In Review Manager (RevMan) (Personal computer program), version five.1. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2008 [13].Qualities of integrated studiesAll have been parallel studies. Individual study traits and risk of bias domains are shown in Table 1. A forest plot in the individual study outcomes is shown in Figure 2. Heterogeneity seemed to be unimportant (I2 = 20 , p = 0.13).Description of network Final results Trial selectionThe search was repeated through the evaluation period, by two authors by turns. The final search was performed July 5, 2012. A flow diagram in the literature search is shown in Figure 1. The PubMed search revealed 1917 references. A search of employing the key-words “rheumatoid arthritis” and “radiographic progression” revealed 3 P2Y2 Receptor manufacturer published research with radiographic information, which also had been identified during our main search, 1 published study with no radiographic information and two completed but not published IL-8 Gene ID 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 included research. After eliminating references which were regarded irrelevant according to the headlines, 334 abstracts were read. On the basis from the abstracts 120 articles were retrieved in complete length. From these a total of 38 references were identified (Figure 1). Till December 31 2009 the present search identified all 28 mixture studies [3,173] identified in our previous search [1] plus 1 extra study published in 2005 [44]. In addition the present search revealed three new references [457] (four investigations) published in 2011 and 6 studies published in 2012 [4853]. In total 38 “combination treatment” references (39 trials, 45 remedy groups) have been integrated. Around the basis of your integrated remedy arms and doses, we defined 6 mixture treatments versus single DMARD: 1) Two DMARDs/LDGC (Double); 2) Three DMARDs/LDGC (Triple); 3) Standard 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) Common dose of CD20 inhibitor therapy (rituximab two g/6 months; ocrelizumab 1 g/6 months); five) Abatacept ten mg/kg/4 weeks; six) Tocilizumab 8 mg/kg/4 weeks. The star shaped network is shown in Figure 3. As a single study incorporated a direct comparison involving TNFi, double and triple [3] and furthermore two studies integrated direct comparisons involving double and triple [28,29], the star contains loops to indicate the direct comparisons amongst TNFi, double and triple.Synthesis of resultsOnly one particular study [27] contributed to heterogeneity in the analyses of all 45 remedy groups (I2 = 78 ) (Figure two) and within the analysis of double DMARD vs. single DMARD (I2 = 89 ) (Figure 4). All other heterogeneity analyses had been non-significant (I2 varying in the range 02 , Figures 5). Consequently we eliminated this study [27] in the statistical analyses (decreasing I2 to 170 ) and used a fixed effect model within the major analyses as well as a random impact model within the secondary analyses. The outcomes with the standard meta-analyses in the six mixture remedies arePLOS A single | plosone.orgTable two. Observed Frequencies of bias variables for therapy groups.x2 pDoubleTripleTNFiABACD20iTZSequence genera.