Remission

Remission means different things to different people. To some it’s the total absence of symptoms, while other patients might feel their in remission if they only have an occasional flare of joint tenderness or morning stiffness.

Measuring Disease Activity in Rheumatoid Arthritis

How do doctors measure disease activity in patients with RA and what do those scores mean?

By Timothy Gower

Most rheumatologists have long relied primarily on their own clinical judgment and intuition when deciding whether a patient with rheumatoid arthritis (RA) requires a change in treatment to keep the disease under control. However, there is now solid evidence that RA patients do best when doctors use a “treat to target” approach – that is, adjusting a patient’s therapy as necessary to achieve a specific goal.

But the treat-to-target philosophy requires information about your disease activity. How can you hit your target unless your doctor knows when to increase a dose or add a drug to your regimen?

In 2012, the American College of Rheumatology (ACR) recommended six tools for the systematic measurement of disease activity in RA. Using these tools consistently can help identify changes that you may not notice and that may escape a physician’s observation, says rheumatologist Salahuddin Kazi, MD, of the Dallas VA Medical Center, a coauthor of the ACR guidelines. Responding to these changes as soon as possible by modifying treatment can help limit the risk for long-term joint damage, says Dr. Kazi.

The sooner you get the right treatment, the less likely you will suffer long-term joint damage, Dr. Kazi points out. Your doctor can’t literally feel your pain, but he or she could help ease it by using formal tools to track your disease activity.

Many Tools Available

While there may be no acknowledged “best” test for measuring disease activity in RA, dozens of methods have been devised. Broadly speaking, these tests fall into three categories:

• Patient questionnaires. A simple version is the Visual Analog Scale (VAS), which features a horizontal line with the words NO PAIN on the left and WORST PAIN on the right; you make a mark on the line to indicate how you are feeling. Other more detailed questionnaires ask about how much difficulty you have performing daily activities, such as bathing, dressing and climbing in and out of cars.
• Joint counts. A doctor examines a specific set of joints and tallies how many are swollen and/or tender. The most common of these tests is the DAS28, which generates a “disease activity score” (hence the acronym “DAS”) based on an examination of 28 joints as well as other factors.
• Lab tests. The most widely used tests to measure markers of body-wide inflammation are erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

Most of the ACR-approved measurement tools combine one or more of these elements. For example, the DAS28 combines a joint count, lab test (either the ESR or CRP) and a VAS. These data are plugged into a formula, which produces a number between 0 and 10 that reflects how well your RA is controlled. If the number rises over time, a change in treatment is probably in order.

In a British study, researchers followed 111 RA patients. Half of the participants were cared for by physicians who relied on their own observations to determine whether a patient’s arthritis was improving or worsening. The other half saw physicians who used DAS28. Two years later, 65% of the patients tracked with DAS28 were in remission, compared to just 16% of patients in the usual-care group.

Assessment Tools Not Always Used

Most disease-activity measuring tools were designed for use in clinical studies, and they can be time-consuming and complicated to use. Rheumatologist Nathan Wei, MD, of Frederick, Md., occasionally uses the DAS28 in his practice. However, he says, “I spend more time asking patients, ‘How are you doing?’” He’ll then consider what the patient says about his or her condition, the results of lab tests, and an occasional imaging exam to make treatment decisions.

Physician surveys, however, show that rheumatologists in general place a much higher value on joint counts than on patient feedback when formulating treatment plans. Yet, studies show that patient questionnaires—which are easy to use and require no time or effort on behalf of the physician—can be as effective as the DAS28 for monitoring disease activity.

One ACR-endorsed tool, the Routine Assessment of Patient Index Data 3 (RAPID3), asks patients how limited they are in performing specific daily activities, whether they are having sleep or emotional difficulties, and to rate their pain and overall health on a scale of 0 to 10. “The RAPID3 takes about a minute to complete, seconds for a nurse to grade, and then you have a numerical value of how a patient is doing,” says Patricia Daul, RN, executive clinical director at Buffalo Rheumatology.

RA patients at Daul’s clinic are monitored with regular VAS and RAPID3 testing, which she says has improved care. “Sometimes we’re like cheerleaders, trying to keep patients on therapy,” says Daul. When a patient complains that her medication isn’t working, Daul can point to how his or her test scores have improved over time. That’s often all the motivation a patient needs to stay the course.

Clinical Judgment Always First

“There’s no advantage of one tool over another. They all have reasonable evidence of validity,” says University of Arkansas rheumatologist Nasim Khan, MD, who studies methods for measuring disease activity in RA patients. “More and more practices are adopting some objective fashion of documenting RA activity and making decisions based on that,” he says. “That’s a good thing.”

Dr. Kazi says that doctors still need to use their training and clinical judgment when treating RA patients. Yet it’s clear that adding any of the ACR-endorsed tests can help doctors better manage your RA.

Why Your RA Went Into Remission, but Relapsed

You may achieve remission, but it doesn’t always last. Here’s a look at why – and what you can do to keep symptoms at bay.

By Timothy Gower

Many people with rheumatoid arthritis (RA) can silence their symptoms and halt progression of the disease thanks to biologic medications and more aggressive treatment approaches. Yet some patients who achieve remission struggle to sustain it, research shows. In a 2012 study published in Arthritis Research & Therapy, doctors at Brigham and Women’s Hospital in Boston tracked the progress of 394 RA patients from the time their disease went into remission. A year later, half of the patients had relapsed at some point. Researchers checked on the patients after another year and found that only about one-quarter of the relapsed patients had returned to a state of remission.

Defining Remission

Remission means different things to different people. To some it’s the total absence of symptoms, while other patients might feel their RA is in remission if they have only an occasional flare of joint tenderness or morning stiffness. The American College of Rheumatology has published specific criteria for defining RA remission. Regardless of how you define remission, there’s little ambiguity when a relapse occurs: symptoms you once had under control return, your quality of life diminishes and damage to your joints could be worsening. Understanding why relapses occur may help you maintain remission or quickly recover if you have a setback.

Stopping Medication Can Trigger Relapse

One reason you may have a remission relapse is simple: you stop taking your medications. When an RA patient achieves remission, some doctors will taper treatment, either by decreasing the dose of medication or increasing the time between treatments. In other cases, a doctor might decide a patient can attempt to go without any medication at all. The purpose of reducing or eliminating a patient’s medication is to minimize the risk of side effects that accompany today’s powerful medications.

However, someone who had been in remission can have their symptoms return, explains rheumatologist Theodore Fields, MD, clinical director of the Early Arthritis Initiative in the Inflammatory Arthritis Center at New York City’s Hospital for Special Surgery. “I have some patients who have been off medication for a couple of years and stayed in remission,” says Dr. Fields. But that’s true for only a small number of patients, he’s quick to add.

Little is known about which RA patients in remission might be able to go drug-free, although some evidence hints that those who received early and aggressive treatment for the disease might be the best. However, patients who have mild symptoms, but aren’t in total remission, are definitely not candidates for the “cold turkey” approach, stresses Dr. Field. The risk of relapse and a worsening of symptoms is too great.

Biologics Can Stop Working and Trigger Relapse

Scientists are examining a more confounding question about patients with RA who are in remission and then relapse: Why does it occur in people who are still taking medications? “That can happen within months or even many years after a patient has been on a drug,” says John Hardin, MD, professor of medicine in the division of rheumatology at the Albert Einstein College of Medicine, in the Bronx, New York.

The problem, explains Dr. Hardin, appears to be that some people with RA eventually become resistant to the very biologic medications that allowed them to attain remission. This phenomenon occurs when the body develops antibodies that counteract the benefit of the drug. Normally, antibodies protect you from germs and other harmful substances that enter the body. However, scientists now know that some patients start producing antibodies that block the work of biologic drugs. As the drug becomes less effective, a patient in remission will discover that his or her joint symptoms have returned.

Switching RA Medications May Help

Fortunately, an antibody that dampens the benefits of one biologic drug typically doesn’t target others, notes Dr. Hardin. “Switching to an alternative TNF inhibitor often provides an effective therapy,” he says. Moreover, there’s a critical strategy that can help prevent biologic-blocking antibodies from causing problems. Combining a biologic medication with a disease-modifying anti-rheumatic drug (DMARD) such as methotrexate or azathioprine significantly reduces the risk of developing blocking antibodies, according to a scientific review published in JAMA Internal Medicine in 2013.

Alternating Remission and Relapse

About one-third of people with RA have alternating periods of remission and relapse no matter what therapy they receive, says Dr. Hardin, although no one knows why this happens. One intriguing, if surprising, theory holds that certain forms of bacteria and other microbes in the human digestive tract may influence the severity of RA. Studies have confirmed that diet and other factors can alter the composition of bacteria in the gut. “A change in that bacterial flora could potentially change activity of the disease in an individual,” says Dr. Hardin. However, this theory is in its infancy, he notes, adding that understanding which RA patients in remission are most at risk for relapse, and why, is a critical and active area of investigation.

See Your Doctor if You Relapse

If you are in remission and joint pain and stiffness start to flare, tell your doctor soon. “Flares are important,” says Dr. Fields. “They may be telling you that a drug that was initially working is losing its effectiveness.” Seeing your doctor promptly allows him or her to adjust your treatment plan, which can prevent serious damage to your joints and help you feel better.

Combating High Disease Activity in Early RA

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

By Tim Gower

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.nbsp;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.”

Remission! Now What?

If your RA is in remission, you may want to take less medication or even a drug holiday.

By Beth Axtell

There is no cure for rheumatoid arthritis (RA), but remission sure feels like one. Today, early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) and biologics makes remission more achievable than ever before. But how likely are you to reach remission, and how likely are you to sustain it? And when you reach it, do you stay on your medications or go off of them?

When remission in RA was first defined 1981, it was characterized as elimination of all disease. “That’s a very hard target. We’re more likely to be able to reach limited or small amount of disease,” explains David T. Felson, MD, professor of medicine at Boston University and a practicing rheumatologist.

With that in mind, the medical community created new guidelines in 2011. Representatives of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) developed criteria for defining remission so researchers could compare the effectiveness of different treatment regimens. (See “Definitions of Remission” below.)

The Odds of Remission

Because the definition of RA remission has been subjective in the past, published rates vary greatly, ranging from as little as 10% to more than 60%. Certain factors will bring you to the higher end of that range, the most important of which is early diagnosis and aggressive treatment.

“When treated early with DMARDs and biologics, remission rates can exceed 60%,” says Paul Emery, MD, director, Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, United Kingdom, and one of the authors of the ACR/EULAR definition. For people who don’t begin treatment within two years of first symptoms or who don’t start biologics early in the course of disease, remission rates will range from 10% to 33%, as reported in various studies.

Having low disease activity levels at the start of treatment is also a predictor of being able to attain and maintain remission. It makes sense – a less active disease is easier to quiet.

Being a man will slightly increase your chance of remission. A study published in Arthritis Care & Research in 2012 found that men are 38% more likely to achieve and sustain remission during the first two years of having RA than women. But those gender differences don’t last once patients have the disease for more than two years.

Being negative for the disease markers anti-cyclic citrullinated peptide (anti-CCP) antibody, rheumatoid factor and the shared epitope have been associated with a higher chance of realizing remission. In a study published in Rheumatology in 2012, 20% of anti-CCP-negative patients attained and maintained remission, but only 2–5% of the anti-CCP-positive patients maintained remission.

Drug-free Remission

Once remission has been achieved, whether you stop taking your RA medication is up to you and your doctor. Vivian Bykerk, MD, director of the Inflammatory Arthritis Center of Excellence, Hospital for Special Surgery, New York City, makes sure her patients maintain remission-level symptoms for at least one year before reducing their medications.

“Generally I will slowly taper drugs one at a time: first steroids [earlier than one year], then biologics and finally methotrexate,” she says.

Dr. Emery keeps patients in a medicated remission for six months and then slowly reduces the medication dosages. “Remission is attainable for a good number of people – if you get diagnosed early and treated aggressively – but sustaining a drug-free remission for more than a year or so is unlikely,” he says. In the BEST study, published in the Annals of Rheumatic Diseases in 2011, 46% of the patients who achieved remission and stopped taking their medication had to restart therapy after five months.

While complete treatment withdrawal may be effective for a small number of patients, maintaining remission with a reduced-dose regimen, as Dr. Emery indicated, is likely the best option for a majority of people. That’s because the disease may still be active even though signs of it appear to be gone. A 2015 study published in Arthritis Care & Research indicates that inflammation and joint damage may continue even in the absence of pain and apparent swelling. In such cases, magnetic resonance images may reveal underlying inflammation.

Other studies strengthen the case for reducing medication dosage rather than stopping completely. The PRIZE study, published in the New England Journal of Medicine in 2014, analyzed patients with early RA. Significantly more patients who received the reduced-dose DMARD therapy remained in remission than patients who received no therapy after remission was achieved.

The RETRO study, presented at the 2014 ACR meeting, evaluated reducing, discontinuing, or continuing therapy in RA patients with stable, long-lasting remission. The patients that reduced or discontinued treatment were more likely to experience flares than the patients who continued full-dose treatment.

Should You Take a Drug Holiday?

Many doctors favor reducing dosages in hopes of maintaining remission, but taking a drug holiday could be an option.

If you and your doctor decide you are a candidate for a drug holiday – a temporary stoppage of treatment – consider a few factors: the potential effect on your medication eligibility with your insurance company, the effectiveness of the drug when you restart it, and whether underlying joint damage continues even when RA is in remission.

“Patients may have to change to another biologic by their insurer if, for example, the formulary has changed,” says Dr. Bykerk. “Also, if the same biologic is reintroduced, there is a chance that the patient may have developed anti-drug antibodies to the biologic, resulting in a worse response when using it the second time around.”

If you achieve remission, you and your doctor can weigh the benefits and risks of taking a drug-free holiday. During this time, it’s important that your doctor monitors you closely for signs of worsening disease activity or joint damage. 

Definitions of Remission in Rheumatoid Arthritis

The ACR and the EULAR developed criteria defining remission in RA in 2011. These criteria are used by scientists when conducting clinical trials. Your rheumatologist may use these or slightly different measures to determine if your disease is in remission:

• One or fewer swollen joints
• One or fewer tender joints
• An assessment by the patient that on a 0–10 scale, arthritis activity is 1 or less
• A blood test showing little or no inflammation in levels of C-reactive protein, a key marker of inflammation

A second definition uses the Simplified Disease Activity Index to measure disease activity. It consists of a sum score of the four measures in the first definition plus a physician assessment.