new oncology pharmacists (or pharmacists seeking to further their understanding of oncology practice), with didactic materials and clinical tools to enhance and standardize quality care delivery.

Methods

This program was comprised of an online platform of 23 one hour-long continuing education accredited sessions, delivered by leading subject matter experts. Pharmacists from two Veteran Integrated Service Networks (VISNs) were invited for the first year of the bootcamp. The curriculum encompassed fundamentals of oncology practice, patient care assessment, chemotherapy protocol review, practice management, and supportive care. Participants also received in-depth training on managing various cancer types, including but not limited to prostate, lung, gastrointestinal and hematologic malignancies. VHA specific information, including utilization of Oncology Clinical Pathways to promote standardized care was included where applicable. The interactive nature of the virtual sessions provided opportunities for real-time discussion and immediate feedback. To measure the impact of this program, a pre and post program evaluation of participants was conducted.

Results

Over the course of the program, more than 40 pharmacists across two VISNs participated in the bootcamp series. Results of the program evaluation showed an increase in self-reported comfort and skill levels in all criteria that were assessed (oncology pharmacotherapy, solid tumor malignancies, hematologic malignancies and oral anti-cancer therapy management). Additionally, 85% of respondents stated the series met their overall goals and over 90% of respondents stated they were either satisfied or very satisfied with the content, speakers and organization of the course.

Implications/Significance

This initiative has established the viability and significance of a highly accessible, VHA pathway specific and Veteran centric platform for oncology pharmacy professional development. Future directions for the program include a broader nationwide audience, increased content coverage and self-paced learning options.

Purpose/Background

Oncology clinical pharmacist practitioners (CPP) play a critical role in optimizing drug therapy, managing side effects, and ensuring medication adherence. As a specialized clinical area, specific training is needed to ensure quality of care. Oncology pharmacy training programs are commercially available but pose a financial burden and are not specific to the Veterans Health Administration (VHA). A comprehensive, virtual Oncology Bootcamp series was implemented to upskill new oncology pharmacists (or pharmacists seeking to further their understanding of oncology practice), with didactic materials and clinical tools to enhance and standardize quality care delivery.

Methods

This program was comprised of an online platform of 23 one hour-long continuing education accredited sessions, delivered by leading subject matter experts. Pharmacists from two Veteran Integrated Service Networks (VISNs) were invited for the first year of the bootcamp. The curriculum encompassed fundamentals of oncology practice, patient care assessment, chemotherapy protocol review, practice management, and supportive care. Participants also received in-depth training on managing various cancer types, including but not limited to prostate, lung, gastrointestinal and hematologic malignancies. VHA specific information, including utilization of Oncology Clinical Pathways to promote standardized care was included where applicable. The interactive nature of the virtual sessions provided opportunities for real-time discussion and immediate feedback. To measure the impact of this program, a pre and post program evaluation of participants was conducted.

Results

Over the course of the program, more than 40 pharmacists across two VISNs participated in the bootcamp series. Results of the program evaluation showed an increase in self-reported comfort and skill levels in all criteria that were assessed (oncology pharmacotherapy, solid tumor malignancies, hematologic malignancies and oral anti-cancer therapy management). Additionally, 85% of respondents stated the series met their overall goals and over 90% of respondents stated they were either satisfied or very satisfied with the content, speakers and organization of the course.

Implications/Significance

This initiative has established the viability and significance of a highly accessible, VHA pathway specific and Veteran centric platform for oncology pharmacy professional development. Future directions for the program include a broader nationwide audience, increased content coverage and self-paced learning options.

Purpose/Background

Oncology clinical pharmacist practitioners (CPP) play a critical role in optimizing drug therapy, managing side effects, and ensuring medication adherence. As a specialized clinical area, specific training is needed to ensure quality of care. Oncology pharmacy training programs are commercially available but pose a financial burden and are not specific to the Veterans Health Administration (VHA). A comprehensive, virtual Oncology Bootcamp series was implemented to upskill new oncology pharmacists (or pharmacists seeking to further their understanding of oncology practice), with didactic materials and clinical tools to enhance and standardize quality care delivery.

Methods

This program was comprised of an online platform of 23 one hour-long continuing education accredited sessions, delivered by leading subject matter experts. Pharmacists from two Veteran Integrated Service Networks (VISNs) were invited for the first year of the bootcamp. The curriculum encompassed fundamentals of oncology practice, patient care assessment, chemotherapy protocol review, practice management, and supportive care. Participants also received in-depth training on managing various cancer types, including but not limited to prostate, lung, gastrointestinal and hematologic malignancies. VHA specific information, including utilization of Oncology Clinical Pathways to promote standardized care was included where applicable. The interactive nature of the virtual sessions provided opportunities for real-time discussion and immediate feedback. To measure the impact of this program, a pre and post program evaluation of participants was conducted.

Results

Over the course of the program, more than 40 pharmacists across two VISNs participated in the bootcamp series. Results of the program evaluation showed an increase in self-reported comfort and skill levels in all criteria that were assessed (oncology pharmacotherapy, solid tumor malignancies, hematologic malignancies and oral anti-cancer therapy management). Additionally, 85% of respondents stated the series met their overall goals and over 90% of respondents stated they were either satisfied or very satisfied with the content, speakers and organization of the course.

Implications/Significance

This initiative has established the viability and significance of a highly accessible, VHA pathway specific and Veteran centric platform for oncology pharmacy professional development. Future directions for the program include a broader nationwide audience, increased content coverage and self-paced learning options.

Background

Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.

Case Presentation

A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.

Discussion

The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.

Conclusions

Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.

Background

Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.

Case Presentation

A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.

Discussion

The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.

Conclusions

Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.

Background

Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.

Case Presentation

A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.

Discussion

The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.

Conclusions

Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.

Background

Pancreatic cancer has one of the highest mortality rates due to its typical late-stage diagnosis and subsequent limited surgical options. However, recent advances in molecular profiling offer hope for targeted therapies. We present a case of locally advanced pancreatic adenocarcinoma which progressed despite surgery and chemotherapy yet showed a positive respond to Alectinib.

Case Description

A 79-year-old male with medical history of tobacco use and ulcerative colitis presented to the clinic with 15lb unintentional weight loss over the past few months in 04/2021. Computed tomography (CT) showed dilated common bile duct due to 2.2 x 1.9 x 1.7 cm mass with no metastatic disease. Biopsy was consistent with pancreatic adenocarcinoma and patient completed 6 cycles of dose-reduced neoadjuvant gemcitabine and paclitaxel in late 2021 due to his severe neuropathy and ECOG. Subsequent CT and PET-CT showed stable disease prior to undergoing pylorus-sparing pancreatoduodenectomy and cholecystectomy with portal vein resection in 05/2022 with surgical pathology grading yPT4N2cM0. The follow- up PET scan in 09/2022 revealed new pulmonary and liver metastases, along with increased uptake in the pancreatic region, suggesting recurrent disease. Next generation sequencing (NGS) identified an ELM4-ALK chromosomal rearrangement on the surgical pathology. Given the patient’s cancer progression and concerns about chemotherapy tolerance, Alectinib, a second-generation ALK inhibitor more commonly used in lung cancer, was considered as a treatment option. Patient began Alectinib 10/2022 with no significant side effects and PET scan on 03/2023 and 06/2023 showing resolution of his lung nodules and liver lesions. Patient remained on Alectinib until he transitioned to hospice after an ischemic stroke in 03/2024.

Discussion

Pancreatic cancer urgently requires novel therapies as about 25% of patients harbor actionable molecular alterations that have led to the success of targeted therapies. ALK fusion genes are identified in multiple cancers, but the prevalence is only 0.16% in pancreatic ductal adenocarcinoma. Alectinib provided an extended progression free survival compared with standard chemotherapy in our patient. ALK inhibitors may demonstrate a remarkable response in metastatic pancreatic cancer even in poor candidates for standard chemotherapy highlighting the emphasis of NGS and targeted therapy options for pancreatic cancer to improve survival.

Background

Pancreatic cancer has one of the highest mortality rates due to its typical late-stage diagnosis and subsequent limited surgical options. However, recent advances in molecular profiling offer hope for targeted therapies. We present a case of locally advanced pancreatic adenocarcinoma which progressed despite surgery and chemotherapy yet showed a positive respond to Alectinib.

Case Description

A 79-year-old male with medical history of tobacco use and ulcerative colitis presented to the clinic with 15lb unintentional weight loss over the past few months in 04/2021. Computed tomography (CT) showed dilated common bile duct due to 2.2 x 1.9 x 1.7 cm mass with no metastatic disease. Biopsy was consistent with pancreatic adenocarcinoma and patient completed 6 cycles of dose-reduced neoadjuvant gemcitabine and paclitaxel in late 2021 due to his severe neuropathy and ECOG. Subsequent CT and PET-CT showed stable disease prior to undergoing pylorus-sparing pancreatoduodenectomy and cholecystectomy with portal vein resection in 05/2022 with surgical pathology grading yPT4N2cM0. The follow- up PET scan in 09/2022 revealed new pulmonary and liver metastases, along with increased uptake in the pancreatic region, suggesting recurrent disease. Next generation sequencing (NGS) identified an ELM4-ALK chromosomal rearrangement on the surgical pathology. Given the patient’s cancer progression and concerns about chemotherapy tolerance, Alectinib, a second-generation ALK inhibitor more commonly used in lung cancer, was considered as a treatment option. Patient began Alectinib 10/2022 with no significant side effects and PET scan on 03/2023 and 06/2023 showing resolution of his lung nodules and liver lesions. Patient remained on Alectinib until he transitioned to hospice after an ischemic stroke in 03/2024.

Discussion

Pancreatic cancer urgently requires novel therapies as about 25% of patients harbor actionable molecular alterations that have led to the success of targeted therapies. ALK fusion genes are identified in multiple cancers, but the prevalence is only 0.16% in pancreatic ductal adenocarcinoma. Alectinib provided an extended progression free survival compared with standard chemotherapy in our patient. ALK inhibitors may demonstrate a remarkable response in metastatic pancreatic cancer even in poor candidates for standard chemotherapy highlighting the emphasis of NGS and targeted therapy options for pancreatic cancer to improve survival.

Background

Pancreatic cancer has one of the highest mortality rates due to its typical late-stage diagnosis and subsequent limited surgical options. However, recent advances in molecular profiling offer hope for targeted therapies. We present a case of locally advanced pancreatic adenocarcinoma which progressed despite surgery and chemotherapy yet showed a positive respond to Alectinib.

Case Description

A 79-year-old male with medical history of tobacco use and ulcerative colitis presented to the clinic with 15lb unintentional weight loss over the past few months in 04/2021. Computed tomography (CT) showed dilated common bile duct due to 2.2 x 1.9 x 1.7 cm mass with no metastatic disease. Biopsy was consistent with pancreatic adenocarcinoma and patient completed 6 cycles of dose-reduced neoadjuvant gemcitabine and paclitaxel in late 2021 due to his severe neuropathy and ECOG. Subsequent CT and PET-CT showed stable disease prior to undergoing pylorus-sparing pancreatoduodenectomy and cholecystectomy with portal vein resection in 05/2022 with surgical pathology grading yPT4N2cM0. The follow- up PET scan in 09/2022 revealed new pulmonary and liver metastases, along with increased uptake in the pancreatic region, suggesting recurrent disease. Next generation sequencing (NGS) identified an ELM4-ALK chromosomal rearrangement on the surgical pathology. Given the patient’s cancer progression and concerns about chemotherapy tolerance, Alectinib, a second-generation ALK inhibitor more commonly used in lung cancer, was considered as a treatment option. Patient began Alectinib 10/2022 with no significant side effects and PET scan on 03/2023 and 06/2023 showing resolution of his lung nodules and liver lesions. Patient remained on Alectinib until he transitioned to hospice after an ischemic stroke in 03/2024.

Discussion

Pancreatic cancer urgently requires novel therapies as about 25% of patients harbor actionable molecular alterations that have led to the success of targeted therapies. ALK fusion genes are identified in multiple cancers, but the prevalence is only 0.16% in pancreatic ductal adenocarcinoma. Alectinib provided an extended progression free survival compared with standard chemotherapy in our patient. ALK inhibitors may demonstrate a remarkable response in metastatic pancreatic cancer even in poor candidates for standard chemotherapy highlighting the emphasis of NGS and targeted therapy options for pancreatic cancer to improve survival.

Purpose

To compare vial utilization and spending between fixed and weight-based dosing of pembrolizumab in Veterans. Promote and assess pembrolizumab extended interval dosing.

Background

FDA approved pembrolizumab label change from weight-based to fixed dosing without evidence of fixed-dosing’s superiority. Retrospective studies demonstrate equivalent outcomes for 2 mg/kg every 3 weeks (Q3W), 200 mg Q3W, 4 mg/kg every 6 weeks (Q6W), and 400 mg Q6W.

Methods

In July 2024 VAAAHS (VA Ann Arbor Healthcare System) initiated an immunotherapy stewardship quality improvement program to deprescribe unnecessary pembrolizumab units and promote extended-interval dosing. Specific interventions included order template modification and targeted outreach to key stakeholders.

Data Analysis

All pembrolizumab doses administered at VAAAHS between July 1, 2024 (launch) and March 31, 2025 (data cutoff) were extracted from EHR. Drug utilization, spending, and healthcare contact hours averted were compared to a fixed-dosing counterfactual.

Results

Sixty-three Veterans received 286 total pembrolizumab doses, of which 107 (37.4%) were Q6W and 179 (62.6%) were Q3W. In total, 741 vials were utilized, against expectation of 786 (5.7% reduction), reflecting approximately $182,000 in savings (annualized, $243,000) and 86.5% of the theoretical maximum savings were captured. Q6W’s share of all doses rose from 27.3% in July 2024 to 53.8% in March 2025. Amongst monotherapy, Q6W’s share rose from 60.0% in July 2024 to 86.7% in March 2025. Q6W adoption saved 381 Veteran-healthcare contact hours, not including travel time.

Conclusions

Stewardship efforts reduced unnecessary pembrolizumab utilization and spending while saving Veterans and VAAAHS providers’ time. Continued provider reinforcement, preparation for Oracle/ Cerner implementation, VISN expansion, refinement of pembrolizumab dose-banding, and development of dose bands for other immunotherapies are underway.

Significance

National implementation would improve Veteran convenience and quality of life, enable reductions in drug and resource costs, and enhance clinic throughput.

Purpose

To compare vial utilization and spending between fixed and weight-based dosing of pembrolizumab in Veterans. Promote and assess pembrolizumab extended interval dosing.

Background

FDA approved pembrolizumab label change from weight-based to fixed dosing without evidence of fixed-dosing’s superiority. Retrospective studies demonstrate equivalent outcomes for 2 mg/kg every 3 weeks (Q3W), 200 mg Q3W, 4 mg/kg every 6 weeks (Q6W), and 400 mg Q6W.

Methods

In July 2024 VAAAHS (VA Ann Arbor Healthcare System) initiated an immunotherapy stewardship quality improvement program to deprescribe unnecessary pembrolizumab units and promote extended-interval dosing. Specific interventions included order template modification and targeted outreach to key stakeholders.

Data Analysis

All pembrolizumab doses administered at VAAAHS between July 1, 2024 (launch) and March 31, 2025 (data cutoff) were extracted from EHR. Drug utilization, spending, and healthcare contact hours averted were compared to a fixed-dosing counterfactual.

Results

Sixty-three Veterans received 286 total pembrolizumab doses, of which 107 (37.4%) were Q6W and 179 (62.6%) were Q3W. In total, 741 vials were utilized, against expectation of 786 (5.7% reduction), reflecting approximately $182,000 in savings (annualized, $243,000) and 86.5% of the theoretical maximum savings were captured. Q6W’s share of all doses rose from 27.3% in July 2024 to 53.8% in March 2025. Amongst monotherapy, Q6W’s share rose from 60.0% in July 2024 to 86.7% in March 2025. Q6W adoption saved 381 Veteran-healthcare contact hours, not including travel time.

Conclusions

Stewardship efforts reduced unnecessary pembrolizumab utilization and spending while saving Veterans and VAAAHS providers’ time. Continued provider reinforcement, preparation for Oracle/ Cerner implementation, VISN expansion, refinement of pembrolizumab dose-banding, and development of dose bands for other immunotherapies are underway.

Significance

National implementation would improve Veteran convenience and quality of life, enable reductions in drug and resource costs, and enhance clinic throughput.

Purpose

To compare vial utilization and spending between fixed and weight-based dosing of pembrolizumab in Veterans. Promote and assess pembrolizumab extended interval dosing.

Background

FDA approved pembrolizumab label change from weight-based to fixed dosing without evidence of fixed-dosing’s superiority. Retrospective studies demonstrate equivalent outcomes for 2 mg/kg every 3 weeks (Q3W), 200 mg Q3W, 4 mg/kg every 6 weeks (Q6W), and 400 mg Q6W.

Methods

In July 2024 VAAAHS (VA Ann Arbor Healthcare System) initiated an immunotherapy stewardship quality improvement program to deprescribe unnecessary pembrolizumab units and promote extended-interval dosing. Specific interventions included order template modification and targeted outreach to key stakeholders.

Data Analysis

All pembrolizumab doses administered at VAAAHS between July 1, 2024 (launch) and March 31, 2025 (data cutoff) were extracted from EHR. Drug utilization, spending, and healthcare contact hours averted were compared to a fixed-dosing counterfactual.

Results

Sixty-three Veterans received 286 total pembrolizumab doses, of which 107 (37.4%) were Q6W and 179 (62.6%) were Q3W. In total, 741 vials were utilized, against expectation of 786 (5.7% reduction), reflecting approximately $182,000 in savings (annualized, $243,000) and 86.5% of the theoretical maximum savings were captured. Q6W’s share of all doses rose from 27.3% in July 2024 to 53.8% in March 2025. Amongst monotherapy, Q6W’s share rose from 60.0% in July 2024 to 86.7% in March 2025. Q6W adoption saved 381 Veteran-healthcare contact hours, not including travel time.

Conclusions

Stewardship efforts reduced unnecessary pembrolizumab utilization and spending while saving Veterans and VAAAHS providers’ time. Continued provider reinforcement, preparation for Oracle/ Cerner implementation, VISN expansion, refinement of pembrolizumab dose-banding, and development of dose bands for other immunotherapies are underway.

Significance

National implementation would improve Veteran convenience and quality of life, enable reductions in drug and resource costs, and enhance clinic throughput.

Statins are widely used to reduce low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) levels for the prevention of atherosclerotic cardiovascular disease (ASCVD).¹ However, despite maximally tolerated statin therapy, many patients may not reach their LDL and non-HDL goals. Some patients may experience adverse events (AEs), particularly muscle-related AEs, which can limit the use of these medications.

The 2022 American College of Cardiology (ACC) expert consensus pathway recommends a goal LDL of < 55 mg/dL in very high-risk patients, defined as those with a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions.² Major ASCVD events include acute coronary syndrome within 12 months, history of myocardial infarction (MI) or ischemic stroke, and symptomatic peripheral arterial disease (ie, claudication with ankle-brachial index < 0.85 or previous revascularization or amputation). Factors for being considered high risk include age > 65 years, heterozygous familial hypercholesterolemia, history of prior coronary artery bypass surgery or percutaneous coronary intervention outside the major ASCVD events, diabetes, hypertension, chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] 15-59 mL/min/1.73 m²), current smoking, persistently elevated LDL cholesterol (LDL-C) levels despite maximally tolerated statin therapy and ezetimibe, and history of congestive heart failure.² For these patients, statin therapy alone may not achieve LDL goal. 

The ACC recommends ezetimibe as the initial nonstatin therapy in patients who are not at their goal LDL.² Ezetimibe works by inhibiting Niemann-Pick C1-Like 1 protein, which causes reduced cholesterol absorption in the small intestine.^2,3 Previous studies have shown the benefit of ezetimibe for LDL reduction and ASCVD prevention.^4-7 The 2015 IMPROVE-IT study found the combination of simvastatin and ezetimibe resulted in a significantly lower risk of cardiovascular events than simvastatin monotherapy. IMPROVE-IT also reported a further clinical benefit when lower LDL targets (ie, < 55 mg/dL) are achieved, which aligns with the expert consensus pathway recommendations for a lower LDL goal for very high-risk patients.^2,5

The RACING trial found that treatment with a moderate-intensity statin and ezetimibe was noninferior to treatment with a high-intensity statin for the primary outcome of occurrence of cardiovascular death, major cardiovascular events, or nonfatal stroke within 3 years. The combination of moderate-intensity statin and ezetimibe achieved lower LDL-C levels and lower incidence of drug intolerance compared to high intensity statin monotherapy.⁶ The SHARP-CKD study assessed major atherosclerotic events in patients with CKD who had no history of MI or coronary revascularization. The study found that lowering LDL-C with the combination of simvastatin plus ezetimibe safely reduces the risk of major atherosclerotic events in a wide range of patients with CKD.⁷

Lastly, the 2019 EWTOPIA 75 study found that ezetimibe noted a statistically significant reduction in the incidence of the composite of sudden cardiac death, MI, coronary revascularization, or stroke compared to placebo. Ezetimibe showed benefits in preventing ASCVD events independently of statin therapy.⁸ These clinical trials provided evidence for the efficacy of ezetimibe for secondary or primary prevention of ASCVD, patients with CKD, and patients who are not at their LDL goal despite maximally tolerated statin therapy.

Reductions in LDL levels with ezetimibe are reported to be 15% to 19% for monotherapy and 13% to 25% when used in combination with a statin.⁴ Given that the ACC now recommends lower LDL goals, patients may need additional lowering despite taking maximally tolerated statin therapy.² Additionally, the package insert for ezetimibe reports increased area under the curve (AUC) values of ezetimibe and its metabolites in patients with severe renal disease. It is anticipated that ezetimibe may show an increased reduction of LDL and non-HDL, but there may also be an increased risk for muscle-related AEs.³

This quality-assurance quality improvement project investigated the use of ezetimibe in patients with CKD to determine whether there is further LDL and non-HDL reduction in this patient population. It sought to determine the LDL and non-HDL percentage reduction in patients with and without CKD at the Wilkes-Barre Veterans Affairs Medical Center (WBVAMC) and whether there is an increased risk for muscle-related AEs. Determining the percentage reduction of LDL and non-HDL within this population can help increase use of ezetimibe in patients not at their LDL or non-HDL goal or for those patients unable to tolerate statin therapy.

Methods

This single-center retrospective chart review investigated patients prescribed ezetimibe by a patient aligned care team (PACT) pharmacist at WBVAMC between September 1, 2021, and September 1, 2023. This project was determined to be nonresearch by the Veterans Integrated Service Network 4 multisite institutional review board. Patients were excluded from the review if they started taking ezetimibe outside of the prespecified time frame, if ezetimibe was initiated by a non-WBVAMC PACT pharmacist, or if there was no follow-up lipid panel obtained within 6 months of initiation of ezetimibe.

The primary outcomes were to determine the percentage mean change in LDL and non-HDL reduction and the incidence of muscle-related AEs after initiation of ezetimibe in patients without CKD. The secondary outcomes were to determine the percentage mean change in LDL and non-HDL levels and the incidence of muscle-related AEs after initiation of ezetimibe in patients with CKD. For this study, CKD was defined as a patient having an eGFR 15 to 60 ml/min/1.73 m². Non-HDL is the combination of LDL-C and very LDL-C and represents all potentially atherogenic particles. The 2022 Expert Consensus Pathway included non-HDL goals in addition to LDL goals.² Non-HDL cholesterol levels can be used for patients with elevated triglycerides where LDL levels may not be as accurate. To account for instances of elevated triglycerides, this study assessed changes in both LDL and non-HDL levels.

Data were collected from the US Department of Veterans Affairs (VA) Computerized Patient Record System (CPRS) and recorded in a spreadsheet. Collected data included age, sex, race, concomitant cholesterol-lowering medications (statin, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor, bempedoic acid, fish oil, niacin, bile acid sequestrants, and fibrates), baseline lipid panel, lipid panel within 6 months of ezetimibe initiation, and eGFR level. If the patient’s LDL or non-HDL levels worsened on the follow-up lipid panel, their baseline LDL and non-HDL levels were used to calculate the percentage reduction; thus, the percentage reduction would be 0%. This strategy was used in prior research, notably the IMPROVE-IT and SHARP-CKD trials. 

Ezetimibe 5 mg once daily was used in this study based on a 2008 VA study that evaluated the use of ezetimibe 5 mg vs ezetimibe 10 mg and the percentage reduction of LDL with each dose. The study found no significant difference between the 5 mg and 10 mg dose.⁹ Most patients included in this study received the 5 mg dose.

Results

This retrospective chart review consisted of 173 patients, 137 (79.2%) without CKD and 36 (20.8%) with CKD at baseline. The mean age was 69.6 years, 155 (89.6%) patients were male, and 18 (10.4%) were female. There were 164 concomitant medications, including 115 patients prescribed a statin and 38 patients prescribed fish oil (Table 1).

Patients without CKD had mean reductions in LDL levels of 23.5% and non-HDL levels of 21.7% (Figure). Patients who had an increase in LDL and non-HDL levels were excluded to control for potential confounding factors such as dietary changes, discontinuation of ezetimibe therapy, nonadherence to ezetimibe, and medication changes that impacted follow-up laboratory tests such as discontinuation of a statin. Fifteen patients experienced an increase in LDL or non-HDL levels. After excluding these patients, those without CKD had a mean reduction in LDL levels of 28.0% and non-HDL levels of 25.5%. Nineteen (13.9%) patients without CKD experienced a muscle-related AE (Table 2). One patient discontinued ezetimibe and statin use following a Lyme disease diagnosis due to concerns over potential muscle-related AEs. 

Patients with CKD had a mean reduction in LDL and non-HDL levels of 27.0% and 24.8%, respectively. Patients with an increase in LDL or non-HDL levels were also excluded to help control for potential confounding factors. After excluding 4 patients with increased LDL and non-HDL levels, the mean reduction in LDL and non-HDL levels was 30.5% and 27.5%, respectively. Five (13.9%) patients with CKD experienced muscle-related AEs thought to be due to ezetimibe. Other AEs (eg, urticaria, diarrhea, reflux, dizziness, headache, upset stomach) were reported that led to discontinuation of ezetimibe, but only muscle-related AEs were analyzed.

Discussion

This retrospective chart review found larger reductions in LDL and non-HDL levels for patients with CKD than reported in the literature.⁴ Based on the findings that indicate a greater cholesterol reduction with ezetimibe, the results suggest an underutilization of ezetimibe in clinical practice, which may be due to clinicians favoring statin therapy and overlooking ezetimibe as a viable option based on recommendation in earlier guidelines. The 2022 guidelines transitioned from a statin focus to a focus on LDL targets and goals.²

According to the ACC, there is evidence to support a direct relationship between LDL-C levels, atherosclerosis progression, and ASCVD event risk.² Absolute LDL-C level reduction is directly associated with ASCVD risk reduction which supports the LDL hypothesis. There appears to be no specific LDL-C level below which benefit ceases.² This suggests that lower LDL-C targets (< 55 mg/dL) should be used when clinically indicated. Many patients are either unable to reach their goal LDL levels with statin monotherapy or are unable to tolerate statin therapy at higher doses, which may require additional pharmacotherapy to reach goal LDL-C. The ACC expert consensus pathway recommends ezetimibe as the initial add-on treatment to statins.² The RACING trial showed the benefit of adding ezetimibe to a moderate-intensity statin vs increasing to a high-intensity statin dose. This trial found patients had lower LDL levels and lower rates of intolerances, which further supports ezetimibe use.⁶

This quality improvement project assessed LDL and non-HDL level reduction in patients with CKD. As anticipated, there was greater reduction in LDL and non-HDL levels seen in patients with CKD. The SHARP-CKD trial also found reductions in LDL levels with ezetimibe in patients with CKD.⁷ Given the reduction in LDL and non-HDL levels with ezetimibe in patients with or without CKD, add-on therapy of ezetimibe should be recommended for patients who do not achieve their LDL goals with statin therapy or for patients who intolerant to statin therapy. 

The ezetimibe package insert reports myalgias incidence to be < 5% in patients and research has shown up to a 20% incidence of muscle-related AEs with statin therapy.^3,10 Based on the package information reporting increased AUC values of ezetimibe and its metabolites in patients with severe renal disease, it was anticipated there may be an increased risk of muscle-related AEs in patients with CKD.³ However, this study found the same incidence of muscle-related AEs in patients with and without CKD. Previous research on statin-intolerant patients found the incidence of muscle-related AEs with ezetimibe to be 23.0% and 28.8%.^11,12 This increased incidence of muscle-related AEs may be the result of including patients with a history of statin intolerance. Collectively, data from clinical trials and this study indicate that patients with prior intolerances to statins appear to have a higher likelihood of developing a muscle-related AEs with ezetimibe.^11,12 Clinicians and patients should be educated on the potential for these AEs and be aware that the likelihood may be greater if there is a history of statin intolerance. To our knowledge, this was the first study to evaluate muscle-related AEs with ezetimibe in patients with and without CKD.

Limitations

This retrospective chart review was performed over a prespecified period and only patients initiated on ezetimibe by a PACT pharmacist were included. This study did not assess the percentage of LDL reduction in patients on concomitant statins vs those who were not on concomitant statins. The study only included 173 patients. Additionally, the study was primarily composed of White men and may not be representative of other populations. In addition, veterans may not be representative of the general population given their high comorbidity burden and other exposures. Some reported muscle-related AEs associated with ezetimibe may be attributed to the nocebo effect.

Conclusions

The results of this retrospective chart review suggest there may be a larger mean reduction in LDL and non-HDL levels seen with ezetimibe therapy than reported within the literature. There was a larger mean reduction in LDL and non-HDL levels in patients with CKD than in patients without CKD. Additionally, there were the same rates of muscle-related AEs with ezetimibe therapy in patients with and without CKD. The rates of muscle-related AEs with ezetimibe therapy were higher than reported in the medication’s package insert, but lower than reported in literature that included statin-intolerant patients. These results indicate there may be a benefit to an increase in use of ezetimibe in clinical practice due to its increased effectiveness and safety in patients with and without CKD. Ultimately, this can help patients achieve their LDL goals as recommended by ACC clinical practice guidelines.

Statins are widely used to reduce low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) levels for the prevention of atherosclerotic cardiovascular disease (ASCVD).¹ However, despite maximally tolerated statin therapy, many patients may not reach their LDL and non-HDL goals. Some patients may experience adverse events (AEs), particularly muscle-related AEs, which can limit the use of these medications.

The 2022 American College of Cardiology (ACC) expert consensus pathway recommends a goal LDL of < 55 mg/dL in very high-risk patients, defined as those with a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions.² Major ASCVD events include acute coronary syndrome within 12 months, history of myocardial infarction (MI) or ischemic stroke, and symptomatic peripheral arterial disease (ie, claudication with ankle-brachial index < 0.85 or previous revascularization or amputation). Factors for being considered high risk include age > 65 years, heterozygous familial hypercholesterolemia, history of prior coronary artery bypass surgery or percutaneous coronary intervention outside the major ASCVD events, diabetes, hypertension, chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] 15-59 mL/min/1.73 m²), current smoking, persistently elevated LDL cholesterol (LDL-C) levels despite maximally tolerated statin therapy and ezetimibe, and history of congestive heart failure.² For these patients, statin therapy alone may not achieve LDL goal. 

The ACC recommends ezetimibe as the initial nonstatin therapy in patients who are not at their goal LDL.² Ezetimibe works by inhibiting Niemann-Pick C1-Like 1 protein, which causes reduced cholesterol absorption in the small intestine.^2,3 Previous studies have shown the benefit of ezetimibe for LDL reduction and ASCVD prevention.^4-7 The 2015 IMPROVE-IT study found the combination of simvastatin and ezetimibe resulted in a significantly lower risk of cardiovascular events than simvastatin monotherapy. IMPROVE-IT also reported a further clinical benefit when lower LDL targets (ie, < 55 mg/dL) are achieved, which aligns with the expert consensus pathway recommendations for a lower LDL goal for very high-risk patients.^2,5

The RACING trial found that treatment with a moderate-intensity statin and ezetimibe was noninferior to treatment with a high-intensity statin for the primary outcome of occurrence of cardiovascular death, major cardiovascular events, or nonfatal stroke within 3 years. The combination of moderate-intensity statin and ezetimibe achieved lower LDL-C levels and lower incidence of drug intolerance compared to high intensity statin monotherapy.⁶ The SHARP-CKD study assessed major atherosclerotic events in patients with CKD who had no history of MI or coronary revascularization. The study found that lowering LDL-C with the combination of simvastatin plus ezetimibe safely reduces the risk of major atherosclerotic events in a wide range of patients with CKD.⁷

Lastly, the 2019 EWTOPIA 75 study found that ezetimibe noted a statistically significant reduction in the incidence of the composite of sudden cardiac death, MI, coronary revascularization, or stroke compared to placebo. Ezetimibe showed benefits in preventing ASCVD events independently of statin therapy.⁸ These clinical trials provided evidence for the efficacy of ezetimibe for secondary or primary prevention of ASCVD, patients with CKD, and patients who are not at their LDL goal despite maximally tolerated statin therapy.

Reductions in LDL levels with ezetimibe are reported to be 15% to 19% for monotherapy and 13% to 25% when used in combination with a statin.⁴ Given that the ACC now recommends lower LDL goals, patients may need additional lowering despite taking maximally tolerated statin therapy.² Additionally, the package insert for ezetimibe reports increased area under the curve (AUC) values of ezetimibe and its metabolites in patients with severe renal disease. It is anticipated that ezetimibe may show an increased reduction of LDL and non-HDL, but there may also be an increased risk for muscle-related AEs.³

This quality-assurance quality improvement project investigated the use of ezetimibe in patients with CKD to determine whether there is further LDL and non-HDL reduction in this patient population. It sought to determine the LDL and non-HDL percentage reduction in patients with and without CKD at the Wilkes-Barre Veterans Affairs Medical Center (WBVAMC) and whether there is an increased risk for muscle-related AEs. Determining the percentage reduction of LDL and non-HDL within this population can help increase use of ezetimibe in patients not at their LDL or non-HDL goal or for those patients unable to tolerate statin therapy.

Methods

This single-center retrospective chart review investigated patients prescribed ezetimibe by a patient aligned care team (PACT) pharmacist at WBVAMC between September 1, 2021, and September 1, 2023. This project was determined to be nonresearch by the Veterans Integrated Service Network 4 multisite institutional review board. Patients were excluded from the review if they started taking ezetimibe outside of the prespecified time frame, if ezetimibe was initiated by a non-WBVAMC PACT pharmacist, or if there was no follow-up lipid panel obtained within 6 months of initiation of ezetimibe.

The primary outcomes were to determine the percentage mean change in LDL and non-HDL reduction and the incidence of muscle-related AEs after initiation of ezetimibe in patients without CKD. The secondary outcomes were to determine the percentage mean change in LDL and non-HDL levels and the incidence of muscle-related AEs after initiation of ezetimibe in patients with CKD. For this study, CKD was defined as a patient having an eGFR 15 to 60 ml/min/1.73 m². Non-HDL is the combination of LDL-C and very LDL-C and represents all potentially atherogenic particles. The 2022 Expert Consensus Pathway included non-HDL goals in addition to LDL goals.² Non-HDL cholesterol levels can be used for patients with elevated triglycerides where LDL levels may not be as accurate. To account for instances of elevated triglycerides, this study assessed changes in both LDL and non-HDL levels.

Data were collected from the US Department of Veterans Affairs (VA) Computerized Patient Record System (CPRS) and recorded in a spreadsheet. Collected data included age, sex, race, concomitant cholesterol-lowering medications (statin, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor, bempedoic acid, fish oil, niacin, bile acid sequestrants, and fibrates), baseline lipid panel, lipid panel within 6 months of ezetimibe initiation, and eGFR level. If the patient’s LDL or non-HDL levels worsened on the follow-up lipid panel, their baseline LDL and non-HDL levels were used to calculate the percentage reduction; thus, the percentage reduction would be 0%. This strategy was used in prior research, notably the IMPROVE-IT and SHARP-CKD trials. 

Ezetimibe 5 mg once daily was used in this study based on a 2008 VA study that evaluated the use of ezetimibe 5 mg vs ezetimibe 10 mg and the percentage reduction of LDL with each dose. The study found no significant difference between the 5 mg and 10 mg dose.⁹ Most patients included in this study received the 5 mg dose.

Results

This retrospective chart review consisted of 173 patients, 137 (79.2%) without CKD and 36 (20.8%) with CKD at baseline. The mean age was 69.6 years, 155 (89.6%) patients were male, and 18 (10.4%) were female. There were 164 concomitant medications, including 115 patients prescribed a statin and 38 patients prescribed fish oil (Table 1).

Patients without CKD had mean reductions in LDL levels of 23.5% and non-HDL levels of 21.7% (Figure). Patients who had an increase in LDL and non-HDL levels were excluded to control for potential confounding factors such as dietary changes, discontinuation of ezetimibe therapy, nonadherence to ezetimibe, and medication changes that impacted follow-up laboratory tests such as discontinuation of a statin. Fifteen patients experienced an increase in LDL or non-HDL levels. After excluding these patients, those without CKD had a mean reduction in LDL levels of 28.0% and non-HDL levels of 25.5%. Nineteen (13.9%) patients without CKD experienced a muscle-related AE (Table 2). One patient discontinued ezetimibe and statin use following a Lyme disease diagnosis due to concerns over potential muscle-related AEs. 

Patients with CKD had a mean reduction in LDL and non-HDL levels of 27.0% and 24.8%, respectively. Patients with an increase in LDL or non-HDL levels were also excluded to help control for potential confounding factors. After excluding 4 patients with increased LDL and non-HDL levels, the mean reduction in LDL and non-HDL levels was 30.5% and 27.5%, respectively. Five (13.9%) patients with CKD experienced muscle-related AEs thought to be due to ezetimibe. Other AEs (eg, urticaria, diarrhea, reflux, dizziness, headache, upset stomach) were reported that led to discontinuation of ezetimibe, but only muscle-related AEs were analyzed.

Discussion

This retrospective chart review found larger reductions in LDL and non-HDL levels for patients with CKD than reported in the literature.⁴ Based on the findings that indicate a greater cholesterol reduction with ezetimibe, the results suggest an underutilization of ezetimibe in clinical practice, which may be due to clinicians favoring statin therapy and overlooking ezetimibe as a viable option based on recommendation in earlier guidelines. The 2022 guidelines transitioned from a statin focus to a focus on LDL targets and goals.²

According to the ACC, there is evidence to support a direct relationship between LDL-C levels, atherosclerosis progression, and ASCVD event risk.² Absolute LDL-C level reduction is directly associated with ASCVD risk reduction which supports the LDL hypothesis. There appears to be no specific LDL-C level below which benefit ceases.² This suggests that lower LDL-C targets (< 55 mg/dL) should be used when clinically indicated. Many patients are either unable to reach their goal LDL levels with statin monotherapy or are unable to tolerate statin therapy at higher doses, which may require additional pharmacotherapy to reach goal LDL-C. The ACC expert consensus pathway recommends ezetimibe as the initial add-on treatment to statins.² The RACING trial showed the benefit of adding ezetimibe to a moderate-intensity statin vs increasing to a high-intensity statin dose. This trial found patients had lower LDL levels and lower rates of intolerances, which further supports ezetimibe use.⁶

This quality improvement project assessed LDL and non-HDL level reduction in patients with CKD. As anticipated, there was greater reduction in LDL and non-HDL levels seen in patients with CKD. The SHARP-CKD trial also found reductions in LDL levels with ezetimibe in patients with CKD.⁷ Given the reduction in LDL and non-HDL levels with ezetimibe in patients with or without CKD, add-on therapy of ezetimibe should be recommended for patients who do not achieve their LDL goals with statin therapy or for patients who intolerant to statin therapy. 

The ezetimibe package insert reports myalgias incidence to be < 5% in patients and research has shown up to a 20% incidence of muscle-related AEs with statin therapy.^3,10 Based on the package information reporting increased AUC values of ezetimibe and its metabolites in patients with severe renal disease, it was anticipated there may be an increased risk of muscle-related AEs in patients with CKD.³ However, this study found the same incidence of muscle-related AEs in patients with and without CKD. Previous research on statin-intolerant patients found the incidence of muscle-related AEs with ezetimibe to be 23.0% and 28.8%.^11,12 This increased incidence of muscle-related AEs may be the result of including patients with a history of statin intolerance. Collectively, data from clinical trials and this study indicate that patients with prior intolerances to statins appear to have a higher likelihood of developing a muscle-related AEs with ezetimibe.^11,12 Clinicians and patients should be educated on the potential for these AEs and be aware that the likelihood may be greater if there is a history of statin intolerance. To our knowledge, this was the first study to evaluate muscle-related AEs with ezetimibe in patients with and without CKD.

Limitations

This retrospective chart review was performed over a prespecified period and only patients initiated on ezetimibe by a PACT pharmacist were included. This study did not assess the percentage of LDL reduction in patients on concomitant statins vs those who were not on concomitant statins. The study only included 173 patients. Additionally, the study was primarily composed of White men and may not be representative of other populations. In addition, veterans may not be representative of the general population given their high comorbidity burden and other exposures. Some reported muscle-related AEs associated with ezetimibe may be attributed to the nocebo effect.

Conclusions

The results of this retrospective chart review suggest there may be a larger mean reduction in LDL and non-HDL levels seen with ezetimibe therapy than reported within the literature. There was a larger mean reduction in LDL and non-HDL levels in patients with CKD than in patients without CKD. Additionally, there were the same rates of muscle-related AEs with ezetimibe therapy in patients with and without CKD. The rates of muscle-related AEs with ezetimibe therapy were higher than reported in the medication’s package insert, but lower than reported in literature that included statin-intolerant patients. These results indicate there may be a benefit to an increase in use of ezetimibe in clinical practice due to its increased effectiveness and safety in patients with and without CKD. Ultimately, this can help patients achieve their LDL goals as recommended by ACC clinical practice guidelines.

Statins are widely used to reduce low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) levels for the prevention of atherosclerotic cardiovascular disease (ASCVD).¹ However, despite maximally tolerated statin therapy, many patients may not reach their LDL and non-HDL goals. Some patients may experience adverse events (AEs), particularly muscle-related AEs, which can limit the use of these medications.

The 2022 American College of Cardiology (ACC) expert consensus pathway recommends a goal LDL of < 55 mg/dL in very high-risk patients, defined as those with a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions.² Major ASCVD events include acute coronary syndrome within 12 months, history of myocardial infarction (MI) or ischemic stroke, and symptomatic peripheral arterial disease (ie, claudication with ankle-brachial index < 0.85 or previous revascularization or amputation). Factors for being considered high risk include age > 65 years, heterozygous familial hypercholesterolemia, history of prior coronary artery bypass surgery or percutaneous coronary intervention outside the major ASCVD events, diabetes, hypertension, chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] 15-59 mL/min/1.73 m²), current smoking, persistently elevated LDL cholesterol (LDL-C) levels despite maximally tolerated statin therapy and ezetimibe, and history of congestive heart failure.² For these patients, statin therapy alone may not achieve LDL goal. 

The ACC recommends ezetimibe as the initial nonstatin therapy in patients who are not at their goal LDL.² Ezetimibe works by inhibiting Niemann-Pick C1-Like 1 protein, which causes reduced cholesterol absorption in the small intestine.^2,3 Previous studies have shown the benefit of ezetimibe for LDL reduction and ASCVD prevention.^4-7 The 2015 IMPROVE-IT study found the combination of simvastatin and ezetimibe resulted in a significantly lower risk of cardiovascular events than simvastatin monotherapy. IMPROVE-IT also reported a further clinical benefit when lower LDL targets (ie, < 55 mg/dL) are achieved, which aligns with the expert consensus pathway recommendations for a lower LDL goal for very high-risk patients.^2,5

The RACING trial found that treatment with a moderate-intensity statin and ezetimibe was noninferior to treatment with a high-intensity statin for the primary outcome of occurrence of cardiovascular death, major cardiovascular events, or nonfatal stroke within 3 years. The combination of moderate-intensity statin and ezetimibe achieved lower LDL-C levels and lower incidence of drug intolerance compared to high intensity statin monotherapy.⁶ The SHARP-CKD study assessed major atherosclerotic events in patients with CKD who had no history of MI or coronary revascularization. The study found that lowering LDL-C with the combination of simvastatin plus ezetimibe safely reduces the risk of major atherosclerotic events in a wide range of patients with CKD.⁷

Lastly, the 2019 EWTOPIA 75 study found that ezetimibe noted a statistically significant reduction in the incidence of the composite of sudden cardiac death, MI, coronary revascularization, or stroke compared to placebo. Ezetimibe showed benefits in preventing ASCVD events independently of statin therapy.⁸ These clinical trials provided evidence for the efficacy of ezetimibe for secondary or primary prevention of ASCVD, patients with CKD, and patients who are not at their LDL goal despite maximally tolerated statin therapy.

Reductions in LDL levels with ezetimibe are reported to be 15% to 19% for monotherapy and 13% to 25% when used in combination with a statin.⁴ Given that the ACC now recommends lower LDL goals, patients may need additional lowering despite taking maximally tolerated statin therapy.² Additionally, the package insert for ezetimibe reports increased area under the curve (AUC) values of ezetimibe and its metabolites in patients with severe renal disease. It is anticipated that ezetimibe may show an increased reduction of LDL and non-HDL, but there may also be an increased risk for muscle-related AEs.³

This quality-assurance quality improvement project investigated the use of ezetimibe in patients with CKD to determine whether there is further LDL and non-HDL reduction in this patient population. It sought to determine the LDL and non-HDL percentage reduction in patients with and without CKD at the Wilkes-Barre Veterans Affairs Medical Center (WBVAMC) and whether there is an increased risk for muscle-related AEs. Determining the percentage reduction of LDL and non-HDL within this population can help increase use of ezetimibe in patients not at their LDL or non-HDL goal or for those patients unable to tolerate statin therapy.

Methods

This single-center retrospective chart review investigated patients prescribed ezetimibe by a patient aligned care team (PACT) pharmacist at WBVAMC between September 1, 2021, and September 1, 2023. This project was determined to be nonresearch by the Veterans Integrated Service Network 4 multisite institutional review board. Patients were excluded from the review if they started taking ezetimibe outside of the prespecified time frame, if ezetimibe was initiated by a non-WBVAMC PACT pharmacist, or if there was no follow-up lipid panel obtained within 6 months of initiation of ezetimibe.

The primary outcomes were to determine the percentage mean change in LDL and non-HDL reduction and the incidence of muscle-related AEs after initiation of ezetimibe in patients without CKD. The secondary outcomes were to determine the percentage mean change in LDL and non-HDL levels and the incidence of muscle-related AEs after initiation of ezetimibe in patients with CKD. For this study, CKD was defined as a patient having an eGFR 15 to 60 ml/min/1.73 m². Non-HDL is the combination of LDL-C and very LDL-C and represents all potentially atherogenic particles. The 2022 Expert Consensus Pathway included non-HDL goals in addition to LDL goals.² Non-HDL cholesterol levels can be used for patients with elevated triglycerides where LDL levels may not be as accurate. To account for instances of elevated triglycerides, this study assessed changes in both LDL and non-HDL levels.

Data were collected from the US Department of Veterans Affairs (VA) Computerized Patient Record System (CPRS) and recorded in a spreadsheet. Collected data included age, sex, race, concomitant cholesterol-lowering medications (statin, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor, bempedoic acid, fish oil, niacin, bile acid sequestrants, and fibrates), baseline lipid panel, lipid panel within 6 months of ezetimibe initiation, and eGFR level. If the patient’s LDL or non-HDL levels worsened on the follow-up lipid panel, their baseline LDL and non-HDL levels were used to calculate the percentage reduction; thus, the percentage reduction would be 0%. This strategy was used in prior research, notably the IMPROVE-IT and SHARP-CKD trials. 

Ezetimibe 5 mg once daily was used in this study based on a 2008 VA study that evaluated the use of ezetimibe 5 mg vs ezetimibe 10 mg and the percentage reduction of LDL with each dose. The study found no significant difference between the 5 mg and 10 mg dose.⁹ Most patients included in this study received the 5 mg dose.

Results

This retrospective chart review consisted of 173 patients, 137 (79.2%) without CKD and 36 (20.8%) with CKD at baseline. The mean age was 69.6 years, 155 (89.6%) patients were male, and 18 (10.4%) were female. There were 164 concomitant medications, including 115 patients prescribed a statin and 38 patients prescribed fish oil (Table 1).

Patients without CKD had mean reductions in LDL levels of 23.5% and non-HDL levels of 21.7% (Figure). Patients who had an increase in LDL and non-HDL levels were excluded to control for potential confounding factors such as dietary changes, discontinuation of ezetimibe therapy, nonadherence to ezetimibe, and medication changes that impacted follow-up laboratory tests such as discontinuation of a statin. Fifteen patients experienced an increase in LDL or non-HDL levels. After excluding these patients, those without CKD had a mean reduction in LDL levels of 28.0% and non-HDL levels of 25.5%. Nineteen (13.9%) patients without CKD experienced a muscle-related AE (Table 2). One patient discontinued ezetimibe and statin use following a Lyme disease diagnosis due to concerns over potential muscle-related AEs. 

Patients with CKD had a mean reduction in LDL and non-HDL levels of 27.0% and 24.8%, respectively. Patients with an increase in LDL or non-HDL levels were also excluded to help control for potential confounding factors. After excluding 4 patients with increased LDL and non-HDL levels, the mean reduction in LDL and non-HDL levels was 30.5% and 27.5%, respectively. Five (13.9%) patients with CKD experienced muscle-related AEs thought to be due to ezetimibe. Other AEs (eg, urticaria, diarrhea, reflux, dizziness, headache, upset stomach) were reported that led to discontinuation of ezetimibe, but only muscle-related AEs were analyzed.

Discussion

This retrospective chart review found larger reductions in LDL and non-HDL levels for patients with CKD than reported in the literature.⁴ Based on the findings that indicate a greater cholesterol reduction with ezetimibe, the results suggest an underutilization of ezetimibe in clinical practice, which may be due to clinicians favoring statin therapy and overlooking ezetimibe as a viable option based on recommendation in earlier guidelines. The 2022 guidelines transitioned from a statin focus to a focus on LDL targets and goals.²

According to the ACC, there is evidence to support a direct relationship between LDL-C levels, atherosclerosis progression, and ASCVD event risk.² Absolute LDL-C level reduction is directly associated with ASCVD risk reduction which supports the LDL hypothesis. There appears to be no specific LDL-C level below which benefit ceases.² This suggests that lower LDL-C targets (< 55 mg/dL) should be used when clinically indicated. Many patients are either unable to reach their goal LDL levels with statin monotherapy or are unable to tolerate statin therapy at higher doses, which may require additional pharmacotherapy to reach goal LDL-C. The ACC expert consensus pathway recommends ezetimibe as the initial add-on treatment to statins.² The RACING trial showed the benefit of adding ezetimibe to a moderate-intensity statin vs increasing to a high-intensity statin dose. This trial found patients had lower LDL levels and lower rates of intolerances, which further supports ezetimibe use.⁶

This quality improvement project assessed LDL and non-HDL level reduction in patients with CKD. As anticipated, there was greater reduction in LDL and non-HDL levels seen in patients with CKD. The SHARP-CKD trial also found reductions in LDL levels with ezetimibe in patients with CKD.⁷ Given the reduction in LDL and non-HDL levels with ezetimibe in patients with or without CKD, add-on therapy of ezetimibe should be recommended for patients who do not achieve their LDL goals with statin therapy or for patients who intolerant to statin therapy. 

The ezetimibe package insert reports myalgias incidence to be < 5% in patients and research has shown up to a 20% incidence of muscle-related AEs with statin therapy.^3,10 Based on the package information reporting increased AUC values of ezetimibe and its metabolites in patients with severe renal disease, it was anticipated there may be an increased risk of muscle-related AEs in patients with CKD.³ However, this study found the same incidence of muscle-related AEs in patients with and without CKD. Previous research on statin-intolerant patients found the incidence of muscle-related AEs with ezetimibe to be 23.0% and 28.8%.^11,12 This increased incidence of muscle-related AEs may be the result of including patients with a history of statin intolerance. Collectively, data from clinical trials and this study indicate that patients with prior intolerances to statins appear to have a higher likelihood of developing a muscle-related AEs with ezetimibe.^11,12 Clinicians and patients should be educated on the potential for these AEs and be aware that the likelihood may be greater if there is a history of statin intolerance. To our knowledge, this was the first study to evaluate muscle-related AEs with ezetimibe in patients with and without CKD.

Limitations

This retrospective chart review was performed over a prespecified period and only patients initiated on ezetimibe by a PACT pharmacist were included. This study did not assess the percentage of LDL reduction in patients on concomitant statins vs those who were not on concomitant statins. The study only included 173 patients. Additionally, the study was primarily composed of White men and may not be representative of other populations. In addition, veterans may not be representative of the general population given their high comorbidity burden and other exposures. Some reported muscle-related AEs associated with ezetimibe may be attributed to the nocebo effect.

Conclusions

The results of this retrospective chart review suggest there may be a larger mean reduction in LDL and non-HDL levels seen with ezetimibe therapy than reported within the literature. There was a larger mean reduction in LDL and non-HDL levels in patients with CKD than in patients without CKD. Additionally, there were the same rates of muscle-related AEs with ezetimibe therapy in patients with and without CKD. The rates of muscle-related AEs with ezetimibe therapy were higher than reported in the medication’s package insert, but lower than reported in literature that included statin-intolerant patients. These results indicate there may be a benefit to an increase in use of ezetimibe in clinical practice due to its increased effectiveness and safety in patients with and without CKD. Ultimately, this can help patients achieve their LDL goals as recommended by ACC clinical practice guidelines.

The impact of obesity in the United States is significant. Between August 2021 and August 2023, the prevalence of obesity (body mass index ≥ 30) in US adults was 40.3%.¹ The prevalence of obesity in adults aged 40 to 59 years was 46.4%, higher than the prevalence in adults aged 20 to 39 years (35.5%) and those aged ≥ 60 years (38.9%).¹ The excess annual medical costs associated with obesity in the US are estimated at nearly $173 billion.²

The first-line treatment for obesity is lifestyle modifications, including a healthy diet and exercise. When lifestyle modifications are not enough to achieve weight-loss goals, bariatric surgery and anti-obesity medications (AOMs) are often considered. Five medications were approved for the long-term tretament of obesity by the US Food and Drug Administration (FDA) between 2021 and 2023, when this study was conducted: semaglutide (Wegovy), liraglutide (Saxenda), phentermine and topiramate, naltrexone and bupropion, and orlistat. The clinically meaningful (and commonly accepted) weight-loss target for these medications is ≥ 5% from baseline by week 12 of the maximally tolerated dose of therapy. A 5% weight loss has been shown to be clinically significant in improving cardiometabolic risk factors.^3,4 These medications are intended to be used as an adjunct to healthy diet and exercise. Of note, semaglutide and liraglutide carry brand names, which are associated with different dosing for the treatment of type 2 diabetes mellitus (T2DM).

All 5 FDA-approved AOMs were available at the Veterans Affairs Sioux Falls Health Care System (VASFHCS) for the treatment of obesity at the time of the study. To qualify for an AOM, a veteran at VASFHCS must first work with a dietitian or be enrolled in the MOVE! clinic to participate in the weight management program, which focuses on dietary, exercise, and behavioral changes. At VASFHCS, AOMs are prescribed by primary care practitioners, clinical pharmacy providers, and advanced practitioners within the MOVE! program.

Ample data exist for the efficacy of AOMs. However, no published research has reported on AOM efficacy by age group (Appendix).^5-11 While most of the AOM clinical trials included older adults, the average age of participants was typically between 40 and 50 years. It is well-known that pharmacokinetic and pharmacodynamic changes occur as age increases. Renal and hepatic clearance is reduced while the volume distribution and sensitivities to some medications may increase. ¹² Although this study did not focus on specific pharmacokinetic and pharmacodynamic changes with respect to AOM, it is important to recognize that this may play a role in the efficacy and safety of AOMs in older adults.

Methods

This retrospective single-center chart review was performed using the VASFHCS Computerized Patient Record System to compare the efficacy of AOMs in older adults (aged ≥ 65 years) vs adults (aged < 65 years). The primary endpoint was the percent change in body weight from baseline to 6 and 12 months after initiation of AOM therapy in the older adult vs adult population. Secondary endpoints included changes in low-density lipoprotein (LDL), hemoglobin A_1c (HbA_1c), and blood pressure (BP) from baseline compared to 12 months on AOM therapy. HbA_1c was assessed in patients with T2DM or prediabetes at the time of AOM initiation. Two safety endpoints were also explored to determine the incidence of medication adverse events (AEs) and subsequent discontinuation of AOM. A subset analysis was performed to determine whether there was a difference in percent change in body weight between patients in 3 age groups: 18 to 40 years, 41 to 64 years, and ≥ 65 years.

The study population included patients who were prescribed an AOM between January 1, 2021, and June 30, 2023. Patients were excluded if they did not continue AOM therapy for ≥ 6 months after initiation or if they underwent gastric bypass surgery while undergoing AOM therapy. Patients taking semaglutide (Ozempic) or liraglutide (Victoza) for both T2DM and weight loss who were eventually switched to the weight loss formulations (Wegovy or Saxenda) were included. Patients who switched between semaglutide and liraglutide for weight loss were also included. Those taking semaglutide or liraglutide solely for T2DM treatment were excluded because they are dosed differently.

Collected data included age, gender, race, weight (baseline, 6 and 12 months after initiation of AOM), metabolic laboratory values/vital signs (HbA_1c, LDL, and BP at baseline and 12 months after initiation of AOM), diagnosis of T2DM or prediabetes, reported AEs associated with AOM therapy, and date of AOM initiation and discontinuation (if applicable). Baseline values were defined at the time of medication initiation or values documented within 6 months prior to medication initiation if true baseline data were not reported. If values were not recorded at months 6 and 12 after AOM initiation, values documented closest to those targets were used. Weights were used for baseline, 6-, and 12-month data unless they were unavailable due to use of virtual care modalities. In these cases, patient-reported weights were used. Patients were included in the 6-month data, but not the 12-month data, if they were taking AOMs for > 6 months but not for 12 months. If patients had been on multiple AOMs, baseline data were recorded at the start of the first medication that was used for 6 months or longer. Twelve-month data were recorded after subsequent medication change. Twelve-month metabolic laboratory values/vital signs were recorded for patients included in the study even if they did not complete ≥ 12 months of AOM therapy.

Statistical Analysis

Data from patients who were prescribed an AOM from January 2021 to June 2023 and who remained on the medication for ≥ 6 months were analyzed. Baseline characteristics were analyzed using descriptive statistics. The primary and secondary endpoints were evaluated using the t test. The safety endpoints were analyzed using descriptive statistics. An analysis of variance test was used for the subset analysis. Results with P < .05 were statistically significant.

Results

A total of 144 participants were included in this study, 116 in the adult group (aged < 65 years) and 28 in the older adult group (aged ≥ 65 years). Sixty-seven patients were excluded due to prespecified inclusion and exclusion criteria.

Other than the predetermined mean age differences (48 years vs 71 years), there were multiple differences in patient baseline characteristics. When comparing older adults and adults, average weight (283 lb vs 269 lb) and White race (89% vs 87%) were slightly higher in the older adult group. Also, a higher prevalence of T2DM (54% and 18%) and a lower prevalence of prediabetes (21% and 33%) was noted in the older adult group. HbA_1c and BP were similar between both groups at baseline, while LDL was slightly lower in the older adult group (Table 1).

Patients in the adult group lost a mean 7.0% and 8.7% of body weight at 6 and 12 months, respectively, while the older adult group lost 5.0% and 6.6% body weight at 6 and 12 months, respectively. The difference in percent change in body weight was not statistically different at 6 (P = .08) or 12 (P = .26) months between patients in the adult group vs the older adult group or in the specific age groups (18-40 years, 41-64 years, ≥ 65 years) at 6 months (P = .24) or 12 months (P = .53) (Figure).

At 12 months, the difference between the adult group vs the older adult group was not statistically significant for HbA_1c in patients with T2DM or prediabetes (P = .73), LDL (P = .95), systolic BP (P = .58), or diastolic BP (P = .51) (Table 2).

For the safety endpoint, the incidence of AEs was found to be different between groups. There were more reported AEs (61.2% vs 39.3%) and a greater increase in therapy discontinuation due to AEs (6.0% vs 0%) in the adult group compared to the older adult group (Table 3).

Discussion

Patients taking AOMs revealed no statistically significant difference in percent change in body weight at 6 or 12 months between adults aged < 65 years and older adults aged ≥ 65 years. The subset analysis also showed no statistically significant difference in change in percent body weight between more narrowly defined age groups of 18 to 40 years, 41 to 64 years, and ≥ 65 years. This suggests that AOM may have similar efficacy for weight loss in all ages of adults.

Secondary endpoint findings showed no statistically significant difference in HbA_1c (in patients with T2DM or prediabetes), LDL, or BP at 12 months between the 2 groups. Although this study did not differentiate secondary outcomes based on the individual AOM, the change in HbA_1c in both groups was expected, given that 70% of the patients included in this study were taking a glucagon-like peptide-1 agonist (liraglutide and semaglutide) at some point during the study. It’s also worth noting that secondary endpoints were collected for patients who discontinued the AOM between 6 and 12 months. Therefore, the patients’ HbA_1c, LDL, and BP may not have accurately reflected the change that could have been expected if they had continued AOM therapy beyond the 12-month period.

Due to the different mechanisms and range in efficacy that AOMs have in regard to weight loss, changes in all outcomes, including weight, HbA_1c, LDL, and BP were expected to vary as patients were included even after switching AOM (collection of data started after ≥ 6 months on a single AOM). Switching of AOM after the first 6 months of therapy was recorded in 25% of the patients in the ≥ 65 years group and 330% of the patients in the < 65 years group.

The incidence of AEs and subsequent discontinuation of AOMs in this study was higher in the adult group. This study excluded patients who did not continue taking an AOM for at least 6 months. As a result, the incidence of AEs between the 2 groups within the first 6 months of AOM therapy remains unknown. It is possible that during the first 6 months of therapy, patients aged < 65 years were more willing to tolerate or had fewer severe AEs compared with the older adult group. It’s also possible that the smaller number of patients in the older adult group was due to increased AEs that led them to discontinue early (before completion of 6 months of therapy) and/or prescriber discomfort in using AOMs in the older adult population. In addition, because the specific medication(s) taken by patients in each group were not detailed, it is unknown whether the adult group was taking AOMs associated with a greater number of AEs.

Limitations

This was a retrospective study with a relatively small sample size. A larger sample size may have shown more precise differences between age groups and may be more representative of the general population. Additionally, data were reliant on appropriate documentation, and adherence to AOM therapy was not assessed due to the retrospective nature of this study. At times, the study relied on patient reported data points, such as weight, if a clinic weight was not available. Also, this study did not account for many potential confounding factors such as other medications taken by the patient, which can affect outcomes including weight, HbA_1c, LDL, blood pressure, and AEs.

Conclusions

This retrospective study of patients taking AOMs showed no statistically significant difference in weight loss at 6 or 12 months between adults aged < 65 years and older adults aged ≥ 65 years. A subset analysis found no statistically significant difference in change in body weight between specific age groups (18-40 years, 41-64 years, and ≥ 65 years). There was also no statistically significant difference in secondary outcomes, including change in HbA_1c (in patients with T2DM or prediabetes), LDL or BP between age groups. The safety endpoints showed a higher incidence of medication AEs in the adult group, with more of these adults discontinuing therapy due to AEs. This study indicates that AOM may have similar outcomes for weight loss and metabolic laboratory values/vital sign changes between adults and older adults. Also, our findings suggest that patients aged < 65 years may experience more AEs than patients aged ≥ 65 years after ≥ 6 months of AOM therapy. Larger studies are needed to further evaluate these age-specific findings.

The impact of obesity in the United States is significant. Between August 2021 and August 2023, the prevalence of obesity (body mass index ≥ 30) in US adults was 40.3%.¹ The prevalence of obesity in adults aged 40 to 59 years was 46.4%, higher than the prevalence in adults aged 20 to 39 years (35.5%) and those aged ≥ 60 years (38.9%).¹ The excess annual medical costs associated with obesity in the US are estimated at nearly $173 billion.²

The first-line treatment for obesity is lifestyle modifications, including a healthy diet and exercise. When lifestyle modifications are not enough to achieve weight-loss goals, bariatric surgery and anti-obesity medications (AOMs) are often considered. Five medications were approved for the long-term tretament of obesity by the US Food and Drug Administration (FDA) between 2021 and 2023, when this study was conducted: semaglutide (Wegovy), liraglutide (Saxenda), phentermine and topiramate, naltrexone and bupropion, and orlistat. The clinically meaningful (and commonly accepted) weight-loss target for these medications is ≥ 5% from baseline by week 12 of the maximally tolerated dose of therapy. A 5% weight loss has been shown to be clinically significant in improving cardiometabolic risk factors.^3,4 These medications are intended to be used as an adjunct to healthy diet and exercise. Of note, semaglutide and liraglutide carry brand names, which are associated with different dosing for the treatment of type 2 diabetes mellitus (T2DM).

All 5 FDA-approved AOMs were available at the Veterans Affairs Sioux Falls Health Care System (VASFHCS) for the treatment of obesity at the time of the study. To qualify for an AOM, a veteran at VASFHCS must first work with a dietitian or be enrolled in the MOVE! clinic to participate in the weight management program, which focuses on dietary, exercise, and behavioral changes. At VASFHCS, AOMs are prescribed by primary care practitioners, clinical pharmacy providers, and advanced practitioners within the MOVE! program.

Ample data exist for the efficacy of AOMs. However, no published research has reported on AOM efficacy by age group (Appendix).^5-11 While most of the AOM clinical trials included older adults, the average age of participants was typically between 40 and 50 years. It is well-known that pharmacokinetic and pharmacodynamic changes occur as age increases. Renal and hepatic clearance is reduced while the volume distribution and sensitivities to some medications may increase. ¹² Although this study did not focus on specific pharmacokinetic and pharmacodynamic changes with respect to AOM, it is important to recognize that this may play a role in the efficacy and safety of AOMs in older adults.

Methods

This retrospective single-center chart review was performed using the VASFHCS Computerized Patient Record System to compare the efficacy of AOMs in older adults (aged ≥ 65 years) vs adults (aged < 65 years). The primary endpoint was the percent change in body weight from baseline to 6 and 12 months after initiation of AOM therapy in the older adult vs adult population. Secondary endpoints included changes in low-density lipoprotein (LDL), hemoglobin A_1c (HbA_1c), and blood pressure (BP) from baseline compared to 12 months on AOM therapy. HbA_1c was assessed in patients with T2DM or prediabetes at the time of AOM initiation. Two safety endpoints were also explored to determine the incidence of medication adverse events (AEs) and subsequent discontinuation of AOM. A subset analysis was performed to determine whether there was a difference in percent change in body weight between patients in 3 age groups: 18 to 40 years, 41 to 64 years, and ≥ 65 years.

The study population included patients who were prescribed an AOM between January 1, 2021, and June 30, 2023. Patients were excluded if they did not continue AOM therapy for ≥ 6 months after initiation or if they underwent gastric bypass surgery while undergoing AOM therapy. Patients taking semaglutide (Ozempic) or liraglutide (Victoza) for both T2DM and weight loss who were eventually switched to the weight loss formulations (Wegovy or Saxenda) were included. Patients who switched between semaglutide and liraglutide for weight loss were also included. Those taking semaglutide or liraglutide solely for T2DM treatment were excluded because they are dosed differently.

Collected data included age, gender, race, weight (baseline, 6 and 12 months after initiation of AOM), metabolic laboratory values/vital signs (HbA_1c, LDL, and BP at baseline and 12 months after initiation of AOM), diagnosis of T2DM or prediabetes, reported AEs associated with AOM therapy, and date of AOM initiation and discontinuation (if applicable). Baseline values were defined at the time of medication initiation or values documented within 6 months prior to medication initiation if true baseline data were not reported. If values were not recorded at months 6 and 12 after AOM initiation, values documented closest to those targets were used. Weights were used for baseline, 6-, and 12-month data unless they were unavailable due to use of virtual care modalities. In these cases, patient-reported weights were used. Patients were included in the 6-month data, but not the 12-month data, if they were taking AOMs for > 6 months but not for 12 months. If patients had been on multiple AOMs, baseline data were recorded at the start of the first medication that was used for 6 months or longer. Twelve-month data were recorded after subsequent medication change. Twelve-month metabolic laboratory values/vital signs were recorded for patients included in the study even if they did not complete ≥ 12 months of AOM therapy.

Statistical Analysis

Data from patients who were prescribed an AOM from January 2021 to June 2023 and who remained on the medication for ≥ 6 months were analyzed. Baseline characteristics were analyzed using descriptive statistics. The primary and secondary endpoints were evaluated using the t test. The safety endpoints were analyzed using descriptive statistics. An analysis of variance test was used for the subset analysis. Results with P < .05 were statistically significant.

Results

A total of 144 participants were included in this study, 116 in the adult group (aged < 65 years) and 28 in the older adult group (aged ≥ 65 years). Sixty-seven patients were excluded due to prespecified inclusion and exclusion criteria.

Other than the predetermined mean age differences (48 years vs 71 years), there were multiple differences in patient baseline characteristics. When comparing older adults and adults, average weight (283 lb vs 269 lb) and White race (89% vs 87%) were slightly higher in the older adult group. Also, a higher prevalence of T2DM (54% and 18%) and a lower prevalence of prediabetes (21% and 33%) was noted in the older adult group. HbA_1c and BP were similar between both groups at baseline, while LDL was slightly lower in the older adult group (Table 1).

Patients in the adult group lost a mean 7.0% and 8.7% of body weight at 6 and 12 months, respectively, while the older adult group lost 5.0% and 6.6% body weight at 6 and 12 months, respectively. The difference in percent change in body weight was not statistically different at 6 (P = .08) or 12 (P = .26) months between patients in the adult group vs the older adult group or in the specific age groups (18-40 years, 41-64 years, ≥ 65 years) at 6 months (P = .24) or 12 months (P = .53) (Figure).

At 12 months, the difference between the adult group vs the older adult group was not statistically significant for HbA_1c in patients with T2DM or prediabetes (P = .73), LDL (P = .95), systolic BP (P = .58), or diastolic BP (P = .51) (Table 2).

For the safety endpoint, the incidence of AEs was found to be different between groups. There were more reported AEs (61.2% vs 39.3%) and a greater increase in therapy discontinuation due to AEs (6.0% vs 0%) in the adult group compared to the older adult group (Table 3).

Discussion

Patients taking AOMs revealed no statistically significant difference in percent change in body weight at 6 or 12 months between adults aged < 65 years and older adults aged ≥ 65 years. The subset analysis also showed no statistically significant difference in change in percent body weight between more narrowly defined age groups of 18 to 40 years, 41 to 64 years, and ≥ 65 years. This suggests that AOM may have similar efficacy for weight loss in all ages of adults.

Secondary endpoint findings showed no statistically significant difference in HbA_1c (in patients with T2DM or prediabetes), LDL, or BP at 12 months between the 2 groups. Although this study did not differentiate secondary outcomes based on the individual AOM, the change in HbA_1c in both groups was expected, given that 70% of the patients included in this study were taking a glucagon-like peptide-1 agonist (liraglutide and semaglutide) at some point during the study. It’s also worth noting that secondary endpoints were collected for patients who discontinued the AOM between 6 and 12 months. Therefore, the patients’ HbA_1c, LDL, and BP may not have accurately reflected the change that could have been expected if they had continued AOM therapy beyond the 12-month period.

Due to the different mechanisms and range in efficacy that AOMs have in regard to weight loss, changes in all outcomes, including weight, HbA_1c, LDL, and BP were expected to vary as patients were included even after switching AOM (collection of data started after ≥ 6 months on a single AOM). Switching of AOM after the first 6 months of therapy was recorded in 25% of the patients in the ≥ 65 years group and 330% of the patients in the < 65 years group.

The incidence of AEs and subsequent discontinuation of AOMs in this study was higher in the adult group. This study excluded patients who did not continue taking an AOM for at least 6 months. As a result, the incidence of AEs between the 2 groups within the first 6 months of AOM therapy remains unknown. It is possible that during the first 6 months of therapy, patients aged < 65 years were more willing to tolerate or had fewer severe AEs compared with the older adult group. It’s also possible that the smaller number of patients in the older adult group was due to increased AEs that led them to discontinue early (before completion of 6 months of therapy) and/or prescriber discomfort in using AOMs in the older adult population. In addition, because the specific medication(s) taken by patients in each group were not detailed, it is unknown whether the adult group was taking AOMs associated with a greater number of AEs.

Limitations

This was a retrospective study with a relatively small sample size. A larger sample size may have shown more precise differences between age groups and may be more representative of the general population. Additionally, data were reliant on appropriate documentation, and adherence to AOM therapy was not assessed due to the retrospective nature of this study. At times, the study relied on patient reported data points, such as weight, if a clinic weight was not available. Also, this study did not account for many potential confounding factors such as other medications taken by the patient, which can affect outcomes including weight, HbA_1c, LDL, blood pressure, and AEs.

Conclusions

This retrospective study of patients taking AOMs showed no statistically significant difference in weight loss at 6 or 12 months between adults aged < 65 years and older adults aged ≥ 65 years. A subset analysis found no statistically significant difference in change in body weight between specific age groups (18-40 years, 41-64 years, and ≥ 65 years). There was also no statistically significant difference in secondary outcomes, including change in HbA_1c (in patients with T2DM or prediabetes), LDL or BP between age groups. The safety endpoints showed a higher incidence of medication AEs in the adult group, with more of these adults discontinuing therapy due to AEs. This study indicates that AOM may have similar outcomes for weight loss and metabolic laboratory values/vital sign changes between adults and older adults. Also, our findings suggest that patients aged < 65 years may experience more AEs than patients aged ≥ 65 years after ≥ 6 months of AOM therapy. Larger studies are needed to further evaluate these age-specific findings.

The impact of obesity in the United States is significant. Between August 2021 and August 2023, the prevalence of obesity (body mass index ≥ 30) in US adults was 40.3%.¹ The prevalence of obesity in adults aged 40 to 59 years was 46.4%, higher than the prevalence in adults aged 20 to 39 years (35.5%) and those aged ≥ 60 years (38.9%).¹ The excess annual medical costs associated with obesity in the US are estimated at nearly $173 billion.²

The first-line treatment for obesity is lifestyle modifications, including a healthy diet and exercise. When lifestyle modifications are not enough to achieve weight-loss goals, bariatric surgery and anti-obesity medications (AOMs) are often considered. Five medications were approved for the long-term tretament of obesity by the US Food and Drug Administration (FDA) between 2021 and 2023, when this study was conducted: semaglutide (Wegovy), liraglutide (Saxenda), phentermine and topiramate, naltrexone and bupropion, and orlistat. The clinically meaningful (and commonly accepted) weight-loss target for these medications is ≥ 5% from baseline by week 12 of the maximally tolerated dose of therapy. A 5% weight loss has been shown to be clinically significant in improving cardiometabolic risk factors.^3,4 These medications are intended to be used as an adjunct to healthy diet and exercise. Of note, semaglutide and liraglutide carry brand names, which are associated with different dosing for the treatment of type 2 diabetes mellitus (T2DM).

All 5 FDA-approved AOMs were available at the Veterans Affairs Sioux Falls Health Care System (VASFHCS) for the treatment of obesity at the time of the study. To qualify for an AOM, a veteran at VASFHCS must first work with a dietitian or be enrolled in the MOVE! clinic to participate in the weight management program, which focuses on dietary, exercise, and behavioral changes. At VASFHCS, AOMs are prescribed by primary care practitioners, clinical pharmacy providers, and advanced practitioners within the MOVE! program.

Ample data exist for the efficacy of AOMs. However, no published research has reported on AOM efficacy by age group (Appendix).^5-11 While most of the AOM clinical trials included older adults, the average age of participants was typically between 40 and 50 years. It is well-known that pharmacokinetic and pharmacodynamic changes occur as age increases. Renal and hepatic clearance is reduced while the volume distribution and sensitivities to some medications may increase. ¹² Although this study did not focus on specific pharmacokinetic and pharmacodynamic changes with respect to AOM, it is important to recognize that this may play a role in the efficacy and safety of AOMs in older adults.

Methods

This retrospective single-center chart review was performed using the VASFHCS Computerized Patient Record System to compare the efficacy of AOMs in older adults (aged ≥ 65 years) vs adults (aged < 65 years). The primary endpoint was the percent change in body weight from baseline to 6 and 12 months after initiation of AOM therapy in the older adult vs adult population. Secondary endpoints included changes in low-density lipoprotein (LDL), hemoglobin A_1c (HbA_1c), and blood pressure (BP) from baseline compared to 12 months on AOM therapy. HbA_1c was assessed in patients with T2DM or prediabetes at the time of AOM initiation. Two safety endpoints were also explored to determine the incidence of medication adverse events (AEs) and subsequent discontinuation of AOM. A subset analysis was performed to determine whether there was a difference in percent change in body weight between patients in 3 age groups: 18 to 40 years, 41 to 64 years, and ≥ 65 years.

The study population included patients who were prescribed an AOM between January 1, 2021, and June 30, 2023. Patients were excluded if they did not continue AOM therapy for ≥ 6 months after initiation or if they underwent gastric bypass surgery while undergoing AOM therapy. Patients taking semaglutide (Ozempic) or liraglutide (Victoza) for both T2DM and weight loss who were eventually switched to the weight loss formulations (Wegovy or Saxenda) were included. Patients who switched between semaglutide and liraglutide for weight loss were also included. Those taking semaglutide or liraglutide solely for T2DM treatment were excluded because they are dosed differently.

Collected data included age, gender, race, weight (baseline, 6 and 12 months after initiation of AOM), metabolic laboratory values/vital signs (HbA_1c, LDL, and BP at baseline and 12 months after initiation of AOM), diagnosis of T2DM or prediabetes, reported AEs associated with AOM therapy, and date of AOM initiation and discontinuation (if applicable). Baseline values were defined at the time of medication initiation or values documented within 6 months prior to medication initiation if true baseline data were not reported. If values were not recorded at months 6 and 12 after AOM initiation, values documented closest to those targets were used. Weights were used for baseline, 6-, and 12-month data unless they were unavailable due to use of virtual care modalities. In these cases, patient-reported weights were used. Patients were included in the 6-month data, but not the 12-month data, if they were taking AOMs for > 6 months but not for 12 months. If patients had been on multiple AOMs, baseline data were recorded at the start of the first medication that was used for 6 months or longer. Twelve-month data were recorded after subsequent medication change. Twelve-month metabolic laboratory values/vital signs were recorded for patients included in the study even if they did not complete ≥ 12 months of AOM therapy.

Statistical Analysis

Data from patients who were prescribed an AOM from January 2021 to June 2023 and who remained on the medication for ≥ 6 months were analyzed. Baseline characteristics were analyzed using descriptive statistics. The primary and secondary endpoints were evaluated using the t test. The safety endpoints were analyzed using descriptive statistics. An analysis of variance test was used for the subset analysis. Results with P < .05 were statistically significant.

Results

A total of 144 participants were included in this study, 116 in the adult group (aged < 65 years) and 28 in the older adult group (aged ≥ 65 years). Sixty-seven patients were excluded due to prespecified inclusion and exclusion criteria.

Other than the predetermined mean age differences (48 years vs 71 years), there were multiple differences in patient baseline characteristics. When comparing older adults and adults, average weight (283 lb vs 269 lb) and White race (89% vs 87%) were slightly higher in the older adult group. Also, a higher prevalence of T2DM (54% and 18%) and a lower prevalence of prediabetes (21% and 33%) was noted in the older adult group. HbA_1c and BP were similar between both groups at baseline, while LDL was slightly lower in the older adult group (Table 1).

Patients in the adult group lost a mean 7.0% and 8.7% of body weight at 6 and 12 months, respectively, while the older adult group lost 5.0% and 6.6% body weight at 6 and 12 months, respectively. The difference in percent change in body weight was not statistically different at 6 (P = .08) or 12 (P = .26) months between patients in the adult group vs the older adult group or in the specific age groups (18-40 years, 41-64 years, ≥ 65 years) at 6 months (P = .24) or 12 months (P = .53) (Figure).

At 12 months, the difference between the adult group vs the older adult group was not statistically significant for HbA_1c in patients with T2DM or prediabetes (P = .73), LDL (P = .95), systolic BP (P = .58), or diastolic BP (P = .51) (Table 2).

For the safety endpoint, the incidence of AEs was found to be different between groups. There were more reported AEs (61.2% vs 39.3%) and a greater increase in therapy discontinuation due to AEs (6.0% vs 0%) in the adult group compared to the older adult group (Table 3).

Discussion

Patients taking AOMs revealed no statistically significant difference in percent change in body weight at 6 or 12 months between adults aged < 65 years and older adults aged ≥ 65 years. The subset analysis also showed no statistically significant difference in change in percent body weight between more narrowly defined age groups of 18 to 40 years, 41 to 64 years, and ≥ 65 years. This suggests that AOM may have similar efficacy for weight loss in all ages of adults.

Secondary endpoint findings showed no statistically significant difference in HbA_1c (in patients with T2DM or prediabetes), LDL, or BP at 12 months between the 2 groups. Although this study did not differentiate secondary outcomes based on the individual AOM, the change in HbA_1c in both groups was expected, given that 70% of the patients included in this study were taking a glucagon-like peptide-1 agonist (liraglutide and semaglutide) at some point during the study. It’s also worth noting that secondary endpoints were collected for patients who discontinued the AOM between 6 and 12 months. Therefore, the patients’ HbA_1c, LDL, and BP may not have accurately reflected the change that could have been expected if they had continued AOM therapy beyond the 12-month period.

Due to the different mechanisms and range in efficacy that AOMs have in regard to weight loss, changes in all outcomes, including weight, HbA_1c, LDL, and BP were expected to vary as patients were included even after switching AOM (collection of data started after ≥ 6 months on a single AOM). Switching of AOM after the first 6 months of therapy was recorded in 25% of the patients in the ≥ 65 years group and 330% of the patients in the < 65 years group.

The incidence of AEs and subsequent discontinuation of AOMs in this study was higher in the adult group. This study excluded patients who did not continue taking an AOM for at least 6 months. As a result, the incidence of AEs between the 2 groups within the first 6 months of AOM therapy remains unknown. It is possible that during the first 6 months of therapy, patients aged < 65 years were more willing to tolerate or had fewer severe AEs compared with the older adult group. It’s also possible that the smaller number of patients in the older adult group was due to increased AEs that led them to discontinue early (before completion of 6 months of therapy) and/or prescriber discomfort in using AOMs in the older adult population. In addition, because the specific medication(s) taken by patients in each group were not detailed, it is unknown whether the adult group was taking AOMs associated with a greater number of AEs.

Limitations

This was a retrospective study with a relatively small sample size. A larger sample size may have shown more precise differences between age groups and may be more representative of the general population. Additionally, data were reliant on appropriate documentation, and adherence to AOM therapy was not assessed due to the retrospective nature of this study. At times, the study relied on patient reported data points, such as weight, if a clinic weight was not available. Also, this study did not account for many potential confounding factors such as other medications taken by the patient, which can affect outcomes including weight, HbA_1c, LDL, blood pressure, and AEs.

Conclusions

This retrospective study of patients taking AOMs showed no statistically significant difference in weight loss at 6 or 12 months between adults aged < 65 years and older adults aged ≥ 65 years. A subset analysis found no statistically significant difference in change in body weight between specific age groups (18-40 years, 41-64 years, and ≥ 65 years). There was also no statistically significant difference in secondary outcomes, including change in HbA_1c (in patients with T2DM or prediabetes), LDL or BP between age groups. The safety endpoints showed a higher incidence of medication AEs in the adult group, with more of these adults discontinuing therapy due to AEs. This study indicates that AOM may have similar outcomes for weight loss and metabolic laboratory values/vital sign changes between adults and older adults. Also, our findings suggest that patients aged < 65 years may experience more AEs than patients aged ≥ 65 years after ≥ 6 months of AOM therapy. Larger studies are needed to further evaluate these age-specific findings.

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

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