Associate Professor of Medicine, Harvard Medical School

Associate Physician, Brigham and Women's Hospital

Mucus plugging is increasingly recognized as a pathophysiological feature of 

chronic obstructive pulmonary disease (COPD)

, associated in prior literature with worse symptoms, poorer quality of life, higher exacerbation risk, and increased mortality. A late-breaking integrated analysis of the replicate phase 3 OBERON and TITANIA trials introduced a segmental mucus plug score, a standardized metric scoring 18 lung segments for the presence or absence of a plug using a centralized double-read CT paradigm.

Nearly 79% of the imaging cohort had at least 1 mucus-plugged segment at baseline, and these patients had worse lung function, higher symptom burden, and more prior exacerbations than those without plugging. Tozorakimab produced a dose-dependent reduction in segmental mucus plug score at week 52, with both current and former smokers contributing to the overall effect. The finding is consistent with the earlier FRONTIER-4 CT substudy, making tozorakimab the first biologic shown to significantly reduce mucus plugging in a broad COPD population.

Tozorakimab is a monoclonal antibody inhibiting both the reduced and oxidized forms of interleukin-33, a dual mechanism the investigators say offers a biologically coherent explanation for effects on mucus dysfunction alongside inflammation. The mucus-plug finding is exploratory and was not adjusted for multiplicity, but it sits alongside the primary result from OBERON and TITANIA, where tozorakimab reduced moderate or severe exacerbations, including those requiring hospitalization or emergency care, by approximately 30% compared with placebo across 2 replicate phase 3 trials.

George Washko, MD, associate professor of medicine at Harvard Medical School and a co-author on the integrated mucus-plug analysis, spoke with 

ERS Congress 2026 held in Barcelona in September

 . In the following interview, Washko discusses what the segmental mucus plug score adds to the clinical picture of tozorakimab in COPD.

HCPLive: Why is the new segmental mucus plug score an important measure, and how does it compare with prior COPD imaging assessments?

The segmental mucus plug score gives us a standardized, quantitative way to assess mucus plugging across the lung. Each of 18 lung segments is assessed for the presence or absence of a mucus plug, producing a score from 0 to 18. This allows us to measure not only how much of the lung is affected by mucus plugging, but importantly, whether that burden changes with treatment over time. This is clinically relevant because mucus plugging is increasingly recognized as an important pathophysiological feature of COPD and has been associated with worse symptoms, poorer quality of life, increased exacerbation risk, and higher mortality. Prior CT studies helped establish those associations. What this analysis adds is a longitudinal assessment within a randomized phase 3 program, the first to show a biologic treatment, tozorakimab, can significantly reduce mucus plugging in a broad COPD population, measured at week 52. The finding is also consistent with the earlier FRONTIER-4 CT substudy, which showed a reduction in segmental mucus plug score with tozorakimab versus placebo.

HCPLive: Does mucus plugging mark a distinct, more severe COPD phenotype, or simply general disease severity?

The most important finding is that mucus plugging identified a group of patients with greater clinical disease burden. Nearly 80% of evaluable patients had at least one mucus plug at baseline, and those with mucus plugging had worse lung function, poorer quality of life, and a greater exacerbation burden than patients without mucus plugs. So mucus plugging appears to be an important imaging feature of clinically more burdensome COPD. Whether it represents a completely distinct biological phenotype independent of other measures of disease severity is a separate question, but these results reinforce that mucus plugging is not simply an incidental CT finding.

HCPLive: The mucus-plugging reduction appeared numerically larger in current smokers than former smokers. How should this be interpreted given the smaller sample?

The most robust finding is the significant reduction in mucus plug burden in the overall population, together with a dose-dependent reduction in segmental mucus plug score. The numerical finding in current smokers is interesting, however the current smoker group was a small subgroup of the overall population and therefore difficult to interpret in isolation. It is important to note that a reduction in mucus plugs was noted in both the smoker and former smoker population, with both populations contributing to the overall effect seen with tozorakimab.

HCPLive: As an exploratory endpoint without multiplicity adjustment, what weight should this finding carry alongside the primary exacerbation results?

Reducing exacerbations is a key aim for COPD treatment, as they are the most clinically meaningful events that drive disease trajectory, patient survival, and economic burden in COPD. For that reason, the most important finding is that these trials represent the first phase 3 evidence of a biologic demonstrating clinically meaningful reductions in COPD exacerbations across this broad COPD population. The mucus-plug analysis is exploratory, but it adds important biological context to the clinical efficacy results. Tozorakimab significantly reduced a CT-defined airway abnormality associated with worse COPD outcomes, and the finding is consistent with the earlier FRONTIER-4 CT substudy. The mucus data can be interpreted as complementary evidence: they strengthen the overall picture that tozorakimab is affecting both clinically meaningful exacerbations and an airway process relevant to COPD pathophysiology.

HCPLive: Is tozorakimab the first biologic to reduce mucus plugging due to a data gap, or does IL-33 blockade act on mucus specifically?

What we can say is that tozorakimab is the first biologic shown to significantly reduce mucus plugging in a broad COPD population, and there is a strong biological rationale for that effect. IL-33 sits upstream of several processes relevant to COPD. More specifically, tozorakimab uniquely inhibits IL-33 signaling in two ways: suppressing inflammation and disrupting the cycle of mucus dysfunction. This provides a biologically coherent explanation for why we would see an effect on mucus dysfunction as well as exacerbations.

HCPLive: If this mucus-plug reduction holds up, what needs to be shown next to confirm it translates into harder clinical outcomes?

What is encouraging is that the mucus-plug finding is not occurring in isolation. Higher mucus plug scores have been associated with increased exacerbation risk, accelerated lung function decline, and increased all-cause mortality. At the same time, the OBERON and TITANIA program showed that tozorakimab significantly reduced mucus plugging and also reduced moderate or severe COPD exacerbations by approximately 30% in two replicate phase 3 trials. We also saw reductions in more consequential events, including exacerbations requiring hospitalization or emergency department care. That convergence is important: the imaging effect is occurring alongside demonstrated clinical efficacy, rather than as an isolated radiographic finding.

Editor's Note: This Q&A has been lightly edited for clarity. Washko’s disclosures include Sanofi and Regeneron.

Washko G, Sciurba F, Watz H, et al. Tozorakimab reduces the number of lung segments with mucus plugs in patients with COPD at high risk of exacerbations: integrated analysis of the replicate OBERON and TITANIA phase 3 studies [late-breaking abstract]. Presented at: ERS Congress 2026; September 5-9, 2026; Barcelona, Spain.

Singh D, Guller P, Reid F, et al. A phase 2a trial of the IL-33 mAb tozorakimab in patients with COPD: FRONTIER-4. Eur Respir J. 2025;66(1):2402231.

Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to prevent COPD exacerbations. N Engl J Med. 2026. doi:10.1056/NEJMoa2606998

Articles

George Washko, MD, discusses a late-breaking OBERON/TITANIA analysis showing tozorakimab reduces segmental mucus plug scores in COPD.

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Tozorakimab Cuts COPD Mucus Plugging, With George Washko, MD

Victoria Johnson joined MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and is now an assistant managing editor for HCPLive and RheumatologyLive. She doesn’t have enough time for her various hobbies. You can reach her at vjohnson@mjhlifesciences.com.

Advanced practice providers (APPs) manage a growing share of patients with 

 and chronic obstructive pulmonary disease (COPD), often handling maintenance care, biomarker workup, and the prior authorizations that biologic therapy requires. Recent approvals have expanded the available options, including dupilumab and mepolizumab for eosinophilic COPD and depemokimab, a twice-yearly anti-interleukin (IL)-5 agent, for severe asthma.

 Access, dosing frequency, and adherence increasingly shape which of these therapies patients receive.

In September 2026, Melissa Dolbec, FNP-C, a nurse practitioner in pulmonary medicine at The Oregon Clinic in Portland, moderated a virtual clinical forum for APPs on type 2 inflammation and biologic therapy. Participants included nurse practitioners and physician assistants from the World Trade Center Health Program at Mount Sinai, NewYork-Presbyterian, and pulmonary, internal medicine, and heart failure practices in Texas, Tennessee, Montana, and California. The discussion covered biomarker workup, oral corticosteroid (OCS) thresholds, agent selection, and the logistics of securing coverage.

Eosinophils, FeNO, and OCS Thresholds in Asthma

Participants said blood eosinophil counts drive most qualification decisions, and several described reviewing records years back, or rechecking during allergy season, to document an elevated count. Few participants had access to fractional exhaled nitric oxide (FeNO), and 1 whose clinic offers it said staffing limits have discouraged its use. Where FeNO is available, 1 participant said it is used to monitor response rather than to qualify patients.

Most participants said more than 2 OCS courses per year signals inadequate control. According to 1 participant, documenting repeated bursts or steroid dependence as evidence of uncontrolled disease when steroids suppress eosinophil counts has not drawn reimbursement pushback. Participants said patients are often unreliable reporters of steroid use and described relying on Epic dispense history, Care Everywhere, and family members, while those serving rural, Indian Health Service, or VA populations described having to request outside records.

Several participants emphasized confirming the diagnosis with spirometry, methacholine challenge, or imaging before escalation, noting that many referred patients have never had pulmonary function testing and that pulmonary hypertension can mimic obstructive disease. In 1 participant's practice, phenotyping and allergy testing begin at diagnosis rather than at Global Initiative for Asthma step 5, since some biologics are approved for moderate asthma.

Selecting Asthma Biologics: Access, Dosing, and Comorbidities

In polling, 54.5% of participants cited biomarkers as the main driver of biologic choice, though in discussion, participants said dosing frequency, payer coverage, and comorbidities such as chronic rhinosinusitis often decide among eligible agents. Participants with in-house specialty pharmacy teams said they often start dupilumab because those teams can secure affordable access, and others cited lower perceived payer pushback and benefit for coexisting rhinosinusitis. Other participants described benralizumab as a frequent choice for its every-8-week maintenance dosing and low out-of-pocket cost in some plans, and anti-IL-5 agents as preferred for eosinophilic granulomatosis with polyangiitis.

For depemokimab, participants described buy-and-bill administration and inconsistent insurance coverage. According to 1 participant, a needle-averse patient with recurrent emergency department visits has had none since starting twice-yearly therapy. Tezepelumab was described as useful when elevated eosinophil counts cannot be captured, though 1 participant said obtaining coverage requires extensive work.

Participants also said payer fill-history requirements limit inhaler de-escalation, with 1 participant reporting a biologic denial after a patient stopped filling maintenance inhalers.

COPD Biologics and Specialty Pharmacy Support

Dolbec noted that an estimated 20% to 40% of patients with COPD have an eosinophilic phenotype. In BOREAS and NOTUS, dupilumab reduced exacerbations and improved lung function in patients with eosinophil counts of 300 cells/µL or higher, and in MATINEE, mepolizumab reduced exacerbations compared with placebo.

 Participants in primary care and maintenance roles said they typically refer patients with frequent exacerbations to pulmonologists for biologic initiation, and Dolbec said she has not observed a difference in benefit between the 2 COPD biologics in her practice.

In polling, access and logistics were the most common nonclinical factors altering escalation decisions, and payer support and reimbursement guidance was the most requested resource. Participants with dedicated pharmacists or nurses handling prior authorizations said this support removed much of the administrative burden, while 1 described a difficult transition to a system pharmacy team unfamiliar with pulmonary medications. Another participant recommended reviewing each agent's prescribing information to align documentation with payer criteria.

For unmet needs, participants cited limited access to pulmonary rehabilitation, inconsistent coverage for virtual programs, and the need for COPD navigators to track patients between hospitalizations. "Just the fact that in some states it has to be a physician to order pulmonary rehab, I think, is so ridiculous, and that there's just not enough access, physical access, to pulmonary rehab," Dolbec said.

Jackson DJ, Wechsler ME, Jackson DJ, et al. Twice-yearly depemokimab in severe asthma with an eosinophilic phenotype. 

. 2024;391(24):2337-2349. doi:10.1056/NEJMoa2406673

Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. 

. 2023;389(3):205-214. doi:10.1056/NEJMoa2303951

Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation. 

. 2024;390(24):2274-2283. doi:10.1056/NEJMoa2401304

Sciurba FC, Criner GJ, Christenson SA, et al. Mepolizumab to prevent exacerbations of COPD with an eosinophilic phenotype. 

. 2025;392(17):1710-1720. doi:10.1056/NEJMoa2413181

Advanced practice providers described how documentation, specialty pharmacy support, and payer requirements shape biologic selection and timing.

Asthma

The HCPLive asthma page is a comprehensive resource for clinical news and insights on asthmatic disease. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for allergic and severe asthma, and more.

Biologic Access in Asthma and COPD: Clinical Forum Perspectives

 and chronic obstructive pulmonary disease (COPD) as a spectrum of treatable traits rather than as fixed diagnoses, with blood eosinophils serving as the most practical marker of type 2 inflammation. The available options for that phenotype have expanded with approvals of dupilumab and mepolizumab for eosinophilic COPD and of depemokimab, a twice-yearly anti-interleukin (IL)-5 agent, for severe asthma.

 Payer criteria, however, do not always align with how clinicians define uncontrolled disease.

In September 2026, Ravi Kalhan, MD, MS, professor of medicine in pulmonary and critical care at Northwestern University Feinberg School of Medicine, moderated a virtual clinical forum on biologic therapy in asthma and COPD. Participants included pulmonary and critical care physicians from Northwestern, Endeavor Health, the Medical College of Wisconsin, and Advocate Health Care. The discussion covered biomarker strategy, oral corticosteroid (OCS) tracking, payer requirements, agent selection, and patient selection in COPD.

Type 2 Biomarkers and Payer Criteria in Asthma

Participants described reviewing 2 to 5 years of prior blood counts and repeating low eosinophil measurements, sometimes at different times of day, to capture type 2 inflammation. Several also order regional allergen panels and total IgE, and Kalhan said persistently low eosinophils and IgE can prompt reconsideration of the asthma diagnosis. Participants said they still identify outside OCS courses manually through the electronic health record and pharmacy fill databases, and Kalhan suggested automated alerts for repeated courses as an opportunity.

Several participants described difficulty obtaining coverage for patients with poor symptom control who do not have OCS-treated exacerbations, citing payer FEV1 cutoffs and peer-to-peer requirements. Kalhan noted that biologic labels vary in how they define eligibility, while payers tend to require exacerbation history. Some participants said documenting frequent rescue inhaler use as evidence of uncontrolled disease has supported approval.

Participants also described payers denying continued biologic coverage when well-controlled patients stop filling maintenance inhalers. In 1 participant's practice, step-down of biologic therapy is offered after about 6 months of control, while Kalhan noted that no evidence base currently guides biologic withdrawal.

Most participants said insurance coverage ultimately determines the agent, though several described a first choice based on phenotype. Participants cited nasal polyps, atopic dermatitis, and dosing interval as common drivers, with several describing dupilumab as their choice for atopic dermatitis and others favoring longer-interval agents for patients averse to injections. Kalhan said his own first choice is often mepolizumab, reflecting his longest experience with it, and noted that mepolizumab's development program included an OCS-reduction study.

On tolerability, Kalhan said he perceives more issues with dupilumab, while noting it may reflect a single patient and that real-world evidence has not shown a different intolerance signal across agents. Another participant said flu-like symptoms and myalgias are the most common limiting adverse effects she sees across biologics. Some participants also raised uncertainty about combining multiple monoclonal antibodies, while others cited long-standing experience with biologics in inflammatory bowel disease and rheumatology.

Participants who have discussed depemokimab described it as an option for frequent travelers and patients who prefer not to self-administer, though views were mixed on bundling office administration with comprehensive asthma care. Several participants questioned whether tezepelumab is effective in patients with truly low eosinophil counts, and 1 suggested type 2 inflammation may be present but undetected by current biomarkers. Mucus plugging data for dupilumab and tezepelumab drew varied responses, with Kalhan describing plugging as an objective marker of treatment response and others questioning its correlation with symptoms.

Eosinophilic COPD and Shared Decision-Making

Participants described COPD and asthma as a continuum, and several said they measure eosinophils routinely in COPD, sometimes repeatedly. In BOREAS and NOTUS, dupilumab reduced exacerbation rates with rate ratios of 0.70 and 0.66, respectively, alongside modest FEV1 gains, while mepolizumab reduced exacerbations in MATINEE among patients with counts of 300 cells/µL or higher.

 Participants said they place more weight on symptoms than on small FEV1 changes, and described responses to both biologics as variable.

Participants said shared decision-making is harder in COPD because biologics are framed around preventing future exacerbations rather than improving daily symptoms, and some described setting expectations accordingly. A prior hospitalization was described as raising therapeutic urgency compared with outpatient exacerbations, and 1 participant cited azithromycin as a lower-cost, well-tolerated alternative for some patients.

Participants identified pulmonary rehabilitation access as a leading unmet need. "If everyone could get to pulmonary rehab, everyone would be better off," Kalhan said.

Participants said payer criteria and patient goals often outweigh mechanism when choosing biologics, and that shared decision-making is harder in COPD.

Treatable Traits in Asthma and COPD: Clinical Forum Perspectives

Jennifer Vittorio, MD, associate professor of pediatrics and medical director of pediatric liver transplantation at NYU Langone Health

Maralixibat (Livmarli), an oral ileal bile acid transporter (IBAT) inhibitor, significantly reduced cholestatic pruritus compared with placebo in the phase 3 EXPAND trial, including among patients with biliary atresia. In the pediatric primary analysis population, the treatment produced a placebo-adjusted 0.98-point improvement in itch severity (

 = .0004), while serum bile acids decreased by 69% relative to placebo across the overall study population.¹

, Jennifer Vittorio, MD, associate professor of pediatrics and medical director of pediatric liver transplantation at NYU Langone Health, explained the rationale for IBAT inhibition and discussed the design and findings of the 

Maralixibat Reduces Cholestatic Pruritus in Phase 3 EXPAND, With Jennifer Vittorio, MD

“A meaningful reduction in pruritus, which is what the study demonstrated, really can translate into better sleep, improved daytime functioning, better quality of life for the whole family,” Vittorio said.

What Is Cholestasis and How IBAT Inhibition Works

Vittorio described cholestasis as an impairment in bile production or flow from the liver to the intestine, resulting in the accumulation of bile acids in the liver and bloodstream. Elevated bile acids are associated with cholestatic pruritus, although the mechanisms underlying itch are multifactorial.

Under normal conditions, bile acids reaching the intestine are largely reabsorbed in the distal ileum through IBAT and returned to the liver. Maralixibat reversibly inhibits IBAT, reducing intestinal bile acid reabsorption and increasing fecal bile acid excretion. This mechanism can lower circulating bile acid concentrations.²

By reducing enterohepatic bile acid recirculation, IBAT inhibition offers a potential approach to managing cholestatic pruritus, although the relationship between circulating bile acid concentrations and itch severity is not fully understood.

EXPAND Trial Design and the ItchRO(Obs) Scale

The phase 3 EXPAND trial enrolled 52 patients, including 46 pediatric and 6 adult patients, with ultra-rare cholestatic liver diseases for which maralixibat is not currently approved. Participants were randomized to maralixibat 285 µg/kg twice daily or placebo during a 20-week double-blind treatment period.¹

Vittorio explained that eligibility required significant cholestatic pruritus alongside biochemical evidence of cholestasis, such as elevated serum bile acids.

The primary endpoint was the change in average worst daily Itch Reported Outcome (Observer) (ItchRO[Obs]) severity score during weeks 13 through 20. The caregiver-reported measure assesses itch severity on a scale from 0, indicating no itch, to 4, indicating debilitating itch.

“The itch reported outcome is a validated tool that’s been used to assess pruritus in cholestatic liver diseases, and the observer reported version, which is the ItchRO(Obs), I think is particularly valuable because young children may not be able to reliably describe their symptoms,” Vittorio said. “This is where the caretakers come in.”

The observer-reported endpoint allows caregivers to document symptoms that young children may be unable to communicate directly, providing a measure of pruritus severity in a population where patient-reported assessments may not be feasible.

Maralixibat Pruritus and Serum Bile Acid Results

In the pediatric primary analysis population, average worst daily ItchRO(Obs) scores improved by 1.81 points with maralixibat compared with 0.83 points with placebo, yielding a placebo-adjusted difference of 0.98 points (

Pruritus improvement was reported on 86.0% of days in the maralixibat group compared with 49.1% in the placebo group (P = .0008). Across the overall study population, serum bile acids decreased by 69.0% relative to placebo (

Vittorio noted that EXPAND demonstrated reductions in both serum bile acids and pruritus severity, findings consistent with the proposed therapeutic rationale for IBAT inhibition in cholestatic liver disease.

The findings were announced as topline results by Mirum Pharmaceuticals on October 12, 2026, and have not yet been published in a peer-reviewed journal.¹

Maralixibat in Biliary Atresia After EMBARK and BOLD

Biliary atresia is a major cause of pediatric liver-related mortality and the most common indication for liver transplantation in children.³ EXPAND included patients with biliary atresia who retained their native liver, allowing investigators to assess whether IBAT inhibition could alleviate pruritus in this population.

Among these patients, maralixibat was associated with a placebo-adjusted 1.15-point improvement in itch severity (P = .0002). Serum bile acids decreased by 75.5% in the maralixibat group compared with 9.0% in the placebo group.¹

Earlier IBAT inhibitor trials in biliary atresia evaluated whether treatment could influence disease progression following Kasai hepatoportoenterostomy. The phase 2 EMBARK trial of maralixibat did not meet its primary endpoint,⁴ while the 

phase 3 BOLD trial of odevixibat (Bylvay)

 did not demonstrate improved native liver survival.⁵

EXPAND addressed a different clinical question, evaluating whether IBAT inhibition could reduce cholestatic pruritus in patients with biliary atresia and other ultra-rare cholestatic liver diseases. Although its findings support a potential symptomatic benefit, they do not establish whether maralixibat alters disease progression or reduces the need for liver transplantation.

Editor’s Note: Disclosures for Jennifer Vittorio, MD, include Mirum Pharmaceuticals.

Mirum Pharmaceuticals announces primary endpoint met in phase 3 EXPAND study of Livmarli (maralixibat) in ultra-rare cholestatic liver diseases. News release. Mirum Pharmaceuticals. October 12, 2026. Accessed October 16, 2026. 

https://ir.mirumpharma.com/news/news-details/2026/Mirum-Pharmaceuticals-Announces-Primary-Endpoint-Met-in-Phase-3-EXPAND-Study-of-LIVMARLI-maralixibat-in-Ultra-Rare-Cholestatic-Liver-Diseases/default.aspx

Livmarli (maralixibat). Prescribing information. Mirum Pharmaceuticals. Accessed October 16, 2026. 

https://files.mirumpharma.com/livmarli/livmarli-prescribinginformation.pdf

Schreiber RA, Harpavat S, Hulscher JBF, Wildhaber BE. Biliary atresia in 2021: epidemiology, screening and public policy. 

. 2022;11(4):999. doi:10.3390/jcm11040999

Mirum Pharmaceuticals announces data from EMBARK phase 2b study for biliary atresia. News release. Mirum Pharmaceuticals. December 18, 2023. Accessed October 16, 2026. 

https://www.businesswire.com/news/home/20231218379840/en/

Ipsen provides update on phase III BOLD trial in biliary atresia. News release. Ipsen. July 24, 2026. Accessed October 16, 2026. 

https://www.ipsen.com/press-release/ipsen-provides-update-on-phase-iii-bold-trial-in-biliary-atresia-3332691/

Videos

Jennifer Vittorio, MD, discusses EXPAND pruritus and serum bile acid results, the ItchRO(Obs) endpoint, and implications for biliary atresia.

Hepatology

Chirag Patel, MD, chief of allergy and immunology at Hackensack Meridian Jersey Shore University Medical Center,

Delayed reaction timing and isolated abdominal pain are the clinical clues most likely to help clinicians recognize 

, according to Chirag Patel, MD, chief of allergy and immunology at Hackensack Meridian Jersey Shore University Medical Center, in an interview with 

Alpha-Gal Syndrome Moves North, Yet Diagnoses Lag Behind

(University of Nebraska Medical Center), and 

 (University of Missouri School of Medicine)

) is now established on Long Island and in Massachusetts, bringing AGS into regions where many clinicians have little experience with it. A 2022 CDC survey of 1,500 health care providers found 42% had never heard of the condition, and fewer than one-third of those familiar with it knew how to diagnose it.¹ Suffolk County, New York, recorded among the highest numbers of suspected cases identified through testing from 2017 to 2022.²

“With alpha-gal, you really have to think outside the box a little bit,” Patel said. “It’s easy to characterize them as chronic spontaneous hives or acute hives because viruses are one of the most common reasons for getting those.”

Alpha-Gal Syndrome Clues Clinicians Miss, With Chirag Patel, MD

Reaction Timing as a Diagnostic Clue in Alpha-Gal Syndrome

Patel said the first step in evaluation is establishing when reactions occur. In contrast with peanut allergy, in which symptoms appear soon after ingestion, alpha-gal reactions are typically delayed. Patients frequently describe hives emerging in the evening or the middle of the night.

“There’s a pattern to it, whereas chronic spontaneous urticaria would occur at any time,” Patel said.

For clinicians in regions newly reached by the lone star tick, Patel identified tick bite history as the first question to ask. He noted a tick does not need to remain attached for the 48 to 72 hours associated with Lyme disease transmission, as a bite alone can lead to alpha-gal sensitization. He also advised asking patients how much mammalian meat they actually consume.

Patel said awareness among his peers has grown considerably. Five years ago, mentioning alpha-gal syndrome to colleagues often drew confusion; now most clinicians he speaks with know something about it, even if they cannot describe it in detail. He credited media coverage and the northward movement of ticks, which he linked to climate change, with bringing the condition to clinicians’ attention.

Isolated Abdominal Pain and Alpha-Gal IgE Test Interpretation

Early descriptions of AGS centered on a typical IgE-mediated presentation, with hives, sweating, and other features of an allergic reaction appearing 4 to 6 hours after a meal. Patel said many patients present with abdominal pain alone.

He pointed to South African oral food challenge studies in which about 20% of women reported abdominal pain as their sole symptom. A 2025 review in the 

 cited a study where 40.7% of the 91 patients with AGS experienced exclusively gastrointestinal symptoms.³

“If somebody comes in with abdominal pain, they don’t think this is IgE-mediated,” Patel said. He described isolated abdominal pain as the presentation most often missed and frequently redirected to gastroenterology.

Patel cautioned against treating alpha-gal IgE values as a diagnosis, particularly in patients without symptoms. He described food allergy testing as carrying a false-positive rate of roughly 50%, making it a risk assessment tool. A larger value signals a greater probability of clinical allergy, not a more severe allergy, despite laboratory reports labeling results as mildly or highly allergic.

“Either you’re allergic or you’re not,” Patel said.

Patel also flagged misinformation circulating about the condition, including claims tying brain fog to alpha-gal syndrome, which he said are not supported by clinical data.

“Awareness is probably the most important thing,” Patel said. “The other thing is to be aware of all the misinformation. There are people who write books about Alpha Gal who don't even have [it]. If you have random reactions that have features of an Ig-mediated reaction, then you should probably consider alpha-gal as part of your differential.”

Read our latest feature on alpha-gal syndrome here: 

Editor’s note: Reported disclosures for Patel include AstraZeneca Pharmaceuticals, GENZYME CORPORATION, Grifols USA, LLC, ARS Pharmaceuticals Operations, CSL Behring, Novartis Pharmaceuticals Corporation, Lilly USA, LLC, Pharming Healthcare, Insulet Corporation, Verona Pharma, Takeda Pharmaceuticals U.S.A., Inc, Amgen Inc, Incyte Corporation, PFIZER INC, and more.

Carpenter A, Drexler NA, McCormick DW, et al. Health care provider knowledge regarding alpha-gal syndrome: United States, March-May 2022. 

Thompson JM, Carpenter A, Kersh GJ, et al. Geographic distribution of suspected alpha-gal syndrome cases: United States, January 2017-December 2022. 

Naseem Z, Muhammad A, Chatterjee A, Rubio-Tapia A. Alpha-gal syndrome: recognizing and managing a tick-bite-related meat allergy. 

Chirag Patel, MD, explains why reaction timing, isolated abdominal pain, and careful test interpretation are central to recognizing alpha-gal syndrome.

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Quin Denfeld, PhD, is an associate professor at Oregon Health & Science University.

Quin Denfeld, PhD, discusses her findings from the BIOMES-HF study, indicating worsening symptoms in patients with HF over time.

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Dyspnea Worsens in 1 in 3 Patients Following Discharge from HF Hospitalization

Jennifer Vittorio, MD, of NYU Langone, explains how itch presents from infancy to adolescence and why off-label options fell short.

Cholestatic Pruritus in Children: Signs, Burden, and Treatment Gaps

Ryan Livingston joined the MJH Life Sciences team in March of 2025, shortly after graduating from TCNJ with a bachelor’s degree in English. He enjoys creative writing, reading, and scuba diving. He can be reached at rlivingston@mjhlifesciences.com.

A single Revita procedure preserved about 80% of tirzepatide-induced weight loss at six months in the REMAIN-1 pivotal cohort.

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Revita Reduces Weight Regain After GLP-1 Discontinuation in REMAIN-1

Diana Isaacs, PharmD, is an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic.

Podcasts

Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss a major breakthrough with the Twiist insulin pump and the recent ADA/EASD T2D guidelines.

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podcasts page features a feed of medical news and interview podcast series, including DocTalk, Lungcast, Derm Discussions, and Heart Trials.

Diabetes Dialogue

Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives is a podcast hosted by Diana Isaacs, PharmD, and Natalie Bellini, DNP, aimed at providing a regular roundup of the latest clinically applicable insights across diabetes and metabolic diseases, with a focus on leveraging technology to improve care.

Diabetes Dialogue: Twiist AID Data and the New ADA/EASD Type 2 Algorithm

David Cotter, MD, PhD, explains how remibrutinib's approval for symptomatic dermographism changes treatment sequencing in chronic urticaria.

Urticaria

The HCPLive urticaria page is a comprehensive resource for clinical news and insights on chronic idiopathic urticaria and chronic spontaneous urticaria. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for urticaria, and more.

Dermatology

The HCPLive dermatology page is a resource for medical news and expert insights on skin disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for dermatologic conditions, and more.

Remibrutinib and the First On-Label Option for Symptomatic Dermographism, With David Cotter, MD, PhD

Ronnie Fass, MD, is the Medical Director of the Digestive Health Center, Chairman of the Division of Gastroenterology and Hepatology, and head of the Esophageal and Swallowing Program at the MetroHealth Medical Center. He is also a tenured professor of medicine at Case Western Reserve University.

Ronnie Fass, MD, discusses phase 3 TRIUMpH-NERD data showing tegoprazan increased heartburn-free and regurgitation-free days vs placebo in NERD.

Gastroenterology

Gastroenterology condition center page is a comprehensive resource for clinical news and insights on digestive and GI conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for 

, IBS and IBD, Crohn's disease, and more.

Tegoprazan Phase 3 Data in Non-Erosive Reflux Disease, With Ronnie Fass, MD

Tina Bhutani, MD, MAS, discusses 3-year VALUE data on risankizumab in high-impact psoriasis and why biologics belong earlier in moderate disease.

Plaque Psoriasis

The HCPLive plaque psoriasis page is a resource for medical news and expert insights on psoriasis. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for psoriatic disease, and more.

Latest News

Tozorakimab Cuts COPD Mucus Plugging, With George Washko, MD

Biologic Access in Asthma and COPD: Clinical Forum Perspectives

Treatable Traits in Asthma and COPD: Clinical Forum Perspectives

Maralixibat Reduces Cholestatic Pruritus in Phase 3 EXPAND, With Jennifer Vittorio, MD

Alpha-Gal Syndrome Clues Clinicians Miss, With Chirag Patel, MD