Teriflunomide real-world evidence: Global differences in the phase 4 Teri-PRO study.

BACKGROUND: The demographics and management of patients with multiple sclerosis (MS) differ across geographical regions, but it is unclear whether/how these differences affect treatment outcomes. The aim of this post-hoc analysis was to assess teriflunomide use and patient-reported outcomes in the United States (US) and the rest of the world (ROW) in the phase 4 Teri-PRO study (NCT01895335). METHODS: In the phase 4, real-world, Teri-PRO study, patients with relapsing forms of MS received teriflunomide for 48 weeks according to local labeling. The primary endpoint was treatment satisfaction measured using the Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM 1.4). Secondary endpoints included scores on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Performance Scale (MSPS), and Patient-Determined Disease Steps (PDDS), and occurrence of adverse events. Primary and secondary endpoints were assessed at baseline and Week 48. An exploratory subgroup analysis assessed PROs in the black patient population. RESULTS: The US and ROW groups included 545 and 455 patients, respectively. The mean age of patients in the ROW group was lower, they had a shorter mean time since first symptoms of MS, and had lower mean EDSS scores at baseline, compared with the US group (all p < 0.0001). Black patients made up 9% of US patients vs 0.2% of ROW patients. TSQM global satisfaction scores and effectiveness, side effects, and convenience subscale scores were significantly improved from baseline to Week 48 (all p < 0.0001). Disability measures were stable from baseline to Week 48 for both groups, despite different baseline level scores between the two groups. The overall proportion of patients who experienced an AE was similar across both groups. Fewer patients in the US group vs the ROW group reported hair thinning (16.1% vs 31.2%). Black patients showed comparable baseline demographics and disease characteristics and similar change over time in PROs compared with the overall US group. CONCLUSION: Patient differences observed at baseline between the US and ROW groups suggest variation in teriflunomide prescribing practices in the real-world Teri-PRO study. Improvement in treatment satisfaction and stability of disability measures were comparable between patients in the US and ROW. This suggests that teriflunomide was effective despite differences in baseline demographics and possible cultural and management differences between these geographical regions.

Patient-reported outcomes in patients with relapsing forms of MS switching to teriflunomide from other disease-modifying therapies: Results from the global Phase 4 Teri-PRO study in routine clinical practice.

BACKGROUND: Patient-reported outcomes (PROs) can assist clinicians in understanding the impact of disease-modifying therapy (DMT) on the daily lives of patients with multiple sclerosis (MS). With an increased number of DMTs becoming available, patients are now switching treatments more frequently in clinical practice. The effects of switching DMTs on a patient's daily life and their disease course may be reflected in PROs. The global, multicenter, open-label, phase 4 Teri-PRO study (NCT01895335), which was conducted in routine clinical practice, previously showed statistically and clinically significant increases in patient-reported treatment satisfaction in patients switching to teriflunomide from other DMTs. The impact of switching to teriflunomide from other DMTs on treatment satisfaction and a range of additional PROs was also evaluated. METHODS: Patients with relapsing forms of MS (N = 1000) received teriflunomide for 48 weeks per local labeling. Outcomes assessed in this analysis included treatment satisfaction (as measured by Treatment Satisfaction Questionnaire for Medication [Version 1.4]), disability worsening (as measured using the Expanded Disability Status Scale [EDSS] score, the Patient-Determined Disease Steps scale, and the Multiple Sclerosis Performance Scale), cognition (as measured using the Symbol Digit Modalities Test [SDMT]), treated relapses, quality of life (as measured by the Multiple Sclerosis International Quality of Life [MusiQoL] questionnaire and the Stern Leisure Activity Scale), and safety/tolerability over the course of the study in the subgroup of patients switching to teriflunomide from another DMT (n = 594). RESULTS: Patients reported significant improvements in treatment satisfaction scores following the switch to teriflunomide regardless of the reason for treating with teriflunomide (Global Satisfaction, disease worsening: baseline, 46.0, Week 48, 65.1; convenience: baseline, 57.4, Week 48, 72.4; intolerance: baseline, 50.9, Week 48, 71.1; side effects: baseline, 49.7, Week 48, 67.2; P < 0.0001 in all comparisons). These patients also showed improvement or stability in PROs evaluating disability worsening, cognition, and quality of life (EDSS: baseline, 3.1, Week 48, 3.0; SDMT: baseline, 0.975, Week 48, 0.978; MusiQoL: baseline, 67.5, Week 48, 69.5). The safety and tolerability profile of teriflunomide was consistent with that observed in other teriflunomide clinical trials. CONCLUSION: This analysis of the Teri-PRO study demonstrates the value of switching to teriflunomide from other DMTs in a real-world, clinical practice setting. The high levels of treatment satisfaction associated with teriflunomide in Teri-PRO may lead to improved adherence and thus improved outcomes.

Patient-reported outcomes in relapsing forms of MS: Real-world, global treatment experience with teriflunomide from the Teri-PRO study.

BACKGROUND: Patient-reported outcomes (PROs) provide clinicians with further understanding of the impact of treatment on patients' daily lives. In addition, real-world studies, which employ broader inclusion criteria than randomized trials, may help to inform prescribing decisions when selecting a disease-modifying therapy (DMT) to treat relapsing forms of MS (RMS). We sought to use PROs to determine patient treatment satisfaction and other treatment outcomes, and report safety and tolerability associated with teriflunomide, in the global, phase 4 Teri-PRO study (NCT01895335). METHODS: Patients with RMS (N = 1000) received teriflunomide for 48 weeks per local labeling. The primary endpoint was Global Satisfaction with teriflunomide treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM, V1.4). Secondary endpoints included TSQM scores at Week (W)48 vs baseline in patients switching to teriflunomide from other DMTs ('switchers'), additional PROs, and safety. RESULTS: Mean TSQM Global Satisfaction score at W48 was high (68.2). Switchers reported significant improvements across all four TSQM domains at W48 vs baseline (all p < 0.0001). Adverse events were consistent with teriflunomide clinical trials. CONCLUSION: Patients reported high treatment satisfaction with teriflunomide, with switchers also reporting improved treatment satisfaction vs baseline. High treatment satisfaction in patients with RMS may lead to improved adherence, and hence treatment outcomes.

Adolescent smokers screened for a nicotine replacement treatment trial: correlates of eligibility and enrollment.

The enrollment process determines the study sample and external validity of clinical trial results; however, few reports describe the process and outcome of screening efforts for smoking cessation studies among adolescents. We describe and evaluate a screening protocol to enroll adolescent smokers for a randomized clinical trial of nicotine replacement therapy. Adolescent smokers obtained the recruitment call-in number (1-800-NO-SMOKE) via media and other advertisements. Trained recruitment staff collected information using an internally developed, targeted telephone screening interview, which was used to determine pre-eligibility for the clinical trial. Correlates of qualification and of study enrollment were determined. Among 1,347 adolescents screened, 329 (24.4%) were eligible to participate in the trial. Light smoking (39.1%) and lack of parental support (14.8%) were the biggest contributors to ineligibility. Eligible adolescents were more likely to be female (66.9% vs. 58.2%, p = .0052) and more likely to be European American (63.5% vs. 52.2%, p = .0003). The higher rates of ineligibility for African Americans and boys were partly explained by lower scores on the Fagerström Test for Nicotine Dependence. Of those eligible to participate in the trial, 159 (48.3%) enrolled. Results underscore the need for screening instruments that are measurement-invariant across ethnicities and gender, and for enrollment strategies that maximize inclusion of eligible participants.

Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction.

OBJECTIVES: To determine the safety and efficacy of the nicotine patch and gum for adolescents who want to quit smoking. DESIGN: Double-blind, double-dummy, randomized, 3-arm trial with a nicotine patch (21 mg), nicotine gum (2 and 4 mg), or a placebo patch and gum; all participants received cognitive-behavioral group therapy. SETTING: Inner-city, outpatient clinic on the East Coast. Subjects. Thirteen- to 17-year-old adolescents who smoked > or =10 cigarettes per day (CPD), scored > or =5 on the Fagerstrom Test of Nicotine Dependence, and were motivated to quit smoking. Intervention. Twelve weeks of nicotine patch or gum therapy with cognitive-behavioral therapy, with a follow-up visit at 6 months (3 months after the end of treatment). MAIN OUTCOME MEASURES: Safety assessed on the basis of adverse event reports for all 3 groups, prolonged abstinence, assessed through self-report and verified with exhaled carbon monoxide (CO) levels of < or =6 ppm, in intent-to-treat analyses, and smoking reduction (CPD and thiocyanate concentrations) among trial completers. RESULTS: A total of 120 participants were randomized (72% white, 70% female; age: 15.2 +/- 1.33 years; smoking: 18.8 +/- 8.56 CPD; Fagerstrom Test of Nicotine Dependence score: 7.04 +/- 1.29) from 1999 to 2003. Participants started smoking at 11.2 +/- 1.98 years of age and had been smoking daily for 2.66 +/- 1.56 years; 75% had at least 1 current psychiatric diagnosis. Mean compliance across groups was higher for the patch (mean: 78.4-82.8%) than for the gum (mean: 38.5-50.7%). Both the patch and gum were well tolerated, and adverse events were similar to those reported in adult trials. Changes in mean saliva cotinine concentrations throughout treatment were not statistically significant. Intent-to-treat analyses of all randomized participants showed CO-confirmed prolonged abstinence rates of 18% for the active-patch group, 6.5% for the active-gum group, and 2.5% for the placebo group; the difference between the active-patch and placebo arms was statistically significant. There was no significant effect of patch versus gum or gum versus placebo on cessation outcomes. Abstinence rates at the 3-month follow-up assessment were sustained but were not significantly associated with treatment group. Mean smoking rates, but not CO or thiocyanate concentrations, decreased significantly in all 3 arms but not as a function of treatment group. CONCLUSIONS: Nicotine patch therapy combined with cognitive-behavioral intervention was effective, compared with placebo, for treatment of tobacco dependence among adolescent smokers. Decreases in the numbers of cigarettes smoked appeared to be offset by compensatory smoking. Additional study of nicotine gum, with enhanced instructional support, is needed to assess its efficacy among adolescent smokers.

Smoking topography and trajectory of asthmatic adolescents requesting cessation treatment.

BACKGROUND: Teenage smokers cite health concerns as their primary motivators for tobacco smoking cessation. Smoke exposure aggravates the clinical course of asthma, yet few reports have examined the association between asthma and smoking topography and trajectory. METHODS: Before their enrollment in a smoking cessation trial, we assessed the smoking topography (i.e., puff volume, maximum puff velocity, puff duration, and interpuff interval) and smoking trajectory (i.e., age of first cigarette, age of daily smoking, time to treatment request, and prior quit attempts) in 30 self-reported asthmatic and 92 nonasthmatic tobacco-dependent teenagers (mean age, 15.2 +/- 1.3 years, 28.7% African-American). Approximately one-half of asthmatics used prescribed medications for their asthma. RESULTS: There was no significant difference in smoking topography or smoking trajectory variables between asthmatic and nonasthmatic adolescents, nor between medicated and nonmedicated asthma subgroups. CONCLUSIONS: Although tobacco smoking exacerbates asthmatic symptoms, these data suggest that age of smoking initiation, as well as smoking topography characteristics in asthmatic adolescents, does not differ from those of adolescents without asthma. These findings highlight the need for more effective health counseling of asthmatic youth regarding the physical and behavioral effects of smoking.

Tobacco smoking trajectory and associated ethnic differences among adolescent smokers seeking cessation treatment.

PURPOSE: To examine smoking trajectories in a clinical sample of adolescent smokers seeking cessation treatment, including: (a) smoking onset (initial, daily) and time intervals from initial to daily smoking and from daily smoking to treatment request, (b) associations between current level of tobacco dependence and smoking history, and (c) differences in smoking trajectory between African-American and non-African-American youth. METHODS: Four hundred and thirty-two adolescent smokers (aged 13-17 years, 61.8% female, 32% African-American) responding to various media advertisement completed a telephone interview as part of pre-eligibility screening for a smoking cessation trial. Smoking trajectory data included age at onset of initial and daily smoking, intervals between those time points, and cigarettes smoked per day (CPD). Tobacco dependence was assessed using the Fagerström Test for Nicotine Dependence (FTND). Data were analyzed using regression models and multiple analyses of covariance. RESULTS: Initial smoking occurred at a mean age of less than 12 years and daily smoking at age 13 years. Earlier onset of daily smoking was associated with higher FTND scores and longer duration from daily smoking to treatment request. For the entire sample, the time interval from initial to daily smoking was 1.14 years. When the sample was divided into early (before age 14 years) and later (at or after age 14 years) initiators, early initiators showed a slower progression from initial to daily smoking compared with late initiators (16 months vs. 6 months). Compared with non-African-American teen smokers, African-American youth reported a 1-year delay in onset of both initial and daily smoking. CONCLUSIONS: Early age of daily smoking and short time interval from initial to daily smoking highlight a brief window of opportunity to prevent the development of tobacco addiction and its consequences. Ethnic differences in smoking trajectory uncovered in this report call for ethnically tailored interventions to reduce youth smoking.

Characteristics of African American teenage smokers who request cessation treatment: implications for addressing health disparities.

BACKGROUND: Ethnoracial disparities in both tobacco-related mortality and treatment outcome for smoking cessation have been reported among adults, but there is a dearth of information on ethnoracial differences among adolescent smokers. OBJECTIVE: To compare smoking-related characteristics in African American and non-African American teenaged applicants for a smoking cessation trial. PARTICIPANTS, DESIGN, AND SETTING: Four hundred thirty-two teenaged smokers (mean [SD] age, 15.6 [1.5] years; 61.8%, female; 31.9%, African American) responded via telephone to various media advertisements. Self-reported sociodemographic, smoking-related, and clinical data were obtained to determine preeligibility for trial participation. MAIN OUTCOME MEASURES: The number of cigarettes smoked per day, Fagerström Test for Nicotine Dependence (FTND) score, motivation to quit, self-reported health problems, and medication use. RESULTS: Compared with non-African Americans, African Americans had lower FTND scores (mean [SD] score, 5.31 [2.24] vs 6.18 [2.18]; P<.01), and smoked fewer cigarettes per day (mean [SD] number of cigarettes, 12.6 [8.3] vs 15.4 [7.5] cigarettes/d; P<.04). The FTND scores were similar in both groups when adjusted for the number of cigarettes smoked per day. African American and non-African American teenagers reported similar motivation to quit (mean [SD] score, 8.64 [1.68] vs 8.53 [1.59], respectively). No difference was found in frequency of physical health problems (eg, asthma), diagnosed psychiatric conditions, or prescribed psychiatric medication although fewer African American teenaged smokers took medication for physical problems (21.2% vs 36.7%). CONCLUSIONS: Cessation treatment interventions designed for African American youths should include lower FTND-defined levels, or the use of other instruments that do not focus on the number of cigarettes smoked per day. Our findings also highlight the importance of ethnocultural issues in treatment research that aims to address health disparities.