Page 38 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
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s­ignificant negative outcomes for patients, have similar systemic effects to 5 mg of pred-
such as bone density loss, hypertension, gas- nisone13, which might be also true for 2500 μg
severe asthma forum 1: severe asthma - basic and clinical views trointestinal bleeding, and have negative im- of budesonide14. Therefore, high doses of in-
pact on mental health7. haled GC should potentially be considered
as harmful as low doses of systemic GC15 and
Evidence from European Registries their effects are accumulative on top of sys-
temic GC7.
The European Respiratory Society (ERS) Se-
vere Heterogeneous Asthma Research collab- Approaches to Systemic GC Taper After
oration (SHARP) was set up in 2018 to har- Introduction of Monoclonal Antibodies
monize severe asthma management across
Europe and to unravel underlying heteroge- Monoclonal antibodies are powerful anti-in-
neity in a patient-centered way10. The current flammatory agents with GC-sparing proper-
project involves the first structured assess- ties16-19. Their availability represents a corner-
ment and comparison of national severe asth- stone for systemic GC taper and withdrawal
ma registries that are part of SHARP to dis- in severe asthma, which is becoming a com-
cover strengths/weaknesses in those registries mon scenario in clinical practice with the in-
and to evaluate severe asthma and its treat- creasing use of biologics. However, a specific
ment across Europe. guidance on how to proceed is lacking20.

Across-sectional retrospective analysis of Accordingly, over 130 international ex-
aggregated patients’ characteristics and their perts employed a modified Delphi method to
treatments before starting biologicals from 11 develop a consensus statement on appropriate
national SHARP affiliated severe asthma reg- systemic GC use and tapering in patients with
istries showed that patients were treated dif- asthma, adverse effects, patient–physician
ferently between countries. Their mean in- shared decision-making, and future research
haled GC daily dose (fluticasone equivalent) domains21. The paper provided a broader
ranged from 700 μg in Slovenia to 1335 μg in guidance on when and how to taper system-
Poland when starting anti-interleukin (IL)-5 ic GC in patients with asthma, regardless of
antibody and from 772 μg in Slovenia to 1344 whether biological therapy has been initiated.
μg in Spain in those starting anti-IgE, respec- According to consensus, tapering should be
tively. Maintenance oral GC use ranged from individualized and attempted in all patients
21.0% (Belgium) to 63.0% (Sweden) and with asthma receiving maintenance systemic
from 9.1% (Denmark) to 56.1% (the UK) in GC therapy, regardless of comorbidities. The
patients starting anti-IL-5 and anti-IgE, re- recommendations generated support for min-
spectively11. The reasons for these differenc- imizing systemic GC use as much as possible.
es are not entirely clear. Potential explana- Global Initiative for Asthma (GINA) recom-
tions, which would require a focused study by mendations restrict systemic GC use to those
the SHARP clinical research collaboration, patients who are ineligible for biologic treat-
might include the cost of treatment and the ment and define the lowest acceptable system-
fear of high-dose treatment-related side-ef- ic GC maintenance daily dose at less than 7.5
fects11. mg of prednisolone2. On the other hand, the
Delphi expert consensus considered a daily
Indeed, a recent systematic review and dose of less than 5 mg of prednisolone as ac-
meta-analysis has suggested that the majori- ceptable, if no alternative treatment is avail-
ty of oral GC-sparing effect of high-dose in- able21. However, even merely 5 mg of pred-
haled GC was likely to be due to their sys- nisolone a day contributes to a cumulative
temic effects12. Regarding the effects on HPA dose of more than 1.8 g per year. A­ dditional
axis, 1000 μg of fluticasone propionate might
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