Professor of Rheumatology, Northwestern Feinberg School of Medicine

Proof of Concept: Targeting Mitochondrial Dysfunction in SLE With NAC, with Rosalind Ramsey-Goldman, MD

N-acetylcysteine (NAC) shows promise as a novel therapeutic strategy for systemic lupus erythematosus (SLE), although these findings remain to be confirmed by the double-blind phase of the ongoing multicenter trial.

Data from the first phase of the trial were presented by Rosalind Ramsey-Goldman, MD, Gallagher Research Professor of Rheumatology, Feinberg School of Medicine, Northwestern University, at the 

American College of Rheumatology (ACR) Convergence 2025

, held October 24–29 in Chicago, Illinois.

Unlike immunosuppressants, NAC aims to correct core metabolic defects driving lupus pathogenesis rather than broadly suppressing the immune system. The therapy is designed to restore intracellular cysteine and glutathione (GSH) levels, thereby reducing mitochondrial oxidative stress, mTOR activation, inflammatory lineage skewing, and antinuclear autoantibody production. The trial uses an enriched-enrollment randomized-withdrawal design, with all eligible patients completing a 3-month open-label titration phase of NAC (2.4–4.8 g/day) prior to randomization into the blinded phase.

In the first 3 months of the study, NAC produced statistically significant reductions in global SLE disease activity among 68 patients. Mean SLEDAI scores decreased from 8.73 (SD, 3.093) at baseline to 4.91 (SD, 2.92) at month 3 (

 = 1.1×10⁻¹²), with a mean difference of 3.671 (SD, 3.201). BILAG total scores demonstrated an even larger shift, falling from 23.808 (SD 5.099) to 8.750 (SD 6.027; 

 = 1.9×10⁻²²), with a mean difference of 15.058 (SD, 8.424).

Importantly, NAC also improved patient-reported cognitive and fatigue symptoms in 54 participants. ADHD-Inattention scores improved from 19.259 (SD, 2.960) to 16.407 (SD, 7.449), a mean difference of 2.851 (SD 6.645; 

 = 1.5×10⁻²), and ADHD-Hyperactivity improved from 14.962 (SD, 7.530) to 13.185 (SD, 7.809), a mean difference of 1.777 (SD, 4.063; 

= 1.3×10⁻²). Physical fatigue decreased from 19.259 (SD, 2.960) to 16.092 (SD, 3.972), a mean difference of 3.166 (SD, 3.318; 

 = 2.5×10⁻⁸), while mental fatigue improved from 14.425 (SD, 4.574) to 12.092 (SD, 4.814), a mean difference of 2.333 (SD, 3.518; 

Adverse events included headache, nausea, gastrointestinal symptoms, constipation, and diarrhea and were transient and reversible. Eighteen participants withdrew during this phase, though only 1 withdrawal was attributed to adverse events.

Ramsey-Goldman emphasized that while these early, open-label results are encouraging, the ongoing double-blind phase will be essential to confirm NAC’s disease-modifying potential and determine whether this mitochondria-directed approach could offer a safer alternative to traditional immunosuppression in SLE.

"What NAC does is it replaces the chemicals that were missing so that the mitochondria function properly, so that the cell doesn't push itself toward overdrive or an inflammatory state, and it diminishes the antibodies that are causing the lupus [with] less side effects," Ramsey-Goldman said.

Ramsey-Goldman's reported disclosures include Ampel Solutions, AstraZeneca, Biogen, Cabaletta, Duke, Exagen Diagnostics, Merck, and SUNY Syracuse.

Ruchi FNU, Coman I, Blaker B, et al. Preliminary Analysis Of Open-Label Dose-Titration Phase Of SLE Treatment With N-Acetylcysteine (SNAC) Shows Evidence For Potential Improvement Of SLEDAI, BILAG, ADHD And Fatigue Scores In Patients With Active SLE. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #0657

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Ramsey-Goldman discussed the potential of NAC for treating systemic lupus erythematosus.

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Nicholas Marston, MD, is a cardiologist and an assistant professor of medicine at Brigham and Women's Hospital.

Olezarsen Proves Efficacy in Severe Hypertriglyceridemia, With Nicholas Marston, MD

The phase 3 CORE and CORE2 trials have highlighted the efficacy of olezarsen in patients with 

 by triggering a highly significant mean reduction in fasting triglyceride levels at 6 months and sustaining it through 12.

Data from both trials were presented at the 

American Heart Association’s Scientific Sessions 2025

 in New Orleans, Louisiana, by Nicholas Marston, MD, cardiologist and assistant professor of medicine at Brigham and Women’s Hospital. The editorial team at 

 sat down with Marston to discuss the implications of these data for cardiovascular care, as well as next steps for olezarsen as indicated in the MRI substudy.

“At this point, we’re not seeing a clinical context here, just an imaging finding,” Marston told 

. “We’re following this over time in the open-label extension, to see if this is something that plateaus. Ultimately, I think it will be something we’ll learn more about, and we’ll keep an eye on it.”

Olezarsen, an investigative antisense oligonucleotide in testing for sHTG treatment, is designed to lower apoC-III production. This protein regulates triglyceride metabolism in the blood, slowing triglyceride clearance and the liver’s uptake of triglyceride-rich particles. Although it has already received approval for chylomicronemia syndrome in the US and EU, its safety and efficacy have not been established for sHTG.

CORE and CORE2 were each double-blind, randomized, placebo-controlled trials by the full names CORE-TIMI 72a and CORE2-TIMI 72b. The primary endpoint in both trials was percent change from baseline in triglycerides at 6 months. Secondary lipid outcomes included the percent change from baseline in triglyceride at 12 months and in apo-C III, remnant cholesterol, and non-HDL-C levels at 6 and 12 months. Additionally, investigators assessed acute pancreatitis events across both trials.

A total of 1063 patients with sHTG were included overall, with 617 in the CORE trial and 446 in the CORE2 trial. They were then randomly assigned in a 1:1:1 ratio to either olezarsen 50 mg, olezarsen 80 mg, or placebo, all of which were administered monthly for 12 months. Both trials included an MRI substudy, assessing changes in hepatic fat at 1 year. The median age across both trials was 54 years, and median baseline triglyceride level was 796 mg/dL.

At 6 months, Marston and colleagues found a placebo-adjusted least-squares mean change in triglyceride level of -62.9 percentage points in the olezarsen 50 mg arm and of -72.2 percentage points in the olezarsen 80 mg arm in the CORE trial. By comparison, mean triglyceride level change in CORE2 was -49.2 percentage points in olezarsen 50 mg and -54.5 percentage points in olezarsen 80 mg.

The team also documented greater decreases in triglyceride, apoC-III, remnant cholesterol, and non-HDL-C in the olezarsen arms compared to placebo across both studies. Acute pancreatitis incidence was also lower with olezarsen than placebo (mean rate ratio, 0.15; 95% CI, 0.05 to 0.4; 

 <.001). Elevations in liver-enzyme levels and thrombocytopenia were more common in the olezarsen 80 mg arms, and a dose-dependent increase in hepatic fat fractions was noted.

Ultimately, Marston discussed potential applications for olezarsen should it receive approval in sHTG. He addressed its potential as an add-on therapy, but ultimately suggested that its relatively rapid effectiveness may position it as a starting therapy for patients at the highest risk levels.

“I think it could be viewed as an add-on, but I think for the highest risk patients, who have already had pancreatitis, we wouldn’t want to delay in getting them on olezarsen,” Marston said. “I could envision it being the first line for those highest-risk patients.”

Marston N, Bergmark B, Alexander V, et al. Olezarsen in Patients with Severe Hypertriglyceridemia: The CORE-TIMI 72a and CORE2-TIMI 72b Trials. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

Marston NA, Bergmark BA, Alexander VJ, et al. Olezarsen for managing severe hypertriglyceridemia and pancreatitis risk. New England Journal of Medicine. Published online November 8, 2025. 

Marston discusses the CORE and CORE2 trials, highlighting olezarsen’s success in lowering fasting triglyceride.

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Dyslipidemia

Vinay Mehta, MD: Board-certified allergist/immunologist with Allergy & Asthma Associates of Southern California

Lebrikizumab Effectively Treats AD in Patients with Skin of Color, With Vinay Mehta, MD

A phase 3b open-label trial conducted exclusively in people of color found that lebrikizumab effectively treats moderate-to-severe 

Vinay Mehta, MD, a board-certified allergist/immunologist with Allergy & Asthma Associates of Southern California, presented findings of ADmirable at the 

2025 American College of Allergy, Asthma, & Immunology (ACAAI) Annual Scientific Meeting

, which took place in Orlando, Florida, from November 6 – 10.

sat down with Mehta to discuss the significance of these findings and any safety concerns clinicians should be aware of when treating patients with skin of color using lebrikizumab.

“The safety was similar to what we saw in the larger phase 3 trials,” Mehta said. “Some of the common things we need to watch out for are conjunctivitis, which can occur often. It is transient, but certainly can occur in patients, especially those with severe atopic dermatitis. The other side effect is injection site reactions. At the site of the injection, there may be pain, there may be discomfort, there may be itching. Again, it didn't really differ from what we found in the broader pivotal trials.”

Lebrikizumab is a high-affinity, selective IL-13 inhibitor designed to block IL-13 signaling, a central driver of type 2 inflammation in AD. Mehta explained that the biologic has a slow dissociation rate, allowing sustained receptor engagement, an aspect that enables clinicians to decrease injection frequency after the initial 16-week induction phase in responsive patients. This pharmacologic durability helps support longer-term disease control while reducing treatment burden.

Data from the ADmirable trial, which exclusively enrolled patients with Fitzpatrick skin types IV–VI and patients who self-identified as either Black or African American, Hispanic or Latino, or Asian, showed that lebrikizumab achieved comparable efficacy outcomes across darker skin tones. Mehta noted that EASI-75 and IGA 0/1 response rates were consistent across Fitzpatrick IV, V, and VI groups, aligning with results from larger phase 3 programs. These findings complement earlier observations from the first half of the study: by week 16, 70% of patients reached EASI-75 and nearly half achieved clear or almost-clear skin.

In the interview, Menta also discussed how to incorporate this data into discussions with patients regarding realistic expectations for disease control. Mehta said a key message for clinicians is to integrate these findings into shared decision-making, particularly by setting expectations that go beyond skin clearance.

“It's not just about the skin. It's not just about the itch. These patients often suffer in terms of quality of life, in terms of work productivity,” Mehta said.

He emphasized the importance of using patient-reported outcome questionnaires, such as the Atopic Dermatitis Tool.

“I think that should be something that everyone should use,” he said. “We need to be cognizant, particularly in patients of skin color, that oftentimes they have certain challenges. Sometimes their disease severity is not recognized just because the erythema is a little bit more difficult to appreciate in these patients. It can present differently compared to what we normally see in the white population, so it's important to be mindful of that. It's also important to…know that there is a biologic that specifically was studied in patients [with] of skin color and that seems to work just as well as in the broader population with a similar side effect profile.”

Mehta, V. Lebrikizumab Improves Disease Control and Work Activity in Atopic Dermatitis Patients With Skin of Color. Presented at ACAAI 2025 in Orlando, Florida, from November 6 – 10.

Alexis A, Moiin A, Waibel J, et al. Efficacy and Safety of Lebrikizumab in Adult and Adolescent Patients with Skin of Color and Moderate-to-Severe Atopic Dermatitis: Results from the Phase IIIb, Open-Label ADmirable Study. Am J Clin Dermatol. 2025;26(5):803-817. doi:10.1007/s40257-025-00970-8

Derman, C. Lebrikizumab Benefits AD Patients With Skin of Color, With Vinay Mehta, MD. HCPLive. 

https://www.hcplive.com/view/lebrikizumab-benefits-ad-patients-skin-of-color-vinay-mehta-md

A phase 3b study in patients with skin of color found lebrikizumab provides reliable efficacy and safety for treating moderate-to-severe AD.


Dermatology

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

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.

Current Standard of Care and Treatment Options in Psoriasis

Panelists discuss the questions below in this video. How have treatment options for moderate-to-severe plaque psoriasis elevated the standard of care over the last decade?

Panelists examine how these emerging therapies compare with existing options and consider what their advances mean for clinicians and patients in everyday practice.

Cytokine Pathways and Their Impact on Plaque Psoriasis

Panelists discuss the questions below in this video.

Cytokines, such as IL-12, IL-23, and type I interferons drive psoriasis through TYK2-dependent Th1 and Th17 signaling. How do these pathways promote inflammation and keratinocyte proliferation? Which pathway do you believe is most critical to suppress for psoriasis control?

New ACAAI 2025 data show lebrikizumab improves disease control, quality of life, and work productivity in patients of skin of color with moderate to severe atopic dermatitis.


Lebrikizumab Benefits AD Patients With Skin of Color, With Vinay Mehta, MD

Michael Schilsky, MD, is a professor of medicine and medical director of adult liver transplant at Yale-New Haven Transplantation Center.

Data presented at AASLD 2025 show patients without severe neurologic involvement can achieve cognitive improvement with early detection and therapy.


Hepatology

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Neurology condition center page is a comprehensive resource for clinical news and insights on nervous system disorders. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for Alzheimer's disease, brain injury, PTSD, and more.

Early Treatment May Protect Cognitive Function in Wilson Disease, With Michael Schilsky, MD

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

Articles

These topline results from the ADHAND trial highlight tralokinumab’s use in adults with atopic dermatitis with moderate-to-severe hand involvement.

Tralokinumab Improves Atopic Dermatitis with Hand Involvement at 32 Weeks

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.

Le discusses the increased risk of mortality and major adverse cardiovascular events in patients with both PAD and AF.

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Atrial Fibrillation in Peripheral Arterial Disease Increases MACE Risk, with Viet Le, DMSc, PA-C

The FDA acceptance of Arcutis's supplemental New Drug Application (sNDA) was announced for roflumilast cream 0.3% (Zoryve).

Plaque Psoriasis

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

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FDA Accepts sNDA for Roflumilast Cream 0.3% in Children Ages 2 to 5 with Psoriasis

Exploration of using tools such as UAS7 and DLQI to quantify disease severity, predict poor response, and guide timely therapy escalation.

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Escalating Therapy in Chronic Spontaneous Urticaria Management

Lindsay Ackerman, MD, explores novel agents and the potential of biomarkers to personalize treatment selection in psoriasis.

Emerging Therapies in Psoriasis and the Role of Biomarkers in Precision-Based Care

Review of updated CSU treatment algorithms and the balance between standardized and individualized care approaches.

Recognizing and Assessing Disease Burden in Chronic Spontaneous Urticaria

Lindsay Ackerman, MD, critiques traditional clinical trial models and proposes ways to improve their relevance to real-world patient populations.

Reforming Trial Designs to Better Address Unmet Needs in Psoriasis Care

Ryan Livingston joined the MJH Life Sciences team in March of 2025, shortly after graduating from TCNJ with a bachelor’s degree in English. He enjoys creative writing, reading, and scuba diving. He can be reached at rlivingston@mjhlifesciences.com.

Data from 4 of the most impactful trials presented at the American Heart Association Scientific Sessions 2025.

Latest News

Proof of Concept: Targeting Mitochondrial Dysfunction in SLE With NAC, with Rosalind Ramsey-Goldman, MD

Olezarsen Proves Efficacy in Severe Hypertriglyceridemia, With Nicholas Marston, MD

Lebrikizumab Effectively Treats AD in Patients with Skin of Color, With Vinay Mehta, MD

Current Standard of Care and Treatment Options in Psoriasis

Cytokine Pathways and Their Impact on Plaque Psoriasis