Hammond JM

Purpose: The purpose of this study is to evaluate the use and dosing strategies of programmed death protein (PD-1) inhibitors and selected immune-mediated adverse effects within the Veteran’s Health Administration (VHA).

Background: The PD-1 inhibitors, nivolumab and pembrolizumab, are two agents used in the treatment of a number of solid tumors. Their dosing varied in clinical trials supporting a change in FDA approved labeling from weight-based to standardized dosing. While these agents have demonstrated efficacy, immune-mediated adverse-effects (IrAEs) have been associated with their use.

Methods: This is a retrospective review of veterans receiving nivolumab or pembrolizumab for the treatment of solid tumors within the VHA between January 2015 and July 2017. Data were collected from the VA Corporate Data Warehouse through the VA Informatics and Computing Infrastructure. The dosing strategy for PD-1 inhibitor was categorized into weight-based versus fixeddosing, where possible, and used to identify actual and potential cost-savings opportunities. The incidence of prespecified IrAEs thyroid dysfunction, pneumonitis, and colitis, was quantified and their management was described. Descriptive statistics will be used for the primary and secondary outcomes.

Results: Nivolumab was the primary PD-1 inhibitor utilized for solid tumor treatment. Both nivolumab and pembrolizumab were primarily dosed based on patient weight. For nivolumab orders there was a total of $8,514,300 estimated actual cost savings with $5,591,250 estimated remaining cost-savings potential identified. Of patients who received nivolumab, 514 (15.8%) developed primary hypothyroidism and 299 (9.2%) developed primary hyperthyroidism. At our local institution, one (1.7%) patient developed pneumonitis and one (1.7%) patient developed colitis which was determined to be related to nivolumab therapy.

Conclusions: Nivolumab was the primary PD-1 inhibitor used, with the primary dosing strategy being weightbased. Pembrolizumab dosing was primarily fixed dosing, which may be due to the available vial size(s). There were substantial actual and potential cost-savings opportunities identified. The incidence of the prespecified IrAEs was similar to the incidence currently available in published literature. This supports the recommendation for continued thyroid laboratory monitoring and recognition of signs and symptoms of IrAEs by all health care providers.

Purpose: The purpose of this study is to evaluate the use and dosing strategies of programmed death protein (PD-1) inhibitors and selected immune-mediated adverse effects within the Veteran’s Health Administration (VHA).

Background: The PD-1 inhibitors, nivolumab and pembrolizumab, are two agents used in the treatment of a number of solid tumors. Their dosing varied in clinical trials supporting a change in FDA approved labeling from weight-based to standardized dosing. While these agents have demonstrated efficacy, immune-mediated adverse-effects (IrAEs) have been associated with their use.

Methods: This is a retrospective review of veterans receiving nivolumab or pembrolizumab for the treatment of solid tumors within the VHA between January 2015 and July 2017. Data were collected from the VA Corporate Data Warehouse through the VA Informatics and Computing Infrastructure. The dosing strategy for PD-1 inhibitor was categorized into weight-based versus fixeddosing, where possible, and used to identify actual and potential cost-savings opportunities. The incidence of prespecified IrAEs thyroid dysfunction, pneumonitis, and colitis, was quantified and their management was described. Descriptive statistics will be used for the primary and secondary outcomes.

Results: Nivolumab was the primary PD-1 inhibitor utilized for solid tumor treatment. Both nivolumab and pembrolizumab were primarily dosed based on patient weight. For nivolumab orders there was a total of $8,514,300 estimated actual cost savings with $5,591,250 estimated remaining cost-savings potential identified. Of patients who received nivolumab, 514 (15.8%) developed primary hypothyroidism and 299 (9.2%) developed primary hyperthyroidism. At our local institution, one (1.7%) patient developed pneumonitis and one (1.7%) patient developed colitis which was determined to be related to nivolumab therapy.

Conclusions: Nivolumab was the primary PD-1 inhibitor used, with the primary dosing strategy being weightbased. Pembrolizumab dosing was primarily fixed dosing, which may be due to the available vial size(s). There were substantial actual and potential cost-savings opportunities identified. The incidence of the prespecified IrAEs was similar to the incidence currently available in published literature. This supports the recommendation for continued thyroid laboratory monitoring and recognition of signs and symptoms of IrAEs by all health care providers.

Purpose: The purpose of this study is to evaluate the use and dosing strategies of programmed death protein (PD-1) inhibitors and selected immune-mediated adverse effects within the Veteran’s Health Administration (VHA).

Background: The PD-1 inhibitors, nivolumab and pembrolizumab, are two agents used in the treatment of a number of solid tumors. Their dosing varied in clinical trials supporting a change in FDA approved labeling from weight-based to standardized dosing. While these agents have demonstrated efficacy, immune-mediated adverse-effects (IrAEs) have been associated with their use.

Methods: This is a retrospective review of veterans receiving nivolumab or pembrolizumab for the treatment of solid tumors within the VHA between January 2015 and July 2017. Data were collected from the VA Corporate Data Warehouse through the VA Informatics and Computing Infrastructure. The dosing strategy for PD-1 inhibitor was categorized into weight-based versus fixeddosing, where possible, and used to identify actual and potential cost-savings opportunities. The incidence of prespecified IrAEs thyroid dysfunction, pneumonitis, and colitis, was quantified and their management was described. Descriptive statistics will be used for the primary and secondary outcomes.

Results: Nivolumab was the primary PD-1 inhibitor utilized for solid tumor treatment. Both nivolumab and pembrolizumab were primarily dosed based on patient weight. For nivolumab orders there was a total of $8,514,300 estimated actual cost savings with $5,591,250 estimated remaining cost-savings potential identified. Of patients who received nivolumab, 514 (15.8%) developed primary hypothyroidism and 299 (9.2%) developed primary hyperthyroidism. At our local institution, one (1.7%) patient developed pneumonitis and one (1.7%) patient developed colitis which was determined to be related to nivolumab therapy.

Conclusions: Nivolumab was the primary PD-1 inhibitor used, with the primary dosing strategy being weightbased. Pembrolizumab dosing was primarily fixed dosing, which may be due to the available vial size(s). There were substantial actual and potential cost-savings opportunities identified. The incidence of the prespecified IrAEs was similar to the incidence currently available in published literature. This supports the recommendation for continued thyroid laboratory monitoring and recognition of signs and symptoms of IrAEs by all health care providers.

Purpose: In patients initiating treatment with anti-CD20 antibodies (Ab), 20-60% with prior hepatitis B (HBV) infection not receiving HBV antiviral prophylaxis experience HBV reactivation—with hepatitis (33%), liver failure (13%), and death (5%). HBV reactivation is prevented with HBV antiviral therapy during and 12 months after anti-CD20 Ab therapy in patients with positive HBV surface antigen (HBsAg+) or HBV core antibody (HBcAb+). Our goal is to widely use anti-CD20 Ab order checks to increase testing and antiviral treatment to prevent HBV reactivation.

Background: Without HBV treatment in those at risk, fatal HBV reactivation affects 1 in 1,000 receiving rituximab. In a VHA analysis of 19,304 patients initiating anti-CD20 Ab (2002-14), > 60% of patients had HBV testing by 2014; 1 in 9 Veterans had either chronic (1-2% HBsAg+) or prior (9% HBcAb+) HBV, yet < 18% received HBV antiviral therapy. While information modestly affects behaviors, order checks with treatment algorithms can be > 95% effective.

Methods: Since 2015, our team has shared information widely, updated pharmacy criteria for use, and enabled HBV antiviral prescribing by all providers. To identify HBV testing or treatment omissions, we launched a Medication Use Evaluation Tracker (MUET), and programmed an anti- CD20 Ab order check that displays only if either HBV testing or treatment has not been done.

Results: Since 2014, HBV testing in patients initiating anti-CD20 Ab increased to 64-78% and HBV antiviral prophylaxis from < 18% to 44%. In November 2016, an anti-CD20 Ab order check was piloted at 3 sites and functional in CPRS with additional sites reporting favorable use. Additionally, a MUET was released for anti-CD20 Ab therapies providing an additional safety check.

Conclusions: VHA has increased HBV testing and antiviral treatment with anti-CD20 antibody initiation—yet more than half of patients remain at risk of HBV reactivation. Successfully used in up to 15 sites, programmed anti-CD20 Ab order checks highlight to providers when HBV testing
or antiviral prophylaxis is needed. Achieving broad use of this order check will increase HBV prophylaxis prescribing and decrease subsequent HBV reactivation. An anti-CD20 Ab MUET provides an additional safety check option for identifying at risk patient.

Purpose: In patients initiating treatment with anti-CD20 antibodies (Ab), 20-60% with prior hepatitis B (HBV) infection not receiving HBV antiviral prophylaxis experience HBV reactivation—with hepatitis (33%), liver failure (13%), and death (5%). HBV reactivation is prevented with HBV antiviral therapy during and 12 months after anti-CD20 Ab therapy in patients with positive HBV surface antigen (HBsAg+) or HBV core antibody (HBcAb+). Our goal is to widely use anti-CD20 Ab order checks to increase testing and antiviral treatment to prevent HBV reactivation.

Background: Without HBV treatment in those at risk, fatal HBV reactivation affects 1 in 1,000 receiving rituximab. In a VHA analysis of 19,304 patients initiating anti-CD20 Ab (2002-14), > 60% of patients had HBV testing by 2014; 1 in 9 Veterans had either chronic (1-2% HBsAg+) or prior (9% HBcAb+) HBV, yet < 18% received HBV antiviral therapy. While information modestly affects behaviors, order checks with treatment algorithms can be > 95% effective.

Methods: Since 2015, our team has shared information widely, updated pharmacy criteria for use, and enabled HBV antiviral prescribing by all providers. To identify HBV testing or treatment omissions, we launched a Medication Use Evaluation Tracker (MUET), and programmed an anti- CD20 Ab order check that displays only if either HBV testing or treatment has not been done.

Results: Since 2014, HBV testing in patients initiating anti-CD20 Ab increased to 64-78% and HBV antiviral prophylaxis from < 18% to 44%. In November 2016, an anti-CD20 Ab order check was piloted at 3 sites and functional in CPRS with additional sites reporting favorable use. Additionally, a MUET was released for anti-CD20 Ab therapies providing an additional safety check.

Conclusions: VHA has increased HBV testing and antiviral treatment with anti-CD20 antibody initiation—yet more than half of patients remain at risk of HBV reactivation. Successfully used in up to 15 sites, programmed anti-CD20 Ab order checks highlight to providers when HBV testing
or antiviral prophylaxis is needed. Achieving broad use of this order check will increase HBV prophylaxis prescribing and decrease subsequent HBV reactivation. An anti-CD20 Ab MUET provides an additional safety check option for identifying at risk patient.

Purpose: In patients initiating treatment with anti-CD20 antibodies (Ab), 20-60% with prior hepatitis B (HBV) infection not receiving HBV antiviral prophylaxis experience HBV reactivation—with hepatitis (33%), liver failure (13%), and death (5%). HBV reactivation is prevented with HBV antiviral therapy during and 12 months after anti-CD20 Ab therapy in patients with positive HBV surface antigen (HBsAg+) or HBV core antibody (HBcAb+). Our goal is to widely use anti-CD20 Ab order checks to increase testing and antiviral treatment to prevent HBV reactivation.

Background: Without HBV treatment in those at risk, fatal HBV reactivation affects 1 in 1,000 receiving rituximab. In a VHA analysis of 19,304 patients initiating anti-CD20 Ab (2002-14), > 60% of patients had HBV testing by 2014; 1 in 9 Veterans had either chronic (1-2% HBsAg+) or prior (9% HBcAb+) HBV, yet < 18% received HBV antiviral therapy. While information modestly affects behaviors, order checks with treatment algorithms can be > 95% effective.

Methods: Since 2015, our team has shared information widely, updated pharmacy criteria for use, and enabled HBV antiviral prescribing by all providers. To identify HBV testing or treatment omissions, we launched a Medication Use Evaluation Tracker (MUET), and programmed an anti- CD20 Ab order check that displays only if either HBV testing or treatment has not been done.

Results: Since 2014, HBV testing in patients initiating anti-CD20 Ab increased to 64-78% and HBV antiviral prophylaxis from < 18% to 44%. In November 2016, an anti-CD20 Ab order check was piloted at 3 sites and functional in CPRS with additional sites reporting favorable use. Additionally, a MUET was released for anti-CD20 Ab therapies providing an additional safety check.

Conclusions: VHA has increased HBV testing and antiviral treatment with anti-CD20 antibody initiation—yet more than half of patients remain at risk of HBV reactivation. Successfully used in up to 15 sites, programmed anti-CD20 Ab order checks highlight to providers when HBV testing
or antiviral prophylaxis is needed. Achieving broad use of this order check will increase HBV prophylaxis prescribing and decrease subsequent HBV reactivation. An anti-CD20 Ab MUET provides an additional safety check option for identifying at risk patient.