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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. 

Interleukin-6 (IL-6) and IL-17 inhibition of patients with psoriatic arthritis (PsA) receiving the oral janus kinase (JAK) inhibitor upadacitinib (UPA) varied in terms of outcomes in those with inadequate response to non-biologic disease-modifying antirheumatic drugs (nbDMARD-IR) and inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR). In nbDMARD-IR patients, a decrease in IL-6 and joint manifestation improvement was reported, while decreases in IL-17A and IL-17F and improvement in psoriasis symptoms were seen in the bDMARD-IR cohort. However, beta-defensin 2 (BD2), a biomarker of Th17-associated skin pathology, was significantly reduced in both groups after treatment with UPA and positively impacted psoriasis improvement.

“The differential contribution of IL-6 and IL-17 pathways to the pathogenesis of psoriatic arthritis is not fully understood,” investigators stated. “Targeted proteomic analysis suggested that UPA modulates multiple biological pathways in innate and adaptive immune systems via direct and indirect inhibition of key regulators, including IL-6 and IL-17 pathways, with a possible shift from Th1 predominance in nbDMARD-IR PsA to a more Th17 bias in bDMARD-IR PsA.”

Patients were randomly selected from the SELECT-PsA 1 (74 patients received UPA 15mg daily, 74 received placebo) and SELECT-PsA 2 studies (90 patients received UPA 15 mg daily, 81 received placebo). IL-6, IL-17A, IL-17F, and BD2 proteins were measured by validated immunoassays at baseline and then again at week 2 and week 12. A Repeated Measure Mixed Linear Model compared the UPA and placebo cohorts overall as well as between responders and non-responders. Response was defined as a Psoriatic Arthritis Disease Activity Score PASDAS score ≤ 3.6 (Minimal Disease Activity, MDA) and Psoriasis Area and Severity Index 75 (PASI75) at week 12. The Pearson’s correlation evaluated any link between cytokines and clinical outcomes (PASI and Disease Activity Score-28 C-reactive protein [DAS28-CRP]) at baseline and at the end of treatment.

At week 12, patients receiving UPA had significantly decreased IL-6 and BD2. IL-17A, IL-17F, and BD2 levels correlated both with each other and with PASI in nbDMARD-IR patients. However, IL-6 levels were independent from the IL-17 pathway and was associated with DAS28-CRP. An increase in IL-6 was more significant in PASDAS MDA responders and was linked to DAS28-CRP improvement. Reductions in BD2 were more significant in PASI75 responders and associated with PASI improvement. Conversely, IL-17A and IL-17F levels did not change after UPA treatment and were not associated with clinical outcomes at week 12.

IL-17A levels were significantly higher in the bDMARD-IR cohort when compared with nbDMARD-IR patients and showed no correlation with PASI. Reductions in IL-6 were not different between responders and non-responders in terms of PASDAS MDA or PASI75 and did not correlate with DAS28-CRP improvement. BD2 decreases remained significant in patients who achieved PASI75 and PASI improvement. The reduction of IL-17F was linked to PASI improvement at the end of the study period.

The study, “Differentiation Between IL-6 and IL-17 Pathway Inhibition in Relationship with Clinical Outcomes in Non-Biological DMARD-IR and Biological DMARD-IR Psoriatic Arthritis Patients Treated with Upadacitinib in SELECT-PSA 1 and SELECT-PSA 2 Studies,” was presented at the 

Annual European Congress of Rheumatology (EULAR 2022)

Articles

“The differential contribution of IL-6 and IL-17 pathways to the pathogenesis of psoriatic arthritis is not fully understood,” investigators stated.

Upadacitinib Significantly Decreases Biomarker BD2 in Patients with PsA

Massimo Radin, MD, PhD: TuTOR App Tailors Oral Therapy in Rheumatoid Arthritis

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Terence Rooney, MD: Innovative Aspects of Future-Facing Research in Psoriatic Arthritis

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Frédéric Lavie, MD, PhD: Efficacy of Guselkumab Across Multiple Disease Domains of Psoriatic Arthritis

Frédéric Lavie, MD, PhD, explains the results of the data presented at EULAR evaluating guselkumab for the treatment of psoriatic arthritis.

Leonard Calabrese, DO: Immunology for the Rheumatologist

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Jeffrey Stark, MD: Latest Bimekizumab Data for Treatment of Psoriatic Arthritis, Psoriasis

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July 7: Pegloticase (KRYSTEXXA) plus Methotrexate

The US Food and Drug Administration (FDA) 

 priority review of the supplemental Biologics License Application (sBLA) that would expand the pegloticase label to include the co-treatment of pegloticase plus methotrexate in patients with uncontrolled gout. The decision was based on results from the phase 4, randomized, placebo-controlled MIRROR trial, which showed that 71% of patients receiving pegloticase combination therapy achieved a complete response when compared with patients receiving pegloticase plus placebo. Pegloticase is a recombinant uricase enzyme that converts urate into allantoin that is more easily excreted from the body.

“I think this is going to show much better promise for patients in the long run,” Jeff Peterson, MD, President of Washington Rheumatology Alliance, Director at Northwest Rheumatism Society, Western Washington Medical Group Arthritis Clinic's clinical research department, hypothesized. “Prior to using immunomodulation with pegloticase, we were getting about a 40% success rate of getting patients all the way through the treatment protocols. Fifty-eight percent of the patients were failing, having infusion reactions, and exhibiting a lack of efficacy from the drug. Since we have been using immunomodulation, that number has essentially doubled.”

July 29: Roflumilast Cream for Plaque Psoriasis

, roflumilast cream 0.3% (ARQ-151), a once-daily topical formulation of roflumilast, would be the first and only topical phosphodiesterase type 4 (PDE4) inhibitor for treating the symptoms of psoriasis in adults and adolescents. The FDA acceptance for review of the new drug application (NDA) is supported by positive efficacy data from the phase 3, randomized, parallel, double-blind, vehicle-controlled, multi-national, multicenter DERMIS 1 and DERMIS 2 trials as well as a long-term phase 2b safety study. Results from DERMIS 1 and DERMIS 2 showed roflumilast met its primary endpoint and had an Investigator Global Assessment (IGA) success rate of 42.4% and 37.5%, respectively. The cream also reduced itch (Worst Itch-Numerical Rating Scale), and improved patient perceptions of symptoms (Psoriasis Symptoms Diary) and Psoriasis Area Severity Index-75 (PASI-75). Durable efficacy of roflumilast cream was observed through 52 and 64 weeks in the long-term safety study.

“Topical treatments are the standard therapies for the majority of psoriasis patients, but they often come with compromises between efficacy, tolerability and long-term use,” Patrick Burnett, MD, PhD, FAAD, Chief Medical Officer, Arcutis, stated. “With these challenges in mind, we developed roflumilast cream as a formulation for chronic use anywhere on the body, including the face and sensitive intertriginous areas.”

 the NDA, with a Prescription Drug User Fee Act (PDUFA) goal date of September 10, 2022, and the European Medicines Agency (EMA) has authorized the Marketing Authorization Application (MAA) for deucravacitinib for the treatment of adults with moderate-to-severe plaque psoriasis. The drug, a first-in-class, oral, selective tyrosine kinase 2 (TYK2) inhibitor, selectively targets and inhibits interleukin-23 (IL-23), IL-12 and Type 1 interferon (IFN).

Applications are based on positive results from the global, multicenter, randomized, double-blind, phase 3 POETYK PSO-1 and POETYK PSO-2 studies, presented at the American Academy of Dermatology Virtual Meeting Experience and the European Academy of Dermatology and Venerology 30th Anniversary Congress, which showed that deucravacitinib (6 mg daily) exhibited significant and clinically meaningful improvements in skin clearance, quality of life, and symptom burden when compared with both placebo and apremilast (30 mg twice daily). Primary endpoints were the percentage of patients who achieved PASI75 response and the static Physician’s Global Assessment (sPGA) score of 0 or 1 at week 16 when compared with placebo. Secondary endpoints were the percentage of patients who achieved PASI75 and sPGA 0/1 at week 16 compared with apremilast. The drug was well-tolerated, and few patients discontinued treatment due to adverse events.

“There is a strong need for more effective and well-tolerated oral therapies for people living with moderate to severe plaque psoriasis, as many remain undertreated or even untreated,” Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb, stated. “Findings from the pivotal POETYK-PSO trials demonstrate the potential of deucravacitinib to elevate the oral standard of care for individuals who are candidates for systemic therapy. We look forward to continuing to work with the FDA and EMA with the goal of bringing deucravacitinib to patients and physicians as quickly as possible.”

September 30: Dupilumab for Prurigo Nodularis

 priority review of the sBLA for dupilumab, a fully human monoclonal antibody that inhibits IL-4 and IL-13 pathways, key drivers of type 2 inflammation, for the treatment of adults with prurigo nodularis based on 2 phase 3 trials, PRIME and PRIME2, that evaluated the safety and efficacy of the drug. The trials met primary and secondary endpoints and showed significant improvement in disease signs and symptoms when compared with placebo, including a reduction in itch and skin lesions. The safety profile was consistent with previously known profile of dupilumab in the treatment of atopic dermatitis, with conjunctivitis reported as the most common adverse event.

Prurigo nodularis, which affects approximately 75,000 patients in the US, is an inflammatory skin condition that causes intense and persistent itch along with thick skin lesions (nodules). Patients also commonly report painful burning, stinging, and tingling of the skin. Uncontrolled prurigo nodularis can negatively impact a patient’s mental health, quality of life, and social interactions. As the safety risks of long-term, high-potency topical steroids are well known, alternate treatment options, such as dupilumab, are critically important.

The approval and implementation of new drugs can vastly improve quality of life and reduce signs and symptoms of disease burden in patients with rheumatic and dermatologic diseases. 

FDA Decisions to Watch in Rheumatology in Second Half of 2022

, AbbVie announced the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommends approving upadacitinib 15 mg, once daily, for the treatment of active non-radiographic axial spondyloarthritis (nr-axSpA) in patients aged 18 years or older with inflammation and inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs). Objective inflammation was determined via magnetic resonance imaging (MRI) and/or elevated C-reactive protein (CRP).

The approval was supported by results from the Phase 3, randomized, double-blind, placebo-controlled SELECT-AXIS 2 nr-axSpA study, which analyzed the efficacy and safety of the drug compared with placebo in 314 patients with a clinical diagnosis of nr-axSpA. Eligible patients had active inflammation and/or high sensitivity C-reactive protein (hs-CRP) > upper limit of normal (2.87 mg/L) at screening, with a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and total back pain score of ≥4.

The study met the primary endpoint of Assessment of Spondyloarthritis International Society 40 (ASAS40) response criteria at week 14 when compared with placebo, as well as 12 of 14 secondary endpoints. No new safety risks were identified. The most common adverse reactions were upper respiratory tract infections, nausea, cough, increased aspartate transaminase (AST), increased blood creatine phosphokinase (CPK), increased alanine transaminase (ALT), bronchitis, and hypercholesterolemia.

Upadacitinib is currently approved in the EU for adults with moderate-to-severe active rheumatoid arthritis (RA) who have inadequate response or intolerability to at least 1 disease-modifying antirheumatic drug (DMARD), patients with psoriatic arthritis (PsA) who have inadequate response or intolerability to at least 1 DMARD, and patients with active ankylosing spondylitis (AS) who have inadequate response to conventional therapy.

"Patients with axSpA often experience delayed diagnosis and once they do receive a diagnosis, there are limited therapies available to help control disease symptoms, such as inflammation, back pain and stiffness,” Neil Gallagher, MD, PhD, Vice President, development, chief medical officer, AbbVie, stated. "The CHMP's recommendation to approve upadacitinib for patients with nr-axSpA is an important milestone in providing a new treatment option to patients in need."

The European Commission (EC) will review the CHMP positive opinion, with a decision anticipated in Q3 2022.

The Committee for Medicinal Products for Human Use (CHMP) recommends approving upadacitinib 15 mg, once daily, for the treatment of active non-radiographic axial spondyloarthritis in adults patients with inflammation and inadequate response to NSAIDs. 

Upadacitinib Receives Positive CHMP Opinion for Treatment of Non-Radiographic Axial Spondyloarthritis 

Gout Flares Predicted by Monosodium Urate Deposits, Subclinical Inflammation

Differences among baseline clinical and laboratory characteristics between cases and controls were observed in those with a presence of subcutaneous tophi and higher serum urate levels.

John K Botson, MD, RPh, CCD: Pegloticase Combination Therapy for Uncontrolled Gout

John K. Botson MD, RPh, CCD, discusses results from the MIRROR trial, which evaluated the efficacy and safety of pegloticase injection in combination with methotrexate in patients with uncontrolled gout.

Patient-Provider Satisfaction Survey Affected by Cultural Norms in Hispanic/Latinx Patients with RA

A recent study, conducted by CreakyJoints, demonstrated that patient-reported satisfaction is affected by both social and cultural norms in Spanish-speaking patients with rheumatoid arthritis.

Line Uhrenholt, MD: Disease Activity-Guided Tapering in Patients with Inflammatory Arthritis

Line Uhrenholt, MD, discusses the results of her randomized, open-label, equivalence trial study evaluating disease activity-guided tapering of biologics in patients with inflammatory arthritis.

Sexual Dysfunction More Common in Rheumatoid Arthritis, Psoriatic Arthritis

New research suggests patients with psoriatic arthritis were at 8 times greater risk of sexual dysfunction and patients with rheumatoid arthritis were at 10 times greater risk when compared to their counterparts without either rheumatic disease.

Take a few minutes to discover Rheumatology Network's most-viewed EULAR 2022 coverage. 

Rheumatology Network: Best of EULAR 2022

Novartis announced that the European Commission (EC) approved secukinumab, either alone or in combination with methotrexate, in juvenile idiopathic arthritis (JIA) enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in pediatric patients aged 6 years and older who had inadequate response or were intolerant to conventional therapy.

The approvals were based on results from the JUNIPERA trial, which showed secukinumab reduced the risk of flare and disease activity when compared with placebo over 2 years in pediatric patients with ERA and JPsA. Additionally, safety was consistent with known safety profiles across both adult and pediatric indications.

Since its initial approval in 2014, secukinumab, the first and only fully human biologic that inhibits interleukin-17A (IL-17A), has treated more than 700,000 patients internationally with sustained efficacy across multiple inflammatory conditions.

“Cosentyx could now provide a treatment option for eligible patients who continue to struggle with the painful symptoms which negatively impact their quality of life, such as inflammation of the joints, swollen fingers and toes,” Todd Fox, Global Head of Medical Affairs Immunology at Novartis, stated. “This approval represents an important step in our ambition to expand Cosentyx to 10 indications for children and adults living with rheumatic and dermatologic diseases.”

The Phase III, 2-year, 3-part, double-blind, placebo-controlled, randomized withdrawal JUNIPERA trial showed that pediatric patients with ERA and JPsA receiving secukinumab had a significantly longer time to flare when compared with placebo. The study included 86 children and adolescents (aged 2 to 18 years) diagnosed according to the modified International League of Associations for Rheumatology classification criteria. The primary endpoint was time to flare in the treatment period 2 (week 12 to week 104). Risk of flare was reduced by 72% in patients receiving secukinumab during treatment period 2 (hazard ratio=0.28, 95% confidence interval: 0.13 to 0.63; 

<0.001). In total, 10 patients in the secukinumab cohort experienced a flare compared with 21 patients in the placebo cohort during the placebo-controlled treatment period 2.

“The approval of Cosentyx is very positive news for children affected by JPsA and ERA across Europe. We are now able to offer a new therapeutic target, which was not on the market for this disease in children and also offers a lower frequency of administration. Cosentyx adds to the body of other approved treatments that may provide children and adolescent patients, with the opportunity to participate in all daily activities, and even sports,” Ivan Foeldvari, M.D., Hamburg Centre for Pediatric Rheumatology, Germany, stated.

The approvals were based on results from the JUNIPERA trial, which showed secukinumab reduced the risk of flare and disease activity when compared with placebo over 2 years in pediatric patients with ERA and JPsA.

Secukinumab Receives Expanded Approvals in EU for Pediatric Arthritic Conditions 

The shortage of rheumatologists in Canada may be impacted and/or heightened by the threat of burnout to workforce retention as well as productivity. Strategies to address these issues are urgently needed, according to a study published in 

“While burnout is prevalent among Canadian physicians, little is known about burnout in Canadian rheumatologists,” investigators stated. “The challenges of an existing rheumatologist workforce shortage, changing workforce demographics, and physician burnout have been compounded by the COVID-19 pandemic.”

The Canadian Rheumatology Association (CRA) created the Workforce and Wellness Survey to learn more about the workforce characteristics of Canadian rheumatologists. The questionnaire, which was provided in both French and English versions, included information about pandemic effects, demographic and practice information, and the Mini Z survey. The Mini Z is a 10-item survey that evaluates stress, burnout, satisfaction, as well as risk factors, also known as “drivers.”

The survey was distributed to members between October 14, 2020, and March 5, 2021. The number of full-time equivalent (FTE) rheumatologists per 75,000 population was determined from the median proportion of time in clinical practice multiplied by provincial rheumatologist numbers from the Canadian Medical Association. Differences between demographic groups (sex/gender, age, career state, type of practice, and ethnicity) were evaluated using univariable logistic regression models.

A total of 183 of 417 (44%) practicing rheumatologists completed the survey (149 adult; 34 pediatric). The median age was 47 years, 62% were female, and 28% planned to retire within the next 5-10 years.

Participants reported that they spent a median of 65% of their time in clinical practice. FTE rheumatologists per 75,000 population were 0.62 nationally, ranging between 0.00 and 0.70 in each province or territory, which represents a deficit of 194 FTE rheumatologists nationally to meet the CRA’s workforce benchmark.

Roughly half (51%) of rheumatologists reported burnout, with women more likely to experience burnout (OR 2.86, 95% CI 1.42–5.93). Women were also more likely to report poor or minimal personal control over their workload and stress due to their job (OR 2.99, 95% CI 1.43–6.55) and were less likely to identify their workplace as a supportive environment when compared with men (OR 0.36, 95% CI 0.16–0.79). Older physicians, regardless of gender, were less likely to experience burnout (OR 0.95, 95% CI 0.92–0.99 per year of age).

Almost all (97%) rheumatologists stated that they were spending more time in virtual care and 74% stated they were spending the same amount of time on research. While 53% of rheumatologists surveyed reported spending more time on clinical paperwork each week, 37% were seeing fewer new patients and 25% had fewer follow-ups per week.

The study was limited by only being distributed to CRA members, eliminating nonmember rheumatologists. Additionally, there is no comprehensive list of rheumatologists in Canada. The Canadian Medical Association (CMA) numbers did not capture any changes to the workforce during the pandemic, such as retirements, as numbers were calculated pre-pandemic. Generalizability may be an issue due to a higher percentage of female respondents and a higher percentage of rheumatologists with academic affiliation when compared with the CMA master file. There is a possibility of response bias as participants may have different opinions and characteristics when compared with nonrespondents. Further, the COVID-19 pandemic may have influenced the survey as it was deployed just after the “first wave” in Canada and the perception of the pandemic’s effect may have changed over the many pandemic waves.

“The pandemic created an immediate threat to the workforce by significantly affecting patient volume, likely affecting rheumatologist remuneration and contributing to delayed care,” investigators concluded. “A further evaluation of the effect of the pandemic and increasing virtual care on rheumatology practices and patient outcomes is warranted. Future advocacy and research efforts should also continue to evaluate the predictors of burnout among rheumatologists as well as to develop strategies to address burnout at local, regional, and national levels.”

Kulhawy-Wibe SC, Widdifield J, Lee JJY, et al. Results From the 2020 Canadian Rheumatology Association's Workforce and Wellness Survey. 

. 2022;49(6):635-643. doi:10.3899/jrheum.210990

"The challenges of an existing rheumatologist workforce shortage, changing workforce demographics, and physician burnout have been compounded by the COVID-19 pandemic."

Shortage of Canadian Rheumatologists Linked to Increase in Burnout

Plasma Levels of Glycoprotein Acetyls Linked to Incident Gout

Investigators identified novel biomarkers of incident gout and replicated novel metabolomic biomarkers of gout, including plasma levels of glycoprotein acetyls.

ACR, AAHKS Updates Guidelines for Patients with Rheumatic Disease Undergoing Knee, Hip Surgery

The American College of Rheumatology (ACR)/American Association of Hip and Knee Surgeons (AAHKS) has published guidance regarding perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty.

4 Ways Rheumatology Practices can Navigate Supply Chain Disruptions

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Rheumatology Network's Rheumatoid Arthritis Quiz Roundup

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Take 5 minutes to catch up on Rheumatology Network's highlights from the week ending June 25, 2022.

Rheumatology Network's Top 5: June 25, 2022

The Lupus Research Alliance (LRA), the largest non-governmental, non-profit funder of lupus research worldwide, recently 

 their inaugural awards promoting diversity in lupus research. Rheumatology Network sat down with Teodora Staeva, PhD, Lupus Research Alliance’s Chief Scientific Officer, to discuss the critical contributions of underrepresented investigators, why it is crucial to award and recognize minority researchers, and the LRA’s plans for the future.

Lupus, a complex and sometimes fatal autoimmune disease, affects millions of people globally. More than 90% of patients diagnosed are women in their childbearing years (aged 15 – 45 years). Additionally, minorities populations, including African, South and Central American, and Native Americans, are 2 to 3 times more likely to develop lupus when compared with Americans with European ancestry. Lupus can attack the kidneys, heart, lungs, brain, blood, skin, and joints of affected patients.

Specific award recipients highlighted below include Andrea Knight, MD, MSCE, affiliated with The Hospital for Sick Children (SickKids), who is studying ways to detect brain changes in high-risk adolescent patients with lupus to identify potential new treatments. Another recipient, Erika Moore, PhD, of the University of Florida, focused on how monocytes promote lupus-related vasculitis to understand how lupus and ancestry can affect monocyte functions and learn how ancestry influences blood vessel inflammation, especially for those who are at a higher risk of cardiovascular disease.

From your perspective, why is it so crucial that the Lupus Research Alliance dedicates grants and awards that specifically recognize minority researchers and promotes diversity in lupus research?

There are several major reasons why we wanted to do so. One of them is that lupus predominantly impacts women and people of color. As you may know, women are 9 times more likely to have lupus than men. And lupus is up to 3 times more prevalent in women of color than white women. And so given that significant overrepresentation of minority populations in our disease, it's critical to have the representations on all sides, both from participation in clinical trials, and also from the research perspective.

The other major reason is that studies have shown repeatedly that teams that are comprised of broad diverse stakeholders consistently outperforms homogeneous teams. And if we look at the research teams in general, not just in lupus, but in all fields of research, they are homogeneous and composed of a significant proportion of white scientists.

A recent National Science Foundation report had done a report on the scientific workforce, and established that the population such as Blacks, Pacific Islanders, Native Americans, and Hispanic people make up just over 10% of the scientific workforce, when those populations comprise about 25% of the general population in our country. So clearly, there is significant disproportionate representation of those groups. And what we really need to do to be most successful in identifying effective therapies for people with lupus is to harness the power of cognitive diversity and address this dire problem of under-representation of specific racial and ethnic groups in biomedical research. And so that's why we felt it was important to create specifically dedicated programs that could foster the development of talented and promising young scientific workforce in lupus research.

 What are some of the critical contributions of underrepresented investigators that were recognized this year?

 Andrea Knight, MD, MSCE, studies cognitive development issues in adolescents with lupus. She has done important studies previously supported by the LRA and now we're continuing our support through this particular program where she is studying changes that occur within the brain using various imaging methods in the adolescent period and comparing those to changes that are happening in the immune system as detected in peripheral blood. She is trying to understand how the disease development in this age group impacts important issues such as depression and other mental issues in children and adolescents, which is significantly understudied. The hope for this study is that she may be able to identify certain biomarkers that would identify children who may be at particular risk for some of these cognitive manifestations of lupus and develop ways to counteract them or combat them.

Another investigator, Erika Moore, PhD, from the University of Florida, is trying to understand different ancestral differences within certain subsets of immune cells in individuals with lupus. Again, this is a unique opportunity to look, in more mechanistic aspects, at some of the contributions of lupus from different immune cells, particularly differences that are reflected in the ethnicities of the patients with the disease.

Some of the other awards that were given were for investigators studying specific type of T cells that are critically important in the disease process as well. These awards reflect the breadth of research that is happening within this community of scientists, an underrepresented minority of scientists, and it's very exciting to be able to support them.

Speaking of the community, where do you see this field heading in the future?

I think that with the various programs that we're establishing, and with the support that we and others are offering to this community, it could really flourish. I hope that 5 years from now there will be a lot more people of color who are participating, not only in basic research and making key discoveries, but also clinicians who are treating lupus patients, who are recruiting them for lupus clinical trials, and importantly, mentoring the next generation of both researchers and scientists. And the other impact of this would be that they will bring much larger participation from a underrepresented minorities in clinical trials so drugs can be developed that actually help the people that need the most. Because that's one of the challenges right now.

Is there anything else that you would like our audience to know before we wrap up?

In addition to providing financial support at different stages of the career development of underrepresented minorities in lupus, we're also creating different mentoring programs and training opportunities. We feel that providing financial support alone, while very important, is not sufficient. And so, we're trying to think more holistically and provide a comprehensive package of financial support, as well as other facilitative services, that could enable these brilliant scientists to flourish in their careers and their research that we're funding.

Teodora Staeva, PhD, discusses how Lupus Research Alliance's is recognizing the critical contributions of underrepresented minority researchers through their Diversity in Lupus Research Award. 


Teodora Staeva, PhD: Promoting Diversity in Lupus Research

Remote care was shown to have similar, and sometimes better, results when compared with face-to-face (F2F) care regarding safety, efficacy, medication adherence, and user perception outcomes. However, heterogeneity and the risk of bias (RoB) in the available literature were the most common limitations, according to a systematic literature review published in 

“Due to the growing number of patients but an inadequate increment of human resources, there is an increasing pressure on the healthcare system, and new forms of care are needed, for example, telehealth-based follow-ups, or self-management interventions in the form of patient education,” investigators stated. “Thanks to the sophistication of communication systems and technologies, remote care interventions have become more widespread over the past 20 years, with presumed benefits for diagnosis, treatment, rehabilitation and follow-up monitoring of patients.”

Investigators developed a search strategy including publications in PubMed, Embase, and Cochrane Library. Eligible studies were published in English, French, German, Portuguese, and Spanish, and were full research articles, qualitative studies, and short reports or research letters of both prospective and retrospective studies. Additionally, unpublished studies from both the American College of Rheumatology (ACR) 2020 and European Alliance of Associations for Rheumatology (EULAR) 2020 conferences were screened for relevancy. Afterwards, 2 independent reviewers performed a standardized data extraction, synthesis, and RoB assessment according to study type.

Of the 2240 references that were initially identified, 129 had a full-text review and 47 fulfilled the inclusion criteria for the analysis (26 randomized controlled trails [RCTs], 8 prospective cohort studies, 8 cross-sectional studies, and 5 qualitative studies). The most frequently studied aspect was remote monitoring (n=35), with telephone or video calls cited as the most common mode of delivery (n=30).

Of the 34 studies that analyzed the outcomes of telemedicine, the majority evaluated efficacy and user perception, with 34% and 21%, respectively, reporting that remote care was superior to F2F care. Major benefits were time and cost savings. However, 13 studies stated technical aspects as a major drawback and barrier of remote care. No studies observed the implementation of remote care. The main limitation was heterogeneity of outcomes and methods, and 50% of studies had significantly high RoB.

A limitation of the study was the lack of blinding of patients and investigators to remote care interventions, which may have led to an overestimation of effect sizes. Additionally, none of the studies had follow-up periods longer than 1 year. In the cross-sectional and qualitative studies, RoB was evaluated exclusively in a descriptive manner because the Joanna Briggs Institute (JBI) Critical Appraisal Checklists do not have cut-offs for low, moderate, and high RoB. Publication bias may also be a factor, as results are more likely to be published if they are positive. Future trials should either compare telehealth with conventional care or use a sham intervention, such as online material only, in a control group.

“The need for new healthcare solutions is imminent due to the COVID-19 pandemic, leading to a recent increase in remote care research in rheumatic and musculoskeletal diseases (RMDs),” investigators concluded. “Currently available studies comparing remote with F2F care reported similar results for various efficacy, safety, adherence and user perception outcomes.”

Marques A, Bosch P, de Thurah A, et al. Effectiveness of remote care interventions: a systematic review informing the 2022 EULAR Points to Consider for remote care in rheumatic and musculoskeletal diseases. 

. 2022;8(1):e002290. doi:10.1136/rmdopen-2022-002290

"Remote care interventions have become more widespread over the past 20 years, with presumed benefits for diagnosis, treatment, rehabilitation and follow-up monitoring of patients.”

Telemedicine Deemed as Effective as Face-to-Face Care in Patients with Rheumatic Disease

Results indicate that the irregular expression and possible regulatory function of long noncoding RNAs (lncRNAs) in the placentas of women with systemic lupus erythematosus (SLE) may play a role in the pathogenesis of these pregnancies. Further, SLE-dysregulated lncRNAs may possibly be used as biomarkers for SLE, according to a study published in 

“During pregnancy, the loss of immune tolerance to the fetus in SLE may cause numerous maternal and fetal complications, including lupus flare, hypertension, preeclampsia (PE), eclampsia, spontaneous abortion, stillbirth, fetal growth restriction (FGR), neonatal lupus, and neonatal deaths,” investigators explained. “The pregnancy outcomes in mothers with SLE and the well beings of fetuses born to SLE mothers have been improved tremendously over the last five decades due to the development of disease management. However, the mechanism underlying SLE-induced pregnancy complications remains unclear.”

To identify SLE-dysregulated lncRNAs and messenger RNAs (mRNAs) in placentas from patients with SLE, as defined by the American College of Rheumatology classification criteria, and normal full-term (NT) pregnancies (n = 8 patients per group), investigators utilized an RNA sequencing analysis. Biological functions of the dysregulated lncRNAs and mRNAs were evaluated via a bioinformatics analysis. Disease activity was determined via the SLE disease activity index (SLEDAI) and a questionnaire collected both demographic data and clinical manifestations. Medical records were used to obtain laboratory data. Patients were excluded if they had cancer, diabetes mellitus, or were current smokers.

Patients with SLE remained on maintenance medication throughout pregnancy (prednisone ≤ 15 mg daily and hydroxychloroquine 200–400 mg daily). While maternal age and body mass index were comparable between both groups, gestation age and newborn body weight was significantly lower in the SLE cohort when compared with the NT cohort (

The RNA-seq analysis ultimately identified 52 dysregulated lncRNAs in the placentas of patients with SLE, which included 37 upregulated and 15 downregulated. A total of 130 SLE-dysregulated mRNAs were also identified, including 122 upregulated and 8 down regulated.

According to the bioinformatics analysis, SLE-dysregulated genes were linked to biological functions and gene networks, most notably regulation of type I interferon-mediated signaling pathway, response to steroid hormone, regulation of mitogen-activated protein kinase (MAPK) cascade, complement and coagulation cascades, Th1 and Th2 cell differentiation, and response to hypoxia. While it is unclear what causes these dysregulations of lncRNAs, investigators theorize that it may be due to tissue oxygen levels.

The study was the first to report the lncRNA profiles in the placentas of patients with SLE, supporting the idea that lncRNAs play an important role in the pathogenesis of SLE placentas. However, the small number of patients limited the study. Investigators urge further validation of dysregulated mRNAs and lncRNAs within a larger cohort. Additionally, analysis of the association between differential expression genes (DEGs) expression levels and disease activity was hindered by the narrow SLEDAI score range (0-6).

“This study demonstrates a comprehensive expression profile of lncRNAs and mRNAs in SLE placentas,” investigators concluded. “The findings suggest regulatory functions of lncRNAs and mRNAs, which are implicated in the development and pathogenesis of SLE pregnancy. SLE-dysregulated lncRNAs may potentially serve as biomarkers for SLE.”

Li HH, Sai LT, Liu Y, et al. Systemic lupus erythematosus dysregulates the expression of long noncoding RNAs in placentas. 

. 2022;24(1):142. Published 2022 Jun 14. doi:10.1186/s13075-022-02825-7

SLE-dysregulated genes were linked to biological functions and gene networks, including regulation of type I interferon-mediated signaling pathway, response to steroid hormone, and response to hypoxia. 

SLE Impacts Long Noncoding RNAs in the Placenta of Pregnant Patients

The American College of Rheumatology (ACR)/American Association of Hip and Knee Surgeons (AAHKS) has published 

 regarding the management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty, with emphasis placed on perioperative use of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The last guideline update was published in 2017.

“Advances in antirheumatic therapy have led to remarkable improvements in treatment and quality of life for people with rheumatic musculoskeletal diseases (RMDs); however, total hip arthroplasty (THA) and total knee arthroplasty (TKA) remain a mainstay of treatment among RMD patients with advanced symptomatic joint damage, most frequently those with inflammatory arthritis (IA), including spondylarthritis (SpA), rheumatoid arthritis (RA), or psoriatic arthritis (PsA), and those with systemic lupus erythematosus (SLE),” investigators stated.

Patients with RA, PsA, SLE, juvenile idiopathic arthritis (JIA), and ankylosing spondyloarthritis (AS) who are undergoing elective THA or TKA: continuing the usual DMARDs through surgery is conditionally recommended for methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, and/or apremilast.

Patients with RA, PsA, JIA, and AS who are undergoing elective THA or TKA: withholding all biologics prior to surgery and planning surgery after the next dose is conditionally recommended.

Patients with RA, PsA, JIA, and AS who are undergoing THA or TKA: withholding tofacitinib, upadacitinib, and baricitinib for 3 or more days prior to surgery is conditionally recommended.

Patients with SLE who are interested in THA or TKA: continuing the usual dose of mycophenolate mofetil, cyclosporine, mizoribine, azathioprine, mycophenolic acid, or tacrolimus, anifrolumab, and voclosporin is conditionally recommended.

Patients with severe SLE undergoing THA or TKA: planning surgery in the last month of the dosing cycle of rituximab and continuing belimumab treatment is conditionally recommended.

Patients with SLE (not severe) undergoing THA or TKA: withholding the current dose of mizoribine, cyclosporine, azathioprine, mycophenolic acid, mycophenolate mofetil, or tacrolimus 1 week before surgery is conditionally recommended. 

Patients with SLE (not severe) undergoing THA or TKA: withholding the usual dose of rituximab and belimumab prior to surgery is conditionally recommended.

Patients with severe SLE undergoing THA or TKA: continuing belimumab and planning surgery in the last month of the dosing cycle of rituximab is conditionally recommended.

Patients with RA, PsA, AS, and SLE who had antirheumatic therapy withheld prior to undergoing THA or TKA: therapy should be restarted once wound begins to heal, there is no significant swelling, erythema, or drainage, sutures and/or staples are out, and there is no nonsurgical site infection. This occurs roughly 2 weeks after surgery and is conditionally recommended. 

Patients with RA, AS, PsA, and SLE undergoing THA or TKA receiving GCs: continuing current dose of GCs instead of administering supraphysiologic doses of GCs on the day of surgery is conditionally recommended.

ACR, AAHKS Updates Guidelines for Patients with Rheumatic Disease Undergoing Knee, Hip Surgery 

, plasma levels of glycoprotein acetyls (GlycA) are associated with reported onset of gout.

“Serum urate (SU) level is the strongest known causal predictor of clinical gout, but only [approximately] 20% with prolonged hyperuricemia develop gout, motivating the need for additional biomarkers for risk prediction and stratification,” investigators stated. “The metabolome represents a compelling intermediate trait between genome and phenome to elucidate disease mechanisms.”

In the discovery-based, large-scale, prospective metabolomics study, investigators identified novel biomarkers of incident gout and replicated novel metabolomic biomarkers of gout, including plasma levels of GlycA, in independent samples. In total, 105,703 patients with no prior gout diagnosis or history of urate lowering therapy and targeted nuclear magnetic resonance (NMR) metabolomic profiling (N=168 metabolites, including routine lipids and amino acids) available from samples taken between 2006 and 2010 in the UKB were included in the study. Ultimately, 46% of patients were males and the mean age was 57.2 years. Incident gout cases were recognized from linked medical records until gout diagnosis, patient death, or the end of the study (December 31, 2019).

A Cox proportional hazard model was used to obtain hazard ratios (HR) and 95% confidence intervals (CIs) per standard deviation (SD) increase for each of the 168 metabolites to evaluate their associations with incident gout. To replicate their findings, investigators analyzed the association of metabolome-wide significant metabolites via a replication set, which was limited to 4804 patients who were able to provide blood in a repeat assessment visit between 2012 and 2013.

The median follow-up period was 10.4 years, during which 1367 cases of incident gout were documented in the discovery set. After correcting multiple comparisons, including adjusting for age, sex, lifestyle, and clinical covariates, GlycA were positively associated with the risk of incident gout (multivariable HR per 1SD increase = 1.34 (1.27 to 1.41), 

= 9.04x 10-28). Further, the association continued after SU adjustment (HR 1.07, 

= 0.0091). The 4804 patients included in the replication set reported 22 cases during the follow-up period (median 6.89 years). Within this dataset, investigators replicated GlycA association with incident gout (multivariable HR per 1SD increase =1.56 (1.08 to 2.25), 

“GlycA is novel for gout, though this pro-inflammatory biomarker has predicted risk of other cardiometabolic-inflammatory phenotypes, independent of C-reactive protein (CRP),” investigators concluded. “These findings may provide insight into the metabolic-inflammatory pathogenesis of gout, with implications for risk prediction, even beyond SU, but call for further investigation with more extensive metabolome profiling and external replication.”

The study, “A Population-Based, Prospective metabolomics Study in the UK Biobank Identifies Glycoprotein Acetyls as a Novel Biomarker of Incident Gout,” was presented at the 

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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.

A biologic DMARD or targeted synthetic DMARD

Sulfasalazine and hydroxychloroquine (ie, triple therapy)