Effect of Intravenous Golimumab on Fatigue and the Relationship with Clinical Response in Adults with Active Ankylosing Spondylitis in the Phase 3 GO-ALIVE Study.

INTRODUCTION: We studied the effect of intravenous (IV)-golimumab on fatigue and the association of fatigue improvement with clinical response post hoc in adults with active ankylosing spondylitis (AS) in the GO-ALIVE trial. METHODS: Patients were randomized to IV-golimumab 2 mg/kg (N = 105) at week (W) 0, W4, then every 8 W (Q8W) or placebo (N = 103) at W0, W4, W12, crossover to IV-golimumab 2 mg/kg at W16, W20, then Q8W through W52. Fatigue measures included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question #1 (fatigue; 0 [none], 10 [worst]; decrease indicates improvement) and 36-Item Short Form Health Survey (SF-36) vitality subscale (0 [worst], 100 [best]; increase indicates improvement). Minimum clinically important difference is ≥ 1 for BASDAI-fatigue and ≥ 5 for SF-36 vitality. GO-ALIVE primary endpoint was Assessment of SpondyloArthritis international Society ≥ 20% improvement criteria (ASAS20). Other clinical outcomes assessed included other ASAS responses, Ankylosing Spondylitis Disease Activity Score, and Bath Ankylosing Spondylitis Functional Index score. The distribution-based minimally important differences (MIDs) were determined for BASDAI-fatigue and SF-36 vitality. The relationship between improvement in fatigue and clinical outcomes was assessed via multivariable logistic regression. RESULTS: Mean changes in BASDAI-fatigue/SF-36 vitality scores were greater with IV-golimumab versus placebo at W16 (- 2.74/8.46 versus - 0.73/2.08, both nominal p ≤ 0.003); by W52 (after crossover), differences between groups narrowed (- 3.18/9.39 versus - 3.07/9.17). BASDAI-fatigue/SF-36 vitality MIDs were achieved by greater proportions of IV-golimumab-treated versus placebo-treated patients at W16 (75.2%/71.4% versus 42.7%/35.0%). A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 increased likelihood of achieving ASAS20 (odds ratios [95% confidence intervals]: 3.15 [2.21, 4.50] and 2.10 [1.62, 2.71], respectively) and ASAS40 (3.04 [2.15, 4.28] and 2.24 [1.68, 3.00], respectively) responses at W16; concurrent improvements and clinical response at W52 were consistent. A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 predicted increased likelihood of achieving ASAS20 (1.62 [1.35, 1.95] and 1.52 [1.25, 1.86], respectively) and ASAS40 (1.62 [1.37, 1.92] and 1.44 [1.20, 1.73], respectively) responses at W52. CONCLUSIONS: IV-golimumab provided important and sustained fatigue improvement in patients with AS that positively associated with achieving clinical response. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02186873.

Ankylosing spondylitis (AS) is a type of arthritis that mostly affects the spine. Patients with AS also often have severe fatigue. Intravenous (IV)-golimumab, which blocks the inflammatory action of tumor necrosis factor, is approved to treat AS. We used information from a clinical trial (GO-ALIVE) to determine whether IV-golimumab reduced fatigue in patients with AS, and if fatigue improvement was associated with improvement in other AS symptoms, including spinal pain, ability to function, and inflammation. In the 1-year GO-ALIVE study, patients were assigned to receive either IV-golimumab or placebo. Patients assigned to placebo were switched to IV-golimumab starting at week 16. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue question and the 36-Item Short Form Health Survey (SF-36) vitality subscale were used to assess fatigue. Improvement in AS symptoms was measured using the Assessment of SpondyloArthritis international Society ≥ 20% and ≥ 40%  improvement criteria (ASAS20 and ASAS40). After 16 weeks of treatment, patients treated with IV-golimumab, on average, had statistically significantly greater improvement in both measures of fatigue than patients treated with placebo. At 1 year, after the placebo group had received IV-golimumab starting at week 16, improvement in fatigue was similar between groups. Improvement in fatigue at week 16 increased the likelihood that ASAS20 and ASAS40 would be achieved at week 16. Similar results were observed at 1 year. Additionally, improvement in fatigue at week 16 predicted the likelihood of achieving ASAS20 and ASAS40 at 1 year. Together, these results demonstrate that IV-golimumab provided important, long-term improvement in fatigue in patients with AS that was positively associated with improvement in AS symptoms.

Towards refining World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations for red and processed meat intake: insights from Alberta's Tomorrow Project cohort.

Current cancer prevention recommendations advise limiting red meat intake to <500 g/week and avoiding consumption of processed meat, but do not differentiate the source of processed meat. We examined the associations of processed meat derived from red v. non-red meats with cancer risk in a prospective cohort of 26 218 adults who reported dietary intake using the Canadian Diet History Questionnaire. Incidence of cancer was obtained through data linkage with Alberta Cancer Registry with median follow-up of 13·3 (interquartile range (IQR) 5·1) years. Multivariable Cox proportional hazards regression models were adjusted for covariates and stratified by age and sex. The median consumption (g/week) of red meat, processed meat from red meat and processed meat from non-red meat was 267·9 (IQR 269·9), 53·6 (IQR 83·3) and 11·9 (IQR 31·8), respectively. High intakes (4th Quartile) of processed meat from red meat were associated with increased risk of gastrointestinal cancer adjusted hazard ratio (AHR): 1·68 (95 % CI 1·09, 2·57) and colorectal cancers AHR: 1·90 (95 % CI 1·12, 3·22), respectively, in women. No statistically significant associations were observed for intakes of red meat or processed meat from non-red meat. Results suggest that the carcinogenic effect associated with processed meat intake may be limited to processed meat derived from red meats. The findings provide preliminary evidence towards refining cancer prevention recommendations for red and processed meat intake.

The effect of different methods to identify, and scenarios used to address energy intake misestimation on dietary patterns derived by cluster analysis.

BACKGROUND: All self-reported dietary intake data are characterized by measurement error, and validation studies indicate that the estimation of energy intake (EI) is particularly affected. METHODS: Using self-reported food frequency and physical activity data from Alberta's Tomorrow Project participants (n = 9847 men 16,241 women), we compared the revised-Goldberg and the predicted total energy expenditure methods in their ability to identify misreporters of EI. We also compared dietary patterns derived by k-means clustering under different scenarios where misreporters are included in the cluster analysis (Inclusion); excluded prior to completing the cluster analysis (ExBefore); excluded after completing the cluster analysis (ExAfter); and finally, excluded before the cluster analysis but added to the ExBefore cluster solution using the nearest neighbor method (InclusionNN). RESULTS: The predicted total energy expenditure method identified a significantly higher proportion of participants as EI misreporters compared to the revised-Goldberg method (50% vs. 47%, p < 0.0001). k-means cluster analysis identified 3 dietary patterns: Healthy, Meats/Pizza and Sweets/Dairy. Among both men and women, participants assigned to dietary patterns changed substantially between ExBefore and ExAfter and also between the Inclusion and InclusionNN scenarios (Hubert and Arabie's adjusted Rand Index, Kappa and Cramer's V statistics < 0.8). CONCLUSIONS: Different scenarios used to account for EI misreporters influenced cluster analysis and hence the composition of the dietary patterns. Continued efforts are needed to explore and validate methods and their ability to identify and mitigate the impact of EI misestimation in nutritional epidemiology.

Strategies to Address Misestimation of Energy Intake Based on Self-Report Dietary Consumption in Examining Associations Between Dietary Patterns and Cancer Risk.

The objective of this study was to determine the influence of strategies of handling misestimation of energy intake (EI) on observed associations between dietary patterns and cancer risk. Data from Alberta's Tomorrow Project participants (n = 9,847 men and 16,241 women) were linked to the Alberta Cancer Registry. The revised-Goldberg method was used to characterize EI misestimation. Four strategies assessed the influence of EI misestimation: Retaining individuals with EI misestimation in the cluster analysis (Inclusion), excluding before (ExBefore) or after cluster analysis (ExAfter), or reassigning into ExBefore clusters using the nearest neighbor method (InclusionNN). Misestimation of EI affected approximately 50% of participants. Cluster analysis identified three patterns: Healthy, Meats/Pizza and Sweets/Dairy. Cox proportional hazard regression models assessed associations between the risk of cancer and dietary patterns. Among men, no significant associations (based on an often-used threshold of p < 0.05) between dietary patterns and cancer risk were observed. In women, significant associations were observed between the Sweets/Dairy and Meats/Pizza patterns and all cancer risk in the ExBefore (HR (95% CI): 1.28 (1.04-1.58)) and InclusionNN (HR (95% CI): 1.14 (1.00-1.30)), respectively. Thus, strategies to address misestimation of EI can influence associations between dietary patterns and disease outcomes. Identifying optimal approaches for addressing EI misestimation, for example, by leveraging biomarker-based studies could improve our ability to characterize diet-disease associations.

Alcohol consumption and low-risk drinking guidelines among adults: a cross-sectional analysis from Alberta's Tomorrow Project. / Consommation d'alcool et lignes directrices pour la consommation d'alcool à faible risque chez les adultes : une analyse transversale de l'Alberta's Tomorrow Project.

INTRODUCTION: Moderate to heavy alcohol consumption is a risk factor for all-cause mortality and cancer incidence. Although cross-sectional data are available through national surveys, data on alcohol consumption in Alberta from a large prospective cohort were not previously available. The goal of these analyses was to characterize the levels of alcohol consumption among adults from the Alberta's Tomorrow Project in the context of cancer prevention guidelines. Furthermore, we conducted analyses to examine the relationships between alcohol consumption and other high-risk or risk-related behaviours. METHODS: Between 2001 and 2009, 31 072 men and women aged 35 to 69 years were enrolled into Alberta's Tomorrow Project, a large provincial cohort study. Data concerning alcohol consumption in the past 12 months were obtained from 26 842 participants who completed self-administered health and lifestyle questionnaires. We conducted cross-sectional analyses on daily alcohol consumption and cancer prevention guidelines for alcohol use in relation to sociodemographic factors. We also examined the combined prevalence of alcohol consumption and tobacco use, obesity and comorbidities. RESULTS: Approximately 14% of men and 12% of women reported alcohol consumption exceeding recommendations for cancer prevention. Higher alcohol consumption was reported in younger age groups, urban dwellers, those with higher incomes and those who consumed more red meat. Moreover, volume of daily alcohol consumption was positively associated with current tobacco use in both men and women. Overall, men were more likely to fall in the moderate and high-risk behavioural profiles and show higher daily alcohol consumption patterns compared to women. CONCLUSION: Despite public health messages concerning the adverse impact of alcohol consumption, a sizeable proportion of Alberta's Tomorrow Project participants consumed alcohol in excess of cancer prevention recommendations. Continued strategies to promote low-risk drinking among those who choose to drink could impact future chronic disease risk in this population.

INTRODUCTION: La consommation modérée ou élevée d'alcool constitue un facteur de risque de mortalité toutes causes confondues et de cancer. Nous disposons de données transversales grâce aux enquêtes nationales, mais jusqu'à présent aucunes données sur la consommation d'alcool en Alberta n'étaient disponibles pour une grande cohorte prospective. Notre objectif est de définir, à la lumière des lignes directrices de prévention du cancer, les niveaux de consommation d'alcool des adultes ayant pris part à l'Alberta's Tomorrow Project. Nous avons également analysé les liens entre la consommation d'alcool et certains autres comportements à risque, en particulier à risque élevé. MÉTHODOLOGIE: Entre 2001 et 2009, 31 072 hommes et femmes de 35 à 69 ans ont participé à l'Alberta's Tomorrow Project, une grande étude de cohorte provinciale. Des données concernant la consommation d'alcool dans les 12 derniers mois ont été obtenues pour 26 842 participants ayant répondu à des questionnaires autoadministrés sur la santé et sur le mode de vie. Nous avons effectué des analyses transversales sur la consommation d'alcool quotidienne et les lignes directrices de prévention du cancer en matière de consommation d'alcool en lien avec des facteurs sociodémographiques. Nous avons aussi examiné la prévalence combinée de la consommation d'alcool, du tabagisme, de l'obésité et de diverses comorbidités. RÉSULTATS: Environ 14 % des hommes et 12 % des femmes ont déclaré consommer davantage d'alcool que ce que préconisent les recommandations en matière de prévention du cancer. Une consommation plus importante d'alcool a été rapportée chez les plus jeunes, les citadins, les personnes à revenu plus élevé et celles consommant davantage de viande rouge. En outre, le volume de consommation quotidienne d'alcool était positivement associé au tabagisme, tant chez les hommes que chez les femmes. De manière générale, les hommes étaient plus susceptibles que les femmes de correspondre aux profils comportementaux à risque modéré et élevé ainsi que de consommer quotidiennement de l'alcool. CONCLUSION: Malgré les messages de santé publique à propos de l'impact négatif de la consommation d'alcool, une proportion considérable de participants de l'Alberta's Tomorrow Project consommait davantage d'alcool que ce que préconisent les recommandations en matière de prévention du cancer. Des stratégies durables en faveur d'une consommation d'alcool à faible risque auprès de ceux qui choisissent de boire pourraient avoir une influence sur le risque de maladie chronique au sein de cette population.

Measures of excess body weight and anthropometry among adult Albertans: cross-sectional results from Alberta's tomorrow project cohort.

BACKGROUND: Excess body weight during adulthood has been consistently associated with all-cause mortality, cardiovascular disease, and cancer at multiple sites among other chronic diseases. We describe the prevalence of excess body weight and abdominal obesity reported by participants enrolled in Alberta's Tomorrow Project (ATP). METHODS: ATP is a geographically-based cohort study conducted among adults aged 35-69 years from across the province of Alberta. Participants completed anthropometric measures and health and lifestyle questionnaires at enrolment. Overweight and obese were categorized as a body mass index (BMI) of 25.0-29.9 kg/m2 and ≥30 kg/m2, respectively. Abdominal obesity was categorized using cut-offs of waist circumference of >94 cm for men and >80 cm for women and waist-tp-hip ratio cut-offs of >0.90 for men and >0.85 for women. RESULTS: BMI and hip and waist circumference data were obtained from 12,062 men and 18,853 women enrolled between 2001 and 2009. Overall, 76.8% of men and 59.5% of women reported a BMI ≥25 kg/m2. The proportions of overweight and obese were significantly higher in older age groups (p < 0.001). In addition, the proportion of participants reporting being overweight and obese was higher among lower education (p < 0.001) and lower income groups (p < 0.001). Overall, approximately two thirds of men and women in ATP cohort reported abdominal obesity. Overweight, obesity and abdominal obesity were all associated with a history of several cardiometabolic chronic conditions including hypertension, heart attack, angina, high cholesterol, stroke and diabetes. CONCLUSION: A large majority of ATP participants were overweight and carried excess abdominal fat. Strategies to improve energy balance among Albertans are encouraged and may have a notable impact on future chronic disease burden.

The Comparative Reliability and Feasibility of the Past-Year Canadian Diet History Questionnaire II: Comparison of the Paper and Web Versions.

Advances in technology-enabled dietary assessment include the advent of web-based food frequency questionnaires, which may reduce costs and researcher burden but may introduce new challenges related to internet connectivity and computer literacy. The purpose of this study was to evaluate the intra- and inter-version reliability, feasibility and acceptability of the paper and web Canadian Diet History Questionnaire II (CDHQ-II) in a sub-sample of 648 adults (aged 39-81 years) recruited from Alberta's Tomorrow Project. Participants were randomly assigned to one of two groups: (1) paper, web, paper; or (2) web, paper, web over a six-week period. With few exceptions, no statistically significant differences in mean nutrient intake were found in the intra- and inter-version reliability analyses. The majority of participants indicated future willingness to complete the CDHQ-II online, and 59% indicated a preference for the web over the paper version. Findings indicate that, in this population of adults drawn from an existing cohort, the CDHQ-II may be administered in paper or web modalities (increasing flexibility for questionnaire delivery), and the nutrient estimates obtained with either version are comparable. We recommend that other studies explore the feasibility and reliability of different modes of administration of dietary assessment instruments prior to widespread implementation.

Design, methods and demographics from phase I of Alberta's Tomorrow Project cohort: a prospective cohort profile.

BACKGROUND: Prospective cohorts have the potential to support multifactorial, health-related research, particularly if they are drawn from the general population, incorporate active and passive follow-up and permission is obtained to allow access by researchers to data repositories. This paper describes Phase I of the Alberta's Tomorrow Project cohort, a broad-based research platform designed to support investigations into factors that influence cancer and chronic disease risk. METHODS: Adults aged 35-69 years living in Alberta, Canada, with no previous cancer diagnosis other than nonmelanoma skin cancer were recruited to the project by telephone-based random digit dialling. Participants were enrolled if they returned a Health and Lifestyle Questionnaire. Past year diet and physical activity questionnaires were mailed 3 months after enrolment. Consent was sought for active follow-up and linkage with administrative databases. Depending on enrolment date, participants were invited to complete up to 2 follow-up questionnaires (2004 and 2008). RESULTS: Between 2001 and 2009, 31 072 (39% men) participants (mean age 50.2 [± 9.2] yr) were enrolled and 99% consented to linkage with administrative databases. Participants reported a wide range of educational attainment and household income. Compared with provincial surveillance data from the Canadian Community Health Survey, Alberta's Tomorrow Project participants had higher body mass index, lower prevalence of smoking and similar distribution of chronic health conditions. Follow-up questionnaires were completed by 83% and 72% of participants in 2004 and 2008, respectively. Robust quality control measures resulted in low frequencies of missing data. INTERPRETATION: Alberta's Tomorrow Project provides a robust platform, based on a prospective cohort design, to support research into risk factors for cancer and chronic disease.