As a response to the rapidly changing world of rheumatoid arthritis treatment, the American College of Rheumatology (ACR) has issued an update to its recommendations, focusing on early treatment, screening for tuberculosis, and special considerations for high-risk patients.

Writing in the May Arthritis Care & Research, the guideline authors, led by Jasvinder A. Singh, MBBS, of the University of Alabama at Birmingham, re-emphasized the importance of more aggressive treatment in early disease per the 2008 guidelines.

They summarized their reasoning for this shift in approach as follows:

  Better outcomes can be expected with earlier intervention
  Joint damage is permanent once it occurs, so prevention is crucial
  Intensive treatment can help patients maintain physical function and quality of life

However, they pointed out that most of the recommendations are based on level C evidence, combining data from the literature and expert opinion.

Disease Activity

A main point of the recommendations is that the goal of early treatment today is remission or at least low disease activity. For patients who have been symptomatic for 6 months or less, the usual approach is monotherapy with a disease-modifying anti-rheumatic drug (DMARD), such as methotrexate.

Monotherapy is recommended whether disease activity is low, moderate, or high if no poor prognostic factors, such as extra-articular disease or bony erosions, are present.

However, if disease activity is moderate or high and poor prognostic factors are present, combination DMARD therapy can be tried, adding a drug such as hydroxychloroquine.

And if disease activity is high in early disease and the prognosis is poor, an anti-tumor necrosis factor (TNF) biologic agent can be tried in combination with methotrexate or alone.

When Patients Fail to Respond

The recommendations next addressed treatment strategies for established disease of 6 months or more duration, when patients fail to respond, deteriorate, or are unable to tolerate treatment.

Patients who have been on anti-TNF therapy for 3 months and have shown no response or a loss of benefit can be switched either to another anti-TNF agent or to a non-TNF biologic drug.

Those who have been on a non-TNF biologic for 6 months and have had inadequate response, or loss of effect, can be switched to a TNF or non-TNF biologic.

The reason for waiting 6 months with a non-TNF agent is that efficacy may take longer with these drugs, the authors explained.

Patients with high disease activity considered to have failed TNF treatment because of serious adverse events should be switched to a non-TNF biologic, but if the adverse event was not considered to be serious, either another anti-TNF agent or a non-TNF biologic can be used.

Disease Assessment

Recommendations on how to assess disease activity were published in a separate paper, also in the May Arthritis Care & Research and led by Salahuddin Kazi, MD, of Dallas VA Medical Center.

Kazi and colleagues recommended six tools for disease assessment.

Three of these rely exclusively on patient input and are easily used in clinical practice. The Patient Activity Scale (PAS) I and II vary slightly in how function is assessed, while the Routine Assessment of Patient Index Data 3 (RAPID3) tool uses a multidimensional health assessment questionnaire.

The other three tools incorporate provider input, such as joint counts in the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), which incorporates measurement of an acute-phase reactant, and the Disease Activity Score in 28 joints (DAS28), which combines numbers of swollen and tender joints with either erythrocyte sedimentation rate or C-reactive protein measurements.

High-Risk Patients

The next section of the revised treatment recommendations addressed the use of biologics for patients with rheumatoid arthritis at higher risk because of comorbid conditions.

For those with hepatitis C, etanercept (Enbrel) might be tried, but biologics should be avoided for chronic hepatitis B that has not been successfully treated because of adverse events or contraindications.

Patients with solid tumors or nonmelanoma skin cancers treated more than 5 years ago can be treated with a biologic if their arthritis warrants it.

Rituximab (Rituxan) can be used for patients who were treated for a solid tumor or nonmelanoma skin cancer within the previous 5 years.

Rituximab also can be used when the patient has had melanoma or a lymphoproliferative malignancy, although the authors cautioned that little is known about biologic therapy in patients with recent cancers because these patients have routinely been excluded from clinical trials.

Anti-TNF biologics should not be used in patients with congestive heart failure class III or IV and whose ejection fraction is below 50%.

Tuberculosis Infection

The third section of the revised guidelines focuses on screening for latent tuberculosis infection, which should be done for all patients before initiating biologic therapy.

Either the tuberculin skin test or an interferon-gamma-release assay can be used, except for patients who have previously been given a Bacillus Calmette Guerin (BCG) vaccination and, therefore, have high rates of false positives with tuberculin skin testing.

A positive result on either of the screening tests should be followed by a chest x-ray and a sputum sample analysis if needed.

Patients found to have latent or active tuberculosis should receive treatment for the condition before initiating biologic therapy.

Finally, the authors recommended that vaccinations for influenza, pneumococcal disease, hepatitis B, human papillomavirus, and herpes zoster be done before patients receive treatment with either a DMARD or a biologic.

“These recommendations, which focus on common clinical scenarios, should be used as a guide for clinicians treating [rheumatoid arthritis] patients, with the clear understanding that the best treatment decision can only be made by the clinician in discussions with patients, taking into account their risk/benefit assessment, including consideration of comorbidities and concomitant medications, patient preferences, and practical economic considerations,” Singh and colleagues concluded.

Evolving Therapies

In an editorial accompanying the recommendations, David I. Daikh, MD, PhD, of the University of California San Francisco, and E. William St. Clair, MD, of Duke University in Durham, N.C., observed that much has changed in the four years since the last recommendations, with the availability of new drugs and increased experience with the older agents.

They called on the ACR to continue refining treatment recommendations as therapeutic strategies evolve.

“The ACR has embarked on a major and important road to provide rheumatologists with sound, evidenced-based guidance for the management of rheumatic disease. The 2012 [rheumatoid arthritis] treatment recommendations represent another step down this road,” wrote Daikh and St. Clair.

Primary source: Arthritis Care & Research
Source reference: Singh J, 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: 625-639; DOI: 10.1002/acr.21641.

Additional source: Arthritis Care & Research
Source reference: Anderson J, et al “Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice” Arthritis Care Res 2012; 64: 640-647; DOI: 10.1002/acr.21649.

Additional source: Arthritis Care & Research
Source reference: Daikh D, St. Clair E “Updated recommendations for the treatment of rheumatoid arthritis: another step on a long road” Arthritis Care Res 2012;64:648-651; DOI: 10.1002/acr.21659.