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In Germany, Tocilizumab (TCZ) is used for the treatment of rheumatoid arthritis both in biologic-naïve patients and those with previous failures of biologic disease-modifying antirheumatic drugs (bDMARDs). The long-term effectiveness and retention rates of TCZ in patients with different numbers of prior bDMARD failures has rarely been investigated. We included 885 RA patients in the analyses, enrolled with the start of TCZ between 2009 and 2015 in the German biologics register RABBIT. Patients were stratified according to prior bDMARD failures: no prior bDMARD or 1, 2 or ≥ 3 bDMARD failures. We applied Kaplan-Meier methods and Cox-regression to examine treatment adherence as well as linear mixed effects models to investigate effectiveness over 3 years of follow-up. Compared to biologic-naïve patients, those with prior bDMARD failures at start of TCZ were younger but had significantly longer disease duration and more comorbidities. DAS28 at baseline and loss of physical function were highest in patients with ≥ 3 bDMARD failures. During follow-up, patients with up to two bDMARD failures on average reached low disease activity (LDA, DAS28 < 3.2). Those with ≥ 3 prior bDMARDs had a slightly lower response. However, after 3 years, nearly 50% of them achieved LDA. Treatment continuation on TCZ therapy was similar in patients with ≤ 2 bDMARD failures but significantly lower in those with ≥ 3 bDMARD failures. TCZ seems to be similarly effective in patients with no, one or two prior bDMARD failures. The majority of patients achieved LDA already after 6 months and maintained it over a period of 3 years. TCZ proved effective even in the high-risk group of patients with more than two prior bDMARD failures. [ABSTRACT FROM AUTHOR]

Indices prognosticating anti-tumor necrosis factor (TNF) response in patients with rheumatoid arthritis are a matter of interest. Differential outcome under anti-TNF and anti-interleukin-6 (IL-6) therapy raises the question whether genetic polymorphisms that have previously been linked to IL-6 production are associated with response to anti-TNF therapy. Fifty (50) rheumatoid arthritis (RA) patients were treated with etanercept (median 36 weeks, range 4-52). In terms of the EULAR response criteria, 25 patients responded well, 17 patients moderately and 8 patients not. By direct sequencing, the patients and 91 matched healthy controls were genotyped for the IL-6 promoter SNPs -597G > A (rs1800797), -572G > C (rs1800796) and -174G > C (rs1800795) and for an AnTn microsatellite tract at -373. Alleles and haplotypes were tested for association with disease susceptibility and therapy response. No significant difference was seen in the genotype distribution between patients and healthy controls. Confirming the results of previous studies, we observed a trend of -174G being more frequent in patients with a good or moderate therapy response. Beyond that, carriage of the A9T11 microsatellite allele within the -174G haplotype was associated most closely with a favourable response (relative risk 1.31; 95 % confidence interval 1.02-1.68). A subtle analysis of the IL-6 promoter giving respect to its complex haplotypic structure results in more precise information as to the association of genotypes with the long-term etanercept response. Despite a conclusive hypothesis that a genetically determined IL-6-dominated RA responds less well to anti-TNF, more work has to be done to provide us with reliable information regarding the functional aspects of these genetic polymorphisms. [ABSTRACT FROM AUTHOR]