Rheumatoid arthritis (RA) is a common autoimmune condition that causes joint pain and swelling, systemic fatigue and ultimately can lead to joint deformity and disability. It afflicts women more than men. The bad news is that RA is getting more common. In Ontario there were almost 100,000 adults with RA in 2010, reflecting a prevalence of 0.9%. The prevalence of RA has steadily increased between 1996 and 2010 from 473 cases per 100,000 population (0.49%) to 784 (95% CI 779–789) per 100,000 population (0.9%) (Figure below). Similar changes in epidemiology have been reported from Mayo Clinic. (Widdifield et al ARTHRITIS & RHEUMATOLOGY Vol. 66, No. 4, April 2014, pp 786–793) The good news is that this is the era of disease modifying drugs (DMARDs). These newer agents can put RA into remission, in many cases, and reduce or eliminate joint deformities, in most patients. In the bad old days patients took high dose aspirin until their ears rang or received regular injections of gold, with modest benefits. Physicians and lay people alike were all too familiar with patients with debilitating joint deformities as a result of RA (Figure below). DMARDs, especially the newer biological therapies, antibodies that target anti-tumour necrosis factor-alpha (anti-TNFα), such as adalimumab, etanercept and infliximab, can tame the disease and prevent joint deformity. These antibodies neutralize inflammatory cytokines, inhibit the inflammatory mediators TNF). Intriguingly, the mortality of RA patients in Ontario has declined 21% between 1996 and 2008, coincident with the widespread use of DMARDs, raising the possibility that new therapies which decrease a patient’s inflammatory burden also reduce mortality. This idea has biologic plausibility because RA patients have increased risk of potentially lethal cardiovascular diseases. In fact in the TEMPO trial adding Enbrel was superior to the older DMARD, methotrexate Arthritis Rheum. 2006 Apr;54(4):1063-74 (Figure above-right panel). However there are a few caveats. First, the biologic DMARDs require the patients self-inject (weekly for etanercept, Enbrel®).They are also expensive ($1900 a month for Enbrel®). For most people the drug is covered by insurance. However, there is another caveat-therapy works best if it is instituted early in the disease. This requires a major change in how physicians view this chronic disease; specifically it requires more sense of urgency in initiation of therapy. A new recruit to the Department of Medicine at Queen’s University Dr. Tabitha Kung has started a clinic to accelerate the institution of therapy early in the course of RA.
Dr. Tabitha Kung, Assistant Professor
Dr. Kung notes, “There has been a paradigm shift in the management of rheumatoid arthritis (RA). In the 1980s, RA was managed using the ‘treatment pyramid’, which started with symptomatic management only (anti-inflammatories, glucocorticoids), followed by disease modifying therapy, and the need for surgical intervention for many patients with RA due to significant damage and disability.(1) Due to the growing evidence at the time showing severe joint destruction with standard management, earlier intervention with disease modifying anti-rheumatic drugs (DMARDs) became standard of care, and there was a push for the development of early arthritis clinics.(2,3). By recruiting patients with early disease, early arthritis clinics are aimed at improving access to Rheumatology care for patients who can benefit most from early intervention as early effective treatment has been shown to improve outcomes and decreases damage and disability in patients with Rheumatoid Arthritis.(4,5) In fact, a study conducted within such an early arthritis clinical cohort in the Netherlands looked specifically at delay in assessment and outcome. “ The study Dr. Kung cited was performed in Leiden where they have an Early Arthritis Clinic cohort. The authors studied 1,674 early arthritis patients (including ~600 with RA). They evaluated the impact in delay in diagnosis and therapy initiation, noting the various contributors to delayed treatment (those attributable to the patient, the GP delay, and the rheumatologist). In the van der Linden study the median total delay to therapy was 13.7 weeks with patient delays accounting for only 2.4 weeks while GP delay added 8.0 weeks. Among RA patients, 69% had delayed definitive treatment (define as occurring >3 months after diagnosis). Compared to those who received early treatment (<3 months) those waiting >3 months to begin therapy were almost twice as likely (hazard ratio of 1.87) to fail to achieve a DMARD-free remission (Figure below). Those RA patients with delayed diagnosis were also at a 1.3 times higher risk of experiencing joint destruction over the 6-years follow-up period. Early assessment within 12 weeks was associated with better outcome with less joint destruction and better chance of remission than those seen after 12 weeks of symptoms.(6) When it comes to RA, Dr. Kung concludes, time matters! The need for timely diagnosis and treatment is greater since the RA treatment armamentarium has increased to include the not only the gamut of conventional DMARDs but an expanding array of biologics and newer small molecules. The Adult Early Inflammatory Arthritis Clinic at Hotel Dieu hospital has been created to identify and treat patients with very early RA (those with < 12 months of symptoms). Patients have already been seen in the Early Arthritis Clinic and some of them have already benefitted from early evaluation and effective intervention. One such patient is Mr. L., a 26-year old gentleman who presented with morning stiffness of 2-3 hours duration, and pain involving his feet, ankles, wrists and hands worst in the morning and improving through the day. He had objective evidence of active RA (swollen joints and a positive rheumatoid factor were highlighted on his referral). He was seen within 12 weeks of symptom onset and started on disease modifying therapy soon after assessment. He was found to have 10 swollen joints on initial assessment, and was also found to be anti-CCP positive (a biomarker of RA). He is currently on combination DMARD therapy and is in remission 9 months after initial assessment. He feels “almost back to normal” and is doing well on therapy, has no functional limitations and is back at his usual work. Goals of the Program:
- Rapid assessment of patients with early RA (<1yr of symptoms)
- Rapid confirmation of diagnosis and initiation on effective DMARD therapy
If you’re a patient with rheumatoid arthirits early diagnosis and referral is an important consideration to discussion with your family physician. It’s also important to be well informed. The Arthritis Society of Canada’s website is a great source of information. It includes a very nice summary of drugs for RA.
My closing thought is how rapidly Medicine is changing. I am a proud member of Queen’s Medicine class of 1981. We were taught that RA should be treated with rest, heat, hot wax and gold injections. I remember my grandmother, Ada Archer’s hands. They bore the mark of her RA, a condition which made life difficult for this indomitable woman. In her day the Medical profession could do little to help her.
Mrs Ada Archer
Fast forward to Dr. Joneja, Acting Chair of Rheumatology (Meds class of 1994). She was taught the 'pyramid approach' of managing RA, which is now obsolete. Over the next 20 years Rheumatology leapt forward as a discipline and its newest practitioners are armed not to palliate but to cure the diseases their patients face. In ~20 years RA has gone from a condition which deforms and causes pain to one which can be cured or managed in the vast majority of cases. Rheumatologists now have access to a powerful new toolkit of biologic therapies. Dr. Kung’s new clinic at the Hotel Dieu Hospital will make these accessible to more patients earlier and hopefully joint deformities will soon be a thing of the past. Bibliography
- Fries JF. Reevaluating the therapeutic approach to rheumatoid arthritis: the “sawtooth” strategy. J Rheumatol 1990;22:12–15.
- Pincus T, Callahan LF, Sale WG, Brooks AL, Payne LE, Vaughn WK. Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis Rheum 1984;27:864–872.
- Quinn MA, Emery P. Are early arthritis clinics necessary? Best Practice & Research Clinical Rheumatology 2005;19:1–17.
- Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 2000;43:22–29.
- Abu-Shakra M, Toker R, Flusser D, Flusser G, Friger M, Sukenik S, et al. Clinical and radiographic outcomes of rheumatoid arthritis patients not treated with disease-modifying drugs. Arthritis Rheum 1998;41:1190–1195.
- van der Linden MPM, Le Cessie S, Raza K, van der Woude D, Knevel R, Huizinga TWJ, et al. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum 2010;62:3537–3546.