A new framework to help guide clinical decision-making on the use of biologics in severe asthma has been proposed by US respiratory experts.
The framework is similar to current thinking on the issue in the UK, local experts say, with some important differences.
In the first instance, before starting any biologic clinicians should determine the specific underlying endotype behind the T2 airway inflammation, through examination of baseline biomarkers such as total and allergen specific IgE, blood eosinophil count and fractional exhaled nitric oxide (FeNO), the authors said, in a paper published in Respirology.
Other factors to be taken into account are symptom frequency, asthma triggers, baseline spirometry, oral corticosteroid (OCS) use, exacerbations and concomitant comorbidities, as well as mode of administration, cost and drug availability.
If the decision to begin biologic therapy is made, anti-IgE therapy (omalizumab) should be considered in patients with moderate to severe allergic asthma who are not taking maintenance OCS, regardless of their baseline eosinophil count.
The authors highlighted anti-IL-5 (mepolizumab, reslizumab)/anti-IL-5Rα (benralizumab) therapies as front runners for use in severe eosinophilic allergic and non-allergic asthma with or without oral glucocorticoid dependence, and the anti-IL-4Rα dupilumab as an option for allergic and non-allergic eosinophilic asthma in patients with FeNO of ≥25 ppb, and in those who are OCS dependent regardless of blood eosinophil count.
Tezepelumab has also recently been approved for use in severe asthma patients following clinical trial data which showed that it can reduce exacerbations in both type 2 and non-type 2 disease, they noted.
According to the proposed treatment framework, response to the initial biologic should be evaluated over 4-6 months by assessing symptoms, rescue inhaler or OCS use, exacerbations, quality of life and lung function.
If there is a good response, clinicians should attempt to taper OCS or high dose ICS but continue biologic therapy for at least 12 months before re-assessing treatment need; if the response is suboptimal of unclear, then the patient should remain on treatment for up to an extra 12 months before re-evaluation.
When there is no response, either initially or after an extended trial period, then clinicians should first consider potentially modifiable reasons for this, such as dosing, circulating antibodies and treatment compliance, before the last step of re-establishing the phenotype: if non-T2, then clinicians should consider non-biologic options or potentially tezepelumab; if a T2 phenotype is confirmed, several options are proposed for switching biologic, depending on the biomarker profile (such as blood eosinophil count, sensitisation to perennial allergens and FeNO), and OCS dependency.
UK advice
Currently in the UK there are no clinical guidelines linking severe asthma guidelines to specific treatments, or consensus switching algorithms, despite significant variation particularly within choice of biologics and their sequential use.
However, the recommendations in the Respirology paper do largely follow those proposed last year by a group of UK respiratory physicians, led by Dr Hitasha Rupani, a Respiratory Consultant at University Hospitals Southampton NHS Foundation Trust, though there are some key differences (aside from various NICE constraints on the positioning of these biologics in the treatment pathway).
For example, while Dr Rupani and colleagues also suggested a 4-6 month review period after biologic treatment initiation, they advised that patients should be reassessed by the severe asthma MDT to consider stopping/switching biologic if 3 or more of the following criteria are met: <0.5 unit improvement in ACQ-5 or ACQ-6; reduction in mOCS dose by <2.5 mg and <25% of baseline prednisolone equivalence; no change in exacerbations and/or hospital admissions for asthma; and patient expectations of improvement are not met.
Also, in patients on maintenance OCS in the UK mepolizumab or benralizumab should be biologics of choice, “as they have been specifically studied in this group of patients and shown to consistently and substantially decrease OCS usage alongside reducing exacerbation frequency”, according to the paper, published in Clinical & Experimental Allergy.
Elsewhere, a Consensus pathway on the management of uncontrolled asthma in adults was also recently published by the AHSN Network and NHS England’s Accelerated Access Collaborative (AAC) to improve timely specialist care for severe asthma and access to asthma biologics.
This recommends that biologic treatment should be initiated within 4 weeks of MDT approval, and that patients are moved to home administration of the biologic as soon as clinically and practically possible (within 6 months).
With regard to monitoring, those not dependent on OCS should be reviewed every 3-6 months in the first year, and 4-8 weekly reviews in OCS dependent patients to help steroid weaning.
Treatment response should be assessed at 6 months, and all decisions around ongoing management of patients should be determined by a severe asthma centre MDT, it was stressed.