10 Facts about Rheumatoid Arthritis: The Clinical Understanding of the Disease
A few days ago I took notice of a review more than worth reading, published in Arthritis Research & Therapy. The article titled Development in the clinical understanding of rheumatoid arthritis; it outlined the current clinical understanding of RA, and it presents the “Top 10 Clinical Facts about Rheumatoid Arthritis”.Even though the article isn’t red-hot I’m positive that the “10 clinical facts on RA” by Josef S. Smolen and Daniel Alehata will be a great help in your daily work. – By the way: The article is available online free of charge and can be downloaded from the journal’s website. So you will be able to pore over the original text.
The review is part of a special collection of articles about The Scientific Basis of Rheumatology: A Decade of Progress. That review series was published in Arthritis Research & Therapy at the occasion of the journal’s 10th anniversary last year (LinkOut to the series). – I’d strongly recommend this web site to anyone who is into rheumatology!
So, what’s the article about? According to Josef S. Smolen and Daniel Aletaha the field of rheumatology has undergone quite a few revolutionary (or rather evolutionary?) changes in the past twenty years. Researchers have recognised that the disease ranges from mild to severe, and the treatment should be individualised.
The authors have spotted most developments in:
- The possibility of influencing the major characteristics going along with rheumatoid arthritis (RA), which are signs and symptoms, joint damage, disability, health-related quality of life, and so on.
- The reporting of clinical trial results.
- The time factor: for quite some time now early diagnosis and adequate treatment in time is regarded as crucial, including the readiness for a swift switching of therapies, if necessary.
- The paradigm change in the field of rheumatology towards remission becomes obvious in novel therapies and novel therapeutic strategies.
Just for the record, and just to bring out authorship: The verbalisation of the clinical facts 1 to 10 in bold type are verbatim quotes from the review Development in the clinical understanding of rheumatoid arthritis. Likewise the italicised text passages in quotation marks are.Clinical fact 1: A new look at assessing disease activity. – “Composite indices are the best depicters of disease activity. The degree of disease activity at the start of a disease-modifying therapy is a major determinant of the disease activity attainable treatment.”
The authors describe that only a limited number of variables are reliable and sensitive to assess disease activity and to monitor therapy. Indeed, only the individual components of these “core sets” are appropriate to reflect different aspects of rheumatoid arthritis. Among these are swollen joint counts, acute-phase reactants and erythrocyte sedimentation rate, tender joint counts, and morning stiffness.
Clinical fact 2: Disease activity is the driver of joint damage. – “Joint damage is a consequence of the inflammatory process (disease activity over time). Joint space narrowing and erosions by radiography depict related but distinct components of joint damage that may develop separately.”
It has been shown that joint damage following the inflammatory process is the main characteristic of rheumatoid arthritis. The change in disease activity (assessed by various composite indices in response to therapy, see clinical fact 1) correlates well with the extend of radiographic joint damage or the degree of inhibition of its progression. Joint damages are comprising both cartilage damage and bone destruction. As these two processes may be related but are distinct, they require detailed analyses and specific therapies, the authors recall to the reader’s mind.
Clinical fact 3: Disability is a multifarious feature. – “Disability comprises an activity-related component that is fully reversible and a destruction-related component that is irreversible. Clinical trial design needs to account for this complexity. Interference with disease activity will reverse the activity-related segment and prevent the accrual of the damage-related part.”
The authors call up that disability is a complex feature comprising disease-specific elements like pain or morning stiffness, as well as non-disease specific elements such as age or psychological well-being not necessarily related to RA. As medication can fully stop the inflammation in many cases, disease activity is a reversible process.
However, joint destruction isn’t! Thus measuring physical functioning only is too narrowly considered, the authors remind. This also indicates the importance of careful clinical trial design that accounts for the potential irreversible disability.
Clinical fact 4: Disease activity and disability correlates with comorbidities, mortality, and costs. – “The reduction in life expectancy as well as comorbidities associated with rheumatoid arthritis, such as cardiovascular disease and lymphoma, and economic consequences, including loss of working capacity, are associated primarily with the severity of RA as manifested by chronic high disease activity and long-term irreversible disability.”
Simply put, mortality is increased in patients with rheumatoid arthritis. Comparing different patients, the severity of the disease appears to be highly variable from one to the next. Greater severity is associated with cardiovascular disease, lymphoma, and incapacity for work.
The clinical facts 1 to 4 cited and summarised above are describing the recent changes in the field of rheumatoid arthritis influencing the major characteristics of the disease. Clinical fact 5 as stated below is on the importance of appropriate disease activity reporting and disease assessment:
Clinical fact 5: It’s the state, not just the change. – “Therapy for rheumatoid arthritis needs to aim at least to achieve low disease activity by composite scores and, ideally, remission. Clinical trial reporting has to account for both improvement and disease activity categories, and the latter also needs to be evaluated during follow-up in clinical practice.”
According to the authors, assessing rheumatoid arthritis has undergone major changes in the past two decades. Assessment of disease has become “both standardized and the standard of care”. States of disease activity as well as for remission have been formulated, and these categories have also become important in clinical practice. The authors call to mind that achieving remission ought to be the ultimate goal when treating rheumatoid arthritis – even though there still is much debate among rheumatologists on whatever the term “remission” exactly means.
Nowadays it’s a well-known fact that time and timing as well as appropriate follow-up are very important aspects of RA treatment. Anyhow, Josef S. Smolen and Daniel Alehata call that fact back to their readers’ mind by the clinical fact 6 and 7 on early diagnosis of rheumatoid arthritis, regular follow-ups and the necessity of switching therapy in case of inefficacy:
Clinical fact 6: Early recognition and therapy are mandates. – “Early recognition of rheumatoid arthritis is important for early institution of disease-modifying anti-rheumatic drug therapy, which is more efficacious than delayed treatment.”Joint destruction in RA patients starts within the first few weeks or months of the disease, very likely even before disease onset, the two authors write. By two years of disease the majority of RA patients have damaged joints. It has been demonstrated by several studies that early initiation of disease-modifying anti-rheumatic drugs therapy (DMARDs) improves outcome of disease.
However, early therapy during this “window of opportunity” requires early diagnosis, but current RA classification is based on patients with long-standing rheumatoid arthritis. Yet again the authors admonish that there is urgent need for new rheumatoid arthritis classification criteria.
Clinical fact 7: Regular tight follow-up and change of therapy are important. – “Tight follow-up examinations (every three months) and appropriate switch of therapy after a maximum of three to six months in patients who do not achieve low disease activity or remission are important constituents of modern therapeutic approaches to rheumatoid arthritis.”
The authors recommend follow-up examinations every three months. According to their advice insufficient medication (“treatment that doesn’t reduce disease activity to a low state”) should be switched quickly.
Clinical fact 8: Tumor necrosis factor inhibitors plus methotrexate lead to profound clinical responses and uncouple the close relationship between disease activity and joint damage. – “Remission has become a highly achievable goal with the advent of biological therapies. Moreover, tumor necrosis factor inhibitors plus methotrexate significantly retard joint damage, even in patients who do not respond well clinically, thus reducing the propensity to accumulate irreversible disability with active disease.”
In the last few years new therapies and therapeutic strategies have revolutionized clinical developments, with the TNF inhibitors coming first (TNF stands for tumor necrosis factor). TNF inhibitors in combination with methotrexate (MTX) are able to arrest rheumatoid arthritis or at least significantly retard joint damage progression even in RA patients with high active disease.
Clinical fact 9: Extinction of extra-articular manifestations and amyloidosis. – “Effective therapy, in particular with methotrexate (MTX) and more pronounced with biologicals plus MTX, has abolished the bulk of extra-articular manifestations and amyloidosis, has reduced disease-related comorbidity such as cardiovascular disease and lymphoma, and has essentially normalized life expectancy.”
Therapy that works for treating rheumatoid arthritis also prevents disease-related comorbidities: extra-articular manifestations such as vasculitis, infections, cardiovascular disease, and malignancy as well as secondary amyloidosis have declined or even have become rare in recent years, the authors describe. That has happened thanks to appropriate use of methotrexate (MTX) and TNF inhibitors, the authors wrote in their review Development in the clinical understanding of rheumatoid arthritis.
The clinical fact 10 can be perceived as a call for action: novel medications are available, new treatment strategies are proven – but money is still the issue. The authors bring forward the argument that applying expensive but appropriate therapies have marked beneficial economic effects, apart from the improvement of health-related quality of life of the persons concerned.
Clinical fact 10: The novel therapies allow for a modification of treatment strategies and have significant economic consequences. – “Novel algorithms that encompass regular disease activity assessment, change or modification of therapy upon insufficient response defined as a lack of achievement of low disease activity or even remission, and the use of glucocorticoids and biological agents may allow for rapid achievement of optimal therapeutic responses in the vast majority of patients. This will not only improve quality of life but also lead to a reduction in the need for joint surgery and to the preservation of working ability.”
The therapeutic efficacy of novel medications as well as flexible treatment strategies has far reaching economic consequences. Even though new kinds of biologicals are costly and they may not be affordable in many cases, the new agents may reduce direct or indirect costs otherwise. Some of the true examples is the declined number of total hip replacements in many countries (the authors quote data for Sweden), and the increase of employment rates and employability of RA patients in the course of effective treatment.
Smolen JS and Aletaha D. Developments in the clinical understanding of rheumatoid arthritis. Arthritis Res Ther. 2009; 11(1): 204. – doi: 10.1186/ar2535 – free article download
Author of this article: Tobias Stolzenberg
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