Switching from Biologic to Biosimilar Products: Insight from an Integrated Health Care System.

Biologics are indicated for the treatment of a wide range of conditions and have transformed care in several therapeutic areas; however, they are expensive for both health care systems and patients. The use of biosimilars, which are approved by the US Food and Drug Administration as being "highly similar" to the originator biologic, has the potential to change the health care landscape in the biologic space through considerable cost savings for both payors and patients. With the introduction of biosimilars, organizations are increasingly evaluating how to switch patients from originator biologics to biosimilars. While published studies have evaluated the outcomes of patients switched from originator biologics to biosimilars, there are few publications describing the process health care systems have used to adopt and switch patients to biosimilars. Since 2016, Kaiser Permanente Colorado (KPCO) has undertaken several biosimilar switches starting with the first biosimilar introduced to the market, filgrastim, and has been able to successfully switch 91.8% of patients receiving infliximab, 99.8% receiving rituximab, and 100% receiving filgrastim, trastuzumab, and bevacizumab originator biologics to their respective biosimilars. In an effort to support other health care systems and provide a framework for implementing biosimilar switches, the purpose of this paper is to describe the biosimilar switch model and share learnings from the KPCO experience.

Technology-Enabled Outreach to Patients Taking High-Risk Medications Reduces a Quality Gap in Completion of Clinical Laboratory Testing.

Clinical laboratory quality improvement (QI) efforts can include population test utilization. The authors used a health care organization's Medical Data Warehouse (MDW) to characterize a gap in guideline-concordant laboratory testing recommended for safe use of antirheumatic agents, then tested the effectiveness of laboratory-led, technology-enabled outreach to patients at reducing this gap. Data linkages available through the Kaiser Permanente Colorado MDW and electronic health record were used to identify ambulatory adults taking antirheumatic agents who were due/overdue for alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC), or serum creatinine (SCr) testing. Outreach was implemented using an interactive voice response system to send patients text or phone call reminders. Interrupted time series analysis was used to estimate reminder effectiveness. Rates of guideline-concordant testing and testing timeliness in baseline vs. intervention periods were determined using generalized linear models for repeated measures. Results revealed a decrease in percentage of 3763 patients taking antirheumatic agents due/overdue for testing at any given time: baseline 24.3% vs. intervention 17.5% (P < 0.001). Among 3205 patients taking conventional antirheumatic agents, concordance for all ALT testing was baseline 52.8% vs. intervention 65.4% (P < 0.001) among patients chronically using these agents and baseline 20.6% vs. intervention 26.1% (P < 0.001) among patients newly starting these agents. The 95th percentiles for days to ALT testing were baseline 149 vs. intervention 117 among chronic users and baseline 134 vs. intervention 92 among new starts. AST, CBC, and SCr findings were similar. Technology-enabled outreach reminding patients to obtain laboratory testing improves health care system outcomes.

Patient Perspectives on Switching from Infliximab to Infliximab-dyyb in Patients with Rheumatologic Diseases in the United States.

OBJECTIVE: The introduction of biosimilars for rheumatologic diseases (RDs) has provided a potentially lower-cost therapy compared with their bio-originator products; however, adoption of biosimilars may be challenged by patient perceptions. The objective of this study was to describe patients' perspectives of switching from infliximab to infliximab-dyyb. METHODS: This was a survey of adult patients with RDs who qualified for switching from infliximab to infliximab-dyyb therapy between September 1 2017 and January 31 2018. Verbal consent was obtained prior to administration of a telephone survey. Survey questions were focused on the safety, efficacy, and knowledge of biosimilar therapy. RESULTS: A total of 108 patients were identified with 52 (48%) patients consenting to study participation. Forty (77%) and 12 (23%) patients reported switching and not switching, respectively, to infliximab-dyyb. Regarding disease control, most respondents (80%) were satisfied to very satisfied with the switch to infliximab-dyyb. Major concerns reported for switching included not knowing enough about the medication (38%), potential side effects (35%), and loss of disease activity control (35%). CONCLUSION: Overall, patients reported satisfaction with switching from infliximab to infliximab-dyyb, but concerns regarding safety and efficacy were expressed. Patient involvement in the switching decision-making process may allay concerns and enhance biosimilar uptake.

Falsely elevated international normalized ratio values in patients undergoing anticoagulation therapy: a descriptive evaluation.

BACKGROUND: Elevated international normalized ratio (INR) values have been linked to bleeding complications; however, elevated INR values are not always physiologic and can be falsely increased. This study describes the rate of falsely elevated INRs and characteristics predictive of falsely elevated INRs. METHODS: This cross-sectional study was conducted among adult patients receiving anticoagulation therapy monitored by a centralized anticoagulation service during January 2000 through December 2004 (n = 29,536). Prevalence rates of all elevated (ie, value >/= 10), falsely elevated, and truly elevated INRs were calculated. Multivariate logistic regression was performed to identify predictors of falsely elevated INRs among elevated INRs. RESULTS: Of the 556,998 INRs included in the analysis, 793 INRs (prevalence, 0.14%; 95% confidence interval [CI], 0.10 to 0.19%), 53 INRs (prevalence, 0.01%; 95% CI, < 0.01 to 0.03%), and 740 INRs (prevalence, 0.13%; 95% CI, 0.09 to 0.18%) were elevated, falsely elevated, and truly elevated, respectively. The strongest independent predictor of a falsely elevated INR was a patient undergoing hemodialysis at the time of the elevated INR (adjusted odds ratio, 9.60; 95% CI, 4.96 to 18.58; p < 0.001). A low target INR was the only other factor found to be an independent predictor of a falsely elevated INR. CONCLUSIONS: Although INR values >/= 10.0 occur infrequently, patients presenting with such values can present a challenge to the anticoagulation provider. Anticoagulation providers should be particularly vigilant for falsely elevated INRs when monitoring patients undergoing hemodialysis.

Multidisciplinary team care may slow the rate of decline in renal function.

BACKGROUND AND OBJECTIVES: A multidisciplinary team (MDT) approach to chronic kidney disease (CKD) may help optimize care of CKD and comorbidities. We implemented an MDT quality improvement project for persons with stage 3 CKD and comorbid diabetes and/or hypertension. Our objective was to decrease the rate of decline of GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used a 4-year historical cohort to compare 1769 persons referred for usual nephrology care versus 233 referred for MDT care within an integrated, not-for-profit Health Maintenance Organization (HMO). Usual care consisted of referral to an outside nephrologist. The MDT consisted of an HMO-based nephrologist, pharmacy specialist, diabetes educator, dietitian, social worker, and nephrology nurse. Both groups received usual primary care. The primary outcome was rate of decline of GFR. Secondary outcomes were LDL, hemoglobin A1c, and BP. RESULTS: In multivariate repeated-measures analyses, MDT care was associated with a mean annual decline in GFR of 1.2 versus 2.5 ml/min per 1.73 m(2) for usual care. In stratified analyses, the significant difference in GFR decline persisted only in those who completed their referrals. There were no differences in the secondary outcomes between groups. CONCLUSIONS: In this integrated care setting, MDT care resulted in a slower decline in GFR than usual care. This occurred despite a lack of significant differences for secondary disease-specific measures, suggesting that other differences in the MDT population or care process accounted for the slower decline in GFR in the MDT group.

Improving prescribing safety in patients with renal insufficiency in the ambulatory setting: the Drug Renal Alert Pharmacy (DRAP) program.

STUDY OBJECTIVE: To determine whether a computerized Drug Renal Alert Pharmacy (DRAP) program could decrease the rate of medication errors in drug selection or dosing for 15 target drugs in patients with renal insufficiency. DESIGN: Randomized, controlled, population-based effectiveness trial. SETTING: A large integrated health care delivery system. PATIENTS: A total of 32,917 health plan members who were at least 18 years old, had an estimated creatinine clearance of 50 ml/minute or lower, and were not receiving dialysis between December 1, 2003, and February 28, 2005, were randomly assigned to either the intervention group (16,577 patients) or usual care (control) group (16,340 patients). Of the 32,917 patients, 6125 patients (3025 in the intervention group and 3100 in the usual care group) were prescribed at least one target drug and were included in the analysis. INTERVENTION: A computerized tool--the DRAP program--was used to alert pharmacists at the time of dispensing to possible errors in target drug selection and dosing for patients with renal insufficiency. The 15 target drugs were previously identified based on frequency of use in our health care system and risk of serious adverse events. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion of medication errors, defined as target drugs that should be avoided or were dosed inappropriately, in the intervention and usual care groups. The Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework was used to evaluate the intervention's potential for translation and generalizability. Among the 6125 patients who received a target drug, no significant differences were noted in age, sex, creatinine clearance, comorbid conditions, and number of target drugs between groups at baseline. Over the 15-month intervention period, the proportion of medication errors was significantly lower in the intervention group than the usual care group (33% vs 49%, p<0.001). After the study period, when the intervention was expanded to both groups, a 20% reduction in errors was sustained in the combined groups over the subsequent 7 months. CONCLUSION: The DRAP program was successful in reducing medication errors for patients with renal insufficiency in an ambulatory setting and was demonstrated to have sustainability after study completion.

An assessment of cholesterol goal attainment in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at significant risk for cardiovascular disease (CVD). The National Kidney Foundation developed clinical practice guidelines (Kidney Disease Outcomes Quality Initiative) for targeting low-density lipoprotein cholesterol (LDL-C) goals. OBJECTIVE: This study evaluated the extent to which these guidelines were adhered to among patients with CKD and to examine factors associated with the attainment of LDL-C goals. METHODS: In this cross-sectional study we evaluated patients with a glomerular filtration rate of 15 to 59 mL/min per 1.73 m². Patients with previous CVD, who were receiving dialysis, or were post kidney transplant were excluded. Administrative databases were used to determine the percentage of patients with a fasting lipid profile performed within the previous year, the percentage who attained a LDL-C goal less than 100 mg/dL, and to determine lipid-lowering medications prescribed. Logistic regression analysis was used to identify factors associated with LDL-C goal attainment. RESULTS: Of the 4541 patients evaluated, 3157 (69.5%) had a fasting lipid profile performed within the previous year. Overall, 60.8% attained a LDL-C less than 100 mg/dL. Among patients at goal, 72.2% were taking lipid-lowering therapy compared with 37.9% of those not at goal (P < .01). Characteristics independently associated with LDL-C goal attainment were increasing age, male gender, increasing chronic disease score, history of diabetes, and statin use. CONCLUSION: Although most patients were screened and attained LDL-C goal, there was room for improvement. Statin use was independently associated with LDL-C goal attainment. Future prospective studies should focus on evaluating clinical outcomes of lipid-lowering interventions within the CKD population.

Impact of prescription benefit coverage limits on sevelamer hydrochloride adherence for patients with ESRD.

OBJECTIVE: To assess the impact of prescription benefit coverage on medication adherence in Medicare-eligible members diagnosed with end-stage renal disease taking sevelamer hydrochloride. METHODS: This pilot study involved a retrospective analysis of patients with end-stage renal disease taking sevelamer, with an annual cap on brand prescription drug spending compared with those without a cap. We compared sevelamer adherence and discontinuation proportions between the 2 groups of Medicare patients in 2003 and 2004. Medication adherence was calculated based on the proportion of available days covered in relationship to capped versus noncapped pharmacy benefit. RESULTS: Rate ratios showed that in 2003, the patients taking sevelamer under a capped benefit (N = 43) had 27% fewer days of drug use compared with those (N = 88) without a capped benefit (relative risk, 0.73; 95% CI, 0.58-0.93). Similarly, in 2004, those taking sevelamer under the capped benefit (N = 21) had 33% fewer days of drug use compared with those (N = 117) without a capped benefit (relative risk, 0.67; 95% CI, 0.46-0.96). CONCLUSIONS: Medication adherence was significantly lower for patients with a capped brand-name drug benefit. These findings provide insight into potential drug utilization patterns, including for sevelamer, under the Medicare Part D benefit, where members could face significant out-of-pocket expenditures once coverage limits are reached.