Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease that mainly affects the joints.1 Patients with RA should be started on treatment as early as possible to prevent disease progression, joint damage, joint deformities, worsening of symptoms, and extra-articular manifestations such as cardiac and pulmonary problems. The treatment of RA follows the treat-to-target (T2T) approach set by the European League Against Rheumatism (EULAR) and also endorsed by the American College of Rheumatology (ACR).2 The main target is to achieve RA disease activity remission, with low-disease activity as an alternative target.3 Remission is defined by the ACR and EULAR in two ways.3 One way is the Boolean-based definition, which considers no more than 1 tender or swollen joint, global assessment of health from the patient and physician, and minimal elevation of inflammatory markers in blood. Another way uses Index-based definition, which consists of a Simplified Disease Activity Index (SDAI) score of ≤3.3. Calculation of the SDAI is the simple linear sum of the outcome parameters: tender joint count and swollen joint count based on a 28-joint assessment, patient global assessment of disease activity visual analogue scale VAS (0 – 10 cm), physician global assessment of disease activity (MDGA VAS 0 – 10 cm), and C-reactive protein (CRP in mg/dl). 4 Remission and low RA disease activity (similar to remission but the range of tender and swollen joints could be between 0 to a few) are the two disease activity states that have been shown to prevent the development of joint damage and other long-term manifestations from RA.3
Control of RA disease activity (either remission or low disease activity) is achieved by using medications called disease-modifying antirheumatic drugs (DMARDs). Since it may take 3-6 months for these medications to achieve improvement, fast-acting medications such as oral, intramuscular, or subcutaneous glucocorticoids, mainly prednisone, are used in this short-term period to alleviate the physical symptoms of the disease. Treatment decisions should be made jointly by the patient and the rheumatologist. Multiple factors, including the duration of disease and prior experience with medications, must be considered. Although there are numerous DMARDs that have been developed, the anchor drug for RA is a DMARD called methotrexate. Patients are started on methotrexate (unless contraindicated) and typically low doses of prednisone (5 – 10 mg/day) for three months. Medication regimen may be adjusted according to the RA disease activity either monthly or every three months. Other DMARDs and biologics, or a combination of both, may be used to achieve low disease activity or remission.
Symptom management such as pain is usually accomplished with glucocorticoids. A common type of glucocorticoid is prednisone, which is used in low doses and preferably for a short period of time. Glucocorticoids can also help control RA disease activity. Double-blinded placebo controlled trials5-10 as well as meta-analyses11-13 have also shown that prednisone has been effective in slowing disease progression, as shown in radiographs and erythrocyte sedimentation rate, in addition to improvement in joint tenderness, swollen joints, pain, and grip strength. In a study of 242 patients with early RA (duration <1 year) who received either 7.5 mg/day prednisone or placebo for two years, the prednisone group had a lower median change in total Sharp score (1.8 vs 3.5, p=0.019), fewer newly eroded joints per patient (0.5 vs. 1.25, p=0.0007), fewer patients who had radiographic progression beyond the smallest detectable difference (25.9% vs. 39.3%, p=0.033), and more patients who had achieved remission (55.5% vs. 32.8%, p=0.005).8 Despite these benefits, prednisone is usually tapered off by six months since studies have shown that high dose (≥5 mg/day) or long term ( >1 year) glucocorticoid use causes significant adverse events.14
- Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis. Lancet 2009; 373 (9664): 659-672.
- Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 2016; 75 (1): 3-15.
- Felson DT, Smolen JS, Wells G, et al. American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 2011; 70 (3): 404-413.
- Smolen JS, Breedveld FC, Schiff MH, et al. A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology (Oxford) 2003; 42 (2): 244-257.
- Boers M, Verhoeven AC, Markusse HM, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997; 350 (9074): 309-318.
- Kirwan JR, Arthritis, Group RCL-DGS. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med 1995; 333 (3): 142-147.
- Möttönen T, Hannonen P, Leirisalo-Repo M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. Lancet 1999; 353 (9164): 1568-1573.
- Svensson B, Boonen A, Albertsson K, et al. 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 Rheum 2005; 52 (11): 3360-3370.
- van Everdingen AA, Jacobs JW, van Reesema DRS, et al. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 2002; 136 (1): 1-12.
- Wassenberg S, Rau R, Steinfeld P, et al. Very low‐dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double‐blind, placebo‐controlled trial. Arthritis Rheum 2005; 52 (11): 3371-3380.
- Bakker MF, Jacobs JW, Welsing PM, et al. Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis: a randomized trial. Ann Intern Med 2012; 156 (5): 329-339.
- Gøtzsche PC, Johansen HK. Meta-analysis of short term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. BMJ 1998; 316 (7134): 811-818.
- Saag KG, Criswell LA, Sems KM, et al. Low‐dose corticosteroids in rheumatoid arthritis. A meta‐analysis of their moderate‐term effectiveness. Arthritis Rheum 1996; 39 (11): 1818-1825.
- Saag KG, Koehnke R, Caldwell JR, et al. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 1994; 96 (2): 115-123.