Combating High Disease Activity in Early RA

Achieving improvement – and possibly remission – in rheumatoid arthritis requires a multifaceted and vigilant approach.


Dramatic improvements in the way rheumatoid arthritis (RA) is treated have given many newly diagnosed people the hope of achieving remission or at least getting inflammation under tight control, a state doctors call “low disease activity.”

Either goal is easier to achieve for some than others. Those who arrive in their rheumatologist’s office with signs that their RA is “operating on all gears” are likely to face challenges getting the inflammation controlled. Having high disease activity for sustained periods raises the risks of permanent joint damage and comorbid conditions. Therefore, disease management requires greater watchfulness and likely more aggressive treatment.

Are You High Risk?

A comprehensive evaluation is critical at diagnosis, says M. Elaine Husni, MD, rheumatologist and director of the Arthritis & Musculoskeletal Treatment Center at the Cleveland Clinic. A solid baseline assessment of disease activity gives your doctor a starting point from which to monitor whether your disease is improving, remaining stable or worsening.

Key factors are measured at regular intervals to determine whether the disease is responding well to treatment. Even with high disease activity, your outcome can still be good with proper treatment. The following indicators help guide your treatment plan. 

  • Number of swollen and tender joints. “If you have three or more affected joints,” says Dr. Husni, “the more likely your RA may progress and need more frequent evaluations.”
  • High baseline level of systemic inflammation. Simple blood tests for erythrocyte sedimentation rate (ESR or “sed rate”) and/or C-reactive protein (CRP) measure body-wide inflammation. Studies suggest that achieving remission can be extremely difficult if your baseline CRP level is 20 mg/L or higher.
  • Evidence of bone erosion on X-rays. Evidence of joint damage in a newly diagnosed RA patient is a good predictor that the disease will be difficult to manage, according to a study published in Arthritis Care & Research in 2013.
  • Positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptides (anti-CCP) antibodies. If you have these immune system proteins in your blood, you are prone to disease progression, Dr. Husni explains.
  • Level of functional limitation. Difficulty climbing stairs, dressing and performing other activities of daily living at diagnosis could be a sign of increased inflammation or joint erosions.
  • Presence of nodules. Rheumatoid nodules (lumps of tissue) may occur under the skin on the elbows and fingers.
  • Presence of one or more conditions related to RA. Having one or more of these arthritis-related conditions signals a potential treatment challenge ahead: vasculitis (blood vessel inflammation), Felty’s syndrome (enlarged spleen and very low white blood cell count) or Sjögren’s syndrome (poor function of the glands that produce tears and saliva).

Crafting the Best Treatment Approach

Many RA patients are treated initially with methotrexate or a similar drug from the class called disease-modifying antirheumatic drugs (DMARDs). But a poor prognosis suggests that methotrexate alone may not be enough to bring disease activity under control. Your doctor may combine two DMARDs. In some cases, a combination of three DMARDs can be very effective.

Another approach is starting treatment with a biologic drug – either with or without methotrexate. A TNF inhibitor is usually tried first, but other types of biologics are also available. TNF inhibitors block the action of tumor necrosis factor, a protein that promotes inflammation.

When Treatment Changes Are Necessary

Biologics have proven to be game-changing drugs for RA patients, but the first one you try may not work for you. A 2009 Arthritis Research & Therapy review showed that up to 40% of RA patients’ disease didn’t respond adequately to a single TNF inhibitor or they experienced an initial period of symptom relief, but the benefits eventually faded.

In some cases, the phenomenon occurs because patients build up a tolerance to the medication, says Olivia Ghaw, MD, assistant professor of medicine in the division of rheumatology at Mount Sinai Hospital in New York City. Over time, she explains, the body’s immune system begins to recognize these medicines as foreign bodies, which they attack, making the drug less effective. However, this problem appears to be less common in patients who take a combination of a biologic plus methotrexate, says Dr. Ghaw, as the latter appears to prevent the body from forming antibodies to biologics, reducing the risk of developing drug tolerance.

If you take a TNF inhibitor for three months and your RA disease activity remains high, switching to another TNF inhibitor is an option. However, if the second TNF inhibitor fails, too, it’s unlikely that a third will help, says Dr. Ghaw. For such patients, the next choice may be a different biologic drug that targets another source of inflammation.

With the many RA medications available today, persistence can help you find a therapeutic plan that does more than stop disease progression. “I don’t want my patients to have just an ok day,” says Dr. Ghaw. “I want them to feel good – back to normal.”

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