6The use of conventional disease-modifying anti-rheumatic drugs in established RA
Section snippets
Literature search
For this review, we used published meta-analyses, systematic reviews and randomised controlled trials (RCTs), if available. We based our search on ‘established RA’ and ‘conventional (synthetic) DMARDs’, including GCs and ‘DMARD strategies’.
Because of the lack of recent high-level literature addressing established RA, we have chosen to use literature addressing early RA as well where there is no high-graded literature available on established RA. Although the magnitude of effects and frequency
Currently available conventional DMARDs
As all available conventional DMARDs are used in all phases of RA, also established RA, we (in short) describe these drugs. The most common and dominant DMARD on the market is MTX [1], [10]. Among the available conventional DMARDs, MTX is also one of the most effective and best tolerated [26], [27], [28], [29]. Because of its favourable characteristics, MTX should be regarded as anchor DMARD; [23], [29], [30], [31], [32], [33], [34] it has several benefits over other DMARDs; see Box 1.
In
DMARD: monotherapy or combination therapy?
When starting to treat RA, treatment with a single DMARD as monotherapy remains a common first choice and is still considered by most rheumatologists the gold standard in treating DMARD-naive patients [15], [26], [28]. For established RA patients in developed countries however, it is not very common to be DMARD naive. If the wanted effect of the treatment is not reached with monotherapy in a preset time frame, combination therapy is initiated [33], [42]. Most established RA patients need
Combination strategies
There are different strategies to address combination DMARD therapy. A switch in strategies can be necessary if disease activity changes or if it flares. Although the approaches described below are mainly studied in early RA populations, they might also apply to the individual established RA patient; see Fig. 2.
Summary
In conclusion, for double and triple DMARD therapy we would recommend MTX as anchor drug, which can be combined with virtually any other (conventional) DMARD, but to restrict the combinations to those with evidence based efficacy and absence of excess toxicity, e.g. MTX-LEF or the MTX-HCQ-SSZ combination. Evidence based efficacy of conventional DMARD combinations excluding MTX is lacking. If the treatment target (low disease activity and preferentially remission) is not met, for their
References (83)
- et al.
Rheumatoid arthritis
Lancet
(2010) - et al.
Established rheumatoid arthritis
Baillière’s Best Practice & Research. Clinical Rheumatology
(1999) - et al.
Pharmacotherapy: concepts of pathogenesis and emerging treatments. Optimising the strategy of care in early rheumatoid arthritis
Best Practice & Research: Clinical Rheumatology
(2010) - et al.
Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis
Lancet
(1997) - et al.
Indications of glucocorticoids in early arthritis and rheumatoid arthritis: recommendations for clinical practice based on data from the literature and expert opinion
Joint Bone Spine
(2010) Challenging the pyramid. A new look at therapeutic approaches for rheumatoid arthritis. Earlier intervention with second line therapies
Journal of Rheumatology Supplement
(1990)Challenging the pyramid. A new look at therapeutic approaches for rheumatoid arthritis. Patient selection
Journal of Rheumatology Supplement
(1990)- et al.
The effectiveness of early treatment with "second-line" antirheumatic drugs. A randomized, controlled trial
Annals of Internal Medicine
(1996) - et al.
Treatment-related improvement in physical function varies with duration of rheumatoid arthritis: a pooled analysis of clinical trial results
Annals of the Rheumatic Diseases
(2008) - et al.
Remodeling the pyramid–a concept whose time has come
Journal of Rheumatology
(1989)
Early referral, diagnosis, and treatment of rheumatoid arthritis: evidence for changing medical practice
Annals of the Rheumatic Diseases
The Utrecht experience with different treatment strategies in early rheumatoid arthritis
Clinical & Experimental Rheumatology
Canadian recommendations for use of methotrexate in patients with rheumatoid arthritis
Journal of Rheumatology
Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility
Annals of the Rheumatic Diseases
Evidence for treating rheumatoid arthritis to target: results of a systematic literature search
Annals of the Rheumatic Diseases
Understanding emerging treatment paradigms in rheumatoid arthritis
Arthritis Research & Therapy
The BeSt story: on strategy trials in rheumatoid arthritis
Current Opinion in Rheumatology
Treating rheumatoid arthritis to target: recommendations of an international task force
Annals of the Rheumatic Diseases
NICE-guidance
American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis
Arthritis & Rheumatism
EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs
Annals of the Rheumatic Diseases
Low-dose glucocorticoid therapy in rheumatoid arthritis: an obligatory therapy
Annals of the New York Academy of Sciences
Defining remission in rheumatoid arthritis: what is it? Does it matter?
Journal of Rheumatology
Treatment of rheumatoid arthritis: a global perspective on the use of antirheumatic drugs
Modern Rheumatology
Can remission be maintained with or without further drug therapy in rheumatoid arthritis?
Clinical & Experimental Rheumatology
American College of Rheumatology/European league against rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials
Arthritis and Rheumatism
Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis
Annals of the Rheumatic Diseases
Aggressive treatment in early rheumatoid arthritis: a randomised controlled trial. On behalf of the Rheumatic Research Foundation Utrecht, The Netherlands
Annals of the Rheumatic Diseases
Methotrexate monotherapy versus methotrexate combination therapy with non-biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis
Cochrane Database of Systematic Reviews
Methotrexate as the "anchor drug" for the treatment of early rheumatoid arthritis
Clinical & Experimental Rheumatology
Are switches from oral to subcutaneous methotrexate or addition of ciclosporin to methotrexate useful steps in a tight control treatment strategy for rheumatoid arthritis? A post hoc analysis of the CAMERA study
Annals of the Rheumatic Diseases
Drug combinations with methotrexate to treat rheumatoid arthritis
Clinical & Experimental Rheumatology
Methotrexate versus leflunomide in rheumatoid arthritis: what is new in 2011?
Current Opinion in Rheumatology
Treatment of rheumatoid arthritis
Leflunomide for treating rheumatoid arthritis
Cochrane Database of Systematic Reviews
Current view of glucocorticoid co-therapy with DMARDs in rheumatoid arthritis
Nature Reviews Rheumatology
Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial
Arthritis and Rheumatism
Remission achieved after 2 years treatment with low-dose prednisolone in addition to disease-modifying anti-rheumatic drugs in early rheumatoid arthritis is associated with reduced joint destruction still present after 4 years: an open 2-year continuation study
Annals of the Rheumatic Diseases
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Selective regulation of IKKβ/NF-κB pathway involved in proliferation inhibition of HFLS-RA cells induced by 1,7-dihydroxyl-3,4-dimethoxylxanthone
2017, Kaohsiung Journal of Medical SciencesCitation Excerpt :Conventional therapy approaches for the patients with RA are treated with synthetic disease-modifying antirheumatic drugs (sDMARDs), which would lead to the superior clinical and radiological outcomes especially interfered in early stage. Hence, DMARDs regimens are universally used as the first-line protocols in clinical practice, but they have little effects on the disease progression partially caused by the individual variation and low durable effect due to an inadequate response to DMARDs [3]. Advances in knowledge about cytokine-mediated pathways in the pathogenesis of RA fostered the arrival of targeted biologic DMARDs (bDMARDs).
SND-117, a sinomenine bivalent alleviates type II collagen-induced arthritis in mice
2015, International ImmunopharmacologyCitation Excerpt :The results suggested that the anti-inflammatory effects of SND-117 on CIA may be associated with the inhibition of phosphorylation and nuclear translocation of NF-κB p65. Conventional synthetic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, sulphasalazine, leflunomide are the main tools to treat any form of RA, especially in early RA [49]. Biologic agents have revolutionized the management of rheumatic diseases, and several anti-TNF agents, such as infliximab, etanercept, adalimumab, certolizumab pegol and golimumab and so on, have been approved in multiple countries for use in a variety of rheumatic diseases [50].
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2020, Siberian Journal of Life Sciences and Agriculture
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