In Review Manager (RevMan) (Personal computer program), version 5.1. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2008 .Traits of incorporated studiesAll had been parallel studies. Individual study characteristics and threat of bias domains are shown in Table 1. A forest plot of the person study final results is shown in Figure two. Heterogeneity seemed to be unimportant (I2 = 20 , p = 0.13).Description of network Benefits Trial selectionThe search was repeated for the duration of the critique period, by two authors by turns. The final search was performed July 5, 2012. A flow diagram of the literature search is shown in Figure 1. The PubMed search CA XII custom synthesis revealed 1917 references. A search of ClinicalTrials.gov applying the key-words “rheumatoid arthritis” and “radiographic progression” revealed 3 IKK-α Biological Activity published research with radiographic information, which also were identified during our key search, 1 published study with no radiographic data and 2 completed but not published studies out of a total of 21 ongoing studies. This search was supplied with a search in Cochrane Central Register of Controlled Trials using the terms “rheumatoid arthritis and radiographic progression” or “rheumatoid arthritis and joint destruction” resulting in 65 hits, none of which supplied the list of incorporated research. After eliminating references which had been viewed as irrelevant according to the headlines, 334 abstracts have been read. Around the basis with the abstracts 120 articles were retrieved in full length. From these a total of 38 references were identified (Figure 1). Till December 31 2009 the present search identified all 28 combination studies [3,173] identified in our earlier search  plus one further study published in 2005 . Moreover the present search revealed 3 new references  (four investigations) published in 2011 and six studies published in 2012 . In total 38 “combination treatment” references (39 trials, 45 therapy groups) had been incorporated. Around the basis of your integrated remedy arms and doses, we defined 6 combination therapies versus single DMARD: 1) Two DMARDs/LDGC (Double); two) 3 DMARDs/LDGC (Triple); 3) Regular dose of TNFi (Infliximab: 3 mg/kg/8 weeks; etanercept: 50 mg/1 week; adalimumab: 40 mg/2 weeks; certolizumab: 200 mg/2 weeks; golimumab: 50 mg/4 weeks); 4) Normal dose of CD20 inhibitor treatment (rituximab two g/6 months; ocrelizumab 1 g/6 months); 5) Abatacept ten mg/kg/4 weeks; six) Tocilizumab eight mg/kg/4 weeks. The star shaped network is shown in Figure 3. As 1 study integrated a direct comparison in between TNFi, double and triple  and also two research incorporated direct comparisons among double and triple [28,29], the star includes loops to indicate the direct comparisons in between TNFi, double and triple.Synthesis of resultsOnly a single study  contributed to heterogeneity in the analyses of all 45 treatment groups (I2 = 78 ) (Figure two) and inside the analysis of double DMARD vs. single DMARD (I2 = 89 ) (Figure 4). All other heterogeneity analyses were non-significant (I2 varying inside the range 02 , Figures five). Consequently we eliminated this study  in the statistical analyses (decreasing I2 to 170 ) and used a fixed effect model in the primary analyses plus a random effect model within the secondary analyses. The results on the standard meta-analyses of your 6 mixture treatment options arePLOS A single | plosone.orgTable two. Observed Frequencies of bias elements for therapy groups.x2 pDoubleTripleTNFiABACD20iTZSequence genera.