Hi, everyone. I'm Sandy Corona at the University of Rochester, Professor of Medicine and Director of the Ameriparks Asthma Center. And it's a pleasure to participate in this session. I want to thank Dr. Mastali for his kind invitation, and also congratulations to CHESS for a wonderful virtual Congress. The selection of biologics is indeed no easy task. And my task in the next 10 minutes or so is to see how we can best together a guide selection of biologics for one of our patients. These are my disclosures. I have some research funding going directly to the institution and royalties for a textbook on asthma that I recently published. So let's consider Dr. Conroy's patient, and we'll call her Carol, who's a 45-year-old nonsmoker with 20-year history of asthma that's poorly controlled despite high-intensity controller therapy and requiring frequent ER visits, treatment with oral corticosteroids. Her lung function is reduced, but does respond to bronchodilator challenge. And she has aeroallergen sensitization with IgE that's slightly elevated, 45, and an eosinophil count that's quite elevated at 500. So the next question to ask here is, is a biologic the appropriate next step? And if yes, then which biologic? Should the biologic be provided at home or in clinic? Once we start Carol on a biologic, how would we monitor the treatment response? When would we stop? Or if we don't stop, how long would we treat for? When will we consider switching? And it's really a problem of plenty, but very confusing for all of us when we're selecting, trying to select, come up with a biologic for somebody who has Carol's asthma phenotype. So what do we know about Carol's asthma phenotype? So far, we know she has late-onset asthma diagnosed in her 20s. She appears to be exacerbation-prone. She is allergic. She has evidence of eosinophilia, so she has clearly type II high inflammation. She has evidence of reversible airflow limitation, so indeed she does have that one hallmark of asthma. And are there additional data that may guide biologic selection? And inherent in this, we are already assuming that Carol has good adherence to her inhalers and medications. She is using her inhalers with good technique, and her comorbidities have been adequately addressed. So questions I often ask when I'm evaluating somebody in my practice for biologic is, do they have other treatable traits, like do they have sinus disease or nasal polyps, aspirin-exacerbated respiratory disease? Do they have histrionic hernia, atopic dermatitis? Is this a patient who may have corticosteroid dependence? Would that affect which biologic we select? Are there triggers that are clearly identifiable for exacerbations? Does she have more viral or respiratory infection-induced exacerbations, or is it more allergen-driven? Is there any history of anaphylaxis? Two of the biologics do have an anaphylaxis warning associated with it, and we may not select one of them if there's history of anaphylaxis. What's her BMI? If she's on an elevated, if she has a very high BMI, would we consider more a weight-based dosing rather than a fixed dose? Is her axonometric oxide level elevated? Is she able to give herself an injection? And if she does, even if she can, does she have a preference to coming into a medical facility for injection or giving it to herself at home? Have there been issues with deterrence in the past, in which case, perhaps observed a clinic injection might be better? Are there plans for allergen immunotherapy? And in childbearing age women, are there plans for pregnancy in the near future? So let's review what we know and the subtle differences between different biologics that are available. Omelazumab or Zolair was the first biologic to get approved for severe asthma in 2003. So it works in that T helper 2, Th2 axis and prevents IgE mediated pathway. Approved for moderate to severe allergic asthma, the dose is based on IgE and weight and given subcutaneously every two to four weeks. And dosing above 375 milligrams every two weeks, there's really no recommendation. So in patients of very high IgE level or high BMI, this can be a problem. It has a 0.2% low risk of anaphylaxis, which may be delayed. So it's only approved for administration in a medical facility, although there were some exceptions in low risk patients during the COVID pandemic. And because of this risk of anaphylaxis, we do ask our patients to carry an epinephrine auto-injector. Elevated EOS and Pheno do predict response, but there are also studies that have shown that patients can respond regardless, irrespective of this. Omelazumab is approved for use in chronic idiopathic urticaria. So in patients who have comorbid urticaria, this may be the preferred drug. Also, it has been utilized to improve safety and efficacy of allergen immunotherapy. So in patients who are being considered for it, this pretreatment can be beneficial. So this may lead us to select Zolair, as you may know. Otherwise, immunotherapy in patients who have severe uncontrolled asthma is not recommended because of risks associated with allergen exposure. And the data on pregnancy is really reassuring. So if pregnancy is planned in the near future, then Zolair would be preferred if absolutely necessary and can be maintained during pregnancy and is really the only biologic that I would consider in a patient in this situation. There are three biologics available in the anti-interleukin-5 strategy. Omelazumab is an anti-interleukin-5 antibody, so it blocks the alphites. And as you've heard from Dr. Hanania, it depletes eosinophils. And it is available in a fixed dose. It can be given at home or in a medical facility. Also approved for eGPH, so that may be a consideration to lean towards MEPL if that's a concern in patients who have severe uncontrolled asthma, maybe corticosteroid-dependent. The risk for anaphylaxis is low. Baseline eosinophils do predict response in pregnancy data, is really not definitively available, and an exposure registry is underway. Beneralizumab is slightly different, as in it's a receptor blocker and not an alpha antibody, but an alpha receptor antibody. And it works by blocking the interleukin-5 receptor on the eosinophil. And then because of lack of the absence of flucose, it can attract other cytotoxic cells like natural killer cells and result in quick and complete depletion of eosinophils through antibody-dependent cytotoxicity. Available in fixed dose initially every four weeks and then every eight weeks after three doses, can be administered at home or in a medical facility, and both eosinophils and exacerbation frequency can predict response. Reslizumab, again, slightly different. It is an anti-L5 antibody like mepelizumab, but given as an intravenous infusion and the only L5 antibody that is weight-based dosing. So there may be a potential advantage in patients with high BMI. Again, no real data to support that, but this is more a theoretical advantage. And it does have a risk of anaphylaxis, so only approved for administration for that reason also, because it's an infusion in a medical facility. And again, our patients carry an epinephrine autoinjector if they end up on this biologic. Dupilumab is an anti-interleukin-4N13 blocker. Both cytokines go through the interleukin-4 receptor alpha, and by blocking this, it can actually impact both the IgE, the allergic pathway, and also the eosinophilic pathway. And it has approval for both eosinophilic asthma and also corticosteroid-dependent asthma, irrespective of the eosinophil count. It's a fixed dose, but two different doses, a higher dose for corticosteroid-dependent asthma, nasal polyps, and atopic derm, which it's also FDA approved for. So in patients who have comorbid atopic dermatitis or sinus disease with nasal polyps, dupilumab would be a good selection. And pheno, more so than eos, does predict response because pheno is thought to reflect IL-13 activity. Dupilumab's only available for home administration, so patients have to be comfortable with that. And then there are, for patients who have corticosteroid-dependent asthma, only three biologics have been systematically studied, mepolizumab, enrelizumab, and dupilumab. So if a patient's stuck on a maintenance oral corticosteroid, I usually will pick one of these biologics, depending on their other treatable traits. I would also encourage you to look at the GINA severe asthma guidelines. It's really quite comprehensive and user-friendly, and they do provide guidance on which biologic to select based on the treatable traits and then what predicts response. Most of these we've already covered. So I will leave you with this, that there's really no direct comparative evidence available in selection of biologics. Meta-analyses have been performed, but they're not really difficult to make comparison because of heterogeneity of the patient population and the outcomes that have been studied. So treatable traits, comorbidities, biomolecules, and patient preference are really used to guide selection. And anytime we select patients, start patients on biologic therapy, it's really important to monitor them objectively and reassess in three to six months for treatment response, using an asthma control test or questionnaire, monitoring their exacerbation frequency, corticosteroid use, and lung function. And for non-responders, a switch to a different biologic should be considered, but in people who are responding, there's really no guidance on duration of therapy. So with this, I will stop here, and I thank you very much for your attention. Be safe and be well.

biologics

asthma treatment

Dr. Sandy Corona

selection factors

available options