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Treating rheumatoid arthritis: Strong recommendations were made for best drugs, but most evidence was not of high quality

Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68:1-26.

Review and guideline question

In people who have rheumatoid arthritis, what are the best recommendations for drug treatments from the American College of Rheumatology (ACR)?


Rheumatoid arthritis is a chronic condition. It causes inflammation of the small joints, usually in the hands and feet. It is an autoimmune disorder that occurs when your own immune system attacks your joints.

Symptoms of rheumatoid arthritis include tender and swollen joints, pain, and stiffness. There is no cure for the condition, and treatment is used to control symptoms and prevent joint damage. Several types of drugs with different side effects are used to treat rheumatoid arthritis. Your doctor will generally prescribe the drugs with the fewest potential side effects first, and try other drugs or combinations of drugs if your symptoms continue or worsen.

How the review was done and recommendations made

The researchers did a systematic review, searching for studies that were published in English up to September 2014. They found 108 systematic reviews, randomized controlled trials, or non-randomized studies.

The key features of the studies were:

  • people were 18 years of age or older and had rheumatoid arthritis; and
  • drug treatments were traditional disease-modifying antirheumatic drugs (DMARDs) (methotrexate, hydroxychloroquine, leflunomide, sulfasalazine), biologic DMARDs including tumor necrosis factor inhibitors (TNFis) (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) and non-TNF biologic drugs (abatacept, rituximab, tocilizumab), and tofacitinib.

A panel of experts, including doctors who specialize in treating arthritis and patient representatives, made recommendations for drug treatments based on the results of the studies, clinical experience, and patient values and preferences. Treatment recommendations could be classified as strong (most patients would want the treatment and few would not) or conditional (more than 50% of patients would want the treatment but many would not). Only the strong recommendations for early (disease or symptom duration of less than 6 months) and established (disease or symptom duration of 6 months of more) rheumatoid arthritis are reported here. Recommendations for people who are considered high risk because of other conditions (e.g., hepatitis B or C infection, congestive heart failure, previous cancer, or previous serious infections) are not reported here.


The American College of Radiology made 8 strong recommendations for drug treatments in rheumatoid arthritis. There wasn’t much high-quality evidence for the treatments.

American College of Rheumatology strong recommendations* for drug treatment in rheumatoid arthritis (RA)



Number of trials (quality of evidence)

People with early RA or established RA

Use a treat-to-target approach

1 trial (low quality) in early RA

3 trials (moderate quality) in established RA

People with early RA or established RA who have low disease activity and have not previously used DMARDs

Use a DMARD alone (with methotrexate as the preferred drug)

9 trials‡ (low quality)

People with early RA who have moderate or high disease activity despite using a DMARD alone

Use a combination of DMARDs or a TNFi or a nonTNF biologic drug, with or without methotrexate

3 trials‡ (low quality)

People with established RA who have moderate or high disease activity despite using a DMARD alone

Use a combination of DMARDs or add a TNFi, a nonTNF biologic drug, or tofacitinib, with or without methotrexate

8 trials (high quality) for tofacitinib;

6 trials‡ (moderate to very low quality) for other drugs

People with established RA who have moderate or high disease activity despite using a TNFi alone

Add 1 or 2 DMARDs

6 trials (high quality)

People with established RA who have low disease activity but not remission

Continue use of DMARDs, TNFis, nonTNFi biologic drugs, or tofacitinib

2 trials (high quality) for TNFis

1 trial (moderate quality) for DMARDs

0 trials‡ for other drugs

People with established RA that is in remission

Do not stop all drugs used to treat RA

0 trials‡

People with early or established RA who are using biologic drugs

Use killed/inactivated vaccines (e.g., pneumococcal vaccine) if indicated

3 trials and 5 other studies‡ (very low quality)

DMARD = disease-modifying antirheumatic drug; TNF(i) = tumor necrosis factor (inhibitor).

*Treatments with strong recommendations are those that most patients would want and few would not want. However, doctors and patients should discuss treatment options, and final treatment decisions should be based on individual patient circumstances.

†Early RA = disease or symptom duration of less than 6 months. Established RA = disease or symptom duration of 6 months or more.

‡No trials directly compared the treatments of interest in the relevant group. Recommendations without direct evidence were based on data from other patient groups (e.g., people with a different level of disease activity), other treatment comparisons, clinical experience, and patient values and preferences.


Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

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