Real-world effectiveness of nicotine replacement therapy in pregnancy

Leonie S. Brose, PhD Andy McEwen, PhD & Robert West, PhD

University College London and National Centre for Smoking Cessation and Training

Background• Smoking in pregnancy in UK 1

– 26% immediately before or during pregnancy– 12% throughout and at delivery– Underreporting likely

• Smoking in pregnancy increases risk of e.g. 2

– Preterm birth – Placental abruption – Low birth-weight – Sudden infant death syndrome– Adult morbidities such as obesity, diabetes, asthma, mental

health problems

• Stopping smoking reduces increased risks

1 NHS Information Centre, 20112 USDHHS, 2004

Background• In general population: Medication increases quit rates

– Single nicotine replacement therapy (NRT)– Combination of two (or more) NRT products – Bupropion (Zyban)– Varenicline (Champix)

Brose et al, 2011, Thorax

Background• Pregnancy: NRT can be used • Review of randomised controlled trials (RCTs) failed to

find evidence for effectiveness 3

– Evaluated single NRT, mostly nicotine patch

• NHS Stop Smoking Services 4

– Behavioural support and medication– Different types of support and range of settings– More than 20,000 pregnant women per year– Many use combination NRT

3 Coleman et al, Cochrane, 20124 NHS Information Centre, 2011

Objective and research questions

To assess the association of single and combination NRT with success of quit attempts of pregnant smokers in clinical practice while adjusting for smoker and treatment characteristics.– Are negative RCT findings for single NRT borne out

in clinical practice?– Combination NRT has not been evaluated in RCTs;

does it confer a benefit for smoking cessation in pregnant smokers?

Sample

Identified as pregnant N=9,587

N=315,721 treatment episodesin 49 Services

April 2009 – June 2011

Missing due date

Main analysisN=3,880

N=8,999(Sensitivity analysis)

Missing age, sex, setting or support type (n=71)

Varenicline or bupropion (n=79) Telephone support (n=438)

Methods

OutcomeCO-validated 4-week quit rates Russell Standard (Clinical)

Clients lost to follow-up counted as smoking 5

Predictors • Medication (none, single NRT, combination NRT)• Treatment setting (specialist clinics, home visit,

primary care, other) • Type of support (group, 1-to-1, drop-in, other) • Occupational grade (employed, not employed,

student, unable to code)• Age • Months pregnant• Ethnicity (white, other)• Year of quit attempt

5 West et al, Addiction, 2005

Dependence: Heaviness of Smoking Index (HSI) completed for 29%. Differences between medications assessed separately.

Methods• Two-level logistic regression models to assess effect of

predictors on quit rates

Sensitivity analysesa. Including those without months pregnant, n=8,999b. Excluding all lost to follow-up, remaining n=2,887

N=3,880No medication n=588 (15.2%)

Single NRTn=1166 (30.1%)

Combination NRTn=2126 (54.8%)

Age, Mean (SD) 25.3 (6.0) 25.7 (6.3) 26.4 (6.1)Months pregnant, Mean (SD) 3.5 (2.1) 4.3 (1.9) 4.3 (1.8)Ethnicity % (n) White 73.3 88.2 90.3 Occupational grade % In employment 24.1 38.6 41.6 Not in employment 24.7 44.9 43.9 Unable to code 48.5 11.1 10.1Intervention setting % Specialist clinic 71.8 51.1 49.2 Home visit a 16.3 29.4 36.0 Primary care 9.7 12.3 8.5

Other 2.2 7.2 6.4Intervention type % One-to-one 79.8 74.1 81.2 Group 1.2 4.1 1.3 Other 11.4 10.9 10.9CO-validated 4-week quit % 16.3 24.8 35.7Lost to follow-up % 29.4 31.7 21.2

a. Provided by specialist practitioners in 75% of cases

Predictors of CO-validated 4-week abstinence2-level multivariable logistic regression, n=3,880

Odds ratio (OR)

95% Confidence interval (CI) p value

Medication, reference: None Single NRT 1.06 0.60 to 1.86 0.84 Combination NRT 1.93 1.13 to 3.29 0.02Intervention setting, reference: Specialist clinic Home visit 1.16 0.89 to 1.51 0.28 Primary care 0.57 0.41 to 0.79 0.001 Other setting 1.00 0.70 to 1.42 0.98Intervention type, reference: One-to-one Group 0.62 0.35 to 1.12 0.11 Drop-in 0.58 0.42 to 0.82 0.002 Other 0.97 0.69 to 1.36 0.85Months pregnant, per month increase 0.95 0.91 to 0.99 0.02

Also adjusted for ethnicity, age, occupational grade

Further results

DependenceThose using combination NRT more dependent. F(2,1124)=14.26, p<0.001

Sensitivity analysesa. Including those without information on stage of pregnancyb. Excluding all lost to follow-up

Results remain: Combination NRT benefit over no medication, single NRT no benefit.

• Single NRT shows no benefit - in line with RCTs • But combination NRT associated with success

– Not due to differences in intervention or client characteristics, including dependence

• Common non-specialist treatment (primary care) and later stage of pregnancy associated with worse outcomes

• Limitation: Correlational design, but adjusted• Suggests need for full-scale RCT

Discussion

Discussion • First evidence on combination NRT in pregnancy

• Exposes foetus to higher levels of nicotine than single NRT or stopping all use of nicotine, but: – Other options associated with resumed smoking– NRT delivers nicotine without carbon monoxide

and other reproductive toxins in cigarettes

• High-quality evidence-based behavioural support 6,7 should be provided regardless of medication

6 Lumley et al, Cochrane, 20097 Lorencatto et al, NTR, 2012

Conclusions

• Use of a combination of nicotine transdermal patch and a faster acting form of nicotine replacement therapy appears to confer a benefit in terms of promoting smoking cessation during pregnancy.

• While this conclusion is based on observational data, it lends support to this treatment option pending confirmation by a randomised controlled trial.

Thank youwww.ncsct.co.uk

leonie.brose@ncsct.co.uk