Tralokinumab in Atopic Dermatitis: Mechanisms, Individualized Therapy, and Emerging Perspectives

J Clin Aesthet Dermatol. 2026;19(7 Suppl 1):S4–S11.

by Naiem T. Issa, MD, PhD; Jenny E. Murase, MD; Shanna Miranti, PA-C; Christopher G. Bunick, MD, PhD

Dr. Issa is with Forefront Dermatology, Vienna, Virginia; the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery at the University of Miami School of Medicine, Miami, Florida; and the George Washington University School of Medicine and Health Sciences, Washington, District of Columbia. Dr. Murase is with the Palo Alto Foundation Medical Group, Mountain View, California; and the University of California, San Francisco, San Francisco, California. Ms. Miranti is with Riverchase Dermatology, Naples, Florida. Dr. Bunick is with the Department of Dermatology and Program in Translational Biomedicine at the Yale School of Medicine, New Haven, Connecticut.

FUNDING: Funding for this article was provided by LEO Pharma.

DISCLOSURES: Dr. Issa has received funding from the following entities either as a speaker, consultant, advisor, or investigator: AbbVie, Almirall, Apogee, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Castle Biosciences, DermTech, Galderma, Incyte, Janssen, Journey, LEO Pharma, Lilly, Novartis, Organon, Ortho Dermatologics, Oruka, Pfizer, Primus, Regeneron, Sanofi, SUN Pharmaceuticals Industry, Topix, UCB, and Verrica Pharmaceuticals. Dr. Murase is on the speakers board for AbbVie, Galderma, LEO Pharma, Lilly, Pfizer, Regeneron, Sanofi, and UCB; has served on advisory boards for Arcutis, Blueprints Medicine, Bristol Myers Squibb, Galderma, LEO Pharma, Lilly, Pfizer, Regeneron, Sanofi, and UCB; and has provided dermatologic consulting services for AbbVie, Apogee Therapeutics, Attovia, Galderma, Lilly, Regeneron, Sanofi, UCB, and UpToDate. Ms. Miranti is currently a speaker, consultant, or advisory board member for the following companies: Arcutis, Dermavant/Organon, Galderma, Incyte, LEO Pharma, Ortho Dermatologics, SUN Pharmaceuticals Industry, SwiftUSA, and Verrica Pharmaceuticals; and is an editorial advisory board member of Dermatology Times (Guest Editor in Chief- Summer 2024) and JDNPPA. Dr. Bunick has served as an investigator and/or consultant for AbbVie, Almirall, Apogee, Arcutis, Castle Biosciences, Connect BioPharma, Dermavant, Galderma, Incyte, LEO Pharma, Lilly, Pfizer, Regeneron, Sanofi, South Beach Symposium, Teladoc, Triveni, UCB, and ZenZema.

Abstract: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease driven by a complex, heterogeneous cytokine milieu that extends well beyond the canonical T helper 2 (Th2) axis. The approval of targeted biologics—dupilumab, tralokinumab, lebrikizumab, and nemolizumab—has transformed the management of moderate-to-severe AD in adults and adolescents, yet fundamental differences in their mechanisms of action remain underappreciated in clinical practice. Tralokinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-13, blocks its engagement with IL-13 receptor alpha 1 (IL-13Rα1) and—unlike lebrikizumab—prevents interaction with IL-13 receptor alpha 2 (IL-13Rα2). Beyond direct IL-13 neutralization, tralokinumab has been shown to secondarily downregulate IL-22 and IL-4 receptor alpha, offering mechanistic advantages in patients with dupilumab-associated head and neck dermatitis and Th17-skewed comorbidities. In the absence of head-to-head trials, matching-adjusted indirect comparisons suggest efficacy parity among the 3 IL-13 targeted biologics, with tralokinumab demonstrating statistically superior Dermatology Life Quality Index outcomes vs dupilumab. Uniquely among approved AD biologics, tralokinumab has published long-term safety data across more than 4,600 patient-years demonstrating no excess malignancy and reduced rates of major adverse cardiovascular events and venous thromboembolism vs background rates in patients with AD. The following expert roundtable explores these mechanistic distinctions, their clinical translatability, the evolving warnings and precautions landscape, diagnostic stewardship, disease modification concepts, and the future of combination and multispecific biologic strategies in AD. Keywords: Eczema, inflammatory skin disease, biologic treatments, cytokine receptor, itch

Introduction

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases worldwide, affecting approximately 20% of children and up to 10% of adults in high-income countries, with a significant subset experiencing moderate-to-severe disease that warrants systemic intervention.^1,2 The immunopathogenesis of AD is characterized by impaired skin barrier function, dysregulated innate and adaptive immune responses, and a cytokine environment dominated, but not exclusively defined, by T helper 2 (Th2) inflammation. Interleukin (IL)-4 and IL-13 are central mediators of Th2-driven barrier dysfunction, pruritus, and immunoglobulin E (IgE) class switching, while Th1, Th17, and Th22 axes contribute variably across disease subtypes, body site involvement, age of onset, and individual patient comorbidity profiles.^3–5

The introduction of dupilumab, a monoclonal antibody blocking the shared IL-4 receptor alpha (IL-4Rα) subunit common to both the IL-4 and IL-13 signaling complexes, represented a watershed moment in AD therapeutics.^6,7 Subsequently, tralokinumab and lebrikizumab, both targeting IL-13 directly at distinct epitopes, extended the therapeutic armamentarium.^8–10 More recently, nemolizumab, targeting the IL-31 receptor alpha and addressing a neuronal itch-dominant pathway, and oral Janus kinase (JAK) inhibitors abrocitinib and upadacitinib, offering comprehensive cytokine suppression, have further diversified the landscape.^11,12

Despite this expansion, several critical gaps persist. Cross-trial comparisons are methodologically fraught due to heterogeneous patient populations, variable washout criteria, and differing concomitant therapy protocols. The mechanistic distinctions among IL-4Rα blockade, selective IL-13 neutralization, and IL-31 receptor antagonism have meaningful but underrecognized clinical implications for adverse event profiles, comorbidity management, and therapeutic sequencing. The potential for off-drug disease control, and whether it constitutes true disease modification, remains an area of active inquiry. Questions surrounding cutaneous T-cell lymphoma (CTCL) risk, diagnostic stewardship before and during biologic therapy, and the role of pharmacologically anticipated immune shifts are increasingly relevant as the prescribing community expands to include advanced practice providers. This roundtable convened 4 expert clinicians to examine these dimensions in depth, with a particular focus on tralokinumab’s distinct mechanism of action (MOA), its clinical profile relative to dupilumab and lebrikizumab, and practical frameworks for individualized biologic selection in adults and adolescents with moderate-to-severe AD.

Immunopathogenesis and the Relevance of Cytokine Architecture

The immunopathology of AD reflects the convergence of skin barrier defects, most notably filaggrin mutations and ceramide deficiency, with dysregulated type 2 immunity.^1,3 Damaged keratinocytes release epithelial alarmins (thymic stromal lymphopoietin [TSLP], IL-25, IL-33) that drive dendritic cell priming and preferential differentiation of naive T cells toward the Th2 phenotype.^4,13 IL-4 and IL-13, the signature Th2 cytokines, act through partially overlapping receptor complexes: the type I receptor (IL-4Rα/γc), primarily expressed on hematopoietic cells and mediating IgE class switching, and the type II receptor (IL-4Rα/IL-13Rα1), broadly expressed on nonhematopoietic cells including keratinocytes, fibroblasts, and smooth muscle, mediating barrier disruption, mucus production, and tissue remodeling.^4,14,15

IL-13 binds first to IL-13Rα1 with high affinity, after which IL-4Rα is recruited to form the signaling heterodimer. A second receptor for IL-13, IL-13Rα2, binds IL-13 with ultra-high affinity and, while its cytoplasmic tail lacks canonical JAK-signal transducer and activator of transcription proteins (STAT) signaling motifs, activates alternative pathways including Akt kinase signaling, with potential relevance to oncogenic processes.^14,15 Notably, IL-13Rα2 upregulation has been documented in metastatic breast cancer, glioblastoma, and colorectal malignancies, and antibodies targeting IL-13Rα2 are under active clinical investigation in oncology.¹⁴

Beyond the Th2 axis, head and neck AD, a particularly treatment-refractory subtype, is characterized by elevated IL-22 levels, implicating Th22 and Th17 pathways.^16,17 Psoriasiform reactions and arthralgias observed with IL-4Rα blockade have been mechanistically linked to Th17 disinhibition that emerges when Th2 suppression is achieved without concomitant modulation of adjacent immune axes, a phenomenon increasingly recognized in real-world practice.^18,19

Mechanisms of Action: Dupilumab, Tralokinumab, and Lebrikizumab

Dupilumab is a fully human IgG4 monoclonal antibody that binds IL-4Rα and competitively inhibits both IL-4 and IL-13 signaling through both the type I and type II receptor complexes.^6,20 Structural analyses have revealed that dupilumab engages only approximately half of the natural IL-4 and IL-13 epitope on IL-4Rα and lacks stabilizing interactions across the hinge region bridging receptor domains 1 and 2, resulting in relatively less stable receptor binding compared to next-generation IL-4Rα inhibitors in development.²¹ Emerging phase 3 data for rademikibart, a next-generation IL-4Rα inhibitor, presented at the 2026 American Academy of Dermatology Annual Meeting demonstrated conjunctivitis rates at or below placebo, raising the hypothesis that some dupilumab-associated adverse events may reflect suboptimal binding efficiency rather than intrinsic hazards of the class.

Tralokinumab is a fully human IgG4 monoclonal antibody targeting an epitope on IL-13 that directly overlaps with the IL-13Rα1 binding interface. By occupying this site, tralokinumab sterically prevents IL-13 from engaging IL-13Rα1, blocking type II receptor assembly upstream of IL-4Rα recruitment.^8,14 Critically, tralokinumab-bound IL-13 cannot engage IL-13Rα2.¹⁴ Transcriptomic analyses from long-term extension trial data (ECZTEND) demonstrate secondary downregulation of IL-22 and IL-4Rα gene expression, effects not captured by its top-line MOA characterization, suggesting more extensive immunomodulatory activity than IL-13 neutralization alone.²²

Lebrikizumab binds IL-13 at a distinct epitope distal to the IL-13Rα1 engagement site. This antibody-IL-13 complex can still engage IL-13Rα1 but sterically prevents IL-4Rα from completing the heterodimeric type II signaling complex.^10,15,23 Importantly, lebrikizumab-bound IL-13 retains the capacity to engage IL-13Rα2. This raises the possibility that lebrikizumab-IL-13-IL-13Rα1 complexes may be internalized and degraded, effectively reducing available IL-13Rα1 surface expression—a mechanism that would constitute indirect IL-4 inhibition by depleting the type II receptor pool.^21,23 This hypothesis may account for the partial overlap in safety signals between lebrikizumab and dupilumab (arthralgias, herpes zoster reactivation) that is less pronounced with tralokinumab.²⁴

Intraclass switching among these biologics is supported by mechanistic and real-world precedent. Just as switching among IL-23 inhibitors, TNF-alpha inhibitors, or IL-17 inhibitors in psoriasis can rescue inadequate responders, switching among AD biologics with distinct epitopes and thermodynamic binding properties can yield meaningful clinical benefit.^21,23 The concept that dupilumab inadequate response precludes favorable response to an IL-13-targeted agent is mechanistically unfounded and clinically inaccurate.

Clinical Trial Design: Limitations of Cross-Trial Comparisons

The pivotal trials for dupilumab (LIBERTY AD SOLO), tralokinumab (ECZTRA), and lebrikizumab (ADvocate, ADhere) share common primary endpoints—Investigator Global Assessment (IGA) 0/1 and EASI-75 at 16 weeks—but differ substantially in patient eligibility criteria, washout periods, background therapy allowances, and permitted rescue medication protocols.^6,8,9,10,25 These design heterogeneities render naive cross-trial comparisons methodologically invalid, yet they remain pervasive in clinical discourse, at podium presentations, and in indirect network meta-analyses.

Tralokinumab’s pivotal trial data, while efficacious in absolute terms, has been systematically underestimated in network meta-analyses due to more stringent entry criteria and limited concomitant topical corticosteroid use in its registration trials, as well as the absence of a higher loading dose strategy later adopted by lebrikizumab.^8,9,26 Real-world observations consistently suggest that tralokinumab’s clinical efficacy exceeds its trial data while maintaining a high degree of safety.^27,28

Matching-adjusted indirect comparisons (MAICs) represent a methodologically superior alternative to aggregate-data network meta-analyses by reweighting individual patient-level data to align baseline characteristics across trials. MAICs comparing tralokinumab and dupilumab, and tralokinumab and lebrikizumab, consistently demonstrate efficacy parity on skin clearance and itch endpoints, with no drug achieving statistically superior outcomes on clinical response measures.^29,30 One important exception is Dermatology Life Quality Index (DLQI) improvement, which was statistically significantly greater with tralokinumab vs dupilumab (mean change: −12.1 vs −10.4; P=0.005 at Week 32), reflecting the impact of reduced adverse events on patient-reported quality of life.²⁹

Warnings, Precautions, and the Adverse Event Landscape

Dupilumab-associated head and neck dermatitis. A clinically important and increasingly recognized phenomenon associated with dupilumab use is the development of de novo facial and head and neck dermatitis (dupilumab facial redness [DFR]), estimated to affect 4% to 43% of treated patients.³¹ Single-cell RNA sequencing of biopsies from affected skin has revealed strong increases in type 22-associated markers (IL-22, aryl hydrocarbon receptor [AhR]) especially in oligoclonally expanded T cells, with enhanced keratinocyte activation and IL-22 receptor upregulation, consistent with a Th22-skewed inflammatory phenotype.¹⁶ Mechanistically, IL-4Rα blockade suppresses Th2 immunity while potentially disinhibiting Th17 and Th22 responses; head and neck AD is already characterized by elevated IL-22 irrespective of dupilumab exposure.^16,17 Dupilumab’s package insert now includes, under postmarketing experience (Section 6.2), facial skin reactions encompassing erythema, scaling, papules, new-onset psoriasis, and vasculitis.²⁰

Tralokinumab’s demonstrated secondary downregulation of IL-22 provides a mechanistic basis for its preferential use in patients with prominent head and neck involvement or those experiencing DFR on dupilumab.²² Switching from dupilumab to tralokinumab has been associated with resolution of facial dermatitis in clinical practice. However, clinicians are cautioned that allergic contact dermatitis may compound or mimic DFR, and patch testing prior to attributing persistent facial redness to the biologic itself is an important diagnostic step before escalating or switching therapy.^32,33

Psoriasis, psoriatic arthritis, and arthralgias. Psoriasiform eruptions and psoriatic arthritis have emerged as recognized complications of dupilumab therapy, now appearing on the drug’s prescribing label with a specific recommendation that providers counsel patients regarding these risks.²⁰ T-cell polarization skewing toward Th17 upon Th2 suppression acts as the core mechanism, characterized by upregulation of the IL-23/Th17 axis.^18,19 Arthralgias are also reported on the dupilumab label and have been observed with lebrikizumab, consistent with indirect IL-4 inhibition via IL-13Rα1 receptor depletion as discussed above.^20,34 Joint pain is notably absent from tralokinumab’s prescribing information, and resolution of pre-existing arthralgias following the switch from dupilumab to tralokinumab has been documented.^24,35 A pharmacovigilance study utilizing the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database reinforces the consistency of these Th17-skewing patterns across biologic agents.³⁶

Conjunctivitis. Conjunctivitis rates in pivotal AD trials show a gradient from dupilumab (highest) to lebrikizumab to tralokinumab (lowest), consistent with the mechanistic hierarchy of IL-4Rα blockade, indirect IL-4 inhibition, and IL-13 cytokine neutralization, respectively.³⁷ Real-world Scandinavian registry data confirm this gradient, with dupilumab-associated conjunctivitis rates of 25% in long-term follow-up vs substantially lower rates with tralokinumab.¹⁷ A shared mechanistic basis—Th17 skewing affecting conjunctival goblet cell homeostasis and tear film stability—unifies the conjunctivitis, psoriasis, psoriatic arthritis, and facial dermatitis observations under a common pathophysiological framework.³⁷

Pharmacologically anticipated immune responses. Inflammatory responses observed in patients receiving nemolizumab, and immune shifts associated with other biologic transitions, are better characterized as pharmacologically anticipated compensatory immune responses than as true paradoxical events.^11,38 In patients with mixed Th2/Th17 or Th2/Th1 inflammatory states, selective suppression of the dominant Th2 component may unmask a previously subordinate inflammatory axis, manifesting as psoriasiform eruptions, photosensitive dermatoses, or clinical worsening.^5,13 Innate lymphoid cells (ILC) 1, 2, and 3 corresponding to Th1, Th2, and Th17 programs play a significant role in this dynamic and are less susceptible to downregulation by regulatory T cells, amplifying the potential for phenotypic unmasking. Combination strategies, such as tralokinumab plus nemolizumab in patients fulfilling criteria for both AD and prurigo nodularis indications, are emerging in clinical practice with promising outcomes.¹¹

Long-term safety: MACE, malignancy, and VTE. Tralokinumab is uniquely positioned among approved AD biologics as the only agent with published comprehensive long-term safety data extending beyond 4,600 patient-years of exposure, reporting rates of malignancy, major adverse cardiovascular events (MACE), and venous thromboembolism (VTE).^27,39 These data demonstrate that tralokinumab does not increase malignancy risk beyond background rates in the AD population, and shows MACE rates of approximately 0.3 events per 100 patient-years compared to a background of approximately 0.63 events per 100 patient-years in untreated AD patients, and a favorable VTE profile.^27,39,40 AD itself is a systemic inflammatory disease associated with elevated cardiovascular and thromboembolic risk, and effective treatment may attenuate these outcomes.⁴¹ Comparable long-term safety publications for MACE, malignancy, and VTE are not yet available for dupilumab, lebrikizumab, or nemolizumab.

CTCL, IL-13Rα2, and the Oncological Landscape in Biologic-Treated AD

The potential association between biologic therapy for AD—particularly dupilumab—and the unmasking or exacerbation of CTCL has garnered substantial attention. CTCL cases have been reported in patients on dupilumab, and isolated cases have emerged with tralokinumab and lebrikizumab, complicating attribution to any single mechanism. Whether these cases represent true drug-associated oncogenic events, diagnostic delays in patients with CTCL mimicking treatment-refractory AD, or coincidental occurrences in a population predisposed to both conditions, remains unresolved.⁴²

Two mechanistic hypotheses warrant consideration. The first implicates IL-4’s role in the differentiation of early undifferentiated T cells—including potential precursors of malignant T-cell clones—as particularly relevant to IL-4Rα blockade. The second centers on IL-13Rα2 and its increasingly recognized oncogenic signaling capacity.

IL-13Rα2 was historically classified as a decoy receptor on the basis of its short cytoplasmic tail and presumed inability to engage canonical JAK-STAT signaling. This characterization is now known to be incomplete. IL-13Rα2-mediated signaling has been demonstrated through multiple STAT6-independent pathways—including activation of activator protein-1 (AP-1), extracellular signal-regulated kinase (ERK), and the Src/PI3K/Akt/mTOR cascade—promoting tumor invasion, metastasis, and TGF-β1 production.^43,44 IL-13Rα2 is overexpressed in a broad range of solid tumors and correlates with advanced disease stage and poor prognosis in glioblastoma (approximately 76% of WHO grade IV gliomas), colorectal carcinoma, adrenocortical carcinoma, pancreatic ductal adenocarcinoma, breast cancer, ovarian cancer, lung cancer, and gastric cancer, among others.^43–45 This tumor-restricted overexpression has made IL-13Rα2 an attractive and actively pursued immunotherapy target across oncology.

Multiple therapeutic strategies targeting IL-13Rα2 are in clinical development. Immunotoxin approaches, most notably cintredekin besudotox (IL-13 fused to truncated Pseudomonas exotoxin PE38QQR), demonstrated feasibility and early signals of activity in phase 1 and phase 2 trials in recurrent glioblastoma via convection-enhanced delivery.⁴³ Chimeric antigen receptor (CAR) T-cell therapies targeting IL-13Rα2 represent the most advanced current strategy. A phase 1 trial in 65 patients with recurrent high-grade glioma, reported in Nature Medicine in 2024, demonstrated the safety and feasibility of locoregionally administered IL-13Rα2–targeting CAR T cells via intratumoral and intraventricular routes, with evidence of bioactivity including central nervous system cytokine elevation and tumor immune contexture changes.⁴⁶ Subsequently, a phase 1 trial of bivalent CAR T cells targeting both EGFR and IL-13Rα2, presented at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting and published in Nature Medicine, demonstrated feasibility and tolerability of intraventricular administration in multifocal recurrent glioblastoma, with signals of clinical activity including a partial response and durable stable disease.⁴⁷ Cancer vaccine strategies targeting IL-13Rα2 are also in development.⁴³

These oncology data are relevant to the AD biologic discussion for 2 reasons. First, they firmly establish that IL-13Rα2 is not a passive decoy receptor but an active signaling molecule with demonstrable oncogenic function, a designation that should be retired from the dermatology lexicon when describing this receptor. Second, the distinct epitopes of tralokinumab and lebrikizumab determine whether the bound IL-13 cytokine can still engage IL-13Rα2: tralokinumab’s epitope overlaps directly with the IL-13Rα2 binding interface, preventing engagement entirely, while lebrikizumab’s epitope permits the lebrikizumab-IL-13 complex to bind IL-13Rα2.^14,23 Whether this differential IL-13Rα2 engagement carries clinical significance in the context of CTCL risk or malignant T-cell biology remains scientifically unresolved. Because CTCL cases have been reported across all three approved AD biologics, caution is warranted before attributing risk solely to any single mechanism or receptor interaction.

Clinically, the CTCL question imposes a heightened obligation for diagnostic vigilance, particularly in adults with new-onset, severe, or treatment-refractory disease; older patients; and those with atypical features such as photosensitivity, mildly positive antinuclear antibody (ANA), or the presence of T-cell clones on biopsy. Dermatology lymphoma specialists have expressed preference for JAK inhibitors (upadacitinib, abrocitinib) over dupilumab in patients in whom CTCL is on the diagnostic differential, reflecting concern about the immunological consequences of IL-4Rα blockade in the presence of potentially malignant T-cell clones.^12,42

Disease Control, Off-Drug Responses, and Patient Counseling

The withdrawal arms incorporated into tralokinumab (ECZTRA 1 and 2) and lebrikizumab (ADvocate 1 and 2) trials offer insights into the durability of treatment response after drug discontinuation. Among tralokinumab-treated patients achieving clear or almost-clear skin (IGA 0/1) at Week 16, approximately one quarter to one third maintained this response through Week 52 off drug.⁹ Lebrikizumab’s off-drug data present numerically higher rates, though methodological differences in imputation strategies and study designs preclude direct comparison.¹⁰

These data do not yet meet the scientific bar for disease modification, a concept requiring mechanistic evidence of sustained immunological reprogramming rather than pharmacokinetic drug persistence. “Off-drug disease control” is a more accurate characterization than “remission” in the oncologic sense, the latter carrying survival-based prognostic implications not yet applicable to dermatologic biologics. Tralokinumab’s secondary downregulation of IL-22, IL-4Rα, and multiple Th17/Th22 pathway genes observed in transcriptomic data at 2 years raises the possibility of cumulative immunomodulatory effects contributing to deeper or more durable responses—a hypothesis warranting prospective investigation.²²

In clinical practice, off-drug response data are most valuably deployed in conversations with biologic-hesitant patients or caregivers. Framing the treatment initiation as a defined therapeutic trial—assessing response at 16 weeks and then considering dose interval extension or a structured drug holiday—may lower the psychological barrier to starting therapy without overpromising durability. The flexibility of tralokinumab’s maintenance dosing (from every-2-weeks to every-4-weeks after initial response) provides a practical tool for patient engagement, particularly among adolescents and adults seeking fewer injections.^9,35

Expert Roundtable Discussions in Atopic Dermatitis

The following expert discussions provide real-world insights on the mechanism of action, clinical differentiation, safety considerations, and patient-centered management of tralokinumab and the broader biologic landscape in atopic dermatitis.

Mechanism of action: does it matter clinically?

Shanna Miranti, PA-C: When I consider starting a biologic for a patient, I am truly weighing all of the data alongside the age of the patient. My practice has a heavy pediatric focus, and familiarity with dupilumab’s younger-age indications gives me a lot of confidence there. That said, I have many teenage patients who don’t want every-two-week injections and are looking for a better dosing schedule. Now that the IL-13 story has matured, I appreciate that we can achieve excellent efficacy with more targeted cytokine blockade, while potentially sidestepping some of the adverse events associated with IL-4 receptor blockade. And I have been genuinely pleasantly surprised when switching patients from dupilumab to an IL-13 agent—we can often recapture efficacy, sometimes with a more favorable dosing schedule.

Jenny Murase, MD: Binding affinity and dissociation rate are important, and we unfortunately do not have head-to-head trials. When you think about the IL-4Rα blockade story vs selective IL-13 neutralization, the mechanism of action is critically relevant—particularly when something goes wrong. I have over a thousand patients on dupilumab, and so I see the head and neck dermatitis more than most. When I put those patients on an IL-13 agent, the facial redness goes away. That is probably one of the strongest arguments I have for reaching for an IL-13 agent in a patient with significant facial involvement. The face is the window to the world—we are not talking about their elbows. We are talking about a cosmetically sensitive area that directly affects self-esteem and emotional wellbeing. When you suppress Th2 so completely and systemically, you run into situations where you may be stripping away a protective IL-4 effect on early T-cell differentiation, potentially allowing autoimmune conditions like psoriatic arthritis to expand, or unmasking a smoldering Th1 or Th17-driven condition. I also think carefully about non-Th2 comorbidities. Conditions that live in a Th1 world—chronic actinic dermatitis, cutaneous lupus, polymorphous light eruption—require us to accept some compromise of cell-mediated immunity to treat. But if a patient has a Th17-driven comorbidity, like psoriatic arthritis or rheumatoid arthritis, we can elect the IL-13 blocker alone and avoid driving further Th17 imbalance. Joint pain is not even on tralokinumab’s label, and in my experience, patients who present with new joint pain on dupilumab often have an underlying condition being unmasked. I always evaluate with a rheumatoid factor and erythrocyte sedimentation rate and refer to rheumatology in those cases.

Christopher G. Bunick, MD, PhD: These are 3 very different drugs—thermodynamically different, pharmacologically different—and you cannot lump them together. Each works on a different thermodynamic step of type I and type II receptor assembly. Intraclass switching is proven across every other biologic class in dermatology—IL-23 inhibitors, TNF-alpha inhibitors, IL-17 inhibitors—and it is equally valid here. The idea that you must leave the class entirely when dupilumab does not work is mechanistically indefensible. Tralokinumab is an excellent biologic of choice in adults and adolescents. The reason is efficacy-to-safety ratio: in my assessment, tralokinumab may have the highest efficacy-to-safety ratio among the approved AD biologics. I saw it firsthand when I began switching patients—conjunctivitis resolved, facial dermatitis cleared, arthralgias improved. On the tralokinumab-vs-lebrikizumab question: when you inhibit at tralokinumab’s epitope, you prevent IL-13 from engaging IL-13Rα1 upstream of any receptor assembly. Lebrikizumab’s bound IL-13 can still engage IL-13Rα1, and I believe that complex is internalized and degraded, effectively reducing available IL-13Rα1—making lebrikizumab an indirect IL-4 inhibitor. That likely explains why we see some arthralgias and herpes signals with lebrikizumab that more closely resemble dupilumab than tralokinumab. Critically, tralokinumab—in its long-term transcriptomic data—is the only IL-13 agent to date shown to secondarily downregulate IL-22, a mechanistic advantage in patients with head and neck AD given that this anatomical site already exists in an IL-22-elevated environment.

Clinical trial design and indirect comparisons.

CB: Cross-trial comparison is something we are explicitly taught not to do, and yet we do it everywhere—at the podium, in publications, in clinic. This has hurt tralokinumab more than any other AD drug, because the trial data are the weakest numerically. But there are reasons why that occurred, and trial data are not real-world data. My own clinical experience with tralokinumab far outperforms its trial data. MAICs are a much more rigorous analytical approach than indirect network meta-analyses, because you are reweighting individual patient-level data rather than comparing aggregates. The main takeaway from both the tralokinumab-vs-dupilumab and tralokinumab-vs-lebrikizumab MAICs is parity—no drug is superior on clinical response measures—with one important exception: DLQI improvement was statistically significantly in favor of tralokinumab over dupilumab. Quality of life matters, and that finding speaks directly to the patient experience. I also want to highlight what I believe is the single most important but least discussed piece of tralokinumab data: it is the only biologic with published long-term safety data reporting MACE, malignancy, and VTE across more than 4,600 patient-years of exposure. The malignancy rates are no different from background AD population rates. MACE rates are approximately halved vs background. VTE rates are lower as well. AD is a systemic inflammatory disease with elevated cardiovascular and thrombotic risk, and tralokinumab is the only biologic that can currently claim published evidence of potentially lowering those event rates.

SM: As all these drugs achieve lower age indications, every one of us is going to need to become very familiar with intraclass switching and biologic sequencing. The pediatric space is particularly exciting and complex. I am watching closely to see whether the IL-13 agents match dupilumab’s impressive data on growth trajectory restoration in pediatric patients—because if they do, or exceed it, that will significantly shift first-line recommendations in that age group.

Warnings, precautions, and diagnostic stewardship.

JM: I am currently deputy chair of the clinical guidelines committee, and when I joined, I noted immediately that there was insufficient mention of diagnostic testing—and that, in my view, is an ethical issue. If a patient is placed on tralokinumab and continues to have redness on their face and hands, and is not offered a patch test, and is instead escalated to a JAK inhibitor, and then develops a venous thromboembolism or a malignancy—when the answer was to change their shampoo—that is unethical. We are diagnosticians, and therefore we are the stewards of these powerful therapeutics. The dupilumab label now specifically states in its warnings and precautions that providers should counsel patients on the risk of psoriasis and arthralgia. How many dermatologists are actually doing that? If more providers read those two paragraphs in the dupilumab label, I believe they would prescribe tralokinumab more often. The company is telling us—we must discuss this with our patients.

SM: I agree completely. A lot of providers appreciate that no mandatory pretesting is required before initiating biologics—but the absence of required testing does not mean testing is unnecessary when outcomes fall short of expectations. We need to take biopsies when the clinical picture does not add up, and offer diagnostic workup before committing a patient to escalating immunosuppression. That is the standard of care, even if it is not always the path of least resistance.

CB: The Th17 skewing mechanism unifies a lot of what we see with dupilumab: facial dermatitis, psoriasis, psoriatic arthritis, conjunctivitis—all of these have a Th17 explanation, and pharmacovigilance data from the FAERS database reinforce these phenotypic shift patterns across drugs, showing consistency that supports everything we are seeing clinically. For providers counseling patients on dupilumab, those label disclosures about psoriasis and arthralgia are not optional—they are required per the product label. Reading those paragraphs in the label should prompt a frank conversation with patients and, in many cases, a reconsideration of first-line agent selection.

CTCL and IL-13Rα2.

CB: The CTCL situation is genuinely puzzling, and I want to be honest about that. Some of the cases are almost certainly diagnostic problems—recognition of CTCL is highly dependent on training and exposure. I think the IL-4 story—the impact of systemic IL-4Rα blockade on early undifferentiated T cells—is a more compelling mechanistic hypothesis at this stage, because CTCL cases have appeared with tralokinumab and lebrikizumab as well, which complicates any argument centered solely on IL-13Rα2. That said, we must stop calling IL-13Rα2 a decoy receptor. That terminology implies no function, and the oncology literature has definitively disproven it. We know this receptor signals through STAT6-independent pathways—AP-1, ERK, Akt/mTOR—to promote tumor invasion, metastasis, and TGF-β production. It is overexpressed in glioblastoma, colorectal cancer, pancreatic cancer, breast cancer, ovarian cancer, and more—and it correlates with advanced disease and poor prognosis in all of them. Oncologists are actively targeting this receptor with CAR T cells and immunotoxins in clinical trials right now. A phase 1 trial of IL-13Rα2–targeted CAR T cells in 65 patients with recurrent glioblastoma was published in Nature Medicine in 2024. Another phase 1 trial of bivalent CAR T cells targeting both EGFR and IL-13Rα2 was presented at ASCO 2025 and published in Nature Medicine. This is a receptor being exploited therapeutically in cancer precisely because of its oncogenic signaling capacity. So the question of whether it matters that tralokinumab prevents IL-13 from binding IL-13Rα2 while lebrikizumab permits it is a scientifically legitimate and deeply important one that we do not yet have the clinical data to answer. I also worry about medicolegal pressure going forward: as CTCL cases accumulate and litigation follows, dermatologists may feel pressure to avoid writing AD biologics altogether if they believe they could be held liable for continuing to prescribe in the face of known risk signals.

JM: I have cared for extremely complex patients—presented at UCSF and Stanford grand rounds—where there were clonal T cells on biopsy, a photosensitive component, a mildly positive ANA, and a clinical picture that sat ambiguously between AD and early mycosis fungoides. The lymphoma specialist I collaborate with allows me to use upadacitinib or abrocitinib in that context, but not dupilumab. That speaks volumes about where expert opinion sits on the oncological risk hierarchy of these drugs. I have seen lymphoma progress rapidly in the context of biologic therapy for presumed AD. The point about IL-13Rα2 resonates with me. If we know from the oncology world that this receptor is a legitimate signaling driver in glioblastoma and colon cancer—significant enough that there are now CAR T-cell trials targeting it—then we have to at least ask the question of whether blocking its engagement, as tralokinumab does, vs permitting it, as lebrikizumab does, has consequences in a patient population that already sits at elevated risk of lymphoma. We do not have the answer yet, but the question is valid and deserves scientific investigation. Any patient in whom CTCL is even remotely on the clinical radar deserves careful diagnostic evaluation before committing to a biologic.

SM: Adult-onset AD rarely exists in a vacuum—particularly in older patients, who carry a much greater comorbidity burden. There needs to be clinical guidance around new-onset, significant adult AD and whether a biopsy to evaluate for CTCL should be standard prior to initiating biologics or systemic JAK inhibitors. That type of algorithmic guidance would be enormously helpful for the advanced practice provider community, which is increasingly comfortable prescribing biologics and gaining confidence with JAK inhibitors, but may lack the clinical framework for recognizing the more complex differential. And as the science around IL-13Rα2 continues to evolve—with oncologists actively targeting it in glioblastoma trials—I think we as dermatology clinicians need to stay engaged with that literature. These are not separate conversations.

Pharmacologically anticipated immune responses and combination strategies.

JM: I do not like the term ‘paradoxical reaction.’ What I am observing clinically is a pharmacologically anticipated response to the therapeutic. We have patients presenting with what looks like classic AD who clear on a Th2 agent—but so many patients actually present with a mix of Th2, Th17, and Th1 inflammation. When we suppress the dominant Th2 component, we unmask the other. You see this most clearly with nemolizumab, because IL-31 has no receptors on T cells—it acts on cutaneous nerves. It addresses itch and burning, but it does not have a meaningful anti-inflammatory effect on the T-cell milieu. I think of this as the ‘lymphocyte trumpet’: if we push down on Th2, we need to ask what is going to happen to Th17 and Th1. My approach when I see Th17 unmasking on tralokinumab—say, psoriasiform changes in the scalp or intertriginous areas—is to add a Th17-targeted therapy rather than switch or escalate to systemic immunosuppression. The combination of tralokinumab plus nemolizumab, for patients who fulfill both an AD and prurigo nodularis indication, works very well in my experience. The future of this disease is going to involve combining targeted biologics rather than defaulting to broad systemic immunosuppression.

SM: Before adding a second biologic, I consider whether a topical PDE4 inhibitor or an aryl hydrocarbon receptor agonist—which has demonstrated potential for blocking Th17, IL-4, and IL-13—might address residual or unmasked inflammation without requiring a systemic switch. If the affected surface area is limited enough, keeping the biologic and managing the breakthrough with an advanced topical is an elegant and immunologically conservative solution.

CB: I agree—it is not paradoxical, it is compensatory. These are predictable immunological responses based on what we know about cytokine biology and drug pharmacology. The reason bi- and trispecific antibodies are being developed is precisely because the cytokine milieu is diverse and heterogeneous in AD. Each patient’s cytokine signature across Th1, Th17, Th2, and Th22 is not fixed—it shifts over time. JAK inhibitors sit at the top of network meta-analyses largely because they suppress more cytokines more completely. The biologic industry’s response is to combine targets in a single molecule, but not all combinations will succeed. My view is that any drug failing to account for IL-22–related head and neck AD will struggle in this disease.

Off-drug response and patient counseling.

CB: At approximately 32 weeks after drug withdrawal, roughly 25% of patients who achieved clear or almost-clear skin on tralokinumab maintain that response. I prefer the term ‘off-drug disease control’ over ‘remission.’ In dermatology, we have to be careful with that word—patients hear ‘remission’ and think cancer, 5-year survival. That is a very high bar, and we are not there yet. None of the underlying science has proven true disease modification in the sense of mechanistic reprogramming we can predict and replicate. What we have is evidence of deep, durable responses in a meaningful subset of patients, and that is still worth discussing. I prefer to underpromise and overdeliver in clinic: I explain the disease is long-term and not curable, get the patient better, and then down the road revisit whether we can space injections or consider a drug holiday.

JM: For me, the clinical question is: are they getting to a point where they forget they have the disease? Can they go on a trip and forget their topicals and still be fine for 2 or 3 weeks? That is what this data is pointing toward—not a cure, but a meaningful reduction in the daily burden of disease. And that is a powerful thing to offer a patient who has been managing this condition for years.

SM: The very first question patients ask after we build a treatment plan together is, “When can I stop?” The honest answer is that it depends. But having the withdrawal data lets me say something concrete: roughly 1 in 4 patients who clear on tralokinumab are still clear a year after stopping. And the ability to extend the injection interval from every 2 weeks to every 4 weeks is something patients respond to very positively. Framing this as a lifelong condition we will manage together—not a permanent daily medication—while using the off-drug data as a realistic milestone, is a much more empowering conversation.

Conclusion

Tralokinumab occupies a distinct and mechanistically well-characterized position within the landscape of approved biologics for moderate-to-severe AD. Its selective neutralization of IL-13—preventing engagement with both IL-13Rα1 and IL-13Rα2, and secondarily downregulating IL-22 and IL-4Rα—distinguishes it thermodynamically and pharmacologically from dupilumab and lebrikizumab, with clinically meaningful implications for adverse event profiles, patient selection, and therapeutic sequencing.^8,14,21,22 MAIC analyses confirm efficacy parity with dupilumab and lebrikizumab, with tralokinumab demonstrating superior patient-reported quality-of-life outcomes vs dupilumab.²⁹ Its comprehensive long-term safety data—uniquely available among approved AD biologics—provides reassurance regarding MACE, malignancy, and VTE risk, and raises the prospect of cardiovascular benefit through effective control of systemic Th2 inflammation.^27,39

The expanding oncology literature on IL-13Rα2 demands a reassessment of how this receptor is discussed in dermatology. Far from a passive decoy receptor, IL-13Rα2 is now established as an active oncogenic signaling molecule—targeted by CAR T cells and immunotoxins in clinical trials for glioblastoma and other solid tumors—whose differential engagement by tralokinumab vs lebrikizumab may carry as-yet-uncharacterized implications for the CTCL risk landscape in AD patients.^43,44,46,47 This question warrants scientific investigation with the same rigor applied to cardiovascular and ocular safety endpoints.

Individualized biologic selection requires integration of cytokine biology, comorbidity assessment, anatomical disease distribution, patient-reported priorities, and diagnostic rigor. Intraclass switching is both mechanistically valid and clinically supported, and the concept that dupilumab failure mandates a change in drug class is scientifically inaccurate.^21,23 Diagnostic stewardship—including patch testing in appropriate candidates and biopsy in treatment-refractory or atypical presentations—remains an ethical and clinical imperative regardless of the biologic selected.^32,33,48 As the biologic therapeutic landscape expands toward bi- and trispecific antibodies and combination biologic strategies, a mechanistic understanding of cytokine biology will only become more essential for optimizing patient outcomes in atopic dermatitis.

References

1. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396(10247):345–360.
2. Laughter MR, Maymone MBC, Mashayekhi S, et al. The global burden of atopic dermatitis: lessons from the global burden of disease study 1990–2017. Br J Dermatol. 2021;184(2):304–309.
3. Weidinger S, Beck LA, Bieber T, et al. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1):1.
4. Brunner PM, Guttman-Yassky E, Leung DYM. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(4S):S65–S76.
5. Czarnowicki T, He H, Krueger JG, Guttman-Yassky E. Atopic dermatitis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol. 2019;143(1):1–11.
6. Simpson EL, Bieber T, Guttman-Yassky E, et al; SOLO 1 and SOLO 2 Investigators. Two phase 3 trials of dupilumab vs placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335–2348.
7. Beck LA, Thaçi D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371(2):130–139.
8. Wollenberg A, Blauvelt A, Guttman-Yassky E, et al; ECZTRA 1 and ECZTRA 2 study investigators. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J Dermatol. 2021;184(3):437–449.
9. Silverberg JI, Toth D, Bieber T, et al; ECZTRA 3 study investigators. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. Br J Dermatol. 2021;184(3):450–463.
10. Silverberg JI, Guttman-Yassky E, Thaçi D, et al; ADvocate1 and ADvocate2 Investigators. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis. N Engl J Med. 2023;388(12):1080–1091.
11. Silverberg JI, Wollenberg A, Reich A, et al; ARCADIA 1 and ARCADIA 2 Study Investigators. Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials. Lancet. 2024;404(10451):445–460.
12. Davis DMR, Drucker AM, Alikhan A, et al. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies. J Am Acad Dermatol. 2024;90(2):e43–e56.
13. Furue M, Chiba T, Tsuji G, et al. Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies. Allergol Int. 2017;66(3):398–403.
14. Popovic B, Breed J, Rees DG, et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13Rα1 and IL-13Rα2. J Mol Biol. 2017;429(2):208–219.
15. Teixeira C, Yilmaz O, Bernardo D, Torres T. IL-13 inhibition in the treatment of atopic dermatitis – new and emerging biologic agents. J Investig Allergol Clin Immunol. 2024;34(5):285–296.
16. Tsoi LC, Hacini-Rachinel F, Fogel P, et al. Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells. Nat Commun. 2024;15(1):2888.
17. Egeberg A, Thyssen JP, Schmid-Grendelmeier P, et al. A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: ineffectiveness in head-and-neck dermatitis. J Eur Acad Dermatol Venereol. 2023;37(5):1046–1055.
18. Bridgewood C, Wittmann M, Macleod T, et al. T helper 2 IL-4/IL-13 dual blockade with dupilumab is linked to some emergent T helper 17-type diseases, including seronegative arthritis and enthesitis/enthesopathy, but not to humoral autoimmune diseases. J Invest Dermatol. 2022;142(10):2660–2667.
19. Su Z, Zeng YP. Dupilumab-associated psoriasis and psoriasiform manifestations: a scoping review. Dermatology. 2023;239(4):646–657.
20. Dupixent (dupilumab) [prescribing information]. Bridgewater, NJ and Tarrytown, NY: Sanofi-Aventis U.S. LLC and Regeneron Pharmaceuticals, Inc.; 2024.
21. Bunick CG. Biologic therapies targeting type 2 signaling in atopic dermatitis: a comparative review of structural and thermodynamic differences in mechanism of action. J Invest Dermatol. 2024. [Epub ahead of print]
22. Guttman-Yassky E, Kabashima K, Staumont-Sallé D, et al. Targeting IL-13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years. Allergy. 2024;79(6):1560–1572.
23. Simpson EL. Tralokinumab therapy for moderate-to-severe atopic dermatitis: clinical outcomes with targeted IL-13 inhibition. Allergy. 2023;78(7):1779–1797.
24. Bunick CG, Cardwell LA, Sadeghian A, et al. Resolution of dupilumab-associated arthralgias following switch to tralokinumab in patients with atopic dermatitis. Dermatol Ther (Heidelb). 2025. [Epub ahead of print]
25. Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287–2303.
26. Silverberg JI, Guttman-Yassky E, Gooderham M, et al. Health-related quality of life with tralokinumab in moderate-to-severe atopic dermatitis: a phase 2b randomized study. Ann Allergy Asthma Immunol. 2021;126(5):576–583.e4.
27. Blauvelt A, Hong HC, Katoh N, et al. Long-term safety and efficacy of tralokinumab in adults and adolescents with moderate-to-severe atopic dermatitis treated for up to 6 years: final results from the open-label extension trial ECZTEND. Dermatol Ther (Heidelb). 2026;16(4):2001–2018.
28. Guttman-Yassky E, Blauvelt A, Eichenfield LF, et al. Long-term efficacy of tralokinumab across clinical response endpoints and disease subtypes: results from ECZTRA 3. J Allergy Clin Immunol Pract. 2023;11(4):1126–1134.
29. Torres T, Sohrt Petersen A, Ivens U, et al. Matching-adjusted indirect comparison of the efficacy at week 32 of tralokinumab and dupilumab in the treatment of moderate-to-severe atopic dermatitis. Dermatol Ther (Heidelb). 2024;14(4):983–992.
30. Kim TK, Shin K, Kim H, et al. Matching-adjusted indirect comparison (MAIC) of tralokinumab vs dupilumab for the treatment of moderate to severe adult atopic dermatitis. Korean J Clin Pharm. 2023;33(2):96–105.
31. Muzumdar S, Skudalski L, Sharp K, et al. Dupilumab facial redness/dupilumab facial dermatitis: a guide for clinicians. Am J Clin Dermatol. 2022;23(1):61–67.
32. Murase JE, Suresh R. The role of expanded series patch testing in identifying causality of residual facial dermatitis following initiation of dupilumab therapy. JAAD Case Rep. 2018;4(9):899–904.
33. Murase JE, Ashbaugh AG, Raffi J, Botto N. Characterization of residual facial dermatitis on dupilumab: a retrospective chart review to delineate the potential role of expanded series patch testing. Dermatitis. 2021;32(6):393–400.
34. Ebklak (lebrikizumab) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; 2024.
35. Adbry (tralokinumab-ldrm) [prescribing information]. Parsippany, NJ: LEO Pharma Inc.; 2024.
36. Yang K, Mircescu A, Okusanya D, et al. Understanding the atopic dermatitis-psoriasis phenotypic switch through a pharmacovigilance-based approach. J Invest Dermatol. 2026;S0022–202X(26):1267–4.
37. Wollenberg A, Kinoshita H, Arima K, et al. Conjunctivitis in adult patients with moderate-to-severe atopic dermatitis: results from five tralokinumab clinical trials. Br J Dermatol. 2022;186(3):453–465.
38. Moyle M, Cevikbas F, Harden JL, Guttman-Yassky E. Understanding the immune landscape in atopic dermatitis: the era of biologics and emerging therapeutic approaches. Exp Dermatol. 2019;28(7):756–768.
39. Weidinger S, Bewley A, Hong HC, et al. Safety of tralokinumab in patients with moderate-to-severe atopic dermatitis followed for up to 4.5 years: an integrated analysis of eight clinical trials. Br J Dermatol. 2026;194(2):225–236.
40. Thyssen JP, Halling-Overgaard AS, Andersen YMF, et al. The association with cardiovascular disease and type 2 diabetes in adults with atopic dermatitis: a systematic review and meta-analysis. Br J Dermatol. 2018;178(6):1272–1279.
41. Brunner PM, Suárez-Fariñas M, He H, et al. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins. Sci Rep. 2017;7(1):8707.
42. Vakharia PP, Silverberg JI. Adult-onset atopic dermatitis: characteristics and management. Am J Clin Dermatol. 2019;20(6):771–779.
43. Knudson KM, Hwang S, McCann MS, Joshi BH, Husain SR, Puri RK. Recent advances in IL-13Rα2-directed cancer immunotherapy. Front Immunol. 2022;13:878365.
44. Jaén M, Martín-Regalado Á, Bartolomé RA, Robles J, Casal JI. Interleukin 13 receptor alpha 2 (IL13Rα2): expression, signaling pathways and therapeutic applications in cancer. Biochim Biophys Acta Rev Cancer. 2022;1877(6):188804.
45. Fujisawa T, Joshi BH, Puri RK. A novel role of interleukin-13 receptor alpha2 in pancreatic cancer invasion and metastasis. Cancer Res. 2009;69(22):8678–8685.
46. Brown CE, Hibbard JC, Alizadeh D, et al. Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial. Nat Med. 2024;30(4):1001–1012.
47. Schmidts A, Srivastava AA, Ramapriyan R, et al. Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Rα2 in recurrent glioblastoma: a phase 1 trial. Nat Med. 2025;31(8):2778–2787.
48. Drucker AM, Eyerich K, de Bruin-Weller MS, et al. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. Br J Dermatol. 2018;178(3):768–775.