In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at

/pdf/eular-recommendations-for-the-management-of-rheumatoid-4fujp4paik.pdf

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

CD4(+) effector T cells have been categorized into two subsets: T helper type 1 (T(H)1) and T(H)2. Another subset of T cells that produce interleukin 17 (IL-17; 'T(H)-17 cells') has been identified that is highly proinflammatory and induces severe autoimmunity. Whereas IL-23 serves to expand previously differentiated T(H)-17 cell populations, IL-6 and transforming growth factor-beta (TGF-beta) induce the differentiation of T(H)-17 cells from naive precursors. These data suggest a dichotomy between CD4(+) regulatory T cells positive for the transcription factor Foxp3 and T(H)-17 cells: TGF-beta induces Foxp3 and generates induced regulatory T cells, whereas IL-6 inhibits TGF-beta-driven Foxp3 expression and together with TGF-beta induces T(H)-17 cells. Emerging data regarding T(H)-17 cells suggest a very important function for this T cell subset in immunity and disease.

T H -17 cells in the circle of immunity and autoimmunity

Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-a-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

https://ard.bmj.com/content/annrheumdis/69/6/964.full.pdf

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(08)60453-5.pdf

Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial

Objective
To establish the safety and efficacy of repeat infusions of tocilizumab (previously known as MRA), a humanized anti–interleukin-6 (IL-6) receptor antibody, alone and in combination with methotrexate (MTX), for the treatment of rheumatoid arthritis (RA).

Methods
The study group comprised 359 patients with active RA in whom the response to MTX was inadequate. During a stabilization period, these patients received their current dose of MTX for at least 4 weeks. Following stabilization, they were randomized to 1 of 7 treatment arms, as follows: tocilizumab at doses of 2 mg/kg, 4 mg/kg, or 8 mg/kg either as monotherapy or in combination with MTX, or MTX plus placebo.

Results
A 20% response (improvement) according to the American College of Rheumatology criteria (ACR20 response) was achieved by 61% and 63% of patients receiving 4 mg/kg and 8 mg/kg of tocilizumab as monotherapy, respectively, and by 63% and 74% of patients receiving those doses of tocilizumab plus MTX, respectively, compared with 41% of patients receiving placebo plus MTX. Statistically significant ACR50 and ACR70 responses were observed in patients receiving combination therapy with either 4 mg/kg or 8 mg/kg of tocilizumab plus MTX (P < 0.05). A dose-related reduction in the Disease Activity Score in 28 joints was observed from week 4 onward, in all patients except those receiving monotherapy with 2 mg/kg of tocilizumab. In the majority of patients who received 8 mg/kg of tocilizumab, the C-reactive protein level/erythrocyte sedimentation rate normalized, while placebo plus MTX had little effect on these laboratory parameters. Tocilizumab was mostly well tolerated, with a safety profile similar to that of other biologic and immunosuppressive therapies. Alanine transaminase and aspartate transaminase levels followed a sawtooth pattern (rising and falling between infusions). There were moderate but reversible increases in the nonfasting total cholesterol and triglyceride levels and reversible reductions in the high-density lipoprotein cholesterol and neutrophil levels. There were 2 cases of sepsis, both of which occurred in patients who were receiving combination therapy with 8 mg/kg of tocilizumab plus MTX.

Conclusion
These results indicate that targeted blockade of IL-6 signaling is a highly efficacious and promising means of decreasing disease activity in RA.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.22033

Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate.

D Thomson

Papers

Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate.