Julia Grapsa, MD, PhD, is the director for education in echocardiography at Brigham and Women's Hospital and a faculty member at Harvard Medical School.

Julia Grapsa, MD, PhD | Image Credit: Brigham and Women's Hospital

 are less frequently referred for aortic valve replacement and suffer from higher mortality risks compared to men. In addition to the notoriously lower number of female participants in clinical trials, women with aortic stenosis also go underreported and untreated.1

Previous research has highlighted this disparity, comparing the risk of all-cause mortality between male and female patients with aortic stenosis. The team found that women were substantially less likely to undergo aortic valve replacement, thereby suffering a higher mortality risk when treated conservatively. Despite this, both sexes displayed notable survival benefits from valve replacement.1

Julia Grapsa, MD, PhD, the director for education in echocardiography at Brigham and Women’s Hospital and a faculty member at Harvard Medical School, gave a presentation during the 

American Heart Association’s Scientific Sessions 2025

 in New Orleans, Louisiana, addressing the disparities faced by female patients, as well as how clinicians can address them.2

For additional insight, the editorial team at 

: What disparities exist in aortic stenosis treatment?


: Starting from diagnosis of aortic stenosis in women, they present quite differently than men. So, for example, women may complain of shortness of breath or chest pain more often than men. The heart also remodels in a different way in women than in men. For example, we are not going to see heavy calcification in a woman: it will be more fibrocalcific aortic stenosis, rather than the heavy calcific aortic stenosis that we see in men. When taking into account the aortic stenosis in women, especially because women are multitasking and have a huge responsibility daily, it may be underdiagnosed or non-diagnosed for years. We may have women who explain that they have shortness of breath or minimal symptoms like palpitations, and they may not get a prompt echo referral.


: How is your presentation addressing these disparities?


:Firstly, we’re discussing that women present differently than men, and second, that they are often underdiagnosed, because we saw in major centers that there was a delay to get an echo when compared to men. And a delay in diagnosis means delay in the treatment. Women also tend to present with what we call paradoxical low flow log gradient, which is when the ventricle gets impaired in the long term, or with significant diastolic impairment, and therefore delayed treatment will affect also the mortality outcomes. So eventually, if we delay treatment for too long, the mortality outcomes are higher.

As we know, another important parameter is that, up to now, not many women have been recruited for valve trials or cardiology trials in general. And our first trial, the SMART trial, was dedicated to women's anatomy and physiology, so it addresses small annuli that we see in women. And then we had the REAL trial that was dedicated to women, and they both proved, in a way, that treating women with TAVI promptly benefits outcomes and rates of hospitalization.


: What progress has been made in recent years towards addressing and resolving these disparities?



: We have gone deeply into addressing awareness, starting from the community: the awareness of primary care professionals in referring women for an echo promptly, and to refer them to specialty valve centers to get treated. When, for example, we diagnose severe, even asymptomatic, aortic stenosis, the patient needs to be referred to a specialty center immediately. And then we went a step further, and we have sex differences in the way we measure in echo, or, for example, in CT units. We know now that the CT calcium score is very different for women than for men. And of course, the even the LV stroke volume the new guidelines they gave it 32 ml per meter squared for women and 40 ml per meter squared in men. This difference did not exist before, so it's something novel. And of course, then we will go a step further and say that we need to treat women differently, given that they have smaller anatomies and a different physiology than men. And based on that and the differences we see between balloon expandable versus self-expandable valves or the rate of pacemakers. Then, when we see a woman in the clinic, we can go from diagnosis and sex differences in measurements up to the differences in valve selection and durability and especially depending on the underage and the functional capacity to aim for a long term prognosis and management plan dedicated and personalized for them.


: On an individual level, how can clinicians address the remaining disparities in cardiovascular treatment for women?


: As I said, awareness is a key word. Everybody needs to be aware that even a woman who presents with minor symptoms may have significant valvular heart disease. And then the next level is good communication with the patient. Last year, we published a small booklet for aortic stenosis in women, and we have a questionnaire that they can fill in and say how they're keeping in everyday household work and exercise, checking if they are managing their everyday duties. So going into depth, spending time with our patient and asking them if they can do today what they could do last year is key the good communication between health professionals and patients to get the diagnosis promptly rather than late.

Editor’s Note: Grapsa reports no relevant disclosures.

Paquin A, Abdoun K, Bienjonetti-Boudreau D, Pibarot P, Clavel MA. Sex-Specific Outcomes in Patients With Aortic Stenosis and Reduced Ejection Fraction. Can J Cardiol. 2025;41(11):2232-2240. 

Grapsa J. Transforming Aortic Stenosis Care with Medtronic TAVR for Women and lower risk patients. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

Articles

Female patients with aortic stenosis face significant disparities in diagnosis and treatment compared to male patients, leading to higher mortality risks. Women often present with different symptoms and heart remodeling patterns, contributing to underdiagnosis and delayed treatment. Recent efforts have focused on increasing awareness among healthcare professionals and improving clinical trial representation for women. Advances in personalized treatment approaches, such as the SMART and REAL trials, have demonstrated benefits of timely transcatheter aortic valve implantation (TAVI) for women. Effective communication and awareness are crucial for addressing these disparities.

Grapsa highlights the significant treatment gap between men and women suffering from aortic stenosis, as well as the skewed mortality risks resulting from them.

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Addressing Disparities in Aortic Stenosis Care for Women, With Julia Grapsa, MD, PhD

John Gill, MD, is a professor of medicine with tenure at the University of British Columbia, Division of Nephrology, Saint Paul's Hospital.

Results from the phase 2 BESTOW trial suggest tegoprubart, a novel anti-CD40L monoclonal antibody from Eledon Pharmaceuticals, provides comparable efficacy and superior safety to tacrolimus as the core immunosuppressant in de novo 

American Society of Nephrology (ASN) Kidney Week 2025

, the multicenter, randomized, open-label study enrolled 127 patients undergoing kidney transplantation, who were randomized 1:1 to receive tegoprubart 20 mg/kg intravenously every 3 weeks or tacrolimus, both in combination with rabbit anti-thymocyte globulin induction, corticosteroids tapered to 5 mg by day 28, and mycophenolate. The primary endpoint was estimated glomerular filtration rate (eGFR) at 12 months, serving as a proxy for long-term graft function.

“The Phase 2 results presented at ASN Kidney Week highlight the potential of tegoprubart to deliver strong graft function after kidney transplantation, while avoiding the long-term toxicities often associated with current standard of care,” said Andrew Adams, MD, PhD, Professor of Surgery and Chief, Division of Transplantation, John S. Najarian Surgical Chair in Clinical Transplantation, Department of Surgery, University of Minnesota. “It’s been more than a decade since we’ve seen true innovation in transplant immunosuppression. These data offer real hope that patients may soon have a transformative therapy that improves their health outcomes and overall quality of life.”

Among patients who completed treatment, mean eGFR at month 12 was 69 mL/min/1.73 m² in the tegoprubart arm compared to 66 mL/min/1.73 m² with tacrolimus. Across all subgroups, including donor type, donor age, and degree of human leukocyte antigen mismatch, tegoprubart demonstrated consistently higher eGFR values, with differences favoring tegoprubart of approximately 3–5 mL/min/1.73 m².

The composite efficacy endpoint, which was defined as death, graft loss, biopsy-proven acute rejection [BPAR], or loss to follow-up, showed non-inferiority for tegoprubart, with rates of 22.2% vs 17.2% for tacrolimus. BPAR occurred in 20.6% of tegoprubart-treated patients and 14.1% of those receiving tacrolimus, though most episodes were mild (Banff IA–IIB) and responsive to standard therapy.

Additionally, tegoprubart demonstrated a distinct safety advantage relative to tacrolimus, showing markedly lower rates of key calcineurin inhibitor–related toxicities. Compared to tacrolimus, tegoprubart was associated with lower incidences of new-onset diabetes (1.6% vs 10.9%), hyperglycemia (9.5% vs 21.9%), hyperkalemia (11.1% vs 26.6%), tremor (1.6% vs 25.0%), and delayed graft function (14.3% vs 25.0%). Investigators also pointed out rates of serious adverse events and opportunistic infections were comparable between groups (52–56% and ~68%, respectively), with no new safety signals observed.

For more on the study, check out our interview with phase 1 trial investigator John Gill, MD, MS, professor of medicine at The University of British Columbia.

Innovation in Transplant Immunosuppression With Tegoprubart, With John Gill, MD

Editors’ Note: Gill reports no relevant disclosures.

Eledon Pharmaceuticals. Eledon Presents Phase 2 BESTOW Trial Results for Tegoprubart for the Prevention of Rejection in Kidney Transplantation at the American Society of Nephrology’s Kidney Week 2025 Annual Meeting. Published November 6, 2025. Accessed November 21, 2025. 

https://ir.eledon.com/news-releases/news-release-details/eledon-presents-phase-2-bestow-trial-results-tegoprubart

Adams AB, Tedesco-Silva H, Potter S, et al. Efficacy and Safety of Tegoprubart for the Prevention of Rejection in Kidney Transplantation: Results from the Phase 2 BESTOW Trial. Presented at: ASN Kidney Week. Houston, Texas. November 5-9, 2025.

Videos

Gill describes tegoprubart’s efficacy and safety for post-kidney transplant immunosuppression and reviews key phase 2 BESTOW trial data from ASN.

Nephrology

The HCPLive nephrology page is a resource for medical news and expert insights on kidney disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in nephrology, and more.

Kidney Compass: Phase 3 Data on Telitacicept in IgA Nephropathy at ASN Kidney Week 2025

New phase 3 data released by Vor Bio underscore the potential of telitacicept, a dual BLyS/APRIL inhibitor, as a disease-modifying therapy for 

, particularly for patients at high risk of progression.

Kidney Compass: Navigating Clinical Trials

, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS sit down with study investigators Jicheng Lv, MD, PhD, and Hong Zhang, MD, PhD, professors of internal medicine at Peking University First Hospital, following their presentation at the 

Telitacicept is a recombinant fusion protein designed to neutralize BLyS and APRIL, upstream drivers of B-cell survival and immunoglobulin class switching, including production of galactose-deficient IgA1, the pathogenic hallmark of IgAN. The 39-week multicenter, randomized, double-blind trial evaluated the agent’s impact on proteinuria, B-cell activity, immunoglobulin levels, and kidney function.

In stage A, adults were randomly assigned 1:1 to telitacicept 240 mg subcutaneous weekly or placebo, in addition to background supportive care. The primary endpoint, which was defined as change in 24-hour urine protein-to-creatinine ratio (UPCR), was met with a −58.9% reduction in the telitacicept arm compared with −8.8% with placebo (

 < .0001). Week-39 data were consistent, with the treatment group showing a 55% 24-hour UPCR reduction.

Clinically meaningful thresholds associated with improved long-term renal outcomes were achieved at substantially higher rates with telitacicept:

24h-UPCR <0.8 g/g: 61% vs 19.5% (placebo)

Investigators highlighted kidney function remained stable across secondary endpoints. Mean eGFR change at week 39 was essentially unchanged with telitacicept (−0.010 mL/min/1.73 m²) compared with a modest decline in the placebo group (−0.77 mL/min/1.73 m²). Investigators also observed a lower risk of ≥30% eGFR decline (27%) with telitacicept versus placebo.

Editor's Note: LV reports relevant disclosures with Chinook Therapeutics, KBP Bioscience, and others. Zhang reports no relevant disclosures

Lv, J, Liu LJ, Wang W, et al. Efficacy and Safety of Telitacicept in Patients with IgAN: Results from Stage A of a Phase 3 Clinical Study. 

Journal of the American Society of Nephrology

Telitacicept Achieved Primary Endpoint in Phase 3 Clinical Study for IgA Nephropathy | Vor Bio. Vor Bio. Published 2025. https://ir.vorbio.com/news-releases/news-release-details/telitacicept-achieved-primary-endpoint-phase-3-clinical-study-0

Podcasts

Dual BLyS/APRIL inhibition with telitacicept cut proteinuria and maintained kidney function in adults with IgA nephropathy.

IgA Nephropathy

The HCPLive Berger disease page is a resource for medical news and expert insights on IgA nephropathy. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in Berger disease, and more.

Hosted by Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, Kidney Compass: Navigating Clinical Trials is a regular podcast exploring and breaking down the latest updates and nuances of clinical trials in nephrology. By listening to Kidney Compass, you'll get the guidance you need to navigate the changing landscape of clinical trials across the spectrum of kidney disease. 

podcasts page features a feed of medical news and interview podcast series, including DocTalk, Lungcast, Derm Discussions, and Heart Trials.

Leveraging BTKi in CSU Management

Bruton tyrosine kinase (BTK) acts as a critical signal transducer in the mast cell degranulation pathway, making it an attractive therapeutic target for chronic spontaneous urticaria (CSU). By blocking BTK, agents such as remibrutinib prevent downstream mast cell activation and subsequent release of histamine and other pro-inflammatory mediators involved in urticaria pathogenesis. This targeted approach allows for suppression of disease activity compared to antihistamines, which impact only a single mediator.

The REMIX 1 and REMIX 2 studies evaluated oral remibrutinib versus placebo in patients with moderate-to-severe CSU. These pivotal phase 3 trials enrolled almost 1000 participants and demonstrated significant improvements in urticaria activity scores and symptom control among those treated with remibrutinib. In addition, remibrutinib’s efficacy extended even to high-need patient subpopulations, including those with previous inadequate response to established biologic therapy.

BTK inhibitors are now poised to occupy a key position within the evolving CSU treatment paradigm. Their oral route, rapid onset, and robust efficacy and safety data make remibrutinib not only a viable alternative for refractory patients but also an option that can be considered earlier in the treatment algorithm. Shared decision-making based on patient history, preferences, and comorbidities will continue to shape the use of BTKi in CSU management, as recommended by emerging guideline updates.

Shyam Joshi, MD, examines the evolving role of BTK inhibition, particularly remibrutinib, in the treatment algorithm for chronic spontaneous urticaria.

Video Series

 Leveraging BTKi in CSU Management

Updates in Chronic Spontaneous Urticaria Management

Chronic spontaneous urticaria (CSU) pathophysiology centers on mast cell activation and degranulation, which causes the release of histamine and pro-inflammatory mediators responsible for the itching, hives, and angioedema experienced by patients. Traditional management has relied on antihistamines and, more recently, the introduction of omalizumab, which has provided new therapeutic avenues over the past decade.

However, as Shyam Joshi, MD, assistant professor of medicine in the Section of Allergy and Clinical Immunology at Oregon Health & Science University (OHSU) School of Medicine, explains, a significant proportion of patients—up to 50%—do not achieve satisfactory symptom control with antihistamine therapy alone, necessitating advanced treatment modalities. The introduction of Bruton tyrosine kinase (BTK) inhibitors, particularly remibrutinib, represents a milestone in CSU management. As the first oral BTK inhibitor approved for the condition, remibrutinib provides providers and patients with an alternative to injectable therapies, addressing issues such as injection-site reactions and offering rapid symptomatic improvement.

These therapy advancements underscore the importance of expanding treatment options for CSU, especially for patients with inadequate antihistamine response or contraindications to established injectables. Joshi emphasizes that the availability of safe, effective oral therapies empowers clinicians to tailor management strategies, thus optimizing patient outcomes and improving quality of life in this challenging chronic disease.

Shyam Joshi, MD, reviews fundamental updates in the management of chronic spontaneous urticaria.

Victoria Johnson joined the MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and now HCPLive. You can reach her at vjohnson@mjhlifesciences.com

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Exploring the New COPD Era: Biologics, Guidelines, and Real-World Barriers

Jürgen Floege, MD, senior professor at RWTH Aachen University’s Medical School

ASN insights on felzartamab, a CD38-targeted therapy, show sustained immune modulation in IgA nephropathy, offering a novel treatment approach.


Post Conference Perspectives

PREVAIL: Felzartamab’s Sustained Clinical Outcomes In IgAN, With Jurgen Floege, MD

Tim Smith joined the MJH Life Sciences team as an assistant editor for HCPLive in August 2022. He graduated from UC Berkeley with a degree in political science, working in multimedia journalism as a staff writer prior to joining MJH. In his spare time, he enjoys reading, watching TV, listening to podcasts, and rock climbing. You can contact him at 

In this analysis, investigators examined the efficacy of baricitinib in terms of its impact on disease activity and progression of frontal fibrosing alopecia.

Alopecia

Dermatology

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Mid Trial Update Released on Baricitinib for Frontal Fibrosing Alopecia

Daniel Manning, MD: An allergy, asthma, & immunology specialist located in Arizona

At ACAAI 2025, Manning highlighted sustained attack reduction and strong patient preference for donidalorsen across long-term and switch data.

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Donidalorsen Shows Durable Long-Term Efficacy for HAE, With Daniel Manning, MD

Bhatt discusses the positive results from the phase 2 trial of quarterly and monthly doses of investigational IL-6 inhibitor pacibekitug.

Atherosclerotic Cardiovascular Disease

Chronic Kidney Disease

TRANQUILITY: Pacibekitug Safely Lowers hs-CRP in ASCVD, With Deepak Bhatt, MD

Naim Alkhouri, MD, is Chief Academic Officer at Summit Clinical Research and the Director of the Steatotic Liver Disease Program at the Clinical Research Institute of Ohio.

Alkhouri explains the importance of differentiating F3 from cirrhosis and the utility of different noninvasive tests for identifying these patients.

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Using Noninvasive Testing to Guide MASH Treatment Decisions, With Naim Alkhouri, MD

These data highlight a super-response following treatment with delgocitinib cream 20 mg/g in a subgroup of patients with moderate to severe CHE.


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Subgroup with Chronic Hand Eczema See ‘Super Response’ with Delgocitinib Cream

University of Colorado Health Sciences Center

A study presented at ACAAI 2025 reveals HAE attacks may start in toddlers, highlighting significant daily burdens and the importance of timely diagnosis and treatment.

HAE Attacks May Begin as Early as 2 Years Old, With Daniel Soteres, MD, PhD

Assistant Professor at the University of Texas Health Science Center at San Antonio

Becker recapped hot topics of discussion during a recent HCPLive clinical forum.

Non-Steroidal Topicals: A Game-Changer for Pediatric Atopic Dermatitis, With Emily Becker, MD

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She joined MJH Life Sciences in August 2023 shortly after graduating from Monmouth University where she earned her BA in Communication with a concentration in Public Relations/Journalism and later an MA in Interactive Digital Media. She enjoys traveling, running, and reading books. She can be reached at abrooks@mjhlifesciences.com.

The living guideline incorporates new medications and the latest data to make recommendations for moderate-to-severely active CD care.

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Latest News

Addressing Disparities in Aortic Stenosis Care for Women, With Julia Grapsa, MD, PhD

Innovation in Transplant Immunosuppression With Tegoprubart, With John Gill, MD

Kidney Compass: Phase 3 Data on Telitacicept in IgA Nephropathy at ASN Kidney Week 2025

Leveraging BTKi in CSU Management

Updates in Chronic Spontaneous Urticaria Management