Treatment comparison in rheumatoid arthritis : head-to-head trials and innovative study designs

Over the last decades, the increasing knowledge in the area of rheumatoid arthritis has progressively expanded the arsenal of available drugs, especially with the introduction of novel targeted therapies such as biological disease modifying antirheumatic drugs (DMARDs). In this situation, rheumatologists are offered a wide range of treatment options, but on the other side the need for comparisons between available drugs becomes more and more crucial in order to better define the strategies for the choice and the optimal sequencing. Indirect comparisons ormeta-analyses of data coming fromdifferent randomised controlled trials (RCTs) are not immune to conceptual and technical challenges and often provide inconsistent results. In this review we examine some of the possible evolutions of traditional RCTs, such as the inclusion of active comparators, aimed at individualising treatments in real-life conditions. Although head-to-head RCTs may be considered the best tool to directly compare the efficacy and safety of two different DMARDs, surprisingly only 20 studies with such design have been published in the last 25 years. Given the recent advent of the first RCTs truly comparing biological DMARDs, we also review the state of the art of head-to-head trials in RA

Transforming growth factor beta1 in the pathogenesis of autoimmune congenital complete heart block : lesson from twins and triplets discordant for the disease

Objective. Clinical evidence and experimental evidence suggest that anli-Ro/La autoantibodies are necessary but not sufficient for the development of congenital complete heart block (CCHB). Maternal, fetal, and environmental factors may also contribute to heart damage in CCHB. The aim of our study was to investigate polymorphisms of transforming growth factor \u3b21 (TGF\u3b21) and tumor necrosis factor \u3b1 (TNF\u3b1) genes in twins and triplets discordant for CCHB whose mothers are anti-Ro/La positive. Methods. We studied 2 families in which 1 of the mothers gave birth to triplets and the other gave birth to twins. Only 1 child in each family was affected by CCHB, although 1 of the triplets had incomplete heart block. We analyzed TNF\u3b1 and TGF\u3b21 polymorphisms in the 2 babies with CCHB and their siblings. TNF\u3b1 polymorphisms at the promoter region and TGF\u3b21 polymorphisms at codons 10 and 25 were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. In addition, the production of TGF\u3b21 and TNF\u3b1 by resting or mitogen-stimulated peripheral blood mononuclear cells in cell culture supernatants was evaluated by enzyme-linked immunosorbent assay. Results. The profibrotic TGF\u3b21 genotype was detected in the twin with CCHB but not in the healthy twin, while all of the triplets displayed the same TGF\u3b21 genotype at codon 10. Peripheral blood mononuclear cells from the children with CCHB displayed higher spontaneous and mitogen-stimulated T6F\u3b21 secretion than was observed in their siblings. No differences regarding TNF\u3b1 polymorphisms and secretion of TNF\u3b1 were observed. Conclusion. The results of this study suggest that, besides anti-Ro/La autoantibodies, a fetal profibrotic response might contribute to the development of CCHB, but additional pathogenic mechanism(s) are also likely to play a role

Eight-year retention rate of first-line tumor necrosis factor inhibitors in spondyloarthritis : A multi-center retrospective analysis

Objective. To evaluate the 8-year survival of the first TNF inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA), identify the predictive factors for withdrawal, and compare the discontinuation rates for infliximab, etanercept, and adalimumab. Methods. We evaluated PsA and axSpA patients treated with a first-line TNFi between 2005 and 2015 at four Italian tertiary centres. 8-year drug survival was calculated by Kaplan-Meier method and risk for discontinuation among treatment groups compared by stratified log-rank test. Univariate and multivariate Cox proportional hazard models were developed to examine predictors of withdrawal. Results. Out of 614 patients (316 axSpA, 298 PsA), 203 received adalimumab, 131 etanercept, and 280 infliximab, with similar frequencies in axSpA and PsA subgroups. The cumulative 8-year retention rate in the whole population was 55.1% (57.2 and 51.9% and for axSpA and PsA, respectively; p=NS). No significant differences were observed in drug persistence among individual TNFi in either group. Male sex (HR 0.595, 95% CI 0.405-0.875; p=0.008) and concomitant methotrexate use (HR 0.648, 95% CI 0.426-0.985; p=0.042) were associated with a lower risk of withdrawal in PsA and high baseline BASDAI (HR 0.9842 95% CI 0.9708-0.9980; p=0.028) in axSpA. No difference was found in the comparative analysis of reasons for discontinuation between PsA and axSpA. Conclusion. We reported that the real-life 8-year retention rate of the first TNFi in axSpA and PsA is over 50%, with no significant differences between axSpA and PsA and irrespective of the individual TNFi

Eight-year retention rate of first-line tumor necrosis factor inhibitors in spondyloarthritis : A multi-center retrospective analysis

Objective. To evaluate the 8-year survival of the first TNF inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA), identify the predictive factors for withdrawal, and compare the discontinuation rates for infliximab, etanercept, and adalimumab. Methods. We evaluated PsA and axSpA patients treated with a first-line TNFi between 2005 and 2015 at four Italian tertiary centres. 8-year drug survival was calculated by Kaplan-Meier method and risk for discontinuation among treatment groups compared by stratified log-rank test. Univariate and multivariate Cox proportional hazard models were developed to examine predictors of withdrawal. Results. Out of 614 patients (316 axSpA, 298 PsA), 203 received adalimumab, 131 etanercept, and 280 infliximab, with similar frequencies in axSpA and PsA subgroups. The cumulative 8-year retention rate in the whole population was 55.1% (57.2 and 51.9% and for axSpA and PsA, respectively; p=NS). No significant differences were observed in drug persistence among individual TNFi in either group. Male sex (HR 0.595, 95% CI 0.405-0.875; p=0.008) and concomitant methotrexate use (HR 0.648, 95% CI 0.426-0.985; p=0.042) were associated with a lower risk of withdrawal in PsA and high baseline BASDAI (HR 0.9842 95% CI 0.9708-0.9980; p=0.028) in axSpA. No difference was found in the comparative analysis of reasons for discontinuation between PsA and axSpA. Conclusion. We reported that the real-life 8-year retention rate of the first TNFi in axSpA and PsA is over 50%, with no significant differences between axSpA and PsA and irrespective of the individual TNFi

FRI0215 Comparative efficacy and retention rate of tocilizumab and tnf inhibitors used in combination with methotrexate as first-line biologic therapy in rheumatoid arthritis: data from a multicentre observational registry

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Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: Results from the GISEA register.

Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX)