No adjustments were made for multiple testing

No adjustments were made for multiple testing. Results Systematic review Study characteristics Searches resulted in 453 unique references. were lower than for first-time use. Conclusions. Sequential TNF- inhibitor use is likely to lead to treatment benefit in terms of the signs and symptoms of disease and physical function. There is also some evidence to suggest that the probability of achieving a response is lower, and the average magnitude of response is lower than the first use. Further BTB06584 evidence from randomized controlled trials is required to confirm and further quantify the role specific anti-TNF- brokers have when used sequentially. Online). Searches were conducted to cover the period from January 2001 to October 2009. Studies were included if they considered RA patients that had withdrawn from either infliximab and/or etanercept and/or adalimumab (but not all three) and had been switched to a different TNF- inhibitor. Studies of patients with other conditions such as juvenile arthritis, Crohns disease, PsA or other forms of SpA were excluded unless RA patients could be distinguished in the results. Studies reporting switches to anakinra, abatacept or rituximab were not included. At least one of the following outcome measures that reflect the signs, symptoms and impact on physical function of RA had to BTB06584 be reported for a study to be included: ACR, EULAR, HAQ or DAS/DAS-28. We did not consider radiographic outcome measures. Identified studies were selected for review by one of us (A.J.W.) based on the title and abstract if available. Articles selected were then assessed against the inclusion criteria on the basis of the full study reports. In addition to the criteria given above, several studies were excluded at this stage because they replicated data reported in other studies included in the review. Data from included studies were extracted independently by two of the authors with any disagreements resolved by consensus. We recorded the TNF- inhibitor being investigated and the TNF- inhibitor patients had switched from. The reason for switching was categorized as intolerance or adverse events, primary inefficacy (a failure to achieve a clinical response from the start of treatment), secondary inefficacy (a loss of response over time in patients that had originally achieved primary response) and other. Outcome data were recorded that consisted of number of patients, proportions of responders in case of ACR and EULAR scores and for continuous outcome measures DAS-28 and HAQ, means and standard errors if available. Otherwise s.d.s, medians or inter-quartile ranges were noted. Where studies reported outcomes at multiple time points after switching treatments, data for each time point were extracted. These outcome measures were recorded for whole cohorts described in each of the included studies as well as for sub-groups of patients defined by sequence of the TNF- inhibitor and by reason for switching. Other patient characteristics extracted from the selected papers included mean age, percentage of females, percentage of patients classified as being RF+, mean disease duration in years, mean number of previous DMARDs, mean duration of previous biologic treatment in months and follow-up time in weeks. Meta-analysis Each of the four outcome measuresACR, EULAR, DAS and HAQwere considered separately in the analysis, although comparable analytic methods were utilized; different measures of effect size were used for the categorical and continuous data. We found that many studies reported only ACR20, not ACR50/70/90, and we, therefore, limit discussion to this outcome measure. Random-effects meta-analysis models were used from the outset due to the BTB06584 known clinical heterogeneity between studies. Where data TMEM8 on sub-groups only were available, a fixed-effects meta-analysis was carried out to obtain the overall outcome for your cohort. For non-comparative research, the meta-analysis for the binary response data was completed using the log-odds to be classed like a responder (changed back again to a percentage for interpretation). The result size for the constant results was the differ from baseline rating (improvement in DAS-28 or HAQ ratings). Missing data had been determined or imputed for the constant outcomes where required (specifically, for the noticeable differ from baseline values as well as the associated s.e.s) using both within-study [15] and across-study imputation strategies [16] (see appendix 2 for information, available while supplementary data in Online). Primarily, meta-analyses were carried out dealing with all TNF- inhibitors like a course (i.e. presuming equal performance). Variability between your scholarly research was assessed using the first-line make use of were extracted where reported. Meta-analysis was utilized to pool the full total outcomes from multiple research. For the non-comparative analyses, where.

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