This Week in Allergy & Immunology — Sep 27, 2026

This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.

Welcome to This Week in Allergy and Immunology. This week we're covering 10 notable papers spanning the real-world safety of type 2 biologics, the push to define remission across the united airway, and rare disease — from lentiviral gene therapy in Wiskott-Aldrich syndrome to diagnostic delay in eosinophilic granulomatosis with polyangiitis. Let's dive in.

We'll start with a theme that runs through three papers in the Journal of Allergy and Clinical Immunology In Practice: what happens when type 2 blockade meets the rest of a patient's allergic phenotype. The most immediately arresting is a retrospective chart review from Hua and colleagues at a single children's hospital in Chicago, covering a decade of paediatric patients who had confirmed food allergy and an outpatient prescription for dupilumab for some other atopic condition [1]. Food-specific immunoglobulin E fell substantially on treatment — median drops ranged from about half to nearly ninety percent from baseline — and that is exactly the kind of number that tempts an allergist toward an oral food challenge. But the challenge outcomes went the other way. Reaction rates during challenges performed on dupilumab were more than double those seen before treatment, rising from about a fifth of challenges to close to half of challenges. Anaphylaxis during challenge occurred in roughly a quarter of post-treatment patients compared with about one in eleven beforehand. This is retrospective, single-centre, and the pre- and post-treatment groups are not randomised, so confounding by severity is entirely plausible — but the direction is the opposite of what the falling immunoglobulin E would predict, and the authors conclude that dupilumab-associated reductions in food-specific immunoglobulin E should not be read as evidence of tolerance.

Two other papers in the same journal address safety signals that come up in every biologic consent conversation. Stone and colleagues used the TriNetX United States collaborative network to match patients aged six and over with moderate-to-severe asthma on a biologic against unexposed controls, following them for up to two years [2]. Overall, biologic exposure was not associated with any increase in respiratory tract infections; if anything, influenza and acute upper respiratory infections were modestly less common. Dupilumab specifically was associated with lower rates of upper respiratory infection, pneumonia, and influenza — influenza risk was roughly halved. That is reassuring but it is electronic health record data with all the surveillance and healthy-user confounding that implies. Alongside it, Tsao and colleagues used the same network in a target trial emulation comparing ocular adverse events between dupilumab and the interleukin-5 inhibitors mepolizumab and benralizumab in adults with asthma, with just over seven thousand propensity-matched pairs [3]. Over six months the overall event rate was low in both arms — 2.6 percent with dupilumab versus 2.1 percent with anti-interleukin-5 — a modest relative increase driven by conjunctivitis, and far below the eight to twenty-eight percent reported in atopic dermatitis populations. Importantly, the signal did not hold up when patients with atopic dermatitis, hypereosinophilic syndrome or Sjögren's were excluded, nor among persistent users, which supports the authors' suggestion that comorbid dermatitis is doing much of the work.

The second theme is remission, which has quietly become the organising ambition of airway disease — and two reviews this week ask whether the construct is earning its keep. In Annals of Allergy, Asthma and Immunology, Yu and colleagues lay out a disease-modification evidence ladder for asthma: clinical, biological, structural, and finally off-treatment remission [4]. Their synthesis is sobering. Most reported remission outcomes sit on the lowest rung — on-treatment clinical remission — with modest placebo-adjusted differences and persistent structural airway abnormalities. Biological remission is achieved by a minority of patients and dissociates from clinical control, with baseline eosinophils and disease duration predicting who gets there. Structural gains, including reversal of fixed obstruction and mucus plugging, are documented, but hard remodelling endpoints remain incompletely reversed. And the decisive evidence, off-treatment remission, is nearly absent: the two randomised withdrawal trials show relapse rather than durable cure. The whole framework, they note, is anchored in type 2 high disease and cannot currently be applied to the type 2 low minority.

Set that against a EUFOREA expert panel paper in the Journal of Allergy and Clinical Immunology In Practice, where Hellings and colleagues take the more optimistic view for chronic rhinosinusitis with nasal polyps [5]. They report that real-life registries put the likelihood of remission after more than eighteen months of biologic therapy at around forty percent in severe uncontrolled disease, and propose four strategic categories — health system, medical community, therapeutic approach, and patient community — that might push that number higher. It is consensus opinion rather than trial data, and it sits in productive tension with the asthma review: one field is consolidating remission as an achievable target while the other is asking whether on-treatment remission is anything more than effective suppression. A companion review in the Journal of Allergy and Clinical Immunology from Peters and colleagues surveys mechanistic and clinical developments in chronic rhinosinusitis over the last three years — a newly defined endotype, novel cell populations, advances in epithelial barrier biology, and four approved type 2 biologics whose comparative efficacy against corticosteroids and surgery is still being worked out [6].

The unresolved remainder of the airway — the patients who are not type 2 high — is the subject of a treatable-trait review, also in Annals of Allergy, Asthma and Immunology, from Hao and colleagues [7]. Their central caution is that neutrophilia on a sputum or nasal sample should not be equated with a stable non-type-2 endotype or with corticosteroid resistance, because it can arise from infection, smoking, obesity, environmental exposure, treatment effects, or simply the biology of a recent exacerbation. Direct airway assessment outperforms blood biomarkers, no neutrophil-specific biologic is approved for asthma, polyps or rhinitis, and trials targeting the CXCR1/2 and interleukin-17 pathways showed that suppressing neutrophils does not reliably produce clinical benefit. Macrolides remain the clearest available bridge in selected patients, though without a validated neutrophil threshold to guide use.

Chronic spontaneous urticaria is the one area where the pharmacology is outrunning the evidence base, and a review in Clinical and Experimental Allergy from Kaur and colleagues maps that expansion [8]. Recognition that mast cell activation proceeds through immunoglobulin E-independent routes has opened up Bruton's tyrosine kinase, the interleukin-4 and 13 axis, KIT, MRGPRX2 and the JAK-STAT pathway. The oral BTK inhibitor remibrutinib is now licensed for adults in the United States and European Union, dupilumab has extended down into paediatric age groups, barzolvolimab has completed phase 3 enrolment of over nineteen hundred adults, and ligelizumab failed to demonstrate superiority over omalizumab. The authors' argument is that the limiting factor is no longer the number of druggable targets but the distribution of evidence: adults dominate trials, adolescents appear as underpowered subgroups, and older adults — where polypharmacy and the cardiovascular and malignancy signals of JAK inhibition matter most — are almost never analysed separately.

Finally, two papers at the rare end of the specialty. In the New England Journal of Medicine, Ferrua and colleagues report pooled data on etuvetidigene autotemcel, an autologous lentiviral gene therapy for Wiskott-Aldrich syndrome, integrating a phase 1-2 study, a phase 3 study and an expanded-access programme — twenty-seven patients in all, with median follow-up among survivors of 5.7 years and follow-up extending beyond thirteen years [9]. Overall survival was 96 percent at both one and five years, with one death. Severe infections fell from two events per person-year before gene therapy to about 0.15 per person-year in the window from six to eighteen months afterwards, and moderate or severe bleeding fell from two per person-year to under one. The most common serious adverse event was central venous catheter-related infection, and there was no evidence of insertional oncogenesis. Then in Allergy, Mulkareddy and colleagues report a single-institution chart review of thirty-six adults with eosinophilic granulomatosis with polyangiitis, where the average time from symptom onset to diagnosis was nearly five years [10]. Asthma and chronic rhinosinusitis were each present in about four in five patients, and more than a quarter had received a biologic before the diagnosis was made. Delay beyond three years was associated with female sex and with prior biologic treatment — each roughly seven-fold on the odds scale — while a positive C-ANCA and renal involvement were associated with earlier recognition. With thirty-six patients and very wide confidence limits, the authors are explicit that this is hypothesis-generating, but the signal that biologic therapy may mask evolving vasculitis is one worth sitting with.

If you only have time for one paper this week, make it the dupilumab and oral food challenge study [1]. It directly challenges an inference many allergists have been making — that falling food-specific immunoglobulin E on dupilumab signals a safer challenge — and it reopens the question of how to interpret specific immunoglobulin E at all in a patient on type 2 blockade.

Here is what this week's evidence adds up to in Allergy and Immunology. First, biomarker movement on dupilumab is not the same as clinical tolerance; the food challenge data are retrospective and single-centre, but they point away from reassurance [1]. Second, the broader safety picture for asthma biologics looks favourable in large real-world United States cohorts — no excess respiratory infection, and an ocular signal for dupilumab that is real but small and largely concentrated in patients with comorbid dermatitis [2][3]. Third, remission is being claimed faster than it is being proven: forty percent attainment in polyp registries sits beside an asthma literature in which off-treatment remission is essentially undemonstrated and structural disease persists [4][5]. Fourth, for the non-type-2 airway there is still no approved targeted therapy and no validated neutrophil threshold, and trials suppressing neutrophils have not reliably improved outcomes [7]. And fifth, at the rare end, gene therapy for Wiskott-Aldrich now has multi-year follow-up showing sustained survival and large reductions in infection and bleeding without insertional oncogenesis [9], while eosinophilic granulomatosis with polyangiitis is still taking years to recognise in patients who are already under allergy care [10].

That's your roundup for This Week in Allergy and Immunology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.