Drug Use Evaluation: Smoking Cessation

Drug Use Research & Management Program Oregon State University, 3303 SW Bond Av CH12C, Portland, Oregon 97239-4501 Phone 503-947-5220 Fax 503-494-1082 Drug Use Evaluation: Smoking Cessation Tobacco cessation products cost the United States $193 billion each year in health care costs and lost productivity. An estimated 14% of Medicaid costs are attributable to tobacco use. In 2006, approximately 35% of Medicaid recipients smoked cigarettes. Tobacco dependence treatments (including FDA-approved pharmacotherapy, individual, group and telephone counseling) are highly cost-effective, even cost-saving in some populations. Oregon is the only state that covers all tobacco cessation treatments recommended by the federal clinical practice guidelines. 1 About 21% of Americans currently smoke cigarettes. Cigarette smoking is the leading cause of death in America. Deaths from tobacco related illnesses number 440,000+ yearly and have not declined in the past few years. 1 According to the Surgeon General, on average, men who smoke cut their lives short by 13.2 years, and female smokers lose 14.5 years. It costs the U.S. $75 billion in direct medical costs and $82 billion in lost productivity. 2 Tobacco Cessation Seventy percent (45.3 million) of U.S. smokers have reported that they want to quit smoking and 44.2% (19.9 million) attempt to quit every year; however, only about 7% become tobacco-free without professional help. 3 For patients motivated to quit smoking, abstinence is the goal. To aid in this endpoint, both non-pharmacotherapy and pharmacotherapy interventions play a role. Fiore, et al, found non-pharmacologic interventions, including individual counseling, group counseling and extra treatment social support helped increase nicotine abstinence rates, even in the absence of pharmacologic treatment, but found quit rates highest when counseling and pharmacotherapy are combined. 4 Evidence supported physician advice as well as interventions lasting up to 3 minutes significantly increased long-term abstinence rates. Behavioral therapies of extended duration in terms of session length, total contact time, and number of sessions were found to be more effective than briefer encounters. There was strong evidence that sessions lasting 10 minutes, and attendance to 4 or more sessions was strongly identified with cessation efficacy. 4 Bentz published research which show MD office counseling >10 minutes, interactive telephone counseling along with pharmacotherapy, and group counseling with pharmacotherapy can increase 1 year abstinence rates up to 10%, 25% and 35% respectively. 5 Others have published results which show, with good smoking cessation programs, 20 to 40 percents of participants are able to quit smoking for up to 1 year. 6 Tobacco cessation has many positive benefits. Stroke is reduced to that of a person who never smoked after 5-15 years of not smoking; cancers of the mouth, throat, and esophagus risks are halved 5 years after quitting. Coronary heart disease risk is cut by half 1 year after quitting and is nearly the same as someone who never smoked 15 years after quitting. Lung cancer risk drops by as much as half 10 years after quitting. Cervical cancer risk, peripheral artery disease, ulcer risk, COPD risk are all reduced after quitting, and bladder cancer risk is halved a few years after quitting. Low birth weight baby risk drops to normal if pregnant women quit before pregnancy or during their first trimester. 7 Male smokers who quit between ages 35-39 add an average of 5 years to their lives. Female quitters in this age group add 3 years. Men and women who quit at ages 65-69 increase their life expectancy by 1 year. 6 Telephone counseling: Proactive telephone counseling was found efficacious in assisting people to quit smoking. One case study found smokers are four times as likely to use quitlines as face-to-face clinics, given the same promotional effort. 8 Multiple studies have looked at abstinence success rates with proactive telephone counseling via quit-lines. All studies with multiple calls (at least one call with one follow-up, up to 6 call backs from the quit-line counselor) increased abstinence rates at 3 months and decreased relapse rates at 1 year. In one large meta-analysis, the younger patients, being male, and the lighter smoker did significantly better at sustaining abstinence rates with proactive telephone counseling. 9 Every state has access to a tobacco quit line and there is evidence that these quit lines are effective as an additional resource for smokers motivated to quit. Only 1% of patients use their states' quit-lines according to a recent survey of state/province quit-line use across the United States and Canada. 10

Hollis J, et al, conducted a randomized trial of 4614 Oregon tobacco callers and compared brief (one 15 minute call), moderate (one 30 minute call and a follow-up call) and intensive (five proactive calls) intervention protocols, with or without offers of free nicotine patches (NRT). Blinded staff assessed tobacco use by phone at 12 months. They found abstinence odd ratios were significant for moderate and intensive intervention especially when NRT was also offered. They concluded that offering free NRT and multi-session telephone support led to higher quit rates, and similar costs per incremental quit, than less intensive protocols. 11 The Oregon Tobacco Quit Line (ORQL) is a free statewide phone-based tobacco treatment program. Services include a one-call program (Help Line Call), and a multi-call program through the Free & Clear Quit For Life Program. The onecall may consist of any or all of the following: phone counseling with a Quit Coach, referrals to community resources, written educational material, and information on potential services offered through the callers' insurance. The multi-call program is an intensive proactive treatment that provides up to four follow-up calls, written stage-based educational material, referrals to community resources and additional caller-initiated Quit Line support. Provision of tobacco cessation medications (nicotine patch and gum) are also offered based on the tobacco user's health insurance status and medication use exclusion status. According to the Oregon Tobacco Quit Line Evaluation Report, Year 09, evaluation of an assessment of callers' satisfaction with the ORQL services as well as their tobacco use and/or abstinence showed about 30% of quit-line users were quit at the time of the survey. Continued tobacco users reported a high interest in quitting in the future and demonstrated successful reductions in smoking. 49.4% of the smokers who weren't quit at the follow-up evaluation had reduced the amount of cigarettes smoked compared to their initial (baseline) amount, and 13.6% reduced the amount of cigarettes by 20 cigarettes. Of those who were still smoking at follow-up, almost 80% reported a strong desire to quit. 12 Medication available Nicotine patches (NRT), Bupropion, and Varenicline (Chantix) are used as first line agents in cessation therapy. Nicotine products (gum, lozenge, spray, inhaler) are often used as rescue agents. Nortriptyline and Clonidine have also been used as second line agents in tobacco cessation. This review focuses on varenicline and defining its place in therapy. Varenicline (Chantix R ) Varenicline blocks the nicotine receptors and increases dopamine release which disrupts the reinforcing effects of nicotine and compensates for withdrawal symptoms. There are 5 published studies using varenicline vs. placebo, and three of these studies also included comparisons between varenicline and bupropion. All studies showed varenicline was significantly more efficacious than placebo for short term and long-term abstinence. Pooled odds ratio (OR) for continuous abstinence at 12 months for varenicline vs. placebo was 3.22 across these studies. Varenicline quit rate averaged 21.4% vs. control quit rate of 8%. 13 When compared to Bupropion, varenicline had higher abstinence rates at 12 weeks, and 1 year in one study, 14 while another study showed a non-significant higher rate for varenicline at 1 year. 15 Pooled OR of quit rates for varenicline vs. bupropion was 1.66, in favor of varenicline. 13 A trial by Tonstad, et al, using 24 weeks of varenicline was superior to 12 weeks for purposes of maintaining smoking abstinence. The first 12 weeks was open label, and only those who were abstinent after this time went on for the next 12 weeks. For weeks 13-52 the quit rates were 43.6% for varenicline and 36.9% for placebo. 16 By eliminating those who failed to quit in the open label part, the authors essentially eliminated around 1/3 of individuals who varenicline was not effective for, so relapse prevention rates are higher than one would see in the real world. 17 Counseling was offered in all the studies, all had numerous inclusion and exclusion criteria, plus significant drop-outs due to adverse reactions. Varenicline was associated with significant nausea (30% average) and abnormal dreams across the studies. 13 Varenicline had higher abstinence rates when compared to nicotine patch at the end of treatment and a non-statistically greater rate at 1 year. 18 Varenicline did statistically reduce craving, withdrawal symptoms and smoking satisfaction compared to NRT at the end of treatment. 18 The FDA issued an alert in February 2008, highlighting important revisions to the warnings and precautions sections of the full prescribing information for varenicline, regarding serious neuropsychiatric symptoms. These symptoms include changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicide. In most cases, neuropsychiatric symptoms developed during varenicline treatment, but in others, symptoms developed following withdrawal of varenicline therapy and even occur before the patient has discontinued smoking. The direct role of varenicline in these reported cases is not clear because smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms that include depression and exacerbation of underlying psychiatric illness.

NRTs are typically discontinued when varenicline is initiated primarily due to increased nausea associated with the combination of these drugs. 5 A small, unpublished trial (n=20) using combined bupropion and varenicline treatment showed good tolerance and effectiveness for control of withdrawal symptoms in high risk smokers. 5 OHP FFS Utilization Analysis Pharmacy and medical encounter claims between 7/1/2006 and 12/31/2007 were reviewed for all patients using varenicline, bupropion, or any NRT. Figure 1 and 2 show claims and ingredient costs per 1,000 and 100 members respectively. Utilization and costs for varenicline have grown significantly over the last 12 months. Figure 1: Prescriptions dispensed Per 1,000 Members Per Month (PMPMx1000) 12 Rx Per 1,000 Members Per Month 10 8 6 4 2 0 month/year Bupropion Nicotine Varenicline Figure 2: Ingredient Costs Per 100 Members Per Month (PMPMx100) $120 Cost Per 1,00 Members Per Month $100 $80 $60 $40 $20 $0 month/year Bupropion Nicotine Varenicline Table 1 shows demographics of bupropion, NRT, and varenicline users during the study period. The usage statistics of each agent as shown in table 1 should be interpreted with caution because each has a different base population (i.e. denominator). Bupropion products are reimbursed as FFS for the entire OHP population (i.e. FFS and managed care).

Because many NRT products are over-the-counter, the OHP FFS program still pays for dual eligible Medicare recipients. This is reflected in the higher prevalence of Medicare enrollment and the more advanced age of patients receiving this product. Varenicline is strictly an OHP FFS reimbursed agent. In the past 18 months, total expenditures for varenicline have approached $400,000. Current monthly expenditures for varenicline are approximately $36,000. The average cost per 30-day supply of bupropion (brand and generics), NRT (all routes), and varenicline is $89, $71, and $104 respectively. The use of tobacco cessation counseling provided either from the ORQL or billed from a provider was very infrequent. Only 1.3% of varenicline users were registered with the ORQL. 7% of varenicline users received counseling from a billing clinician. However, similar to other things estimated with billing records, this is likely an underestimate of clinic counseling. Table 1: Demographics Bupropion NRT Varenicline n 10,907 2,092 1,793 Total Costs (18 months) $5,607,050 $214,721 $393,753 Cost / 30 Day Supply $89.42 $70.97 $103.93 Avg Age 36 45 43 Female 8,008 (73.4%) 1,438 (68.7%) 1,320 (73.6%) Race White 9,777 (89.6%) 1,914 (91.5%) 1,669 (93.1%) Black 328 (3.0%) 31 (1.5%) 8 (0.4%) Native American 259 (2.4%) 92 (4.4%) 61 (3.4%) Hispanic 238 (2.2%) 26 (1.2%) 10 (0.6%) Asian 61 (0.6%) 6 (0.3%) 6 (0.3%) Other/Unknown 244 (2.2%) 23 (1.1%) 39 (2.2%) Quitline Use 14 (0.1%) 45 (2.2%) 24 (1.3%) LTC 307 (2.8%) 257 (12.3%) 45 (2.5%) Medicare 194 (1.8%) 479 (22.9%) 21 (1.2%) Table 2 shows use characteristics of a cohort of varenicline users since initial drug launch in July 2006. Over this period, 1,793 unique OHP FFS members started using this drug. Nearly half of using patients had a psychiatric disorder documented using medical claim diagnosis data. Depression and anxiety were the predominate disorders. The average length of therapy for patients starting treatment was 7 weeks (median 4.1 weeks). The recommended therapy for varenicline is one 12-week regimen, with an option for continuation up to 24 weeks. Our analysis suggests 2/3 of users had a length of therapy less than 6 weeks (1,199; 67%). Another 20% used varenicline for another 6 weeks (<12 weeks total treatment) to bring the total 86% of all users. Only 14% of patients starting therapy completed at least 12 weeks of therapy. Concurrent treatment with either bupropion or NRT was relatively uncommon. Conclusions: A very low percentage of smoking cessation users have a record of receiving smoking cessation counseling and very few varenicline users complete the recommended 12 weeks of treatment. A small percentage of patients use varenicline longer than 12 weeks or concurrently with other smoking cessation products. Policy Options: 1. Increase patient and prescriber awareness about Oregon Tobacco Quit Line via a. DUR Newsletter b. Retrospective patient letter to patients with NRT or varenicline highlighting the importance of completing medication regimen and utilizing the quit-line counseling program i. Disadvantage: 2-3 week delay from prescription claim may be too late for effectiveness 2. Require prior authorization of varenicline or NRT to require Oregon Tobacco Quit Line enrollment a. Disadvantage: Medication access and increased administrative cost of PA b. Work with Quit Line to contact PA desk of enrollment? Pharmacist component? 3. Apply 12-week treatment limit and deny claims with concurrent smoking cessation medication use. 4. Allow FFS Medicaid clients to obtain NRT via quit-line In process.

Table 2: Varenicline User Characteristics Count Percent n 1,793 Diagnoses Anxiety 373 (20.8%) Bipolar Disorder 174 (9.7%) Depression 472 (26.3%) Insomnia 111 (6.2%) Personality Disorder 46 (2.6%) Post-Traumatic Stress Disorder 177 (9.9%) Schizophrenia 97 (5.4%) Any Psychiatric Diagnosis 867 (48.4%) Therapy characteristics Avg Length of Therapy (wks) 7.0 Count of Patients by Length of Therapy < 6 weeks 1,199 (66.9%) < 12 weeks 1,546 (86.2%) >=12 weeks 247 (13.8%) >=24 weeks 54 (3.0%) >=48 weeks 8 (0.4%) Avg Dose (mg) 0.868 Mean Modal Dose (mg) 0.837 Pharmacologic Treatments With bupropion 119 (6.6%) With nicotine drugs 82 (4.6%) Non-Pharmacologic Treatments QuitLine Use 24 (1.3%) Tobacco Counseling 120 (6.7%) Any Tobacco Conseling 141 (7.9%) References: 1. MMWR- "State Medicaid Coverage for tobacco-dependence treatments- United States, 2006".CDC. National Center for Health Statistics. Available at: http://www.cdc.gov/nchs/data/nhis/earlyrelease/200706_08.pdf. Accessed 2/1/08. 2. New Surgeon General s Report Expands List of Diseases Caused by Smoking. US Dept of Health and Human Services News Release. May 27,2004. Available at http://www.hhs.gov/news/press/2004pres/20040527a.html 3. (No author). The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives A Clinical Practice Guideline for Treating Tobacco Use and Dependence: A US Public Health Service Report. JAMA. 283(24):3244-3254, June 28, 2000. 4. Fiore Mc, Bailey WC, et al. Treating tobacco use and dependence, clinical practice guideline. U.S. Department of Health and Human Servies. Public Health Services. June 2000. available at http://www.surgeongeneral.gov/tobacco/treating_tobacco_use.pdf. Accessed Feb 11,2008. 5. Ferry L. Management of high-risk tobacco users: where practice guidelines and clinical judgment meet. Medscape December 2007. Available at: http://www.medscape.com/viewprogram/8486_pnt. Accessed 2/1/08. 6. Le Foll, B, George TP; Treatment of tobacco dependence: integrating recent progress into practice. CMAJ 177(11): 1373-1380, Nov 2007. 7. Smoking and Tobacco Use. CDC Available at: http://www.cdc.gov/tobacco. Accessed 2/4/08. 8. McAfee T, Sofian NS, Wilson J, Hindmarsh M. The role of tobacco intervention in population-based health care: a case study. Am J Prev Med 1998;14:46-52. 9. Pan W. Proactive telephone counseling as an adjunct to minimal intervention for smoking cessation: a meta-analysis. Health Education Research. 21(3):416-27, June 2006. 10. Cummins SE, Bailey L, Campbell S, et al. Tobacco cessation quitlines in North America: a descriptive study. Tobacco Control 2007; 16(suppl 1):i9-i15. 11.Hollis JF, McAfee TA, et al. The effectiveness and cost effectiveness of telephone counseling and the nicotine patch in a state tobacco quitline. Tobacco Control 2007;16(supp 1):i53-59. 12. Yepassis-Zemb rou P. Oregon Tobacco Quit Line Evaluation Report Year 09. Free & Clear, Inc. 2007. 13. Cahill K, Stead L, Lancaster T. Nnicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2007;1:CD006103. 14. Jorenby DE, Leischow SJ, Nides MA, et al. Efficacy of varenicline, an alpha4beta2 nicotine acetylcholine receptor partial agonist vs. placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 2006;296:56-63 15. Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist vs. sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006; 296:47-55. 16. Tonstad S, Tonnesen P, Hajek P, Williams KE, et al. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA 2006;296(1):640-71. 17. Klesges RC, Johson KC, Somes G, Varenicline for Smoking cessation Definite promise, but no panacea. JAMA 2006;296:94-95 18. Chantix NDA. www.fda.gov/medwatch/safety/2007/chantix_pi.pdf Accessed 2/10/08.