Allergy Notes, Evidence-based Information by Board-certified Physicians

Deucrictibant: a swallowed, on-demand option for hereditary angioedema

2026-10-29T08:04:00.000-04:00

Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) causes recurrent, unpredictable swelling attacks. Untreated, they can be severe and last 3–5 days, and they do not respond to antihistamines, steroids, or epinephrine.

Since 2008, treatment has expanded to five approved on-demand drugs and six for long-term prophylaxis, with the goal now being a normal life. But breakthrough attacks still occur even on prophylaxis, which makes early on-demand treatment critical.

The key mediator is bradykinin. In HAE-C1INH, factor XIIa and plasma kallikrein generate bradykinin, which binds the bradykinin B2 receptor on endothelium and increases vascular permeability. Icatibant blocks that receptor and is highly effective, but it must be injected — a real barrier for many patients.

Deucrictibant is also a bradykinin B2 receptor antagonist, but it is taken by mouth. In a phase 3, multicentre, randomized, double-blind, placebo-controlled trial across 24 countries, patients received two randomly allocated treatments — one deucrictibant, one placebo — with a median time from symptom onset to treatment of about 1.5 hours in both arms.

In the 88 patients with HAE-C1INH in the analysis, median time to symptom improvement was 1.28 hours with deucrictibant versus more than 12 hours with placebo (p < 0.0001). The secondary endpoints all favored deucrictibant as well: time to end of attack progression 17.47 vs. 228.67 minutes, substantial symptom relief 2.85 hours vs. more than 12 hours, and complete resolution 11.95 hours vs. more than 48 hours. No safety signals were seen in 201 attacks treated among 113 patients who received at least one dose.

There is also an early broader signal: two patients with HAE-plasminogen, in which bradykinin is generated without factor XIIa/kallikrein, responded similarly. That fits the idea that blocking the receptor downstream could work across bradykinin-mediated subtypes.

Two caveats matter. Bradykinin via this receptor also has cardioprotective effects, so use during reperfusion after acute ischemia could theoretically blunt that protection — a risk that could grow if it were used regularly as prophylaxis. And an oral drug is problematic in severe laryngeal edema when swallowing is impossible, or with vomiting during an abdominal attack.

Still, the combination of fast efficacy, no severe or serious treatment-related adverse events observed, and a swallowed rather than injected route makes deucrictibant a potentially important addition to on-demand treatment — mainly because it lowers the barrier to treating early, when stopping an attack matters most.

Reference:

Zuraw & Christiansen. Deucrictibant: a novel oral on-demand treatment for hereditary angioedema. The Lancet, Volume 408, Issue 10565.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01855-6/fulltext

The Steroid Smell Test in CRSwNP: A Simple Rule for a Hard Decision

2026-10-28T20:36:00.000-04:00

Loss of smell is often the symptom patients with chronic rhinosinusitis with nasal polyps (CRSwNP) care about most — and the hardest to restore.

In his editorial introducing the October 2026 sinonasal issue of Annals of Allergy, Asthma & Immunology, Larry Borish offers a practical rule that cuts through the biologics-versus-surgery debate: the steroid smell test.

If a short course of systemic corticosteroids restores smell, the olfactory epithelium is still capable of responding. That response argues for chronic type 2–targeted therapy — the inflammation injuring the epithelium (with loss of integrity, sensory neuron apoptosis, and impaired regeneration) is reversible, and it should be treated as such.

If a short steroid course does not restore smell, pharmacologic restoration is unlikely. That patient should not cycle through repeated steroid bursts or escalating medical therapy in hope of a different result. Olfactory training may still help, but expectations — and the treatment plan — should change.

Borish pairs this with two other stewardship points from the same issue.

First, frequent “acute sinusitis” is usually not an immunodeficiency problem: the most common cause of recurrent acute sinusitis is underlying chronic rhinosinusitis, and that is where the evaluation should start.

Second, surgery is not the old-fashioned option. Functional endoscopic sinus surgery plus follow-on medical therapy can produce long-term remissions and creates the access needed for irrigant-delivered therapy — without which medical therapy often fails. Biologics, by contrast, shrink polyps only by about 50%, and a year of a biologic costs roughly 3 to 4 times FESS with medical therapy.

His sequence, in short: operate first, reserve biologics for early recurrence — with one clear exception. Severe asthma argues for an early biologic, where one drug can treat both the upper and lower airways.

It is a refreshingly testable framework: one short steroid course, one objective question — did smell come back? — and a decision that follows from the answer.

References

Borish L. Recent advances in our understanding of the comorbid complications and treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). Ann Allergy Asthma Immunol. 2026 Oct;137(4):409-410. doi:10.1016/j.anai.2026.07.023

https://www.annallergy.org/article/S1081-1206(26)00361-3/fulltext

Depemokimab is comparable in efficacy and safety to all other severe asthma biologics, with advantage of 6-month dosing

2026-10-27T20:13:00.000-04:00

Severe asthma affects 13-26 million people worldwide. We now have 6 biologics, but many require injections every 2-8 weeks and we've never had a head-to-head trial of the newest one.

In the September 2026 Annals of Allergy, Asthma & Immunology, Bourdin et al. (p329-339) address this with an indirect treatment comparison of depemokimab.

What is it?

Depemokimab is the first ultra-long-acting anti-IL-5 biologic - engineered for high potency and extended half-life, dosed twice yearly. Efficacy was shown in SWIFT-1 and SWIFT-2.

Why an indirect comparison?

No trial randomizes depemokimab vs mepolizumab vs benralizumab vs dupilumab vs tezepelumab vs omalizumab. Trials from 2003-2025 also enrolled very different populations. The authors did a systematic review (Embase, MEDLINE, Cochrane) - 17 trials for exacerbations, 22 for safety - and used both standard network meta-analysis and multilevel network meta-regression adjusting for prior exacerbation history, ICS/OCS use, and eosinophil count.

What they found:

Unadjusted model: depemokimab better than placebo, omalizumab, benralizumab, dupilumab 300mg

Fully adjusted model (most relevant): depemokimab significantly reduced annualized exacerbation rates vs placebo, with no significant difference vs any other biologic

Safety: odds of AEs and SAEs similar across biologics, with fewer SAEs than dupilumab in this analysis

What it means:

For severe type 2 asthma, twice-yearly dosing appears to deliver the same exacerbation reduction as biologics given 6-26 times per year. That has major implications for adherence, access, and quality of life.

Limitations: ITC is not a head-to-head trial, and this analysis focused on exacerbations, not lung function, OCS sparing, or non-T2 traits where other biologics have distinct benefits.

Bottom line: If your patient needs IL-5 pathway blockade, depemokimab offers parity on efficacy and safety with a lot less frequent dosing.

References:

Bourdin A et al. Depemokimab reduces asthma exacerbations similarly to other biologics. Ann Allergy Asthma Immunol 2026;137:329-339.

https://www.annallergy.org/article/S1081-1206(26)00218-8/fulltext

Biologics for severe CRSwNP: dupilumab still leads in a network meta-analysis of 7 agents

2026-10-26T20:32:00.000-04:00

Seven biologics are now in play for severe chronic rhinosinusitis with nasal polyps (CRSwNP), with no head-to-head trials among them. In JACI, Ouranos and colleagues compared them indirectly in a systematic review and network meta-analysis of 15 randomized trials (n=3,642): dupilumab, omalizumab, mepolizumab, benralizumab, depemokimab, tezepelumab, and stapokibart. The primary outcomes were changes in nasal polyp score and nasal congestion score at 20–24 and 48–56 weeks.

At 20–24 weeks, dupilumab and stapokibart produced greater reductions in polyp and congestion scores than depemokimab, omalizumab, and benralizumab. There was no significant difference between dupilumab and stapokibart on either outcome.

At 48–56 weeks, dupilumab and tezepelumab led, with greater reductions than depemokimab, mepolizumab, or benralizumab — and again, no significant difference between dupilumab and tezepelumab.

Safety was comparable across all seven agents.

The bottom line: dupilumab is the only agent at the top at both time points, and it remains the best-supported choice on indirect evidence. Neither stapokibart early nor tezepelumab late was shown superior to dupilumab — that question can only be settled by direct, head-to-head comparative trials.

References:

Ouranos K, et al. J Allergy Clin Immunol. 2026;158(4):1047-1057.

DOI: 10.1016/j.jaci.2026.06.016

Macrolides for asthma: better control, fewer severe exacerbations

2026-10-25T20:27:00.000-04:00

An old antibiotic class still has a role in asthma. In JACI, Ologundudu and colleagues pooled the randomized trial evidence on macrolides for asthma — a systematic review and meta-analysis done for the upcoming AAAAI/ACAAI severe-asthma guidelines.

The evidence base. 19 randomized trials, 1,825 participants, macrolides versus placebo or standard care, with certainty rated by GRADE.

Control and exacerbations. Macrolides improved asthma control — ACQ-6 mean difference −0.23 (95% CI −0.32 to −0.13, high certainty), with 40.6% vs 21.6% of patients improving by the 0.5-point minimally important difference. They likely reduced severe exacerbations: incidence rate ratio 0.75, or 0.26 fewer events per patient-year (moderate certainty). Quality of life improved modestly.

Not T2-restricted, and no safety signal. The benefit was similar in type 2–high and type 2–low asthma, which sets macrolides apart from most add-on options that are phenotype-specific. There was little to no effect on serious adverse events or mortality.

The takeaway. The average effects are modest — the ACQ-6 gain sits below the 0.5-point MID — but the exacerbation reduction is real and phenotype-independent.

That makes macrolides a guideline-relevant option to weigh in severe asthma, balanced against the usual stewardship concern of antimicrobial resistance with long-term antibiotic use.

References:

Ologundudu LM, et al. J Allergy Clin Immunol. 2026;158(4):970-981.

https://doi.org/10.1016/j.jaci.2026.01.024

From CD20 to CD19: Deeper B-Cell Depletion in Autoimmune Disease

2026-10-24T20:25:00.000-04:00

For two decades, B-cell depletion has meant anti-CD20 — and that choice was deliberate. In a Paradigms and Perspectives piece in JACI, Rivière and colleagues trace how the field is now moving to CD19, and why going deeper can produce durable remission where rituximab falls short — at a greater immune cost.

Why CD20 came first. CD20 was the cautious target: it is expressed on mature B cells but spares stem cells and plasma cells, so depletion is substantial yet reversible, and antibody production is partly preserved. That safety margin made rituximab the workhorse of B-cell depletion in autoimmunity.

Where CD20 falls short. The same sparing is its limit. Tissue-resident B cells, plasmablasts, and long-lived plasma cells can survive anti-CD20 therapy and keep driving disease — a plausible explanation for relapses and for refractory SLE, NMOSD, autoimmune encephalitis, and ITP that do not remit on rituximab.

What CD19 adds. CD19 is expressed more broadly across B-cell development, including on plasmablasts. CD19-directed antibodies, bispecifics, and CAR-T cells therefore deplete a deeper and wider compartment, and in refractory autoimmune disease that deeper depletion can reset the B-cell repertoire and produce durable, drug-free remission.

The cost — and the next step. Deeper is not free: hypogammaglobulinemia, blunted vaccine responses, and infection, plus cytokine release syndrome and neurotoxicity with CAR-T approaches. The authors' conclusion is that the future is smarter, not just deeper, depletion — matching the depth of depletion to the disease, and preserving protective immunity wherever possible.

References:

Rivière E, et al. From CD20 to CD19: The shift from cautious to deeper B-cell depletion in autoimmune diseases. J Allergy Clin Immunol. 2026;158(4):951-953.

https://doi.org/10.1016/j.jaci.2026.07.015

Signs of fatal perioperative anaphylaxis: pale and bradycardic

2026-10-23T20:19:00.000-04:00

Not all perioperative anaphylaxis looks the same. In a Paris cohort of 72 patients with severe, IgE-proven reactions, Dewachter and colleagues found that every fatal or near-fatal case — 6 of 27, vs 0 of 45 — began with early cutaneous vasoconstriction: pallor, piloerection, sweating, sometimes cyanosis, paired with bradycardia instead of the expected tachycardia.

That pattern signals profound hypovolemia from capillary leak, and the lessons are practical: lead with aggressive, don't reach reflexively for atropine to "fix" the bradycardia — it preceded ventricular fibrillation in these cases — and titrate epinephrine in small doses rather than reflex 1 mg boluses. Some apparent "refractory anaphylaxis" was actually catecholamine-stressed, failing myocardium.

Pale and bradycardic is not mild anaphylaxis. It may be the most dangerous kind.

Dewachter P, et al. J Allergy Clin Immunol Pract. 2026;14(10):2295-2309.e2.

https://www.jaci-inpractice.org/article/S2213-2198(26)00585-4/fulltext

New targets in allergy: Siglec-6, SMURF2, IgE class-switch, KIT+ ILC2, SPRR2A-CSTA

2026-10-22T20:39:00.000-04:00

Most current allergy biologics block a cytokine, its receptor, or IgE itself.

Five papers in the October 2026 issue of JACI (Vol. 158, Issue 4) point one step deeper — at the cells and signaling switches that decide whether an allergic response happens at all. None is a clinical treatment yet, but together they map where the next generation of targets may come from.

Siglec-6 — nanocarriers carrying midostaurin and targeted to Siglec-6 selectively eliminated human mast cells, with limited off-target effects.

SMURF2 — an intracellular amplifier of FcεRI signaling; mast-cell knockout attenuated anaphylaxis and airway disease.

BCR restraint of IgE — B-cell receptor ligation selectively inhibits IgE class-switch recombination — a built-in checkpoint on IgE production.

KIT+ ILC2 — a poised, plastic precursor state, maintained by IL-2/IL-7 via STAT5 and enriched for asthma and autoimmunity risk variants.

SPRR2A-CSTA — an IL-17A-driven epithelial axis behind steroid-resistant allergic rhinitis; serum levels separated resistant from responsive patients.

References:

J Allergy Clin Immunol. 2026;158(4) — Thames et al., pp. 1073-1084; Liang et al., pp. 1101-1116; Wade-Vallance et al., pp. 1085-1100; Olsthoorn et al., pp. 1117-1132; Xie et al., pp. 994-1009.

Issue: https://www.jacionline.org/current

Anaphylaxis: "No response after two IM or nasal Epi doses — prepare to infuse Epi"

2026-10-22T20:14:00.000-04:00

Intranasal epinephrine (neffy) is now approved on several continents, but how should it fit into anaphylaxis care — especially when a reaction doesn't respond? A 30-expert international panel addresses this in JACI: In Practice.

Their pathway is simple: remove the allergen, position the patient correctly, give epinephrine intramuscularly or intranasally every 5-15 minutes, and support airway, breathing and circulation. The key change: the two routes are treated as equally effective and interchangeable — every dose counts, whichever route it came by.

If there is no response after two doses, prepare an IV epinephrine infusion and start it after the third. Without infusion capability, keep redosing every 5 minutes, give fluids, and transfer to ICU fast.

Dribin TE, et al. J Allergy Clin Immunol Pract. 2026;14(10):2254-2261.

https://www.jaci-inpractice.org/article/S2213-2198(26)00583-0/fulltext

Genetic testing in immunology: the right test for the right question

2026-10-21T19:59:22.464-04:00

Only about 28% of US patients with suspected inborn errors of immunity ever get genetic testing — and even exome or genome sequencing finds the answer in only 30-40% of cases. In JACI: In Practice, Yang, Chinn, Orange and Peng offer a practical guide to doing better.

Their main points: keep the threshold low, but test when the result could change management. Phenotype first — history, exam and functional immune assays should drive the choice of test. And the biggest test is not always the best: a targeted panel often beats an exome when the phenotype points to one pathway.

Expect uncertainty, too. Variants of uncertain significance are common, and many patients wait over a decade for a diagnosis. Counsel before you order, and plan to reinterpret results over time.

References:

Yang R, et al. J Allergy Clin Immunol Pract. 2026;14(10):2200-2208.e6.
https://doi.org/10.1016/j.jaip.2026.06.034

Summary of September editions of JACI, JACI-IP, Annals

2026-09-13T11:06:00.000-04:00

JACI — Vol 158, Issue 3 (pp. 629–926)

Inflammaging: older adults show 1–5× higher IL-6, TNF, TNFR1 than younger adults (mild-flu-level).

This is driven by CD8+ T-cell GZMK production, CHIP-mutant HSCs with myeloid bias, and senescent-cell secretomes.

The PRACTALL 2025 AI consensus notes 1 in 6 adults now get health information from AI (nearly 1 in 4 under 30), with ambient listening and LLM summaries as the main near-term tools.

JACI: In Practice — Vol 14, Issue 9 (pp. 1941–2178)

The aging in asthma in older adults: immunosenescence → neutrophilic/type-2-low, less ICS-responsive, cognitive impairment/depression bidirectionally worsening asthma.

Secondary immunodeficiency: vaccinate COVID/flu/RSV/zoster/pneumococcus.

The acupressure review notes auricular acupressure evidence is very low certainty for food allergy/asthma, with possible rhinitis benefit.

Antihistamines & dementia (n>100k matched): no dementia signal for any antihistamine vs controls; intranasal steroids slightly protective (P=.007).

GLP-1RA in asthma: consistently fewer exacerbations/utilization in obesity/T2D, partly independent of BMI.

FARE registry (n=2,601): top triggers sunflower/mustard/flaxseed, garlic/black pepper/cinnamon.

Annals of Allergy — September 2026, Vol 137, Issue 3 (pp. 269–408).

Shared decision-making has a striking figure — patients engaged in SDM were up to 80% less likely to contact a lawyer, and SDM adds only ~7% to encounter length.

The AD precision-medicine review maps the current biologic/small-molecule landscape:

- nemolizumab with itch improvement by week 1 for itch-dominant disease

- upadacitinib works for EASI/IGA/pruritus but has a boxed warning

The biomarker-guided asthma review makes a strong case for the "fast and slow lane" model, FeNO ≥40 ppb is 90% specific for asthma when spirometry is nondiagnostic, 80–90% of ICS benefit comes at low–medium doses while higher doses quadruple serious risks.

SCIT vs SLIT have similar clinical benefit via partially nonoverlapping pathways

2026-09-12T09:58:46.837-04:00

Allergen immunotherapy (AIT) remains the only intervention with potential disease-modifying capacity for allergic rhinitis, an IgE-mediated disease of increasing prevalence that affects approximately 18% of adults worldwide.

AIT consists of the subcutaneous (SCIT) or sublingual (SLIT) administration of high doses of the causative allergens.

CRTH2+CD49d+CD161+CD27− TH2A cells represent a pathogenic TH2 cell subset that is enriched in individuals with allergy.

SCIT vs SLIT have similar clinical benefit via partially nonoverlapping pathways:

- SCIT depleted CRTH2hiCD27lo TH2A cells

- SLIT depleted CRTH2loCD27hi cells

References:

https://www.jacionline.org/article/S0091-6749(26)00421-5/fulltext

How Seasonal Allergies May Trigger Anxiety and Depression

2026-05-23T10:53:55.337-04:00

A fascinating new study published in The Journal of Allergy and Clinical Immunology reveals a striking seasonal connection between allergies and mental health.

Researchers analyzed Google search trends in the U.S. from 2020 to 2025 and found that peaks in searches for “allergies” (especially allergic rhinitis) consistently lined up with increased searches for “depression” and “anxiety.” These mental health search spikes occurred during the classic allergy seasons — spring (March–May) and fall (September–November) — often rising at the same time or within a few weeks after allergy symptoms surged.

The authors point to two likely mechanisms:

- Sleep disruption caused by nasal congestion, sneezing, and itchy eyes

- Systemic inflammation from allergy-related cytokines that can affect brain function and mood

Even in 2020, when the COVID-19 pandemic added extra stress, the allergy-anxiety pattern was clearly visible.

Bottom line for patients and doctors:

Allergies aren’t just annoying — they can genuinely impact mental wellbeing. Better allergy control (especially improving sleep) during peak seasons may help protect mood.

This study highlights why allergists should routinely discuss sleep and mental health with patients, and why public education during allergy season should include mental wellness tips.

https://www.jacionline.org/article/S0091-6749(25)01680-X/fulltext

Beyond Weight Loss: Could Popular GLP-1 Drugs Like Ozempic Help Keep Asthma Attacks at Bay?

2026-03-25T12:08:00.015-04:00

Popular GLP-1 receptor agonists - medications best known for revolutionizing diabetes care and weight management (think Ozempic, Wegovy, Mounjaro) - may offer an unexpected bonus: helping control asthma in people who are overweight or obese but do not have diabetes.

New research unveiled at the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting analyzed real-world data from hundreds of patients with asthma. The results were striking: initiating treatment with a GLP-1 agonist was tied to significantly fewer severe asthma episodes (exacerbations) over time.

Overweight patients saw about a 14.6% lower risk of asthma flares.

Obese patients had a 12.2% reduction.

Those with morbid obesity experienced a 13.3% drop.

While GLP-1 drugs are already blockbuster treatments for metabolic conditions, this study (one of the largest of its kind in non-diabetic asthmatics) hints at broader benefits - possibly through reduced airway inflammation or other mechanisms.

The findings are promising but preliminary. They don't mean everyone with asthma should start these drugs - consult your allergist or pulmonologist. Still, it's an intriguing glimpse into how medications designed for one purpose might help in surprising ways for chronic respiratory conditions.

References:

https://www.aaaai.org/about/news/news/2026/glp1

Dupilumab + OIT for Food Allergy Desensitization

2026-03-24T11:59:00.020-04:00

Food allergies remain a major challenge, especially for those allergic to multiple foods like peanut and others. Oral immunotherapy (OIT) helps build tolerance, but side effects - particularly gastrointestinal symptoms - often limit success.

The COMBINE trial, presented at AAAAI 2026, tested adding dupilumab (a biologic blocking IL-4/IL-13 pathways, already used for asthma/eczema) to omalizumab-assisted multi-allergen OIT in 108 patients.

The good news: Dupilumab dramatically boosted desensitization. At the 32-week mark, 92% of patients on the dupilumab combo tolerated a high 4,043 mg peanut allergen dose during challenges—compared to just 63% without it.

The caveat: It didn't significantly increase sustained unresponsiveness (long-term tolerance off therapy) - 55% vs. 39%, not statistically different.

This could help patients who struggle with GI reactions or miss doses, but real-world use faces hurdles like cost and access. Ongoing work aims to uncover biomarkers to predict responders and refine biologic strategies for food allergy.

References:

https://www.hcplive.com/view/dupilumab-improves-desensitization-outcomes-oit-sayantani-sindher-md

New Hope for Peanut Allergy: Oral Remibrutinib (Rhapsido) Shows Rapid Protection

2026-03-23T11:50:00.026-04:00

A promising new oral treatment could transform how we manage severe food allergies. At the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in Philadelphia, researchers presented phase II trial results for remibrutinib (Rhapsido), an oral Bruton's tyrosine kinase (BTK) inhibitor developed by Novartis.

In the study, adults (ages 18-55) with confirmed peanut allergy received different doses of remibrutinib twice daily for 4 weeks or placebo. The goal was to see if the drug could help them tolerate peanut protein without a reaction.

The results were striking and dose-dependent:

- 40% of those on the lowest dose (10 mg twice daily) tolerated at least 600 mg of peanut protein - roughly 2.5 peanuts.

- 50% succeeded on 25 mg twice daily.

- An impressive 87% on the highest dose (100 mg twice daily) reached this threshold.

The safety profile looked reassuring, with no major concerns around infections, blood counts, liver enzymes, or other worrisome side effects.

Experts were enthusiastic. Session co-moderator Yamini Virkud, MD (UNC Chapel Hill) called it a potential "game changer" - an easy-to-take pill (no injections), shelf-stable, and fast-acting (protection in as little as 1 week vs. months for injectable omalizumab). This could offer real-world benefits, like extra protection during travel, camps, or accidental exposures.

While the results compare favorably to omalizumab (which showed ~67% tolerance in a multi-food allergy trial in children), remibrutinib has the advantage of being oral and quick to work.

Food allergies affect millions, and accidental exposures remain a constant fear. An effective oral therapy like this could dramatically improve quality of life - and maybe one day reduce reliance on strict avoidance alone.

References:

https://www.medpagetoday.com/meetingcoverage/aaaai/120100

Under-the-Tongue Treatment for Food Allergy: New Peanut Allergy Tablet Proves Safe in Early Trial Results

2026-03-22T11:47:00.018-04:00

Peanut allergy affects millions of children worldwide, often persisting lifelong and carrying the risk of severe reactions. Current management relies heavily on strict avoidance, but immunotherapy options are evolving.

Exciting early data from the ALLIANCE trial suggest a once-daily peanut SLIT tablet is well-tolerated in children, adolescents, and adults. In the open-label phases, most participants handled dose increases with only mild, local side effects like mouth itching - far fewer systemic issues than seen in some other therapies, and no serious events requiring epinephrine or causing study halts.

This study highlights a potentially easier, home-based approach compared to oral immunotherapy.

References:

https://www.pharmacytimes.com/view/alliance-trial-peanut-sublingual-immunotherapy-is-well-tolerated-in-children-with-peanut-allergy

A Game-Changer for Multi-Food Allergies? Omalizumab Matches Oral Immunotherapy's Long-Term Success - With Far Less Hassle

2026-03-21T11:47:00.000-04:00

For patients and families dealing with multiple food allergies, new follow-up data from the landmark OUtMATCH trial bring encouraging news: the biologic medication omalizumab (Xolair) performs just as well as multi-food oral immunotherapy (mOIT).

In this analysis of 80–81 participants who completed initial treatment for 1–3 food allergies, both groups transitioned to real-world dietary consumption plans. Success meant regularly tolerating at least 300 mg per day of each allergen - roughly a meaningful, protective amount in accidental exposures or intentional inclusion.

Daily diary tracking at 3 and 6 months showed nearly identical outcomes: mOIT hit about 77% success at 3 months and 65% at 6 months, while omalizumab reached 66% and 63% (differences not statistically significant). Clinician reviews through a full 12 months confirmed the same pattern across foods, including peanut - no meaningful gaps between the approaches.

Safety remained comparable, with very few serious reactions (rare anaphylaxis) and only one new EoE case after omalizumab.

These Stage 3 results build on earlier OUtMATCH findings, where omalizumab proved superior to mOIT during active treatment due to fewer side effects and dropouts. Now, even after treatment stops, the benefits hold up similarly - suggesting omalizumab could be a game-changing, lower-burden option for multi-food desensitization.

Food allergy management is evolving fast - and for those with multiple triggers, this could open doors to more freedom and peace of mind. Always discuss with your allergist, as individual responses vary.

References:

https://opmed.doximity.com/articles/aaaai-omalizumab-as-effective-as-multi-food-oral-immunotherapy-for-multiple-food-allergies

Biologics vs. JAK Inhibitors for Atopic Dermatitis: Which One Wins for Your Patient? A 2026 Practical Guide

2026-03-08T12:31:00.045-04:00

Atopic Dermatitis (AD) remains a burdensome chronic inflammatory skin condition affecting quality of life, often accompanied by comorbidities such as asthma, allergic rhinitis, or food allergies. While most patients respond to topicals, 10 -30% require systemic therapy. The review article in JACI goes over targeted options beyond older immunosuppressants (e.g., cyclosporine, methotrexate), focusing on:

Biologics (monoclonal antibodies targeting type 2 inflammation):

- Dupilumab (blocks IL-4/IL-13) - widely used, approved from 6 months of age, strong for comorbid asthma or other type 2 diseases, but can cause conjunctivitis.

- Tralokinumab and lebrikizumab (IL-13 specific) - similar efficacy, potentially better ocular tolerability.

- Nemolizumab (targets IL-31) - stands out for rapid itch (pruritus) relief.

The biologics requires subcutaneous injections, have slower onset (4–8 weeks), but also require minimal lab monitoring, and have a generally favorable safety in patients with cardiovascular risks, infections, or malignancy history.

Janus Kinase (JAK) Inhibitors (oral, daily dosing):

- Abrocitinib, upadacitinib (primarily JAK1 selective), baricitinib (JAK1/2).

JAK inhibitors have faster onset and often superior short-term efficacy (especially high doses) in reducing eczema severity (EASI), itch (PP-NRS), and quality-of-life scores (DLQI/POEM), per network meta-analysis rankings.

However, they carry boxed warnings and require regular monitoring (CBC, lipids, liver function, infection screening) due to risks like venous thromboembolism (VTE), serious infections, herpes zoster, acne, nausea, and potential long-term concerns (malignancy). An elevated malignancy risk has been reported, although for abrocitinib, baricitinib, and upadacitinib the overall incidence remains low. They are contraindicated in pregnancy/breastfeeding.

The authors provide a stepped-care algorithm (starting with adherence, trigger avoidance, and phototherapy if possible), an "option grid" comparing factors side-by-side, and guidance on response evaluation (aim for clear improvement by 3 months, optimal by 6 months), tapering (possible with good control, especially biologics via extended intervals), and switching therapies.

Treatment choice is highly individualized:

Prefer biologics for patients with significant comorbidities, younger children, or when minimizing monitoring/risk is key.

Consider JAK inhibitors for rapid control of severe flares or when oral convenience and higher peak efficacy matter most.

Shared decision-making, considering patient preferences, age, comorbidities, and practical factors (injection vs. pill, monitoring burden), is essential.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01121-3/fulltext

2025: A Breakthrough Year for Chronic Urticaria - New FDA Approvals Reshaped Treatment

2026-03-07T12:18:00.030-05:00

Chronic urticaria, encompassing chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), affects a substantial portion of the population worldwide and imposes a heavy burden due to persistent symptoms like hives, itching, and angioedema, often inadequately controlled by standard treatments.

Current first-line therapy relies on nonsedating H1-antihistamines, with omalizumab (an anti-IgE biologic) as the mainstay for refractory cases.

However, omalizumab achieves complete resolution in only about 45% of patients and rarely induces lasting remission after discontinuation.

Excitingly, the therapeutic landscape for refractory CSU has expanded dramatically in recent years, with several new approvals and promising agents targeting both IgE-dependent and non-IgE pathways.

Dupilumab (Dupixent), an IL-4/IL-13 inhibitor, gained FDA approval in April 2025 for H1-antihistamine-refractory CSU in adults and adolescents ≥12 years, validating the role of type 2 inflammation in CSU pathogenesis.

Remibrutinib (Rhapsido), the first oral Bruton's tyrosine kinase inhibitor (BTKi), received FDA approval in September 2025 for adults with symptomatic CSU despite antihistamines. Phase 3 trials (REMIX-1 and REMIX-2) showed rapid, significant reductions in Urticaria Activity Score (UAS7), itch, and hives, with about one-third of patients achieving complete symptom resolution by week 12.

Omalizumab biosimilars, such as Omlyclo are offering more accessible IgE-targeted options.

Emerging c-Kit inhibitors like barzolvolimab have demonstrated efficacy in CSU and CIndU, with effects persisting post-treatment in trials, highlighting mast cell targeting potential.

Other mechanisms in development include additional BTKis, JAK inhibitors, TYK2/JAK inhibitors, MRGPRX2 antagonists, and more.

While some candidates (e.g., fenebrutinib, THB001, EP262) were discontinued due to safety issues, and others (e.g., tezepelumab, mepolizumab, benralizumab, lirentelimab, AK006) due to insufficient efficacy, these outcomes have refined our understanding of CSU pathways.

Overall, 2025 marked a transformative year for CSU management, shifting toward more targeted, effective systemic therapies - both injectable biologics and convenient oral options - that promise better symptom control and quality of life for patients with refractory disease. The pipeline remains active, with phase 3 programs underway to further broaden choices.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01144-4/fulltext

Revolutionizing Respiratory Care: How Type 2 Biologics Are Changing the Game for Severe Asthma and Beyond

2026-03-06T11:59:00.017-05:00

In the rapidly evolving field of allergy and respiratory medicine, few advances have been as game-changing as the arrival of biologics that precisely target type 2 inflammation - the underlying driver in many cases of severe asthma, nasal polyps, and related conditions.

A new review in The Journal of Allergy and Clinical Immunology: In Practice offers a timely overview of the major players:

- omalizumab (anti-IgE)
- mepolizumab and reslizumab (anti-IL-5)
- benralizumab (anti-IL-5 receptor)
- dupilumab (anti-IL-4/IL-13)
- tezepelumab (anti-TSLP)

These monoclonal antibodies have dramatically reduced exacerbations, improved lung function, and cut reliance on oral corticosteroids for many patients.

The authors highlight how the introduction and broad use of these therapies mark an "unprecedented" shift in treatment paradigms, moving from broad immunosuppression to targeted pathway inhibition.

As real-world evidence grows, these biologics are increasingly considered earlier in the disease course for type 2–high patients - and their benefits may extend to other respiratory and allergic diseases sharing similar inflammatory pathways.

For allergists, pulmonologists, and patients struggling with uncontrolled symptoms, this class of drugs represents hope for better control and quality of life. The era of personalized, biology-driven respiratory care is here - and it's only expanding.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01181-X/fulltext

New Targeted Systemic Therapies Are Revolutionizing Allergy Care

2026-03-05T11:53:00.038-05:00

For decades, allergists and immunologists have prioritized topical treatments - like inhaled or nasal steroids, intranasal antihistamines, and topical steroids and calcineurin inhibitors - to minimize the risks associated with systemic steroids such as prednisone.

These localized approaches work well for many patients but fall short in severe or complex conditions like severe asthma, nasal polyps, extensive atopic dermatitis, hereditary angioedema (HAE), chronic spontaneous urticaria (CSU), or cases with multiple comorbid allergic diseases that demand broader, systemic impact.

Advances in molecular understanding of allergic and immunologic disorders have paved the way for a new era: highly targeted systemic therapies, including biologics and small-molecule inhibitors. These precision medicines attack specific pathways with impressive efficacy and far better safety profiles than traditional systemic options.

There are emerging systemic options for asthma and allergies, including repurposed drugs, novel targets (e.g., TSLP receptor, IL-33 axis, OX40 ligand), and even unconventional approaches like GLP-1 agonists or medium-chain triglycerides.

HAE management is shifting from outdated therapies to modern prophylactic and on-demand options - now including oral plasma kallikrein inhibitors, novel monoclonal antibodies, and hepatocyte-targeted antisense oligonucleotides.

Kinase inhibitors (e.g., JAK, BTK, KIT) selectively block key signaling in mast cells, type 2 cytokines, and more, marking a new frontier for urticaria and atopic dermatitis.

CSU treatments are advancing from anti-IgE (omalizumab) to kinase inhibitors and emerging targets like MRGPRX2 and Siglec.

Evidence-based algorithm for atopic dermatitis in children and adults includes biologics (IL-4/IL-13/IL-31 pathways) and JAK inhibitors.

These targeted systemic therapies represent a game-changer, enabling precise, multi-organ treatment for chronic, debilitating conditions with reduced side effects. As the field evolves, further research into disease heterogeneity and biomarkers will refine their use even more.

Clinicians now have powerful, accessible resources in this issue to transform patient care - moving from symptom management to true disease modification. The future of allergy and immunology is here, and it's more targeted than ever.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01185-7/fulltext

Tezepelumab in Real-World Danish Severe Asthma Study: Benefits Even After Biologic Switches

2026-03-04T11:50:00.023-05:00

Tezepelumab, the "upstream" biologic that blocks TSLP to interrupt allergic and inflammatory pathways early, is gaining traction for severe asthma.

Researchers analyzed data from the Danish Severe Asthma Register on 270 patients started on tezepelumab. Notably, nearly two-thirds (63%) were switching from other biologics - suggesting clinicians turned to tezepelumab when previous options fall short.

After 12 months, the results were impressive across both groups:

- Exacerbations dropped by 69%.

- Maintenance oral corticosteroid use decreased significantly.

- Asthma symptoms improved

The majority achieved a clinical response - rates on par with other biologics in Denmark.

Even more encouraging: biologic-naïve patients were more than twice as likely to reach full clinical remission (35% vs. 15% in switchers).

These real-world findings reinforce tezepelumab's potential as a versatile option in severe asthma, effective in complex cases with mixed or low type 2 inflammation and a good choice for patients needing to switch therapies.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)00849-9/fulltext

Tezepelumab vs. Dupilumab in Severe Asthma: Head-to-Head Real-World Data Shows No Clear Winner

2026-03-03T11:41:00.027-05:00

In the evolving landscape of biologic therapies for severe asthma, two heavy hitters stand out: dupilumab (targeting IL-4/IL-13 downstream in the type 2 inflammatory pathway) and tezepelumab (blocking TSLP upstream, with potential broader effects across T2-high and T2-low phenotypes). While both are FDA-approved for severe asthma, direct comparative real-world evidence has been scarce -until now.

The study authors conclude that, in this real-world cohort, dupilumab and tezepelumab appear comparably effective at preventing exacerbations and reducing steroid reliance - no evidence that tezepelumab's upstream mechanism translated to superior outcomes overall.

For clinicians managing severe asthma, this suggests that - pending more data - either biologic is a reasonable option, guided by patient-specific factors like T2 biomarker profile, comorbidities, insurance/cost, administration preferences, and side-effect considerations rather than expecting a dramatic efficacy edge from one over the other.

As biologic options expand, studies like this help ground decisions in real-world practice rather than trial extrapolations alone.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01129-8/fulltext

Omalizumab Helps High-Risk Patients Tolerate Honeybee Venom Allergy Shots

2026-03-02T11:37:00.025-05:00

Venom immunotherapy (VIT) is the gold-standard, potentially life-saving treatment for honeybee venom allergy, but for some patients, the buildup phase triggers severe allergic reactions (SARs), making it tough or impossible to continue.

A new retrospective study from Fiona Stanley Hospital in Perth, Western Australia, reviewed 350 adults on honeybee VIT between 2015 and 2024. About 16% experienced SARs during standard therapy, and 10% ultimately received the anti-IgE monoclonal antibody omalizumab as an add-on to improve tolerance.

Key predictors for needing omalizumab included:

- history of severe sting-induced anaphylaxis
- co-existing asthma
- elevated baseline tryptase levels (a marker often linked to mast cell issues)

Among the 35 patients who used omalizumab during the VIT dose escalation (uptitration), 63% successfully reached maintenance dose without ongoing omalizumab support. Another 20% stopped due to persistent SARs, and 14% continued on omalizumab.

The most effective and well-tolerated approach was a semi-rush protocol: omalizumab 300 mg loading dose 2 weeks before starting a 12-week VIT buildup to 100 μg, followed by 150 mg every two weeks until maintenance was achieved.

For patients with recurrent severe reactions during standard honeybee VIT, adjuvant omalizumab offers a valuable option to enable safe desensitization. This larger real-world dataset strengthens the case for considering it earlier in high-risk cases, potentially transforming outcomes for those at greatest risk from bee stings. Always discuss with an allergist, as protocols should be individualized.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)00935-3/fulltext