New research indicates that a disruption of brain signals for reward and punishment contributes to increased pain sensitivity, known as hyperalgesia, in fibromyalgia patients. Results published in Arthritis & Rheumatism, a journal of the American College of Rheumatology, suggest that this altered brain processing might contribute to widespread pain and lack of response to opioid therapy in patients with fibromyalgia.
Fibromyalgia is a chronic, musculoskeletal syndrome characterized by widespread joint and muscle pain along with other symptoms such as fatigue, sleep disturbances, and cognitive difficulty. Previous research estimates that fibromyalgia affects 3.4% of women and 0.5% of men in the U.S. Prevalence of this pain disorder increases with age, affecting more than 7% of women between 60 and 79 years of age.
“In patients with fibromyalgia there is an alteration in the central nervous system pain processing and a poor response to topical pain treatments, trigger point injections and opioids,” said lead author Dr. Marco Loggia from Massachusetts General Hospital and Harvard Medical School in Boston. “Our study examines the disruption of brain function involved in the individual experience of pain anticipation and pain relief.”
For the present study, the research team enrolled 31 patients with fibromyalgia and 14 healthy controls. Functional magnetic resonance imaging (MRI) and cuff pressure pain stimuli on the leg were performed on all subjects. During the MRI, participants received visual cues alerting them of impending pain onset (pain anticipation) and pain offset (relief anticipation).
Results show that during pain anticipation and relief, fibromyalgia patients displayed less robust response within brain regions involved in sensory, affective, cognitive and pain regulating processes. The ventral tegmental area (VTA) — a group of neurons in the center of the brain involved in the processing of reward and punishment — displayed activation during pain anticipation and stimulation, but deactivation during anticipation of relief in healthy controls. In contrast, VTA responses during periods of pain, and anticipation of pain and relief, in fibromyalgia patients were significantly reduced or inhibited.
Dr. Loggia concludes, “Our findings suggest that fibromyalgia patients exhibit altered brain responses to punishing and rewarding events, such as expectancy of pain and relief of pain. These observations may contribute to explain the heightened sensitivity to pain, as well as the lack of effectiveness of pain medications such as opioids, observed in these patients. Future studies should further investigate the neurochemical basis underlying these dysfunctions.”
It may seem counterintuitive, but young and middle-aged fibromyalgia patients report worse symptoms and poorer quality of life than older patients, a Mayo Clinic study shows. Fibromyalgia most often strikes women. It is characterized by widespread musculoskeletal pain with fatigue, sleep, memory and mood issues. The research, one of several Mayo studies being presented at the American College of Rheumatology annual meeting, suggests the disorder plays out differently among different age groups.
Researchers studied 978 fibromyalgia patients and divided them into three age groups: those 39 or younger, those 50 to 59, and those 60 or older. The younger and middle-aged patients were likelier to be employed, unmarried, smokers and have a higher education level, lower body mass index, more abuse history and a shorter duration of fibromyalgia symptoms than older patients.
“Among the three age groups of young, middle-aged and older, symptom severity and quality of life differs,” says senior author Terry Oh, M.D., a physical medicine and rehabilitation physician at Mayo Clinic in Rochester, Minn. The study’s findings were surprising, because quality of life and physical health are considered to be negatively associated with age, Dr. Oh says.
Dr. Oh notes that women in all three groups with fibromyalgia reported a lower quality of life than average U.S. women, and that the difference between their physical health and that of the average woman was more significant than mental health differences, particularly in young patients.
*About 7 percent of fibromyalgia patients had inflammatory rheumatic conditions, and that in general, those fibromyalgia patients didn’t do as well with treatment as those without rheumatic diseases.
*Fibromyalgia patients may also have skin-related symptoms such as excessive sweating or burning or other sensations.
*Obese patients with polymyalgia rheumatica have more pain and disability than other polymyalgia rheumatica patients. They also tend to need higher doses of glucocorticoids.
*Rheumatoid arthritis patient experiences and symptoms do not always reflect what medical literature shows when it comes to pain, morning stiffness, the relationship between swelling and damage, and what worsens or improves symptoms.
More than 100 million Americans suffer from chronic pain. But treating and studying chronic pain is complex and presents many challenges. Scientists have long searched for a method to objectively measure pain and a new study from Brigham and Women’s Hospital advances that effort. The study appears in the January 2013 print edition of the journal Pain.
“While we need to be cautious in the interpretation of our results, this has the potential to be an exciting discovery for anyone who suffers from chronic pain,” said Marco Loggia, PhD, the lead author of the study and a researcher in the Pain Management Center at BWH and the Department of Radiology at Massachusetts General Hospital. “We showed that specific brain patterns appear to track the severity of pain reported by patients, and can predict who is more likely to experience a worsening of chronic back pain while performing maneuvers designed to induce pain. If further research shows this metric is reliable, this is a step toward developing an objective scale for measuring pain in humans.”
Specifically, researchers studied 16 adults with chronic back pain and 16 adults without pain and used a brain imaging technique called arterial spin labeling to examine patterns of brain connectivity (that is, to examine how different brain regions interact, or “talk to each other”). They found that when a patient moved in a way that increased their back pain, a network of brain regions called Default Mode Network exhibited changes in its connections. Regions within the network (such as the medial prefrontal cortex) became less connected with the rest of the network, whereas regions outside the network (such as the insula) became connected with this network. Some of these observations have been noted in previous studies of fibromyalgia patients, which suggests these changes in brain connectivity might reflect a general feature of chronic pain, possibly common to different patient populations.
“This is the first study using arterial spin labeling to show common networking properties of the brain are affected by chronic pain,” said study author Ajay Wasan, MD, MSc, Director of the Section of Clinical Pain Research at BWH. “This novel research supports the use of arterial spin labeling as a tool to evaluate how the brain encodes and is affected by clinical pain, and the use of resting default mode network connectivity as a potential neuroimaging biomarker for chronic pain perception.”
A recent University of Iowa study reveals a biological link between pain and fatigue and may help explain why more women than men are diagnosed with chronic pain and fatigue conditions like fibromyalgia and chronic fatigue syndrome.
Working with mice, the researchers, led by Kathleen Sluka, Ph.D., professor in the Graduate Program in Physical Therapy and Rehabilitation Science in the UI Roy J. and Lucille A. Carver College of Medicine, found that a protein involved in muscle pain works in conjunction with the male hormone testosterone to protect against muscle fatigue.
Chronic pain and fatigue often occur together — as many as three in four people with chronic, widespread musculoskeletal pain report having fatigue; and as many as 94 percent of people with chronic fatigue syndromes report muscle pain. Women make up the majority of patients with these conditions.
To probe the link between pain and fatigue and the influence of sex, the UI team compared exercise-induced muscle fatigue in male and female mice with and without ASIC3 — an acid-activated ion channel protein that the team has shown to be involved in musculoskeletal pain.
A task involving three one-hour runs produced different levels of fatigue in the different groups of mice as measured by the temporary loss of muscle strength caused by the exercise.
Male mice with ASIC3 were less fatigued by the task than female mice. However, male mice without the ASIC3 protein showed levels of fatigue that were similar to the female mice and were greater than for the normal males.
In addition, when female mice with ASIC3 were given testosterone, their muscles became as resistant to fatigue as the normal male mice. In contrast, the muscle strength of female mice without the protein was not boosted by testosterone.
“The differences in fatigue between males and females depends on both the presence of testosterone and the activation of ASIC3 channels, which suggests that they are interacting somehow to protect against fatigue,” Sluka said. “These differences may help explain some of the underlying differences we see in chronic pain conditions that include fatigue with respect to the predominance of women over men.”
The study, which was published in the Feb. 28 issue of the American Journal of Physiology — Regulatory, Integrative and Comparative Physiology, indicates that muscle pain and fatigue are not independent conditions and may share a common pathway that is disrupted in chronic muscle pain conditions. The team plans to continue their studies and investigate whether pain enhances fatigue more in females than males.
“Our long-term goal is to come up with better treatments for chronic musculoskeletal pain,” Sluka said. “But the fatigue that is typically associated with chronic, widespread pain is also a big clinical problem — it leaves people unable to work or engage in social activities. If we could find a way to reduce fatigue, we could really improve quality of life for these patients.”
In addition to Sluka, the UI research team included Lynn Burnes, a research assistant and lead author of the study; Sandra Kolker; Jing Danielson; and Roxanne Walder. The study was funded in part by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
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.
Screening is important because silent hepatitis B and Cinfections can spring to life when you start biologics or new synthetic DMARDs.
Before you start taking a biologic drug or one of the new targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), several screening tests are recommended. These include tests to see whether you have hepatitis B or C in your body that isn’t causing symptoms but might be reactivated after you start these powerful immune-suppressing drugs.
But there’s a big gap between what’s recommended and what’s really happening, as a new study reveals that fewer than one in four patients in a national registry received hepatitis screening before starting these medications.
“I think that we all believe that we are doing an excellent job taking care of our patients, but what we found is that there is a gap of care around screening for these infections,” Gabriela Schmajuk, MD, of the University of California, San Francisco, told Healio Rheumatology. Dr. Schmajuk was senior author of the new study, which was presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting in Atlanta.
The researchers looked at electronic health records from 23,597 patients (average age 57, 72 percent female) being treated at 196 different practices participating in the Rheumatology Informatics System for Effectiveness national registry. Each received their first prescription for a biologic or new synthetic DMARD in 2017, with the majority (63 percent) starting a tumor necrosis factor inhibitor.
Prior to the first prescription, 77 percent were not screened for hepatitis B virus (HBV) and 86 percent were not screened for hepatitis C virus (HCV). Only 6 percent of patients were fully screened for HBV, including both HBV surface antigen and HBV core antibody, prior to their first prescription. Another 17 percent had received one of the tests. Only 14 percent of patients received complete testing for HCV prior to their first prescription.
Of the patients who were fully screened, 83% had screening completed before receiving their first prescription, and a total of 97% had completed screening within 60 days of receiving their prescription.
“We actually looked to see, among the patients who were screened, how many had a positive test, and we found a rate of about 2 to 3 percent, so it is not insignificant,” Dr. Schmajuk told Healio Rheumatology. “If we can prevent one of those people from reactivating, that is going to save all of the money that we spent in screening them.”
Reactivation of HBV may lead to a hepatitis flare, liver failure, and sometimes even death, so patients who screen positive for the virus are often treated with an antiviral medication to prevent reactivation and its complications. HCV reactivation can also lead to hepatitis, but it may not be as severe as that caused by HBV reactivation.
The researchers acknowledge that their data, which can only capture screening entered into electronic health records at the rheumatology practices, could be missing hepatitis screening that was only noted in writing in the patient chart or conducted elsewhere and faxed to the practice, not making it into the electronic record.
Pre-medication screening percentages differed wildly between practices, with 0 percent to 63 percent of patients screened for HBV and 0 percent to 80 percent of patients screened for HCV.
If you’re not sure whether you have been screened for hepatitis B or C and you’re starting a biologic medication make sure you ask your health care provider.
Although biologics cross the placenta, research shows they lead to few infections in babies after they’re born.
The prospect of pregnancy can be daunting for women with inflammatory arthritis. Not only can disease flares occur, but a host of medications — including the commonly prescribed methotrexate — are off-limits because of concerns about birth defects and complications. There’s also a worrisome information gap on the effects of many medications during pregnancy, since pregnant women are usually excluded from clinical trials.
One type of medication, tumor necrosis factor inhibitors (TNF inhibitors), is increasingly used during pregnancy after animal studies did not show a risk to the developing fetus. But that left open the question of whether the drugs, as they suppress the immune system in expectant moms in order to manage their disease, might also lessen immune response in their newborns, leaving babies more vulnerable to infection after they’re born.
Last year, researchers at McGill University in Canada used a large health database in the United States to address that question for women with rheumatoid arthritis (RA). They found that that there was no excess risk for babies exposed to anti-TNF biologics compared to offspring of women with RA who didn’t take these drugs and to women without RA.
This year, the group is back with a similar analysis of serious infections in babies exposed to non-TNFi biologics, such as abatacept (Orencia), rituximab (Rituxan), tocilizumab (Actemra), ustekinumab (Stelara), and vedolizumab (ENTYVIO). Like TNFis, non-TNFi biologics can cross the placenta, leading to medication exposure than can equal or surpass that of the expectant woman. They also evaluated tofacitinib (Xeljanz), a small-molecule drug that may also cross the placenta (although that has not been confirmed).
“Our project innovates by using the largest cohort of pregnant women with chronic inflammatory diseases ever assembled to address drug safety in pregnant women, who are regularly excluded from clinical trials,” lead author Evelyne Vinet, MD, PhD, told the American College of Rheumatology in a press release.
The investigators tallied infections that occurred in 16,490 babies before their first birthdays that were serious enough to require hospitalization. All of their mothers had been diagnosed with an inflammatory disease, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, or inflammatory bowel disease. During pregnancy, 105 of the mothers took tofacitinib or non-TNFi biologics and 1,611 took TNFis. Infections in those children were compared to those in 164,553 babies born to unaffected mothers matched for age, year of delivery, and state of residence.
The researchers found just two cases of serious infections in exposed children, one whose mother received tofacitinib and one whose mother received abatacept. Overall, the proportion of serious infections in offspring of mothers with inflammatory disease was: 1.9% in those exposed to tofacitinib or non-TNFi biologics; 2.3% in those exposed to TNFis; and 2.1% of those exposed to neither type of drug. In comparison, the percent of serious infections in children born to unaffected mothers was 1.6%.
“Our data will help guide counseling and management of pregnant women with inflammatory arthritis that require non-TNFi biologics and tofacitinib during pregnancy,” says Dr. Vinet. Still, she considers this analysis to be just the first step in understanding the effect of these drugs during pregnancy.
“We need more data to confirm safety, particularly regarding other pregnancy outcomes. It is imperative that we further study this issue to provide firm evidence to guide treatment decisions prior to conception and throughout pregnancy,” she says.
‘Art enables me to face my body and my life with courage.’
Chronic 24/7 pain, fatigue, swelling, and a host of other symptoms are all part of my journey with rheumatoid arthritis, axial spondyloarthritis, osteoarthritis, fibromyalgia, and other chronic conditions I’ve been living with for years. I’ve loved drawing since I was a child, and after my RA diagnosis in 2011, I started to create art more regularly. As my diseases progressed and multiplied, my art became more integral to expressing my experiences.
Over this past year, I’ve been fortunate to start sharing my artwork on a much bigger platform than my own social media pages. Chronicwoman started publishing my art regularly — and the supportive, empathetic, and eye-opening responses I’ve been receiving from the chronic illness community have gone beyond my wildest expectations. I gave a keynote address about how my arthritis impacts my art at the annual meeting of the National Organization of Rheumatology Managers (NORM) and presented my artwork at the Spring/Summer 2020 New York Fashion Week show of designer Michael Kuluva, who also lives with rheumatoid arthritis.
I’m particularly proud of developing an abstract about how my artwork helps me cope with arthritis for the 2019 American College of Rheumatology/Association of Rheumatology Professionals (ACR/ARP) Annual Meeting in Atlanta. It’s part of the Patient Perspectives Poster Session, which invites patients like me to address “adaptations developed with their health care team that have improved their health.” I gave a lot of thought to the specific ways that creating artwork that visually conveys patients’ experiences of arthritis symptoms has helped me and others cope with our diseases.
Here’s what I realized — and shared in my ACR abstract:
Art helps me to listen to my body, enabling a more flexible reaction to pain episodes or flares. Listening to my body in the first place got me diagnosed and got me the medical help that I needed. My health and body took an upturn when I learned to not fight the cycles of flares, pain, and disease. Listening to my body for cues allowed me to function more because I rested or pushed when needed. I learned my patterns and strengths, allowing me to accomplish more when I have energy without overdoing it.
2. Visual art enables me to express my journey while reaching out to others.
I am an expressive person and found myself discussing my diseases a lot due to the need for accommodation or support. But symptoms like constant exhaustion, lack of sleep, high pain levels, RA flares, and bouts of back pain left me without the capacity to use words.
When I began to publish these pieces on social media, the overwhelming response reminded me that I’m not alone on this journey and that my body is telling the truth.
I’m able to process my grief over lost abilities, deteriorating health, and describe my experience and journey with inflammatory arthritis in a more universal way, without words.
3. My art allows me to show my life and struggles in a way that makes abled folks stop and take notice.
Visual representation helps other patients point to a piece that validates their pain and creates better connections between people.
4. People with inflammatory arthritis need to know that what they are experiencing is normal.
My art helps me and others cope better because we see visually what is happening invisibly to our bodies. It validates our experiences and lets us know we are not alone in what is happening to us.
5. Art reminds me how powerful my mind and heart are so I can pick myself up one more day and live for good instead of being lost in pain.
It gives me the ability to look back on a piece of artwork and remember the pain and my resilience and power in the face of intense circumstances.
It fulfills my need to be creative but also my need to take control of my life and body in a way that makes sense, allowing me to accept where I am.
It gives me the chance to process what is happening so I don’t fight the disease process. Art enables me to face my body and my life with courage and hope.
