Future Directions for Psoriasis Treatment

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Panelists discuss how the future of psoriasis treatment is evolving toward more personalized approaches with earlier biologic intervention for patients with high-impact disease regardless of body surface area, improved assessment tools that better capture disease burden, greater consideration of comorbidities and quality-of-life impacts, increased diversity in clinical trials, expanded patient education, innovative delivery systems, combination therapies, and targeted treatments for specific psoriasis phenotypes—all aimed at addressing current treatment gaps and moving closer to disease modification rather than merely symptom management.

James Song, MD

Jennifer Flemming, MD, is an associate professor of medicine and public health sciences at Queen's University.

Flemming describes increasing rates of AH among adolescents and young adults, with females facing the greatest increases and worse outcomes than males.

Understanding the Shifting Burden of Alcohol-Associated Hepatitis

 (AH) is on the rise among adolescents and young adults, but long-term liver-related outcomes for affected individuals vary by sex, according to findings from a recent study.

The population-based study of more than 3000 patients 13-39 years of age in Canada highlights rapid increases in the rates of AH in this patient population over the past 2 decades, especially among women. Additional analyses reveal female sex is independently associated with a 47% greater risk of cirrhosis and/or decompensation, and the cumulative incidence of liver-related mortality at 10 years is higher among women than men.

According to alcohol-associated liver disease practice guidance from the American Association for the Study of Liver Diseases, women have a greater risk of liver injury compared with men for any level of drinking. Additionally, while rates of alcohol use disorder and high-risk drinking have grown in recent years, some of the greatest increases have been observed among women.

“Myself, in addition to many others, noticed this switch in the demographic of individuals who were coming in with acute alcohol-associated hepatitis,” Jennifer Flemming, MD, an associate professor of medicine and public health sciences at Queen's University, told 

, explaining how AH has historically been known to affect middle-aged men but has recently been observed more frequently in younger individuals, especially females.

To determine the extent of this phenomenon, she and a group of colleagues conducted a population-based retrospective cohort study of 3340 adolescents and young adults 13-39 years of age with an incident diagnosis of alcohol-associated hepatitis without a history of cirrhosis and/or decompensation in Ontario, Canada.

“What we found, concerningly, is that rates of [AH] were going up in all ages in this young group,” Flemming said. “When we stratified it based on sex, kind of similar to what we were seeing clinically, we saw that the rates were going up much higher among females.”

Flemming went on to emphasize the importance of multidisciplinary management of alcohol-associated liver disease and underlying alcohol use disorder, citing the importance of addressing both the liver-related and 

 aspects of these conditions. Additionally, she called attention to the need to develop sex-based interventions addressing the heightened risk of alcohol-associated liver disease observed in female patients.

Editors’ note: Flemming has no relevant disclosures.

Brooks A. Young Women Face Worse Long-Term Alcohol-Associated Hepatitis Outcomes Than Men. 

. January 8, 2025. Accessed January 13, 2025. 

https://www.hcplive.com/view/young-women-face-worse-long-term-alcohol-associated-hepatitis-outcomes-than-men

Crabb DW, Im GY, Szabo G, et al. Diagnosis and Treatment of Alcohol‐Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology. doi:10.1002/hep.30866

Jennifer Flemming, MD: Understanding the Shifting Burden of Alcohol-Associated Hepatitis

Jennifer Flemming, MD

Experts discuss emerging gene therapies for age-related macular degeneration (AMD) or diabetic macular edema (DME) and key end points considerations. 

Emerging Gene Therapies for Retinal Diseases

Jonathan Jonisch, MD

 What can we do with our patients to bridge the gap until we have a more solid cure? I think I can start off, and then Linda can jump in, or anybody. Are these hybrid closed-loop systems? We have 4 different ones on the market. I think you all would agree with automatic insulin delivery, modulating basal rate, alerts, and alarms that you could set individually that, for adults with type 1, my clinic has gotten so boring. Patients come in, their [hemoglobin A1C (HbA1C)] is good, time below range is really low, glycemic variability—and it’s not like you slapped [it] on, they have perfect control. You do some adjustments, a patient gets engaged in their care.

 We are still struggling on the pediatric side with some of the closed-loop technologies. We have some families that plug it in, go chug, and then we’re just tweaking little things, but kids’ insulin continues to change throughout childhood because of adolescent behaviors that lead to that. We had that nice type 1 diabetes exchange graph with peak [HbA1C] in there with 9.2%, same as before [the] DCCT [trial] across the population. So at least in our clinics, I’m still having kids [on Control-IQs walk in with HbA1Cs] of 10. And then, I got to go back, and it’s usually bolus, bolus, bolus, but don’t bolus after you’ve eaten because the system has already given you insulin; that’s why you’re going low. Avoiding the next bolus is not going to help you here. On the flip side, when we can manage them or when they manage well themselves—having just come off diabetes camp earlier this month, I have never seen so many blood sugars of 120, 130 in the morning. Still, the days are a little bit unpredictable. I don’t think we did much ketone testing at all in the morning. I’ve been doing camp for 25 years. It never looked that way before.

 I was up more of the night with the alerts and alarms from the CGMs [continuous glucose monitors] with the staff trying to figure out what to do with them. I think it’s [promising], and access is important. We know that underrepresented populations are still much less likely to be using those devices. We’re doing well in kids right now with CGM incorporation across our clinics, but we need people to be insured, [and for] the underinsured to get them and to have access. As pediatric endocrinologists, getting that stuff down to the little kids is also going to be important, and there have been huge advances there.

 I’m going to take that as your final point. Egils, do you want to end our program with some final thoughts?

 Well, we just celebrated the centenary of the discovery of insulin. I have a [Toronto, Ontario, Canada] newspaper that says, “Diabetes cured” that I show my patients; so, 101 years later and even though overnights are great with AID [automatic insulin delivery], insulin is still a pretty poor hormone replacement. I look forward to the day that we’re using teplizumab to prevent progression of diabetes.

 Well said. I think you emphasized, Linda, that although we do have these hybrid closed-loop, automatic insulin delivery systems, we have a long way to go, even for people who have access to them. Justin, my good friend, any final thoughts before we end the program officially?

 I just feel so fortunate to get to work in a field where we can have these discussions. About just a few years ago, we [had] been trying immunotherapy right and left. We’ve been doing antigen therapy right and left and disappointment after disappointment. Now we’re talking about how to implement immunotherapy in the way that we treat type 1 diabetes. I think of it as we’re at the dawn of the immunotherapy era. As endocrinologists, we don’t usually use immunotherapy drugs, unlike some of our other subspecialist colleagues. It’s an exciting era, but we’ve talked a lot about some of the challenges that we’re just starting to get our arms around as we enter that era. I look forward to getting to do it with people like you.

 Well, thank you for that. Very exciting time as well. Schafer, you get the final word on that.

 Well, I would just say I learned a lot today. Thank you for all that expert knowledge, that was fantastic. I’m going to echo a little bit what was just said to some degree that it does feel sort of a dawn of a new era. Thank God for insulin, but it has been limited, and despite all these great technologies and CGM and closed-loop, the picture is not quite as rosy as Steve painted it in his clinic, where everything’s great. We see people come into the hospital, wearing their pump, but they’re in full-blown DKA [diabetic ketoacidosis]. There are a lot of problems still that we haven’t been able to solve even with great insulin therapies, new and faster insulins, and longer-acting insulins. There are still issues with increased cardiovascular disease, with the majority of patients not meeting glycemic goals, and issues with DKA. There’s a lot of work to do, but it’s such an exciting time to have some therapies, that we’re not just trying to play catch-up and treat by giving more insulin and figuring out different ways to use insulin, but to actually be able to get ahead of the curve a little bit is just very exciting and optimistic.

 Well, thank you, Schafer, Linda, Justin, and Egils, I learned a lot myself. It’s been a pleasure working with all of you, and I wanted to thank everyone for viewing and watching this 

program. Don’t forget, they have an e-newsletter, where you can look at prior programs and future programs on different topics. Thank you very much for watching.

Expert endocrinologists provide final thoughts on addressing unmet needs and improving the management of T1D.

Bridging the Gap for T1D Management

Justin M. Gregory, MD, MSC

As one of the most common diseases in the United States, diabetes impacts more than 37 million Americans with 90-95% having type 2 diabetes.

 Type 2 diabetes symptoms can develop slowly over time, and may lead to serious complications including cardiovascular disease, retinopathy, nephropathy, and neuropathy.

 However, it is possible to manage the disease, and clinicians like yourself can play an important role in helping people living with type 2 diabetes achieve their health goals.

We know it is challenging for many people living with type 2 diabetes to manage the disease. In fact, a recent cross-sectional analysis of the U.S.-based National Health and Nutrition Examination Survey (NHANES) data found that the U.S. is trending in the wrong direction. After more than a decade of progress in the early 2000s, glycemic and blood-pressure control have declined in the adult population.

 This is particularly concerning given, today, more than ever before, the efficacy of new therapies, evidence-based treatment guidance for earlier and tighter management of both blood glucose and excess weight, and what patients are looking for in terms of their disease management line up well.

We are in a new era of care – or at least we 

Consistency Across Medical Capability, Guidelines and Patient Aspirations

After decades of science, research, and advancement, we have reached a time in type 2 diabetes care where medical capabilities align with what professional organizations and patients have been demanding — treatments that help control their A1C and reduce excess weight.

On the medical capability front, we have seen new, more innovative treatment options become available for patients over the last few years. These new treatments, including incretin-based therapies, are demonstrating efficacy in improving both A1C and body weight to greater extents than previously seen, while also potentially addressing other underlying issues patients may have. And many companies have even more treatments in the pipeline that offer various mechanisms of action and modes of administration, catering to an array of patient preferences.

From a science and guidelines perspective, there is also alignment. The science around type 2 diabetes care has demonstrated promise around early glucose control and weight management for the long-term health of patients.

 About 90% of people with type 2 diabetes also have obesity or overweight, demonstrating the importance of addressing excessive weight when treating these patients.

 And the American Diabetes Association (ADA) agrees. In its 2023 Standards of Care in Diabetes, ADA recommends early and consistent glucose and weight management since effective management of both can help reduce the risk of diabetes-related complications.

And importantly, the innovation in treatment and care guidelines reflect what patients are looking for when it comes to managing their type 2 diabetes.

 When looking at treatment-related attributes that encouraged patients with type 2 diabetes to initiate and stay on their medications, treatment efficacy in managing A1C and losing weight, or at least not gaining weight, were the two most important factors.

 For likely the first time in type 2 diabetes care, patients can access treatments that match their wishes after decades of insulin and other treatments that resulted in weight gain instead of weight loss.

More Needs To be Done to Improve Type 2 Diabetes Care and Clinicians Play an Important Role

Unfortunately, despite the new era of care we are in, many people living with type 2 diabetes are not reaching care goals. In fact, it is estimated that only 45-60% of adults with type 2 diabetes have achieved the ADA-recommended A1C target of <7%.

Clinicians may hesitate to incorporate new treatments into their practice for several reasons, including patient-related factors (education, engagement with treatment and therapy preferences), costs of the new medicine and reimbursement, among others.

However, this new era of type 2 diabetes care only benefits patients if health systems and clinicians incorporate the latest research, care guidelines and medications where appropriate to help patients manage their type 2 diabetes. To start, clinicians can refer to the evidence-based treatment guidelines, tackle the issue of therapeutic inertia, and leverage patient desire for better glucose control and weight reduction through patient-centric care.

The ADA recommends that a person-centered approach be taken when choosing a treatment for people with diabetes, which may include the treatment of other risk factors to help improve patient outcomes across the board.

 Once those risk factors have been identified, clinicians and their patients can determine together which treatment options work best for them, while considering individual preferences.

Even though type 2 diabetes care has changed immensely over the years, and we’ve discovered new treatments that meet patient expectations, it will continue to evolve. Embracing this constant change and innovation will benefit patients and help them get back to the life they want to live with their disease more effectively managed.

Type 2 diabetes. Centers for Disease Control and Prevention. April 18, 2023. Accessed August 2023. https://www.cdc.gov/diabetes/basics/type2.html#:~:text=More%20than%2037%20million%20Americans,adults%20are%20also%20developing%20it.

Type 2 diabetes. Mayo Clinic. March 14, 2023. Accessed August 2023. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193.

Fang M, Wang D, Coresh J, Selvin E. Trends in diabetes treatment and control in U.S. adults, 1999–2018. June 10, 2021. Accessed August 2023. https://www.nejm.org/doi/full/10.1056/NEJMsa2032271.

 Ko JH, Kim TN. Type 2 Diabetes Remission with Significant Weight Loss: Definition and Evidence-Based Interventions. J Obes Metab Syndr. 2022;31(2):123-133. doi:10.7570/jomes22001.

Laiteerapong N, Ham SA, Gao Y, et al. The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study). Diabetes Care. 2019;42(3):416-426. doi:10.2337/dc17-1144.

Type 2 diabetes and metabolic surgery: ASMBS. American Society for Metabolic and Bariatric Surgery. September 24, 2020. Accessed August 2023. https://asmbs.org/resources/type-2-diabetes-and-metabolic-surgery-fact-sheet.

ElSayed NA, Aleppo G, Aroda VR, et al. Glycemic Targets: Standards of Care in Diabetes—2023. American Diabetes Association. December 12, 2022. Accessed August 2023. https://diabetesjournals.org/care/article/46/Supplement_1/S97/148053/6-Glycemic-Targets-Standards-of-Care-in-Diabetes.

ElSayed NA, Aleppo G, Aroda VR, et al. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes—2023. American Diabetes Association. December 12, 2022. Accessed September 8, 2023. https://diabetesjournals.org/care/article/46/Supplement_1/S128/148043/8-Obesity-and-Weight-Management-for-the-Prevention.

Sims TJ, Boye KS, Robinson S, Kennedy-Martin T. Treatment-Related Attributes of Diabetes Therapies and How People with Type 2 Diabetes Report Their Impact on Indicators of Medication-Taking Behaviors. Patient Preference and Adherence. August 4, 2022. Accessed August 2023. https://www.dovepress.com/treatment-related-attributes-of-diabetes-therapies-and-how-people-with-peer-reviewed-fulltext-article-PPA.

Avramidis I, Apsemidou A, Lalia AZ, et al. Lessons From a Diabetes Clinic: Achieving Glycemic Goals and Clinical Use of Antidiabetic Agents in Patients With Type 2 Diabetes. Clin Diabetes. 2020;38(3):248-255. doi:10.2337/cd19-0090.

Avramidis I, Apsemidou A, Lalia AZ, et al. Lessons From a Diabetes Clinic: Achieving Glycemic Goals and Clinical Use of Antidiabetic Agents in Patients With Type 2 Diabetes . American Diabetes Association. July 1, 2020. Accessed August 2023. https://diabetesjournals.org/clinical/article/38/3/248/32205/Lessons-From-a-Diabetes-Clinic-Achieving-Glycemic.

Medlinskiene K, Tomlinson J, Marques I, Richardson S, Stirling K, Petty D. Barriers and facilitators to the uptake of new medicines into clinical practice: A systematic review - BMC health services research. BioMed Central. November 5, 2021. Accessed August 2023. https://doi.org/10.1186/s12913-021-07196-4.

ElSayed NA, Aleppo G, Aroda VR, et al. 4. Comprehensive Medical Evaluation and assessment of comorbidities: Standards of care in Diabetes-2023. American Diabetes Association. December 12, 2022. Accessed August 2023. https://diabetesjournals.org/care/article/46/Supplement_1/s49/148058/4-Comprehensive-Medical-Evaluation-and-Assessment.

Embracing change in the new era of type 2 diabetes care 

Kristina Boye, Associate Vice President, Value, Evidence, and Outcomes, Eli Lilly and Company

The prevalence of diagnosed disorders from recurrent use of sedative, hypnotic and antianxiety medications in adolescents and young adults has increased sharply since 2001, according to Rutgers Health researchers.

, examined diagnoses of these disorders in adolescents and young adults between 2001 to 2019.

Sedative, hypnotic and antianxiety medications are used to treat a variety of conditions, including sleep and anxiety disorders. According to Harvard Health, 

 of these drugs can lead to a higher tolerance for their effects, meaning patients require higher doses to achieve the intended effects.

For some, a problematic pattern of use of these medications can lead to significant impairment and distress. When this happens, patients may be diagnosed with sedative, hypnotic or anxiolytic use disorders, which are 

 2.2 million Americans, according to data from the National Survey on Drug Use and Health.

Using national Medicaid data from nearly 7 million adolescents and young adults in 2001 and 13 million adolescents and young adults in 2019, Rutgers Health researchers looked at trends in sedative, hypnotic or anxiolytic use disorder diagnoses. The prevalence increased threefold in adolescents and increased fivefold in young adults from 2001 to 2019.

“The increase in diagnoses of these disorders may be due to changes in the availability, use and misuse of sedatives, hypnotics and anxiolytics, as well as an increase in detection, awareness and diagnosing of these disorders,” said 

, an assistant professor at the Rutgers Center for Pharmacoepidemiology and Treatment Science (PETS) and lead author of the study.

Sedative, hypnotic and anti-anxiety medications are accessed in number of ways, including through medical prescriptions as well as through nonmedical sources such as a friend or in a medicine cabinet. Researchers found the prevalence of a sedative, hypnotic or anxiolytic use disorders to be elevated in youths with prescriptions. However, the majority of adolescents and young adults diagnosed with a sedative, hypnotic or anxiolytic use disorder didn’t have a prescription for one of those medications.

“Efforts to target nonmedical use of these drugs is important as a means to reduce this disorder,” said Bushnell, who also is an assistant professor of epidemiology at Rutgers School of Public Health, “as is cautious prescribing in this young population.”

Researchers also found that most adolescents and young adults with sedative, hypnotic or anxiolytic use disorders had another comorbid substance use disorder diagnosis; in adolescents, cannabis use disorder was the most common and opioid use disorder in young adults.

“While sedative, hypnotic and anxiolytic use disorders are less common than other substance use disorders, it warrants attention from clinicians and researchers given treatment difficulties and the association with other substance use issues,” Bushnell said.

Examining trends in youth diagnosed with this disorder can lead to a better understanding of the population and improve support through care and resources, say researchers.

Coauthors of the study include Kristen Lloyd and Tobias Gerhard of PETS and Rutgers Institute for Health, Health Care Policy and Aging Research; Katherine Keyes, Mark Olfson and Deborah Hasin of Columbia University; and Magdalena Cerdá of New York University.

The prevalence of sedative, hypnotic, and anxiolytic use disorders in adolescents and young adults has significantly increased since 2001, as per Rutgers Health research. The study highlights a threefold increase in adolescents and a fivefold increase in young adults from 2001 to 2019. Factors contributing to this rise include increased availability, misuse, and improved detection of these disorders. Most affected individuals did not have prescriptions, and many had comorbid substance use disorders. The findings underscore the need for targeted interventions and cautious prescribing practices in this demographic.

The trend warrants attention, given treatment difficulties and the association with other substance use issues, says lead author of Rutgers Health study.


Researchers Track Sharp Increase in Diagnoses for Sedative, Hypnotic and Anxiety Use Disorder in Young Adults

Nicole Swenarton

Patient Education Tips for CSU and Final Thoughts

Can you describe the importance of patient education and shared decision-making when selecting an appropriate therapy?

What are the unmet needs in CSU management? How is the field evolving?

What advice do you have for allergists for managing CSU based on your experience and the data available?

Patient education and shared decision-making are crucial in selecting appropriate therapies, as they empower patients and ensure treatment plans align with their values and preferences. In chronic spontaneous urticaria (CSU) management, unmet needs include more effective treatments and better understanding of disease mechanisms. The field is evolving with advancements in biologics and personalized medicine approaches. Allergists should stay informed about emerging therapies, engage patients in discussions about treatment options, and tailor management strategies to individual patient needs and responses, leveraging the latest data and clinical experience.

Panelists discuss the importance of patient education and shared decision-making in selecting appropriate therapies for chronic spontaneous urticaria (CSU), addressing unmet needs in CSU management and the evolving nature of the field, while also offering practical advice for allergists based on their experiences and available data.

Priya Bansal, MD 

Artificial Intelligence in Cataract Surgery and Optometry at Large with Harvey Richman, OD, and Rebecca Wartman, OD

2025 American Optometric Association Conference

 in Minneapolis, MN, Harvey Richman, OD, Shore Family Eyecare, and Rebecca Wartman, OD, optometrist chair of AOA Coding and Reimbursement Committee, presented their lecture on the implementation of artificial intelligence (AI) devices in cataract surgery and 

AI has been implemented in a variety of ophthalmology fields already, from analyzing and interpreting ocular imaging to determining the presence of diseases or disorders of the retina or macula. Recent studies have tested AI algorithms in analyzing fundus fluorescein angiography, finding the programs extremely effective at enhancing clinical efficiency.

However, there are concerns as to the efficacy and reliability of AI programs, given their propensity for hallucination and misinterpretation. To that end, Drs. Richman and Wartman presented a study highlighting the present and future possibilities of AI in cataract surgery, extrapolating its usability to optometry as a whole.

Richman spoke to the importance of research in navigating the learning curve of AI technology. With the rapid advancements and breakneck pace of implementation, Richman points out the relative ease with which an individual can fall behind on the latest developments and technologies available to them.

“The problem is that the technology is advancing much quicker than the people are able to adapt to it,” Richman told 

. “There’s been research done on AI for years and years; unfortunately, the implementation just hasn’t been as effective.”

Wartman warned against the potential for AI to take too much control in a clinical setting. She cautioned that clinicians should be wary of letting algorithms make all of the treatment decisions, as well as having a method of undoing those decisions.

“I think they need to be very well aware of what algorithms the AI is using to get to its interpretations and be a little cautious when the AI does all of the decision making,” Wartman said. “Make sure you know how to override that decision making.”

Richman went on to discuss the 3 major levels of AI: assistive technology, augmented technology, and autonomous intelligence.

“Some of those are just bringing out data, some of them bring data and make recommendations for treatment protocol, and the third one can actually make the diagnosis and treatment protocol and implement it without a physician even involved,” Richman said. “In fact, the first artificial intelligence code that was approved by CPT had to do with diabetic retina screening, and it is autonomous. There is no physician work involved in that.”

 that a significant amount of surgical technology is already using artificial intelligence, mainly in the form of pattern recognition software and predictive devices.

“A lot of our equipment is already using some form of artificial intelligence, or at least algorithms to give you patterns and tell you whether it’s inside or outside the norm,” Wartman said.

Richman H, Wartman R. A.I. in Cataract Surgery. Presented at the 2025 American Optometric Association in Minneapolis, MN, June 25-28, 2025.

Shao A, Liu X, Shen W, et al. Generative artificial intelligence for fundus fluorescein angiography interpretation and human expert evaluation. NPJ Digit Med. 2025;8(1):396. Published 2025 Jul 2. doi:10.1038/s41746-025-01759-z

Drs. Richman and Wartman discuss the benefits of using predictive and diagnostic AI, while cautioning about the implicit risks of overreliance on early, imperfect technology.

Rebecca Wartman, OD

Robert S. Rosenson, MD is a professor of cardiology at the Icahn School of Medicine at Mount Sinai.

Solbinsiran, a GalNAc-conjugated small interfering RNA targeting hepatic angiopoietin-like protein 3 (ANGPTL3), at a dose of 400 mg, achieved sustained reductions in apolipoprotein B concentration among patients with 

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

, results from the Phase 2 PROLONG-ANG3 study showed solbinsiran was well tolerated, with a low incidence of adverse events, but its impact on cardiovascular outcomes has yet to be determined.

“These data related to the efficacy and the safety of the medication set the foundation for a phase three cardiovascular outcome trial,” trial investigator Robert S. Rosenson, MD, a professor of cardiology at the Icahn School of Medicine at Mount Sinai, told 

. “I'm quite excited about ANGPTL3 inhibitors as adjunctive therapy to what we have available today

Mixed dyslipidemia is characterized by raised levels of circulating triglycerides and low-density lipoprotein cholesterol (LDL) linked to an elevated likelihood of atherosclerotic cardiovascular disease (ASCVD). Solbinsiran achieved targeted reductions in both levels of triglycerides and LDL-C in a Phase 1 trial.

Investigators sought to further evaluate the therapy, specifically its durability and efficacy, in reducing concentrations of atherogenic lipoprotein in adults with mixed dyslipidemia. A double-blind, parallel-arm, randomized, placebo-controlled trial, the team enrolled adults with mixed dyslipidemia at 41 clinical units across 7 countries.

Enrollment criteria included patients receiving moderate-intensity or high-intensity statins, with concentrations of fasting triglycerides between 1.69 mmol/L and 5.64 mmol/L, LDL-C of >1.81 mmol/L, and non-HDL-cholesterol of ≥3.36 mmol/L.

Patients were randomly assigned 1:2:2:2 to either solbinsiran 100 mg or solbinsiran 400 mg, solbinsiran 800 mg, or placebo, by subcutaneous injection on Days 0 and 90. Follow-up occurred for at least 270 days in all patients. The primary outcome was the percent change in apoB concentration from baseline to Day 180 with solbinsiran, compared with placebo, as analyzed by an efficacy estimand: patients who received ≥1 dose of solbinsiran.

Among 585 screened patients, 205 were enrolled between July 2022 and March 2024. The population was more than half (54%) female, and the median age was 57 years. Randomization assigned patients to solbinsiran 100 mg (n = 30), solbinsiran 400 mg (n = 58), solbinsiran 800 mg (n = 59), or placebo (n = 58).

Baseline mean concentrations were 111 mg/dL for apoB, 2.64 mmol/L for triglycerides, and 3.16 mmol/L for LDL-C. Upon analysis, the placebo-adjusted percent change in apoB concentration at Day 180 was –2.8% (95% CI, –15.5 to 11.9; 

 =.69) for solbinsiran 100 mg, –14.3% (95% CI, –23.6 to –3.9; 

 =.0085) for solbinsiran 400 mg, and –8.3% (95% CI, –18.3 to 2.9; 

Safety analysis revealed treatment-emergent adverse events in 18 (60%) of 30 patients in the solbinsiran 100 mg cohort, 30 (52%) of 58 patients in the solbinsiran 400 mg cohort, 26 (44%) of 59 patients in the solbinsiran 800 mg cohort, and 37 (65%) of 57 patients in the placebo cohort. Notably, the 400 mg dose was associated with reductions in hepatic fat fraction of 27.6%.

“By these therapies, often we're thinking about adverse changes in the liver with statins, fibrates, and other agents. These data contrast and actually show improvement in the hepatic fat fraction,” Rosenson told 

. “I'm quite encouraged about the opportunities for some of our very difficult to treat patients.”

Learn more about the trial in an interview with Rosenson at ACC.25.

Solbinsiran Significantly Reduces apoB in Mixed Dyslipidemia in Phase 2 Trial

Ray, Kausik K et al. Durability and efficacy of solbinsiran, a GalNAc-conjugated siRNA targeting ANGPTL3, in adults with mixed dyslipidaemia (PROLONG-ANG3): a double-blind, randomised, placebo-controlled, phase 2 trial. The Lancet, Volume 0, Issue 0. March 31, 2025. Accessed March 31, 2025.

Ray KK, Linnebjerg H, Michael LF, et al. Effect of ANGPTL3 inhibition with solbinsiran in preclinical and early human studies. JACC (in press) 10.1016/j.jacc.2025.03.005

At ACC.25, Robert S. Rosenson, MD, discusses the efficacy and safety of solbinsiran, an ANGPTL3 inhibitor, in a population with mixed dyslipidemia.

Robert S. Rosenson, MD

 You touched on the brand-new drug anifrolumab. It’s another breakthrough in lupus, developed for SLE [systemic lupus erythematosus]. In the mid-1990s, they found that interferons were highly expressed in SLE, and particularly in the pathogenesis…

 Maybe so. But the trials had showed efficacy in both high and low responders, but maybe we’ll get there later.

 Yeah, it’s interesting. But it means you need to inhibit it a little—that’s all, right? There’s only so much you can get with interferon-alpha blocker probably.

 But it’s so new, we don’t know yet, right?

 Right. But that drug was developed out of genome-wide studies and that showed multiple SNPs, or single-nucleotide polymorphisms, in genes that encoded for the expression of interferon alpha. It’s this idea of rational drug design that’s being applied to SLE, that had been applied to other rheumatic diseases. We’re finally here, where we’re going to be at the breakthrough with new therapies.

 I’m very curious because it’s been approved in the United States for a number of months. Are you now—I mean 

 in the plural, so rheumatologists practicing in the United States—gaining experience with anifrolumab? Is it available?

 We are. It’s becoming available in the community setting. Most academic centers are getting it on their formulary. I have patients on the medication, and I’m doing a clinical trial incorporating that medication with Joan Merrill. We’re starting pick up, and it’s still too early to know how important this may be in the treatment of lupus and when it should be employed in SLE. As you know, the study showed an effect that was fairly rapid, so that there was a divergence of the treatment curves at 2 or 3 months, from what I recall. There was a particular improvement in skin disease with lupus. This might be an agent that 1 may try for rapid amelioration of skin manifestation of lupus.

 Interesting. There are also data that in the skin, interferon is upregulated. If you do a molecular analysis, you can see that.

 That stands to reason. But I’m also still intrigued by how lupus may be several pathophysiologies. In some people you have the high interferon signature or the low interferon signature, going back to belimumab you have patients for whom B-cell activity is very high, and they have all these other antibodies. Other patients might have lupus, but they may have only antinuclear antibodies and not the other ones. There could be a difference also. It might be that in the future, which is what I hope, we’ll do these analyses, immunological analyses, and it will tell us this patient should be treated with anifrolumab, this patient should be treated with belimumab, this patient will do best with a conventional therapy. That’s also possible. We might be able to start doing it that way. We’re not there yet by a long shot, but I want it for the future.

 Right, and there may be cycles of therapy. They may want to treat patients with anti-interferon therapy followed by B-cell therapy or combinations, particularly if there’s severe disease, and we’ll learn how to use them in combination to get our patients better. But it’s an exciting breakthrough.

 Interesting. I was involved in a combination trial with—I don’t know if you knew about this—the combination of belimumab with rituximab. That’s quite strange because rituximab is not approved for lupus. It’s used off-label, but it’s not approved. Then there’s a trial. There were several trials where these were combined with the idea that you could get some sort of a synergy. It’s a very interesting scientific concept, and it could work. The patients in the trials did well, but it was not so clear that the combination gave an added benefit. That’s still a little unclear. Some parameters said they did, but others said that it was the same. It will be very interesting to see it.

 You showed this data in an abstract at the American College of Rheumatology, am I right?

 I was a coauthor, so there were others who showed it.

 Right. After 52 weeks, though, you had stopped therapy, so of course lupus will flare. One wondered why these were not continued.

The rationale for using a newer monoclonal antibody therapy, anifrolumab, to manage patients with systemic lupus erythematosus.

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