Oral corticosteroid stewardship for asthma: Time to move from theory to routine clinical practice

First reported in the 1950s,1 the therapeutic benefit of corticosteroids in asthma revolutionized outcomes for those living with the condition. Whilst oral corticosteroids (OCS) remain critical for the treatment of acute exacerbations, their use as maintenance therapy has long since been supplanted by inhaled corticosteroid (ICS) preparations in all but those with the most severe manifestations of asthma, who may still require maintenance OCS in addition to ICS.

The effectiveness of corticosteroid treatment in asthma comes at the cost of additional disease burden: nearly all patients with severe asthma in a large database study suffered morbidity, which may have been induced by corticosteroids, and most suffered more than two such co-morbidities.2 Recent evidence implicates the cumulative effect of repetitive courses of OCS for acute asthma in such adverse effects.3, 4

Although the anti-inflammatory activities of OCS are non-specific, early observations that responsiveness to this treatment was associated with sputum eosinophilia have been consistently confirmed using other markers of what is now termed Type 2 (T2) inflammation, such as exhaled nitric oxide and peripheral blood eosinophil count. The advent of treatment approaches utilizing monoclonal antibodies, initially with omalizumab in 2003, has permitted specific targeting of T2 inflammatory pathways. With additional biologic treatments licensed in the years since 2015, an alternative to OCS now exists for many patients who, despite using high-dose ICS-long-acting beta-agonist, suffer exacerbations requiring systemic corticosteroids or require maintenance OCS.

In this context, and with the recent achievement of expert consensus on the tapering of maintenance OCS,5 the requirement to promulgate principles of OCS stewardship is imperative. The TSANZ position paper on OCS for asthma in adults and adolescents,6 recently published in Respirology, draws on expert consensus in its recommendations on screening for steroid-induced morbidities such as diabetes, osteoporosis, hypertension, cataracts, glaucoma and obesity.5 Concerns about adrenal insufficiency may represent a significant barrier to the tapering of maintenance OCS dose in severe asthma and this position paper offers guidance on the assessment and management of adrenal insufficiency in the continuing absence of consensus on this point. We anticipate that the ongoing PONENTE trial, incorporating a protocol for evaluation of adrenal insufficiency, will further inform practice on the tapering of OCS dosage following biologic initiation in OCS-dependent patients with severe eosinophilic asthma.7

The paper highlights the potential of existing management approaches such as the personalized asthma action plan (PAAP) in OCS stewardship, but there are significant challenges with this approach: success will rely on their widespread adoption to be fully realized and PAAPs remain underutilized.8 Although PAAPs incorporating the use of both ICS and OCS improve asthma outcomes and may reduce OCS use,9 systemic effects from increased ICS use may be similar to those encountered resulting from an OCS course used to treat an exacerbation.10 Furthermore, PAAPs may prompt escalation of treatment based on symptoms alone, and inappropriate use of OCS may result, particularly for symptom combinations of lower specificity, such as those that do not include wheeze.11 Recent developments in remote patient monitoring such as home digital spirometry may support decision-making in such cases, but while dedicated study of these newer tools in the context of PAAPs is awaited, early work has shown the potential of remote patient monitoring supported by home spirometry in tapering maintenance OCS.12

Digital health technology also presents an opportunity to advance another principle of OCS stewardship proposed herein, namely optimization of adherence to controller inhalers. Low adherence to controller inhalers is associated with increased OCS use,13 but while device monitors and other digital approaches generally improve adherence, evidence of an associated reduction in OCS use remains limited.14 New models of care increasingly integrated between the primary, secondary and tertiary levels in combination with digitalization will support another important instrument in OCS stewardship, which might recently have been aspirational: mechanisms for review of OCS prescriptions, now feasible across healthcare organizations, including primary care, the source of significant OCS prescribing.

In conformity with existing asthma guidelines and echoing successful elements of antimicrobial stewardship, this position paper recommends the referral of patients being considered for maintenance OCS for specialist assessment. This may facilitate an important distinction between steroid-resistant and steroid-insensitive asthma, and other multidimensional approaches in optimizing asthma management, thus reducing OCS treatment.15 T2 inflammation drives disease in the greater part of asthma cases, yet in a significant proportion, the T2 molecular signature is absent. Proposed molecular phenotypes associated with this T2 low group have not been validated into endotypes, and in the absence of biomarkers, patients with asthma in this category continue to receive guideline-based corticosteroid treatment, which may be relatively ineffective,16 underlining the urgency of research to elucidate mechanisms driving pathophysiology in T2 low asthma, with the goal of identifying associated biomarkers to distinguish patients within this group and developing effective treatments, which would enhance OCS stewardship.

Most importantly, this first-of-its-kind blueprint for the novel paradigm of OCS stewardship places the individual with asthma at its centre, co-developed by members of the asthma community and informed by extensive qualitative research into the perspectives and priorities of those living with asthma.

Notwithstanding the recent advances in targeted therapy and an investigative treatment pipeline with increasingly steady flow, the importance of OCS in the management of asthma is unlikely to recede in the near future. We commend this pioneering initiative which, building as it does around the existing severe asthma toolkit, holds great promise for real and measurable progress in increasingly formalized OCS stewardship.

CONFLICT OF INTEREST

Andrew Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Sanofi and Teva; has received speaker fees from AstraZeneca, Novartis, Roche and Teva; has participated in research with AstraZeneca, for which his institution has been remunerated; has attended international conferences with Teva; and has consultancy agreements with AstraZeneca and Sanofi. David Watchorn has nothing to disclose.

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