A Look Into 2011 Drug Utilization Trend and Beyond

In the first quarter of 2011, we continued to confront a marketplace with weary consumers. Although the jobless rate fell slightly (0.8%) from November 2010 to April 2011, the unemployment rate remained high at 9.0%, representing 13.7 million Americans who are still out of work.¹ In addition, the price of gasoline reached nearly $4 a gallon on average in early May.² Numerous studies and surveys have shown that those hit hard in difficult economic times are more likely to cut back on their use of medical services and prescription drugs.

A Commonwealth Fund survey conducted between July and November 2010 found that an estimated 9 million working-age adults lost their health insurance in the last 2 years. The survey also found that 52 million adults went without coverage at some point in 2010, up from 38 million in 2001. In addition, 75 million adults did not get needed healthcare last year, skipping prescriptions, doctor visits, and recommended tests and treatments because of costs that were 60% higher than a decade ago.³ Other anecdotal evidence also suggests that many Americans continue to postpone or forgo medical care as the result of a lingering recessionary mind-set. UnitedHealth Group told analysts that so far this year, insured hospital stays actually decreased in some instances. Cigna has also talked about the “low level” of medical use. Even with a halting economic recovery, doctors and others say many people are still extremely budget conscious, signaling the possibility of a fundamental change in Americans’ appetite for healthcare.⁴

The CVS Caremark overall gross trend in the first quarter of 2011, excluding Medicare Part D, was 2.0% and the days of supply per member per month (PMPM) utilization trend was 1.7%. The slower-than-expected utilization trend is impacted by an intersection of circumstances, including the continued economic uncertainty, severe weather,5 the launch of over-the-counter (OTC) Allegra6 in March 2011, and an ongoing change in the underlying demographics of commercial members. Although more Americans are delaying retirement due to the economy,⁷ an estimated 10,000 Baby Boomers—the largest generational segment of our population—come eligible for retirement each day (which will be true for years to come).⁸ Many of these retirees move straight into a Medicare program and out of the employer groups to which they previously belonged, resulting in a shift of demographics of utilizing members.

BACKGROUND

The major drivers for prescription utilization trend include changes to the demographics (including the number of members utilizing a drug), change in members’ underlying health, and shift in age. In addition, a change in the days of supply or number of prescriptions utilized may be due to the availability of new therapies, an aging population, change in prescribing guidelines, reported adverse reactions, changes in drug benefit, and shift of prescription drugs to OTC status.

The shift in the underlying employer demographics may be driven by employers who reduce or eliminate healthcare coverage for retirees, which would certainly reduce average utilization in the employer segment of society. Most private-sector workers will never become eligible for health insurance in retirement through a former employer. Fewer employers are offering health benefits to future retirees; when those benefits are offered, eligibility criteria are becoming harder to meet; and employer subsidies are disappearing. In 2008, 26% of people aged 65 to 69 years had retiree health benefits, down from 32% in 1994, and the numbers were lower for older retirees. It is possible that the decline in coverage would have been even larger had it not been for changes in the work status of individuals eligible for Medicare. In 1995, 59% of individuals aged 65 to 69 years considered themselves retired, a percentage which fell to 53.6% in 2008, while those saying they were working increased from 28% in 1995 to 35% in 2008. The annual (2010-2011) Prescription Drug Benefit Cost and Plan Design Report published by the Pharmacy Benefit Management Institute found that the number of employers providing retiree drug coverage dropped to 31.5% in 2010 from 45.9% in 2007.¹⁰

Another reason for a change in employer demographics is the extended age for dependents covered by an employee’s benefit. The coverage of persons aged 21 to 26 years due to the recent enactment of healthcare reform legislation would cause an increase in acute drug utilization and a decline in use of chronic medications since younger persons are less likely to be high utilizers.

Change in utilization may also be due to implementation of compliance and/or adherence programs. More attention has been focused on adherence in the benefit arena. Our data show that on average 40% of individuals are not being treated in accordance with current recommended therapeutic guidelines. To support physicians and individuals where evidencebased guidelines are clear, pharmacy benefit managers (PBMs) and health plans are implementing unique approaches to closing these gaps in therapy. One example is CVS Caremark’s adherence approach, which is delivered on behalf of PBM clients over the phone or on a face-to-face basis in CVS pharmacies to support individuals by reminding them to take their medication; CVS Caremark also works with patients’ physicians as necessary to close any gaps in therapy that may exist. Adherence outreach, when effective, has the ability to impact utilization and health.

Therapeutic class changes in utilization are due to prescription drugs moving to OTC status, Food and Drug Administration (FDA) safety warnings, or adverse studies reported in the lay press. There have been several year-to-date (YTD) studies in 2011 (

Table 1

). In the last few years, several major blockbuster drugs have seen a significant decline in utilization due to an adverse safety profile (eg, Avandia).

Sales of the class and of Avandia in particular have suffered since a May 2007 meta-analysis of Avandia (rosiglitazone) studies published in the New England Journal of Medicine showed a statistically significant increase in the risk of myocardial infarction and an increased risk of death from cardiovascular causes with borderline significance.²⁵ CVS Caremark Industry Analytics subsequently undertook to examine and understand the impact of the published results in the company’s Book of Business (BOB) on the Avandia franchise (Avandia, Avandaryl, and Avandamet). Results of this analysis showed that of the base group of Avandia franchise users, 37.4% failed to renew theirprescriptions as of June 30, 2007. Of Avandia users, 40.3% failed to renew their prescriptions for the drug.

According to the results of a retrospective study published in June 2010, an estimated 48,000 elderly patients experienced serious cardiovascular harm or death as a result of using Avandia instead of Actos between 1999 and 2009. The study, which examined the records of 227,000 patients 65 years and older who received either drug between 2006 and 2009, found that use of Avandia was associated with a 27% greater chance of suffering a stroke and a 25% increased risk of suffering heart failure compared with Actos. Data also showed that patients who took Avandia had a 13% greater chance of dying. In addition, Avandia increased the overall risk of experiencing heart attack, stroke, heart failure, or death by 17%, the study found.²⁶

In compliance with a 2010 FDA directive, GlaxoSmith-Kline finalized new labeling for Avandia in February 2011, restricting the drug’s use to patients already taking it or to those who have failed other antiglycemic drugs. According to the new label, Avandia may be started only in patients who “are unable to achieve adequate glycemic control on other diabetes medications, and, in consultation with their healthcare provider, have decided not to take Actos for medical reasons.” In addition, a previous boxed warning has been amended to highlight the increased cardiovascular risks associated with Avandia—citing data from a meta-analysis of 52 earlier studies as well as 3 stand-alone trials that found higher rates of myocardial infarction in patients taking Avandia versus placebo or another comparator drug. The warning also notes that Avandia has not been compared with Actos in a head-to-head study of cardiovascular risks; however, a placebo-controlled trial of the latter drug did not indicate an increase in myocardial infarctions or deaths. The new label also expands previous language related to heart failure and associated conditions, such as edema and fluid retention. Patients with New York Heart Association class III or IV heart failure should not receive Avandia, and the drug may increase other cardiovascular risks in patients with milder forms of heart failure.²⁷

Changes in prescribing guidelines usually increase prescription utilization. However, in some cases when a single new therapy or combination is better than multiple separate existing therapies, utilization decreases. In January 2011, The American Geriatrics Society updated its 10-year-old guidelines on preventing falls in older persons. Recommendations for interventions that are new since the 2001 guidelines include medication reduction or withdrawal, particularly for sedatives, antidepressants, and other drugs affecting the central nervous system, regardless of the number of medications prescribed. This is a change from the 2001 guidelines, which recommended reducing medications only if patients were taking 4 or more. The new guidelines also specify that all older adults at risk for falls, and those with known or suspected vitamin D deficiency, should receive a daily vitamin D supplement.²⁸ The updated guidelines could have an inhibitory effect on prescribing to the elderly in specific classes such as atypical antipsychotics and other central nervous system drugs, while driving increased utilization of prescription vitamin D.

More Lenient Guidelines for Atrial Fibrillation Include Pradaxa

Pradaxa (dabigatran) twice-daily capsules were approved by the FDA in October 2010 for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, or abnormal heart rhythm. It is the first anticoagulant to enter the market since warfarin (Coumadin and generics) was approved in the 1950s. Pradaxa is exponentially more expensive than generic warfarin, which has been available since 1997. Pradaxa’s competitive advantage relates to its superior efficacy; in a pivotal study used to support approval, Pradaxa patients had 34% fewer strokes and systemic embolisms than warfarin patients.²⁹ The shift from generic warfarin to branded Pradaxa will impact both generic dispensing rate and cost.

More lenient management of atrial fibrillation is safe for many patients, according to an update of existing guidelines from the American College of Cardiology and the American Heart Association, published online December 20, 2010. Under the new recommendations, treatment will aim to keep a patient’s heart rate at rest to fewer than 110 beats per minute in those with stable function of the ventricles, the heart’s lower chambers. Prior guidelines stated that strict treatment was necessary to keep a patient’s heart rate at fewer than 80 beats per minute at rest and fewer than 110 beats per minute during a 6-minute walk. The new thinking could lead to patients taking fewer daily medications, more convenient treatment, and perhaps the elimination of significant side effects from some of the drugs. Other treatment changes in the updated guidelines include prescribing a combination of aspirin and Plavix (clopidogrel) for patients who are poor candidates for warfarin; and prescribing Multaq (dronedarone), a newer antiarrhythmic, in place of amiodarone (Cordarone and generics), an older antiarrhythmic, to reduce side effects and hospitalizations.

While the approval of Pradaxa in October came too late for inclusion in the new guidelines published in December,³⁰ an additional update was published by the groups in February 2011 that said that Pradaxa can be used as an alternative to warfarin to prevent blood clots and stroke in patients who have either recurrent episodes of atrial fibrillation that stop after 7 days (called “paroxysmal”) or ongoing (“permanent”) atrial fibrillation, and who have risk factors for blood clotting and stroke, provided that they don’t have a prosthetic heart valve, significant heart valve disease, severe kidney failure, or advanced liver disease.³¹

The Centers for Disease Control and Prevention (CDC) laid out interim recommendations in January 2011 for use of Gilead Sciences’ Truvada (emtricitabine/tenofovir) as the US Public Health Service compiles the final guidelines for the drug, which is currently approved for treatment, not prevention, of HIV. Truvada, which was approved in 2004, combines 2 Gilead drugs, Viread and Emtriva, in a single pill. After a study last year found it can avert 44% of infections, haphazard use of the drug may give men a false sense of security and increase their chance of developing resistance to treatment if they contract the disease, the CDC said in its weekly report.³² It is essential for men to take the drug every day. Prevention rates soared to 73% for those who took the medicine regularly, and plunged to 21% among those who missed even 1 in 10 tablets. Truvada, if used properly, may help reduce the estimated 56,000 infections that occur each year, the agency said. The recommendations and the medication are intended only for men who engage in high-risk sexual practices, including unprotected sex and multiple partners. Additional studies will show in the next 2 years whether the drug provides similar protection against HIV during heterosexual intercourse or from intravenous drug use.³² Even an interim guidance validating use of Truvada as an HIV preventive measure is likely to be a utilization driver for the drug.

A major impact on utilization on the level of therapeutic class is a prescription-to-OTC switch. The most significant prescription blockbusters to have lost utilization to OTC products are the nonsedating antihistamines and proton pump inhibitors. The patent for prescription Prevacid expired on November 10, 2009. That was followed by the immediate launch of 2 competing generic versions as well as an OTC product, Prevacid 24HR (lansoprazole 15 mg). The OTC launch by Novartis was accompanied by a $200 million integrated marketing campaign. The campaign’s message focuses on offering a better quality of life and more choices to heartburn sufferers, and affordability and convenience to patients who had been taking the prescription version of the drug.³³

In January, sanofi-aventis announced that the FDA granted OTC status to all prescription versions of Allegra, and that the agency also approved behind-the-counter sale of Allegra-D. The company launched its branded line of OTC Allegra in the first week of March, with an April entry of a private-label line marketed by Perrigo.³⁴ The second-generation antihistamine is a latecomer to the crowded nonprescription antihistamine category, and will immediately face competition from previously switched Claritin (loratadine) and Zyrtec (cetirizine) and their private-label counterparts.

Another major impact on prescription utilization is the continued drag on the economy and lack of consumer confidence. Increases in gasoline prices to ~$4 a gallon are forcing consumers to choose between gasoline purchases to get to work and other variable expenditures. It is an old story; a prescription copayment is too high, so the member decides to either go without the prescription entirely or selectively chooses to fill his or her prescriptions on a monthly basis.

METHODS

A baseline client cohort was established to track changing marketplace and drug trends. The 2011 client cohort (excluding Medicare Part D) had more than 1200 clients and represented an average of 28 million members. Among the members, 62% were in the employer segment, 27% belonged to health plans, and the remainder were in the Medicaid segment. Only clients with stable membership (limited to a ±20% change in eligibility over 24 months) who had prescription claims in the entire study period were included. The CVS Caremark computerized deidentified database was used to study the utilization by days of supply and gross cost per member per year. The time frame was January 1, 2010, through March 31, 2011. Utilization was based on the change in the number of unique utilizers, average days of supply, and total prescriptions compared year-overyear (YOY). All metrics increased, including the number of utilizers, total number of scripts, and volume based on total days of supply YTD March 2010 compared with YTD March 2011.

KEY FINDINGS

The CVS Caremark overall gross trend in the first quarter of 2011, excluding Medicare Part D, was 2.0% and the days of supply PMPM utilization trend was 1.7%.

Impact to Utilization Trend

We calculated utilization trend as the change in days of supply PMPM. Utilization can be affected by many factors, including new drug approvals and/or new approved indications, reformulations, off-label drug use, changing demographics (eg, our aging population), benefit designs, pharmaceutical promotional spending, new treatment guidelines, and the economy. The slower utilization growth during first quarter of 2011 might be tied to the decline in consumer confidence in the economy and rising gasoline prices.

Figure 1

shows the potential correlation between the average monthly price of gasoline in the United States and the change in prescription utilization.

With gas prices hovering at $4 a gallon, many Americans are making tough choices. An Associated Press—GfK poll showed that more than 40% of respondents expected the price of gas to cause serious financial hardship, while 71% said the rising prices would cause some hardship for them. Some seniors are reportedly choosing a tank of gas over their prescriptions.³⁵

New Drug Approvals 2011

A full list of new drug approvals can be found in

Table 2

, including all new molecular entities, therapeutic biologics, and other novel biologic products (eg, vaccines, immunoglobulins). The most significant of these identified by Industry Analytics as having a strong potential impact on utilization, cost, and overall trend include 2 new biologics (Benlysta for lupus and Yervoy for melanoma) and a protease inhibitor (Victrelis for hepatitis C).

On March 9, 2011, the FDA approved Human Genome Sciences’ Benlysta (belimumab), the first new drug for lupus in more than 50 years.³⁶ The company said Benlysta would cost (at launch) $443 for a 120-mg vial and $1477 for a 400-mg vial. The FDA estimates the systemic lupus population to be at least 300,000.³⁷

On March 25, 2011, the FDA approved Bristol-Myers Squibb’s injectable drug Yervoy (ipilimumab) for latestage or metastatic melanoma, the first drug shown to prolong the lives of patients with advanced skin cancer. It will be priced at $30,000 per injection, for a total price of $120,000. Melanoma is the deadliest type of skin cancer, but the FDA has approved only 2 other drugs for advanced melanoma. The newer of those drugs was cleared more than 13 years ago. Neither drug has been shown to significantly extend patient lives.³⁸

On May 13, 2011, the FDA approved Merck’s Victrelis (boceprevir) for hepatitis C, which the company announced would be available to pharmacies within a week. The wholesale acquisition cost for Victrelis will be $1100 per week, Merck said.³⁹ As new drugs become available, prescribing guidelines are updated and may impact utilization trend.

Influenza Season 2010-2011

Flu cases started to peak in mid-December, and the peak ended in early February, according to the CDC. Statistics point to this flu season as a relatively mild one. The number of cases stayed low between October and mid-December before the winter peak. This year’s flu season also seems to be milder than last year’s because of the extent to which people developed antibodies to the H1N1 strain during last year’s flu season (see

Figure 2

).^40,41

In January 2011, the CDC’s Advisory Committee on Immunization Practices issued updated guidelines regarding the use of antiviral agents for the treatment and chemoprophylaxis of influenza. The new recommendations update those issued by the committee in 2008, principal changes or updates to which include the following:

• Antiviral treatment should be started as soon as possible in patients with confirmed or suspected influenza that is severe, complicated, or progressive, or that necessitates hospitalization.

• Antiviral treatment should be started in outpatients with confirmed or suspected influenza who are at greater risk for complications of influenza based on age (<5 years and especially <2 years, or ≥65 years) or underlying medical conditions.

• Tamiflu (oseltamivir) and Relenza (zanamivir) are the recommended antiviral medications because recent viral surveillance and resistance data show that more than 99% of currently circulating influenza virus strains are sensitive to these drugs. The recommended duration of treatment is 5 days, but longer treatment regimens may be needed in severely ill, hospitalized patients or in immunosuppressed persons.

• Either Tamiflu or Relenza can be used to treat persons with influenza caused by 2009 H1N1 virus, influenza A (H3N2) virus, or influenza B virus, or when the influenza virus type or influenza A virus subtype is unknown.⁴²

The new guidelines advocating early use in at-risk populations may bolster utilization of Tamiflu in particular.

DISCUSSION

In 2011 slower utilization may continue due to wavering of consumer confidence in the economy. Another impact from the economy is continued unemployment. If the consequences of individual budget pressure due to the recession include pill splitting or deferring refills, adherence will dwindle and there could be adverse outcomes. Estimates of the cost of nonadherence to pharmacy therapy nationally have been reported to be over $290 billion.⁴³ A recent study from CVS Caremark showed that the healthcare costs of adherent individuals were actually lower than those of nonadherent individuals. Healthcare costs for patients who stayed on their diabetes medications came in $3756 a year lower than costs for patients who did not take the medicine. Costs for those who stuck with the medicine for congestive heart failure were $7823 a year less. For high blood pressure, the difference was $3908; for high cholesterol, it was $1258.⁴⁴ Recent studies have shown that interventions face-to-face in the pharmacy are most impactful.⁴⁵ However, getting the scale to deliver these types of outcomes face-to-face as well as via technology is time consuming and costly. The true public health advantage will come from being able to deliver impactful interventions across large populations.

Continued unemployment has the Medicaid segment growing. Another impact from the economy is that states are modifying coverage in the Medicaid programs.⁴⁶ In fact, the Medicaid clients included in the cohort experienced the greatest enrollment change, a 5.5% increase in membership. With the continued high rate of unemployment, the Medicaid membership will continue to grow.

A demographic shift would be expected to have the greatest impact on the cholesterol-reducing statins and antiulcer proton pump inhibitors, as a previous analysis found that these 2 classes held either a top place or a second-ranked position in the oldest 3 generational segments in the CVS Caremark BOB: GI, Silent, and Baby Boomer.⁴⁷ The aging population does increase utilization; however, with the shift away from employer-provided retiree coverage and the increasing number of Medicare Part D recipients (partly due to the wave of retiring Baby Boomers), this trend will continue.

The continued drug pipeline shift to specialty drugs and new therapies will also increase utilization. Three newly approved potential blockbusters in the first quarter of 2011 (Benlysta for lupus, Yervoy for melanoma, Victrelis for hepatitis C) will impact long-term trend.

THE FUTURE: 2011 AND BEYOND

Utilization potentially will increase because of the aging population and use of cholesterol-reducing agents such as statin drugs. According to a report published by the CDC in February, far more patients are taking statin drugs today than were taking them 20 years ago. Among Americans 45 years and older, 25% were on lipid-lowering therapy in the period from 2005 to 2008, up from just 2% in 1988-1994, according to the National Center for Healthcare Statistics. The report shows that the percentage of adults with high cholesterol has fallen, from 20% in 1988-1994 to 15% in 2005-2008. While heart disease deaths have declined across age groups, heart disease prevalence has remained stable over the last 10 years.⁴⁸

Another potential driver of utilization and cost is emerging oral therapies for multiple sclerosis patients that will improve patient compliance and persistency in therapy. Unfortunately, the agents are very expensive. The first of these agents to hit the market was Novartis’s Gilenya, approved in September 2010 and priced at ~$48,000, which may raise the bar for the cost of therapy in this class. In April 2011, Teva and Biogen Idec both announced that their investigational oral multiple sclerosis therapies had met their individual goals in pivotal Phase III studies. A New Drug Application submission for Teva’s laquinimod is expected by the end of 2011.⁴⁹ Separately, pending success in another ongoing Phase III study, Biogen plans to submit a New Drug Application to the FDA for BG-12 in the first half of 2012.⁵⁰

Severe weather in winter and spring 2011 may prevent or delay many members from getting prescriptions filled, so rebound utilization may occur in the remainder of 2011. The significant factors that will impact 2011 prescription utilization include the prolonged economic recession, change in employment rate, new generic and brand launches, and the changes in retirement plans of Baby Boomers.