Victoria Johnson joined the MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and now HCPLive. You can reach her at vjohnson@mjhlifesciences.com

Victoria Johnson

Over the last decade, the landscape of respiratory care has undergone a dramatic transformation, driven by advances in the understanding of asthma and chronic obstructive pulmonary disease (COPD) pathophysiology and the emergence of 

. Where treatment once centered largely on inhaled corticosteroids and bronchodilators, the field has entered a new era defined by phenotypic precision, biomarker-driven strategies, and earlier, more tailored intervention. For clinicians and patients alike, this progress has shifted expectations for disease control and long-term outcomes, particularly in populations that previously had few effective options.

In asthma, the approvals of biologics like dupilumab (Dupixent), benralizumab (Fasenra), and most recently tezepelumab (Tezspire) have allowed treatment to move beyond allergen or eosinophil-based models toward broader and more inclusive criteria. Tezepelumab’s 2021 FDA approval, in particular, marked a turning point as the first biologic approved for severe asthma regardless of baseline eosinophil count.

 These developments have redefined what “uncontrolled” asthma means and raised the bar for treatment goals—including reduced exacerbation rates, improved lung function, and steroid-sparing potential. As a result, allergists and pulmonologists are increasingly aligned in a shared, multidisciplinary approach to asthma management, focused on identifying the right therapy for the right patient as early as possible.

COPD, historically considered less amenable to targeted therapy, has begun to follow a similar trajectory. In 2024, dupilumab became the first biologic approved for eosinophilic COPD in the US, signaling new therapeutic possibilities in a field where treatment had long stagnated.

 At the same time, a growing understanding of COPD endotypes and inflammatory mechanisms is prompting a reevaluation of how the disease is diagnosed and managed. These changes are leading to greater overlap in how clinicians think about asthma and COPD care and are presenting new challenges in integrating advanced therapeutics into real-world workflows.

To explore these evolving questions and clinical implications, HCPLive convened a clinical forum event featuring expert perspectives from pulmonologists and allergists at the forefront of respiratory care, led by Igor Barjaktarevic, MD, PhD, Director of Bedside ultrasound and Medical Director of Liver-transplant Intensive Care Units at Ronald Reagan Medical Center, and Medical Director of COPD at the David Geffen School of Medicine at University of California – Los Angeles (UCLA).

The panelists discussed how asthma is now widely accepted as a heterogeneous disease, with type 2 inflammation (especially eosinophilic) being the most actionable phenotype for biologic intervention. They touched on biomarkers such as eosinophils, IgE, and FENO as being essential, though imperfect, tools for guiding therapy. They also emphasized increasing interest in personalized combinations or early biologic use in difficult-to-treat asthma.

“If you pick the right biomarker, it's not just a number. It's actually a target and something that you can follow over time to ascertain if the disease state is improving. So, I think a couple of points there I would kind of solidify is that we now know that asthma is heterogeneous. You see a lot of patients with shortness of breath, chest tightness, wheezing, and cough. If you zoom in, they do not have the same inflammatory state, and if you're able to find a biomarker to hone in on which kind of inflammation is going on, you can just identify that patient and find a target,” Lorraine Anderson, MD, allergist-immunologist at UCLA said.

Moving on to COPD, they acknowledged that it is even more heterogeneous than asthma and is now recognized to include a significant subset of patients with eosinophilic inflammation who benefit from therapies traditionally used in asthma. Dupilumab and mepolizumab both show efficacy in patients with ≥300 eosinophils/μL, but their relative positioning and long-term roles are still debated. Biomarker development remains a challenge, with limited predictive reliability and interference from factors like smoking.

“Asthma is in young population. COPD is usually in the older population. So that's a big difference in terms of inflammation. They're far gone. So, then you feel the rush to reverse, which sometimes is not reversible. Asthma, you want to prevent chronic steroid use because they're in a young age. So, I think inflammation is very different in the 2 diseases,” participants said.

They also touched on bronchiectasis, asthma-COPD overlap, and fixed obstruction in non-smokers, and looked forward to upcoming research into biologics' potential in these settings.

“We’re seeing more bronchiectasis because it's being identified. These people were being labeled as chronic bronchitis before COPD. And so, and there is one phenotype of COPD in bronchiectasis, right? There is the COPD patient with bronchiectasis, that's one of the many potential etiologies of bronchiectasis, right? But yes, it's a hot topic right now because we're going to finally have a targeted drug specifically for bronchiectasis,” participants said.

Overall, the participants emphasized that biologics and personalized medicine, especially biomarker-guided approaches, are growing in importance across conditions, although the field must keep in mind the limits of current trial designs and the gap between real-world patients and study populations.

FDA Approves Tezspire™ (Tezepelumab-ekko) in the U.S. for Severe Asthma. News release. Amgen. December 17, 2021. 

https://www.amgen.com/newsroom/press-releases/2021/12/fda-approves-tezspire-tezepelumabekko-in-the-us-for-severe-asthma

Dupixent® (dupilumab) Approved in the U.S. as the First-ever Biologic Medicine for Patients with COPD. Regeneron Pharmaceuticals, Inc. September 27, 2024. https://www.globenewswire.com/news-release/2024/09/27/2954552/0/en/Dupixent-dupilumab-Approved-in-the-U-S-as-the-First-ever-Biologic-Medicine-for-Patients-with-COPD.html.

Articles

Advancements in respiratory care have significantly transformed asthma and COPD management, emphasizing phenotypic precision and biomarker-driven strategies. The introduction of biologics like dupilumab, benralizumab, and tezepelumab has expanded treatment options, particularly for severe asthma and eosinophilic COPD. These developments have redefined disease control expectations and fostered a multidisciplinary approach to care. Despite progress, challenges remain in biomarker reliability and integrating advanced therapies into clinical practice. The field continues to explore personalized medicine's potential, especially in conditions like bronchiectasis and asthma-COPD overlap.

Explore the latest advancements in biologic therapies for asthma and COPD discussed in a recent clinical forum highlighting personalized medicine and biomarker-driven strategies for improved patient outcomes.

Biologics and Beyond: Clinical Perspectives on Managing Complex Airway Inflammation

A new post-hoc analysis of the MITIGATE trial, a pivotal trial for the approval of inebilizumab for people with IgG4-related disease (IgG4-RD), supports the use of the therapy across various demographic subgroups of the disease.

European Alliance of Associations for Rheumatology (EULAR) Congress 2025 

in Barcelona, Spain, taking place June 11-14, 2025.

“IgG4-RD is a progressive, systemic, fibroinflammatory disease characterized by unpredictable and recurring flares, leading to organ damage and decreased quality of life. The disease can affect nearly any organ,” lead investigators John H. Stone, MD, MPH, principal investigator, and a professor of medicine at Harvard Medical School and Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, and colleagues wrote in their abstract.

MITIGATE (NCT04540497) is an international, randomized, blinded, placebo-controlled Phase 3 trial that evaluates the safety and efficacy of inebilizumab as treatment for IgG4-RD. Inebilizumab is a humanized, glycoengineered, CD19-directed, B-cell depleting monoclonal antibody that was approved by the FDA under the name Uplizna as the first and only treatment for adult patients with IgG4-RD in April 2025.

The trial enrolled 135 adult participants who met the ACR/EULAR Classification Criteria for IgG4-RD with a score ≥20 who had a history of multiorgan IgG4-RD and had experienced an IgG4-RD flare that required glucocorticoid treatment during the screening period. The trial stratified participants by first or subsequent IgG4-RD manifestation to account for potential differences in flare risk and randomized them 1:1 to inebilizumab (n = 68) or placebo (n = 67). Treatments took place on day 1, day 15, and week 26 of the 1-year randomized controlled period (RCP).

The trial’s primary end point was time to first adjudication committee (AC)-determined and investigator-treated IgG4-RD flare during the RCP. It also evaluated key secondary endpoints including annualized flare rate during the RCP and the proportion of participants achieving flare-free, treatment-free complete remission or flare-free, corticosteroid-free complete remission at Week 52. Investigators also evaluated safety.

The trial’s 2 treatment groups had generally well balanced baseline demographics. Participants had a mean age of 58.2 years in the study, with 31.1% of participants aged 65 years or older, and 34.8% of participants were female, consistent with the known male predominance of of IgG4-RD. A total of 46.7% of participants were Asian, 39.3% were White, and 7.4% did not report. The remaining 6.6% of participants consisted of Black, American Indian or Native Alaskan, Native Hawaiian or other Pacific Islander, unknown or other races.

The investigators found that inebilizumab treatment significantly reduced the risk of flare relative to placebo regardless of age, sex, or race, with each subgroup exhibiting a hazard ratio similar to the overall study population, and consistent trends were observed across all regions.

They also found that inebiliuzmab reduced annualized flare rates relative to placebo in all demographic subgroups. Similar results were observed for all subgroups with sufficient representation for the proportion of participants achieving flare-free, treatment-free complete remission or flare-free, corticosteroid-free complete remission at Week 52. Furthermore, safety findings were similar in each subgroup to that observed in the overall population.

Stone JH, Culver EL, Khosroshahi A, et al. Safety and Efficacy of Inebilizumab in IgG4-Related Disease Across Various Participant Demographics: Subgroup Analysis from the MITIGATE Study. Presented at: EULAR Congress 2025; Barcelona, Spain; June 11-14. Presentation #OP0189

The post-hoc analysis of the MITIGATE trial supports the efficacy and safety of inebilizumab for treating IgG4-related disease (IgG4-RD) across diverse demographic subgroups. The trial, a Phase 3 international, randomized, placebo-controlled study, demonstrated that inebilizumab significantly reduced the risk of disease flares compared to placebo, regardless of age, sex, or race. The treatment also decreased annualized flare rates and increased the proportion of patients achieving complete remission. Safety profiles were consistent across all subgroups, aligning with the overall study population.

Inebilizumab was approved by the FDA under the name Uplizna as the first and only treatment for adult patients with IgG4-RD in April 2025

Inebilizumab Efficacy and Safety Consistent Across Demographic Subgroups of IgG4-RD

Credit: Charité-Universitätsmedizin Berlin

New research examining the rates of serious infections in people with giant cell arteritis (GCA) supports the use of 

 15 mg with a shorter glucocorticoid (GC) tapering than placebo with a longer taper.

“In the SELECT-GCA phase 3 trial, upadacitinib once daily in combination with a protocolized 26-week GC taper demonstrated a favorable benefit-risk profile compared with placebo with a protocolized 52-week GC taper, providing an alternative option to reduce GC dependency while maintaining disease control in patients with GCA5,” lead investigator Frank Buttgereit, MD, Professor of Rheumatology and Deputy Head of the Department of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, and colleagues wrote in their presentation.

 “To assess the occurrence of adverse events of serious infection, herpes zoster, and opportunistic infection during concomitant treatment with GCs and after GC tapering in patients with GCA receiving upadacitinib or placebo.”

In the SELECT-GCA trial, participants underwent an open-label GC taper regimen until the dose reached 20 mg per day, after which it was blinded. The glucocorticoid taper regimens were tailored to each patient on the basis of the starting dose, with the patients in the upadacitinib groups discontinuing by week 26 and those in the placebo group discontinuing by week 52. Baseline characteristics, including GC doses, were similar across treatment groups, and most patients received a glucocorticoid dose between 20 to 40 mg at baseline. Based off safety and efficacy data from SELECT-GCA, upadacitinib 15 mg once daily was 

 for the treatment of adults with GCA under the name Rinvoq in April 2025.

The investigators found that the rates of serious infections were numerically lower with both 15- (7.9 events/100 patient-years [E/100 PY]; 95% CI, 4.3-13.2) and 7.5-mg (7.9 E/100 PY; 95% CI, 3.2-16.3) doses of upadacitinib than with placebo (12.7 E/100 PY; 95% CI, 6.6-22.2) through week 52. In contrast, rates of herpes zoster, a known risk for JAK inhibitors including upadacitinib were higher with UPADACITINIB15 mg (7.3 E/100 PY; 95% CI, 3.9-12.5) but not upadacitinib 7.5 mg (4.5 E/100 PY; 95% CI, 1.2-11.6) compared with placebo (4.2 E/100 PY; 95% CI, 1.2-10.9).

The rates of opportunistic infections were low in all groups, and although numerically higher in the upadacitinib 15 mg group compared to placebo, these were based on a small number of events, and no opportunistic infections were reported in the upadacitinib 7.5 mg group. One case of opportunistic infection, that of Pneumocystis jiroveci pneumonia, was considered serious and led to discontinuation of upadacitinib in the 15 mg group. All other opportunistic infections were mild or moderate in severity and none led to discontinuation.

Notably, serious infection rates were numerically lower in the post-taper period with upadacitinib 7.5 mg (3.4 E/100 PY; 95% CI, 0.7-9.9) or 15 mg (3.9 E/100 PY; 95% CI, 1.6-8.1) relative to placebo (8.5 E/100 PY; 95% CI, 3.7-16.7) and Herpes zoster rates were similar with upadacitinib15 mg relative to placebo during and after the prespecified GC taper. Of the 4 opportunistic infections with upadacitinib 15 mg, 3 occurred during the prespecified GC taper and 1 after in a patient receiving GC escape therapy. The investigators also found that baseline GC dose did not have a clear impact on the occurrence of serious infections.

“The decrease in serious infection rates during the GC-free phase suggests concomitant use of GCs may contribute to the risk of serious infections,” Buttgereit and colleagues wrote.

 “Overall, these results, together with the superior efficacy of upadacitinib15 mg with a 26-week GC taper compared to placebo with a 52-week GC taper, support the potential benefits of a shorter GC taper period.”

During EULAR, AbbVie also presented biomarker data from SELECT-GCA. Among the key findings were that upadacitinib inhibits key immune pathways driving pathogenesis of GCA, including IL-6 and IFN-related proteins; UPA reduced IL-6 and IL-18, the monocyte attractant CCL7, and the IFN-associated chemokines CXCL9, CXCL10, and CXCL11, compared to placebo, indicating broad suppression of inflammatory mediators; and IL-6 levels distinctly differentiated responders from non-responders, which may offer insights into the mechanisms of response to treatment.

Buttgereit F, Winthrop KL, Calabrese LH, et al. Impact of Glucocorticoid Tapering in Giant Cell Arteritis: Analysis From the SELECT-GCA Trial. Presented at: EULAR Congress 2025; Barcelona, Spain; June 11-14. Presentation #OP0057

RINVOQ® (upadacitinib) Receives U.S. FDA Approval for Giant Cell Arteritis (GCA). News release. AbbVie. April 29, 2025. 

https://news.abbvie.com/2025-04-29-RINVOQ-R-upadacitinib-Receives-U-S-FDA-Approval-for-Giant-Cell-Arteritis-GCA

Christ L, Taylor S, Xu Y, et al. Impact of Treatment with Upadacitinib on Biomarkers Identified by Proteomics in Giant Cell Arteritis. Presented at: EULAR Congress 2025; Barcelona, Spain; June 11-14. Presentation #OP0022

New research supports the use of upadacitinib 15 mg with a shorter glucocorticoid tapering regimen in patients with giant cell arteritis (GCA), demonstrating a favorable benefit-risk profile compared to placebo with a longer taper. The SELECT-GCA trial showed lower rates of serious infections with upadacitinib, although herpes zoster rates were higher. Biomarker data revealed that upadacitinib inhibits key immune pathways, including IL-6 and IFN-related proteins, offering insights into treatment response mechanisms. These findings suggest potential benefits of a shorter glucocorticoid taper period in managing GCA.

New findings reveal upadacitinib's effectiveness in treating giant cell arteritis, highlighting reduced infection rates with shorter glucocorticoid tapering.

New Data Further Support Safety of Upadacitinib With 26-Week GC Taper for Giant Cell Arteritis

 and a history of cigarette-smoking who were treated with upadacitinib (RINVOQ) for up to 6 years had comparable incidence rates of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancy (excluding non-melanoma skin cancer) to those observed in a real-world population of people living with atopic dermatitis, new data suggest.

These data were the result of a recent study presented at the 2

025 Revolutionizing Atopic Dermatitis (RAD) Conference

 The study authors included such investigators as Naiem Issa, MD, PhD, a board-certified dermatologist at Forefront Dermatology. Issa et al highlighted atopic dermatitis as a persistent inflammatory condition linked to various complications such as VTE, MACE, and different forms of cancer (excluding nonmelanoma skin cancer or NMSC).

The investigators pointed to a pooled safety analysis from phase 3 clinical trials on upadacitinib, the results of which had demonstrated that rates of VTE, MACE, and malignancy in those with moderate-to-severe atopic dermatitis who were treated for up to 6 years with the drug were similar to—or even lower than—rates observed in the general population with the same skin condition. They sought in the current analysis to explore smoking history as a risk factor.

The long-term incidence of these events in those with moderate-to-severe atopic dermatitis treated with upadacitinib was assessed by Issa and coauthors, with participants being stratified by their smoking status at the point of baseline. The group included current/former smokers and compared them to ‘never smokers.’

Data in the investigators’ analysis were drawn from 3 randomized, multicenter, double-blind, placebo-controlled phase 3 studies: Measure Up 1 and 2 (NCT03569293, NCT03607422) and AD Up (NCT03568318).

 Adolescents and adults aged 12 to 75 years were included as subjects in these 3 studies, and they were randomized in a 1:1:1 ratio to be given oral upadacitinib at 15 mg, at 30 mg, or a placebo.

Throughout the Measure Up 1 and 2 studies, treatment was provided as monotherapy, whereas in the AD Up analysis, upadacitinib had been administered alongside topical corticosteroids. After the initial 16-week treatment period, patients on placebo were re-randomized to receive either UPA 15 mg or 30 mg, while those being given upadacitinib carried on with their assigned dose.

Issa and colleagues looked at rates of MACE, which was defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. They also looked at VTE, defined either as pulmonary embolism or deep vein thrombosis. Additionally, malignancies excluding NMSC were assessed. All of these were measured via exposure-adjusted incidence rates (EAIRs) per 100 patient-years (n/100 PY).

Comparisons with these outcomes were made to baseline rates in the general population of US patients with atopic dermatitis, with information on these patients being derived from a retrospective claims-based analysis of the Optum Clinformatics Data Mart. The investigators’ reference population would involve 50,447 individuals aged 12–75 years diagnosed with the skin disease between March 2017 - September 2024.

Those involved would be required to have either ≥1 inpatient or ≥2 outpatient atopic dermatitis claims. Issa et al statistically weighted the age and sex distribution of this reference group to match that of the upadacitinib phase 3 trial population.

Overall, the investigative team had included 2,683 participants from the upadacitinib trials in their safety analysis. Specifically, there were 1,337 in the 15 mg arm and 1,346 in the 30 mg arm. Among both the smoker and nonsmoker cohorts in this analysis who had been treated with the medication, VTE incidence was shown to be ≤0.2 per 100 PY, MACE incidence was shown to be ≤0.3 events per 100 PY, and malignancy incidence (not including NMSC) was shown to be ≤0.7 per 100 PY.

“Among patients with moderate-to-severe [atopic dermatitis] who received [upadacitinib] treatment for up to 6 years, incidence rates of MACE, VTE, and malignancy (excluding NMSC) were low,” the investigators concluded.

 “These rates were lower than or consistent with background rates observed in a real-world population of patients with [atopic dermatitis], regardless of smoking history.”

For any additional information on this topic or related topics in the atopic dermatitis space, including late-breaking data, view the 

Issa N, Stein Gold L, Guttman-Yassky E, et al. Patients with a Smoking History and Atopic Dermatitis: Long-Term Safety of Upadacitinib for MACE, VTE and Malignancy. Poster presented at: 2025 Revolutionizing Atopic Dermatitis Conference; June 6-7, 2025; Nashville, TN.

Irvine A, Silverberg J, Pechonkina A, et al. Efficacy and Safety of Upadacitinib Through 188 Weeks in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results. Presented as part of the 2024 Revolutionizing Atopic Dermatitis Mid-Year Virtual Update. December 8, 2024. Accessed June 12, 2025.

Stein Gold L, Shahriari M, Guttman-Yassky E, et al. Patients with Atopic Dermatitis Using Oral Contraceptive Pills or Hormone Replacement Therapy: Long-Term Safety of Upadacitinib for Major Adverse Cardiovascular Events, Venous Thromboembolism, or Malignancy (Excluding Nonmelanoma Skin Cancer). Poster presented at: 2025 Revolutionizing Atopic Dermatitis Conference; June 6-7, 2025; Nashville, TN.


These data suggest that smoking history did not impact rates of malignancy, MACE, and VTE among those with atopic dermatitis treated with upadacitinib.