RA is a chronic disease characterized by inflammation in the synovium, the tissue that covers the inner surface of the joint cavity. Although usually accompanied by joint pain, swelling and deterioration, the level of inflammation varies from patient to patient, potentially requiring customized treatment plans. “What is surprising to us is that there are some patients who have clinical remission, yet continue to experience pain and show radiographic progression of the disease with high levels of synovial inflammation, while others have high disease activity with many swollen and tender joints and little inflammation in the synovial tissue” said Susan M. Goodman, MD, rheumatologist at HSS and principal investigator of the study. She explained that even when standard tests suggest the disease is under control, the joint fluid can still show high levels of inflammation. “By analyzing synovial fluid characteristics, we expected it might give us some insight into the disparity between disease progression and apparent remission,” she added.

The team analyzed samples from 64 patients with RA, 90.6% of whom were women, and with a median age of 65.3 ±11.7 years. The physicians collected synovial fluid samples to analyze and compare with the synovial tissue biopsy counterpart, which defines the inflammatory profile of the disease.

Dr. Goodman and the team measured the total white blood cell count, as well as the percentage of neutrophils, lymphocytes and monocytes in each synovial fluid sample. They then compared those findings to two additional key pieces of clinical information: the patient’s disease activity (such as joint swelling, pain, etc.) and the level of inflammation seen in the tissue.

Their analysis revealed that the total white blood cell count in the synovial fluid did not correlate with disease activity, however, the counting of individual cell types gave insights into tissue inflammation. As such, a higher percentage of neutrophils was associated with increased inflammation in the tissue, while a higher percentage of monocytes was associated with lower inflammation in the tissue.

Because the white blood cell counts in synovial fluid provided distinct and different information from standard disease activity measures and correlated well with tissue inflammation, the team believes it could help guide the selection of personalized anti-inflammatory therapies more efficiently.

“Synovial fluid extraction is already a routine part of care, but until now, it has never been used to analyze disease state in this way,” explained Dr. Goodman. In other words, the approach could be adopted without placing additional burden on healthcare providers.

"It's important that we're gaining new methods of investigating patients with RA,” Dr. Goodman added, “since choosing the appropriate therapy and choosing it in an efficient way is clearly the best way to achieve the best outcomes.”

According to Dr. Goodman, the next phase of this study, led by HSS rheumatologists Melanie H. Smith, MD, MPH, and Dana Orange, MD, MS, will look at both the proteomics and genetics of the cells within the fluid with more molecular and immunologic techniques, with the goal of finding even more clinically relevant and important information.

Poster details

Title: Can synovial fluid features be used to predict synovial tissue pathotype?

Authors: Susan M. Goodman, Michael Parides, Solana Cushing, Daniel Ramirez, Edward DiCarlo, Rebecca B. Blank, Laura Donlin, Anna Helena Jonsson, Amit Lakhanpal, Bella Mehta, Dana Orange, Melanie Smith.

Abstract n°: 2057

Presentation: June 12^th, 2025. 2:45 PM CEST

Advancements in surgical techniques and the increased use of a medication called tranexamic acid for preventing and controlling bleeding have made it possible for many patients undergoing knee replacement to avoid needing a transfusion, which requires hospital admission for at least a day.

Despite these advancements, it was believed that patients with RA undergoing orthopedic surgeries had an elevated risk of transfusion since they tend to have higher rates of anemia compared to the individuals without the disease. RA occurs in about 1% of the general American population.² About 4% of patients having joint replacement surgeries at HSS have the disease.

“Learning that rheumatoid arthritis was not a transfusion risk factor was unexpected,” said HSS rheumatologist Susan M. Goodman, MD, co-author of the study. “However, we believe presurgical care, including proactively managing chronic anemia before surgery, played a key role in minimizing transfusion risk.”

For their study, Dr. Goodman, HSS rheumatologist Linda A. Russell, MD, and colleagues analyzed hospital records for more than 29,000 patients who had a single total knee arthroplasty procedure at HSS from February 2016 to December 2022. A total of 822 patients, or 2.8%, received transfusions. The transfusion rate declined significantly during the study period from 5.7% in 2016 to 0.9% in 2022.

The investigators reviewed patient demographics such as age and sex, preoperative hemoglobin levels, RA diagnosis and the use of tranexamic acid during surgery, and then looked for associations with transfusion risk.

“In addition to finding that rheumatoid arthritis was not a transfusion risk factor, analysis revealed that a higher preoperative hemoglobin level and the use of tranexamic acid significantly decreased transfusion risk, while being male and having a greater burden of other diseases increased risk,” said HSS pre-doctoral student and research assistant Stephen Batter, BA, the presenting author of the poster summarizing the study.

The research team plans to use their unexpected findings to develop a tool to identify patients with different levels of transfusion risk based on preoperative hemoglobin level, sex, age and health status. This initiative may help orthopedic surgeons better anticipate which patients can safely avoid transfusion and may be suitable candidates for outpatient knee replacement surgery.

Authors: Stephen Batter, BA, Huong Do, MA, Dongmei Sun, PhD, Ahmed Deeb, BA, Trang Bui, MD, Jason L. Blevins, MD, Mark P. Figgie, MD, Gwo-Chin Lee, MD, J. Alex B. Gibbons, BA, Bella Mehta, MD, MS, MBBS, Susan M. Goodman, MD, Linda Russell, MD.

Reference:

¹ Batter S, Do H, Sun D, Deeb A, Bui T, Blevins J, Figgie M, Lee G, Gibbons J, Mehta B, Goodman S, A Russell L. Investigating Predictors of Transfusion in Rheumatoid Arthritis and Osteoarthritis Patients Undergoing Knee Arthroplasty [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/investigating-predictors-of-transfusion-in-rheumatoid-arthritis-and-osteoarthritis-patients-undergoing-knee-arthroplasty/. Accessed October 10, 2024.

² Xu Y, Wu Q. Prevalence Trend and Disparities in Rheumatoid Arthritis among US Adults, 2005-2018. J Clin Med. 2021;10(15):3289. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348893/. Accessed October 10, 2024.

The study, presented today at the annual meeting of the American College of Rheumatology, ACR Convergence 2024, was led by researchers at the University of Colorado School of Medicine in collaboration with investigators from HSS and other centers within the Accelerating Medicines Partnership® Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP® RA/SLE) Network.¹

“These research findings validate the importance of certain immune cells in the development of RA, particularly in how they drive the change from asymptomatic to symptomatic,” said Laura Donlin, PhD, scientist and co-director of the HSS Precision Medicine Program and co-principal investigator of the National Institutes of Health-supported AMP Rheumatoid Arthritis research consortium. “We hope that one day we can use these insights to stop RA before it even begins.”

Rheumatoid arthritis is a type of inflammatory arthritis that can occur when specific types of immune cells attack the body’s healthy tissues, resulting in pain, swelling and stiffness in joints. It can also result in problems in other areas of the body, such as the heart, lungs, eyes, nerves and skin. Diagnosis typically relies on an evaluation by a rheumatologist for clinical signs and symptoms supported by further evidence from X-rays and blood tests.

For the study, the participating rheumatologists collected tissue and blood samples from patients who either had RA or were considered at risk due to specific antibodies, called ACPA, in their blood and having a first-degree relative with the disease. Researchers at the Broad Institute of MIT and Harvard then used advanced single-cell sequencing techniques to analyze the samples and compared the results to those from healthy individuals.

The analysis found higher numbers of certain immune cells in the patients at risk for RA, including CCR2+ T helper cells, T peripheral helper cells, type 1 T helper cells, and granzyme B-positive memory T helper cells. Advanced sequencing also gave the investigators a better understanding of which genes were activated in these cells, offering insight into how the immune cells in patients with RA differ from those in at-risk individuals and healthy people.

“We knew that the presence of ACPA in blood and having a first-degree relative with rheumatoid arthritis indicate risk, but this new research has allowed us to learn more about the underlying biology driving increased risk,” said HSS rheumatologist Susan M. Goodman, MD, a co-author of the study. “These insights will pave the way toward helping us develop a new tool for determining which patients may benefit from early intervention.”

“There is some evidence that existing RA drugs, such as abatacept or rituximab, may help prevent the disease, but they are relatively expensive and come with side effects,” said co-author S. Louis Bridges, Jr., MD, PhD, physician-in-chief and chief of the Division of Rheumatology at HSS. “Pending validation in larger studies, the new patterns of immune cells identified in this research could represent potential targets for the development of new, more effective therapies.”

HSS Authors: S. Louis Bridges, Jr., MD, PhD, Vivian P. Bykerk, BSc, MD, FRCPC, Susan M. Goodman, MD, Laura Donlin, PhD.

Reference:

¹ Inamo J, Keegan J, Griffith A, Ghosh T, Horisberger A, Howard K, Pulford J, Murzin E, Hancock B, Eisenhaure T, Dominguez S, Gurra M, Gurajala S, Jonsson A, Seifert J, Feser M, Norris J, Cao Y, Apruzzese W, Bridges S, Bykerk V, Goodman S, Donlin L, Firestein G, Bathon J, Hughes L, Tabechian D, Filer A, Pitzalis C, Anolik J, Moreland L, Hacohen N, Guthridge J, James J, Cuda C, Perlman H, Brenner M, Raychaudhuri S, Sparks J, Holers M, Deane K, Lederer J, Rao D, Zhang F. Deciphering Pathogenic Phenotypes by Multi-modal Deep Single-cell Blood Immunophenotyping in Individuals At-risk for Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/deciphering-pathogenic-phenotypes-by-multi-modal-deep-single-cell-blood-immunophenotyping-in-individuals-at-risk-for-rheumatoid-arthritis/. Accessed October 10, 2024.

Researchers at HSS and other institutions have noted that women with knee osteoarthritis report more pain than men, but the reason for this difference has been unclear. “Others have speculated that women tend to delay surgery more than men, but when we looked in our database, that wasn’t true,” said HSS rheumatologist Dana Orange, MD, MS, assistant professor at The Rockefeller University and senior author of the study. “We studied synovial tissue removed at the time of total knee arthroplasty to look for a biological reason that may explain the difference in reported pain between sexes.”  

Synovial tissue lines the knee joint and produces fluid that helps the joint move. It can become inflamed as osteoarthritis progresses. Pathologists at HSS have been generating data on different types of cells found in synovial tissue, including mast cells, which are also found in many other tissues throughout the body and are commonly known for producing inflammatory chemicals called histamines during allergic reactions and asthma. Basic research by other scientists has suggested a link between mast cells and osteoarthritis progression and pain.

Dr. Orange and colleagues, including HSS rheumatologist Bella Mehta, MBBS, MS, lead author of the study, studied joint tissue obtained from 96 women and 61 men who underwent total knee replacement at HSS. They counted the number of cells for more than a dozen cell types typically found in synovial tissue and examined synovial fluid and blood using a high-powered microscope. They also evaluated patient-reported pain outcomes collected with two validated surveys. “At HSS, we were in a unique position to conduct this research because we have synovial tissues collected from patients with end-stage osteoarthritis undergoing arthroplasty and expert musculoskeletal pathologists who systematically grade tissue samples for 13 characteristics,” Dr. Mehta said.  

The investigators discovered that synovial tissue from women had significantly more mast cells, 63 per sample area, compared to 46 in tissue from men, on average. They also found higher levels of a byproduct of mast cells called tryptase in synovial tissue from women than men, providing further evidence of increased mast cell activity. No other differences in synovial tissue between sexes were observed. Finally, as expected, women reported worse pain than men on both surveys.

“We hope our findings encourage other researchers to start thinking about biological factors that may contribute to sex differences in patient-reported pain in knee osteoarthritis,” Dr. Orange said.

Authors: Bella Mehta, MBBS, MS, Edward F. Dicarlo, MD, Miguel Otero, PhD, Peter K. Sculco, MD, Mark P. Figgie, MD, Susan M. Goodman, MD (HSS), Fei Wang, PhD (Weill Cornell Medicine), Eun Kyung Song, PhD (Stanford University School of Medicine), Dana Orange, MD, MS (HSS and The Rockefeller University). 

The studies focus on the tapering of treatment in patients whose disease is well controlled, real-world outcomes for targeted therapies, assessing the effects of biologic treatments on immune cells from patients with RA, and the underlying mechanisms of arthritis triggered by immune checkpoint therapies used to treat cancer.

What follows are some highlights from the meeting:

Effectiveness of Upadacitinib in the Treatment of Rheumatoid Arthritis: Analysis of 6-Month Real-World Data from the United Rheumatology Normalized Integrated Community Evidence (UR-NICETM) Database

Upadacitinib, an oral Janus kinase (JAK) inhibitor, was approved for the treatment of RA in 2019 after clinical trials suggested that it reduced symptoms and had acceptable side effects. But since that time, few real-world data have been reported on how patients respond to upadacitinib outside of clinical trials. This six-month study looked at outcomes for 140 patients receiving upadacitinib alone and 223 receiving upadacitinib plus conventional synthetic disease-modifying antirheumatic drugs (DMARDs). The investigators, led by HSS rheumatologist Allan Gibofsky MD, JD, MACR, FACP, FCLM, found that overall 46% of patients receiving upadacitinib achieved low disease activity and 14% achieved remission, with better results for patients in the combination therapy group than those who got upadacitinib alone. The effectiveness of upadacitinib was not impacted by prior therapy with a tumor necrosis factor inhibitor or tofacitinib. This study supported the use of upadacitinib in clinical practice, including in patients with prior exposure to advanced therapy.

Authors: Allan Gibofsky, MD, JD, MACR, FACP, FCLM (HSS), Mark E. Pearson, MD (West Suburban Center for Arthritis), Andrew Concoff, MD (United Rheumatology), Anna Shmagel, MD, Patrick Zueger, PhD, Yanna Song, MS, Lauren D. Smith, MD (AbbVie Inc.), Grace C. Wright, MD, PhD (Grace C. Wright MD PC, Association of Women in Rheumatology).

Can Patients with Controlled RA Receiving Any Class of Targeted Therapy with Methotrexate (MTX) Sustain Disease Control after Tapering MTX? A Systematic Review and Meta-Analysis 

People with RA frequently wish to taper the use of methotrexate therapy due to its side effects, but there are questions about the best way to do that. Guidelines that recommend tapering methotrexate before tapering biologic DMARDs are not based on direct evidence. In this study, a team of HSS investigators led by rheumatologist Charis F. Meng, MD, and Director of the Inflammatory Arthritis Center Vivian P. Bykerk, MD, FRCPC, conducted a literature search to look at whether patients who are taking the combination of methotrexate and targeted therapy (biologic therapies and JAK-inhibitors) can taper methotrexate and still be in remission from their RA, while continuing their targeted therapies. They identified 10 studies that met their inclusion criteria. These studies included a number of different targeted therapies. Based on their analysis, the team concluded that patients with controlled RA have a high probability of maintaining disease control for at least 18 months after tapering their methotrexate and continuing targeted therapies. They noted that this review may inform patients who are experiencing controlled disease while taking methotrexate in combination with any of a range of targeted therapies and who are struggling with methotrexate-related side effects. However, they concluded longer follow-up studies are needed to confirm the disease will not worsen over time and that patients should be told about this possibility.

Authors: Charis F. Meng, MD, Diviya Rajesh, Deanna Jannat-Khah, DrPH, Omar Bruce, MPH, Bridget Jivanelli, MLIS, Vivian P. Bykerk, BSc, MD, FRCPC (HSS).

Differential Pharmacodynamic Alterations After Treatment with Abatacept or Adalimumab in MTX-Inadequate Responder Patients with Early RA: Whole Blood RNA-Seq Analysis of the Early AMPLE Study

A number of novel agents for RA are now available for treatment, but tools to predict which patients are likely to respond to specific drugs are lacking. To ensure that patients are matched with the best treatment, more research is needed to determine the molecular signatures of these drugs and their mechanisms of action. In this study, part of a Phase 4 trial called Early AMPLE, investigators including HSS Physician-in-Chief and Chair of the Department of Medicine S. Louis Bridges, Jr., MD, PhD, and Director of the Inflammatory Arthritis Center Vivian P. Bykerk, MD, FRCPC, looked at pharmacodynamic changes in patients in response to treatment with either abatacept or adalimumab. The aim was to identify and differentiate the impact of each drug on modulation of immune cells at the molecular level. The investigators performed pharmacodynamic and other analyses for 14,540 protein-coding genes in 664 RNA- Seq samples, with materials collected from 79 patients with RA who were predicted to respond better to abatacept. They found that after treatment, twice as many genes and pathways were significantly altered in the adalimumab arm versus the abatacept arm and that abatacept treatment decreased immune cell cycle gene expression while adalimumab treatment increased expression of these genes. The differential gene expression was seen in genes known to correlate with RA disease activity. The investigators concluded that these findings may explain the greater clinical improvements seen with abatacept versus adalimumab. Because patients in the Early AMPLE study were predicted to respond differentially to abatacept, these findings may be relevant only to this subgroup of patients. These findings warrant further studies to investigate the potential positive correlation between RA-relevant effects and better therapeutic outcomes.

Authors: Chun Wu (Bristol Myers Squibb), Yicong Li (Parexel International), Neelanjana Ray, Michael A. Maldonado, Peter Schafer (Bristol Myers Squibb), S. Louis Bridges, Jr., MD, PhD (HSS), William Rigby (Dartmouth-Hitchcock Medical Center), Vivian P. Bykerk, MD, FRCPC (HSS), Jane Buckner (Benaroya Research Institute at Virginia Mason), Jinqi Liu (Bristol Myers Squibb).

The Probability of Sustaining Rheumatoid Arthritis Remission in Patients Tapering Targeted Therapy Used as Monotherapy: a Systematic Review and Meta-Analysis 

A second study led by HSS rheumatologist Charis F. Meng, MD, and Director of the Inflammatory Arthritis Center Vivian P. Bykerk, MD, FRCPC, also used a literature review to look at the effects of tapering drugs for RA in people whose disease is well controlled. This study focused on patients receiving either biologic DMARDs or JAK inhibitors being used alone. A search resulted in five studies that compared tapering of targeted monotherapy (TNF-i, tocilizumab, abatacept, or baricitinib) with continuing therapy or other tapering regimens. A meta-analysis including data from 800 patients found a trend for lower odds of disease remission with targeted therapies versus comparator treatment regimens, but these data were not conclusive. The investigators noted that the lack of trials designed to compare tapering targeted monotherapy to continuing it led to a significant gap in knowledge in an area of research that is increasingly relevant for patients. Their review suggests that stopping targeted monotherapy is unlikely to maintain disease control, but that more gradual tapering schemes, dose reduction, and early treatment of disease may be associated with more successful tapering. More studies are needed to better inform patients, and it is not recommended to stop targeted monotherapy in RA based on this analysis.

Authors: Charis F. Meng, MD, Diviya Rajesh, Deanna Jannat-Khah, DrPH, Omar Bruce, MPH, Bridget Jivanelli, MLIS, Vivian P. Bykerk, MD, FRCPC (HSS).

Less ACPA Epitope Expansion Is Found in ACPA-Positive Immune Checkpoint Inhibitor Arthritis Patients Compared to ACPA-Positive Rheumatoid Arthritis Patients

Immune checkpoint inhibitors (ICI) have improved the treatment of many advanced cancers. However, they can lead to immune-related adverse events, including treatment-induced arthritis. This form of arthritis is similar to RA. About 9% of people with this condition test positive for the anti-citrullinated peptide antibody (ACPA). In RA, the increase in ACPA occurs over the years prior to onset of clinical disease. In this study, led by HSS rheumatologist Nilasha Ghosh, MD, MS, investigators examined the degree of ACPA epitope expansion in patients receiving ICI to determine whether treatment-induced arthritis is similar to early RA, or more suggestive of the pre-clinical phase of disease. The analysis employed clinical data and serum samples from 12 patients with ICI arthritis (ICI-A) as well as from 39 ACPA-positive RA patients. There were a number of differences between the patients in the two groups, including age and smoking history. The investigators reported that, overall, people with ICI-A had lower ACPA titers and targeted fewer ACPA epitopes than people with early RA, suggesting that ICI-A may represent an accelerated model of RA pathogenesis with ICI triggering an early transition from pre-clinical to clinical disease. They noted that sequential sampling and analysis are warranted to further determine how the pathogenesis of ICI-A relates to that of RA.

Authors: Diviya Rajesh, Nilasha Ghosh, MD, MS (HSS), Jessica Kirschmann (Stanford University), Karmela Kim Chan, MD, Deanna Jannat-Khah, Susan M. Goodman, MD, Vivian P. Bykerk, BSc, MD, FRCPC (HSS), William Robinson, MD, PhD (Stanford University), Anne R. Bass, MD (HSS).

TKR is often the only management option for patients with severe knee joint damage. Identifying which disease caused the joint damage is essential for guiding treatment plans, given that RA is a systemic, inflammatory disease that may also affect the eyes or lining around the heart, while OA affects just the joints. “We know there are many more immune cells present in the synovium, or joint tissue, of patients with RA compared to those with OA,” said Bella Mehta, MBBS, MS, rheumatologist at HSS and lead author of the study. “But precisely how many more has not been clear.”

“Pathologists typically assess images of synovium to determine the extent of inflammation using a combination of approaches, including assigning the level of immune cell infiltration on a scale from 0 to 4,” said Dana Orange, MD, MS, rheumatologist at HSS, assistant professor at Rockefeller University and senior author of the study. “However, these methods are imperfect.” For example, a recent study by HSS investigators found that assessments from two highly experienced pathologists evaluating the infiltration of one type of immune cells known as lymphocytes on the same slides agreed only 67 percent of the time.¹

Drs. Orange, Mehta and colleagues at HSS and collaborating institutions developed and validated a computer vision tool that rapidly counts tens of thousands of cell nuclei in whole-slide images of synovium.² For their present study, they measured 14 different pathologist-scored features in synovium from 60 patients with RA and 147 patients with OA who underwent TKR, and used the computer vision tool to determine cell density.

The investigators identified significant differences between RA and OA features in synovium. The RA samples showed increased cell density; low numbers of mast cells, a type of white blood cell; and lower evidence of fibrosis or scarring compared to the OA samples. The probability of correctly distinguishing between RA and OA in synovium was 85 percent when using the 14 pathologist-scored features alone, 88 percent when using the computer’s score for cell density alone and 91 percent when the researchers combined the pathologists’ scores and the computer’s cell density calculation. The researchers determined a cutoff point for distinguishing RA from OA, determining that synovium containing more than 3,400 cells per mm² should be classified as RA.

“While our innovation is not ready for clinical use yet, it holds promise for assisting pathologists in the future,” Dr. Orange said. “Right now, we see it as a valuable tool for research purposes because it provides an accurate and 100% reproducible score of inflammation and look forward to developing it further.”

Dr. Orange added that in the future computer vision could be trained to glean other types of information from tissue samples, including which types of cells are present and whether they are close enough together that they are likely to be communicating with each other. This more granular assessment might enable clinicians to know more precisely which cells are causing tissue damage and tailor treatments accordingly.

Authors: Bella Mehta, MBBS, MS, Susan M. Goodman, MD, Edward F. DiCarlo, MD, Deanna Jannat-Khah, J. Alex Gibbons, Miguel Otero, PhD, Laura Donlin, PhD (HSS), Tania Pannellini, MD, PhD (Weill Cornell Medicine), William Robinson, MD, PhD (Stanford University), Peter K. Sculco, MD, Mark P. Figgie, MD, Jose A. Rodriguez, MD (HSS), Jessica Kirschmann (Stanford University), James Thompson, David Slater, Damon Frezza (The MITRE Corporation), Zhenxing Xu, Fei Wang, PhD (Weill Cornell Medicine), Dana Orange, MD, MS (HSS and Rockefeller University).

References

1. Orange DE, Agius P, DiCarlo EF, et al. Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning Integration of Synovial Histologic Features and RNA Sequencing Data. Arthritis Rheumatol. 2018;70(5):690-701. doi:10.1002/art.40428

2. Guan S, Mehta B, Slater D, et al. Rheumatoid Arthritis Synovial Inflammation Quantification Using Computer Vision. ACR Open Rheumatol. 2022;4(4):322-331. doi:10.1002/acr2.11381

Bella Mehta, MBBS, MS, a rheumatologist at HSS and lead author of the study, presented the results today at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress in Copenhagen. “Lupus is a chronic autoimmune disorder that often affects women in their childbearing years,” explained Dr. Mehta. “In our previous work, we demonstrated that over the years, maternal and fetal mortality in lupus patients have improved significantly, and that was very reassuring to patients. However, less was known about morbidity. We set out to evaluate and quantify the indicators of fetal and maternal morbidity in women with lupus compared to those who did not have the disease.”

Using retrospective data from the National Inpatient Sample database, the researchers identified delivery-related hospital admissions from 2008 to 2017. Fetal morbidity indicators included preterm delivery and intrauterine growth restriction. Twenty-one indicators of severe maternal morbidity were identified and defined as unexpected outcomes of labor and delivery that result in significant short- or long-term consequences to a woman’s health.

Among the 40 million delivery-related hospital admissions, 51,161 patients were reported to have lupus. These patients were more likely to be older than women who did not have lupus (30.1 years versus 28.2 years), to be African American (25% versus 15%), and to receive Medicare (5% versus 1%).

During delivery, women with lupus were 15 times more likely to develop acute renal failure than those who did not have lupus (1.5% versus 0.1%), four times more likely to develop a cerebrovascular disorder (4.8% versus 1.1%), and nearly four times more likely to require a blood transfusion (4.0% versus 1.1%). Women with lupus were also more likely to develop cardiovascular and peripheral vascular disorders (1.1% versus 0.1%).

In terms of fetal morbidity, mothers with lupus were twice as likely to deliver prematurely (14.5% versus 7.3%) and nearly three times more likely to experience growth restriction in the womb compared to pregnant patients without lupus (8.0% versus 2.7%).

“The number of co-existing health conditions in pregnant women with lupus was much higher compared to women who did not have lupus. It seems likely that these comorbidities are responsible – at least in part – for the increased risk of fetal and maternal morbidity in lupus patients,” Dr. Mehta said. “It is noteworthy that a large percentage of deliveries by women with lupus were at large hospitals and urban teaching hospitals, reflecting the complexities of managing these patients.”

Dr. Mehta continued, “Our study is not meant to discourage women with lupus from getting pregnant. We believe our findings can help both patients and their physicians to assess risk, establish appropriate interventions and ensure that a multidisciplinary medical team is in place to counsel patients and manage their care.”

Authors: Bella Mehta, MBBS, MS, Katharine Kayla J. Glaser, Deanna Jannat-Khah (HSS), Yiming Luo (National Institutes of Health, Medicine, Bethesda), Lisa R. Sammaritano, MD, Jane E. Salmon, MD, Susan M. Goodman, MD (HSS), Fei Wang (Weill Cornell Medicine).

“Patient satisfaction related to the hospital experience following surgery is an important aspect of patient care,” said Susan M. Goodman, MD, a rheumatologist at Hospital for Special Surgery (HSS) and senior investigator. “The Press Ganey inpatient survey is commonly administered to patients to assess their satisfaction with the process of care. Our aim was to determine whether overall patient assessment scores differed by race or socioeconomic status.”

Dr. Goodman and a team of researchers reviewed the Press Ganey survey responses of more than 4,600 patients who had surgery at HSS from July 2010 to February 2012. Individuals having a primary knee or hip replacement who resided in New York, New Jersey or Connecticut were included in the study.

Researchers analyzed the data to establish an overall score, calculated as the mean of a patient’s ratings for three questions in the “Overall Assessment” section of the Press Ganey survey. The results were categorized as either “completely satisfied” (score of 100) or “not completely satisfied” (score <100).

The analysis, which included 2,516 individuals who underwent hip replacement and 2,113 who had a knee replacement, found that Black patients were more likely to indicate they were “not completely satisfied” compared to white patients in both joint replacement groups.

Dr. Goodman said that although Black patients indicated they were less satisfied with the process of care right after surgery, there was no difference in satisfaction with their joint replacement outcome. Factors such as pain and function are part of the outcome assessment, which is generally conducted two years after surgery.  

With respect to socioeconomic status, researchers considered the patient’s primary health insurance coverage. The study found that the individual’s primary payor was not associated with satisfaction in either joint replacement group.

“The study is important because we know that Black patients generally wait longer to seek treatment, presenting with worse pain and function prior to surgery, and we are trying to sort out the barriers to seeking timely care,” said Mark P. Figgie, MD, chief emeritus of the Surgical Arthritis Service at HSS and co-author of the study.

“Patient outcome measures indicate that although Black patients achieve significant improvement after surgery, it does not reach the same level as those who seek timely treatment,” he added. “Confidence in the health care system may contribute to the delay in seeking care, and this is something we need to address.”

Dr. Goodman added, “More research is needed to investigate other factors, such as perceived staff courtesy and baseline pain and function, to understand why disparities exist so we can achieve a high level of patient satisfaction for everyone.”

Authors: Anne R. Bass, MD, Emily Ying LAI, MSc, Huong Do, MA (HSS), John A. Gibbons, BA, Letitia Bradford, MD, FAAOS, FACS (Nth Dimensions), Mark P. Figgie, MD, Michael L. Parks, MD (HSS), Orett Burke, BS (Rutgers Robert Wood Johnson Medical School), Susan M. Goodman, MD (HSS).

“What we found was that at one year, those patients who had active disease were not as likely to do well, but the flares themselves didn’t really contribute to pain or poor function,” said lead study author Susan Goodman, MD, a rheumatologist at HSS. “I think this study gives us an idea that in RA, disease activity is really the bad actor when it comes to hip and knee replacement outcomes.”

Dr. Goodman and colleagues conducted the study after noticing that patients with RA have outcomes that aren’t consistently as good as patients with osteoarthritis after hip or knee replacement. Most RA patients undergoing THA and TKA have active RA and report post-operative flares, but whether RA disease activity or flares increased the risk of higher pain and lower function scores one year later was unknown. Understanding the reason for poor pain and function scores in RA patients can help optimize postoperative care. “One of the things we were suspicious of given the high likelihood of having a flare of RA after hip or knee replacement was that maybe those patients who flared couldn’t complete their physical therapy and wouldn’t be able to advance as quickly, leading to worse outcomes,” said Dr. Goodman.

To find out, the researchers launched the RA Perioperative Flare Study, a prospective observational cohort study of patients with RA undergoing a THA or TKA at HSS from November 2014 through April 2018. At baseline, the researchers obtained a full set of clinical data on the state of a patient’s disease, assessing the severity and activity of disease. Patient-reported outcome measures were collected prior to surgery and were repeated at one year and included the Hip and Knee Osteoarthritis/Disability and Injury Outcomes Scores (HOOS/KOOS) and physician assessments of disease characteristics and activity (DAS28, CDAI). Participants answered a questionnaire each week for six consecutive weeks postoperatively that addressed RA status and whether patients were experiencing a disease flare. The final analysis included 122 patients, 56 undergoing a THA and 66 undergoing a TKA.

The researchers found that although HOOS/KOOS pain was worse for patients who flared within six weeks of surgery, absolute improvement was not different. In multivariable models, baseline DAS28, disease activity, predicted one-year HOOS/KOOS pain and function with each 1 unit increase in DAS28 worsening one-year pain by 2.41 and one-year function by 4.96 (P=0.0001). High BMI also increased the risk of worse function. Postoperative flares were not independent risk factors for pain or function scores.

Dr. Goodman explained that patients with RA should anticipate a significant improvement in pain and function if they undertake hip or knee replacement surgery and that clinicians should target patients with higher disease activity for extra attention, such as increased physical therapy. She said that part of being an optimal candidate for surgery should include having less active disease. “One of the problems we have found is that many patients have longstanding active disease and have been on multiple different medications,” said Dr. Goodman. “It is not like getting a patient with new onset disease into low disease activity or remission; this is much more challenging.”

Dr. Goodman said that for patients with uncommon and challenging diseases, such as lupus and RA, it is important to seek care in a center that specializes in treating patients with these conditions. “That is one of the clearest ways to optimize your outcomes,” she concluded.

The study found that such a program could be helpful to patients scheduled for a knee replacement, according to Iris Navarro-Millan, MD, MSPH, a rheumatologist at HSS who served as principal investigator. She presented the study at the American College of Rheumatology/Association of Rheumatology Professionals annual meeting on November 12 in Atlanta.

“On a national level, up to 30% of patients may have persistent pain after knee replacement surgery for osteoarthritis,” Dr. Navarro said. “One possible approach to improve outcomes is to optimize muscle strength, physical condition and mental preparation before surgery. Social cognitive theory posits that self-efficacy, peer or social support, sociocultural factors and expectations influence goals and outcomes.”

“There are successful programs in other areas of medicine, such as diabetes care, in which patient navigators share their experience and knowledge with their peers to help them better manage the disease,” said Lisa Mandl, MD, MPH, senior study author and a rheumatologist at HSS. “The thinking is that having the right mindset could optimize outcomes.”

The HSS researchers established focus groups of people who had a knee replacement at HSS to obtain information about their thoughts and experiences. The researchers sought to determine if a “pre-hab” program with trained peer coaches could be helpful and of interest to future patients scheduled for knee replacement surgery.

The investigators defined a peer coach as a patient who has already undergone knee replacement surgery and has been trained to provide personalized pre- and post-knee replacement support.

The 31 patients in the focus groups ranged in age from 65 to 89 and had had a knee replacement at HSS at least 12 months earlier with a good outcome. For almost half the patients, it was their second knee replacement, as they had undergone a previous surgery on their other leg.

“We asked patients about their challenges before and after knee replacement, potential barriers to accessing a pre-habilitation program and perspectives on what it might be like working with a peer coach to encourage exercise prior to knee replacement,” Dr. Navarro said.

The following themes emerged from the focus groups:

• Many patients with osteoarthritis delayed knee replacement for many years, often until the pain became very bad.
• Many weren’t sure of the best way to prepare for knee replacement surgery.
• They appreciated advice from other patients about preparation and recovery, and learning about the positive experiences of others often motivated them to have the surgery.
• The concept of peer coaches was well received.
• A few participants were already informally helping others scheduled for surgery and found it very rewarding.

The researchers concluded that preparation and expectations for surgery were influenced by patients’ own prior experience with a knee replacement, as well as by the experience of other patients who had already had the surgery.

“Patients with high outcome expectations who had had a previous knee replacement learned from their first experience and reported feeling motivated to engage in physical activity for muscle strengthening before their second knee replacement,” Dr. Navarro explained. “They expressed that their own experiences made them more informed, self-efficacious and physically active to prepare for their surgery.”

Patients who had had their first knee replacement reported that informally connecting with another individual who had already had the surgery was important in their decision to go ahead with the procedure, and also in preparing for it. They indicated that working with a peer coach would be beneficial for both preparation and recovery.

“Our findings suggest that formal peer-to-peer counseling that prepares patients for their first knee replacement surgery may hold promise to improve outcomes,” Dr. Navarro said. “Future studies could focus on the best way to establish such a program.”

Other study authors include Sarah R. Young, PhD (Binghamton University); Geyanne Lui, BS (Weill Cornell Medicine); Mariana B. Frey, BA (HSS); Janey C. Peterson, RN, MS, EdD (Weill Cornell Medicine); Susan M. Goodman, MD (HSS); and Monika M. Safford, MD (Weill Cornell Medicine).

Lead study author Susan M. Goodman, MD, a rheumatologist at HSS, said that while patients with rheumatic diseases are more prone to developing PJIs, it is also harder to make a PJI diagnosis in this population because many of the typical inflammation features of PJIs are similar to those seen in inflammatory arthritis flares. “If a patient with osteoarthritis comes in with a swollen and inflamed prosthetic joint, it is an infection until proven otherwise, but for patients with rheumatoid arthritis, it can be very hard to sort out whether this is part of an overall flare of disease or if it is a true infection,” she said. “None of the available tests are that helpful.”

The researchers launched the new study to examine the clinical and microbiological features of total hip and total knee arthroplasty PJIs in patients with rheumatic diseases and osteoarthritis. The researchers used the HSS institutional PJI registry to create a retrospective cohort of total hip/total knee replacement PJIs from 2009 to 2016. They identified 807 PJI cases, including 36 in patients with rheumatic disease and 771 in patients with osteoarthritis. Culture-negative cases were defined as PJIs with no evidence of microbial growth in intraoperative cultures; culture-positive PJIs were defined by positive microbial growth.

Among the findings, the researchers discovered that patients with rheumatic diseases had a higher proportion of culture-negative PJIs (27% vs 14%; P=0.02). “Patients with rheumatic diseases who were culture negative were less likely to meet the pathology criteria for infections than the ones who were culture positive, and they did a little worse,” said Dr. Goodman. One-year survivorship of culture-negative osteoarthritis and culture-negative rheumatic disease were 87% and 66%, respectively, and 47% for culture-positive rheumatic disease.

“The main message is that patients with rheumatic disease seem to have more culture-negative prosthetic joint infections than patients with osteoarthritis, but what we don’t know is what that means in terms of long-term management,” said Dr. Goodman. “We had the feeling that we were missing something with our rheumatic disease patients who were coming in with prosthetic joint infections, so I wasn’t surprised by our findings, but it pointed out how much more we need to do to really understand this.”

Dr. Goodman said the next step is to do a prospective study in patients with rheumatic disease, which will provide the standard diagnostic tests for PJIs but also use Next Generation Sequencing including cell-free DNA methods to better identify bacteria present in tissue.

Bella Mehta, MBBS, MS, a rheumatologist at Hospital for Special Surgery (HSS) in New York City, presented the findings at the American College of Rheumatology/Association of Rheumatology Professionals annual meeting on November 11 in Atlanta.

“With the aging of the population, elective total hip replacement has become one of the fastest-growing procedures to manage severe osteoarthritis,” said Dr. Mehta. “By 2030, the number of hip replacements is expected to reach 572,000 annually in the US. Medicare, the largest payer of joint replacement surgery, has introduced several payment reform models that target discharge destination and risk of hospital readmission after surgery. Our study examined how the socioeconomic status of the community in which one resides influences discharge destination and the odds of 90-day hospital readmission after hip replacement.”

Dr. Mehta noted that where a patient receives post-op care and rehab has a considerable impact on the total cost of hip replacement surgery. Previous studies have demonstrated significant variations in outcomes and costs due to individual factors such as race. There have been far fewer studies on the impact of community-level factors.

“Our study pushes the envelope by examining the role of where one lives in understanding variations in post-op care after elective joint replacement surgery. And it reflects the growing academic collaboration in clinical research between HSS and Weill Cornell Medicine investigators,” explained Said Ibrahim MD, MPH, MBA, senior investigator and chief of the Division of Healthcare Delivery Science and Innovation at Weill Cornell Medicine.

For the analysis, the investigators identified almost 85,000 patients in the Pennsylvania Health Care Cost Containment Council database who had elective hip replacement surgery between 2012 and 2016. The researchers used the Area Deprivation Index (ADI) from the American Census Survey, which reflects a geographic area’s level of socioeconomic deprivation and is associated with health outcomes.

In addition to discharge destination, the investigators assessed the risk of 90-day readmission for patients sent to a facility compared to those who received their post-op care and rehab at home. The researchers also assessed the interaction of race and ADI on outcomes.

The study found that patients from impoverished communities were more likely to be discharged to an institution compared to home after a hip replacement. The interaction effect of race and ADI on discharge destination was statistically significant in African American patients 65 years and older, but not in patients under 65 years old. The level of community deprivation did not have an effect on 90-day hospital readmission, nor did the interaction of ADI and race.

As a possible explanation for the study findings, Dr. Mehta noted that patients from impoverished communities may have less access to community-based services such as social support. Thus, discharge to a facility for post-operative and rehabilitative care might be perceived as a safer option in clinical decision-making.

“Our study is important because it advances our understanding of the relationship between health care and social determinants of health,” said Dr. Ibrahim. “Future studies should determine which specific community factors influence discharge destination and how they could be modified to allow more patients to go home after a hip replacement.”

Dr. Mehta added, “The ultimate goal of research is to design socially informed health policies to improve quality of care and outcomes.”

Susan M. Goodman, MD, and Michael L. Parks, MD, of HSS and Kaylee Ho, MS, of Weill Cornell Medicine were also involved in the study.

Susan M. Goodman, MD, rheumatologist at HSS, explains that fat tissue releases pro-inflammatory chemicals that may have a role in systemic inflammation.

According to Dr. Goodman, losing weight may increase the changes of achieving rheumatoid arthritis (RA) remission. In a 2017 study of 982 women with early RA, Dr. Goodman and her colleagues found that overweight participants were 25 percent less likely and obese participants were 47 percent less likely than those of a healthy weight to achieve remission over three years.

Read the full article at Blog.Arthritis.org.

"For those with advanced renal disease, careful attention to dose adjustment and avoiding nephrotoxic agents such as cyclosporine or long-term maintenance with NSAIDs is important. Reduced renal function is associated with CVD [chronic kidney disease] risk factors such as age and hypertension and does not seem to be linked to disease duration or severity," she says.

Read the full article at RheumatologyAdvisor.com.