Rituximab or a Second Anti-Tumor Necrosis Factor Therapy for Rheumatoid Arthritis Patients Who Have Failed Their First Anti-Tumor Necrosis Factor Therapy? Comparative Analysis From the British Society for Rheumatology Biologics Register

University of Manchester, UK.
Arthritis care & research 07/2012; 64(8):1108-15. DOI: 10.1002/acr.21663
Source: PubMed

ABSTRACT To compare the effectiveness of rituximab (RTX) or a second anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients who had failed their first anti-TNF and switched to either RTX or a second anti-TNF, in routine clinical practice.
RA patients were registered with the British Society for Rheumatology Biologics Register. Response to treatment 6 months after switching was assessed using European League Against Rheumatism (EULAR) criteria and improvements in a Health Assessment Questionnaire (HAQ) score (0.22 unit or more). Regression analyses were used to compare EULAR response and improvement in HAQ score between the 2 groups, adjusting for propensity scores.
In total, 1,328 patients were included in the analysis of EULAR response, and 937 patients were included in the analysis of HAQ scores. Six months after switching, 54.8% of patients who switched to RTX were EULAR responders compared to 47.3% of those who switched to a second anti-TNF. A total of 38.4% of RTX patients achieved a clinically important improvement in HAQ score compared to 29.6% in anti-TNF patients. After adjustment using propensity scores, patients who switched to RTX were significantly more likely to achieve EULAR response (odds ratio [OR] 1.31; 95% confidence interval [95% CI] 1.02, 1.69) compared to those who switched to an alternative anti-TNF. RTX patients were also significantly more likely to achieve improvements in HAQ score (OR 1.49; 95% CI 1.07, 2.08).
The results suggest that switching to RTX may be of more benefit than switching to an alternative anti-TNF therapy after failing the first anti-TNF therapy in RA patients.

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    • "Only 12% of our patients had disease duration of less than one year reflecting the importance of early referral and early disease control. The first choice of biological therapy was ADA and the second choice biological therapy after the failure of the first was RTX, which is consistent with the ACR/EULAR recommendations [14] [15] [23]. The choice of biological agent was strongly associated with the preferences of the individual doctors, the year of treatment initiation, and availability of the drug in the hospital. "
    Open Journal of Rheumatology and Autoimmune Diseases 09/2015; 04(04). DOI:10.4236/ojra.2014.44027
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    ABSTRACT: Evaluation of: Gomez-Reino JJ, Maneiro JR, Ruiz J et al. Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study. Ann. Rheum. Dis. doi:10.1136/annrheumdis-2012-201324 (2012) (Epub ahead of print). Rheumatoid arthritis is a chronic immune-mediated disease affecting approximately 1% of the population. The prognosis of this chronic condition has considerably improved over the past decade with the earlier use of antirheumatic drugs and the introduction of new biologic therapies. Current treatment guidelines recommend using these agents after a failed response to conventional disease-modifying antirheumatic drugs, but the relative positioning of the various available biologic agents is not yet well established. All biologic agents have been proven to be superior to placebo in large trials, but only very few randomized controlled trials have compared directly competing therapeutic options. This article evaluates the effectiveness of rituximab compared with an alternative TNF antagonist (anti-TNF) in rheumatoid arthritis patients who experienced a previous failed response to anti-TNF. The results of this large observational cohort study suggest that rituximab offers a greater benefit on rheumatoid arthritis disease activity than alternative monoclonal anti-TNFs.
    11/2012; 1(6):481-4. DOI:10.2217/cer.12.50
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    ABSTRACT: Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10(-8)), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3' UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10(-11) in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry.
    PLoS Genetics 03/2013; 9(3):e1003394. DOI:10.1371/journal.pgen.1003394 · 8.17 Impact Factor
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