Michelle O'Donoghue, MD, is the McGillycuddy-Logue Endowed Chair in Cardiology at Brigham and Women's Hospital and associate professor at Harvard Medical School

Olpasiran Lowers Lp(a) Irrespective of Apo(a) Isoform Size, With Michelle O’Donoghue, MD

atherosclerotic cardiovascular disease (ASCVD)

, irrespective of apolipoprotein(a) isoform size, according to results from the OCEAN(a)-DOSE trial.

Lp(a) concentration is predominantly driven by genetics, with a well-documented inverse correlation between it and the number of Kringle IV-2 (KIV-2) repeats on apolipoprotein(a) alleles. However, the relationship between the size of these apo(a) isoforms and the response to Lp(a) lowering via RNA interference via olpasiran has not been studied. To that end, this analysis of the OCEAN(a)-DOSE trial was undertaken.

 spoke with Michelle O’Donoghue, MD, the McGillycuddy-Logue Endowed Chair in Cardiology at Brigham and Women’s Hospital and associate professor at Harvard Medical School, to discuss the implications of this finding, not only for olpasiran, but for apo(a)-targeting ASCVD care at large.

“This is relevant because a lot of studies are looking at participants and individuals who have the highest levels of Lp(a),” O’Donoghue told 

. “We really need to better understand whether all people will have a similar type of response to these therapies, even if we end up pushing down to lower baseline Lp(a) concentrations.”

OCEAN(a)-DOSE was a phase 2, dose-finding randomized clinical trial evaluating 4 active doses of olpasiran – 10 mg every 12 weeks (Q12W), 75 mg Q12W, 225 mg Q12W, and 225 mg Q24W. For inclusion, patients were required to have ASCVD and Lp(a) levels >150 nmol/L. Investigators also measured the number of Kringle IV-2 (KIV-2) repeats, which are inversely correlated to the concentration of Lp(a), in each patient via a gel electrophoresis and immunoblotting system.

A total of 277 patients were enrolled in the trial, with a mean age of 62 years (interquartile range [IQR], 56-69). At baseline, the median Lp(a) concentration was 260.2 (IQR, 197.9-358.5) nmol/L. Lp(a) concentration was generally higher among patients with a lower number of KIV-2 repeats (

 = 0.02). Patients were then randomly assigned to 1 of 4 of the active subcutaneous doses of olpasiran or placebo; the final dose was administered at week 36 for the Q12W arms and at week 24 for the Q24W arm.

By week 36, the placebo-adjusted LSM percent change from baseline in Lp(a) with olpasiran was consistent irrespective of baseline KIV-2 repeat number (

 = .66). Additionally, no significant change was observed over time in the percent expression of the dominant apo(a) isoform with olpasiran versus placebo (mean change from baseline [+/- standard deviation] +1.1 [+/-9.8] % with olpasiran and + 2.1 [+/- 12.8] % with placebo; 

“Most people carry 2 different copies of an apo(a) allele, so they have a variable number of KIV-2 repeats in their blood, reflecting each of those 2 alleles – the dominant isoform is really just determined by what percent expression you have of one or the other,” O’Donoghue said. “We found that olpasiran really seems to target both isoforms equally; it doesn’t seem to matter how many KIV-2 repeats you have. It’s being taken out.”

Editor's Note: O'Donoghue reports disclosures with Amgen, Novartis, AstraZeneca, Janssen, Novo Nordisk, Verve, and others.

Monguillon V, Lopez A, Rosenson R, et al. Efficacy of Olpasiran by Apolipoprotein(a) Isoform Size: Insights from the OCEAN(a)-DOSE Trial. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

Rosenson RS, López JAG, Gaudet D, et al. Olpasiran, Oxidized Phospholipids, and Systemic Inflammatory Biomarkers: Results From the OCEAN(a)-DOSE Trial. JAMA Cardiol. 2025;10(5):482-486. 

Videos

O’Donoghue discusses the results of the recent OCEAN(a)-DOSE trial and addresses the implications for Lp(a)-lowering therapies moving forward.

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Cardiology condition center page is a comprehensive resource for clinical news and insights on cardiovascular and cardiometabolic diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for heart disease and cardiovascular events, as well as associated diabetes, renal failure, and more...

Atherosclerotic Cardiovascular Disease

Dyslipidemia

Yasmine Kirkorian, MD, is a dermatologist and chief of Dermatology at Children's National Hospital.

Guidelines on Genetic Disorders of the Skin and Pediatric Patients, With Yasmine Kirkorian, MD

2025 Society of Dermatology Physician Associates (SDPA) Fall Conference

 by Yasmine Kirkorian, MD, dermatologist and chief of Dermatology at Children's National Hospital.

In a new interview at this dermatology meeting, Kirkorian highlighted several key takeaways for clinicians on the topics covered in her sessions. First, she was asked about her session ‘The ABC's of Genetic Disorders of the Skin: Guidelines for Recognition and When to Refer.’

“My session focused on genetic skin disorders, and the first section was really thinking through who would even be screened for genetic skin disorders,” Kirkorian explained. “We talked a lot about putting the skin in the context of the child since child development is so critical, and we were looking at their physical growth. [These were] things like head circumference, but also looking at their development.”

Kirkorian also discussed developmental milestones, which can be noted on the Centers for Disease Control and Prevention (CDC) website. She noted a developmental delay, and skin findings can lead to an increase in the likelihood of referring such a child to genetics for evaluation.

“The rest of the lecture focused on more specific genetic syndromes, and we kind of broke it down into those with hyperpigmented birthmarks, those with hypopigmented lesions, those with keratinocytic lesions, and those that are at risk for internal malignancies,” Kirkorian said. “Because you want to catch people early that might have a cancer risk and get them into surveillance.”

Later, Kirkorian was asked about several highlights from her second talk, ‘It's Just a Little Different in Peds: Demystifying Complex Pediatric Dermatology Cases.’

“This session focused on complex medical dermatology in children, and so we looked at a number of conditions, including infections such as herpes simplex virus infections and other cutaneous infections,” Kirkorian said. “I also had a large chunk on reactive infectious mucocutaneous eruptions. That's a mouthful, which we call ‘RIME.’ RIME is a condition that occurs primarily in children, but can occur in adults, where people develop a reactive mucositis of multiple sites, the eyes, the mouth, or the genitals, in the setting of a recent infection. It's quite morbid and people can be hospitalized.”

This condition, Kirkorian noted, can lead to hospitalization among children for several weeks at a time. Early recognition and understanding is necessary, she added.

The quotes used in Kirkorian’s interview summary were edited for clarity.

Kirkorian had no relevant financial disclosures of note.

Kirkorian Y. The ABC's of Genetic Disorders of the Skin: Guidelines for Recognition and When to Refer. Presented at the Society of Dermatology Physician Associates (SDPA) Fall Conference, November 5-9, San Antonio, TX.

Kirkorian Y. It's Just a Little Different in Peds: Demystifying Complex Pediatric Dermatology Cases. Presented at the Society of Dermatology Physician Associates (SDPA) Fall Conference, November 5-9, San Antonio, TX.

Kirkorian speaks in this interview about her sessions at SDPA Fall on genetic disorders in pediatric dermatology patients.

Dermatology

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Halpin reviews the state of triple therapy inhaler prescribing strategies in the era of new biologic options.

COPD Inhaler Use in the Biologic Era, with David Halpin, MBBS, DPhil

Single inhaler triple therapy options reached the US market in the last decade, providing clinicians a number of options to effectively treat the common symptoms of 

 without tasking a patient to adhere to multiple devices; options like fluticasone furoate / umeclidinium / vilanterol (Trelegy Ellipta)

 and budesonide / glycopyrrolate / formoterol (Breztrai Aerosphere)

 have simplified a patient’s means to receive a regular dose of inhaled corticosteroid (ICS), long-acting beta agonist (LABA) and long-acting muscarinic antagonist (LAMA).

But this drug class hasn’t come without its own practical hang-ups.

Chronic Obstructive Lung Disease (GOLD) International COPD Conference

 in Philadelphia, PA, this month, David Halpin, MBBS, DPhil, Clinical Lead of Respiratory Medicine at the University of Exeter, discussed the advantages and challenges alike that have emerged in the era of multiple-therapy inhaler devices to treat COPD.

While there are more opportunities to now fit a suitable device to a patient with COPD, the amplification of choices warrants an adequate understanding of each option.

“It's confusing for clinicians about how you should use them optimally,” Halpin said. “And so even though many devices are available, many clinicians default to a limited number that they're familiar with.”

There’s even differing methodology between single inhaler multiple therapy options — some warrant a twice-daily administration, others only one. Some do require an add-on treatment, others do not.

“Patients get very confused, and as a result, don't take it as well as they should and are more likely to have exacerbations and not get as good symptom control as they could achieve,” Halpin said. “There’s still a lot of work to do to educate the prescribers and to train the patients that having a single inhaler is much more convenient — patients are going to be more adherent and more likely to get the benefits from that treatment.”

Halpin also discussed general prescribing strategy trends in COPD. He noted that some of his colleagues may initiate a long-acting bronchodilator, wait to assess its benefit, then add a second bronchodilator, wait again, and finally add an ICS to a patient’s regimen. He stressed that this strategy is only delaying the time to optimal care — and time is everything in COPD treatment.

“The evidence suggests that if a patient needs the treatment, the sooner you start all of the components together, the better the outcomes will be,” he said.

The advent of biologic therapies to treat COPD further evidences the need to start timely, robust maintenance treatment as soon as the patient needs it; an add-on biologic is now available for most patients with severe cases.

“Biologics offer an opportunity to add on to the triple therapy, to further reduce those exacerbation rates,” Halpin said. “And they have to be tailored to the individual patient. But if you've got the right patients with the right biomarkers to indicate the need for a biologic, the biologics really offer something new.”

Walter K. FDA Approves COPD Triple Therapy. 

. Published July 24, 2020. https://www.hcplive.com/view/fda-approves-copd-triple-therapy

Hoffman M. FDA Grants New Indication to Trelegy Ellipta for COPD. 

. Published online April 24, 2018. https://www.hcplive.com/view/fda-grants-new-indication-to-trelegy-ellipta-for-copd

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COPD condition center page, resources on the topics of medical news and expert insight into chronic obstructive pulmonary disease can be found. Content includes articles, interviews, videos, podcasts, and breaking news on COPD research, treatment, and drug development.

Associate Professor, University of Alabama and Chief Medical Officer for AllerVie Clinical Research

Shared Decisions, Better Outcomes in Atopic Dermatitis, With Weily Soong, MD

Atopic dermatitis management has evolved rapidly in recent years, and allergists are playing a central role in that transformation. What was once a treatment landscape dominated by topical and systemic steroids has transformed into one defined by precision-targeted options, including biologics, JAK inhibitors, and next-generation non-steroidal topicals. Several recent FDA approvals have accelerated this shift. Nemolizumab (Nemluvio), an IL-31 receptor–blocking biologic, received approval in December 2024 for patients aged 12 and older.

 That same month, tapinarof cream 1% (VTAMA), a once-daily, non-steroidal aryl hydrocarbon receptor agonist, was approved for children as young as 2 years old.

 Most recently, in October 2025, the FDA expanded the indication for roflumilast cream 0.05% (Zoryve) to include children ages 2 to 5, introducing another long-acting, steroid-free option for young patients.

 in Orlangdo, Florida, dermatologists and allergists led by Weily Soong, MD, Associate Professor, University of Alabama at Birmingham and Chief Medical Officer for AllerVie Clinical Research, gathered to explore how these developments are transforming real-world care for children with atopic dermatitis and the evolving collaborations of allergists and dermatologists.

 caught up with Soong to learn more about some of the hot topics discussed during the forum. He noted that allergists routinely care for people with atopic dermatitis because it is the starting point of the atopic march and one of the strongest risk factors for asthma, allergic rhinitis, and food allergies. As a result, allergists regularly evaluate AD within the broader context of multisystem allergic disease, often seeing children and adults whose conditions require a long-term chronic disease framework.

Shared decision-making plays a central role in Soong’s practice, whether selecting between faster-acting agents like ruxolitinib or longer-term disease controllers such as tapinarof. He emphasized that itch, sleep disruption, and caregiver burden carry significant weight in treatment planning—reflecting atopic dermatitis's profound psychological and emotional toll.

Despite advances, access remains a critical barrier. Insurance payers continue to default to low-cost topical steroids, leaving many families struggling to obtain safer, more effective non-steroidal therapies. Soong advocated for improved coverage policies and hopes growing clinical evidence will help shift first-line standards toward modern, steroid-free treatments that meaningfully reduce the burden of atopic dermatitis for patients and families.

"Newer creams have much better efficacy, [a] much better safety profile than than  topical steroids. Hopefully one day, they will become the first line treatment instead of topical steroids... [I hope] one day we can improve access, because we really could relieve the burden of atopic dermatitis on patients, if all these newer creams [were] better covered," Soong said.

Galderma Receives U.S. FDA Approval for Nemluvio® (Nemolizumab) for Patients with Moderate-to-Severe Atopic Dermatitis. News release. Galderma. December 13, 2024. https://investors.galderma.com/news-releases/news-release-details/galderma-receives-us-fda-approval-nemluvior-nemolizumab-patients

FDA Approves VTAMA® (tapinarof) cream, 1% for the Treatment of Atopic Dermatitis in Adults and Children 2 Years of Age and Older. News release. Organon. January 3, 2025. https://nationaleczema.org/blog/press-release-vtama-tapinarof-cream-atopic-dermatitis/?utm_source=chatgpt.com

FDA Approves Arcutis’ ZORYVE® (roflumilast) Cream 0.05% for the Treatment of Atopic Dermatitis in Children Ages 2 to 5. News release. Arcutus. October 6, 2025. https://investors.arcutis.com/news-releases/news-release-details/fda-approves-arcutis-zoryver-roflumilast-cream-005-treatment?utm_source=chatgpt.com

Soong discussed the role of allergist's in atopic dermatitis care at a recent HCPLive clinical forum.

Atopic Dermatitis

Atopic Dermatitis condition center page, audiences can find a variety of coverage mediums for medical news and updates, including articles, video interviews, podcasts, and breaking news on dermatitis research, treatment, and drug development.

This video segment synthesizes long-term safety data for JAK inhibitors and biologics, highlights the risks of undertreated inflammation, and closes with practical “art of medicine” pearls for selecting and tracking therapy in atopic dermatitis.

Special Report: Safety, Future Directions, & the Art of Therapy Selection in Atopic Dermatitis

Long-term safety considerations are central to decisions about initiating and continuing advanced systemic therapies in 

In this video, host Mona Shahriari, MD, notes that several years of clinical trial and real-world data with upadacitinib now support its use in diverse patient subgroups, including individuals who smoke, use hormonal contraception or hormone replacement therapy, or have cardiovascular risk factors. She stresses that adverse events of special interest—such as malignancy, major adverse cardiovascular events, and venous thromboembolism—must be interpreted in the context of baseline risk inherent to the general and atopic dermatitis populations. Current data suggest that rates of such events with JAK inhibitors in atopic dermatitis appear broadly consistent with background rates, which helps her counsel patients and colleagues with greater confidence.

 on switching therapeutic classes in atopic dermatitis, expert guest Andrew Mastro, MS, PA-C, underscores the importance of correlating real-world evidence, such as the CorEvitas-type data sets, with clinical trial outcomes to validate both efficacy and safety expectations during therapy switches. The discussion then turns to recent long-term safety data for tralokinumab, which report rates of major cardiovascular events, thromboembolism, and malignancy that are comparable to those observed with upadacitinib. Mastro explains that while these findings did not change his personal practice—because he already viewed these agents as viable long-term options—they provide valuable reassurance for clinicians and patients who may have been hesitant about JAK inhibitors. Shahriari distills this into a practical message: if a clinician is comfortable with the long-term safety of tralokinumab, they should feel similarly comfortable with upadacitinib when used in appropriately selected patients.

The segment broadens to address the risk of not treating atopic dermatitis aggressively enough. Shahriari emphasizes that uncontrolled inflammation is not benign and that atopic dermatitis is associated with systemic comorbidities, including cardiovascular disease and other inflammatory conditions. She frequently discusses this with parents of pediatric and adolescent patients who may be reluctant to start systemic therapy, explaining that persistent, moderate to severe disease is unlikely to “just go away” and that appropriately selected systemic treatment may mitigate long-term consequences. Mastro describes the “light bulb” moment when patients realize their disease is more than “just an itchy patch,” and how connecting internal inflammation to external manifestations facilitates acceptance of injectable or oral therapy. The discussion concludes with practical pearls: Mastro reminds clinicians to see “a person in the room with a problem,” not just a diagnosis, and Shahriari offers a simple “ART of medicine” framework—assess burden beyond BSA, pick the right mechanism of action, and track response using AHEAD recommendations. 

Relevant disclosures for Shahriari include AbbVie, Apogee, Arcutis, Bristol Myers Squibb, Dermavant, Galderma, Incyte, Johnson & Johnson, LEO, Lilly USA, Novartis, Regeneron, Sanofi-Genzyme, Takeda, UCB, Pfizer, and others. Mastro has no relevant disclosures to report.

Silverberg JI, Gooderham M, Katoh N, et al. Combining treat-to-target principles and shared decision-making: International expert consensus-based recommendations with a novel concept for minimal disease activity criteria in atopic dermatitis. 

Silverberg JI, Bunick CG, Hong HC, et al. Efficacy and safety of upadacitinib versus dupilumab in adults and adolescents with moderate-to-severe atopic dermatitis: week 16 results of an open-label randomized efficacy assessor-blinded head-to-head phase IIIb/IV study (Level Up). 

Explore the long-term safety and efficacy of JAK inhibitors in atopic dermatitis, enhancing patient care and clinician confidence.

Healthcare providers discuss the importance of effective communication when switching patients from biologics to JAK inhibitors.

Special Report: Overcoming Therapeutic Inertia and Communicating Safety of  JAK Inhibitors

Special Report: Inadequate Response and When to Switch Systemic Therapy in Atopic Dermatitis

Explore the evolving landscape of atopic dermatitis treatment, focusing on advanced therapies and long-term patient management strategies.

Special Report: Treat-to-Target in Atopic Dermatitis—Applying the AHEAD Recommendations

Healthcare professionals explore effective questioning techniques to uncover deeper emotional and physical impacts of skin pain in patients.

Special Report: Practical Communication Strategies for Skin Pain in Atopic Dermatitis 

This video explores skin pain as a key symptom of atopic dermatitis and reviews clinical trial data with JAK inhibitors.

Special Report: Reframing Skin Pain in Atopic Dermatitis

Viet Le, DMSc, PA-C, is a preventive cardiology PA at Intermountain Health and the former president of the Academy of Physician Associates in Cardiology.

Special Reports

RX Review: Barriers, Real-World Implementation, and Future Directions in FCS

Explore the critical role of nutrition and pharmacologic therapies in managing hypertriglyceridemia and preventing pancreatitis effectively.

RX Review: Monitoring and Safety Considerations in FCS

Experts discuss the future of psoriasis treatment, highlighting the potential of oral therapies to enhance patient adherence and quality of life.

Challenges with Current Psoriasis Therapies

In this episode, the panelists explore the concept of disease interception and how early intervention may address unmet needs in psoriatic arthritis (PsA). The experts discuss emerging evidence suggesting that PsA can be reframed as a preventable disease when treated before clinical joint symptoms appear. They note that subclinical inflammation, detectable through imaging such as Doppler ultrasound or MRI, often exists in patients with psoriasis, particularly at the entheses. This early immune activation highlights the potential to intervene upstream by targeting shared cytokine pathways, such as IL-23 and IL-17. The panel emphasizes that dermatologists, often the first point of contact, play a pivotal role in identifying high-risk patients—those with scalp or nail involvement—and considering systemic therapy even in the absence of joint symptoms. Current biologic treatments that address both skin and joint inflammation may help modify disease progression and prevent irreversible PsA-related damage.

Video Series

Disease Interception and Addressing Unmet Needs in PsA

Jason Hawkes, MD, MS discusses strategies for addressing patient hesitancy regarding oral versus injectable therapies in the treatment of CSU.


Latest News

Olpasiran Lowers Lp(a) Irrespective of Apo(a) Isoform Size, With Michelle O’Donoghue, MD

Guidelines on Genetic Disorders of the Skin and Pediatric Patients, With Yasmine Kirkorian, MD

COPD Inhaler Use in the Biologic Era, with David Halpin, MBBS, DPhil

Shared Decisions, Better Outcomes in Atopic Dermatitis, With Weily Soong, MD

Special Report: Safety, Future Directions, & the Art of Therapy Selection in Atopic Dermatitis