Rheumatology-Rhumatologie
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Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised...

Abstract

 

Results 432 patients were screened: 107 were randomised to tumour necrosis factor inhibitors and 101 started taking; 107 were randomised to the combined drug strategy and 104 started taking the drugs. Initial assessments were similar; 16 patients were lost to follow-up (seven with the tumour necrosis factor inhibitor strategy, nine with the combined drug strategy); 42 discontinued the intervention but were followed-up (19 and 23, respectively). The primary outcome showed mean falls in scores on the health assessment questionnaire of −0.30 with the tumour necrosis factor inhibitor strategy and −0.45 with the alternative combined drug strategy. The difference between groups in unadjusted linear regression analysis favoured the alternative strategy of combined drugs. The mean difference was −0.14, and the 95% confidence interval (−0.29 to 0.01) was below the prespecified non-inferiority boundary of 0.22. Improvements at 12 months in secondary outcomes, including quality of life and erosive progression, were similar with both strategies. Initial reductions in disease activity were greater with the biologic strategy, but these differences did not persist beyond six months. Remission was seen in 72 patients (44 with biologic strategy; 36 with alternative strategy); 28 patients had serious adverse events (18 and 10, respectively); six and 10 patients, respectively, stopped treatment because of toxicity. The alternative strategy reduced health and social care costs per patient by £3615 (€4930, $5585) for months 0-6 and £1930 for months 6-12.

Conclusions In patients with active rheumatoid arthritis who meet English criteria for biologics an alternative strategy with combinations of intensive synthetic disease modifying drugs gives non-inferior outcomes to treatment with tumour necrosis factor inhibitors. Costs are reduced substantially.


Via Krishan Maggon
Krishan Maggon 's curator insight, March 16, 2015 1:30 PM
Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial

BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h1046 (Published 13 March 2015)Cite this as: BMJ 2015;350:h1046

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Differential expression of pro-inflammatory cytokines IL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluid from Rheumatoid arthritis patients

Differential expression of pro-inflammatory cytokines IL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluid from Rheumatoid arthritis patients | Rheumatology-Rhumatologie | Scoop.it
Pro-inflammatory cytokines are directly implicated in the pathogenesis of Rheumatoid arthritis (RA). Variable clinical response to cytokine targeted therapies as TNFalpha and IL-6, strongly highlights the heterogeneity of inflammatory process in RA.

 

Results

We found higher and significant levels of TNFalpha, IL-6 and IL-15Ralpha but not of IL-15 in RA compared with the OA group. Additionally, a high inter-individual variability in the levels of these 4 cytokines was observed in RA, although we identified 4 patients’ subgroups by cluster analysis of cytokines concentration in SF. We also found a positive correlation between IL-15Ralpha-IL-6 and IL-15Ralpha-IL-15, but not for other pairs of cytokines in RA. In addition we found correlation between the value of IL-15Ralpha in SF and disease activity score, DAS28.

Conclusions

In our current work we found a high inter-individual variability in the levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha in SF of RA patients and were identified four principal clusters of cytokines concentration in SF, suggesting the importance of identifying disease subset of patients for personalized treatment. Finally, we found a correlation between IL-15Ralpha-IL-6, IL-15Ralpha-IL-15, but we did not find any correlation between other pairs of studied cytokines in SF.


Via Krishan Maggon
Krishan Maggon 's curator insight, March 15, 2015 1:48 PM

Research article

Differential expression of pro-inflammatory cytokines IL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluid from Rheumatoid arthritis patients

Alicia Santos Savio1*, Ana Cecilia Machado Diaz1, Araceli Chico Capote2, Jamilet Miranda Navarro3, Yunier Rodríguez Alvarez1, Ricardo Bringas Pérez3, Miguel Estévez del Toro2and Gerardo E Guillen Nieto1

*Corresponding author: Alicia Santos Savio alicia.santos@cigb.edu.cu

Author Affiliations

1Pharmaceutical Division, Center for Genetic Engineering and Biotechnology, Havana CP 10600, Cuba

2Rheumatology Department, H. Ameijeiras Hospital, San Lazaro 701, Havana, Cuba

3Bioinformatics Department, Center for Genetic Engineering and Biotechnology, Havana CP 10600, Cuba

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BMC Musculoskeletal Disorders 2015, 16:51  doi:10.1186/s12891-015-0516-3

The electronic version of this article is the complete one and can be found online at:http://www.biomedcentral.com/1471-2474/16/51

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The BMJ Today: Treatments for inflammatory diseases

The BMJ Today: Treatments for inflammatory diseases | Rheumatology-Rhumatologie | Scoop.it
A combination of old drugs is not inferior to biologics for rheumatoid arthritis • Tumor necrosis factor inhibitors are safe and effective therapies for patients with rheumatoid arthritis resistant to methotrexate and other disease modifying drugs,...

Via Krishan Maggon
Krishan Maggon 's curator insight, March 16, 2015 1:18 PM

The BMJ Today reports the results of an open label pragmatic trial—the TACIT trial—that compared the impact on disability at 12 months of a TNF based strategy (as recommended by the National Institute for Health and Care Excellence) versus a combined disease modifying drug strategy, which includes methotrexate. In this study, the combination of older drugs was non-inferior to the biologic agents.

In a related editorial, Pierre Miossec concludes that the TACIT trial “gives fresh hope to more patients around the world that they can achieve equal or better disease control with combinations of established, low cost, and easy to produce alternatives [to the more expensive newer biologics].”