Read the most up-to-date information about the latest developments in psoriatic arthritis

Clinical Updates in Psoriatic Arthritis

The impact of psoriatic arthritis on patients’ quality of life and importance of an early, accurate diagnosis.

Expert Perspective on the Management of Psoriatic Arthritis

Rheumatoid Arthritis Quiz

Learn more about the latest developments in rheumatoid arthritis

Focus on Rheumatoid Arthritis

Lana Dykes is the Editor of Rheumatology Network. She is an experienced editor and technical writer with a demonstrated history of working in the banking and publishing industries. She enjoys cooking, yoga, and drawing. 

Rheumatology Network's Top 5: January 21, 2022

Articles

Take 5 minutes to catch up on Rheumatology Network's highlights from the week ending January 21, 2021.


This article was originally published on 

In the wake of new research indicating some patients with rheumatic heart disease were dying from cardiovascular compromise following injections of benzathine penicillin G (BPG), the American Heart Association has released a presidential advisory to address the issue.

Published on January 20 with the intent of building awareness and providing strategies for risk reduction, the advisory from the AHA recommends oral penicillin, rather than BPG, for patients with high-risk rheumatic heart disease, which includes patients with severe mitral stenosis, aortic stenosis, left ventricular systolic dysfunction, or active symptoms of rheumatic heart disease.

”Until recently, deaths within the minutes and hours after BPG injection have been assumed to be due to anaphylaxis,” said Chair of the presidential advisory writing group Amy E. Sanyahumbi, MD, pediatric cardiologist at Texas Children’s Hospital and Assistant Professor of Pediatrics at Baylor College of Medicine, in a 

. “However, a growing number of reports of BPG-related deaths did not have the features of classic anaphylaxis, and, instead, point to cardiovascular reactions. This distinction is important, as it indicates the need for different strategies to prevent or stop these reactions to BPG.”

An 8-page document with more than 3 dozen references, the presidential advisory was composed by Sanyahumbi and a team of 10 colleagues with the intent of raising awareness, providing risk stratification, and providing strategies for risk reduction. Using contemporary evidence, investigators developed criteria for stratifying patients as low risk and elevated risk of death from vasovagal compromise, which clinicians can use to determine which patients would benefit most from oral antibiotics as opposed to intramuscular BPG prophylaxis.

The statement from the AHA highlights multiple standard practices that should be followed by clinicians for patients receiving BPG. These include reducing injection pain and patient anxiety, ensuring patients are well-hydrated prior to injection, advising patients to eat a small amount of solid food within the hour before injection, the have patients receive the injection while laying down, and ensuring providers who administer BPG should be well-versed in recognizing and treating symptoms such as low blood pressure, low heart rate, or fainting.

“This advisory is urgently needed to raise awareness, provide risk stratification and guide health care professionals on easily implementable protocols to reduce risk and overcome reluctance to administer and receive BPG treatment for rheumatic heart disease,” said Andrea Z. Beaton, MD, vice-chair of the advisory writing group, a pediatric cardiologist at Cincinnati Children’s Hospital and associate professor of pediatrics at the University of Cincinnati School of Medicine.

Penicillin Reactions in Patients With Severe Rheumatic Heart Disease: A Presidential Advisory From the American Heart Association

Journal of the American Heart Association.

The AHA released a statement recommending oral penicillin for patients with high-risk rheumatic heart disease, including patients with severe mitral stenosis, aortic stenosis, left ventricular systolic dysfunction, or active symptoms of rheumatic heart disease.

American Heart Association Recommends Oral Penicillin for Patients With High-Risk Rheumatic Heart Disease 

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, showed early response and improved clinical efficacy outcomes, including quality of life (QoL), in patients with moderate-to-severe plaque psoriasis, according to a study published in 

“The mechanism of action of deucravacitinib is distinct from that of other TYK2 or Janus kinase inhibitors in that deucravacitinib selectively binds to a unique pocket in the regulatory domain of TYK2 instead of the highly conserved active site of the catalytic domain, allowing high selectivity of action on TYK2 via allosteric inhibition versus related kinases,” investigators explained. “This leads to targeted inhibition of immune pathways that are central to psoriasis while limiting off-target effects.”

In the post-hoc analysis of a randomized, double-blind, placebo-controlled, Phase 2, 12-week trial (

), patients were randomized to receive deucravacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg once daily (QD), or placebo. Efficacy was measured by improvements in body surface area (BSA) involvement, Psoriasis Area and Severity Index (PASI), and static Physician’s Global Assessment (sPGA). QoL was determined by the Dermatology Life Quality Index (DLQI), with the goal of an overall score of 0/1, indicating no effect on the patient’s life.

Eligible patients were diagnosed with moderate-to-severe plaque psoriasis and were able to receive phototherapy or systemic therapy.

A total of 267 patients were enrolled, with 84% (n = 224) completing the 12-week trial. Demographics and disease characteristics at baseline were similar among the treatment groups.

Compared with placebo, deucravacitinib produced greater improvements in all 3 dosage groups as early as Week 1 for PASI and continued through Week 12.

At Week 12, changes in BSA were greater in the deucravacitinib groups (3 mg BID: -18.6, 75.9% decrease; 6 mg BID: -17.2, 69.4% decrease; 12 mg QD: -15.2, 73.7% decrease) when compared with placebo (-7.7). BSA ≤ 1% was achieved in 26.7% of patients in the 3 mg BID group, 37.8% of those in the 6 mg BID group, and 38.6% in the 12 mg QD group, compared with 0% of those receiving the placebo.

QoL showed a similar pattern of efficacy throughout the 12-week period. At Week 4, a greater percentage of patients in the deucravacitinib treatment groups had achieved DLQI 0/1 compared with the placebo group. This continued to increase through Week 12 for those receiving 6 mb BID and 12 mg QD. At the end of Week 12, 55.2% of those receiving deucravacitinib achieved a DLQI 0/1, compared with only 4.4% of those in the placebo cohort.

Patients who had more improvements in their clinical signs and symptoms of skin clearance concurrently had more improvement in QoL. At Week 12, patients who had DLQI 0/1 responses in the deucravacitinib dosage groups also achieved PASI 75 (70.1%), PASI 90 (44.0%), and sPGA (71.6%). Those who attained PASI ≤ 1, PASI 100, BSA ≤ 1%, or BSA ≤ 3% were more likely to have a DLQI score of 0/1.

The rate of achievement of DLQI 0/1 by PASI response was hindered by the limited number of patients in the PASI categories. Additionally, clinical and patient-reported outcomes were not adjusted for statistical significance in the deucravacitinib and placebo groups. Lastly, the sample size was relatively small, and the treatment period was short. However, larger, longer trials are currently ongoing or have been completed.

This analysis demonstrated that deucravacitinib treatment produced early, clinically meaningful, and similar improvements across several assessments of clinical response (PASI, BSA, sPGA). These improvements were mirrored by QoL improvements, as measured by DLQI,” investigators concluded. “At the three highest dosages tested, a substantial percentage of the deucravacitinib-treated patients met thresholds of clinically meaningful improvement in PASI as well as treat-to-target BSA values recommended by the National Psoriasis Foundation and acceptable response.”

Thaçi D, Strober B, Gordon KB, et al. Deucravacitinib in Moderate to Severe Psoriasis: Clinical and Quality-of-Life Outcomes in a Phase 2 Trial [published online ahead of print, 2022 Jan 13]. Dermatol Ther (Heidelb). 2022;10.1007/s13555-021-00649-y. doi:10.1007/s13555-021-00649-y

Deucravacitinib selectively binds to a unique pocket in the regulatory domain of TYK2 instead of the highly conserved active site of the catalytic domain,” investigators explained. “This leads to targeted inhibition of immune pathways that are central to psoriasis while limiting off-target effects.” 

Deucravacitinib Effectively Treats Moderate-to-Severe Plaque Psoriasis 

Among patients with rheumatic disease, men and members of the Hispanic community were significantly less likely to utilize complementary and alternative medicine (CAM), according to a recent 

Common CAM strategies include tai chi, massage, meditation, yoga, acupuncture, and vitamins, and may help patients manage chronic arthritis symptoms.

Participants were recruited via the CreakyJoints and COVID-19 Patient Support Program mailing lists and invited to complete a 6-question survey between December 2 and December 16, 2021. Patients were asked about their rheumatic disease, CAM therapies, and which approaches they found the most helpful.

Eligible patients had a clinical diagnosis of psoriatic arthritis (PsA), rheumatoid arthritis (RA), ankylosing spondylitis (AS) or axial spondyloarthritis (axSpA), osteoarthritis (OA), or juvenile idiopathic arthritis (JIA).

“At the start of a new year, many people reflect on their goals for the next 12 months. We conducted this survey to better understand how people with arthritis manage their condition going beyond prescribed medications and to start a conversation about why a holistic, patient-centered approach is key to maintaining physical, emotional, and mental wellness all year long,” stated Daniel Hernandez, MD, Director of Medical Affairs and Hispanic Outreach, CreakyJoints.

Of 847 patients surveyed, 87% were female, 81% identified as White, and the average age was 61 years. Most (65%) had either RA or JIA, and 25% reported having spondyloarthritis (SpA) of some kind.

Most participants (89%) used CAM as a part of their arthritis management, including vitamins (71%), herbs (34%), and joint supplements (47%). Among alternative medicine strategies, the most helpful among patients were massage (76%), Chi Gong (76%), yoga (74%), relaxation and mind/body activities (72%), and spiritual practice (71%).

A total of 27% of men reported never using CAM and only 11% incorporated it into their disease management routine. Conversely, 89% of women surveyed had tried alternative medicine at some point.

White respondents were significantly more likely to have used CAM than never having used it (82% vs 71%m p=0.007) when compared with Hispanic or Latino participants (13% vs 32%, p<0.001).

“An arthritis diagnosis requires a lifetime management commitment and there will be times when a person living with arthritis feels better and worse. Our CreakyJoints survey, and other existing peer-reviewed studies, show that CAM can have a positive impact on the experience of symptoms,” Hernandez explained. “However, our survey also suggests that more education is needed to encourage men and members of the Hispanic community to understand the range of CAM therapies available and to encourage them to speak with the health provider team about which therapy may offer benefit to them.”

® is an international digital community for patients and caregivers to receive education, support, advocacy, and patient-centered research. Patients are encouraged to use their 

® research registry, a free mobile and desktop app for those living with arthritis, joint, bone, and inflammatory skin conditions, and rheumatologic expressions of the gastrointestinal-tact. Patients can participate in research studies and track their rheumatic disease experience, including medication and treatment, signs and symptoms, and CAM. The app is also available in 

Women were significantly more likely to utilize complementary and alternative medicine strategies, such as yoga, acupuncture, and vitamins, to help manage chronic arthritis symptoms.

Men, Hispanic Patients Less Likely to Incorporate Alternative Medicine

Today, UCB announced that they achieved all primary and ranked secondary endpoints from the Phase 3 BE MOBILE 1 study, which evaluated safety and efficacy of the dual interleukin 17A (IL-17A) and IL-17F inhibitor, bimekizumab, in adult patients with non-radiographic axial spondyloarthritis (nr-axSpA).

“Today’s positive findings from the Phase 3 

 study provide clear evidence supporting bimekizumab in the treatment of nr-axSpA, and suggest that targeting IL-17F in addition to IL-17A may be a promising treatment approach for this painful, chronic rheumatic condition that often starts in young adulthood,” Stated Atul Deodhar, MD, MRCP. Deodhar is Professor of Medicine, Division of Arthritis and Rheumatic Diseases, at Oregon Health and Science University.

BE MOBILE 1, a randomized, multicenter, double-blind, placebo-controlled, clinical trial, is the first study to determine safety and efficacy of bimekizumab in this patient population. It is the second Phase 3 study UCB conducted to analyze the drug across the axial spondyloarthritis spectrum. The first study, which focused on ankylosing spondylitis, also supported the clinical potential of bimekizumab to improve patient outcomes for those with axSpA.

Eligible patients met Assessment of SpondyloArthritis International Society (ASAS) classification criteria, had no radiographic sacroiliitis, and experienced inflammatory back pain for 3 or more months. Inflammation was determined via magnetic resonance imaging (MRI) and/or an elevated C-reactive protein (CRP).

The primary endpoint was a significant and clinically meaningful improvement in the percentage of patients who attained the Assessment of SpondyloArthritis International Society 40 (ASAS40) by week 16 when compared with those receiving placebo. ASAS40 assesses physical function, spinal pain, inflammation, and disease activity.

Other endpoints included improvements in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which measured signs and symptoms of nr-axSpA, ASAS partial remission (PR), the nocturnal spinal pain score, and Ankylosing Spondylitis Disease Activity Score (ASDAS) Major Improvement (MI).

No new safety concerns were reported, and results were consistent with previous safety data.

The 52-week study is ongoing. Bimekizumab is not yet approved for treating nr-axSpA or ankylosing spondylitis. UCB plans to submit regulatory applications for the drug in axSpA in both the United States and European Union later in 2022.

AxSpA affects the spine and joints surrounding the pelvis and lower spine, which results in fatigue, stiffness, and back pain that often improves with exercise, but not with rest. Other symptoms may include enthesitis, dactylitis, peripheral arthritis, psoriasis, acute anterior uveitis, and inflammatory bowel disease. Roughly half of patients with axSpA have nr-axSpA, defined as the absence of structural damage to the sacroiliac joints. While axSpA is more commonly diagnosed in men, nr-axSpA is seen more frequently in women.

Bimekizumab, an interleukin 17A (IL-17A) and IL-17F inhibitor, met both primary and secondary endpoints for treating adult patients with non-radiographic axial spondyloarthritis. 

Bimekizumab Meets Primary and Secondary Endpoints for Treating Axial Spondyloarthritis 

Ingrid Torjesen is a UK-based freelance health journalist with more than 30 years of experience in health and medical communications. She works for numerous publications including Rheumatology Network, the BMJ and the Economist’s Intelligence Unit. Before her freelance career, her staff jobs included news editor of both Pulse and GP (the two leading UK weekly titles for primary care doctors), and opinion and features editor of the Health Service Journal (the UK’s leading health policy title). She also spent a few years working in Australia, including on Australian Doctor.

Physical activity is known to improve function, quality of life, and pain in rheumatoid arthritis. How has the pandemic affected patients’ participation in physical activity? Test your knowledge with this quiz.

Rheumatoid Arthritis Quiz: Physical Activity During the COVID-19 Pandemic

A novel, patient-directed, video-based intervention, focused on treatment changes and escalation, improved a patient’s inclination to change treatment if and when suggested by their rheumatologist, according to a study published in 

“To maximize long-term health-related quality of life and prevent structural damage in affected joints in patients with rheumatoid arthritis (RA), current guidelines recommend that the goal of RA treatment is to achieve remission or low disease activity,” investigators explained. “Despite the availability and efficacy of many treatment options, fewer than half of patients with RA with moderate/high disease activity enrolled in a United States physician-based registry received treatment escalation.”

CONTROL-RA was a controlled, randomized trial that utilized the ArthritisPower registry, which contains information on over 27000 patients with rheumatic diseases, to assess participants’ current disease activity and disease control, as well as their beliefs regarding RA medication, modifying their treatment plan, and any decisional conflicts. A baseline survey included questions about general health, health literacy, and whether the goals of RA treatment were recently discussed with a rheumatologist. Eligible patients were aged 19 years or older and had a clinical diagnosis of RA.

Participants in the intervention cohort viewed educational videos, including information about the treat-to-target (T2T) strategy, while the control group watched vaccination-related videos. The intervention video program highlighted the benefits of a T2T approach and addressed patient-reported concerns, such as worsening symptoms and medication side effects that may occur during escalations in treatment. Those in the control group watched 2 videos: “Living with RA: why get vaccinated?” and “Living with RA: which vaccines should I get?”

Two subsequent follow-up surveys were performed: one immediately after viewing the videos and one after a clinical visit with their rheumatologist. Patients’ willingness to modify treatment and decisional conflict was analyzed and compared between both groups.

A total of 208 patients completed the post-video follow-up survey, of which 90% were White, 90% were women, and the mean age was 50 years. Of these patients, 64% (n = 132) completed the second follow-up questionnaire. Approximately half (52%) were familiar with the RA T2T approach, although most had discussed treatment goals and disease activity with their rheumatologist.

Those in the intervention group were much more likely to accept treatment changes when compared with the control group (0.49 [95% confidence interval 0.09-0.88], P = 0.02). There was a significantly higher willingness to alter treatment within the subgroup of participants who were unfamiliar with T2T (50 patients in each arm) in the intervention group when compared with the control group (0.52 [95% CI 0.001-1.04], P = 0.049).

While decisional conflict decreased in both groups, differences were not significant.

A lack of generalizability, due to the similar demographics of the patient population, limited the study. While patients in the intervention arm were more likely to change RA treatment if needed, investigates did not collect disease activity measures, and were therefore unable to determine whether these patients were more likely to achieve remission or low disease activity when compared with the controls. Future studies should address this concern.

“Educational interventions, such as the one we developed and tested, could be part of behavioral intervention programs that include counselling about shared decision-making on RA management,” investigators concluded. “Further studies are needed to evaluate whether this change in patients’ willingness translates into actual behavior modification, namely, RA treatment escalation at the appropriate time.”

Danila MI, Chen L, Ruderman EM, et al. Evaluation of an Intervention to Support Patient-Rheumatologist Conversations About Escalating Treatment in Patients with Rheumatoid Arthritis: A Proof-of-Principle Study [published online ahead of print, 2021 Dec 27]. 

. 2021;10.1002/acr2.11393. doi:10.1002/acr2.11393

While the goal of rheumatoid arthritis treatment is low disease activity and remission, many patients are apprehensive about changing or escalating RA treatment. 

Online Intervention Improves Willingness to Accept RA Treatment Changes

Rheumatology Network interviewed Stephen Balevic, MD, an adult and pediatric rheumatologist at Duke University and clinical researcher at the Duke Clinical Research Institute (DCRI), to discuss his study, “

Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes

Make sure you never miss an article by signing up for our

What first sparked your team's interest to study hydroxychloroquine (HCQ) levels and medication adherence in this patient population?

Our treatment armamentarium in pregnant women with lupus is unfortunately very limited. And we know that having active lupus in pregnancy can worsen pregnancy outcomes. For example, there is an increased risk of preterm birth. However, one drug that we know reduces the risk of active disease and is safe in pregnancy is hydroxychloroquine. That really underscores the reason why we must make sure pregnant women are taking hydroxychloroquine regularly and at the right dose. Now, a very important point is that we can't assume that medication dosing in pregnancy is the same or should be the same as in non-pregnant women. There's a number of changes to the body that occur during pregnancy that can affect how the body handles a drug, or what we call pharmacokinetics (PK). For example, the kidney filtration system can increase by 30% or 40% by the third trimester. So that means medications like hydroxychloroquine could leave the body quicker and therefore require a dosage adjustment. That is why we really wanted to do this study.

Why is it so critical that patients with SLE adhere to their medication prior to pregnancy, during pregnancy, and into postpartum?

To really get all the benefits from hydroxychloroquine, it's very important that enough of the medication actually in the body, which means, of course, taking it very regularly and as prescribed. If lupus becomes active during pregnancy, sometimes other medications, like glucocorticoids, might be necessary. But these medications have their own risks and side effects, so it is best to have a lupus pregnancy where the disease is not active at the start and stays inactive throughout the pregnancy and postpartum period. Hydroxychloroquine is one of our key medications to help us do that. We also know that adherence to medications in lupus is very hard for our patients. Many of our patients don't feel well and are often overwhelmed with the number of medications that they have to take. Additionally, many women who are pregnant may feel nauseated or may have concerns about potential side effects to their unborn child. Collectively, that can make medication adherence even worse, but also really underscores why we have to have good communication with our patients because a number of medications, like hydroxychloroquine, are safe and we can reassure them that these medications can be used safely and effectively.

How does a diagnosis of lupus impact a woman who is pregnant or planning to become pregnant?

Although many women with lupus can, with good physician guidance, have healthy pregnancies, lupus does bring a number of challenges. One of the most important guiding principles is good pregnancy planning. A number of medications we use in non-pregnant women with lupus, such as methotrexate or mycophenolate, should not be used in pregnancy. When a pregnancy is being planned, it's important that women work with their rheumatologist to make sure that they are on medications that are safe to use in pregnancy. And secondly, having controlled lupus ideally 6 months before becoming pregnant is also very important and increases the chances of having the healthiest pregnancy possible. That also highlights the importance of very reliable contraception. So, if a woman is sexually active and not intending to become pregnant, having very reliable contraception is super important. And if an unintended pregnancy does happen, it's important that we counsel our patients not to panic and just to contact the rheumatologist right away.

We learned several important things. First, we did find that pregnancy really changes how hydroxychloroquine is handled in the body. For clinicians, we found the clearance of the medication increases progressively with each trimester. That increased clearance means lower average levels of the medicine in the body, smaller peak concentrations, and a shorter half-life by about 10 days. To maintain the same average level of medication the body, for example, the dosage would need to be increased by about 60% pre-pregnancy compared with the third trimester.

For several reasons that we discussed in the manuscript, the need for dosage adjustment for hydroxychloroquine in pregnancy is not straightforward. At this point, we're not advocating that clinicians change dosage until we have a little bit more data. Secondly, we found that medication non-adherence had the greatest impact on the amount of hydroxychloroquine in the serum. Serum hydroxychloroquine levels that were ≤100 ng/mL were strongly suggestive of medication non-adherence. For example, if there were no missed doses at all, we would expect to see a level that low only about 0.3% of the time in women taking the most common dose of 400 milligrams a day. In other words, even though there's these physiologic changes, really low hydroxychloroquine levels in serum are still pretty uncommon. Conversely, if 60% of hydroxychloroquine doses are missed, we would expect to see those average hydroxychloroquine levels being ≤100 ng/mLabout 25% of the time. And thirdly, we found that women with persistently low serum hydroxychloroquine levels throughout the pregnancy, so that's an average level ≤100 ng/mL, had significantly higher odds of preterm birth. And that was the case even when we controlled for potential confounders, like lupus nephritis, race, and concomitant medications.

The take home message here is that our study suggests that monitoring serum hydroxychloroquine levels during lupus pregnancies can really help identify non-adherence. And that's one way we can easily intervene to hopefully improve adherence and possibly improve pregnancy outcomes.

Were you surprised by the results of the study?

I think the results make sense if we think about the pharmacology of hydroxychloroquine. Yes, we would expect the medication to be affected by pregnancy, but this is the first time we were able to quantify those changes and determine the clinical significance. I think we were surprised to learn that medication non-adherence was so common. We found that about 1 in 4 pregnancy visits had a serum hydroxychloroquine level that was very low and suggestive of non-adherence.

Are there any strengths or limitations of the study that you'd like to highlight?

The major strength of this study was our use of something called PK modeling, which really allowed us to figure out what was happening to hydroxychloroquine in the body due to physiologic changes, what was happening due to medication non-adherence, and what the combined effect was. PK modeling is a very powerful tool that is used frequently by the FDA and other regulatory authorities and industry, and something I hope will be used more commonly in academic rheumatology.

The most important limitation for your readers is the fact that we used the serum and not whole blood to measure hydroxychloroquine levels. Without going into too much detail, hydroxychloroquine does partition into blood cells. Target whole blood levels cannot be compared directly with serum and plasma and vice versa. Most of the existing literature on hydroxychloroquine levels, especially in non-pregnant patients with lupus, have been using whole blood. It’s typically a little bit more precise. I do want to highlight that measuring serum levels, though, does have some advantages in pregnancy. For example, it's usually less impacted by the physiologic anemia that can occur during pregnancy. I must refer readers to the discussion in our manuscript to really know what the strengths and limitations of using whole blood versus serum are, but I think that is an important thing for researchers or clinicians to be aware of.

Does your team plan on doing any further research on this topic?

Yes. This is a growing area where we need more research on optimal dosages of our antirheumatic drugs, especially in vulnerable populations, like pregnant women and in children. We're very fortunate to have our Duke Autoimmunity in Pregnancy Registery, which is an ongoing registry where we collect information from pregnancy. We are planning to study the PK of other drugs in lupus pregnancies as well.

For more information about this study, refer to our recent 

Stephen Balevic, MD, explains hydroxychloroquine PK and exposure-response in pregnancies with lupus and the importance of adhering to treatment both during pregnancy and postpartum. 

Stephen Balevic, MD: Importance of Adherence in Pregnant Patients with SLE 

Rheumatology Network's Top 5: January 14, 2022

Take 5 minutes to catch up on Rheumatology Network's highlights from the week ending January 14, 2021.


W. Benjamin Nowell, PhD, in partnership with CreakyJoints, discusses his study, "Patient-Repo

rted Nausea and Fatigue Related to Methotrexate: A Prospective, Self-Controlled Study in the ArthritisPower® Registry

Rheumatology Network interviewed W. Benjamin Nowell, PhD, to discuss his study, “

Patient-Reported Nausea and Fatigue Related to Methotrexate: A Prospective, Self-Controlled Study in the ArthritisPower® Registry

.” Nowell is the Director of Patient-Centered Research at CreakyJoints, part of the Global Healthy Living Foundation, and principal investigator of ArthritisPower.

Through use of a smartphone app, the proprietary ArthritisPower Research Registry, patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) were able to track their experience of methotrexate (MTX)-related side effects.

“Currently, a gap exists in patient-centric studies that focus on the patient experience with MTX, including beliefs regarding its benefits and behavioral distress and anxiety experienced by patients in anticipation of their upcoming dose,” investigators stated.

During the first phase, patients completed a cross-sectional survey which included questions about symptoms and side effects related to MTX, as well as their personal opinions about medicine. In the second phase, participants discussed current MTX usage and self-assessed any nausea, vomiting, and fatigue that occurred in the hours and days following a dose of MTX via Patient-Reported Outcomes Measurement Information System (PROMIS®).

A total of 671 patients with RA (n = 528) and PsA (n = 193) completed the first phase of the study. Most patients (61%) experienced adverse effects from the drug, of which 46% reported fatigue.

Results indicate that the ArthritisPower mobile app is an innovative way to identify and analyze a patient’s tolerability of their medication in real time. Further, it demonstrated that patients were willing and able to utilize this platform for research that can lead to further remote patient monitoring, which is especially helpful during this time of social distancing and telehealth.

“The entirely virtual nature of this longitudinal study is promising for future research with RA and PsA patients adopting remote patient monitoring as an essential component of digital health, where out-of-office data capture from patients is critical,” investigators concluded.

Videos

W. Benjamin Nowell, PhD, Director, Patient-Centered Research, CreakyJoints, discusses his study, "Patient-Reported Nausea and Fatigue Related to Methotrexate: A Prospective, Self-Controlled Study in the ArthritisPower® Registry.”

W. Benjamin Nowell, PhD: ArthritisPower Mobile App Identifies MTX-Related Side Effects

Concomitant duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), did not have added benefits for patients with chronic osteoarthritis (OA), according to a study published in 

“OA is one of the major chronic pain conditions of the musculoskeletal system and approximately 15% of the population suffers from OA. Persistent pain and loss of function are two important complaints of patients with OA,” investigators explained. “Duloxetine is hypothesized to reduce chronic pain by central inhibition of pain and acts by modulation of descending (inhibitory) pain pathways in the central nervous system.”

In this open-label, cluster randomized trial, investigators enrolled patients from general practices who had OA and were experiencing chronic hip or knee pain with an insufficient response or adverse reactions to paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were randomized to either receive duloxetine 60 mg/day or continue with usual care alone. Patients were started at a 30 mg/day dose to minimize adverse events. Effects were analyzed at 2 weeks, and then 1, 3, 6, 9, and 12 months. Usual care included diet, physiotherapy, analgesics, lifestyle advice, and education.

Patients completed questionnaires at week 6 and then at 3, 6, 9, and 12 months. Patient-reported adverse events and co-interventions were reported. Satisfaction of treatment was measured on a scale of 0 to 10 and improvement was evaluated via a 7-point Likertscale.

Primary outcome was the Western Ontario Mc Master Universities (WOMAC) Osteoarthritis Index for pain (0-20) at the 3-month mark. The goal was to identify a difference between groups of a clinically significant effect of 1.9. A painDETECT score of >12, the secondary outcome, was used to categorize centralized pain.

A total of 132 patients, 66 receiving duloxetine and 66 receiving usual care, were included in the study. The 12-month follow-up was completed by 80.3% of patients (53 in each cohort). The duloxetine cohort had fewer women when compared with the control group (59.1% vs 75.8%, respectively), were younger (63.2 years vs 65.4 years, respectively), and had fewer comorbidities (15.2% vs 33.2% with 2 or more comorbidities, respectively). Participants with centralized pain (40%) had higher WOMAC pain scores.

No significant differences were detected between the groups for WOMAC pain at 3 months (adjusted difference -0.58 95% CI) or at 12 months (adjusted difference -0.26 95% CI. Analyses were adjusted for comorbidities, age, sex, depression scores, and a modified painDETECT score.

The duloxetine subgroup reported no effect on symptoms or pain with the inclusion of the drug (-0.32 95% CI). Quality of life and patient satisfaction showed small, clinically insignificant differences between both cohorts.

For those chosen to receive duloxetine, 15% opted to not begin duloxetine for fear of adverse events. By the 3-month follow-up, 61% of patients were still being treated with the drug, which further reduced to 35% at 1 year. Reasons for discontinuing the medication included side effects (49%), no effect (24%), or a combination of side effects and no effect (18%). At 3 months, 75.2% of patients in the usual care cohort reported 1 or more adverse events, compared with 89.3% of those in the duloxetine cohort. Common side effects included nausea, constipation, hyperhidrosis, weight loss, and yawning for those receiving the drug. Additionally, the duloxetine group contacted their physician significantly more than those receiving usual care treatment (51.8% vs 30.8%, respectively).

The study was strengthened by its cluster design, which allowed for evaluating implementation of the drug in a “real-life” setting. Unfortunately, investigators were unable to recruit the number of patients they initially desired. However, results were still deemed clinically relevant.

“There was no clinically relevant effect of duloxetine added to usual care compared to usual care alone for chronic OA pain and it should not be implemented,” investigators concluded. “For patients with symptoms of centralized pain an effect cannot be ruled out and future research in this subgroup is needed to confirm our results.”

van den Driest JJ, Schiphof D, Koffeman AR, Koopmanschap MA, Bindels PJE, Bierma-Zeinstra SMA. No added value of duloxetine for patients with chronic pain due to hip or knee osteoarthritis: a cluster randomised trial [published online ahead of print, 2022 Jan 6]. 

. 2022;10.1002/art.42040. doi:10.1002/art.42040

While investigators were hopeful that duloxetine, an SNRI, would reduce chronic pain in patients with knee osteoarthritis, results were lackluster and clinically insignificant. 

Duloxetine Does Not Improve Pain in Patients With Knee Osteoarthritis 

Katie Robinson is a medical writer. She covers various health and medical topics for a professional audience.

Patients with systemic lupus erythematosus (SLE) and congestive heart failure (CHF) experience more severe SLE, but treatment with antimalarials was associated with a lower prevalence of CHF, according to a study published in 

“Patients with SLE and CHF experience more severe SLE, with more pronounced cumulative damage, higher overall SLE-related mortality, and greater refractoriness to SLE treatments,” stated Iñigo Rúa-Figueroa, MD, Hospital Universitario de Gran Canaria Doctor Negrin, Spain, and colleagues. “Treatment with antimalarials, as usually administered in patients with SLE, is not only safe for the heart, but might confer cardioprotective effects.”

Despite the high prevalence of cardiovascular disease in patients with SLE, the risk factors associated with CHF in these patients is not well studied.

In this cross-sectional study, the researchers aimed to identify the factors associated with CHF in patients with SLE and looked at the cardiac safety of long-term therapy with hydroxychloroquine in this population. The study included 117 patients with SLE and CHF and 3,506 SLE control patients registered in the retrospective phase of the Spanish Society of Rheumatology Lupus Register who met at least 4 of the American College of Rheumatology (1997) criteria. Of the participants, 90% were female and 93% were Caucasian. The study excluded patients with CHF prior to diagnosis of SLE.

Results showed that patients with CHF presented with greater SLE severity, organ damage, and mortality when compared with those without CHF. The mean age of patients with CHF was higher than the controls without CHF, at 59.8 years and 46.2 years, respectively. Meanwhile, factors associated with CHF were ischemic heart disease, cardiac arrhythmia, pulmonary hypertension, valvulopathy,non-cardiovascular damage, and calcium/vitamin D treatment. However, female sex and antimalarial use were found to be protective.

Investigators determined that CHF is a late complication of SLE and is linked with high mortality rates. Causes of CHF in SLE were similar to causes seen in the general population.

“The use of antimalarials was associated with a lower prevalence of CHF in our large multicenter retrospective SLE cohort, and, interestingly, this effect occurred independently of disease severity,” investigators concluded. “This apparently cardioprotective effect was also documented independently of ischemic heart disease, suggesting that mechanisms other than antithrombotic effects could be involved, for example, better control of subclinical myocarditis or overall disease activity.”

Rúa-Figueroa I, Rúa-Figueroa D, Pérez-Veiga N, et al. 

Antimalarials exert a cardioprotective effect in lupus patients: Insights from the Spanish Society of Rheumatology Lupus Register (RELESSER) analysis of factors associated with heart failure.

https://doi.org/10.1016/j.semarthrit.2021.11.012

The use of antimalarials was associated with a lower prevalence of congestive heart failure in a large Spanish cohort of patients with SLE.

Antimalarial Use in SLE May be Cardioprotective 

Participation in physical activity (PA) during the first COVID-19 lockdown period was significantly lower among patients with rheumatoid arthritis (RA), according to a study published in 

“This sustained period of reduced PA may have adverse health implications. Indeed, among people with RA, PA is a major determinant of obesity and even associates with disease activity and frequency of hospitalization,” investigators explained. “Therefore, it is important to understand how the pandemic may have impacted PA and associated health aspects of people with RA.”

Data from 128 UK participants, comprised of 27 patients with RA and 101 non-RA controls, was collected via an online questionnaire between April and June 2020. Questions included RA diagnosis, demographics, COVID-19-related information, body weight, dietary questions, mental wellbeing, PA before and after lockdown, any barriers participants may have faced, and the International Physical Activity Questionnaire—short form (IPAQ). Respondents with RA were asked about disease activity and were evaluated based on the visual analogue scale (VAS) for pain and fatigue, Health Assessment Questionnaire (HAQ), and the RA quality of life questionnaire (RAQoL). Non-RA participants received World Health Organization Quality of Life Questionnaire Short Form (WHOQoL-BREF), VAS fatigue, and the Short Warwick Edinburgh Mental Wellbeing Scale (SWEMWBS).

Patients with RA had significantly lower levels of PA when compared with non-RA respondents. Pre-lockdown, 48% of patients with RA and 64% of non-RA participants reported that they were physically active. During the lockdown, PA levels were reduced by 38% across both groups, with a more significant decrease in the RA population (59% vs 33%, respectively). Body weight increased by 40% across all participants, with the RA cohort experiencing weight gain significantly more than the non-RA group (59% vs 35%, respectively). Despite this, those without RA reported eating more during this time than patients with RA (25% vs 15%, respectively).

The biggest barrier participants faced regarding PA was access to equipment and facilities (RA: 37%; non-RA: 33%), although home-based exercises increased 53% during this time.

Mental wellbeing was low in both groups (RA: 20.8 ± 4.2; non-RA: 22.2 ± 3.4, 

 = 0.080). Nearly half of patients with RA (44%) and 28% of non-RA respondents fell into the low mental wellbeing category.

A group of 27 non-RA participants were matched for age, sex, height, weight, and BMI with the 27 patients with RA. In this evaluation, patients with RA were less likely to be physically active when compared with the matched controls (67% vs 48%, respectively) and were more likely to further reduce PA during the lockdown (59% vs 41%, respectively). Mental wellbeing scores were lower for RA respondents when compared with non-RA participants (44% vs 33%, respectively).

Results may have been affected by the convenience sampling approach, which hindered an accurate response rate. Further, assessment of causality was unavailable due to the study’s cross-sectional design. The small sample size and demographic differences limited the study and potentially underpowered the analysis. Investigators found, however, that after matching groups, results were similar throughout the sample. Lastly, there is always a risk of bias for all self-reported data.

“The key reason for reduced PA participation appears to be limited access to equipment and facilities, which has then impacted on types of exercise performed. Therefore, our findings show the lockdown has perhaps unintentionally created restrictions on incidental and volitional PA,” investigators concluded. “The combination of low PA levels and obesity could negatively impact on disease activity and overall health for people with RA. Following the COVID-19 pandemic, PA promotion specifically for people with RA will be needed to prevent a pandemic of inactivity.”

Balchin C, Tan AL, Wilson OJ, McKenna J, Stavropoulos-Kalinoglou A. Participation in physical activity decreased more in people with rheumatoid arthritis than the general population during the COVID-19 lockdown: a cross-sectional study [published online ahead of print, 2021 Nov 30]. 

. 2021;1-10. doi:10.1007/s00296-021-05054-4

For patients with rheumatoid arthritis, reduced levels of PA may impact disease activity, increase the likelihood of obesity, and may even lead to more frequent hospitalizations. 

Physical Activity Decreased in Patients With RA During COVID-19 Pandemic 

A low patient-reported wellness/health score for patients with rheumatoid arthritis (RA) was linked to poor sleep quality, longer sleep duration on weekends, longer nap duration on weekdays, and decreased mood, according to a study published in 

“Self-rated wellness/health has been shown to provide a reliable subjective picture of well-being and health status,” investigators stated. “It seems there are bidirectional relationships among the three sides of triangle: chronic disease manifestations, lifestyle factors and self-rated wellness/health. Then, understanding the complex inter-relationships in this triangle in RA might be an important aspect for any patient-centered clinical practice and management plan.”

In this cross-sectional study, investigators evaluated patients with RA based on patient-reported wellness and health, mood, sleep, diet, smoking history, disease activity, demographics, body mass index (BMI), and laboratory records. Sleep quality was analyzed by Mini-Sleep Questionnaire, with a higher score indicating worse sleep quality. Mood was measured using the Gallup Wellbeing Index, in which a higher score implied worse mood status. A multivariable generalized additive model (GAM) was performed to examine any connection between the data.

A total of 142 patients were identified. The mean age was 52 years, 116 patients were female, and BMI was generally classified as overweight. The wellness/health score averaged 7.2/10, with 10 being the healthiest, the mean number of tender joints was 4.42, and the average number of swollen joints was 4.00. Common comorbidities included hypothyroidism (14.1%), diabetes mellitus (2.8%), and cardiovascular disease (2.8%). Nearly all (96%) of patients were being treated with corticosteroids. Mean sleep score was 29.5 out of 70. Mood and diet scores averaged 18.5/35 and 22.5/42, respectively.

Mood status and time to fall asleep were the 2 most significant variables were linearly associated with the wellness/health score. In the multivariable GAM regression, mood status, sleep quality, sleep duration, and nap duration during weekends were the most significant variables.

When compared with patients who reported the best sleep, a 20% drop in self-reported wellness/health score was observed for those who had the worst sleep quality. Six out of 10 sleep quality assessments were more common in patients with RA. A total of 76% reported sleep fragmentation and 86% stated they woke up too early more than 3 nights per week. Additional factors associated with poor sleep quality were difficulty falling asleep (45%), falling asleep during the day (45%), feeling tired upon waking (49%), and snoring (35%).

Patients went to bed earlier and woke earlier during the weekdays when compared with the weekends (22:45 vs 23:52 PM; 6:08 vs 7:20 AM, respectively). Those who woke up at 7 AM or earlier tended to have a higher self-rated wellness/health score when compared with those who woke up later (7.23 vs 7.14, respectively). Patients who went to bed between 11:00 PM and midnight had the highest scores (7.59) when compared with those who went to bed before 11:00 PM (6.96) or after midnight (6.11).

Naps averaged approximately 30 minutes longer on the weekends when compared with weekdays (48.02 vs 19.75 minutes, respectively). Any nap longer than 30 minutes was linked to a lower wellness/health score. The mean score for patients who took 5- to 30-minute naps was 7.39, compared with a score of 6.33 for those who took longer naps.

The highest scores were seen in 55 individuals who went to bed between 11:00 PM and midnight, woke up at 7 AM or earlier, and napped between 0 to 30 minutes when compared with the rest of the group (7.66 vs 6.94, respectively).

Strengths of the study included using patient-reported outcomes as the primary endpoint, with a focus on sleep quality and quantity during both the weekday and weekend. Analyzing lifestyle factors, clinical findings, and disease activity helped to design the multivariable GAM. However, the cross-sectional nature did not allow for cause-and-effect examination between wellness/health score and sleep quality. Further, unless witnessed by a third party, self-reported snoring statistics may be inaccurate.

“Mood and sleep emerged as the most important factors in the final GAM regression model associated significantly with self-rated wellness/health score in patients with rheumatoid arthritis,” investigators concluded. “The model showed that too much sleep duration on weekend, more than 30-minute naps on weekdays, and lower sleep quality were the main sleep indices associated with lower self-rated wellness/health score.”

Tabaraii R, Masoumi M, Bagherzadeh-Fard M, Yazdanifar MA, Balasi J, Smiley A. Association of lifestyle and disease characteristics with self-rated wellness/health score in patients with rheumatoid arthritis. 

. 2021;5(1):55. Published 2021 Dec 22. doi:10.1186/s41927-021-00227-x

Analysis of self-reported wellness and health may provide insight into an overall subjective picture of wellbeing and health status. Mood, sleep quality, and sleep quantity were shown to impact these scores. 

Low Wellness/Health Score Associated With Poor Sleep Quality

A unique set of biomarkers may help identify active systemic juvenile idiopathic arthritis (sJIA) from both inactive sJIA as well as healthy controls, according to a study published in 

“There is no pathognomonic feature that distinguishes sJIA from other conditions, but few laboratory parameters may be supportive for diagnosis of sJIA, such as elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil and platelet counts,” investigators stated. “Manifestations of sJIA, including macrophage activation syndrome (MAS), neurological complications, limitation in functional outcome by arthritis, and long-term damage from chronic inflammation can be severe and have significant impacts on patients’ quality of life.”

Plasma samples were collected from 21 sJIA patients and 60 healthy controls matched for age and sex (ranging from 3 to 16 years) at Astrid Lindgren’s Children Hospital in Stockholm, Sweden. Inactive sJIA was defined as experiencing no clinical signs of disease activity, a Physician’s Global Assessment (PGA) of disease activity score of 0, and CRP and ESR levels within normal range. Immunoprofiling was conducted via a proteomic immunoassay. The biomarker panel consisted of 92 immune-related proteins. Canonical pathways and cellular functions were analyzed by Ingenuity Pathway Analysis (IPA) based on whether biomarkers were up- or down-regulated.

Of the 69 biomarkers included, Hierarchical Clustering Analysis (HCA) and Principal Component Analysis (PCA) could not completely separate the 3 groups during analysis. A cross-sectional analysis was conducted in an attempt to further separate the cohorts, with an emphasis on 10 proteins. The most notable biomarkers that aided in the classification were interleukin 6 (IL-6), IL-18, and S100 calcium-binding protein A12 (S100A12), which were increased in patients with active sJIA when compared with healthy controls. Other factors, such as CD6, CXCL1, CXCL11, CXCL5, CASP8, SIRT2, and KITLG were expressed differently in patients with either active or inactive sJIA when compared with controls. Interestingly, IL-18 was increased during inactive sJIA when compared with the control cohort. This may indicate that suppressive mechanisms are activated when patients are in a state of remission.

Nine patients with sJIA were further examined, with 11 proteins showing significantly different levels between inactive and active sJIA. IL-6, MMP1 and S100A12 had p-values lower than 0.0001, which confirmed results from the cross-sectional analysis.

High Mobility Group Box 1 (HMGB1), a damage-associated molecular pattern, levels were upregulated in patients with active sJIA in comparison with inactive sJIA. Of the 9 patients studied, 8 exhibited higher HMGB1 levels during active disease state.

Proteins in 3 groups (active sJIA vs controls, inactive sJIA vs controls, and active sJIA vs inactive sJIA) were analyzed using IPA. However, it could not predict significant pathway activation, due to a limited about of input factors.

The small sample of patients and differing medication schedules limited the study, as medications affect immune activity and inflammatory proteins. However, focusing on biomarkers and prognosis is more practical, as patients in real-world settings have a variety of symptoms and complex medical histories. Another limitation is that several proteins, including IL1β and S100A8/9, were not available and therefore not incorporated into the analysis.

“Further studies of the pathogenic features of the newly revealed biomarkers and their potential use as diagnostic tools and as new targets for therapy development are highly warranted,” investigators concluded.

Qu H, Sundberg E, Aulin C, et al. Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study. 

. 2021;19(1):173. Published 2021 Dec 28. doi:10.1186/s12969-021-00660-9

Plasma samples, collected from 21 patients with systemic juvenile idiopathic arthritis (sJIA), indicate 11 proteins that may help identify patients with active and inactive sJIA. 