Real-world use of PCSK-9 inhibitors by early adopters: cardiovascular risk factors, statin co-treatment, and short-term adherence in routine clinical practice

Abstract

BackgroundInconsistency of real-world medication use with labeled indications may affect cost and clinical value of pharmacotherapy. PCSK-9 inhibitors are labeled in the US for use with statins to reduce low-density lipoprotein cholesterol in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH).ObjectiveTo assess consistency with labeled indications and treatment persistency for early (first 5 post-launch months) adopters of PCSK-9 inhibitor pharmacotherapy.MethodsRetrospective analysis of commercially insured cohorts derived from the Truven Health MarketScan® database was performed. Subjects were aged 18–64 years, initiated PCSK-9 inhibitor or highest-intensity statin (rosuvastatin 40 mg/day or atorvastatin 80 mg/day) pharmacotherapy from August to December 2015, and were enrolled throughout 2015 and during separate baseline (pre-treatment) periods of 6 and 18 months. Baseline ASCVD, FH, and ASCVD events (myocardial infarction, transient ischemic attack, and cerebrovascular occlusion) were measured. Persistency was measured through December 2015 for subcohorts of patients initiating treatment from August to September 2015.ResultsBaseline disease rates were higher for patients treated with PCSK-9 inhibitors (n=390) compared with highest-intensity statins (n=26,306): ASCVD (68.5% vs 33.4%, respectively); FH (39.7% vs 15.5%); both P<0.001. In 18 months pre-treatment, 35.6% of PCSK-9 inhibitor-treated patients had ≥1 ASCVD event, and 87.9% had a labeled indication. Rates of 60-day nonpersistency for PCSK-9 inhibitors and highest-intensity statins were 33.3% and 39.8%, respectively (P=0.207). During PCSK-9 inhibitor pharmacotherapy, 33.8% of patients had evidence of statin supply and, of those initiating treatment from August to September, 40.9% filled ≥1 statin prescription. Of those with sustained pre-treatment statin use, 34.8% had no statin supply during PCSK-9 inhibitor pharmacotherapy.ConclusionAmong early-adopting PCSK-9 inhibitor-treated patients, the off-label diagnosis rate was 12%; a majority lacked statin co-treatment; and one third filled prescriptions for ≤60 days. Inconsistency with labeled uses may reflect prescriber/patient decisions, health-insurance coverage determinations, or statin intolerance not reported on claims.

PCSK-9 Inhibitors in a Real-World Setting and a Comparison Between Alirocumab and Evolocumab in Heterozygous FH Patients

“…There was a 66% average reduction in initial LDL-C, and it was maintained throughout 12 months. Similar reports are made in other studies evaluating the effect of PCSK9 inhibitors in clinical practice [ 17 ]. Both commercially available PCSK9 inhibitors have similar lipid-lowering effects, with a significant reduction on LDL-C.…”

“…This has been observed in other studies such as the study by Kathleen A. Fairman et al, in which a cohort of 390 patients with PCSK9 inhibitor treatment was analyzed in clinical practice. Of the patients analyzed, 39.8% did not continue treatment after 60 days because it required authorization and periodic evaluation in order to continue with PCSK9 inhibitor treatment [ 17 ]. The percentage of suspension or nonadherence to treatment was higher than that reported in other studies (between 8% and 10%) [ 15 , 18 ].…”

Alirocumab in high-risk patients: Observations from the open-label expanded use program

“…The observations from this program were consistent with analyses of real-world use of PCSK9 inhibitors, which also indicate high rates of statin intolerance and higher LDL-C levels among users of PCSK9 inhibitors. [19][20][21][22] Although the alirocumab expanded use program started before the approval of alirocumab in the US, the inclusion criteria are similar to the approved indications for alirocumab. Moreover, the characteristics of patients enrolled in this program align with patient characteristics that are highlighted in recent US guidelines/recommendations.…”

Changes in PBM Business Practices in 2019: True Innovation or More of the Same?

“…62 ■■ Headwind #3: Provider Prescribing Patterns Payers may experience challenges resulting from the "evidence to practice gap," defined as inconsistency between available scientific evidence and clinical practice that has persisted for decades (Table 2, Box A). [10][11][12][63][64][65][66][67][68][69][70][71][72][73][74][75][76] The estimated 17-year lag time between translational (application-oriented) research and routine care contributes to sometimes clinically questionable utilization. [10][11][12][65][66][67] Examples include pegfilgrastim for initiatives publicized by some PBMs in response to these concerns include collaborative employer-PBM arrangements described as transparent cost passthroughs building on previous movements toward transparency; innovative manufacturer contracts (e.g., "value-based" coverage, long-term payment plans); new clinical performance requirements; increased formulary exclusions for brand drugs; and increased biosimilar use.…”

“…[10][11][12][63][64][65][66][67][68][69][70][71][72][73][74][75][76] The estimated 17-year lag time between translational (application-oriented) research and routine care contributes to sometimes clinically questionable utilization. [10][11][12][65][66][67] Examples include pegfilgrastim for initiatives publicized by some PBMs in response to these concerns include collaborative employer-PBM arrangements described as transparent cost passthroughs building on previous movements toward transparency; innovative manufacturer contracts (e.g., "value-based" coverage, long-term payment plans); new clinical performance requirements; increased formulary exclusions for brand drugs; and increased biosimilar use. 4,[20][21][22][23] Although potentially positive, these changes should be understood in the context of 3 challenges, or "headwinds," in specialty drug management: pharmaceutical manufacturer practices, U.S. Food and Drug Administration (FDA) changes, and provider prescribing patterns.…”