New RA therapy recommendations cover 5 domains

Most patients with a confirmed diagnosis of rheumatoid arthritis (RA) use nonbiologic disease-modifying antirheumatic drugs (DMARDs), and the rate of biologic DMARD use is increasing rapidly, according to the American College of Rheumatology (ACR).The organization last updated recommendations for the use of nonbiologic DMARDs in 2002 and had not developed recommendations for using biologic agents. Recently, however, the ACR issued new and revised recommendations that address the use of both types of therapies in patients with RA when they are starting or resuming them.

A Core Expert Panel of clinicians and methodologists used an evidence- based approach with an extensive literature review in guiding development of the recommendations for the use of DMARDs in RA. The ACR prespecified the following 5 key areas of therapy: (1) indications for use, (2) screening for tuberculosis, (3) monitoring for adverse effects, (4) assessing the clinical response, and (5) the roles of cost and patient preference in decision making. Also considered were disease duration, disease severity, and prognostic features.

The ACR's 2008 recommendations for the use of nonbiologic and biologic DMARDs in RA include the following:
• Patients with all disease durations and all degrees of disease activity start with methotrexate (MTX) or leflunomide therapy, regardless of prognostic features.
• Patients without poor prognostic features, with low disease activity, and with disease duration of 24 months or less or short disease duration use hydroxychloroquine (HCQ) or minocycline, respectively.
• Patients with all disease durations and all degrees of disease activity but with poor prognostic features use sulfasalazine (SSZ).
• Patients with moderate to high disease activity use MTX plus HCQ, regardless of disease duration or poor prognostic features; patients with various disease durations and prognostic features use other dual-DMARD combinations.
• Patients with poor prognostic features and moderate to high levels of disease activity, regardless of disease duration, use a triple-DMARD combination (MTX plus HCQ plus SSZ).
• Only patients with early RA (duration of less than 3 months) who have high disease activity and never received DMARDs use an anti–tumor necrosis factor α (anti–TNF-α) agent-etanercept, infliximab, or adalimumab-with MTX.
• Patients with intermediate- and longer-term RA for whom previous MTX monotherapy led to an inadequate response and who have moderate disease activity and features of a poor prognosis, as well as patients with high disease activity, irrespective of prognostic features, use anti–TNF-α agents.
• Patients with at least moderate disease activity and a poor prognosis for whom MTX in combination with DMARDs or sequential administration of other nonbiologic DMARDs led to an inadequate response use abatacept.
• Patients with high disease activity and a poor prognosis for whom MTX in combination with DMARDs or sequential administration of other nonbiologic DMARDs led to an inadequate response use rituximab.

In addition, the ACR recommended against initiating or resuming treatment with MTX, leflunomide, or biologic agents for patients with RA who have active bacterial infection, active herpes zoster viral infection, active or latent tuberculosis, or acute or chronic hepatitis B or C. Contraindications to DMARD use also included severe upper respiratory tract infections, previous lymphoproliferative disease, moderate or severe heart failure, multiple sclerosis or demyelinating disorders, and pregnancy.

The investigators noted that the recommendations are intended to help guide therapy rather than proscribe appropriate therapies and that applying them to clinical practice will require individualized patient assessment and clinical decision making. They are described as extensive but not comprehensive, and they will be updated regularly.

Other recommendations for the treatment of patients with RA, other rheumatologic conditions, and comorbidities emerged from the 2008 Annual Congress of the European League Against Rheumatism, held recently in Paris. For details, see the Box, "Research report: EULAR 2008," below.

For more information about the updated ACR recommendations, visit the ACR Web site at www. rheumatology.org. Or, contact the organization at American College of Rheumatology, 1800 Century Place, Suite 250, Atlanta, GA 30345-4300; telephone: (404) 633-3777; fax: (404) 633-1870.

Research report: EULAR 2008

Rheumatoid arthritis (RA) is an important cardiovascular disease (CVD) risk factor, according to research reports at the 2008 Annual Congress of the European League Against Rheumatism (EULAR). Investigators recommended at the meeting that patients with RA, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) undergo compulsory CVD risk management and that current CVD risk calculators be adapted to the increased CVD risk in patients with inflammatory disease.

The risk of CVD in patients with RA was found to be comparable to that in patients with type 2 diabetes mellitus (DM). In one study, at least 1 CV event was reported in 8.6% of participants who had RA, compared with 4.3% in the general population (4.3%). In another study, the age- and sex- adjusted prevalence odds ratios for CVD in participants with type 2 DM and those with RA were similar-2.3 and 2.0, respectively. Investigators concluded that physicians treating patients with RA should be aware of the increased risk and advise them to maintain a healthy diet and lifestyle and stay alert to the early signs of CVD.

Inflammation may be the key to increased CVD risk in patients with RA, according to the EULAR Task Force, which reviewed current evidence and expert opinion based recommendations for management of CVD in inflammatory rheumatologic disease to devise EULAR recommendations for clinical practice. The task force recommendations included the following:
• RA, AS, and PsA be clinically accepted as new CVD risk factors.
• Adapt existing CVD risk calculators (eg, the Framingham risk score and the Systematic Coronary Risk Evaluation [SCORE]) by a multiplier to reflect the increased CVD risk in patients with inflammatory disease.
• Conduct annual CVD risk screening for all patients with RA and consider annual screening for patients with AS or PsA.
• Make lifestyle recommendations (eg, diet, exercise, and cessation of cigarette smoking) to all patients with inflammatory disease.
• Consider treatment with statins or antihypertensives and set CVD management targets according to local guidelines; if there are none, consider treatment when the 10- year CVD mortality risk with the Framingham/SCORE function is higher than a certain value.
• Aggressively suppress inflammation to further lower CVD risk in patients with inflammatory disease.

Investigators noted that disease-modifying antirheumatic drugs and biologic agents may lower the CVD risk in patients with inflammatory rheumatologic disease. They also pointed out that the use of statins and hypertensives, such as angiotensin-converting enzyme inhibitors and angiotensin blockers, may result in even greater benefits than in the general population because of their anti-inflammatory properties.

Researchers also reported on the following:
• New initiatives designed to improve RA management through patient participation included the Elaboration and validation of the EULAR patient-derived Rheumatoid Arthritis Impact of Disease (RAID) score-based on patients' perceptions of the impact of disease on dimensions of health-and a study that sought to understand patient perspectives and motivators for participating in clinical trials to encourage active participation in future research. In the RAID scoring system, patients rated pain, function, and fatigue as having the most important impact on their lives, followed by emotional well-being, sleep, coping, and physical well-being.
• Researchers reported on a new DNA microarray chip (the "ARTchip") that may be used to predict severe disability and remission in patients with RA.
• Joint distraction (using a surgical frame around a degenerated joint to strengthen it and promote repair) promotes cartilage repair in severe knee osteoarthritis.

For more information about the latest research in rheumatology, visit the EULAR Web site at www.eular.org. Or, contact the organization at the European League Against Rheumatism, EULAR Secretariat, Seestrasse 240, CH 8802-Kilchberg, Switzerland; telephone: + 41 44 716 30 30; fax: + 41 44 716 30 39.