Real-Life Asthma Biologic Cases
As the Fall season arrives, there are increasing challenges for patients with asthma. Between an increased incidence of respiratory viruses, fall allergen exposure, and dramatic weather change, this time of year is particularly hard for asthma patients. When these patients experience recurrent exacerbations despite adherence to daily ICS-LABA , control of co-morbidities and environmental modifications, the next step may be to consider biologic therapy.
For many novice providers or those who do not specialize in the management of asthma, the selection of a biologic may be challenging. While specific prescribing guidelines exist, there are limitations in these guides. For example, oftentimes a patient’s phenotyping will qualify them for multiple biologics at one time. This scenario leads to enhanced clinical decision making beyond the guidelines and leaves pulmonary providers with a frequent question of: What is the most appropriate biologic for my patient?
The Asthma Subspecialty Committee of APAPP has compiled a few real-life patient cases to highlight a variety of scenarios in which nuanced and thorough decision making in biologic selection either helped lead to a positive outcome, or where a failure of therapy highlighted opportunities for further evaluation.
A Classic Asthma Case: Should a biologic be started?
Demographics & Background: A 74 year old female patient with diagnosis of cough variant asthma who appeared for acute visit due to worsened cough. Started Trelegy 200/62.5/25 mcg 5 months prior without improvement in cough. In the last three months, she was treated for bronchitis with antibiotics x 1 by urgent care. She had reported being treated with prednisone for her asthma x 2 in the last year. Cough occurs during day and night, only occasionally wheezing with chest tightness. She did not recognize any new triggers associated with her cough and did not notice a pattern throughout the day but reported that it was constant and nonproductive.
PMH: Vocal cord inflammation via fiberoptic laryngoscopy with ENT, felt to be due to acid reflux and suspected to contribute to cough. HFpEF, recently optimized for no difference in cough.
PE: Frequent cough.
Pertinent Data: Screening spirometry in the past had shown an FEV1/FVC ratio of 80%, an FEV1 of 70% of predicted, (FEF 25-75% was 45.7% of predicted).
Absolute eosinophil count was 900 cells/uL and 15% Eos.
Further work up to rule out EGPA and parasitic infection all unremarkable.
Total IgE was non-elevated.
Treatment Plan: Due to her persistent symptoms, exacerbations requiring OCS, and peripheral eosinophilia, the patient started mepolizumab (Nucala) 100 mg every 28 days.
Outcome: Since starting mepolizumab, her lab work has shown significant improvement in her eosinophil count, Eos % 2.4 and Absolute eosinophil count 100 cells/uL, with overall improvement in her cough and no exacerbations of her symptoms requiring OCS since initiation of biology therapy.
Take-aways: Patients with evidence of poorly controlled eosinophilic asthma, and perhaps no allergic sensitivity, may benefit from biologics that target the IL-5 pathway, such as mepolizumab.
Does my patient have eosinophilic asthma?
Demographics & Background: A 29 year old female presents to an asthma clinic with uncontrolled asthma, diagnosed as a young adult after having pneumonia. She had been evaluated at an outside facility and relocated to the area. At that time, she was on Dulera twice a day and albuterol PRN. Her triggers are activity and strong perfumes. She smoked in the past, quitting in August of 2022. Her cough is productive of a thick whitish-yellow sputum. She also reported nocturnal symptoms several days a week. She does have dogs and cats at home. She was started on Trelegy at this visit.
PMH: None.
PE: Unremarkable.
Pertinent Data: Eos are 9.2% and 900 cells/uL. No IgE or RAST on file. Prior PFTs confirm mild airway obstruction.
Treatment Plan: Some improvement with Trelegy after the first visit. Then, she had one asthma flare up requiring prednisone and one leading to emergency room visit and prednisone. Albuterol use remained high and CBC was repeated: Eos are 16% with absolute count of 1600 cells/uL. Benralizumab (Fasenra) was started shortly after.
Outcome: Her asthma control greatly improved a few months after, and her albuterol need declined. Follow-up is ongoing.
Take-aways: Despite a more limited evaluation for a patient with previously moderate persistent asthma, it was clear that the patient had worsening asthma control and step-up to a biologic was instrumental in controlling her disease. With eosinophil counts over 1000 cells/uL, anti-IL5 or anti-IL5R therapies (ie mepolizumab and benralizumab) are excellent options to target the eosinophilic inflammation which is likely driving asthma flares.
What if asthma exacerbations return after a period of control?
Demographics & Background: Hispanic 16 year old female presents for a follow up. She complains of a recent ER visit and has been out of omalizumab (Xolair) and Dulera x2-3 months due to new insurance. She also complains of intermittent wheezing in the last week and chest tightness. She has been on Xolair since October 2018 and had previously stayed out of the hospital, with need for oral steroids twice since 2018. Previously OCS dependent.
PMH: allergic rhinitis, severe persistent asthma, hospitalizations for asthma exacerbations x2, GERD.
PE: cough, mild biphasic wheezes, nasal mucosal inflammation present.
Pertinent Data: PFTs with mild obstruction, FEV1 is 75%. FeNO elevated at 95 ppb. Environmental allergens: dust, mountain cedar, dogs, mold, pollen, weeds. IgE 2700.
Treatment Plan: Restart Dulera 200mg 2puffs BID[SB1] , singulair 10mg PO qPM, cetirizine 10mg daily, Flonase nasal spray BID. Advised a switch to tezepelumab (Tezspire). [SB2]
Outcome: She has been on Tezspire for 2 months along with her Dulera and has not had any asthma flares, has not required oral steroids, and has required albuterol twice with activity.
Take-Aways: If patients have a return of asthma flares despite use of a biologic, a switch may be beneficial. Omalizumab is a good treatment option for allergic asthma, pediatric patients, and those with concurrent urticaria or other allergic disease. Tezspire, anti-TSLP, can be helpful in patients both with and without allergies and eosinophilic inflammation. [SB3]
What if my patient is oral corticosteroid-dependent?
Demographics & Background: 22 year old Hispanic woman with history of childhood onset asthma and OCS dependence, daily marijuana inhalation, PTSD, who initially presented to the asthma clinic after hospitalization due to status asthmaticus requiring BiPAP.
On initial meeting, she was non-adherent to ICS-LABA, with very high albuterol use. ED visits were frequent, currently on a taper of prednisone at 20mg/day and chronic prednisone use of varying amounts. It was clear she was at risk for poor asthma outcomes and education was provided, inhaler plan, technique, and rationale were reviewed with plan for short-interval follow-up to start a biologic.
She was hospitalized with acute hypoxemic respiratory failure after the first asthma clinic visit, delaying care.
PMH: Low socioeconomic resources, lack of transportation, exposures in her home (smokers, pests, pet bird, and mold), workplace exposures, untreated PTSD, daily marijuana smoking via blunts, needle phobia, and language barrier.
PE: Diffuse wheezing with a prolonged expiratory phase.
Pertinent Data:
– Absolute eosinophil count is 670 (on prednisone).
– RAST is entirely positive with a high total IgE of 2968.
– Bird panel is positive for canary, finch, and parrot feathers IgE.
– ABPA panel negative.
– ANCA screen negative, as are MPO/PR3.
– CXR clear, Chest CT ordered but outstanding.
– Normal spirometry, lung volumes, diffusing capacity, but markedly elevated FeNO at 99 ppb. BD responsiveness not assessed due to use of OCS.
Treatment Plan: Benralizumab (Fasenra) was initiated at the post-hospitalization follow-up, for in-clinic administration due to needle phobia and less frequent dosing schedule, and eosinophilic phenotype. She was referred to allergy/immunology and provided counseling regarding rehoming pets, environmental control, etc. Smoking cessation emphasized.
Outcome: She had 2 doses of benralizumab, missed another follow-up, then was admitted in status asthmaticus, ultimately requiring VV ECMO due to failure of mechanical ventilation. Chest CT (while on ECMO) showed GGOs in all 5 lobes. She unfortunately was non-adherent with inhalers and recommendations at the follow-up, resumed daily OCS and planned for 1 more dose of benralizumab before considering a switch. She had another asthma exacerbation leading to hypoxemic respiratory failure with another intubation one month later.
She presented for follow-up and was extensively counseled on the severity of her asthma, need for adherence, and PFTs showed FeNO 240 ppb, FEV1 dropped to 60% (previously 81%). It was not clear if benralizumab was ineffective, however given her markedly elevated FeNO and concurrent allergies, and OCS-dependence, she was then offered dupilumab (Dupixent). She received support in-clinic for the first few injections to overcome needle phobia. She quit smoking and connected with social work. [SB4]
Since initiating dupilumab, she has been free from emergency room visits, has needed prednisone burst only once, no daily OCS. After providing support and coaching, she has been able to continue dupilumab at home. She had significant improvement in FEV1 to 87%, FeNO to 8 ppb, asthma control score (ACA) was 20, and there was no wheezing on exam at the follow-up after 8 months of dupilumab therapy.
Take-aways: Barriers to care can impact biologic selection and asthma care in general, but with [SB5] the proper support they can be overcome. In patients with high IgE and eosinophilic inflammation, especially with OCS-dependence, dupilumab can be a great choice. At home administration of biologics may be helpful in overcoming barriers to care including transportation issues but some patients, such as this young woman, may require additional support while getting accustomed to self-injection.
What if the patient has not responded to multiple biologics?
Demographics & Background: A 57 year old man with childhood onset asthma, worsening in adulthood, allergic rhinitis on allergen immunotherapy. Asthma flares occur 5-6 times per year requiring prednisone. No hospitalizations or intubations, and remote emergency room visits. Triggers include Springtime allergens. Prior occupations include warehouse work, sandblasting, chemical plants.
Previously on omalizumab (Xolair) by a prior pulmonologist, switched to dupilumab (Dupixent) due to lack of response. New to asthma clinic in 11/2023, at that time on Breztri plus budesonide BID, and chronic azithromycin three times weekly. Eventually switched to tezepelumab (Tezspire) while undergoing work-up with the referring pulmonologist.
PMH: HTN, HLD, h/o bladder cancer on BCG treatment, tobacco use of 5pyhx, quit 2008. Marijuana smoking daily, no vaping, no other drug use.
PE: Unremarkable.
Pertinent Data:
- PFT pre-bronchodilator spirometry with mildly reduced FVC and FEV1, preserved ratio.
- Post-bronchodilator moderate obstructive pattern. Flow volume loop with obstructive morphology.
- FeNO of 6 ppb.
- DLCO is normal. increased RV/TLC ratio indicates air-trapping.
- Absolute eosinophil count of 200 cells/uL. IgE 30 international units/mL with serum allergy profile (+) dust, cat, dog, grass, trees, weeds. Negative Aspergillus titers.
- HRCT showed top normal mediastinal lymph nodes: prominent bilateral axillary and mediastinal lymph nodes. Additionally there is a right periaortic lymph node adjacent to the right diaphragmatic crus measuring 1.2 x 2.0 cm. Submental lymph nodes measuring up to 1.1 cm. Multiple additional enlarged abdominal mesenteric lymph nodes as described below. Diffuse air trapping is noted throughout the lung parenchyma demonstrating a basilar predominance.
Treatment Plan: A trial of tezepelumab vs. bronchoscopy was discussed. Given his enlarged lymph nodes and failure to omalizumab and dupilumab, complete diagnostic asthma bronchoscopy with EBUS and lymph node biopsy was pursued (of note, asthma bronchoscopy includes airway inspection and airway biopsy). He also elected to start tezepelumab during this time.
Outcome: The patient continued to have persistent symptoms, not responding to therapy. Bronchoscopy revealed non caseating granulomas in the lymph nodes consistent with sarcoidosis. Patient was referred to the sarcoid team and began on systemic treatment with daily prednisone.
Take-aways: When the patient fails multiple biologics, consider a non-asthma evaluation, even when you may have to be bold enough to disagree with the prior diagnosis from another pulmonologist to get your patient the proper treatment.
Overall, the selection of a biologic for the severe asthmatic is a complex and evolving process. It requires an understanding of prescription guidelines, asthma phenotyping and identifying concurrent treatable diseases such as nasal polyps or eczema, considerations for dosing, cost and insurance coverage, and understanding response to prior therapies. Without significant improvement in asthma control or reduction in exacerbations in the first 3-6 months of treatment, a biologic switch or further investigation may be warranted. We hope these clinical vignettes have highlighted some important elements that asthma specialists consider with biologic selection and welcome further discussion.
Discussion and cases provided by APAPP’s Asthma Subspecialty Committee:
Chair & Author: Jennifer Weber, APRN | Please email to get involved with the asthma committee at:
Members & Co-Authors: Stephanie Bork, APRN; Chelsea Buchanan, APRN; Jennifer Chrysler, APRN; Olivia Dorman, CRNP
