10Therapeutic strategies in early rheumatoid arthritis
Section snippets
The stage
The erosive nature of rheumatoid arthritis (RA) mandates intensive interference with the pathogenic processes, since increasing joint destruction leads to increasing disability.1, 2 Erosions may be seen within the first few years of disease3, 4, and even patients with less than 3 months duration of symptoms may already have evidence of destruction.5 Therapy with disease-modifying antirheumatic drugs (DMARDs) effectively impedes the disease process. In particular, data obtained with tumour
What is early RA?
The definition of early RA is hampered by the lack of diagnostic criteria, given that the classification criteria of the American College of Rheumatology (ACR)13 were developed for chronic RA and for research purposes rather than diagnosis. Their application in early disease often fails to classify many patients correctly; some patients do not yet fulfil the criteria, while others are classified wrongly.5, 14 With the lack of better criteria, it has been suggested that a cumulative fulfilment
What is a clinically relevant response?
Since RA is an inflammatory disease that leads to joint destruction and long-term disability, assessment of response must relate to all three of these characteristics. However, in RA, inflammation is associated with destruction and both features are linked to subsequent disability.1, 9, 27, 28, 29, 30, 31, 32 The inflammatory response is traditionally measured by composite indices.33, 34, 35, 36, 37 In clinical trials, the categorical ACR improvement criteria and the continuous Disease Activity
Should we go for remission? Is cure possible?
In established RA, full and sustained remission is rare even when biological agents are employed. However, in early disease, remissions appear to be more frequently achievable.10, 12, 45, 46, 47, 48, 49 Although remission in very early disease may be spontaneous rather than induced by therapy, this is unlikely to occur beyond 12 weeks (see above) it may be assumed that the process leading to joint destruction is still reversible in many patients with early RA, in terms of both reversal from a
When to start therapy and how aggressive should it be?
Joint pain, swelling and stiffness are the main presenting clinical symptoms of patients with RA. Accordingly, these symptoms require appropriate therapeutic intervention. Such intervention, however, must pay attention to the fact that symptom modification alone is insufficient to cope with the intermediate- and long-term fate of RA, joint damage and disability. Moreover, the most effective symptom modification is currently achieved by therapies that modify the disease process at the same time.
The role of NSAIDS and glucocorticoids
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase 2 (COX-2) inhibitors, are symptomatic agents that do not affect the propensity of RA towards destruction and thus do not change its long-term fate; this is clearly exemplified in dozens of clinical trials in which one group of patients received a DMARD and the control arm received placebo including NSAIDs. The fact that NSAIDs reduce swelling and pain may even obscure a patient's risk of developing persistent,
The role of DMARDS and combination therapy
DMARDs are the mainstay of RA therapy due to their significant effect on inflammation, damage and function. Meta-analyses and retrospective analyses of large patient cohorts revealed that response to DMARDs or their retention rates are better in early stages of disease.77, 78 Two important studies suggested that delay of the institution of DMARDs leads to impaired clinical, radiographic and functional outcome. Egsmose et al79 treated patients with RA <2 years' duration in a double-blind
Control of effectiveness
Rather than the drug chosen, it appears to be the tight clinical control examinations with frequent (every 2–4 months) assessment of disease activity and consequent changes of regimens in patients with continuing active disease that allow achievement of the best results.97 In this study, 110 patients with active early RA (<5 years) were started on sulphasalazine and were to be switched to triple-combination DMARD therapy, then to increased prednisolone and then to other DMARDs or combinations
Summary
Early recognition of RA (or arthritis with a poor prognosis) and early intervention with DMARDs in conjunction with glucocorticoid therapy appear to be key to optimal management of early RA. With the currently available therapeutic armamentarium, very early therapy has been demonstrated to be superior to more traditional, delayed treatment. Such treatment primarily rests on the use of MTX. Importantly, patients ought to be followed intensively (every 2–4 months) with respect to the effect of
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Development of biomedical hydrogels for rheumatoid arthritis treatment
2024, Asian Journal of Pharmaceutical SciencesDiscovery of new inhibitor for the protein arginine deiminase type 4 (PAD4) by rational design of α-enolase-derived peptides
2021, Computational Biology and ChemistryCitation Excerpt :Currently, there are three classes of drugs available in the market to alleviate the symptoms of RA, i.e. disease modifying anti-rheumatic drugs (DMARD), non-steroidal anti-inflammatory drugs (NSAID), and corticosteroids (Burmester and Pope, 2017), with DMARDs being the most widely used. In addition to its having an unspecific target, the side effects of long term use of DMARD remain unknown because short term use does not provide enough data for prognosis and estimation of toxicity (Smolen et al., 2005). Methotrexate (MTX) is a drug that falls under the classification DMARD.
Modulation of methotrexate efficacy by green tea polyphenols in rat adjuvant arthritis
2020, PharmaNutritionCitation Excerpt :Biological treatments, such as etanercept and infliximab, are a newer form of treatment for RA, but the high cost and the need of repeated injections inhibited their widespread use. Thus, conventional DMARDs such as MTX have been continued to be used in clinical setting [18,19]. MTX became the most frequently used DMARD in the therapy of RA, but its administration is limited being sometimes ineffective and for the presence of manifold adverse effects [20–22].
Risk profiling for a refractory course of rheumatoid arthritis
2019, Seminars in Arthritis and RheumatismCitation Excerpt :Many risk factors of severe RA have been reported, and they include high disease activity at presentation, seropositivity, and presence of early structural damage [8–10]. Other factors include the question of whether short time to treatment can modify the disease course, a hypothesis that has frequently been referred to as the “window of opportunity” [11,12]. However, observational studies investigating this suffer from the inherent issue of an unknown background prevalence of a priori self-limiting disease (i.e., non-RA) [13].
Structure-based design of peptide inhibitors for protein arginine deiminase type iv (PAD4)
2018, Encyclopedia of Bioinformatics and Computational Biology: ABC of BioinformaticsAnti-arthritis activity of roots of Hemidesmus indicus R.Br. (Anantmul) in rats
2012, Asian Pacific Journal of Tropical Medicine