Bansback N, Sizto S, Sun H, Feldman S, Willian MK, Anis A

AIMS: To compare the efficacy of psoriasis treatments through a systematic literature review and meta-analysis. METHODS: Randomized controlled trials evaluating the Psoriasis Area and Severity Index (PASI) were identified and assessed for quality. PASI responses were modeled using a mixed-treatment comparison, which enabled the estimation of the relative effectiveness of several treatments. Sensitivity analyses were performed. RESULTS: Twenty-two trials were included. Tumor necrosis factor (TNF) inhibitors were most likely to achieve PASI 75, with a mean relative risk (RR) of 15.57 (95% CI 12.46-19.25) versus mean RRs of 9.24 (95% CI 5.33-13.91) for systemic and 5.65 (95% CI 3.74-7.97) for T-cell therapies. Infliximab (81%) and adalimumab (71%) had greater probabilities of achieving PASI 75 than etanercept (50%). Dosage was an important determinant of outcome. CONCLUSIONS: TNF inhibitors were more effective than T cell agents; adalimumab and infliximab were more effective than systemic therapies and etanercept. Evidence-based comparisons support patient and physician decisions. (c) 2009 S. Karger AG, Basel.

Dermatology. 2009;219(3):209-18

Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH

BACKGROUND: Overweight and obese persons are at risk of a number of medical conditions which can lead to further morbidity and mortality. The primary objective of this study is to provide an estimate of the incidence of each co-morbidity related to obesity and overweight using a meta-analysis. METHODS: A literature search for the twenty co-morbidities identified in a preliminary search was conducted in Medline and Embase (Jan 2007). Studies meeting the inclusion criteria (prospective cohort studies of sufficient size reporting risk estimate based on the incidence of disease) were extracted. Study-specific unadjusted relative risks (RRs) on the log scale comparing overweight with normal and obese with normal were weighted by the inverse of their corresponding variances to obtain a pooled RR with 95% confidence intervals (CI). RESULTS: A total of 89 relevant studies were identified. The review found evidence for 18 co-morbidities which met the inclusion criteria. The meta-analysis determined statistically significant associations for overweight with the incidence of type II diabetes, all cancers except esophageal (female), pancreatic and prostate cancer, all cardiovascular diseases (except congestive heart failure), asthma, gallbladder disease, osteoarthritis and chronic back pain. We noted the strongest association between overweight defined by body mass index (BMI) and the incidence of type II diabetes in females (RR = 3.92 (95% CI: 3.10-4.97)). Statistically significant associations with obesity were found with the incidence of type II diabetes, all cancers except esophageal and prostate cancer, all cardiovascular diseases, asthma, gallbladder disease, osteoarthritis and chronic back pain. Obesity defined by BMI was also most strongly associated with the incidence of type II diabetes in females (12.41 (9.03-17.06)). CONCLUSION: Both overweight and obesity are associated with the incidence of multiple co-morbidities including type II diabetes, cancer and cardiovascular diseases. Maintenance of a healthy weight could be important in the prevention of the large disease burden in the future. Further studies are needed to explore the biological mechanisms that link overweight and obesity with these co-morbidities.

BMC Public Health. 2009 Mar 25;9:88

Nixon R, Bansback N, Brennan A

OBJECTIVE: New treatments that inhibit the cytokines tumour necrosis factor alpha (TNFalpha) and interleukin 1 (IL-1) in the treatment of rheumatoid arthritis have proven clinical effect against placebo and methotrexate (MTX) in several clinical trials in early and late-stage disease and different severity groups. Since there are no head-to-head randomized controlled trials directly comparing the currently available treatments, etanercept, adalimumab, infliximab or anakinra, we perform a meta-analysis that adjusts for differences between study characteristics, and allows indirect comparisons between treatments. METHODS: Thirteen trials of cytokine antagonists were included from a systematic review of the literature. They reported the primary outcome of American College of Rheumatology (ACR) response criteria at 6 months or beyond. Meta-analytical methods are used to quantify relative treatment effects, using the log odds ratio of an ACR20 or ACR50 response at 6 months, whilst adjusting for study-level variables. RESULTS: In each of the trials, cytokine treatment was efficacious in comparison with placebo or MTX. For each treatment, the inclusion of MTX in combination improved the response. After adjustment for study-level variables, we found TNFalpha antagonists to be more efficacious compared with anakinra (P < 0.05). Indirect comparisons between the three TNFalpha antagonists indicated no difference in efficacy. Sensitivity analysis using a different statistical model structure confirmed these results. CONCLUSION: When the outcome of interest is the probability of an ACR20 or ACR50 response at 6 months we found: (i) treatment with the IL-1 antagonist anakinra is better than placebo; (ii) for each treatment, the use of combination MTX improves the probability of response; (iii) treatment with any of the TNFalpha antagonists is better than with the IL-1 antagonist anakinra; and (iv) all drugs in the TNFalpha antagonist class are no different from each other.

Rheumatology (Oxford). 2007 Jul;46(7):1140-7

Nixon RM, Bansback N, Brennan A

Mixed treatment comparison (MTC) is a generalization of meta-analysis. Instead of the same treatment for a disease being tested in a number of studies, a number of different interventions are considered. Meta-regression is also a generalization of meta-analysis where an attempt is made to explain the heterogeneity between the treatment effects in the studies by regressing on study-level covariables. Our focus is where there are several different treatments considered in a number of randomized controlled trials in a specific disease, the same treatment can be applied in several arms within a study, and where differences in efficacy can be explained by differences in the study settings. We develop methods for simultaneously comparing several treatments and adjusting for study-level covariables by combining ideas from MTC and meta-regression. We use a case study from rheumatoid arthritis. We identified relevant trials of biologic verses standard therapy or placebo and extracted the doses, comparators and patient baseline characteristics. Efficacy is measured using the log odds ratio of achieving six-month ACR50 responder status. A random-effects meta-regression model is fitted which adjusts the log odds ratio for study-level prognostic factors. A different random-effect distribution on the log odds ratios is allowed for each different treatment. The odds ratio is found as a function of the prognostic factors for each treatment. The apparent differences in the randomized trials between tumour necrosis factor alpha (TNF- alpha) antagonists are explained by differences in prognostic factors and the analysis suggests that these drugs as a class are not different from each other. Copyright (c) 2006 John Wiley & Sons, Ltd.

Stat Med. 2007 Mar 15;26(6):1237-54

Ward S, Morris E, Bansback N, Calvert N, Crellin A, Forman D, Larvin M, Radstone D

Health Technol Assess. 2001;5(24):1-70

Lloyd Jones M, Hummel S, Bansback N, Orr B, Seymour M

Health Technol Assess. 2001;5(25):1-128