More recent trials have been developed with the objective of clarifying CVD risk with TCZ use. why significant differences were not found (Figure 2). Open in a separate window Figure 2 DAS and HAQ scores for tight-control vs. conventional care treatment approaches in patients with only moderately active rheumatoid 6-Mercaptopurine Monohydrate arthritis. Upper: mean DAS at each time point. Middle: remission rates (percentage of patients with DAS 1.6) at each time point. Bottom: median HAQ scores at baseline, 1 and 2 years. Open dots represent the tight-control group and closed dots represent the conventional care group (17). While the aforementioned trials compared biologics KIAA0078 with aggressive DMARDs therapy, results from head to head clinical trials (CT) comparing anti-TNF biologics to one another or to non-anti-TNF biologics are now available. A trial where patients with established 6-Mercaptopurine Monohydrate active RA despite prior or current use of two DMARDs including MTX and who were biologic naive compared ADA 40 mg every 2 weeks vs. ETA 50 mg weekly, both in combination with MTX. The proportion of good, moderate and non-responders based on DAS28 at 52 weeks were 26.3%, 33.3% and 40.4%, respectively, for ADA versus 16.7%, 31.7% and 51.7%, respectively, for ETA (p=0.158) (18)**. Another study comparing ETA vs. ADA with respect to immunogenicity showed that the overall treatment response was comparable between ETA and ADA-treated patients (adjusted odds ratio (OR) 0.81 [95% confidence interval (CI) 0.54C1.21]) (19)**. In a comparison between ETA and patients receiving ADA without anti-ADA antibodies the odds ratio (OR) for achieving better clinical outcome was 0.55, 95% CI (0.37C0.83) (p= 0.004), favoring adalimumab; when ETA was compared to ADA patients with anti-ADA antibodies the OR was 2.62 (1.19C5.75) (p = 0.017), favoring etanercept. This data suggest that ADA appears to be more effective in patients who do not develop antibodies to the drug and that those who developed anti-ADA antibodies (26% of ADA patients) had far less favorable treatment outcomes when compared to ETA (19)**. The Abatacept (ABA) or infliximab versus placebo, a Trial for Tolerability, Efficacy and Safety in Treating rheumatoid arthritis (ATTEST) trial (20), found no difference in efficacy between ABA vs. infliximab in patients with incomplete response to MTX-IR that were biologic na?ve. An open extension study of the ATTEST trial showed that changing from infliximab, regardless of clinical response, to ABA provided sustained or increased efficacy after the change in medications according to DAS28 (21)*. A larger non-inferiority trial compared ADA vs. ABA SC in combination with MTX in MTX-IR patients showed at 1 year, 64.8% and 63.4%of patients demonstrated an ACR20 response; the estimated difference [95% CI] between groups was 1.8 [?5.6, 9.2]) demonstrating the non-inferiority of ABA versus ADA. All efficacy measures showed similar results and kinetics of response. Rates of radiographic non-progression using van der Heijde modified Sharp total scores smallest detectable change (mTSS.SDC) were 84.8% and 88.6%; mean changes from baseline in mTSS of 0.58 and 0.38. Discontinuation due to adverse events were 3.1% versus 6.1%, due to SAEs were 1.3% versus 6-Mercaptopurine Monohydrate 3% ABA vs. ADA respectively (22)**. Preliminary results of a trial designed to test the superiority of biologic monotherapy in patients with RA of 6-mo duration who were MTX intolerant compared TCZ monotherapy to ADA. Results of that study showed more favorable TCZ compared to ADA (change in DAS28 of ?3.3 and ?1.9, p 0.001) (23). Anti-TNF discontinuation trials Discontinuation of biologic therapy, particularly anti-TNF therapy, has been suggested as a possibility to consider whether patients doing well and who stop therapy might maintain low disease activity (LDA) or remission off biologic treatment, with or without background therapies like MTX. A prospective cohort studied which factors were associated with successful discontinuation of anti-TNF and found that early combination therapy (MTX + anti-TNF) within the first 6 months of symptoms of RA (24) was the only clinical predictor identified. Another study conducted among patients who agreed to discontinue ADA as part of routine clinical practice after sustained remission for 6 months (DAS28 2.6), showed that 12-months after discontinuing ADA, 36% of patients remained in remission by DAS28 2.6 and 45% were in remission based upon a simplified disease activity index (SDAI) 3.3. Additionally, 95% showed no evidence of radiographic progression over that year (25). A post-hoc analysis after 4 years of treatment of the Behandel Strategie?n BeST study (26), was published in which patients who have achieved a DAS44 1.6 discontinued treatment gradually until be completely.