Ana Marenco Flores, MD, is a research fellow in medicine in the division of gastroenterology at Beth Israel Deaconess Medical Center and Harvard Medical School.

Validating the Amsterdam-Oxford Model for PSC Prognosis, with Ana Marenco Flores, MD

New research is confirming the validity of the Amsterdam-Oxford Model for predicting long-term 

Study findings were presented at Digestive Disease Week (DDW) 2025 by Ana Marenco Flores, MD, a research fellow in medicine in the division of gastroenterology at Beth Israel Deaconess Medical Center and Harvard Medical School, and demonstrate the Amsterdam-Oxford Model’s ability to successfully predict adverse outcomes in a US cohort of PSC patients, supporting its generalizability across diverse populations and clinical settings.

The Amsterdam-Oxford Model, which was developed from Dutch and UK cohorts, incorporates 7 clinical variables to predict long-term PSC outcomes: PSC subtype, age at diagnosis, aspartate aminotransferase, alkaline phosphatase, total bilirubin, albumin, and platelet count.

“[This is] a tool that can help you and the patient see what the possibilities of their outcomes are,” Marenco Flores explained to 

. “You as a clinician may be able to save time and resources by doing an equation with some labs or questions and see if you have to dedicate more time to this patient… that can give you a perspective of the follow ups that you have to do with the patient or if you need to refer them to another specialist. I think doing an assessment like this in your first visit is really important to see every patient as a single case, because not all PSC patients behave the same way.”

While the model has demonstrated strong predictive accuracy, Flores and colleagues recognized the need for external validation to assess its generalizability. To do this, they analyzed data from patients with PSC enrolled in an autoimmune prospective registry between 2018 and 2024. For inclusion, patients were required to ≥ 18 years of age with confirmed PSC, complete datasets for calculating both risk scores, and ≥ 4 years of follow-up.

Predictive performance was assessed using the area under the receiver operating characteristic curve. Investigators conducted Kaplan-Meier survival analysis, stratified by Mayo Risk Score classification and corresponding Amsterdam-Oxford Model values, to compare clinical outcomes, with survival defined as time to liver transplantation or death.

In total, the study included 109 patients with PSC. Their mean age was 45 ± 15 years, and the majority of patients (51%) were female. Among the cohort, 85% of patients remained alive without liver transplantation (LT), 12% underwent LT, and 3% died after a median follow-up of 4.63 years.

The median Amsterdam-Oxford Model score was 1.48 (interquartile range [IQR], 1.04 to 1.83) and the median Mayo Risk Score was -0.5 (IQR, -1.03 to -0.02). Logistic regression identified the Amsterdam-Oxford Model (odds ratio [OR], 4.95; 

 = .027) as independent predictors of LT or death, and multivariate analysis confirmed the Amsterdam-Oxford Model’s significance (OR, 4.96; 

Further survival analysis demonstrated worse outcomes in patients classified as high risk by both the Mayo Risk Score and Amsterdam-Oxford Model, with a 2-year survival rate of 66% compared to 92% for intermediate-risk and 95% for low-risk patients.

“ I think for us at every clinic or hospital, your resources and time are really valuable,” Marenco Flores said. “By applying a score with data that you have at your everyday assessment of the patient, you can get a sense of personalized medicine, and that's something that we want to achieve in the future.”

Editors’ note: Marenco Flores has no relevant disclosures.

Marenco-Flores A, Amaris NR, Kahan TF, et al. EXTERNAL VALIDATION OF THE AMSTERDAM-OXFORD MODEL FOR PREDICTING LIVER TRANSPLANTATION AND MORTALITY IN U.S. PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: A COMPARATIVE ANALYSIS WITH THE MAYO RISK SCORE. Abstract presented at Digestive Disease Week 2025 in San Diego, CA, from May 3 - May 6, 2025.

de Vries EM, Wang J, Williamson KD, et al. A novel prognostic model for transplant-free survival in primary sclerosing cholangitis. 

The Amsterdam-Oxford Model successfully predicted adverse outcomes in a US cohort of PSC patients, validating its generalizability.

Ana Marenco Flores, MD

Real-World Treatment Strategies Using Next-Generation Therapies for Neovascular AMD and DME

Summary of "Real World Treatment Strategies Using Next Generation Therapies for Neovascular AMD and DME"

This discussion among Dr Ehsan Rahimy, Dr David Miller, and Dr Michael Klufas covers practical strategies for managing neovascular AMD and DME with newer, more durable anti-VEGF therapies.

Real-world data supplements clinical trials by providing safety insights from larger patient populations

Clinical trials typically involve treatment-naive patients while physicians often use new agents in previously treated patients

Real-world practice often differs from trial protocols, especially regarding loading doses and switching therapies

For treatment-naive patients, physicians generally follow recommended loading doses to maximize vision gains

For previously treated patients switching to newer agents (faricimab, aflibercept 8 mg), complete reloading may not be necessary

Disease-specific considerations: AMD typically requires more strict adherence to loading protocols than DME

Both physicians have become more comfortable with 4-week extensions for DME patients

For neovascular AMD, especially in monocular patients, 1- to 2-week extensions remain standard practice due to risk of hemorrhage

Physicians note a sweet spot of 3- to 4-month intervals for most patients, as compliance drops significantly beyond this timeframe

Traditional 12-week caps are being reconsidered with newer agents

Some physicians now feel comfortable extending to 16 weeks in appropriate patients

For DME, extensions to 20 weeks may be appropriate, particularly when hemoglobin A

For neovascular AMD, most remain cautious about extending beyond 16 weeks due to monitoring concerns

Some patients prefer more frequent visits as a “security blanket” despite drug durability

Patient preferences and vision dependence should factor into treatment decisions

Physicians should balance optimal disease control with patient convenience

Extended intervals create challenges in monitoring fellow eyes for conversion

Home monitoring technologies (OCT) show promise but reimbursement and workflow concerns exist

Patient compliance decreases significantly with intervals beyond 4 months

When switching from aflibercept 2 mg to 8 mg, physicians typically see a 2- to 4-week extension in treatment intervals

Benefits of extension often improve over time rather than immediately after switching

Gene therapy shows promise, particularly subretinal injection approaches

Better geographic atrophy treatments remain an unmet need

Tyrosine kinase inhibitors may offer a balance between efficacy and delivery convenience

Suprachoroidal delivery for DME shows potential

This summary provides key clinical insights on treatment strategies using newer anti-VEGF agents, balancing protocol adherence with real-world considerations to optimize patient outcomes.

Ehsan Rahimy, MD; David G. Miller, MD; and Michael Klufas, MD, discuss how real-world treatment strategies for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) with next-generation anti-VEGF therapies differ from clinical trials, including individualized loading dose approaches, extension interval considerations, and the challenges of balancing durability with appropriate monitoring.

Real-World Treatment Strategies Using Next-Generation Therapies for Neovascular AMD and DME 

Esther Kim, MD 

 So in the last few minutes, I'm going to ask each of you as you look into the future caring for our patients with obstructive HCM [hypertrophic cardiomyopathy] and non-obstructive HCM, what other things are you excited about? We talked a little bit about the myosin inhibitors, but clearly there are other things that Milind alluded to that are coming down the pike for us. It's an exciting time to be in HCM position. What are the things that you're most looking forward to and Jim, I'll start with you.

 Yeah, thanks very much. I'll put my clinical trial hat on. We've fully enrolled a clinical trial looking at metabolic manipulation of myocardial function using a partial fatty acid oxidase inhibitor in patients with HCM. So approaching the question from a completely different angle that would be additive together with cardiac myosin inhibition, so thinking about newer pathways to address in patients with HCM to improve their symptoms. That's really exciting to me.

 So speaking as a heart failure, transplant cardiologist is what I spend most of my time doing. I think we still have so many unanswered questions in patients with non-obstructive HCM with advanced symptoms. What's the role of guideline directed medical therapy—was just traditional garden variety heart failure with preserved ejection fraction therapy like mineralocorticoid antagonists, angiotensin receptor neprilysin inhibitors, SGLT2 inhibitors. Do they work? Will they be effective in non-obstructive HCM? I think that is an unmet need in a huge space that I'm hopeful in the future we'll have more answers.

 I agree with you completely. That group of patients are perhaps the most difficult and challenging to treat in the clinic and hopefully will make some headway there. Milind, what are you looking forward to?

 I will start with what Michelle alluded to the next frontier is the non-obstructive HCM. So I am not a heart failure transplant doctor, but can mavacamten or CMIs [cardiac myosin inhibitors] work in this space because it's not all about the LVOT [left ventricular outflow tract] obstruction. There are structural changes that are happening, and we are answering this question in an ongoing randomized clinical trial, RCHCM, and there is another one with aficamten, that is being planned coming down the pike. That will help us clear some of that air. Of course, we need to understand the other drugs like SGLT. Could that work? But the bigger picture I think is the genetic space, the gene therapies, the adenovirus-based therapies that can help modulate the deficient protein in the heart of MYBPC3 so that space is active and brewing the business of gene editing CRISPR, etcetera. All these things obviously, I often joke as long as it does not create mutant Ninja Turtles down the road, meaning the uncertain offshoot effects, I think the future is bright. Honestly, I just told this to one of my patients a couple of days ago is that I can excitedly look forward to having a potential cure for this disease before I hang my boots into retirement. So I'm looking forward to all and plus the PROs [patient reported outcomes] and the shared-decision making. The other thing is the HCMR trial, hypertrophic cardiomyopathy registry from NIH which I am also part of, so I have to plug it in. That is going to start reading out in the next year or so that will help understand the risk stratification space a lot more.

 What's left? They've taken all the low hanging fruit And even the high hanging fruit from the tree. No fruit left on the tree.

 You're climbing all the way up the tree to the top.

 No fruit left on the tree. So I would echo what Jim said. I think that the potential for positive remodeling of the left ventricle not only pathologically with hypertrophy, but maybe reducing the progression of fibrosis would be a major advancement. If we can show that a therapy reduces progressive fibrosis that we can see on late gadolinium enhancement, we know its association with worsening progressive heart failure as well as ventricular arrhythmias, that would be a huge benefit. As Milind said that fibrosis is also shown with severe diastolic dysfunction as well, and many of our patients have some symptoms with outflow tract relief from diastolic dysfunction. So I think that is another unmet need. The last thing I would say is you know how normal can we make patients feel? With obstructive hypertrophic cardiomyopathy, will they be safe to be highly competitive, vigorous athletes, even with this condition? Can we really get close to normalizing what they really can do and feel like they can do and want to do?

 Yeah, that's what's a wonderful goal. It is a lofty goal, but one that we may meet. So with that, I'd like to thank you all for joining our panel today. This has been a very rich, informative and lively discussion and thank you audience for watching our HCPLive Peer Exchange®. You can subscribe to the enewsletter and receive other great content right in your inbox. Thanks again everyone.

Transcript is AI-generated and edited for clarity and readability.

Andrew Wang, MD; James Januzzi, MD; Michelle M. Kittleson, MD, PhD; and Milind Desai, MD, MBA, share a look into the future of oHCM treatment.

The Future of oHCM Treatment

Michelle M. Kittleson, MD, PhD

The complexity and heterogeneity of asthma reflects its wide range of potential triggers, clinical manifestations, and underlying drivers. Various disease pathways – spanning both innate and adaptive immunity – can serve as tributaries to the chronic inflammatory state at the core of the disease.

In many individuals with severe, uncontrolled asthma, pathogenic processes can overlap dynamically in ways that can change over time.

 This can makes it difficult to base clinical management decisions the apparent predominance of a specific inflammatory pathway and its constituent mediators.

 As a result, the estimated 1 million people in the U.S. contending with severe, uncontrolled asthma face ongoing challenges that can evolve into exacerbations, hospitalizations and consequent use of health care resources.

In recent years, new insights into the role of the airway epithelium in asthma have provided a framework for understanding how diverse and changeable inflammatory signals can converge to promote severe clinical disease. The significance of airway epithelium in asthma derives not only from the well-known structural damage it undergoes but from the proinflammatory signals it initiates.

As the first point of contact between potential asthma triggers and the lungs, the epithelium sits at the headwaters of multiple distinct inflammatory cascades. Whether the immediate trigger is a pathogen, allergen, or irritant, the epithelium can respond by releasing proinflammatory cytokines including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP).

 First identified as a growth factor in the early 1990s, TSLP has more recently attracted considerable scientific interest because of its capacity to drive multiple downstream innate and adaptive immune responses.

TSLP Action Across Major Inflammatory Categories

Despite its vast phenotypic diversity, asthma can be categorized at a high level based on major patterns of inflammation. About two-thirds of individuals with severe asthma exhibit type 2 (T2) inflammatory patterns.

 T2 inflammation includes classic allergy, where antigen presentation to type 2 helper T (Th2) cells promotes the production of allergen-specific IgE antibodies, mast cell degranulation, and release of proinflammatory mediators.

T2 inflammation also encompasses nonallergic pathways that share key features with allergic inflammation. In lieu of antigen presentation and clonal selection of IgE-producing B cells, type 2 innate lymphoid cells (ILC2s) directly provide cytokine signals promoting recruitment and activation of eosinophils.

While a significant proportion of patients with severe asthma exhibit T2 inflammation, there remains a substantial portion of patients with severe asthma who exhibit a non-T2 inflammatory pattern, where target-tissue inflammation is primarily mediated by IL-17A, produced by Th17 cells. Eosinophils do not play a major role in non-T2 inflammation, although neutrophil proliferation may occur. Non-T2 inflammation is commonly associated with late-onset asthma.

, each of these broad inflammatory pathways can ladder back to the epithelial release of TSLP. A broad array of innate and adaptive immune cells – including dendritic cells, naïve and differentiated T cells, ILC2 cells, and mast cells – respond to TSLP via TSLP receptors. TSLP thus is capable of activating diverse downstream inflammatory cascades.

Regardless of the underlying inflammatory processes at play, airway narrowing through progressive tissue remodeling poses major challenges to asthma management that increase in urgency with disease severity.

Early research demonstrates a potential role of TSLP in airway remodeling. Fibroblasts and airway smooth muscle cells (ASMCs) both express TSLP receptors. TSLP has been shown in vitro to stimulate collagen production by fibroblasts and promote ASMC proliferation. ASMCs produce TSLP as well as respond to it; airway remodeling may be mediated in part through TSLP cross-talk between ASMCs and mast cells.

Multiple lines of evidence suggest a central role of TSLP in the pathogenesis of severe asthma, largely independent of inflammatory phenotype and biomarker patterns:

Airway TSLP is overexpressed in patients with asthma and increases with disease severity.

 Airway TSLP expression has been found to be higher in patients with asthma compared with healthy controls, and the elevated levels correlated significantly with asthma severity.

Airway TSLP expression correlates with reduced lung function.

 A study of 70 patients with asthma of varying severity found that airway TSLP concentrations were inversely correlated with FEV

TSLP may drive reduced corticosteroid responses.

 ILC2s obtained by bronchoalveolar lavage from patients with severe asthma showed a reduced in vitro response to dexamethasone after exposure to TSLP. Further, the reduced response to dexamethasone was greater in patients with higher airway TSLP expression.

Our increased understanding of the role of TSLP in asthma underscores the importance of the airway epithelium as the first point of contact with environmental stimuli. TSLP, a key epithelial cytokine produced in response to environmental triggers, can drive multiple downstream inflammatory pathways that may contribute to severe, uncontrolled asthma. Because TSLP sits at the top of these disparate inflammatory cascades, there is evidence that it plays a central role in the pathogenesis of severe asthma.

Global initiative for Asthma. Global strategy for asthma management and prevention, 2020. Available from: 

Roan F, Obata-Ninomiya K, Ziegler SF. Epithelial cell-derived cytokines: more than just signaling the alarm. 

Kupczyk M, Dahlen B, Sterk PJ et.al. Stability of phenotypes defined by physiological variables and biomarkers in adults with asthma. 

Busse WW. Biological treatments for severe asthma: a major advance in asthma care. 

Price D, Canonica GW. Biomarker relatability in the International Severe Asthma Network. 

Centers for Disease Control and Prevention. https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm. 2021.

Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. 

Wang E, Wechsler ME, Tran TN, et al. Characterization of severe asthma worldwide: data from the International Severe Asthma Registry. 

Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. 

Rochman Y, Leonard WJ. Thymic stromal lymphopoietin: a new cytokine in asthma. 

Peters MC, Mekonnen ZK, Yuan S, et al. Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma. 

Bartemes KR, Kita H. Dynamic role of epithelial-derived cytokines in asthma. 

Li Y, Wang W, Lu Z et.al. Elevated expression of IL-33 and TSLP in the airways of human asthmatics In vivo: a potential biomarker of severe refractory disease. 

Liu S, Verma M, Michalec L, et al. Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: The role of thymic stromal lymphopoietin. 

Cao L, Liu F, Liu Y, et al. TSLP promotes asthmatic airway remodeling via p38-STAT3 signaling pathway in human lung fibroblast. 

Ko HK, Cheng SL, Lin CH, et al. Blood tryptase and thymic stromal lymphopoietin levels predict the risk of exacerbation in severe asthma. 

Ying S, O'Connor B, Ratoff J, et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. 

The Proinflammatory Role of Epithelial TSLP in Severe Asthma 

Nestor Molfino, Executive Medical Director and Global Development Lead, Amgen

Parissa Tabrizian, MD, MSc, is a surgeon who specializes in hepatobiliary and liver transplantation at the Recanati/Miller Transplantation Institute and an associate professor of surgery at Mount Sinai School of Medicine.

Pretransplant Immunotherapy for Hepatocellular Carcinoma, with Parissa Tabrizian, MD

Immunotherapy has reshaped the treatment of 

, offering survival benefits once thought unattainable. While its success in advanced disease is well established, its potential in surgical and transplant settings remains a subject of debate.

The use of immunotherapy before liver transplantation presents both promise and risk, raising hopes for improved outcomes while also sparking concerns about immune-mediated rejection. With limited long-term data and no formal guidelines supporting its use in this setting, ongoing research is necessary to determine which patients may benefit, how to mitigate risks, and whether this approach could become a viable strategy for bridging patients to transplant.

“The role of immunotherapy in surgery and in the neoadjuvant setting really started with the experience that we had with resection cases,” Parissa Tabrizian, MD, MSc, a surgeon who specializes in hepatobiliary and liver transplantation at the Recanati/Miller Transplantation Institute and an associate professor of surgery at Mount Sinai School of Medicine, explained to 

. “As a high-volume center here at Sinai and many others, we explored the use of the neoadjuvant therapy in resectable HCC cases and we've shown excellent outcomes in a small group of patients.”

However, she notes current guidelines do not support the use of pretransplant immunotherapy, and she says this is “rightfully so” due to concerns about immune-mediated rejection, adverse events, and a lack of positive long-term data.

Tabrizian cites key studies in the field, including a large retrospective study from China and a meta-analysis showing that shorter washout periods correlate with higher rejection rates. Her own multi-center study, the VITALITY study, demonstrated the feasibility of immunotherapy in 117 consecutive patients with HCC assessed for liver transplantation and treated preoperatively with immune checkpoint inhibitors, reporting no severe adverse effects and promising survival outcomes.

“Unfortunately, we have a lot of unanswered questions because we don't do not have robust data or level one evidence,” Tabrizian said.

Specifically, she outlines lingering unanswered questions about optimal patient selection, the best timing for discontinuation before transplant, and the management of immunosuppression post-transplant, although she suggests that patients at high risk of disease progression or those with long waitlist times may benefit most from a neoadjuvant approach.

While preliminary data is encouraging, Tabrizian stresses that more research is necessary to define the role of immunotherapy in transplantation and ensure its safe integration into clinical practice.

Editors’ note: Tabrizian has relevant disclosures with Boston Scientific and AstaZeneca.

Tabrizian P, Abdelrahim M, Schwartz M, et al. Immunotherapy and transplantation for hepatocellular carcinoma. Journal of Hepatology. doi:

Tabrizian P, Holzner ML, Ajmera V, et al. Intention-to-treat outcomes of patients with hepatocellular carcinoma receiving immunotherapy before liver transplant: The multicenter VITALITY study. Journal of Hepatology. doi:

Tabrizian discusses neoadjuvant immunotherapy for HCC, describing its success in the adjuvant setting but uncertainties about its use before transplant.

Parissa Tabrizian, MD, MSc

Iltefat Hamzavi, MD, explores key areas of patient communication that may shape adherence and outcomes in patients with vitiligo.

Communication With Patients With Vitiligo

Pearl E. Grimes, MD

HCPLive Five at SLEEP 2025 

 SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies,

 from June 9 – 11th in Seattle, Washington, to share new sleep medicine data.

As a part of HCPLive’s on-site coverage, the editorial team conducted > 15 interviews on various topics, from new pharmacotherapy treatments for OSA and AI in sleep medicine to changes to the restless legs syndrome (RLS) guidelines and the association between napping and mortality risk in older adults.

In this edition of the HCPLive Five, the team captured the top 5 interviews at the meeting, featuring research on a VeNS device for insomnia and PTSD, latest pharmacotherapy developments for sleep apnea, new RLS guidelines, the link between naps and mortality risk, and AD109 for obstructive sleep apnea (OSA).

VeNS Device Improves PTSD, Insomnia Symptoms in RCT, with Peter Colvonen, PhD

Peter Colvonen, PhD, an associate clinical professor at the University of California, San Diego, presented results from a randomized controlled trial showing that vestibular nerve stimulation (VeNS) significantly improved PTSD and insomnia symptoms. The 12-week trial involved over 380 adults with PTSD, many of whom face years-long waits for 1-on-1 therapy.

VeNS, a non-invasive, at-home device, led to significantly greater reductions in PTSD and Insomnia Severity Index scores compared to a sham. Colvonen emphasized its potential as an interim solution for patients stuck on long waitlists, highlighting VeNS as a scalable option to stabilize symptoms until gold-standard care becomes available.

Latest Pharmacotherapy Developments for Sleep Apnea, with Danny Eckert, PhD

Danny Eckert, PhD, a professor at Flinders University, highlighted emerging pharmacotherapies for obstructive sleep apnea (OSA), addressing both anatomical and non-anatomical causes. The FDA-approved GLP-1 agonist tirzepatide helps reduce OSA in obese patients through weight loss.

For non-obese individuals, AD109, a combination of aroxybutynin and atomoxetine, showed promise in a phase 3 trial, resolving OSA in 25% of patients. Eckert also discussed potassium channel blockers that reset airway reflexes and acetazolamide, which lowers loop gain and reduces OSA severity. These advances mark a shift toward personalized, drug-based OSA treatments, especially for patients who struggle with traditional therapies like CPAP.

RLS Guidelines Advise Against Dopamine Agonists, With John Winkelman, MD, PhD

John Winkelman, MD, PhD, chief of the sleep disorders clinical research program at Massachusetts General Hospital, discussed the AASM’s updated restless legs syndrome (RLS) guidelines, which now advise against routine use of dopamine agonists due to high augmentation risk. Up to 50% of patients on these drugs may experience symptom worsening over five years. The guidelines recommend iron therapies and alpha-2-delta ligands (gabapentin, gabapentin enacarbil, pregabalin) instead.

Winkelman emphasized identifying and managing exacerbating factors like antidepressants, antihistamines, or sleep apnea. He advises a slow, careful taper of dopamine agonists over 6–12 months, warning patients of temporary worsening but long-term improvement once off the medication.

Naps at Noon Linked to Mortality Risk in Older Adults, with Chenlu Gao, PhD

Chenlu Gao, PhD, from Massachusetts General Hospital and Harvard Medical School, presented findings linking longer, irregular, and early afternoon naps to increased all-cause mortality in middle-to-older adults. Using UK Biobank data from over 86,000 participants, the study found that greater nap duration, high day-to-day variability, and naps between 11 am–3 pm were associated with higher mortality risk over an 8-year follow-up.

Gao emphasized the study was observational and not causal—napping patterns may reflect underlying health issues like sleep disorders or chronic illness. She advised clinicians to address root causes of excessive napping rather than eliminating naps entirely.

AD109 Improves OSA in Phase 3 SynAIRgy Trial, With Patrick Strollo, MD

Patrick Strollo, MD, from the University of Pittsburgh Medical Center, presented phase 3 SynAIRgy trial results showing that AD109, a once-daily oral neuromuscular modulator, significantly improved obstructive sleep apnea (OSA). In the 26-week trial of 646 participants intolerant of CPAP, AD109 reduced apnea-hypopnea index (AHI) by 55.6% and improved oxygenation measures. More than half of participants had reduced OSA severity, and 22.3% achieved full disease control (AHI < 5).

AD109, a first-in-class combination of aroxybutynin and atomoxetine, works by enhancing upper airway muscle tone during sleep. Apnimed plans to submit an FDA application in early 2026, with additional phase 3 data expected later in 2025.

Sleep experts gathered at SLEEP 2025 to discuss advancements in sleep medicine, including new treatments and guidelines. Key topics included a VeNS device for PTSD and insomnia, pharmacotherapy for sleep apnea, updated RLS guidelines, and the link between napping and mortality risk. The VeNS device showed promise in reducing PTSD and insomnia symptoms, while new pharmacotherapies like AD109 and tirzepatide offered hope for OSA patients. Updated RLS guidelines advised against dopamine agonists, and research linked irregular naps to increased mortality risk, emphasizing the need to address underlying health issues.

Check out the top 5 interviews from SLEEP 2025.

Peter Colvonen, PhD

Siddharth M. Patel, MD, MPH, is a TIMI Study Group Investigator, Associate Physician in the Cardiovascular Division at Brigham and Women’s Hospital, and Instructor of Medicine at Harvard Medical School.

Abelacimab Benefits Spectrum of Bleeding Risk with Siddharth Patel, MD, MPH

Abelacimab, a novel factor XI inhibitor, achieved reductions across the spectrum of bleeding risk, compared with rivaroxaban, in patients with 

, with a greater absolute safety benefit in those at high bleeding risk.

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

, the analysis compared the safety of abelacimab to rivaroxaban using the direct oral anticoagulant (DOAC) score among 1287 patients with atrial fibrillation enrolled in the AZALEA-TIMI 71 trial.

“If you think about the risk factors for predisposition to bleeding, including advanced age, renal impairment, use of other concomitant medications, these are folks who have an indication for reducing ischemic risk, but typically post a significantly higher bleeding risk,” Siddharth Patel, MD, MPH, an associate physician in the cardiovascular division at Brigham and Women’s Hospital, told 

. “We’re really encouraged by the results, the fact that even in that very high bleeding risk group, we saw the same substantial reduction in bleeding risk in those receiving abelacimab, compared with rivaroxaban.”

Results from AZALEA-TIMI 71 showed abelacimab significantly lowered the risk of major and clinically relevant non-major bleeding in patients with AF, compared with rivaroxaban. Both abelacimab doses (90 mg and 150 mg) were pooled for this analysis. Using the validated DOAC score, 8%, 33%, 37%, 16%, and 5% of patients were categorized as very low (0-3), low (4-5), moderate (6-7), high (8-9), and very high (10) bleeding risk, respectively.

Upon analysis, rates of major or clinically relevant nonmajor bleeding per 100 patient years increased stepwise based on risk scores in the rivaroxaban arm, from 5.6% in the low risk category to 21.2% in the very high risk category. In contrast, bleeding rates in the pooled abelacimab arm were 2.5% in the low-risk category versus 7.1% in the very high-risk category.

Further analysis showed the absolute risk reduction (ARR) increased from 3.1% in the low risk category to 14.1% in the very high risk category (

-trend <.001). Pending further research, regulatory approval of abelacimab could be particularly beneficial for patients with AF at high bleeding risk.

“If these therapies are confirmed to be effective for the prevention of thromboembolism in ongoing Phase 3 trials, this could really represent an opportunity to expand the armamentarium of therapies to patients who have traditionally not been anticoagulated due to history of bleeding, or even the perceived fear of bleeding,” Patel told 

Patel reports relevant disclosures with Janssen Pharmaceuticals.

Patel SM, Giugliano RP, Morrow DA, Goodrich EL, et al. Factor XI Inhibition with Abelacimab in Atrial Fibrillation Across the Spectrum of Bleeding Risk. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

Anthos Therapeutics shares new data from the landmark Azalea-TIMI 71 study demonstrating the factor XI inhibitor Abelacimab significantly reduced bleeding in patients regardless of age or bleeding risk. Anthos Therapeutics. March 29, 2025. Accessed April 4, 2025. 

https://anthostherapeutics.com/press-release/anthos_2025-03-29_release/

In a new analysis at ACC.25, abelacimab reduced bleeding rates across the risk spectrum, with more benefits for those at higher bleeding risk.

Siddharth M. Patel, MD, MPH

Older adults often need to manage multiple medications to treat different conditions, but the pharmacological mix can have negative interactions that cause unintentional harm. For this reason, many clinicians who care for older patients engage in the process of deprescribing—identifying and discontinuing medications that cause more harm than benefit.

Deprescribing begins with a conversation between the clinician and patient, but this step has proven to be a daunting obstacle for both sides engaged in the dialogue. That’s because the patient doesn’t always understand the benefit of stopping certain medications, while the clinician may not fully appreciate the patient’s treatment preferences.

To develop a framework to improve the deprescribing conversation across healthcare and community organizations, 

, MD, Humana Foundation Professor of Medicine at Yale School of Medicine, led a multi-institutional, international Communications Working Group composed of 14 experts in geriatrics, pharmacology, and communication, along with community outreach stakeholders who conducted a literature search of deprescribing articles published over the past two decades. The results, which included recommendations for improvements, were recently published in the 

“More is not always better,” said Fried. “We have to recognize that when we add on medications to treat multiple chronic conditions, inevitably there is a tipping point where having more is associated with greater risks.”

Prescribing guidelines may not benefit older adults

Currently, clinicians follow clinical practice guidelines, typically written by professional medical organizations, when providing care, but this approach may be counterproductive for older adults. Fried points to high blood pressure medications as an example. The medication can lower a patient’s blood pressure to a target range, but it could also make the individual vulnerable to dizzy spells and falls.

“In many ways, deprescribing is going against years and years of effort to promote appropriate prescribing,” said Fried. “Physicians can follow clinical practice guidelines that make it easy to prescribe the correct medications for, say, diabetes or high blood pressure, but following these guidelines can sometimes cause more harm than good. When older persons with multiple conditions are prescribed all of the individual medications included in the different guidelines, these medications can interact with one another, side effects can begin to accumulate, and a medication prescribed to help one condition may worsen another. Medications need to be prioritized depending upon the outcomes that matter most to the patient.”

A new communication framework for prescribing practices takes form

The working group conducted a review of articles, published over the past two decades, that explored different approaches to deprescribing—a term that was introduced in an article published in 2003 in the 

Journal of Pharmacy Practice and Research

 describing the principles and practice of removing unnecessary or inappropriate medications and avoiding polypharmacy.

From the 78 papers identified, the Communications Working Group determined that most interventions consist of a clinician being alerted to a potential problem with the patient’s medication but does not provide guidance to the clinician about how to communicate with the patient. Moreover, these interventions do not consider the larger context in which a patient’s view of medications is shaped.

To improve this effort, the team developed a framework that expands the sphere of influence for this important decision-making process. The framework consists of “nested spheres,” in which the innermost sphere is the traditional doctor–patient office visit. Each additional sphere captures opportunities to initiate and continue the deprescribing conversation across the greater healthcare system as well as at different community interactions. This framework allows for input from additional practitioners, including nurses and other specialists, and community partners, such as pharmacists, faith-based groups, and other community-focused organizations.

“Broadening the spheres in which communication about deprescribing occurs can help to normalize the process, address concerns that deprescribing is somehow related to rationing, and help to counteract the prevailing messaging around medications that ‘more is better,’” said Fried.

The literature review is limited by the content that has been published, which only addresses the patients’ priorities and views concerning the benefits and risks of their current medication regimen. While the proposed framework offers a new approach that incorporates shared decision-making, Fried acknowledges that more studies are needed to explore how the deprescribing conversation unfolds during an office visit. These studies could evaluate communication content and style to advance this conversation, especially addressing sensitivities among a more diverse patient population.

“Our community partners helped us remember the bigger world beyond the individual patient and clinician, and reminded us of the need to build trust in the patient–clinician relationship,” said Fried. “Our insights will benefit the next generation of interventions that will be designed for deprescribing.”

Fried and her team received funding from the National Health and Medical Research Council and the National Institute on Aging.

Deprescribing in older adults is crucial to mitigate negative drug interactions, yet challenging due to communication barriers between clinicians and patients. A multi-institutional team led by Dr. Terri Fried developed a framework to enhance deprescribing conversations, emphasizing shared decision-making and broader community involvement. Current prescribing guidelines may not suit older adults, as they can lead to harmful polypharmacy. The new framework involves "nested spheres" to facilitate deprescribing discussions beyond traditional doctor-patient interactions, involving various healthcare and community stakeholders. Further studies are needed to refine communication strategies.

Most deprescribing interventions consist of a clinician being alerted to a potential problem with the patient’s medication but does not provide guidance to the clinician about how to communicate with the patient.

When Drugs Cause More Harm Than Good for Older Adults

Stacy Kish

2025 Revolutionizing Atopic Dermatitis (RAD) Conference

 editorial team sat down with Tejesh Patel, MD/MBBS, about his portion of the session at RAD titled ‘Dose Flexibility in Adult Atopic Dermatitis.’

Patel, a professor and department chair at the University of Tennessee Health Science Center Department of Dermatology, was asked about examples of dose flexibility in the context of 

 treatment. He spoke about the current landscape in terms of dose adjustments in various treatments for the skin condition.

Discussing Dose Flexibility in Adult Atopic Dermatitis, with Tejesh Patel, MD

“It's a really exciting time for atopic dermatitis,” Patel explained. “There are lots of different medications coming out and different ways we can deliver them. We have oral medications, we have injections, and we have new topical medications coming out also. In real clinical practice, we're seeing patients’ clinical responses to these medicines vary from the standard regimes that are out there. We're seeing that we can, in fact, actually have some flexibility in the way we manage these patients and maybe even extend times for maintenance. In that respect, [we can] decrease exposure to medicine, and therefore some of the side effects and so forth.”

Patel noted that there are biologics and Janus Kinase (JAK)-inhibitors, highlighting systemic drugs as an example of a drug that can have some flexibility in its use.

“In terms of the biologics, these are subcutaneous injections,” Patel said. “For maintenance, once we've got a clinical response, this data out there shows that you can actually increase the length of injections and maintenance of these injections. For dupilumab, you can go from around 2 weeks to maybe Q4W to, in some instances, Q8W. That's really exciting for both the patient and the clinician, because there's less frequency of administering this medicine. [This leads to] increased compliance, and they're less exposed to the medicine so some of the side effects may be decreased. Overall, there may be a decrease in cost to the healthcare system as well, because you're not administering these medicines as frequently.”

Patel highlighted that he believes it is an exciting time to talk to patients about dose flexibility in their atopic dermatitis drugs.

“I think in terms of compliance, if we're administering a medication less frequently or at a lower dose, I think that's appealing to the patients in terms of compliance,” Patel explained. “...I think one major takeaway from the talk is that you can really involve your patient with the decisions you're making. Give them the data, and see what appeals to them if they want to do an oral medicine or an injection. Involve them in every step, and also let them know that there's new data that come that's coming out that may mean that you're not needing to take the medicines as frequently, or you can lower the dose in the future.”

To find out more about dose flexibility in atopic dermatitis, as well as other related facts, view the full interview posted above. For more on these topics and others, view the 

This interview at RAD 2025 highlights a session on dose flexibility in adult patients with atopic dermatitis, presented by Tejesh Patel, MD.

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