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.

Research highlights include studies that have found an initial high-risk antibody profile for antiphospholipid syndrome (APS) tended to remain high in pediatric patients, a correlation between obesity and more severe disease flare symptoms in patients with early rheumatoid arthritis (RA), people with inflammatory arthritis face challenges in maintaining employment, a link between aging and physical activity, and people with vasculitis frequently suffer from frailty, new research findings in antiphospholipid syndrome (APS)  insights on improving communications with diverse patient populations, and and new research on reproductive health.

A High-Risk Antiphospholipid Antibody Profile Matters in Pediatric Patients with Antiphospholipid Syndrome

A new study by HSS investigators including Jheel Pandya, MD, Karen Onel, MD, Doruk Erkan, MD, MPH has found that an initial high-risk antibody profile for APS tended to remain high in pediatric patients.

HSS Research Shows Obesity Is Associated with Worse Flare Symptoms and Quality of Life in People with Early Rheumatoid Arthritis 

A recent study from HSS and others has found a correlation between obesity and more severe disease flare symptoms that negatively affect quality of life in patients with early RA, a systemic, autoimmune, inflammatory disorder affecting multiple joints in the body. 

Study Finds People with Inflammatory Arthritis Face Significant Psychological Challenges in Maintaining Employment

An HSS study presented by Joan Westreich, MSW, LCSW, social work coordinator, Early Arthritis Initiative at HSS reveals a significant psychological impact related to inflammatory arthritis patients’ efforts to maintain employment while coping with the challenges of their illness.

New Study Shows Perception of Aging is Linked to Level of Physical Activity in Arthritis Patients

People with arthritis who report more negative feelings about how they are aging tend to get less physical activity and perceive themselves as less healthy, according to a new study by researchers at HSS and Weill Cornell Medicine. However, self-perception of good health explained the effect of negative thinking – providing an opportunity for clinicians to focus on a patient’s outlook on aging as well as their overall health. 

New Study Identifies Outcomes Associated With Frailty in Patients With Vasculitis

According to a new study from researchers at HSS and colleagues from the University of Pittsburgh and the University of Pennsylvania, 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.

New Antiphospholipid Syndrome Research Findings Presented at ACR Convergence 2023

Investigators from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) presented new research findings in antiphospholipid syndrome (APS) at the American College of Rheumatology (ACR) Convergence 2023, the ACR’s annual meeting.

HSS Shares Strategies to Enhance and Enable Communication with Language-Diverse Patients at Annual ACR Convergence

Bella Elogoodin, vice president, Service Excellence & Language Access at HSS, shared strategies to enhance and enable communication with language-diverse patients at the American College of Rheumatology (ACR) Convergence 2023 in a session titled, “Lost in Translation: Creating Access Pathways for Language-Diverse Patients in Rheumatic Care Settings.”

HSS Presents New Reproductive Health Research at the ACR Convergence 2023  

At this year’s American College of Rheumatology (ACR) annual meeting, HSS presented a number of 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.

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.