What I did before
As the most common autoimmune disease, Rheumatoid Arthritis (RA) affects about 300,000 Canadians.1,2 The disease is often diagnosed in adults between the third to fifth decades of life. Furthermore, women are 2-3 times are as likely to have the disease.2 The chronic synovial inflammation can lead to articular damage, causing physical disability and lower quality of life in this population.
Twenty-five years ago, RA was diagnosed on average 2 years after onset and the limited available treatment was escalated depending on symptoms. This resulted in significant physical disability, chronic pain and an overall disease mortality of 20% over 10 years.3
During my training in the 1990s, according to national and international guidelines at the time, the “treatment pyramid” of RA started with rest and exercise, education, physical therapy and NSAIDs. The next tier consisted of disease modifying drugs including Methotrexate. Meanwhile, glucocorticoids (GCs) and surgical treatment were “backbones” of the treatment throughout the course of the disease.4
What changed my practice
The past two decades, however, have seen a major paradigm shift in treatment of patients with RA. The Canadian Rheumatology Association (CRA)5, American College of Rheumatology (ACR)6, and European League against Rheumatism (EULAR)7 have put forward revised guidelines in the recent years in their treatment approaches for rheumatoid arthritis. More than ever there is an emphasis on early diagnosis and appropriate treatment with disease-modifying anti-rheumatic drugs (DMARDs). Furthermore, newer treatments have provided options for those patients that were once deemed to have refractory disease.
What I do now
1. Diagnosing RA early makes it easier to treat
In order to optimize long term prognosis, we need to confirm the presence of RA early. While the complete criteria for diagnosis of RA is covered elsewhere8, the most common features include inflammatory arthritis (AM pain/stiffness lasting >30 minutes) affecting >3 joints, elevated markers of inflammation (CRP/ESR), and Rheumatoid Factor or Anti-CCP positivity. Additional points are awarded for duration of symptoms.
Early in the course of the disease, radiological evidence of inflammation/erosion may not be present, and are certainly not necessary for diagnosis. In MRI studies, there is evidence of joint erosions as early as 4 months from the onset of symptoms in absence of any X-ray findings.9 However, if joint erosions are visible at diagnosis, no other findings are needed for diagnosis. Once diagnosis of RA is suspected, RF, anti-CCP and CRP levels should be obtained.
2. All patients with RA should be on a DMARD (Methotrexate is the preferred first choice)
It has been repeatedly demonstrated that early diagnosis and treatment, can prevent joint damage and make remission easier to achieve. Initiation of DMARDS in the first 6 months of diagnosis can reverse loss of function in 80% of patients, and induce remission in 42-48% of patients.10
Furthermore, early diagnosis and treatment can prevent loss of function that can often mark the natural history of the disease. This has led to coining of the term, “therapeutic window” in diagnosis and treatment of RA, in which opportunity exists for DMARDs to decisively influence the long-term prognosis including remission of the disease.11,12
Numerous studies over the past decade have set to determine the optimal steps in treatment of RA with DMARDS. While the patient’s preference and risk profile has to be taken into consideration, in absence of any contraindication, Methotrexate has been consistently recommended to be the initial agent of choice for treatment of RA as well as the component of any multidrug treatment plan.13
Overall, Methotrexate offers an excellent risk-benefit ratio and long-term adherence compared with other DMARDS. Major side effects include GI upset, increased liver enzymes, myelosuppresion and stomatitis. Rarely, patients may develop liver toxicity or pneumonitis.
Methotrexate monotherapy can achieve remission in 25-30% of patients with RA.10 However, if remission is not achieved, options for additional agents include traditional DMARDs including hydroxychloroquinolone, sulfasalazine, leflunomide or the new biologics (anti-TNF (Tumor necrosis factor) agents, abatacept, tocilizumab, rituximab).
The website, www.rheuminfo.com, includes patient information sheet as well as an educational video. Prior to starting patients on Methotrexate, we recommend that physicians ensure patients are not pregnant or breastfeeding, obtain screening labs including CBC, Creatinine, liver enzymes, HepB, HepC, HIV, CRP. Methotrexate can be started at 15 mg weekly PO. Follow up CBC, Creatinine, AST, ALT and CRP should be done on monthly basis.
3. NSAIDS do not change the outcomes in RA
NSAIDS decrease inflammation in RA by inhibiting the COX enzyme, which converts arachidonic acid to inflammatory prostaglandins. Therefore, NSAID use in patients with RA is almost universal. However, NSAIDS are associated with major morbidities including increased risk of GI ulceration (2% per year).14 They also play a role in development of hypertension and impairing the anti-platelet function of Aspirin, which may further contribute to the cardiovascular risk of patients with RA.15
Therefore, given their adverse event profile along with lack of disease modifying property, the aim should be to minimize the use of NSAIDS in patients with RA. They can be used as ‘bridging’ therapy while waiting for DMARDs to take effect.
4. Steroids increase morbidity in RA
GCs have been used in treatment of RA for more than 60 years. While they exert potent anti-inflammatory effects, their adverse reaction profile is extensive.16 Today, the use of GC is often limited to “bridge therapy” (as above), treatment of RA flares or intra-articular injection.
A recent study, using the RA cohort in BC, showed that use of GCs was associated with a 68% increased risk of myocardial infarction (MI). They also showed that the current dose and cumulative use were also independently associated with an increased risk of MI (10% per additional year on GCs and 13% per 5 mg/day increase).17 Similar studies have demonstrated that RA patients on GCs have higher incidence of carotid plaque, congestive heart failure and hypertension.18-20
Given this, I aim to minimize the use of GCs for the smallest dose and the shortest period in my patients with RA.
5. Smoking increases incidence and severity of RA
I recommend smoking cessation to all my patients with RA. Smoking is the best-studied environmental factor in RA. In addition to causing more severe disease, it also increases the risk of seropositive RA (RF or anti-CCP positivity).21 Disease onset in smokers occurs earlier and they have greater radiologic progression compared to the non-smokers.22
Furthermore, smokers have been shown to have poorer response to DMARDs including anti-TNF agents even when adjusted for RF or anti-CCP status.23 While the exact reason for this remains unknown, it is hypothesized that interaction between smoking and DMARDs may contribute.
All Rheumatologists in BC have committed to see a new inflammatory polyarthritis within 3 months and most will see the patients with suspected diagnosis of inflammatory arthritis within 2-4 weeks. We recommend the family physicians who suspect their patients have early RA, contact their local rheumatologist to expedite the referral.
- O’Dell JR. Rheumatoid arthritis. In: Goldman L, Schafer AI, eds. Goldman’s Cecil Medicine, 24th ed. Philadelphia, PA: Saunders Elsevier; 2011:1681–1689. (Request from CPSBC)
- Canadian Arthritis Network factsheet. http://www.arthritis.ca/document.doc?id=925
- Pincus T, Callahan LF, Sale WG, et al. Severe functional decline, work disability, and increased mortality in 75 rheumatoid arthritis patients studied over 9 years. Arthritis Rheum 1984; 27: 864–72. (Request from CPSBC)
- Fries JF. Reevaluating the therapeutic approach to rheumatoid arthritis: the “sawtooth” strategy. J Rheumatol Suppl. 1990;22:12-5 (not available locally)
- Bykerk VP, Akhavan P, Hazlewood GS, et al. Canadian Rheumatology Association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol. 2012;39(8):1559-82. (Request from CPSBC or view with UBC)
- Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res. 2012;64(5):625-39. (Request from CPSBC or view with UBC)
- Smolen JS, Landewé R, Breedveld FC. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010 Jun;69(6):964-75. (View article)
- Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid Arthritis Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010; 69:1580– 1588. (View article)
- McQueen FM, Stewart N, Crabbe J, Robinson E, Yeoman S, Tan PL, et al. Magnetic resonance imaging of the wrist in early rheumatoid arthrit- is reveals a high prevalence of erosions at four months after symptom onset. Ann Rheum Dis. 1998;57(6):350–6.) (View article)
- Klarenbeek NB, Güler-Yüksel M, van der Kooij SM, et al.: The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis 2011; 70: 1039–46. (Request from CPSBC or view with UBC)
- Boers M. Understanding the window of opportunity concept in early rheumatoid arthritis. Arthritis Rheum. 2003;48(7):1771–4. (View with CPSBC or UBC)
- O’Dell JR. Treating rheumatoid arthritis early: a window of opportunity? Arthritis Rheum. 2002;46(2):283–5. (View with CPSBC or UBC)
- Schneider M, Krüger K. Rheumatoid arthritis–early diagnosis and disease management. Dtsch Arztebl Int. 2013;110(27-28):477-84 (View article)
- Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999 Jun 17;340(24):1888-99. (Request from CPSBC or view with UBC)
- Hudson M, Baron M, Rahme E, et al. Ibuprofen may abrogate the benefits of aspirin when used for secondary prevention of myocardial infarction. J Rheumatol 2005;32:1589–93. (Request from CPSBC or view with UBC)
- Sholter DE, Armstrong PW. Adverse effects of corticosteroids on the cardiovascular system. The Canadian journal of cardiology. 2000;16(4):505-511. (Request from CPSBC)
- Aviña-Zubieta JA, Abrahamowicz M, De Vera MA, et al. Immediate and past cumulative effects of oral glucocorticoids on the risk of acute myocardial infarction in rheumatoid arthritis: a population-based study. Rheumatology. 2013;52(1):68-75. (Request from CPSBC)
- Panoulas VF, Douglas KM, Stavropoulos-Kalinoglou A, et al. Long-term exposure to medium-dose glucocorticoid therapy associates with hypertension in patients with rheumatoid arthritis. Rheumatology (Oxford) 2008;47:72-5. (View article)
- Myasoedova E, Crowson CS, Nicola PJ, et al. The influence of rheumatoid arthritis disease characteristics on heart failure. J Rheumatol 2011;38: 1601-6 (Request from CPSBC or view with UBC)
- del Rincon I, O’Leary DH, Haas RW, et al. Effect of glucocorticoids on the arteries in rheumatoid arthritis. Arthritis Rheum 2004;50:3813-22 [erratum appears in Arthritis Rheum 2005;52:678] (View with CPSBC or view with UBC)
- Heliovaara M, Aho K, Aromaa A, Knekt P, Reunanen A. Smoking and risk of rheumatoid arthritis. J Rheumatol 1993;20:1830-5. (Request from CPSBC)
- Ruiz-Esquide V, Gomez-Puerta JA, Canete JD, et al. Effects of smoking on disease activity and radiographic progression in early rheumatoid arthritis. J Rheum. 2011:38(12):2536-9 (Request from CPSBC) or view with UBC)
- Saevarsdottir S, Wedren S, Seddighzadeh M, et al. Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: Observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts. Arthritis Rheum 2011;63:26-36. (View with CPSBC or view with UBC)
BC Guidelines for RA http://www.bcguidelines.ca/pdf/rheumatoid_arthritis.pdf