Newsroom Hospital for Special Surgery

Study Shows Avacopan Effective for Most Serious Vasculitis Cases

Mon, 18 Nov 2024 10:30:00 -0500

New research to be presented by an investigator from Hospital for Special Surgery (HSS) shows avacopan is effective in achieving disease control with less steroid exposure in patients with ear, nose and throat (ENT) manifestations of ANCA associated vasculitis -

Robert F. Spiera, MD, Director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery (HSS), helped lead this latest analysis which was presented at the ACR Convergence 2024, the annual meeting of the American College of Rheumatology. The study built on the pivotal ADVOCATE trial, focusing on patients with the most severe manifestations of vasculitis in the ENT region, which has historically been harder to treat.

Avacopan (Tavneos, Amgen) was approved by the US Food and Drug Administration in 2021 for the treatment of severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, a rare autoimmune disorder that can cause potentially life-threatening inflammation by restricting blood flow to vital organs.

Once considered a fatal condition, ANCA associated vasculitis is now treatable, especially if identified early and treated with appropriate immunsosuppressive medications. Avacopan is a targeted therapy that offers a safer and more effective alternative to prednisone which had traditionally been a mainstay of remission induction therapy in these disorders but carries with it high risks such as infections, weight gain, diabetes, and bone thinning.

While the original ADVOCATE trial established the avacopan as an improved treatment option, the new analysis zeroes in on a group of patients whose disease has historically been more difficult to treat – those with ENT involvement. These patients often experience debilitating symptoms such as pain, hearing loss, and chronic inflammation, which severely impact quality of life.

“We know patients with this disease often achieve remission in their kidneys and lungs, but ENT disease frequently becomes a significant factor impacting their quality of life,” Dr. Spiera said. “This analysis provides crucial insights, showing that avacopan not only brings faster relief but sustains improvement over time in patients with those manifestations.”

The new analysis focused on a subgroup of 144 patients from the ADVOCATE trial, all of whom had severe ENT symptoms. Findings revealed that patients treated with avacopan showed significant improvements as early as week 4, with results continuing to favor avacopan over prednisone at week 52. Remarkably, 71% of these patients reached remission at 26 weeks, closely mirroring the remission rates in the broader trial.

Beyond clinical improvement, patients taking avacopan reported higher quality of life scores compared to the group taking prednisone. “Avacopan offers these patients a real opportunity to live with fewer limitations,” noted Dr. Spiera.

Equally important, the study showed that avacopan’s safety profile was comparable to that of prednisone, with similar rates of adverse events such as infections.

“These encouraging results underscore the importance of considering avacopan, for patients with microscopic polyangiitis and granulomatosis with polyangiitis with active ENT symptoms,” Dr. Spiera said.

HSS Presents New Research at the ACR Convergence 2024

Sat, 16 Nov 2024 10:30:00 -0500

At this year’s American College of Rheumatology (ACR) annual meeting, HSS presented exciting research related to rheumatology and orthopedics.

Research highlights include a study showing that online search trends can lead to more personalized rheumatic disease care, and blood changes in people at risk for rheumatoid arthritis, a study revealing that having rheumatoid arthritis was not a risk factor for needing a blood transfusion during or after total knee replacement, new discoveries in antiphospholipid syndrome, the effectiveness of avacopan for severe vasculitis, new insights on rheumatic diseases and reproductive health and a study that shows knee osteoarthritis causes more pain and inflammation in women.

New Study Signals How Online Search Trends Could Lead to More Personalized Rheumatic Disease Care

Physicians are learning how to better support the needs of people with rheumatoid arthritis from online search trends, according to a new study from researchers at HSS and colleagues at Columbia University Vagelos College of Physicians & Surgeons.

New Research Reveals Alterations in Blood of People at Risk of Developing Rheumatoid Arthritis

A new study by HSS and collaborating centers identified distinct immune cell patterns in the blood that signal an increased risk of developing rheumatoid arthritis before symptoms occur.

Surprising Study Finds No Link Between Rheumatoid Arthritis and Transfusion Risk After Knee Replacement

Having rheumatoid arthritis was not a risk factor for needing a blood transfusion during or after total knee replacement, according to a new study by HSS researchers.

New Antiphospholipid Syndrome Research Findings Presented at ACR Convergence 2024

Investigators from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) presented new research findings in antiphospholipid syndrome (APS). These studies explore differences in clinical manifestations of APS in children versus adults, identify key risk factors for thrombosis in persistently antiphospholipid antibody-positive patients, and investigate the prevalence and implications of lupus-related autoantibodies in patients without lupus.

Study Shows Avacopan Effective for Most Serious Vasculitis Cases

New multicenter study by HSS and others by HSS shows avacopan is effective in achieving disease control with less steroid exposure in patients with ear, nose and throat manifestations of ANCA associated vasculitis.

HSS Presents Cutting-Edge Discoveries in Rheumatic Disease and Reproductive Health at ACR Convergence 2024

HSS presented a number of studies focused on reproductive health for patients with rheumatic diseases including factors influencing infant feeding, predicting pregnancy outcomes in lupus, and improving contraception screening for women on teratogenic medications in rheumatology.

Study Shows Knee Osteoarthritis Causes More Pain and Inflammation in Women

Women with knee osteoarthritis experience more pain and inflammation than men, according to a new study led by researchers at HSS and The Rockefeller University.

Study Assesses Sarilumab for Polymyalgia Rheumatica

Thu, 25 Jan 2024 09:12:00 -0500

The Rheumatologist reports that in an ACR Convergence 2022 session, Robert F. Spiera, MD, rheumatologist at HSS, discussed the use of sarilumab as a potential glucocorticoid-sparing therapy in a phase 3 study in patients with treatment-refractory polymyalgia rheumatica (PMR), one of the most common inflammatory diseases of the elderly.

“Polymyalgia rheumatica is relatively easy to treat with glucocorticoids, but unfortunately relapses are common, resulting in prolonged courses of glucocorticoid therapy with its attendant morbidities,” Dr. Spiera said. “So we have recognized that a steroid-sparing therapy is an unmet need in PMR.”

Dr. Spiera and his colleagues designed the SAPHYR trial, a randomized, double-blind, placebo-controlled phase 3 study, to assess the efficacy and safety of another IL-6 antagonist, sarilumab, in PMR patients aged 50 or older. Dr. Spiera pointed out that they studied patients who were refractory to steroid treatment, the PMR population with the greatest unmet treatment needs.

Read the full article at the-rheumatologist.org.

How to Treat Refractory Polymyalgia Rheumatica

Thu, 25 Jan 2024 09:07:00 -0500

The Rheumatologist reports that patients with polymyalgia rheumatica (PMR) who had relapsed while tapering glucocorticoid therapy were more likely to achieve sustained remission at one year and have a lower glucocorticoid exposure if they were treated with sarilumab (Kevzara) plus a rapid, 14-week glucocorticoid taper than if they received placebo plus a standard, 52-week glucocorticoid taper. This is according to a study published in The New England Journal of Medicine.

“PMR is among the most common inflammatory diseases, and although corticosteroids are extremely effective in controlling disease activity, flares, which generally necessitate raising the corticosteroid dose, are common, meaning that most patients have a prolonged course of treatment,” explains Robert F. Spiera, MD, rheumatologist at HSS. “This results in many corticosteroid-related complications in this vulnerable group of patients. There is a major unmet need for an effective corticosteroid-sparing strategy in this disease, particularly in refractory patients.” Previous studies have implicated IL-6 in the pathophysiology of PMR and suggested that IL-6 inhibition may be clinically useful in treating the condition.

“It is exciting to see an understanding of disease pathophysiology ultimately result in the demonstration of a targeted therapy being effective in a rheumatic disease,” said Dr. Spiera. “This is truly a bench-to-bedside journey, as it has been for many of the other biologics and targeted therapies that have led to improved outcomes for patients with inflammatory and autoimmune diseases. Our improved sophistication in clinical trial design and execution also contributed enormously to the ability to prove this strategy as effective.”

Read the full article at the-rheumatologist.org.

Sarilumab superior to placebo for achieving sustained remission in polymyalgia rheumatica

Mon, 18 Dec 2023 11:05:32 -0500

Healio speaks to Robert F. Spiera, MD, rheumatologist at HSS on his study published in The New England Journal of Medicine demonstrating the efficacy of sarilumab in adult patients with refractory polymyalgia rheumatica (PMR).

“Patients with polymyalgia rheumatica who have a relapse while tapering glucocorticoid therapy or have glucocorticoid-related adverse effects have limited treatment options,” explained Dr. Spiera. Thurs, treatments that hasten disease remission, decrease symptoms, reduce overall dependance on glucocorticoid and the associated toxic effects, and improve quality of life and function are needed,” he said.

To analyze the effectiveness of sarilumab in patients with polymyalgia rheumatica Dr. Spiera and colleagues conducted SAPHYR, a phase 3, multicenter randomized, double-blind, placebo-controlled study. The researchers included patients with polymyalgia rheumatica who flared glucocorticoid tapering in the 12 weeks leading up to enrollment.

Upon enrollment, patients were randomized 1:1 to receive 52 weeks of a twice-monthly injection of sarilumab 200 mg, plus 14 weeks of prednisone tapering, or placebo and 52 weeks of prednisone tapering. To manage adverse events and complications, patients receiving sarilumab could receive reduced doses every other injection.

The primary outcome at 52 weeks was sustained remission, defined as the achievement of clinical remission by week 12, with a lack of flares and sustained improvements in CRP and prednisone tapering adherence through 52 weeks. Key secondary endpoints included cumulative glucocorticoid dose through 52 weeks and the time until onset of first disease flare.

Read the full article at healio.com.

HSS Presents New Reproductive Health Research at the ACR Convergence 2023

Tue, 14 Nov 2023 12:05:00 -0500

At this year’s American College of Rheumatology (ACR) annual meeting, HSS presented a number of important studies focused on reproductive health for patients with systemic lupus erythematosus, rheumatoid arthritis, and other rheumatic diseases, including issues related to fertility, sexual function, use of contraception and HPV vaccination.

What follows are some highlights from the meeting:

Association of Menstrual Cycles and Disease Flare Activity in Women with Systemic Lupus Erythematosus and Rheumatoid Arthritis
In this study, researchers surveyed female rheumatology patients to determine whether the menstrual cycle affects the timing of disease flares. More than 300 patients responded to the survey, and the analysis reported at the meeting included data from 122 respondents with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) — 49 with SLE and 73 with RA.

Overall, 39% reported an association between their menstrual cycle and disease flares, with similar rates in both the SLE and RA groups. Those who experienced these flares usually had them within the week before or during their periods. The investigators say these findings could inform physician counseling and that closer monitoring of patients during vulnerable phases of the menstrual cycle could enable more timely intervention and better disease control. Additional research is planned to assess whether demographics, lifestyle and medical conditions may influence this potential association.

Authors: Lucy Masto, BS; Amaya Smole, BA, Caroline H. Siegel, MD, MS, Sarah B. Lieber, MD, MS, Sanjana Adurty (Weill Cornell Medical College), Jonah M. Levine, BA, Bessie Stamm, BA, Lisa A. Mandl, MD, MPH, Michael D. Lockshin, MD, Lisa R. Sammaritano, MD, Medha Barbhaiya, MD, MPH.

Contraception Choices in Individuals with Inflammatory Arthritis and Lupus-like Disease Differ Based on Diagnosis and Teratogen Use
This study surveyed women of reproductive age with systemic rheumatic disease about their use of contraceptives. Certain drugs prescribed for rheumatic disease are teratogenic, or can damage a fetus. Data were collected on 249 women with reproductive capacity, including 147 with inflammatory arthritis and 102 with lupus-like disorders.

The 52 participants taking teratogenic medication were more likely to discuss contraception with their rheumatologist compared with those not taking teratogenic medication (44.2% vs. 21.8%), and more frequently reported using permanent contraception (8.0% vs. 1.1%). Those taking teratogenic medication were no more likely to use effective contraception than those who were not: 44.0% reported using less effective methods such as barrier methods and fertility awareness/withdrawal or using no contraception. Those with lupus were less likely to use more effective methods containing estrogen (31.5% vs. 14.7%), even though these methods are safe for some (but not all) lupus patients. The findings highlight the importance of using educational interventions to optimize safe and effective contraception use in patients with systemic rheumatic diseases, especially those taking teratogenic medications and those with lupus-like diseases.

Authors: Caroline H. Siegel, MD, MS, Medha Barbhaiya, MD, MPH, Lucy Masto, BS, Amaya Smole, BA, Bessie Stamm, BA, Jonah M. Levine, BA, Sarah B. Lieber, MD, MS; Lisa A. Mandl, MD, MPH; Michael D. Lockshin, MD; Lisa R. Sammaritano, MD.

Demographic and Clinical Factors Associated with HPV Vaccination in Young Adults with Rheumatic Disease
Although the HPV vaccine is known to be safe and effective in people with rheumatic disease (RD), many do not get vaccinated. This study used data from the electronic health record of patients diagnosed with a rheumatic disease in adolescence, seen at HSS, to look at factors associated with HPV vaccination. Overall, the investigators found that among 321 individuals with rheumatic disease between the ages of 16 and 22, half were not fully vaccinated against HPV (2 or more doses).

Those who were white and non-Hispanic/Latino and those who had commercial insurance were less likely to be fully vaccinated —factors that are associated with lower vaccination rates in the general population. Those who were unvaccinated were more likely to have inflammatory arthritis versus other connective tissue diseases. Those who were fully vaccinated were also more likely to have received flu and COVID-19 vaccines. Further research is needed to identify and mitigate barriers to HPV vaccination in this high-risk group.

Authors: Caroline H. Siegel, MD, MS, Lauren Robinson, MD, Deanna Jannat-Khah, DrPH, Avi Mikhaylov, Nancy Pan, MD, Lisa R. Sammaritano, MD.

Educational Intervention to Increase Contraception Screening and Documentation for Reproductive-Aged Women Seen in an Academic Rheumatology Clinic

Only one-third of reproductive-aged women with rheumatic disease are prescribed effective contraception, despite the widespread use of teratogenic medications which can harm a fetus. This initiative aimed to increase the rate of provider screening and documentation of contraception use in the electronic health record for female rheumatology patients ages 18 to 45.

Interventions from the research team included educational presentations and motivating reminders for clinical staff. Over the 24-week study period, the rate of contraception documentation for these patients increased from 11% to 54%. Future phases of this initiative will focus on encouraging rheumatologists to provide contraceptive counseling and referrals to women’s health providers for patients taking teratogenic medications.

Authors: Caroline H. Siegel, MD, MS, Deanna Jannat-Khah, DrPH, Avi Mikhaylov, Erika Abramson (Weill Cornell Medicine), Nancy Pan, MD; Lisa R. Sammaritano, MD.

Experiences and Attitudes Related to Assisted Reproductive Technologies Among Women with Systemic Rheumatic Disease
Because systemic rheumatic diseases may be associated with decreased fertility in women, those with such diseases may pursue assisted reproductive technologies such as oocyte cryopreservation (OOC, or egg freezing). This study evaluated how sociodemographic factors and medical history influence OOC experiences and overall attitudes toward reproductive technologies among women with these conditions.

Among the 265 surveyed patients of reproductive age, 21 had done OOC (most before 35 years of age) and 102 had considered OOC. The factors that increased openness to OOC included having no previous pregnancies, having greater infertility concerns, lacking a spouse or partner, having a bachelor’s degree or higher, and having a history of taking certain immunosuppressive drugs. Among those who did not already have fertility issues, 64% reported that, if necessary, they would consider using these technologies only if their rheumatologist advised it was safe. The investigators say this study highlights the importance of studying the use of assisted reproductive technologies in women with systemic rheumatic diseases, and counseling patients regarding these options.

Authors: Sanjana Adurty (Weill Cornell Medical College), Lucy Masto, BS, Amaya Smole, BA, Caroline H. Siegel, MD, MS, Sarah B. Lieber, MD, MS, Jonah M. Levine, BA, Bessie Stamm, BA, Lisa A. Mandl, MD, MPH, Michael D. Lockshin, MD, Medha Barbhaiya, MD, MPH, Lisa R. Sammaritano, MD.

HPV Vaccination in Adolescent and Young Adult Patients Seen in an Academic Rheumatology Center
This study looked at rates of HPV vaccination in adolescents and young adults living in New York State who had received care from a rheumatologist. The investigators reviewed data from the electronic health record, including vaccination information from a New York State database, for 534 HSS patients ages 16 to 22. Less than half of patients had been vaccinated for HPV. The study found that HPV vaccination was more common in people with a rheumatic disease diagnosis compared to those who did not have a rheumatic disease, but not after accounting for demographic variables and receipt of other elective vaccines. Additionally, those who had received flu and COVID-19 vaccines were more likely to have been vaccinated for HPV.

The overall low rate of HPV vaccination was concerning because young people with rheumatic diseases may be at increased risk for HPV infection and HPV-associated cancers due to immune dysregulation, immunosuppression, and gaps in preventive healthcare delivery. The researchers note that interventions are needed to improve HPV vaccination rates in this population and that targeting elective vaccine uptake in general may be a useful approach.

Authors: Caroline H. Siegel, MD, MS, Lauren Robinson, MD, Deanna Jannat-Khah, DrPH, Avi Mikhaylov, Nancy Pan, MD, Lisa R. Sammaritano, MD.

Knowledge and Misconceptions about Contraception Among Individuals with Inflammatory Arthritis and Lupus-like Diseases
This study looked at what patients with systemic rheumatic disease know about the use of contraceptives, comparing the knowledge of women with inflammatory arthritis to those with lupus-like diseases. This analysis included female patients aged 18-49 years who were seen by a rheumatologist at HSS two or more times between 2020 and 2022, excluding those who reported menopause, oophorectomy, hysterectomy, or other causes of infertility.

The participants were surveyed about the effectiveness of various contraceptives and about misconceptions related to specific methods in the context of having a rheumatic disease. The researchers found that despite being highly educated (93.2% held a bachelor’s degree or higher), about half of all patients responded incorrectly to questions about the effectiveness of various contraceptive methods. Those with lupus-like diseases were more likely to report that certain hormone-based methods have contraindications, in response to both accurate and inaccurate statements. The researchers say the results reveal the need for better counseling of patients with systemic rheumatic disease.

Authors: Caroline H. Siegel, MD, MS, Medha Barbhaiya, MD, MPH, Lucy Masto, BS, Amaya Smole, BA, Bessie Stamm, BA, Jonah M. Levine, BA, Sarah B. Lieber, MD, MS, Lisa A. Mandl, MD, MPH, Michael D. Lockshin, MD, Lisa R. Sammaritano, MD.

Knowledge Related to Fertility and Infertility Treatments Among Women with Systemic Rheumatic Disease
Systemic rheumatic diseases can be associated with decreased fertility, but patients are not always aware of this connection. This study looked at patients’ understanding of these issues, taking into consideration the patient’s race, ethnicity, and socioeconomic status.

In an interim analysis of 142 reproductive-aged women treated at HSS for rheumatic disease who completed the Fertility & Infertility Treatment Knowledge Score (FIT-KS) test, the investigators found that — compared with women in the general population previously administered the FIT-KS — women with rheumatic diseases were more likely to be non-White, Hispanic/Latina and highly educated, and less likely to have had successful pregnancies. This population was more aware of the risks of infertility due to smoking, sexually transmitted infections and being underweight. These women also had a better understanding of success rates for vitro fertilization in older women but were less knowledgeable about the effectiveness of oocyte cryopreservation (OOC, or egg freezing). Future work will focus on highlighting important knowledge gaps among women with these diseases, particularly related to options for fertility preservation.

Authors: Sanjana Adurty (Weill Cornell Medical College); Lucy Masto, BS, Amaya Smole, BA, Caroline H. Siegel, MD, MS, Sarah B. Lieber, MD, MS, Jonah M. Levine, BA, Bessie Stamm, BA, Lisa A. Mandl, MD, MPH, Michael D. Lockshin, MD, Medha Barbhaiya, MD, MPH, Lisa R. Sammaritano, MD.

Reproductive History and HPV Vaccination Awareness Among Women with Systemic Lupus Erythematosus and Rheumatoid Arthritis
Women with systemic rheumatic diseases, particularly those with systemic lupus erythematosus (SLE), may be more vulnerable to HPV infection and HPV-related cervical cancer, but HPV testing and vaccination rates are low in these patients. This study compared HPV vaccination status and awareness in female patients with SLE to female patients with rheumatoid arthritis (RA).

The analysis included 295 participants with similar demographics; notably, those with SLE were slightly younger than those with RA. Both groups were similarly likely to be sexually active and had similar rates of having regular Pap smears; however, women with lupus were more likely to have persistent abnormal smears (13.3% vs. 1.7%). While not statistically significant, two women with lupus reported a cervical cancer diagnosis compared to none with rheumatoid arthritis. HPV vaccination rates were similar for the two groups, with 37% of 158 women eligible for the vaccine (including those made eligible given extended eligibility approved in 2019 for those aged ≤45 years if clinically appropriate) reporting having received full vaccination. Among the 79 women who had never received the vaccine yet were eligible, 90% reported that it had never been offered. These findings underscore the importance of increasing HPV vaccination rates and discussions about cervical cancer screening in women with SLE and RA.

Authors: Amaya Smole, BA, Lucy Masto, BS, Caroline H. Siegel, MD, MS, Sarah B. Lieber, MD, MS, Sanjana Adurty (Weill Cornell Medical College), Jonah M. Levine, BA, Bessie Stamm, BA, Lisa A. Mandl, MD, MPH, Michael D. Lockshin, MD, Lisa R. Sammaritano, MD, Medha Barbhaiya, MD, MPH.

Self-Reported Sexual Dysfunction and Perceptions of Rheumatologist Engagement on This Issue in Patients with Systemic Sclerosis
This study looked at the prevalence and risk factors of sexual dysfunction among people with systemic sclerosis (SSc). HSS researchers developed the Sexual Function in SSc Questionnaire (SFSScQ) to anonymously survey patients on whether they had problems with their sexual function and, if so, whether they had ever discussed it with their rheumatologist. Participants who completed the SFSScQ were also asked to complete the already-established Female Sexual Function Index or the International Index of Erectile Function Questionnaire.

More than half of those who completed both surveys (26 out of 41) reported that they had sexual problems. The researchers note that while the number of survey participants was small, age, sex, race, SSc subtype and time since SSc diagnosis did not appear to be predictors of sexual dysfunction. Importantly, although about half of participants agreed it was important to discuss problems of sexual function with their doctors, 64% of those who reported sexual problems had not done so.

Authors: Liza Morales, Robert F. Spiera, MD, Jessica K. Gordon, MD, Deanna Jannat-Khah, DrPH, Kimberly S. Lakin, MD, MS.

New Study Identifies Outcomes Associated With Frailty in Patients With Vasculitis

Mon, 13 Nov 2023 14:05:00 -0500

People with vasculitis frequently suffer from frailty, a process that can affect our ability to recover after an illness or a fall, which in turn is linked to poor health outcomes, according to a new study from researchers at Hospital for Special Surgery (HSS) in New York City and colleagues from the University of Pittsburgh and the University of Pennsylvania.

“Our study highlights the importance of incorporating frailty in the care of patients with vasculitis, and the potential to develop interventions to ameliorate frailty to minimize adverse outcomes and improve the care of these patients,” said Sebastian E. Sattui MD, MS, an Assistant Professor of Medicine and Director of the UPMC Vasculitis Center at the University of Pittsburgh School of Medicine, and former rheumatology and vasculitis fellow at HSS. Dr. Sattui presented the findings at the ACR Convergence 2023 annual meeting of the American College of Rheumatology.

Vasculitis is a rare inflammatory condition that affects the blood vessels and can lead to organ damage. The disease can be triggered by infections, medications, and certain cancers, as well as systemic autoimmune disease.

The latest findings come from the ongoing VascStrong study, a prospective, longitudinal analysis of 272 men and women with vasculitis who agreed to participate in two surveys over a 12-month period.

At baseline, Dr. Sattui and his colleagues collected information on demographics, the types of medications patients were taking, and the specific nature of their condition. They also looked at various patient-reported outcome measures (PROMs), as well as frailty using the self-reported FRAIL scale, which classifies people as robust, pre-frail, and frail.

Of the participants, 71% were female and the average age was 62.5 years. The most common forms of vasculitis in the group were granulomatosis with polyangiitis (39%), eosinophilic granulomatosis with polyangiitis (14.3%), and microscopic polyangiitis (12.9%).

At the start of the study, the prevalence of robustness, pre-frailty, and frailty was 47.1%, 33.8%, and 19.1%, respectively. A year later, most people had stayed in those categories (75%, 50.9%, and 66.1% for robust, pre-frailty, and frailty, respectively).

However, roughly 21% of people who had been robust at the start of the study reported being pre-frail at the second assessment and 10.2% went from pre-frail to frail. In the other direction, 39% went from pre-frail to robust and 25% from frail to pre-frail. Transitions from frail to non-frail (8.9%) or non-frail to frail (3.7%) were uncommon, the researchers found.

The pattern was similar for patient-reported outcomes, with pre-frail and frail patients reporting worse pain, fatigue, depression, and physical function a year after the initial survey. Significant health events such as hospitalizations, infections, and vasculitis flares occurred more often in patients who were classified as frail at baseline.

“We know that frailty is associated with worse health outcomes”, said Robert F. Spiera, MD, Director of the Vasculitis and Scleroderma Program at HSS and the senior author on this study. “These findings demonstrate just how common frailty and pre-frailty are in patients in vasculitis, and that frailty is dynamic. This means that it is potentially modifiable in a subset of patients, and interventions that could ameliorate frailty could in this population could be a meaningful outcome measure in clinical trials in vasculitis that could help identify interventions that would improve the lives of our patients with vasculitis.”

Sattui, Spiera, et al. The Association of Frailty with Outcomes in Patients with Vasculitis. Abstract 1543. Presented Monday Nov. 13, 2023 at ACR Convergence 2023.

International Clinical Trial Results in Promising New Treatment Option for Refractory Polymyalgia Rheumatica Patients

Tue, 24 Oct 2023 11:16:07 -0400

(New York, New York) – The New England Journal of Medicine published positive results from a Phase 3 international clinical trial demonstrating the efficacy of sarilumab (Kevzara®) in adult patients with refractory polymyalgia rheumatica (PMR). Robert Spiera, MD, rheumatologist and Director of the Scleroderma, Vasculitis and Myositis Center at Hospital for Special Surgery (HSS), served as primary investigator for the trial, which led to the U.S. Food and Drug Administration (FDA) approval of a new treatment option for patients with PMR who have difficulty tapering off steroids. Steroid related side effects are common in this group of patients and can often result in complications including osteoporosis, diabetes, myopathy, glaucoma, bruising, bleeding and sleep disturbances.

Polymyalgia rheumatica (PMR) among the most common inflammatory musculoskeletal diseases affecting individuals over the age of 50, causes severe pain, stiffness, fatigue, and at times low grade fever. Traditionally, treatment has relied heavily on steroids, leading to prolonged therapy and severe side effects, particularly in older patients. However, the recent trial, led by Dr. Spiera, validates the efficacy of a new treatment option for select patients suffering from the disease.

The trial, sponsored by and supported by Sanofi and Regeneron, focused on a drug called sarilumab, an interleukin-6 receptor blocker, and involved patients with refractory PMR – those who experienced flares despite having been previously treated with a substantial amount of corticosteroids. Patients were randomly assigned to receive either a very rapid 14-week steroid taper with sarilumab or a one-year steroid taper with placebo. The study demonstrated that patients on sarilumab were three times more likely to achieve sustained remission, reduce their overall steroid use, and experience significant improvements in their quality of life compared to the placebo group.

"Prior to the FDA approving sarilumab earlier this year as the first and only biologic to treat select patients with PMR, patients and physicians were limited in their treatment options,” Dr. Spiera said. “This trial represents a crucial advance in the management of PMR. It offers new hope to those who have struggled with the condition, especially older patients who are particularly susceptible to serious side effects associated with long-term steroid use.”

The approval of sarilumab for refractory PMR patients marks a monumental achievement in the treatment landscape for PMR patients, underscoring HSS’s commitment to providing specialized care and innovative treatments for patients with rheumatic conditions.

Dr. Spiera continued, “Whether there is a role for sarilumab as first line therapy in PMR, particularly in patients in whom steroid complications has not been addressed in the SAPHYR study; hopefully future clinical trials will address that question.”

Plenary III highlights emerging insights into knee OA, PMR, APS, gout, JIA, and RA

Fri, 02 Dec 2022 10:54:00 -0500

American College of Rheumatology (ACR) reports on emerging insights into knee osteoarthritis (OA), polymyalgia rheumatica (PMR), antiphospholipid syndrome (APS), gout, juvenile idiopathic arthritis (JIA), and rheumatoid arthritis (RA) presented at the ACR Convergence 2022 by experts including Robert Spiera, MD, rheumatologist at HSS.

PMR is one of the most common inflammatory diseases of older individuals. It can usually be treated with glucocorticoids (GC), but relapses are common, which can subject patients to long, repeating regimens of high-dose GC treatment.

“We need a steroid-sparing treatment for PMR,” said Dr. Spiera. “The phase 9 SAPHYR trial showed that sarilumab, an interleukin 6 (IL-6) receptor inhibitor, has greater and clinically relevant improvements in disease remission, risk of PMR flare, and quality of life and function compared to conventional GC treatment in this difficult-to-treat population.”

Sarilumab is currently approved by the U.S. Food and Drug Administration for. The agent targets the IL-6 receptor and inhibits IL-6 signaling.

SAPHYR randomized 59 patients to sarilumab 200 mg administered subcutaneously every two weeks with a 14-day GC taper and 58 patients to the conventional 52-week GC taper. All patients were on 7.5 mg or more GC and had a flare within 12 weeks of their initial screening. The trial was powered for 280 patients but was halted early due to COVID-19.

The primary endpoint was disease remission by week 12 and sustained through week 52, C-reactive protein normalization, and adherence to per protocol GC taper from weeks 12–52.

“This was a typical group of patients for PMR, early 70s, two-thirds female, and 80 percent white,” noted Dr. Spiera. “Sustained remission was significantly higher in the sarilumab arm, 28.4 percent versus 10.3 percent (p=0.0193). All of the components of sustained remission, patient-reported outcomes, and most physician-reported outcomes favored sarilumab with no surprises in safety. The protocol set a very high bar for sustained remission and in clinical terms, these are very significant results.”

Read the full article at https://www.acrconvergencetoday.org/.

Additional coverage: www.mdedge.com and www.the-rheumatologist.org

Clinical Signs Differ Between Kids and Adults With Vasculitis

Sat, 12 Nov 2022 14:46:00 -0500

Medscape reports on a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

The findings, presented at the American College of Rheumatology (ACR) 2022 Annual Meeting, may have implications for research and treatment, especially in children.

Robert F. Spiera, MD, rheumatologist and Director of the Vasculitis and Scleroderma Program at HSS noted the work highlights interesting information about the fact that disease features are skewed differently in children — “in particular the higher likelihood of upper airway (subglottic) disease, and potentially severe lower airway disease (alveolar hemorrhage).” However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA (more often children and more likely to be female) may offer insights into disease pathogenesis.”

Read the full article at medscape.com/.

Three new ACR guidelines recommend treatment for six forms of vasculitis

Wed, 14 Jul 2021 08:39:00 -0400

MDedge reports new guidelines from the American College of Rheumatology (ACR), in partnership with the Vasculitis Foundation, offer evidence-based recommendations for managing and treating six different forms of systemic vasculitis and includes commentary from Robert F. Spiera, MD, rheumatologist at HSS.

Dr. Spiera discussed the conditional recommendation of noninvasive vascular imaging of the large vessels in patients with newly diagnosed Giant cell arteritis (GCA).

He explained, “It is well recognized that a substantial portion of patients with GCA have unrecognized evidence of large vessel involvement, and patients with GCA in general are at higher risk of aneurysms later in the disease course. These guidelines suggest screening even patients with purely cranial presentations for large vessel involvement with imaging to possibly identify the patients at higher risk for those later complications.”

He continued, “What they didn’t offer were recommendations on how to follow up on that imaging,” adding, “which is an important and as-yet-unanswered question.”

Regarding the ANCA-associated vasculitis (AAV) guidelines, Dr. Spiera said, “The literature supports that in patients with relapsing disease, rituximab works better than cyclophosphamide for remission induction. But in these guidelines, even in new disease, rituximab is suggested as the agent of choice to induce remission. I would say that that is reasonable, but you could make an argument that it’s maybe beyond what the literature supports, particularly in patients with advanced renal insufficiency attributable to that initial vasculitis flare.”

He concluded, “There has been progress in terms of well-done clinical trials to inform our decision-making, particularly for ANCA-associated vasculitis, both in terms of how to induce and maintain remission. Though the recommendations were conditional, I think there’s very strong data to support many of them.”

Read the full article at MDedge.com.

Vaccine Watch: Protecting immunosuppressed patients

Wed, 23 Jun 2021 11:24:00 -0400

ABC News discusses the protection against COVID-19 for people who are immunosuppressed and immunocompromised, and may be unable to produce antibodies after being fully vaccinated, including commentary from Robert F. Spiera, MD, rheumatologist and Director of the Vasculitis and Scleroderma Program at HSS.

Dr. Spiera said, “This has been very painful for us to go through with our patients, many of whom were waiting with bated breath to get their vaccine so they could have their child go back to school or so that they could hug their grandchildren, and then getting this news that you didn’t have antibodies was devastating for them.”

Dr. Spiera underscored the importance of ongoing research and large studies that will look at the rate of COVID-19 infections among people with autoimmune diseases who have been vaccinated.

Watch the full segment at Abcnews.go.com.

Lenabasum fails efficacy outcomes in diffuse cutaneous systemic sclerosis, may improve FVC

Sat, 05 Jun 2021 17:36:00 -0400

Healio Rheumatology discusses the findings of a new study presented at the EULAR 2021 Congress by Robert F. Spiera, MD, rheumatologist and Director of the Vasculitis and Scleroderma Program at HSS.

According to Dr. Spiera, although lenabasum failed to meet its efficacy endpoint in a trial of patients with diffuse cutaneous systemic sclerosis, a post-hoc analysis suggests an impact on forced vital capacity (FVC).

To examine the efficacy, safety and tolerability of lenabasum compared with placebo, Dr. Spiera and colleagues conducted the double-blind, randomized, phase-3 RESOLVE-1 trial. Study participants were allowed to receive background immunosuppressive therapies because it “reflects real-world clinical practice in the treatment of systemic sclerosis,” Dr. Spiera explained.

The researchers found that mycophenolate also impacted outcomes. Dr. Spiera noted, “Patients who entered the trial on mycophenolate were more likely to have a more favorable response with regard to FVC, whereas other features, including the region they came from or disease duration did not. Baseline FVC also came up statistically significant in this model.”

Dr. Spiera concluded, “Evidence for an effect of lenabasum on forced vital capacity [FVC] was suggested by post-hoc analyses that considered the effect of background immunosuppressive therapies on outcomes.”

He added, “Results from the post-hoc analyses will require confirmation in additional studies to determine the potential of lenabasum for treating patients with systemic sclerosis. Treatment with lenabasum was safe and well-tolerated in this study.”

Read the full article at Healio.com.

Additional coverage: Medscape.com, MDedge.com.

Tocilizumab improves GCA outcomes in patients with polymyalgia, cranial symptoms

Thu, 08 Apr 2021 19:49:00 -0400

Healio Rheumatology reports on the findings of an HSS study published in the Seminars in Arthritis & Rheumatism by rheumatologist Robert F. Spiera, MD and colleagues, showing tocilizumab improves outcomes in patients with Giant-cell Arteritis (GCA) who present with polymyalgia rheumatica symptoms only, cranial symptoms only or both at baseline.

“Giant-cell Arteritis [GCA] is a heterogeneous disorder with a variety of recognized clinical presentations,” noted Dr. Spiera. “Some patients present with cranial ischemic symptoms such as severe headaches or visual loss. Others can present primarily with systemic complaints related to their underlying inflammatory state including prominent polymyalgia rheumatica-like symptoms.” Dr. Spiera explained, “Some of those patients have cranial symptoms as well, but some do not, and there is a recognized subtype of patients with ‘large vessel vasculitis’ in whom inflammation is recognized in the aorta or its major branches but without localizing cranial complaints.” He added, “In the GiACTA trial, tocilizumab was demonstrated to be effective in affording disease control and having a significant steroid-sparing benefit in GCA. The trial included patients with these different presenting features.”

Read the full article at Healio.com/news/rheumatology.

Novel Biologic Promising in Mid-Stage Scleroderma Trial

Mon, 28 Sep 2020 15:36:00 -0400

MedPage Today reports on study findings available online in Annals of the Rheumatic Diseases which found anti-interleukin agent romilkimab demonstrated significant benefits on skin fibrosis among patients with systemic sclerosis in a Phase II trial.

HSS rheumatologist Robert F. Spiera, MD who was not involved in the study, provided comments on the results, noting, "This was a really interesting study looking at a novel strategy for patients with early diffuse systemic sclerosis, which is a real challenge in terms of identifying effective therapies.” He cited, “This was a trial design that is very impressive to me in the sense that they did what we do in the real world, which was to allow background therapy.” Dr. Spiera added, "Here they were adding the experimental treatment to standard of care therapy, meaning that all patients were able to receive such therapies, which could in theory make it harder to demonstrate that the study medication was having a beneficial effect."

While the study was limited by its brief duration, the impact on skin met the prespecified endpoint, which is the first time that this has been achieved in a Phase II study in diffuse cutaneous systemic sclerosis. "It definitely showed signals of efficacy and was acceptable in terms of safety. This would warrant a further look in a large Phase III clinical trial," he concluded.

Read the full article at MedPageToday.com.

ACR CRISS Score a Reliable Measure of Therapy Effectiveness in dcSSc Patients, Corbus Says

Mon, 13 Jul 2020 13:04:00 -0400

HSS rheumatologist Robert F. Spiera, MD presented new data at the sixth Systemic Sclerosis World E-Congress suggesting the American College of Rheumatology Combined Response Index in diffuse cutaneous systemic sclerosis (ACR CRISS) score reflected patient-reported outcomes better than the modified Rodnan Skin Score (mRSS), which assesses skin thickening.

As the principal investigator, Dr. Spiera and researchers analyzed data from the ongoing phase 2 clinical trial evaluating investigational treatment lenabasum’s safety and effectiveness in 42 adults with diffuse cutaneous systemic sclerosis (dcSSC). Participants were randomly assigned to receive either lenabasum or placebo, plus their stable standard care for 12 weeks. They could then enter the ongoing open-label extension phase, in which all participants were receiving the therapy. The researchers looked at four patient-reported outcomes to assess how patients feel and function: the Health Assessment Questionnaire - Disability Index (HAQ-DI) and patient global assessment – both included the ACR CRISS score; the SSc Skin Symptoms Patient-reported Outcome (SSPRO), and the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) score.

Results showed that the ACR CRISS score consistently reflected changes in patient-reported outcomes, and this association was stronger than that observed between the mRSS score and patient-reported outcomes.

Read the full article at Sclerodermanews.com.

Ustekinumab for Behçet’s Disease? The Study Results Are In

Mon, 15 Jun 2020 10:29:00 -0400

The Rheumatologist reports on the results of a multicenter, prospective, open-label study, which found ustekinumab therapy was effective in treating oral ulcers resistant to colchicine in patients with Behçet’s disease.

HSS rheumatologist, Robert F. Spiera, MD, who was not involved in the study, provided commentary on the findings, noting “Refractory oral aphthous ulcerations in patients with Behçet’s disease is a clinical challenge, and the suggestion of efficacy and tolerability of an intervention with which rheumatologists are comfortable offers hope for expanding our therapeutic armamentarium in this disease.” Dr. Spiera added, “There is potentially a need for other therapies for managing this less ‘organ-damaging’ manifestation of the disease, which nevertheless has an important impact on quality of life.”

Read the full article at the-rheumatologist.org.

How Does Scleroderma Affect the Esophagus? The Red Flags to Be Aware Of

Fri, 28 Feb 2020 11:50:00 -0500

CreakyJoints reports on the causes, symptoms, treatment and management of esophageal scleroderma, according to experts, including HSS rheumatologist Robert F. Spiera, MD.

“Esophageal involvement in scleroderma is incredibly common, but some of that depends on how it is defined and how aggressively it is searched for,” explained Dr. Spiera. “About half of patients with scleroderma have GERD [gastroesophageal reflux disease] or dysphagia (difficulty swallowing),” he added.

Treating GERD and other GI issues begin with lifestyle changes, such as eating smaller and more frequent meals throughout the day. “Since your motility is diminished, it is hard for the GI tract to handle a larger volume load,” noted Dr. Spiera. “You don’t, however, want to restrict total calorie consumption.” Dr. Spiera also advised not to eat within a few hours of bedtime. “Since gastric emptying can be delayed, eating earlier can be helpful as more of the food can move down the GI tract and enter the small intestine or beyond by the time you go to bed,” he said. Elevating the head of your bed a few inches can also help. “This helps use gravity to assist food moving along the GI tract, in particular the esophagus,” cited Dr. Spiera.

Read the article at Creakyjoints.org.

What Is Scleroderma Renal Crisis? The Key Symptoms You Need to Watch For

Wed, 26 Feb 2020 11:28:00 -0500

CreakyJoints reports the scleroderma renal crisis (SRC) is a serious complication that can infrequently affect people who have systemic sclerosis. Experts including HSS rheumatologist Robert F. Spiera, MD discussed the signs, symptoms and treatment of SRC.

SRC is characterized by sudden hypertension (high blood pressure) and rapidly progressive renal failure, typically without previous significant kidney disease. SRC can also involve hypertensive encephalopathy (brain disfunction due to high blood pressure), congestive heart failure, and/or microangiopathic hemolytic anemia (loss of red blood cells). Dr. Spiera explained an early diagnosis of scleroderma is critical to reduce the risk of complications like SRC. “You have to be vigilant and take this condition seriously upfront,” he said. “About 10 percent of people with scleroderma renal crisis will still have normal blood pressure, though their blood pressure levels are elevated relative to their own baseline,” cited Dr. Spiera. “Patients who have hypertension often have some protein in the urine,” he added.

Patients with scleroderma will have their blood tested for certain antibodies, which can help confirm a diagnosis with SRC. “Checking blood levels of renin can be helpful,” noted Dr. Spiera, the enzyme that helps control your blood pressure, and is produced by cells in the kidneys. Treatment of SRC aims to control blood pressure with angiotensin-converting enzyme inhibitors (ACEIs). “You need to treat aggressively with ACEIs, pushing for the highest dose that’s tolerable by your blood pressure,” said Dr. Spiera.

Read the article at Creakyjoints.org.

What Is Scleroderma? These Are the Signs You Could Have it

Tue, 24 Dec 2019 09:12:00 -0500

CreakyJoints features an educational article on scleroderma - the causes, symptoms and how to know if you may have the autoimmune disease.

"It may be that different patients have different triggers," explained Robert F. Spiera, MD, rheumatologist at HSS, who noted that the underlying cause of scleroderma is unknown.

There are two general types of scleroderma: localized and systemic. Lindsay S. Lally, MD, rheumatologist at HSS, explains that systemic scleroderma is defined based on the extent of skin involvement and other factors.

While there is currently no cure, treatment such as medications, exercise and physical and occupational therapy, can help control symptoms and prevent complications. If you experience Raynaud's disease, Dr. Lally adds that keeping your extremities and core warm in cold weather is crucial.

Read the full article at CreakyJoints.org.

IL-6 Blocker Effective Two Years After Withdrawal

Mon, 16 Dec 2019 12:33:00 -0500

MedPage Today interviews Robert F. Spiera, MD, rheumatologist at HSS, at the 2019 American College of Rheumatology meeting to discuss the findings of the GiACTA trial extension, of which tocilizumab for giant cell arteritis proved to be durable in nearly half of the patients who were treated weekly.

Dr. Spiera noted, “The most important observations from this extension phase trial was that patients who entered the extension phase or the extended observation phase in remission who had been on tocilizumab in the first phase of the study, almost 50 percent of those patients remained in remission during the duration of 2 further years of follow-up, meaning initial treatment of a giant cell arteritis patient with tocilizumab and a 26-week prednisone taper resulted in nearly 50 percent of those patients being in maintained remission at 3 years' follow-up. That's really important for one of the most important questions or common questions physicians ask is, ‘When do we stop tocilizumab?’ It means then in a large number of patients that are in remission, they may do well stopping tocilizumab with the recognition you could continue it or resume it at a later point in time.”

Watch the video at MedPageToday.com.

Clinical Trial to Test Potential New Therapy for Giant Cell Arteritis

Tue, 24 Sep 2019 11:07:03 -0400

An international, multicenter phase II clinical trial is evaluating the efficacy and safety of mavrilimumab co-administered with a 26-week corticosteroid taper in patients with giant cell arteritis (GCA). The study is sponsored by Kiniksa Pharmaceuticals, Ltd. Hospital for Special Surgery (HSS), in New York City, is one of the centers participating in the research.

GCA, sometimes referred to as temporal arteritis, is the most common form of systemic vasculitis in adults. It typically occurs in people over age 50, with a peak in the mid 70s, and is more common in women than men. “HSS has a great history of being able to enroll vasculitis patients in clinical trials,” said Lindsay S. Lally, MD, a rheumatologist and trial co-investigator who serves as the site principal investigator at HSS. “HSS is one of the only places in the New York City area that has a dedicated vasculitis center, with physicians who have clinical and research expertise in diagnosing and treating these diseases. We have been at the forefront of a lot of the recent advancements in the understanding of giant cell arteritis, in terms of pathogenesis and treatment.”

GCA, an inflammatory autoimmune disease, is classified as a large vessel vasculitis (affects the large blood vessels of the scalp, neck and arms) but typically also involves medium sized arteries of the scalp, neck and arms, particularly the superficial temporal arteries—hence the term temporal arteritis. Inflammation causes a narrowing or blockage of the blood vessels, interrupting blood flow. The causes of GCA are uncertain. One of the most feared complications of the disease is vision loss or blindness.

For decades, the mainstay of treatment for GCA has been high doses of prednisone and other systemic glucocorticoid steroids, which work quickly to reduce inflammation but come with a host of potential side effects and toxicities. Many people with GCA are elderly and have other medical comorbidities, such as diabetes and osteoporosis. “Being on high doses of steroids for months can lead to worsening blood sugar control and elevated blood pressure and fractures,” said Dr. Lally. “More than 80 percent of patients will have some toxicity related to being on systemic steroids. What we have really tried to do as a vasculitis community is to explore other medications that can adequately control the inflammation, prevent blood vessel damage and end organ complications like blindness or strokes while minimizing toxicity to patients.”

One drug, tocilizumab, which was approved for GCA in 2017, has been effective in limiting the amount of steroids that some patients need, but it is not appropriate for everyone. “We still need to find other treatment strategies that can adequately control the inflammation while minimizing the amount of steroids that we expose patients to,” said Dr. Lally.

Mavrilimumab is a human monoclonal antibody that binds to the granulocyte macrophage colony-stimulating factor (GM-CSF) receptor alpha, inhibiting the GM-CSF signaling. “Granulocyte macrophage colony-stimulating factor is a chemical that should, in normal situations, be signaling for certain types of white blood cells to grow and expand,” said Dr. Lally. “We think that in giant cell arteritis, there are aberrations in this pathway. Certain types of white blood cells are present in higher levels and are more active, and that results in the inflammation that we see in the blood vessels. Data in preclinical models suggest that blocking this chemical may stop the proliferation of inflammatory cells in GCA.”

The clinical trial consists of a screening period of up to six weeks; a 26-week double-blind placebo-controlled period during which subjects receive blinded subcutaneous mavrilimumab injections weekly or placebo co-administered with a 26-week corticosteroid taper; and a 12-week washout safety follow-up period during which subjects no longer receive mavrilimumab or placebo and are transitioned back to standard of care. “The primary objective is sustained remission at week 26,” said Dr. Lally. “Endpoints include time to flare, sustained remission, and cumulative steroid doses. The goal is to see if patients can be on clinical remission, off of steroids, within 26 weeks.”

To be eligible for the trial, patients need to show evidence of active disease based on clinical symptoms and levels of inflammatory markers in the blood. “Patients also need to have hard evidence of the disease, which would either be a biopsy or ultrasound of the temporal artery, showing evidence of inflammation in that blood vessel, or an MRI or CT scan of the large blood vessels that shows evidence of active inflammation,” said Dr. Lally.

Female trial participants must be postmenopausal or permanently sterile following documented hysterectomy with bilateral salpingectomy, bilateral oophorectomy or tubal ligation; be nonpregnant or nonlactating and have a male partner with a vasectomy; or have agreed to use birth control if sexually active. Male subjects must have a documented vasectomy or, if sexually active, must agree to use a highly effective method of contraception.

Mavrilimumab has been previously studied in over 500 patients with rheumatoid arthritis. Dr. Lally will review the safety profile of mavrilimumab with patients who qualify for this study. Patients will be followed very closely for any potential side effects.

According to Robert F. Spiera, MD, director of the Vasculitis and Scleroderma Program at HSS, there is a heterogeneity to large vessel vasculitis. “This trial targets a mechanism that we would expect to be relevant to these disorders,” he said. “We continue to strive to help develop better therapies and are excited to have this trial available to our patients."

For information on how to enroll in the trial at HSS, call 646-797-8443.

Trial Will Test New Treatment for Diffuse Cutaneous Systemic Sclerosis

Wed, 20 Mar 2019 08:00:00 -0400

Hospital for Special Surgery is evaluating a novel therapeutic approach for diffuse cutaneous systemic sclerosis (dcSSc), one of the most serious, potentially disabling and life-threatening rheumatic diseases. The double-blind, randomized, placebo-controlled phase II trial is only available at HSS and will test the combination of rituximab (Rituxan, Genentech) and belimumab (Benlysta, GSK) plus standard therapy with mycophenolate.

"Better therapies for scleroderma are a major unmet medical need," said Robert F. Spiera, MD, Director of the Vasculitis and Scleroderma Program at HSS. "Our current treatments depend on the symptoms and organ systems involved, and there are no therapies that are specifically approved by the FDA to treat systemic sclerosis."

DcSSc is a subtype of systemic scleroderma characterized by widespread skin thickening and problems in many organs that can occur at any age, but often begins in people between ages 30 through 50. Symptoms vary and include Raynaud’s syndrome; skin hardening and thickening beginning on fingers and face that can rapidly generalize; severe heartburn; dry mouth and dental involvement; joint pain; muscular pain; heart problems, and severe problems involving the lungs and kidneys. The exact cause of dcSSC is unknown.

Different arms of the immune system are overactive in patients with scleroderma, and in the past ten years, several lines of evidence suggest that B cells are important. "We know there is evidence of B cell activation in the skin and lungs of patients with scleroderma, and there have been a few studies looking at strategies to inhibit B cells that have shown promise," said Dr. Spiera. "The first were some studies looking at rituximab, which is a drug that targets B Cells and is relatively well-tolerated in scleroderma patients. Belimumab is a drug known to work in lupus, and there was rationale to think that the target of belimumab would be promising in systemic sclerosis patients. A protein that belimumab blocks is overexpressed in patients with scleroderma and higher levels of that protein correlate with people with scleroderma doing worse observationally."

The HSS team previously evaluated belimumab, which is approved for the treatment of adult patients with systemic lupus erythematosus, in a double-blinded trial in patients with dcSSc and found acceptable safety and tolerability, as well as a trend suggesting possible efficacy, although the differences between patients treated with active belimumab vs placebo did not reach statistical significance in that small pilot study.

The 52-week trial now being launched will evaluate whether rituximab and belimumab plus standard therapy with the immunosuppressive agent mycophenolate mofetil (MMF, CellCept,) is safe and tolerable in the treatment of patients with early dcSSc. "Everyone will be getting background active therapy with mycophenalate which we think is a good drug for skin involvement," said Dr. Spiera. The trial will enroll 30 patients, and 20 will receive the experimental treatment consisting of 2 rituximab infusions (1000mg separated by 2 weeks), followed by weekly self-injected belimumab (as is used in lupus) or placebo infusions followed by placebo injections. Neither the patients nor the treating physicians will know whether they are receiving the active treatment. The researchers are hoping to see improvements in a few different domains.

"The most common thing we look at in a trial outcome in scleroderma is the amount of skin involvement as measured by the Modified Rodnan Skin Score. That is an important outcome, but we are also looking at a more holistic outcome measure called the combined response index in systemic sclerosis or CRISS," said Dr. Spiera. "CRISS is an outcome measure provisionally endorsed by the American College of Rheumatology for scleroderma clinical trials, which looks not only at skin, but also incorporates the patient’s general sense of how well they are doing, the patient’s lung function measured by the forced vital capacity of the lung function test, and how the physician globally feels the patients are doing, and an index that measures how patients are functioning."

CRISS incorporates change in the modified Rodnan Skin Score, forced vital capacity percent predicted, physician and patient global assessments, and the Health Assessment Questionnaire Disability Index. Patients will also be evaluated using hemoglobin corrected diffusion capacity, the Medsger Disease Severity Scale and with other physician and patient-derived outcome measures. The biological activity of the two treatments will be determined by evaluating skin histology; gene expression in skin and blood; B-Cell profiles including assessment of B regulatory cells; and serological and cutaneous biomarkers of disease activity. "We want to see if what we are finding signals that the biology is changing in a favorable way that suggests improvements or lack thereof," said Dr. Spiera.

This investigator-initiated trial is sponsored by HSS and supported by funding and belimumab supply from GSK.

Lenabasum Safe and May Be Effective in Diffuse Scleroderma Patients

Mon, 19 Nov 2018 07:00:00 -0500

Robert F. Spiera, MD, rheumatologist at HSS, is interviewed at the annual ACR conference by MedPage Today talking about the study that he presented on the safety and efficacy of lenabasum in diffuse scleroderma patients.

He explains how his team saw significant improvements in skin scores, and in the primary efficacy outcome measure, the CRISS (Combined Response Index in diffuse cutaneous Systemic Sclerosis), over the course of this study.

"Most patients achieved a CRISS of greater than 90 percent by one year, which was encouraging… both in regard to safety and efficacy."

Dr. Spiera notes that there will be a phase III in the future.

This coverage originally appeared in MedPageToday.com. The original article is no longer available online.

All in the Rheumatology Family

Wed, 08 Aug 2018 07:00:00 -0400

The Rheumatologist published a feature article on rheumatologists whose children followed in their footsteps to practice medicine and interviewed HSS rheumatologist Robert F. Spiera, MD, who was influenced by his father Harry Spiera, MD, to become a rheumatologist.

"My dad was the quintessential role model of a clinician-educator-scholar. I grew up seeing how taken he was with what he did, how good he was at what he did and how much he loved what he did," said Dr. Spiera.

According to the article, both father and son discussed cases together to improve patient care.

"There's a lot of evidence-based practice in rheumatology, as there is in other specialties. But there is also a lot of art to rheumatology. And my dad had such a huge clinical experience, seeing patients and not only really taking care of them, but really intimately, deeply caring about them. … He is a great sounding board," Dr. Spiera added.

Read the full article at the-rheumatologist.org.

Lenabasum Continues to Show Promise for Treatment of Systemic Sclerosis in Extension Study

Thu, 21 Jun 2018 07:00:00 -0400

Scleroderma News reported on a study that found that lenabasum, a potential treatment of diffuse cutaneous scleroderma, was shown to be safe and beneficial for patients during a Phase 2 clinical trial.

HSS rheumatologist Robert F. Spiera, MD, the trial's principal investigator, presented research findings at the European League Against Rheumatism (EULAR) 2018 Annual Meeting in Amsterdam.

According to the article, the trial found that patients experienced improvements in inflammation and fibrosis.

"Our results are very encouraging and reinforce the positive findings from the double-blinded placebo-controlled part of the study with regard to safety and tolerability. We look forward to continuing our investigations to assess the role of lenabasum as a new treatment option for patients with diffuse cutaneous systemic sclerosis," said Dr. Spiera.

Read the full article at sclerodermanews.com.

Expert Insight: Detecting Pulmonary Arterial Hypertension in Patients With Systemic Sclerosis

Fri, 18 May 2018 07:00:00 -0400

Rheumatology Advisor interviewed HSS rheumatologist Robert F. Spiera, MD, about risk factors and treatment strategies for pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc).

"PAH is an important complication of SSc, and one of the leading causes of mortality in this disease. Although it occurs in a minority of patients, clinicians must be attentive to it, as it can emerge at any point over the course of the disease," Dr. Spiera explained.

In terms of screening, Dr. Spiera noted that "a good history and physical are important at each visit".

"Treatment of SSc-associated PAH uses the same strategies as those used for idiopathic PAH, including vasodilators, endothelin receptor antagonists, prostacyclins, and in many patients, combination therapy," added Dr. Spiera.

This coverage originally appeared in rheumatologyadvisor.com. The original article is no longer available online.

#EULAR2018 - Lenabasum Safe and Effective in Diffuse Scleroderma Patients, One-year Trial Data Show

Thu, 17 May 2018 07:00:00 -0400

Scleroderma News highlighted a study that found that lenabasum, a potential treatment of diffuse cutaneous scleroderma, was shown to be safe, well-tolerated and beneficial for patients.

HSS rheumatologist Robert F. Spiera, MD, the trial's principal investigator, will present research findings at the European League Against Rheumatism (EULAR) 2018 Annual Meeting in Amsterdam.

Data collected from 25 patients showed an improvement of 56 percent on their ACR CRISS (American College of Rheumatology's diffuse cutaneous systemic sclerosis) score after completing 52 weeks of lenabasum treatment.

According to the article, the trial's next phase is currently underway.

Read the full article at sclerodermanews.com

Better Arthroplasty Outcomes, Hope in Scleroderma, and Other Rheumatology Advances

Wed, 03 Jan 2018 07:00:00 -0500

Medscape interviewed HSS rheumatologists Robert F. Spiera, MD and Susan M. Goodman, MD about their research presented at the 2017 American College of Rheumatology (ACR) Annual Meeting.

Dr. Goodman gave several presentations about social factors, such as income and education, that could affect joint replacement outcomes.

"What we found was that if you were highly educated, it didn't really matter where you lived; your outcome was the same. But those patients who weren't well-educated had worsening outcomes as the poverty level increased," noted Dr. Goodman.

Additionally, Dr. Spiera discussed his research about new drug compounds for scleroderma patients. During the clinical trial, patients treated with the new compound experienced an improvement in their symptoms.

Dr. Spiera and his team collected skin biopsies before and after treatment, which were reviewed by an experienced scleroderma investigator.

"He found that paired specimens from lenabasum-treated patients were clearly more likely to show improvement in inflammation. Of note, and perhaps surprising, they also were much more likely to show improvement and stabilization in fibrosis, which we did not traditionally think would likely change impressively in such a short period of time," said Dr. Spiera.

Read the full article at medscape.com [subscription required].