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Changing the RA Referral Paradigm


With a growing shortfall of rheumatologists, primary care may play a greater role in the initiation of long-term therapy. Part 3 of a Special Report.

Diagnosis and early initiation of disease modifying antirheumatic drug (DMARD) therapy for rheumatoid arthritis (RA) leads to improved long-term outcomes.1,2 This places a burden on primary care physicians (PCPs) to identify disease early and then initiate referral to rheumatology for further care. [[{"type":"media","view_mode":"media_crop","fid":"55953","attributes":{"alt":"","class":"media-image media-image-right","height":"196","id":"media_crop_6869494857584","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7024","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"border-width: 0px; border-style: solid; margin: 5px; float: right;","title":" ","typeof":"foaf:Image","width":"209"}}]]

To date, this paradigm has been the typical pathway of RA management, largely because the perceived and real toxicities of DMARDs have made many PCPs understandably uncomfortable with their use without direct guidance from a rheumatologist.

Given the realities of current long wait times for rheumatology visits in many areas, insurance issues, and worsening workforce issues likely in the near future, the paradigm may need to change. PCPs may play a greater role in the initiation of long-term therapy as well as management.

The PCP's typical RA referral

The following are included in a referral to rheumatology for suspected RA:

History and physical examination, with attention to the joint examination and tender and swollen joints.

Laboratory findings, such as rheumatoid factor (RF) and antibodies to citrullinated protein antigens (ACPA).

• Inflammatory test results, such as the erythrocyte sedimentation rate and C-reactive protein level.

• Results of other autoimmune testing (eg, antinuclear antibody testing).

• Lab results from complete blood cell counts, metabolic panels, and infection testing (eg, hepatitis B and C, HIV, and tuberculosis), which can help the rheumatologist assess the patient’s overall health and potential safety issues regarding treatment.

Results of imaging. If possible, have the patient hand-carry the images to the rheumatologist.

Documentation of any treatments that have been provided and their efficacy.

Next: Treatment Caveat

Caveat for initiating treatment for rheumatoid arthritis

As to which therapies PCPs may initiate, here’s an important caveat:

Because agents such as NSAIDs make patients with RA feel better but in most cases do not alter long-term outcomes, they should not be used as monotherapy to manage RA beyond an initial diagnostic period.

A safe, universal approach that PCPs may take to initiate DMARD therapy in RA has not yet been developed. However, if based on the above discussion the PCP has a high degree of diagnostic certainty that a patient has RA, initiation of corticosteroid therapy at a prednisone equivalent of 20 mg/d or less is reasonable.

An important consideration for a PCP who is considering starting prednisone:

Once started, corticosteroids can resolve or improve the synovitis fairly quickly, making confirmation of diagnosis by the consulting rheumatologist difficult, especially in the absence of other supportive objective data, such as positive RF or ACPA or both.

The first-line DMARD

Methotrexate (MTX) generally is considered to be the first-line DMARD for RA, because 30% of patients respond well to MTX monotherapy.3 Although PCPs do not typically start DMARD therapy, it is not unreasonable for a PCP to initiate MTX (typically at 15 mg orally per week) if there is diagnostic certainty, the PCP is comfortable doing so, and the appropriate safety issues have been addressed.

Important considerations before initiation of MTX include assessing for underlying comorbidities (eg, alcohol use and infectious hepatitis) that may affect drug safety, pregnancy testing and appropriate birth control in women of child-bearing age, and adequate explanation of risks and benefits. If a timely evaluation by a rheumatologist is not available, at minimum a conversation with a local rheumatologist may help guide the PCP in initial management.

Next: An Explosion of Biologics

An explosion of biologics and other medications

There has been an explosion of additional therapies for RA, including multiple synthetic DMARDs (sDMARDs) and biologic DMARDs (bDMARDs), since the late 1990s. Initiation of these agents is likely beyond the scope of most PCPs, but familiarity with the medications and their mechanisms of action may be useful.

Following are the more common medications currently used in treating patients with RA:

Synthetic small molecules (sDMARDs)

MTX: Interferes with folic acid metabolism and B cell and T cell function and proliferation. Increases intracellular adenosine levels. Typically dosed orally but can be administered subcutaneously, which delivers more potent therapy and may alleviate GI adverse effects.

Leflunomide: Blocks DNA formation by inhibiting pyridmidine synthesis through the enzyme dihydrooroteate dehydrogenase, leading to decreased B cell and T cell proliferation and inflammation.

Hydroxychloroquine: Raises intracellular pH and downregulates inflammation and antigen presentation.

JAK/STAT inhibitors (eg, tofacitinib): Oral agents that block janus kinases (JAKs), resulting in decreased DNA transcription of inflammatory factors.

Biologic agents (bDMARDs)

Anti–tumor necrosis factor (anti-TNF) therapies (eg, etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab): Block the action of TNF, a powerful driver of inflammation in RA joints.

Anti-interleukin-1 therapy (anakinra): Blocks IL-1 receptors and thereby decreases IL-1 effect.

Anti–B cell therapy (eg, rituximab): Depletes B cells at some phases of development. Reduces B cell– generated inflammation and antigen presentation. May also decrease autoantibody production.

Anti–IL-6 receptor therapy (eg, tocilizumab): Binds to the IL-6 receptor and thereby decreases IL-6 effect.

Costimulatory inhibitor (eg, abatacept): Multiple molecules need to interact between antigen-presenting cells and T cells to drive T cell activation. Costimulatory inhibitors such as abatacept (a fusion protein of CTLA-4 and Ig) bind to proteins (B7) that participate in activating antigen-presenting cell and T cell interactions and result in decreased T cell activation or increased tolerance.

Other medications

Corticosteroids (eg, prednisone): Powerful, broad, and quick-acting immunosuppressive actions and DMARD activities. Many adverse effects-many rheumatologists use early in RA but try to stop after 6 to 12 months, although many patients receive corticosteroids for RA for years.

NSAIDs: Block prostaglandins and reduce local inflammation and pain. These agents do not stop joint destruction and therefore should not be used alone to treat RA.

• Click here to go to the next installment in this Special Report, RA Comanagement and the Future.

For earlier installments:

8 New Rheumatoid Arthritis Findings-Slide Show Part 2: Early Diagnosis of Rheumatoid Arthritis in Primary CarePre-test: Rheumatoid Arthritis Special ReportPart 1-Introduction: Rheumatoid Arthritis in Primary Care



1. Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388:2023-2038.

2. Espinoza F, Fabre S, Pers YM. Remission-induction therapies for early rheumatoid arthritis: evidence to date and clinical implications. Ther Adv Musculoskelet Dis. 2016;8:107-118.

3. 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 (Hoboken). 2012;64:625-639.

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