Reducing COPD Exacerbations With Tozorakimab, With Frank Sciurba, MD

Tozorakimab, an investigational monoclonal antibody targeting the IL-33 pathway has demonstrated statistically significant and clinically meaningful reductions in 

 (COPD) exacerbations in 2 phase 3 trials, with benefit extending across all blood eosinophil counts and all stages of lung function severity, according to an announcement by AstraZeneca on the phase 3 OBERON and TITANIA trials.

spoke with investigator Frank C. Sciurba, MD, about the new findings, who argued that tozorakimab could open a new therapeutic avenue for the majority of COPD patients who remain inadequately served by current biologic options.

Sciurba, tenured professor of medicine and director of the Emphysema COPD Research Center at the University of Pittsburgh School of Medicine, serves as chief investigator of the LUNA program evaluating tozorakimab (AstraZeneca) in COPD.

Both TITANIA and OBERON were randomized, double-blind, placebo-controlled trials with a combined enrollment of 2,306 patients, recruited irrespective of blood eosinophil count, smoking status, or lung function severity stage, all of whom received tozorakimab 300 mg subcutaneously once every 4 weeks or placebo for 52 weeks on top of standard-of-care inhaled maintenance therapy. The primary endpoint in both trials was the annualized rate of moderate-to-severe COPD exacerbations in the primary population of former smokers; key secondary endpoints assessed the overall population of former and current smokers combined. Both studies met their primary and key secondary endpoints, with tozorakimab demonstrating a statistically significant reduction in moderate-to-severe exacerbations versus placebo in the primary population and in the broader overall population. The safety profile was described as generally favorable and consistent with prior tozorakimab experience. Full results will be presented at a forthcoming scientific meeting; no specific effect-size data have yet been disclosed.

Sciurba described tozorakimab's mechanism as mechanistically upstream of every currently approved biologic in COPD. IL-33 is released by the airway epithelium in response to a variety of stimuli — microbial, irritant, and allergic — and upon release, it engages both innate and adaptive immune responses, feeding into the Th2-mediated pathway that drives eosinophilic inflammation as well as the Th1 and Th17 pathways associated with neutrophilic inflammation. Tozorakimab uniquely inhibits both the reduced and oxidised forms of IL-33, potentially disrupting not only the inflammatory cascade but also the cycle of mucus dysfunction that contributes to disease progression in COPD. This positioning upstream of existing therapeutic targets means the drug theoretically modulates pathways that IL-4 receptor antagonists such as dupilumab and IL-5 inhibitors do not reach — in particular the Th1-dominant inflammatory environment that characterizes most COPD patients.

That distinction has direct clinical implications. The currently approved biologics for COPD — dupilumab, which targets the IL-4 receptor α chain and thus blocks IL-4 and IL-13 signaling, and IL-5 inhibitors — are mechanistically specific to the Th2 pathway and are most effective in patients with elevated blood eosinophil counts. Sciurba estimated that Th2-predominant patients represent approximately 30% of the overall COPD population, leaving the majority — those with low eosinophil counts and a Th1- or Th17-dominant inflammatory phenotype — without a targeted biologic option. This group tends to respond poorly to inhaled corticosteroids and, data suggest, may also derive less benefit from systemic steroids during exacerbations. The OBERON and TITANIA finding that tozorakimab reduced exacerbations across all blood eosinophil counts therefore carries particular significance: it raises the possibility that IL-33 blockade may provide benefit regardless of the dominant inflammatory subtype, addressing a population for which no comparable agent currently exists.

Sciurba noted a pharmacological nuance in this context: the Th1 pathway, while contributing to pathological inflammation in COPD when excessively activated, also serves important homeostatic functions in antimicrobial defense, antiviral immunity, and cancer surveillance. Therapeutic strategies that broadly suppress Th1 responses therefore carry theoretical risks that pathway-specific targeting approaches must carefully calibrate. The OBERON and TITANIA safety data, described as favorable, will be scrutinized in this context when full results are disclosed. Additional trials under the LUNA program — including PROSPERO, a long-term extension study enrolling completers from OBERON and TITANIA, and MIRANDA, assessing an alternative dosing regimen — are ongoing, with data expected in the first half of 2026.

“Tozarakimab is a monoclonal against the IL-33 ligand, and it's involved in a lot of the inflammatory pathways that are affected in COPD. It interestingly affects both Th2 pathways as well as Th1 pathways, and that is of great interest in COPD,” Sciurba said.

Sciurba has reported disclosures including AstraZeneca, COPD Foundation, Gala Therapeutics, GlaxoSmithKline, National Institute of Health, Nuvaira, Patient-Centered Outcomes Research Institute, Pulmonx Corporation, Sano, U.S. Department of Defense, University of Pittsburgh, and Verona Pharma.

AstraZeneca. Tozorakimab met primary endpoint in both OBERON and TITANIA phase III trials in patients with COPD. Press release. March 27, 2026. Accessed March 27, 2026. 

https://www.businesswire.com/news/home/20260327464200/en/Tozorakimab-met-primary-endpoint-in-both-OBERON-and-TITANIA-Phase-III-trials-in-patients-with-COPD

Videos

Tozorakimab significantly reduced moderate-to-severe exacerbations in COPD regardless of blood eosinophil count.

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What's New in Atopic Dermatitis Management, With April Armstrong, MD, MPH

The atopic dermatitis treatment landscape is evolving at an unprecedented pace, according to April W. Armstrong, MD, MPH, of UCLA's David Geffen School of Medicine, and those working in the field are working to keep up.

2026 American Academy of Dermatology (AAD) Annual Meeting

 in Denver, Colorado, Armstrong spoke about various key developments spanning long-term safety data, emerging mechanisms of action, and the increasing role of personalized treatment strategies in the moderate-to-severe atopic dermatitis space.

“Some of the things that I highlighted in my session included long-term data for the FDA-approved therapies, both in the biologic realm as well as oral JAK inhibitors,” Armstrong expressed.

On the topic of safety data, Armstrong provided reassurance related to oral Janus kinase (JAK) inhibitors. She noted long-term findings show rates of serious infections and major adverse cardiovascular events (MACE) in the atopic dermatitis population appear to be comparable to background rates seen in patients with moderate-to-severe disease. With this in mind, Armstrong stressed the value of Zoster vaccination prior to, or concurrent with, beginning oral JAK inhibitor treatment, given the link to elevated risk of Zoster infection.

Later in the interview, Armstrong turned her attention to the drug pipeline, touching on the wave of innovations seen across both familiar and novel therapeutic pathways. Longer-term data were noted as currently available for agents targeting the OX40 ligand pathway. Newer approaches are also exploring more precise inhibition of the interleukin (IL)-4 receptor alpha.

Outside of biologics, Armstrong also spoke about oral drugs targeting STAT6, as opposed to JAK molecules, emerging as noteworthy in dermatology. She also pointed to the growing interest in bi-specific and tri-specific molecules designed to simultaneously inhibit multiple targets, an approach aimed at addressing the heterogeneity of disease presentations.

Despite the momentum, Armstrong later described the management of moderate-to-severe atopic dermatitis as continuing to be a highly individualized challenge. For individuals with refractory disease, she encouraged clinicians in the field not to be discouraged, emphasizing combination therapy as potentially appropriate for certain patients.

The quotes used in this video summary were edited for clarity.

Armstrong has served as a consultant for and received honoraria from AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, EPI, Incyte, Janssen, LEO Pharma, Eli Lilly, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun, and UCB and has participated in advisory boards for Boehringer Ingelheim and Parexel.

Armstrong A, et al. S065 What's New in Dermatology. Session presented at: 2026 American Academy of Dermatology Annual Meeting; March 27–31, 2026; Denver, CO.

Armstrong AW, Rubin C, Jarell A, et al. Real-world effectiveness of 12 months tralokinumab treatment in patients with skin of color and moderate-to-severe atopic dermatitis: final data from the prospective, non-interventional, international TRACE study. Presented at the 2026 American Academy of Dermatology Annual Meeting; March 27-31, 2026; Denver, CO. Poster ID: 77199. Oral Poster Presentation.

At AAD, April W. Armstrong, MD, MPH, discussed recent innovations in the atopic dermatitis treatment space, highlighting long-term safety data and more.

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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.

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Nancy Reau, MD, is Professor of Internal Medicine, Richard B. Capps Chair of Hepatology, Associate Director of Solid Organ Transplantation, and Section Chief of Hepatology at Rush University Medical Center.

Kimberly Brown, MD, is division chief of gastroenterology and hepatology and the Associate Medical Director of the Henry Ford Hospital Transplant Institute at Henry Ford Hospital. She is also a Professor of Medicine at Wayne State University

Meena Bansal, MD, is director of the MASLD/MASH (NAFLD/NASH) Center of Excellence at Mount Sinai and System Chief, Division of Liver Diseases for the Mount Sinai Health System.

PCOS, Pregnancy, and MASLD Risk: What Clinicians Need to Know

metabolic dysfunction-associated steatotic liver disease (MASLD)

 continues to grow, increasing attention is being paid to how reproductive and metabolic conditions uniquely shape risk in women. Among these, 

 and pregnancy represent critical but often underrecognized periods where hormonal and metabolic factors intersect to influence liver health.

In this segment from a recent episode of 

Liver Lineup: Updates and Unfiltered Insights

, Meena Bansal, MD, joins hosts Nancy Reau, MD, and Kimberly Brown, MD, to examine the complex relationship between PCOS, pregnancy, and MASLD.

Bansal emphasizes that PCOS is a well-established risk factor for MASLD and its more advanced form, MASH, largely driven by underlying insulin resistance. While the condition is widely recognized in endocrinology, its implications for liver health are often underappreciated. She notes that patients with PCOS should be evaluated for liver fibrosis using noninvasive tools, and those with evidence of stage 2 or 3 fibrosis may be appropriate candidates for currently approved therapies.

The discussion then shifts to pregnancy as a critical period of risk. Women entering pregnancy with metabolic comorbidities such as obesity or diabetes may already be predisposed to MASLD, and the physiologic changes of pregnancy, including weight gain, can further exacerbate disease progression. According to Bansal, emerging data suggest that MASLD during pregnancy is associated with increased risks of adverse maternal outcomes, including gestational diabetes and preeclampsia, as well as complications for the fetus, such as preterm birth and abnormal growth patterns.

The conversation also touches on the potential for long-term, intergenerational effects. Bansal highlights research suggesting that maternal metabolic health may influence fetal outcomes through epigenetic mechanisms, potentially increasing a child’s lifetime risk of metabolic disease and liver dysfunction. While she says these findings require further validation, they underscore the broader implications of MASLD beyond the individual patient.

Reau and Brown further explore how current therapies fit into this landscape, particularly for younger, premenopausal women. Although GLP-1 receptor agonists have shown benefits in weight loss and metabolic regulation and may even improve menstrual regularity in some patients with PCOS, their use is contraindicated during pregnancy. Bansal points out the challenges this creates in preconception care, including uncertainty around weight regain after discontinuation and its potential impact during pregnancy.

As Bansal notes, more research is needed to better understand how to tailor care for women with MASLD, especially during periods of hormonal and metabolic transition.

Editors’ note: Relevant disclosures for 

 include AbbVie, Gilead, Salix, Arbutus, and VIR. Relevant disclosures for 

 include Mallinckrodt Pharmaceuticals, Gilead, Salix, Intercept, Ipsen, and Madrigal. Relevant disclosures for 

 include Boeheringer-Ingelheim, Boston Pharma, Fibronostics, GSK, Madrigal, Merck, NOVO Nordisk, and The Kinetix Group.

DiStefano JK. NAFLD and NASH in Postmenopausal Women: Implications for Diagnosis and Treatment. Endocrinology. 2020;161(10):bqaa134. doi:10.1210/endocr/bqaa134

Sarkar M, Kushner T. Metabolic dysfunction-associated steatotic liver disease and pregnancy. J Clin Invest. 2025;135(10):e186426. Published 2025 May 15. doi:10.1172/JCI186426

Mass General Brigham. Patients Who Discontinued GLP-1s Had More Weight Gain, Complications During Pregnancy. November 24, 2025. Accessed April 17, 2026. 

https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/pregnancy-effects-from-discontinued-glp-1-use

Experts discuss how metabolic and hormonal factors in women influence MASLD risk, progression, and potential long-term outcomes.

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The HCPLive endocrinology page is a comprehensive resource for clinical news and insights on endocrine system conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for diabetes, hormonal disease, and more.

Hepatology

Polycystic Ovary Syndrome

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MASLD and Women’s Health: The Roles of PCOS and Pregnancy

Roy Beck, MD, PhD, is the founder of the Jaeb Center for Health Research.

INHALE-3 Analysis Supports Need for Increased Technosphere Insulin Doses, With Roy Beck, MD, PhD

Technosphere insulin (TI), an ultrarapid-acting inhaled insulin, has shown its efficacy in glucose management in higher doses than have been approved for adults with 

, according to an analysis from INHALE-3.

“One of the challenges that we have in treating patients with injectable insulin is that it’s injected underneath the skin,” Roy Beck, MD, PhD, founder of the Jaeb Center for Health Research, told 

 in an exclusive interview. “It takes some time to be absorbed into the bloodstream, and so there’s a delay much greater than what we see with a pancreas producing insulin normally. When insulin is inhaled and goes into the lung, it distributes into the bloodstream very rapidly and becomes something very close to endogenous insulin.”

TI is the first and only ultrarapid-acting inhaled insulin to receive approval from the 

 for the improvement of glycemic control in patients with diabetes mellitus. Initially approved under the brand name Afrezza, TI received an update to its prescribing information on January 26, 2026, revising the recommendations for starting mealtime dosage when patients switch from subcutaneous mealtime insulin regimens.

INHALE-3 was a multicenter, randomized, controlled study comparing the safety and efficacy of TI combined with insulin degludec versus standard care in adults with T1D. This latter group included treatment regimens of multiple daily injections or insulin pump therapy, including automated insulin delivery (AID) systems. Patients were not blinded to treatment.

Upon randomization, patients in the TI treatment arm transitioned from their previous insulin therapy using a conversion ratio modified from existing recommendations, wherein the TI dose is calculated by multiplying the patient’s usual subcutaneous rapid-acting insulin analogue (RAA) dose by 2 and rounding down to the nearest available cartridge size from among 4, 8, or 12 U, or a combination thereof. The first dose of TI was administered in-clinic, after which patients were instructed to titrate their TI dose over time based on glucose response.

The present analysis analyzed a specific subgroup of patients who had been randomized to the T1D and degludec arm and had complete insulin dosing data at all 3 key timepoints – baseline, week 17, and week 30. Patients were eligible for inclusion if they had non-missing data for total daily insulin doses and mealtime dosing at each time point. A total of 35 patients from INHALE-3 met these criteria and were included.

Among these patients, the mean age was 46 years with a baseline A1c of 7.72% (standard deviation [SD] +/- 1; 61 mmol/mol). Prior to TI initiation, 40% of participants were using AID. The mean baseline bolus and basal dose of RAA insulin were 23.9 U/d, with a bolus/basal ratio of roughly 50%/50%. After 30 weeks of monitoring, mean total daily TI dose increased from 36 U at baseline to 48 U at 17 weeks (

 <.001). By 30 weeks, the TI bolus/basal ratio had also shifted to around 70%/30% (

 <.001). At 17 weeks, 57% of participants had increased their TI dose by >4 U, which then increased to 74% at 30 weeks. Notably, investigators recorded no new safety signals with TI treatment.

Given these data, the FDA’s approval of higher starting doses for TI is no surprise. Investigators did, however, emphasize that higher overall dosing requirements are needed to support individualized titration and help patients reach their glycemic goals.

“All patients could potentially improve with this, because everyone who has diabetes has the potential for a spike after they eat,” Beck said. “There’s a real benefit to trying to reduce that by getting insulin into the bloodstream faster, although the effect of that insulin goes away pretty quickly. There were a substantial proportion of participants who improved quite a bit, but there were some who didn’t, and I think it’s largely because it took a certain regimented approach to frequent inhaling if your glucose was still high.”

Editors’ Note: Beck reports that his institution has received funding on his behalf from Insulet, Tandem Diabetes Care, Beta Bionics, Abbott, Dexcom, Sequel Med Tech, and others.

Rittenberry J, Sylvan J, Mycue L-E, Griparic L, Kaiserman K. Inhaled insulin dosing in a randomized trial in adults with type 1 diabetes. 

MannKind Corporation. MannKind Announces FDA Approval of Updated Afrezza Label Providing Starting Dose Guidance when Switching from Multiple Daily Injections (MDI) or Insulin Pump Mealtime Therapy. January 26, 2026. Accessed April 17, 2026. 

https://investors.mannkindcorp.com/news-releases/news-release-details/mannkind-announces-fda-approval-updated-afrezzar-label-providing

Beck discusses a recent analysis of the phase 4 trial comparing TI and degludec against standard treatment, highlighting the need for individualized titration.

Type 1 Diabetes

Marie-José van Tol, PhD, from the University of Groningen.

Preventive Therapy Targeting Positive Affect May Reduce MDD Relapse, With Marie-José van Tol, PhD

New findings suggest preventive cognitive therapy (PCT) may lower relapse risk in remitted recurrent 

by improving pleasure and modifying dysfunctional attitudes.

, Marie-José van Tol, PhD, from the University of Groningen, discussed new data examining the cognitive and affective mechanisms underlying preventive cognitive therapy (PCT), highlighting the role of positive affect and anhedonia in reducing relapse risk.

“In order to change dysfunctional attitudes that are very quite rigid and related to depressive relapse, we need to also focus on increasing the ability to experience pleasure and to up regulate positive emotions,” van Tol said.

The study included 69 unmedicated individuals with remitted MDD at high risk for recurrence from the NEWPRIDE randomized controlled trial. The findings showed a 3-month PCT intervention directly improved consummatory pleasure, the inverse of anhedonia, and increased use of cognitive reappraisal, which together contributed to reductions in dysfunctional attitudes associated with relapse vulnerability. Change in anhedonia (odds ratio [OR], 0.79; 95% CI, 0.68–0.92; 

 =.003] and dysfunctional attitudes (OR, 0.93; 95% CI, 0.86–0.99; 

 =.041) predicted relapse status at 18-month follow-up in PCT-recipients.

The analysis demonstrated that improvements in pleasure mediated the relationship between PCT and reductions in maladaptive beliefs (P =.003). Van Tol described this as a “cross-valence” mechanism, in which strengthening positive affective experiences may buffer against the impact of negative life events.

“It seems that if we focus on improving the ability to have positive feelings, this might lower the impact that negative events have on us, and thereby also lower the impact it has on an individual, and thereby de-learning, in a sense, these negative beliefs about yourself,” she said.

The study focused on unmedicated individuals, but van Tol noted prior evidence suggests PCT may also provide benefit when combined with maintenance antidepressant therapy. She added that the observed mechanisms involving positive affect require further validation in broader populations.

From a practical standpoint, van Tol suggested clinicians consider incorporating strategies that actively promote positive emotional experiences alongside traditional cognitive techniques. These approaches may include encouraging engagement in rewarding activities, fostering savoring of positive experiences, and strengthening emotion regulation skills through reinterpretation of situations. She said these interventions may improve resilience and reduce vulnerability to recurrence.

Although cognitive reappraisal improved following PCT, it did not independently predict relapse in this study. Van Tol indicated that reappraisal likely contributes as part of a broader set of skills rather than as a standalone therapeutic target.

“Focusing on improving a reappraisal probably will not be enough,” van Tol said.

Angeles-Valdez D, van Kleef R, van Valen E, Garza-Villarreal EA, Bockting C, van Tol MJ. The role of cognitive and affective changes in preventing depressive relapse: A network analysis approach to understanding the mechanisms of preventive cognitive therapy. 

Research suggests preventive cognitive therapy reduced relapse risk in recurrent depression by improving positive affect and anhedonia, van Tol explained in an interview.

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Hanna, MD, shares results from reni-cel, a one-time gene editing therapy for patients with sickle cell disease. 

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Can Gene Editing Be A 'Functional Cure' For Sickle Cell Disease?

Vinod E. Nambudiri, MD, MBA, MPH, is affiliated with Brigham and Women's Hospital and specializes in Dermatology and Internal Medicine.

Nambudiri discusses the AAD Clinical Image Collection, launched in January 2025 to address the lack of diverse representation in dermatology education.


Dermatology

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How the AAD Clinical Image Collection Can Help Dermatologists, With Vinod Nambudiri, MD, MBA, MPH

Abigail Brooks is an assistant managing editor for 

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

Articles

Experts discuss diagnostic challenges, variable presentations, and strategies to improve outcomes in Wilson disease.

From Diagnosis to Management: Addressing Gaps in Wilson Disease 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.

Results from the largest and longest trial of orforglipron to date have displayed the drug’s efficacy in reducing all-cause cardiovascular death and MACE incidence.

Breaking News

Type 2 Diabetes

ACHIEVE-4: Orforglipron Non-Inferior to Insulin Glargine for Cardiovascular Protection in T2D

Learn how subtle liver enzyme changes and age-specific movement symptoms signal Wilson disease, plus the latest on newborn screening and tests.

Video Series

Early Clinical Signs and the Evolution of Diagnosis in Wilson Disease

Psoriasis care shifts beyond skin: treat-to-target goals, heart risk reduction, and new oral TYK2 pills with strong safety data.

Zasocitinib in Plaque Psoriasis from the LATITUDE Trials

Clinicians across specialties spot red flags, refer early to GI, and follow guidelines to improve diagnosis and management.

Who Diagnoses EPI? Defining Roles Across the Care Team

Wilson disease mimics tremor, dystonia, Parkinsonism or psychosis; watch for subtle liver signs and screen early to avoid delay.

Understanding Pathophysiology and Copper Transport in Wilson Disease

Discover how oral TYK2 inhibitors deliver targeted psoriasis control with strong safety data and biologic-like clearance, including insights on deucravacitinib and zasocitinib.

The Role of TYK2 Inhibitors in Modern Psoriasis Care

Why EPI stays missed: barriers to enzyme therapy, targeted fecal elastase testing, and preventing malnutrition, bone loss, and QoL decline.

Latest News

Reducing COPD Exacerbations With Tozorakimab, With Frank Sciurba, MD

What's New in Atopic Dermatitis Management, With April Armstrong, MD, MPH

MASLD and Women’s Health: The Roles of PCOS and Pregnancy

INHALE-3 Analysis Supports Need for Increased Technosphere Insulin Doses, With Roy Beck, MD, PhD

Preventive Therapy Targeting Positive Affect May Reduce MDD Relapse, With Marie-José van Tol, PhD