Adolescents with fibromyalgia who are physically active report lower levels of pain and disability, according to findings of a multicenter study published in The Journal of Pain, published by the American Pain Society.
Led by researchers at Cincinnati Children’s Hospital, this study is the first to use actigraphy-based physical activity monitoring to measure the relationship of pain, perceived functional impairment and depressive symptoms in adolescents with juvenile primary fibromyalgia syndrome (JPFS). For the research, 104 adolescents ages 11-18 were fitted with hip-mounted actigraphs for one week. The battery-powered device measures the amount and intensity of human physical activity.
The research objectives were to measure physical activity levels in adolescents with JPFS, examine differences and characteristics of high and low activity subjects, and explore the impact of psychiatric disorders on physical activity. The objective activity measurements were intended to address concerns about the reliability of self reports on the impact of pain on physical activity, and validate observations that some JPFS patients remain vigorously active while enduring significant pain.
Results showed that adolescents with JPFS did not engage in physical activities and aerobic exercise at levels recommended by their physicians. Just 23 percent of the subjects participated in 30 minutes of daily moderate-to-vigorous physical exercise, and only one adolescent engaged in 60 minutes of exercise every day. Low levels of exercise in these patients are troubling to clinicians who view exercise as a major component for improved pain management.
Another key finding was that higher pain intensity ratings were not significantly associated with lower levels of activity in the group as a whole. The authors noted that adolescents with JPFS have other symptoms that may diminish interest in physical activity, such as fatigue and impaired sleep. The authors also noted that higher pain levels in the least active group may be related to their decreased activity or vice versa.
Further, the inactive group had higher levels of depressive symptoms and functional disability, according to parent reports. However, in the small number of JPFS patients who maintained very high levels of physical exercise, the reported pain levels were lower than the inactive group, perhaps due to exercising, and their parents reported they had lower depressive symptoms and disability than inactive subjects.
Is the science of diagnosing pain causing a number of pain sufferers to defend their honor? Research out of the University of Cincinnati is examining the diagnosis of pain that evades scientific testing, and the additional emotional suffering that can result for the patient.
The research by Elizabeth Sweeney, a doctoral candidate in UC’s Department of Sociology, was presented August 16 at the 105th annual meeting of the American Sociological Association in Atlanta. The paper, “Defining Reality: How Biomedical Researchers Determine the Existence of Pain,” analyzed more than 20 articles randomly selected from the peer-reviewed international academic journal PAIN®, the official publication of the International Association for the Study of Pain.
Sweeney examined the journal’s content to determine how pain is measured and defined in terms of type of pain, location of pain, its causes, severity, duration, response to treatment, methods of detection and symptoms. Because of these evidence-based diagnostic tests, the paper states that sufferers of chronic pain — conditions that frequently cannot be localized or pointed out on a scan or test — are often put in the position of defending the legitimacy or the reality of their condition.
Examples of these chronic pain sufferers of unexplained or “contested” illnesses can include patients with Chronic Fatigue Syndrome, Complex Regional Pain Syndrome (CRPS), fibromyalgia and Gulf War Syndrome.
“It is apparent from this research that the missing link in much of biomedical research is any viable attempt to understand the subjective experience of pain,” Sweeney writes.
“A diagnosis, simple though it may seem, constitutes not only the legitimacy of one’s illness, but also the validation of one’s sanity and honor — evidence that the patient is not psychologically unstable and is not ‘faking’ it,” says Sweeney.
The paper details that the journal, PAIN®, which for more than 30 years has focused on the study and research of pain, is considered one of the world’s premiere sources of biomedical research on pain. The articles that were analyzed were published between May 2008 and May 2009.
Demonstrating the challenges that pain and chronic pain pose to Western medicine, Sweeney concludes that deconstructing biomedical research on pain will better pave pathways of understanding in diagnosing and treating chronic pain sufferers.
People who have the common chronic pain condition fibromyalgia often report that they don’t respond to the types of medication that relieve other people’s pain.
New research from the University of Michigan Health System helps to explain why that might be: Patients with fibromyalgia were found to have reduced binding ability of a type of receptor in the brain that is the target of opioid painkiller drugs such as morphine.
The study included positron emission tomography (PET) scans of the brains of patients with fibromyalgia, and of an equal number of sex- and age-matched people without the often-debilitating condition. Results showed that the fibromyalgia patients had reduced mu-opioid receptor (MOR) availability within regions of the brain that normally process and dampen pain signals — specifically, the nucleus accumbens, the anterior cingulate and the amygdala.
“The reduced availability of the receptor was associated with greater pain among people with fibromyalgia,” says lead author Richard E. Harris, Ph.D., research investigator in the Division of Rheumatology at the U-M Medical School’s Department of Internal Medicine and a researcher at the U-M Chronic Pain and Fatigue Research Center.
“These findings could explain why opioids are anecdotally thought to be ineffective in people with fibromyalgia,” he notes. The findings appear in The Journal of Neuroscience. “The finding is significant because it has been difficult to determine the causes of pain in patients with fibromyalgia, to the point that acceptance of the condition by medical practitioners has been slow.”
Opioid pain killers work by binding to opioid receptors in the brain and spinal cord. In addition to morphine, they include codeine, propoxyphene-containing medications such as Darvocet, hydrocodone-containing medications such as Vicodin, and oxycodone-containing medications such as Oxycontin.
The researchers theorize based on their findings that, with the lower availability of the MORs in three regions of the brains of people with fibromyalgia, such painkillers may not be able to bind as well to the receptors as they can in the brains of people without the condition.
Put more simply: When the painkillers cannot bind to the receptors, they cannot alleviate the patient’s pain as effectively, Harris says. The reduced availability of the receptors could result from a reduced number of opioid receptors, enhanced release of endogenous opioids (opioids, such as endorphins, that are produced naturally by the body), or both, Harris says.
The research team also found a possible link with depression. The PET scans showed that the fibromyalgia patients with more depressive symptoms had reductions of MOR binding potential in the amygdala, a region of the brain thought to modulate mood and the emotional dimension of pain.
The study subjects were 17 women with fibromyalgia and 17 women without the condition.
The senior author of the paper was Jon-Kar Zubieta, M.D., Ph.D., the Phil F. Jenkins Research Professor of Depression in the U-M Department of Psychiatry and a member of U-M’s Molecular and Behavioral Neuroscience Institute, Depression Center and Department of Radiology. Other authors were Daniel J. Clauw, M.D.; David J. Scott, Ph.D.; Samuel A. McLean, M.D., MPH; and Richard H. Gracely, Ph.D.
The research was supported by grants from the Department of the Army; the National Center for Research Resources, a component of the National Institutes of Health; and the NIH. Harris was supported by an NIH–National Center for Complementary and Alternative Medicine Grant. McLean was supported by an NIH grant.
Pregnant women with fibromyalgia (FM) experience significant pain, fatigue and psychological stress, symptoms that are often misdiagnosed or undertreated as a normal part of pregnancy, according to a pilot study by Karen M. Schaefer, D.N.Sc., R.N., assistant professor of nursing at Temple University’s College of Health Professions. Her research, the first to look at the impact of pregnancy on women with FM, was recently presented at the 2006 Association of Women’s Health, Obstetrics and Neonatal Nurses’ convention in Baltimore.
Fibromyalgia is a chronic condition commonly found in women that causes pain in the muscles and soft tissues of the body. Many sufferers feel weak from fatigue, and the condition, at its worst, can lead to disability.
“Until now, there was only anecdotal evidence suggesting that women with FM had a rougher time during pregnancy,” said Schaefer. “This data is the first step toward gathering hard evidence of FM effects on this group and will hopefully help us identify ways to reduce the impact of fibromyalgia during pregnancy.”
For this study, Schaefer recruited pregnant women with and without FM through an Internet announcement on a fibromyalgia Web site. Study subjects were between the ages of 29 and 31, in their third trimester, with no history of stillbirth and free of chronic illnesses other than FM.
The women were then mailed a questionnaire about fatigue, depression, pain and ability to function. A demographic form was also used to assess the number of painful areas in the body as well as age, marital status, education, hours slept and use of medication.
Schaefer’s results revealed that the pregnant women with fibromyalgia had a hard time functioning, felt more stiff and tired, and experienced pain in more body areas than women without FM.
“Most women with FM have trouble getting this condition properly diagnosed, let alone knowing where to turn for help once their condition is identified. We need to start looking at how FM affects all areas of these women’s lives and come up with ways to provide as much comfort and support as possible,” she said.
Schaefer, whose research focuses on women with chronic illness (fibromyalgia, lupus, ovarian cancer) is currently expanding her study to include a larger group of subjects.
GAINESVILLE, Fla.—The millions of Americans who suffer from fibromyalgia live with a two-edged sword: excruciating pain, accompanied by the doubts of many who dismiss it as a made-up illness invented by a troubled mind.
But researchers at the University of Florida and elsewhere are beginning to piece together clues that reveal the physical basis of the puzzling syndrome that causes severe fatigue and aches, and has defied easy diagnosis.
UF scientists have found an abnormal central nervous system reaction in those with fibromyalgia-the body magnifies ordinary repetitive stimulation into an experience of crippling pain.
“This is particularly important because it has been unclear if fibromyalgia was just an imagined illness or a real syndrome,” said Dr. Roland Staud, an associate professor of medicine at UF’s College of Medicine who also is affiliated with the UF Brain Institute. “We now have good evidence that shows that it’s not a psychological abnormality, butthat there is a neurological abnormality present.”
Staud, who presented his research findings at the annual meeting of the American College of Rheumatology last November, recently was awarded a National Institutes of Health grant worth nearly $800,000 to continue his studies for the next four years. Donald Price, a UFprofessor of oral and maxillofacial surgery, and Charles Vierck, a UF professor of neuroscience, are collaborating on the research. Their goal is to develop a better understanding of the condition, with an eye toward improving diagnostic tests and treatments.
An estimated 3.7 million people in the United States – primarily women who are diagnosed during their 30s and 40s – have fibromyalgia, according to the NIH. A chronic illness with no known cure, its cause also is not known. Researchers have theorized that an injury to the central nervous system or an infectious agent might be responsible for triggeringit in people who have inherited susceptibility. Symptoms include persistent and widespread musculoskeletal pain, fatigue and tenderness in the neck, spine, shoulders and hips.
Staud and colleagues found the central nervous system abnormality byconducting a series of repetitive stimulation tests on people with thesyndrome as well as healthy research participants. The tests involved repeatedly placing warm plates on their hands and arms. The healthy participants felt the sensation but did not report it as pain.
For those with fibromyalgia, however, the sensation would magnify with each repetition into an experience of crippling and unbearable pain.
“When a sensation signal reaches the spinal cord, the signal can be omitted, changed or augmented,” Staud said. “If it is augmented, then something that is innocuous, such as pressure on the skin, can then be perceived as a painful stimulus.”
Jessica LeMay, one of Staud’s patients, has been battling fibromyalgia since 1993. The 30-year-old Lake City resident said the pain starts in one area and usually spreads, sometimes becoming overwhelming.
“I imagine if someone had taken a baseball bat and beaten me with it,that’s got to be what it feels like,” she said. “Depending on the day, I’ll just move out of the way if someone tries to touch me.”
The pain of fibromyalgia often interferes with a person’s working life.
“These are people who are diagnosed in their productive years. Many have personal or professional problems adjusting to the pain experience,” Staud said. “The illness makes some people feel dysfunctional because they can’t do the activities they once did.”
The condition can worsen from stress and inadequate sleep, Staud said. Because living with fibromyalgia often causes stress, and pain makes sleeping difficult, a vicious cycle develops.
LeMay said many people dismiss her condition, not understanding the “huge difference” between her severe fatigue and the healthy person’s occasional tiredness.
“When this fatigue would come about, it’s almost like a weight being dropped on you, and you can’t function anymore,” she said.
LeMay said she is hopeful that Staud’s research will lead to more effective treatment for fibromyalgia patients and better understanding by the general public.
“In our society, you either get better or you die, and fibromyalgiapatients don’t do that,” she said. “We don’t fit in the mold, so people don’t know what to do with us.”
Lupus patients have been waiting a while for some good news. Only one drug, belimumab (Benlysta), has been FDA-approved for lupus in more than 50 years — and that happened back in 2011. Since then, scientists have been trying to develop additional therapeutic agents (and failing for various reasons). But research presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals (ACR/ARP) Annual Meeting in Atlanta suggests that a new lupus medication, anifrolumab, might have the potential to get approved and make its way to market.
The manufacturer, AstraZeneca, is expected to file for FDAapproval in 2020. It’s hardly a slam dunk: The company conducted two phase 3 trials on anifrolumab, and one of them did not hit its primary endpoint, though secondary endpoints suggested that the drug had benefits. The second phase 3 study, which was presented for the first time at the recent ACR/ARP meeting, yielded more consistently positive results.
“I’m optimistic and hopeful that this drug will be approved,” says Chronicwoman medical advisor Vinicius Domingues, MD. “We have one [phase 3] study that was technically negative but with a lot of positives because of the secondary endpoints, plus a second [phase 3] study that was all positive. Patients should know that this is promising.”
The first phase 3 trial was called TULIP 1 (Treatment of Uncontrolled Lupus via the Interferon Pathway). Last August, AstraZeneca reported that anifrolumab failed to meet its primary target in TULIP 1, which was a “statistically-significant reduction in disease activity… as measured by the SLE Responder Index 4 (SRI4) at 12 months.”
SRI4 is a composite score that is often used to measure disease activity in patients with systemic lupus during clinical trials. According to SRI4, anifrolumab was as flop: Patients who added the drug to their treatment regimen did not, on average, fare better than those who added a placebo.
However, secondary endpoints in TULIP 1 found that anifrolumab beat the placebo. Those secondary endpoints included a different composite score of disease activity, called BICLA (British Isles Lupus Assessment Group-Based Composite Lupus Assessment), as well as reduced reliance on corticosteroid drugs.
The results of TULIP 1 appear in the journal Lancet Rheumatology and were discussed at the 2019 ACR/ARP meeting.
TULIP 2, the second phase III study of anifrolumab, used BICLA as its primary endpoint — and met it. TULIP 2, which was also presented at the 2019 ACR/ARP meeting, found that the drug beat the placebo as far as BICLA was concerned. It also determined that patients using it had greater improvements in skin disease and decreased use of corticosteroids.
While it’s true that researchers deliberately switched to a primary endpoint that they were likely to meet when moving from TULIP 1 to TULIP 2, there’s no clear consensus among rheumatologists that SRI4 is “better” than BICLA. In fact, a 2014 study compared these two outcome measures and determined that either one could “likely be an optimal primary endpoint” in a given clinical trial.
According to Northwestern University rheumatologist Michael Putman, MD, reporting on the trials for RheumNow, the SRI4 requires 100 percent improvement in some domains, “whereas with the BICLA you can get a little better across the board.” That might be part of why one endpoint seemed to work and the other didn’t, he said.
Anifrolumab is a monoclonal antibody that inhibits type 1 interferons, proteins that are involved in inflammation. Some lupus patients (but not all) have a “high interferon gene signature.” Scientists are simultaneously developing a test that can be used to identify those individuals. “It can be used to help predict who may or may not respond to this drug,” says Dr. Domingues. “This is an example of precision medicine, and it’s how cancer is being treated nowadays.”
“There has been a case building for many years about the importance of interferons in the pathogenesis of lupus,” Timothy Niewold, MD, Judith and Stewart Colton Professor of Medicine and Pathology and Director of the Colton Center for Autoimmunity at the New York University School of Medicine, told the ACR Daily News. “One of the most exciting recent developments is that drug companies have created agents to target the interferon pathway. It’s been a rocky road, but there have been some positive results.”
If anifrolumab gets the green light from the FDA, patients who haven’t responded well to other lupus treatments — especially those who have a high interferon gene signature — might benefit by including it in their current drug regimen, says Dr. Domingues. (The drug would be an add-on, not a replacement.)
If the drug eventually gets approved, label specifics such as recommended dosing and warnings about side effects would be revealed at that time. In the TULIP 2 study, participants in the treatment group used 300 mg of anifrolumab via infusion every four weeks. Serious adverse events were rare and occurred more frequently among those in the placebo group. The most common side effect experienced by those using anifrolumab was shingles, which occurred in 7 percent of anifrolumab users.
“Giant cell arteritis requires ongoing management, but it does not necessarily require continuous treatment.”
In 2017, tocilizumab (Actemra), a biologic drug that inhibits interleukin-6 (IL-6), was FDA-approved for giant cell arteritis — an inflammation of the lining of the arteries. At the time there was sufficient research showing that tocilizumab was better than prednisone (a steroid) for helping many patients reach remission in GCA. Yet it was unclear whether those who had reached remission should stop taking the drug or if they needed to continue using it.
Now a new study, presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting in Atlanta, offers good news: A sizeable group of those who reached remission with tocilizumab were still in remission two years after stopping the drug.
The new study was an extension of an earlier 52-week study that led to tocilizumab’s FDA approval for giant cell arteritis. The drug is also approved for rheumatoid arthritis, juvenile idiopathic arthritis, and severe cytokine release syndrome.
More than 200 patients who had reached remission by using tocilizumab either once a week or every other week entered the post-marketing arm and were instructed to stop using the drug. According to their findings, 47 percent of those who had been previously taking tocilizumab weekly and 36 percent of those who had previously been taking it every other week remained in remission two years later.
Those who did experience flares were restarted on tocilizumab and/or given steroids. Those who resumed using tocilizumab (with or without a steroid) were once again able to reach remission.
“Giant cell arteritis requires ongoing management, but it does not necessarily require continuous treatment,” lead author John H. Stone, MD, MPH, told the ACR/ARP Daily News. “Patients should be started on tocilizumab as soon as they are diagnosed. The goal should be to get them off steroids as quickly as possible and maintain their response with tocilizumab.”
Some people with rheumatoid arthritis (RA) take a disease-modifying antirheumatic drug (DMARD) and/or a biologic and reach remission. Others try drug after drug after drug and never find one that’s effective — or that treats their symptoms without causing intolerable side effects. At the same time, other patients with active disease refuse to take the most powerful and effective medications on the market or can’t take them because of their medical history or personal risk factors that would make doing so dangerous.
While many scientists are continuing to explore better drug options, some are focused on developing new treatments that aren’t medications at all. One such experimental approach that’s gaining some traction is called vagus nerve stimulation, which entails using electrical impulses to stimulate the vagus nerve — the longest of the cranial nerves that stem from the brain.
The vagus nerve runs from the brain, through the face and neck, and down into the abdomen. It’s a key part of the autonomic nervous system, the division of your nervous system that controls functions you don’t have to think about, such as breathing, digesting food, and the beating of your heart. The vagus nerve is also the home of the inflammatory reflex, a pathway that appears to be crucial for detecting and modulating inflammation.
When something in your body gets injured or attacked by an invader (like a virus or bacteria), the vagus nerve helps decide how strong of an immune response the body should mount. When that response is appropriate, germs get killed off and injured tissue starts to heal. But when it’s too aggressive for the threat at hand — imagine trying to put out a small candle by holding it under a waterfall — you end up with chronic inflammation, which results in joint and tissue damage.
If you have an autoimmune condition, you already know that your immune system is far more revved up than it should be. In the case of RA, the immune system mistakenly tries to attack healthy tissue in the joints as well as in other organs. No one knows exactly what sets RA in motion, but experts do know that inflammatory substances called cytokines play an important role in causing tissue damage. Those cytokines include tumor necrosis factor (TNF) and interleukins (IL), among others.
Scientists now know that the vagus nerve has the power to reduce the production of them.
Vagus Nerve Stimulation vs. RA Medication: Same Targets, Different Approach
Many people with RA take drugs that target specific cytokines. Biologic medications such as etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade) target the ctytokine TNF, whereas anakinra (Kineret) targets IL-1 and tocilizumab (Actemra) and sarilumab (Kevzara) target IL-6.
But these drugs don’t work for everyone with RA. For these patients, stimulating the vagus nerve seems to be another way to reduce the production of cytokines that cause inflammation.
“The premise is that when you stimulate the vagus nerve it leads to the production of acetylcholine [a neurotransmitter], which binds to receptors on cells that secrete cytokines. When acetylcholine binds to those cytokine-producing cells, it inhibits them from producing TNF and interleukin-6,” says rheumatologist Mark Genovese, MD, a professor of medicine at Stanford University who conducted a pilot study on vagus nerve stimulation that was presented at the 2019 European Congress of Rheumatology (EULAR) conference.
In Genovese’s study, which was published as an abstract in the journal Annals of the Rheumatic Diseases, 14 people with RA who had tried and failed to respond to at least two medications had a small “MicroRegulator” — about the size of a nickel — implanted on the left side of the neck along the vagus nerve.
Although the primary goal of this small trial was to assess the safety of the device, half of patients who had impulses sent to the MicroRegulator once a day had significant improvements in their RA disease activity scores. A decrease in cytokine production was also measured.
A few adverse effects were reported, but all were temporary. Those included pain and swelling at the incision site as well as one patient who had temporary vocal cord paralysis.
Dr. Genovese is now helping SetPoint Medical, the company that is investigating vagus nerve science and sponsored the pilot study, design a much larger, multi-center clinical trial to learn more about whether vagus nerve stimulation can be used to treat RA, especially in people who don’t respond sufficiently to drugs.
Earlier studies, including another small trial that involved RA patients in Europe, similarly found that that implantable vagus nerve stimulator could be used to reduce TNF production and, in turn, inflammation.
While Dr. Genovese and SetPoint Medical are focused on implantable stimulators, other non-invasive approaches in this growing area of bioelectronic medicine are also being explored: One small study, published in the journal Bioelectronic Medicine this year, found that holding up a vibrational device to the ear could be used to stimulate the vagus nerve and inhibit the production of TNF, IL-1, and IL-6.
At the same time, researchers are trying to determine whether it’s possible to predict who is likely to respond well to RA medication and who’s apt to be a non-responder. One way to do that might be by testing vagal nerve tone: Low vagal tone has already been linked to more inflammation and a greater risk of autoimmune conditions.
Although more research is needed, RA patients with low vagal tone may turn out to be good candidates for vagus nerve stimulation. That’s the premise behind a medical device called ANS Neuroscan that’s being developed by Inmedix, says Vibeke Strand, MD, adjunct clinical professor in the division of immunology/rheumatology at Stanford University and a pharmaceutical and biotech consultant for companies including SetPoint Medical and Inmedix.
If ANS Neuroscan gets FDA clearance, rheumatologists might be able to use it as an in-office tool to help determine which patients are most likely to respond to biologics and who might fare better on an emerging therapy such as vagus nerve stimulation. This device provides information about vagal tone by measuring heart rate variability (as do electrocardiograms and a number of apps and gadgets like the Apple Watch).
Dr. Strand also notes that while patients who are found to have low vagal tone might very well benefit from vagus nerve stimulation, electrical impulses aren’t the only way to do it. You might be able to improve your vagal tone on your own by learning some specific breathing techniques or employing other mind-body strategies, though substantial training is likely to be involved.
“There’s a lot of stress associated with having rheumatoid arthritis, or any autoimmune disease, and that’s probably leading to some of the immune system over-activity and the autoimmune response” as modulated by the vagus nerve, says Dr. Strand.
The vagus nerve, she explains, is integral to the mind-body connection. It’s a major route by which messages travel between the brain and the gastrointestinal tract (gut-brain axis), which is why vagus nerve stimulation has also gained attention as a treatment for psychiatric and digestive disorders.
“The autonomic nervous system is part and parcel of our immune response,” says Dr. Strand. “It takes a little time for some people to wrap their heads around that.”
If ongoing and future studies are positive, vagus nerve stimulation might one day become a viable option for RA patients who don’t respond to medication, can’t take it, or don’t want to, says Dr. Strand. Some new research is also examining whether electrical nerve stimulators might be used in conjunction with drug therapies to boost their effectiveness, says Dr. Genovese.
While all this might sound a bit futuristic, vagus nerve stimulators are already on the market — just not yet for RA. Implantable stimulators have been FDA-approved for patients with drug treatment-resistant epilepsy and depression since 1997, and there’s an FDA-cleared non-invasive device aimed at people who get migraine attacks and cluster headaches. In addition to RA, vagus nerve stimulation is being investigated for a wide range of potential applications including inflammatory bowel disease, bipolar disorder, and Alzheimer’s disease.
Will rheumatoid arthritis patients soon be able to make use of a similarly FDA–approved implant or non-invasive device? Stay tuned, as the results of upcoming trials are expected in the near future.
New data compares what happens when the dosage of DMARDs such as methotrexate is tapered or kept steady.
For most rheumatoid arthritis (RA) patients, sustained remission (inactive disease) is the goal of taking methotrexate or biologic DMARDS to manage their disease. However, what to do after reaching that goal hasn’t been clear. Should RA patients stick with the medication dose that’s working or gradually taper the dose — and thus lessen both the expense of the medication and possible side effects of these powerful RA medications?
Whether or not to taper is usually determined on an individual basis during discussions between individual patients and their doctors, based on shared decision-making around achieving and maintaining remission or low disease activity.
Now, there’s more data to help those discussions. It comes from a trial called ARTIC REWIND (Remission in Rheumatoid Arthritis: Assessing Withrawal of Disease-Modifying Antirheumatic Drugs in a Non-Inferiority Design) that enrolled patients who had been diagnosed with rheumatoid arthritis less than five years earlier and had no swollen joints for at least 12 months while taking a DMARD (about 80 percent on methotrexate). The researchers compared 78 people who were kept on their current DMARD dose with 77 who were moved to a half-dose of the same medication.
In the main finding, over the next 12 months, 6.4 percent of patients on the stable dose and 24.7 percent of patients moved to a half dose experienced a disease flare, defined as a combination of at least two swollen joints, a change in disease activity score, or both patient and physician agreeing that a clinically significant flare had occurred.
In other measures, 79.5 percent of patients continuing the stable DMARD dose had no progression of joint damage on imaging during the year, compared with 62.7 percent in the half-dose arm. Using Disease Activity Scores to define who was still in remission after a year, remission continued in 91.8 percent of patients on a stable dose and 85.1 percent of those moved to a half-dose.
More people (75) who continued on their prior dose experienced a drug side effect during the year, compared with 53 people who were moved to a half-dose. However, serious adverse events were more common in the tapered arm (four patients, including two serious infections) than in the stable-dose arm (two patients).
The researchers, primarily from Norway, concluded that continued DMARD therapy with stable doses led to significantly fewer disease activity flares and less frequent joint damage progression on imaging than tapered DMARD treatment.
The hard data should provide a helpful starting place for patients and rheumatologists to make decisions about tapering, which still need to take into account more subjective factors such as patients’ fears of RA disease progression and patients’ experiences with medication side effects.
Knowing there could be a lag between objective measures of improvement and patient–reported outcomes could help prevent over-treatment.
When a rheumatologist measures disease activity in a patient with rheumatoid arthritis (RA), objective clinical measures like C-reactive protein levels in the blood and swollen joint count are essential to factor in, but so are patient-reported measures including pain and fatigue. While both are certainly important, there may be some benefit to evaluating clinical factors and patient-reported measures independently rather than combining both into a composite disease activity score.
(You can use our ArthritisPower app to track your symptoms and disease activity and share your results with your doctor.)
According to a new study, presented at the 2019 American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting in Atlanta, there may be some lag time between when objective tests show that patients are getting better and when patients actually start to feel better.
The researchers, led by Janet Pope, MD, MPH, at Western University in Ontario, analyzed data on 986 patients. They found that the time it took for to reach remission or low disease activity varied widely depending on whether or not patient-reported factors were used as the goalpost.
When the Clinical Disease Activity Index (CDAI), which relies on solely clinical measures, was used, it took patients an average of 12.4 months to reach low disease activity. Yet it took the same group of patients getting the same exact treatment nearly 19 months to reach low disease activity when it was defined by patient global assessment of disease activity (PtGA).
Knowing that this lag time of several months exists is important, because it suggests that health care providers shouldn’t necessarily rush to change up a patient’s treatment regimen if clinical scores are good; waiting it out a few months to see if pain and inflammation improve might be a better option.
“Careful interpretation of [patient-reported outcomes] and composite scores could impact management, including prevention of overtreatment and unnecessary switching of DMARDs,” the authors concluded.
