Rheumatology-Rhumatologie

The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA).

Via Krishan Maggon

In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases.

Via Krishan Maggon

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

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

 In this article, we review the mechanism of anti-IL-6 in the treatment of RA, provide the key efficacy
and safety data from clinical trials of approved anti-IL-6, TCZ, as well as six candidate IL-6 blockers
including sarilumab, ALX- 0061, sirukumab, MEDI5117, clazakizumab, and olo ...Cited by 1 Cite Save

Via Krishan Maggon

The objective of this study was to directly compare the safety of tocilizumab (TCZ) and TNF inhibitors (TNFIs) in rheumatoid arthritis (RA) patients in clinical practice.

Via Krishan Maggon

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

Novartis today announced that two pivotal Phase III studies (FUTURE 1 and FUTURE 2) of AIN457 (secukinumab) in psoriatic arthritis (PsA) met primary and key secondary endpoints. Endpoints included improving signs and symptoms of psoriatic arthritis (PsA), including improving peripheral joint disease and preventing joint damage versus placebo, while delivering clear or almost clear skin (PASI 90). Secukinumab is an investigational medicine that works by stopping the action of interleukin-17A (IL-17A)[4], a protein that is central to the development of inflammatory diseases[5]. FUTURE 1 and FUTURE 2 enrolled a combined total of more than 1,000 patients. Detailed results of the studies will be presented at an upcoming medical congress.

 

FUTURE 1 and FUTURE 2 are randomized, placebo-controlled, multicenter studies designed to demonstrate efficacy of secukinumab in PsA compared to placebo and to assess safety and tolerability. The American College of Rheumatology response criteria (ACR20) was the primary endpoint in the studies. Secukinumab was well tolerated in both studies. The observed safety profile was consistent with previously reported results from the large psoriasis clinical trial program involving nearly 4,000 patients[17]

 

 

Via Krishan Maggon