American College of Rheumatology Updates Rheumatoid Arthritis Guidelines 2008

The American College of Rheumatology (ACR) has updated its 2002 guidelines on the use of nonbiologic disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA), which now include data on the use of biologic agents as well. The updated recommendations are reported in the June 15 issue of Arthritis Care and Research.

"The majority of patients with a confirmed diagnosis of . . . RA use nonbiologic. . . DMARDs and the rate of biologic DMARD use is rising rapidly," write Kenneth G. Saag, MD, MSc, from the University of Alabama, Birmingham, and colleagues.

"The . . . ACR has not updated its recommendations for nonbiologic DMARDs since 2002 and has not previously developed recommendations for biologic agents. Although past guidelines have been derived from an informal consensus approach, we used a formal group process to develop recommendations that were as evidence-based as possible."

These guidelines were developed following the principles set forth by the Appraisal of Guidelines for Research and Evaluation Collaboration. A systematic review of scientific evidence was conducted to create an evidence report and draft guidelines addressing 5 domains prespecified by the ACR: (1) indications for use, (2) screening for tuberculosis (TB; for biologic DMARDs only), (3) monitoring for adverse effects, (4) evaluating clinical response, and (5) the roles of cost and patient preferences in decision making (for biologic DMARDs only).

A Task Force Panel that critiqued and rated proposed recommendations included internationally recognized clinicians, methodologists, and patient representatives with broad expertise in the use of nonbiologic and biologic DMARDs, evidence-based medicine, patient preference, and healthcare economics.

Indications for starting or resuming a nonbiologic or biologic DMARD highlight the use of these agents on the background of optimal and appropriate use of nonmedical therapy such as physical and occupational therapy as well as the use of nonsteroidal anti-inflammatory drugs and intraarticular and oral glucocorticoids.

Biologic DMARDs should be used only after failure of nonbiologic DMARDs. Patients with RA should be seen regularly to evaluate disease activity and severity and to determine whether alternative therapies should be used.

The only nonbiologic agents included in these recommendations are hydroxychloroquine, leflunomide, methotrexate, minocycline, and sulfasalazine, and the only biologics included are abatacept, adalimumab, etanercept, infliximab, and rituximab. The remaining DMARDs were not included because of very infrequent use, the high incidence of adverse events, or both.

Nonbiologic DMARD combinations best supported by evidence and used most commonly are methotrexate plus hydroxychloroquine, methotrexate plus sulfasalazine, methotrexate plus leflunomide, sulfasalazine plus hydroxychloroquine, and sulfasalazine plus hydroxychloroquine followed by methotrexate.

Methotrexate or leflunomide monotherapy should be started for patients with all disease durations and for all degrees of disease activity irrespective of poor prognostic features.

Hydroxychloroquine monotherapy is recommended for patients without poor prognostic features, with low disease activity, and with disease duration not greater than 24 months.

Minocycline monotherapy is recommended for patients without poor prognostic features, with low disease activity, and with short disease duration.

Sulfasalazine monotherapy is recommended for patients with all disease durations and without poor prognostic features and includes those with all degrees of disease activity.

Methotrexate plus hydroxychloroquine is recommended for patients with moderate to high disease activity regardless of disease duration or poor prognostic features.

Methotrexate plus leflunomide is recommended for patients with intermediate or longer disease duration (≥ 6 months), with high disease activity irrespective of prognostic features.

Methotrexate plus sulfasalazine is recommended in patients with all disease durations provided they have high disease activity and poor prognostic features.

Hydroxychloroquine plus sulfasalazine is recommended only for patients with intermediate disease duration (6 - 24 months) and high disease activity but without poor prognostic features.

The triple DMARD combination of sulfasalazine, hydroxychloroquine, and methotrexate is recommended for all patients with poor prognostic features and moderate or high levels of disease activity, regardless of disease duration.

Recommendations for the use of biologic DMARDs are separated according to disease duration (<>

An anti-TNFα agent plus methotrexate is recommended for patients with high disease activity for 3 months or longer with poor prognosis and no barriers related to treatment cost and no insurance restrictions to accessing medical care.

In intermediate-duration and longer-duration RA, the anti-TNFα agents can be used interchangeably in patients with inadequate response to prior methotrexate monotherapy, moderate disease activity, and features of a poor prognosis as well as for patients with high disease activity, regardless of prognostic features.

Anti-TNFα agents can also be used interchangeably in patients with inadequate response and at least moderate residual disease activity after previous therapy with methotrexate in combination or with sequential administration of other nonbiologic DMARDs, regardless of prognostic features.

Contraindications to the use of nonbiologic and biologic DMARDs may include infectious disease or pneumonitis, or both; and hematologic, oncologic, cardiac, liver, renal, neurologic, and pregnancy and breast-feeding contraindications.

"Using a formal group process and the scientific evidence as much as possible, we provide recommendations for the use of nonbiologic and biologic therapies in patients with RA when starting or resuming these therapies," the guidelines authors conclude. "These recommendations are not meant to take the place of personalized patient care and are intended to help guide therapy rather than proscribe appropriate therapies. The recommendations are extensive but not comprehensive, and it is intended that they will be regularly updated to reflect the rapidly growing scientific evidence in this area along with changing practice patterns in rheumatology."

Dr. Saag's work was supported by the Agency for Healthcare Research and Quality, the University of Alabama, Birmingham Center for Education and Research on Therapeutics of Musculoskeletal Diseases, and the American College of Rheumatology. Four other guidelines authors have received support from the ACR, and one of these authors also was supported by the National Institutes of Health. Some of the guidelines authors have disclosed various financial relationships with Roche, UCB, Nitec, Amgen, Abbott, Centocor, Wyeth, Merck, Procter and Gamble, Eli Lilly, Novartis, Mathematica, Bristol-Myers Squibb, WellPoint, Genentech, Pfizer, Incyte, Hoffman-LaRoche, Actelion, Array, Biogenidec, Gilead, GlaxoSmith-Kline, Encysive, TAP, Xoma, Actelion, and Celgene.

Arthritis Care Res. 2008;59:762-784.

Clinical Context

The ACR has not updated its recommendations for the use of nonbiologic DMARDs since 2002 and has not previously developed recommendations for biologic agents. The use of biologic DMARDs has increased significantly recently. This is a systematic review of evidence for the use of both types of DMARDs by a panel of experts familiar with the assessment and treatment of RA and is intended to provide guidance to clinicians in the care of their patients with RA.

The investigators conducted a search of the literature for studies up to February 2007. Articles were selected based on quality, and the strength of evidence for 5 domains was assessed. The 5 domains examined were indications for use, screening for TB (biologic DMARDs only), adverse effects, clinical response, and cost and patient preferences. For nonbiologic agents, hydroxychloroquine, leflunomide, methotrexate, minocycline, and sulfasalazine were considered. For biologic agents, abatacept, adalimumab, etanercept, infliximab, and rituximab were considered. Other DMARDs were not considered because of a high incidence of adverse events or infrequent use and limited evidence. Disease activity was rated as low, moderate, or high, and disease duration was categorized as less than 6 months, 6 to 24 months, and more than 24 months.

Study Highlights

• Methotrexate or leflunomide is recommended as the initiating therapy for most patients with RA for all disease durations and all degrees of disease activity.
• For patients with moderate to high disease activity, the combination of methotrexate plus hydroxychloroquine is endorsed irrespective of disease duration or poor prognostic features.
• Triple DMARD therapy with methotrexate, hydroxychloroquine, and sulfasalazine is recommended for moderate to high disease activity irrespective of disease duration or poor prognostic features.
• For patients with early RA of 3 months' duration or less and high disease activity who have never received DMARDs, the anti-TNFα agents etanercept, infliximab, or adalimumab are recommended.
• For those with intermediate or longer duration of RA, the anti-TNFα agents etanercept, infliximab, or adalimumab are recommended for those with failed response to methotrexate.
• For those patients with at least moderate disease activity and poor prognosis in whom methotrexate combined with sequential administration of other nonbiologic DMARDs led to an inadequate response, the fusion protein abatacept and the B-cell antibody rituximab are recommended.
• DMARDs are contraindicated in those with a history of active or latent TB, severe upper respiratory tract infection, or nonhealing skin ulcers.
• Methotrexate is contraindicated in the presence of RA-associated pneumonitis or interstitial lung disease of unknown cause.
• Leflunomide and methotrexate are contraindicated with a history of myelodysplasia.
• For anti-TNFα agents, a history of lymphoproliferative disease within 5 years, multiple sclerosis or demyelinating disorders, and class III to IV heart failure are contraindication for use.
• For those considering biologic DMARDs, potential risk factors for TB should be assessed and a TB skin test conducted regardless of previous Bacillus Calmette-Guérin status.
• Those at high risk for TB such as the homeless or prison inmates are at higher risk for reactivation of latent TB with anti-TNFα agents.
• The preferred regimen for management of latent TB infection is 9 months of daily isoniazid.
• Therapy for TB should be initiated by clinician with expertise in TB management.
• Use of DMARDs is contraindicated in the presence of acute hepatitis B or C, and use of nonbiologic DMARDs in patients with chronic hepatitis B or C should be stratified according to hepatitis type, Child-Pugh grade, and use of antiviral agents.
• Elevation of liver transaminase levels of 2 times or higher is a contraindication to initiating or resuming therapy with methotrexate, leflunomide, and sulfasalazine.
• When starting or resuming a DMARD, baseline tests of complete blood count, liver transaminase, and creatinine levels are recommended.
• In those receiving methotrexate, leflunomide, or sulfasalazine, the test should be repeated every 2 to 4 weeks for 3 months for new treatment or dose escalation.
• Hepatitis B and C screening is recommended for high-risk patients.
• Influenza and pneumococcal vaccine status should be updated before starting therapy.
• Live vaccines are contraindicated during biologic therapy.
• Patients starting hydroxychloroquine should have a complete ophthalmologic examination within the first year of treatment with dilated pupils and central field testing, and the examination should be repeated annually for those in a high-risk category and in 5 years for those with low risk.
• Patients with RA planning for pregnancy should avoid methotrexate, leflunomide, and minocycline before and during pregnancy and breast-feeding.

Pearls for Practice

• Methotrexate or leflunomide is recommended as the initiating therapy for most patients with RA for all disease durations and all degrees of disease activity, with other regimens recommended for other levels of disease activity and response.
• Contraindications for DMARD use include a history of TB infection, lymphoproliferative disease, hepatitis B or C infection, pregnancy, and lactation.

Más información en :


http://www.medscape.com/viewarticle/575597