Selecting a Biologic in Severe Asthma: Biomarkers, Comorbidities, and Payers

In "Selecting a Biologic in Severe Asthma: Biomarkers, Comorbidities, and Payers," our experts turn to the decision every clinician faces once the diagnosis is settled.

Dr. Chupp asks Dr. Hanania whether anti-TSLP availability has shifted him toward using an anti-alarmin first, given trial data showing efficacy across the spectrum without requiring a biomarker, and whether he considers combination therapy or overlapping agents when switching. Dr. Hanania says the choice remains multifactorial. For an oral steroid-dependent patient with no high eosinophils and no elevated FeNO, anti-IL-4 receptor therapy would be his choice, though emerging anti-TSLP data in that group are being presented.

Otherwise, he reads the biomarker profile and the comorbidities. Atopic dermatitis with severe asthma leaves only one approved option. Polyposis leaves several. For severe asthma with low biomarkers, anti-TSLP is the only agent that targets non-type 2 disease. For very high eosinophils above 1,500 with polyposis he may choose an anti-IL-5, though anti-TSLP might also work. Patient preference and payer coverage matter just as much: some patients refuse injections every two weeks but accept monthly, every two months, or the twice-yearly agent, which is approved only in eosinophilic asthma.

On assessment, he tells patients to be patient with him. This is not one injection and a verdict; he waits three to four months, unless side effects intervene. Exacerbations are hard to judge over three months, so he assesses how the patient feels. If nothing changes and exacerbations continue, he returns to biomarkers and phenotyping to choose the next agent.

Asked about two biologics at once, he says he does not, though colleagues have obtained reimbursement for it. He expects bispecific and tri-specific agents to change that soon. He asks Dr. Wechsler the question patients ask him constantly: once remission is reached, is this treatment for life?

Dr. Wechsler lays out the options a patient in remission faces. The default is continuing both the biologic and background therapy. Most patients feel so well they see no reason to change. But some want to reduce cost or exposure.

The second option is cutting back the background inhaled steroids. He cites the SHAMAL study with anti-IL-5 receptor therapy in well-controlled patients, notes ongoing anti-TSLP tapering studies, and adds that real-world data show many patients taper background therapy and do well.

The third is stopping the biologic and continuing background inhalers. Real-world data argue against it: exacerbations increase rapidly in about 50% of patients. The fourth, which his group is studying, is continuing both while extending the dosing interval, from every two weeks to four, or four to six or eight. Because these are largely long-acting drugs, control may hold, and the cost to society would fall. Data in chronic sinusitis with nasal polyps suggest it can be done safely; the equivalent asthma study is still needed.

In "Tapering Inhalers and Initiating Biologics Earlier in Severe Asthma," the panel will close on tapering and the fight to start earlier.