David Gonzales

Immunogenicity and Smoking Cessation Outcomes for a Novel Nicotine Immunotherapeutic

NicVAX, a nicotine vaccine (3′AmNic‐rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double‐blinded, placebo‐controlled multicenter clinical trial (N = 301 smokers) tested the results of 200‐ and 400‐µg doses administered four or five times over a period of 6 months, as compared with placebo. 3′AmNic‐rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14–6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five‐injection, 400‐µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3′AmNic‐rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.

Bupropion SR as an aid to smoking cessation in smokers treated previously with bupropion: a randomized placebo-controlled study.

Many persons who attempt to quit smoking have made previous unsuccessful attempts to quit with pharmacologic aids. An understanding of the impact of these previous attempts to quit is vital for selecting medications that may be more successful in a future attempt to quit. In particular, the effect of repeated use of bupropion SR (Zyban; INN, amfebutamone) on abstinence rates has not been studied previously.

Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in Their Newborn Infants: A Randomized Clinical Trial

IMPORTANCE Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00632476.

Effects of gender on relapse prevention in smokers treated with bupropion SR

BACKGROUND Recent data suggest that women smokers respond differently than men to cessation pharmacotherapies, particularly nicotine replacement therapy (NRT). Lower abstinence and higher relapse rates are often reported for women treated with NRT. Gender effects for those treated with non-nicotinic, bupropion-hydrochloride sustained release for relapse prevention have not been studied. METHODS Data from a multicenter relapse-prevention (RP) trial of bupropion (November 1995-June 1998) were analyzed for gender differences. Men and women smokers (N=784) were treated with open-label bupropion for 7 weeks. Those abstinent at Week 7 (n=432) were enrolled in the double-blind relapse-prevention phase and randomized to placebo or continued bupropion for 45 additional weeks. RESULTS Differences in point-prevalence abstinence rates between men (61.8%) and women (55.6%) in open-label bupropion (Week 7) were not significant. In the RP-phase Week 52, continuous abstinence rates for men and women were 37.8% and 36.4% (bupropion) and 36.6% and 29.9% (placebo), respectively; point-prevalence abstinence rates for men and women were 54.1% and 55.9% (bupropion) and 42.9% and 41.3% (placebo), respectively. Abstinence rates and time to relapse were superior for both men and women who received longer treatment. Gender differences within treatment groups were not significant. Median time to relapse was equal for men and women within each treatment group: Week 32 for bupropion and Week 20 for placebo. CONCLUSIONS Our data suggest that bupropion is a promising pharmacotherapy for preventing relapse, particularly for women.

A randomized controlled trial of adding the nicotine patch to rimonabant for smoking cessation: efficacy, safety and weight gain

AIMS Because smoking cessation rates might be improved by combining drugs and by reducing post-cessation weight gain, we tested the smoking cessation efficacy, safety and effect on body weight of adding the nicotine patch to rimonabant, a cannabanoid type-1 receptor antagonist that reduces body weight. DESIGN Randomized double-blind placebo-controlled trial. SETTING Fifteen US research centers. PARTICIPANTS A total of 755 smokers (> OR = 15 cigarettes/day). Intervention Rimonabant (20 mg daily) was given open-label for 9 weeks. The 735 participants completing week 1 were randomized at day 8 (target quit day) to add a nicotine patch (n = 369) or placebo patch (n = 366) for 10 weeks (21 mg daily for 8 weeks plus a 2-week taper). Participants received weekly smoking counseling and were followed for 24 weeks. MEASUREMENTS Biochemically validated 4-week continuous abstinence at end-of-treatment (weeks 6-9; primary end-point); 7-day point prevalence abstinence at weeks 9 and 24; sustained abstinence (weeks 6-24); change in body weight; and adverse events. FINDINGS Rimonabant plus nicotine patch was superior to rimonabant plus placebo in validated continuous abstinence at weeks 6-9 (39.0% versus 21.3%; odds ratio 2.36, 95% confidence interval: 1.71-2.37; P < 0.01) and in all other efficacy measures. Mean end-of-treatment weight gain among quitters did not differ between groups (0.04 kg for combination versus 0.49 kg for rimonabant only, P = 0.15) and was similar in weight-concerned smokers. Serious adverse event rates did not differ between groups. Depression- and anxiety-related adverse events occurred in 32 (4.2%) and 44 (5.8%) subjects, respectively; eight (1.1%) and nine (1.2%) subjects stopped the drug due to depression and anxiety, respectively. CONCLUSIONS Adding a nicotine patch to rimonabant was well tolerated and increased smoking cessation rates over rimonabant alone. There was little post-cessation weight gain in either group, even among weight-concerned smokers, during drug treatment.

Bupropion for pharmacologic relapse prevention to smoking: predictors of outcome.

The aim of this study was to identify predictors of successful relapse prevention in smokers receiving long-term sustained-release bupropion. Smokers (N= 784) who were interested in stopping smoking were enrolled in a 7-week, open-label bupropion phase. Abstinent subjects at the end of treatment and eligible to proceed (N= 429) were randomized to active bupropion or placebo through Week 52 and then followed for an additional year. The best overall predictor of less relapse to smoking was assignment to active bupropion. In aggregate, the results indicate that bupropion can be prescribed to diverse populations of smokers with expected comparable results. There was a medication effect that was independent of any predictor except older age and those who gained no or minimal weight during the open-label phase. Predictors of successful relapse prevention included lower baseline smoking rates, a Fagerström Tolerance Questionnaire score of < 6, and initiation of smoking at an older age. These data should encourage others to perform similar pharmacologic relapse prevention studies with this or other pharmacotherapies.

Immediate versus delayed quitting and rates of relapse among smokers treated successfully with varenicline, bupropion SR or placebo.

Aims We assessed to what degree smokers who fail to quit on the target quit date (TQD) or lapse following TQD eventually achieve success with continued treatment. Design A secondary analysis of pooled data of successful quitters treated with varenicline (306 of 696), bupropion (199 of 671) and placebo (121 of 685) from two identically-designed clinical trials of varenicline versus bupropion sustained-release and placebo. Setting Multiple research centers in the US. Participants Adult smokers (n = 2052) randomized to 12 weeks drug treatment plus 40 weeks follow-up. Measurement The primary end-point for the trials was continuous abstinence for weeks 9–12. TQD was day 8. Two patterns of successful quitting were identified. Immediate quitters (IQs) were continuously abstinent for weeks 2–12. Delayed quitters (DQs) smoked during 1 or more weeks for weeks 2–8. Findings Cumulative continuous abstinence (IQs + DQs) increased for all treatments during weeks 3–8. Overall IQs and DQs for varenicline were (24%; 20%) versus bupropion (18.0%, P =0.007; 11.6%, P <0.001) or placebo (10.2%, P <0.001; 7.5%, P <0.001). However, DQs as a proportion of successful quitters was similar for all treatments (varenicline 45%; bupropion 39%; placebo 42%) and accounted for approximately one-third of those remaining continuously abstinent for weeks 9–52. No gender differences were observed by quit pattern. Post-treatment relapse was similar across groups. Conclusions Our data support continuing cessation treatments without interruption for smokers motivated to remain in the quitting process despite lack of success early in the treatment.

Support for spirituality in smoking cessation: results of pilot survey.

Patient spiritual resources are increasingly included in the treatment of medical conditions such as cancers and alcohol and drug dependence, but use of spiritual resources is usually excluded from tobacco dependence treatment. We hypothesized that this omission may be linked to perceived resistance from smokers. To examine this hypothesis, we conducted a pilot survey to assess whether current smokers would consider spiritual, including religious, resources helpful if they were planning to quit. Smokers at least 18 years of age at Oregon Health & Science University in Portland, Oregon, (N=104) completed a brief survey of smoking behaviors and spiritual beliefs. None were attempting to quit. Of these individuals, 92 (88%) reported some history of spiritual resources (spiritual practice or belief in a Higher Power), and of those respondents, 78% reported that using spiritual resources to quit could be helpful, and 77% reported being open to having their providers encourage use of spiritual resources when quitting. Results of logistic regression analysis indicated that those aged 31-50 years (OR=3.3), those over age 50 years (OR=5.4), and women (OR=3.4) were significantly more likely to have used spiritual resources in the past. Of the 92 smokers with any history of spiritual resources, those smoking more than 15 cigarettes/day were significantly more receptive to provider encouragement of spiritual resources in a quit attempt (OR=5.4). Our data are consistent with overall beliefs in the United States about spirituality and recent trends to include spirituality in health care. We conclude that smokers, especially heavier smokers, may be receptive to using spiritual resources in a quit attempt and that spirituality in tobacco dependence treatment warrants additional investigation and program development.

Two Years in the Life of a University Hospital Tobacco Cessation Service: Recommendations for Improving the Quality of Referrals

BACKGROUND Hospitalization, when patients may be more receptive to quitting, provides an opportunity to provide tobacco cessation services for patients who otherwise might not seek help. Although specialized tobacco cessation services are shown to be effective if evidence-based treatment, including follow-up, is completed, resources are limited and guidelines are needed, and few smokers complete all treatment steps. Experience drawn from an analysis of two-year implementation data from the Oregon Health & Science University (OHSU) Tobacco Cessation Consult Service is presented. METHODS Data for 5,827 smokers discharged from OHSU University hospital between January 2011 and December 2012 were analyzed to determine patient characteristics and identify predictors of completing each of four treatment steps: consult ordered, consult completed, follow-up arranged, and follow-up completed. RESULTS Smokers were younger and male (p<0.0001) and significantly different with respect to insurance class, admission type, history of mental disorders, primary discharge diagnoses, and length of stay (p<0.0001) than nonsmokers. Predictors of having a tobacco consult order were admission for elective medical procedures; orders for medications to treat withdrawal; history of mental health/substance use disorders; primary diagnoses of cardiovascular, endocrine, gastrointestinal, or pulmonary disease; and longer hospitalizations. Smokers admitted through the emergency department had the lowest rates of follow-up completion and abstinence. Admission for an elective surgery was the only predictor of completing all treatment steps through followup (p≤0.05). CONCLUSIONS This study adds important information about how hospitalized smokers respond to each step of tobacco treatment in a real-world setting and offers strategies for improving referrals.