Review of Inhaled Corticosteroids (ICS) in patients with COPD This guidance should be used with the Treatment Guidelines for COPD and should be individualised for each patient. It provides an algorithm to identify people with COPD who might benefit from ICS treatment (consider switch to Triple Therapy Inhalers) and those in whom ICS may not be appropriate, an approach to reduce and withdraw ICS inhalers.

At Review and before therapy changes check and consider the following: Correct diagnosis? Asthma or COPD or Asthma-COPD Overlap (ACO)

Inhaler Technique?

Adherence?

Clinical effectiveness / side-effects?

Self-management plan up to date?

Treatment at

assessment

consultation

ICS + LABA

ICS + LABA + LAMA

(Triple therapy)

Does the patient have asthma or asthmatic features?

Documented history of asthma, with or without atopy (note: consider diagnoses made in people under 40 more likely to be correct)

A large degree of reversibility of airflow limitation (>12% and 200ml in post-bronchodilator FEV1)

Experienced more than one exacerbation* (or hospital admission) in last 12 months

NO

Does the patient have a high exacerbation risk?

>2 exacerbations or >1 exacerbation leading to hospitalisation in the previous 12 months?

AND

Does the patient have elevated blood eosinophils?

If needed please contact the AIRS service for advice.

NO

If YES, continue ICS

treatment.

Consider titration

to the lowest

effective dose to

prevent airways

exacerbations and

/ or asthma

symptoms

For COPD (ACO) patients stable & appropriately on

triple therapy (LAMA+ICS+LABA),

consider switch to a single combination inhaler (Trimbow (MDI) or Trelegy

(DPI))

Yes

NO

Monitor for

potential ICS-

related adverse

events; continued

exacerbation

despite biomarker

may indicate lack

of efficacy of ICS

or need for

additional therapy

Blood eosinophil

counts (BEC). BEC may be a useful

biomarker to predict

ICS responsiveness and

exacerbation risk.

GOLD suggests counts

should help guide

treatment decisions but

should be used in

conjunction with other

clinical assessments.

Treatment decisions,

such as whether to add

ICS to a treatment

regimen to reduce

exacerbations, may be

supported by BEC.

However, given the

increased risk of

pneumonia associated

with ICS use, blood

eosinophil counts

should be carefully

considered alongside

other clinical

assessments to support

individualised

treatment decisions for

your patients.

Yes

Use with local Prescribing Guidelines for stable COPD or Asthma-COPD Overlap

If No, consider step down / stop ICS as guide below (Record CAT or MRC score before changing treatment)

Nikki Woodhall (Pharmacy Advisers, MKCCG) March 2020 FINAL V4 Approved by MKPAG: March 2020 Review Date: March 2022 Page 1

Non-smoker?

Immunised? Pneumococcal and annual Flu?

Pulmonary Rehabilitation or other respiratory education?

For people with COPD who do not need ICS

Step down / stop ICS - Taper or stop ICS immediately according to dose potency then switch to LABA+LAMA

combination inhaler (Consider patient history, preferences and clinical needs). Options include:

Low/medium-dose* ICS STOP ICS

Switch to LABA/LAMA

(optimise bronchodilation)

E.g. Spiolto Respimat® 2 puffs once daily (Aerosol)

OR

E.g. Duaklir Genuair® 1 dose twice daily (DPI)

High-dose* ICS reduce ICS dose every 4 weeks (to

medium/low dose) before stopping.

Then start LABA/LAMA (optimise bronchodilation)

E.g. Spiolto Respimat® 2 puffs once daily (Aerosol)

OR

E.g. Duaklir Genuair 1 dose twice daily (DPI)

Interim call with patient

(approx. 2 weeks) to check

compliance and ensure

stability

Patient should be

encouraged to contact

monitoring clinician if any

worsening of symptoms or

conditions

Reassess need for ICS use

if:

Moderate or severe

exacerbations

Airflow limitation

worsening (FEV1

decrease >100mL)

Optional (blood

eosinophil count >300)

Consider referral to

AIRS respiratory service

for review (&

consideration for triple

therapy if clinically

indicated)

If stable or improved

continue with LABA/LAMA

(optimise bronchodilation)

If stable or improved, reduce ICS

dose further (50%)

4 Weeks

4 Weeks

4 Weeks

If stable or improved

continue with LABA/LAMA

(optimised bronchodilation)

Follow-up with monitoring clinician for full clinical review

See the patient

Twice yearly review during the first year of ICS withdrawal

Followed by an annual review if the patient’s COPD is stable and “exacerbation-free”

If the patient experiences a deterioration in symptoms or symptoms that impact on quality of life, consider Triple Therapy trial or referral to AIRS clinic.

6 months 6 months

Low/Medium dose

ICS can be stopped

immediately

High dose ICS must be

tapered / reduced slowly

before stopping! *

If stable or improved

STOP ICS and start LABA/LAMA

(optimise bronchodilation)

4 Weeks

* See table on Page 3

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High Dose ICS/LABA inhalers Step down to Medium / Low dose

ICS/LABA inhalers then STOP Then switch to LABA/LAMA

combination inhaler Seretide 250/25 2 puffs BD (MDI) (equivalent to 2000mcg BDP#/Clenil Modulite®)

(MDI unlicensed in COPD)

Seretide 125/25 2 puffs BD (MDI)

Then Seretide 125/25 1 puff BD (MDI)

Maintain LABA/LAMA

(e.g. Spiolto 2 puffs OD) (Aerosol)

Seretide 500/50 Accuhaler 1 dose BD (DPI)

(equivalent to 2000mcg BDP#/Clenil Modulite®)

Seretide 250/50 Accuhaler 1 dose BD (DPI)

Then Seretide 100/50 Accuhaler 1 dose BD (DPI)

Maintain LABA/LAMA

(e.g. Duaklir Genuair 1 dose BD) (DPI)

Symbicort 400/12 Turbohaler 2 doses BD (DPI)

(equivalent to 1600mcg BDP#/Clenil Modulite®)

Symbicort 200/12 Turbohaler 2 doses BD (DPI)

Then Symbicort 200/6 Turbohaler (DPI) 1 dose BD (DPI)

Maintain LABA/LAMA (e.g. Duaklir Genuair 1 dose BD) (DPI)

Fostair 200/6 2 puffs BD (MDI)

(equivalent to 2000mcg BDP/ Clenil Modulite®)

Fostair 100/6 2 puffs BD (MDI)

Then Fostair 100/6 1 puff BD (MDI)

Maintain LABA/LAMA

(e.g. Spiolto 2 puffs OD) (Aerosol)

Fobumix 320/9 Easyhaler 2 doses BD (DPI) (equivalent to 1600mcg BDP#/Clenil Modulite®)

Fobumix 160/4.5 Easyhaler 2 doses BD (DPI)

or Fobumix 160/4.5 Easyhaler 1 dose BD (DPI)

Maintain LABA/LAMA (e.g. Duaklir Genuair 1 dose BD) (DPI)

Stepping down Inhaled Corticosteroids (ICS) in Chronic Obstructive Pulmonary Disease

Do not stop ICS in patients with Asthma Features!

o This guideline is for people with COPD with NO features of asthma. Confirm diagnosis if unsure and exclude patients with asthma or suspicion of asthma

o Discontinuing ICS rapidly decreases the risk of serious pneumonia. Step down by approx. 50% every four weeks and follow up with a telephone call

after two weeks

o The benefits of ICS for patients with COPD are greater in the subset of patients with evidence of eosinophilic airway inflammation. Review the treatment of

patients with NO evidence of eosinophilic airway inflammation

o Increasing evidence suggests that prescribing high dose inhaled corticosteroids (ICS), defined as >1000mcg beclomethasone or equivalent, can cause harm

in people with COPD without any further clinical benefit than moderate doses. A steroid Card should be given if patient is taking high dose ICS.

o High doses of ICS should be reduced to prevent potential side effects such as pneumonia, adrenal suppression, reduced bone mineral density, diabetes and

glaucoma. Titrate down to the lowest effective dose. All patients receiving high dose ICS who have risk factors for osteoporosis should be considered for a DEXA scan.

o Check and optimise inhaler technique, support adherence, check for prescribed duplication of inhaled medicine and ensure prescribing is by brand to ensure

device continuity.

Commonly prescribed ICS treatments for COPD – stepdown every 4 weeks then stop and switch to LABA/LAMA. Please contact the Pharmacy Advisers for information on other combinations.

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#BDP= Beclomethasone Dipropionate

Long-term ICS use is associated with a significant risk of pneumonia and systemic effects, therefore ICS-containing

regimens are not recommended in low-risk COPD patients, and should only be considered for high-risk COPD

patients with features of asthma, or as triple therapy if exacerbations persist despite treatment with a LABA+LAMA.

Recent studies have indicated that ICS can be withdrawn in both low and high risk patients, provided adequate

bronchodilator therapy is in place (and they have NO asthma features)

Blood eosinophilia in COPD relates more to trying to decide which patients are likely to gain benefit (rather than

suffer harm) from Inhaled Corticosteroids, as compared to maximal bronchodilation through different physiological

and pharmacological pathways.

Notes on step down guidelines:

Eosinophils are measured as part of a full blood count (FBC) and readings are available in SystmOne as “Eosinophil count-observation (10^9/L)”

The risk of adrenal crisis is reduced by stepping down from a high dose to a moderate dose inhaled corticosteroid before stopping the ICS altogether

Seretide evohalers (MDI) are not licensed for use in COPD at any dosage

Make sure you refer to the local COPD guidelines: refer to local stop smoking program, refer to pulmonary rehab and offer annual flu vaccination and pneumococcal vaccination.

If patient has been diagnosed with pneumonia – review and reduce / stop ICS where appropriate, or discuss with AIRs for further guidance.

References:

GOLD. Gold Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2019 Report). 2019.

Rossi A, Guerriero M, Corrado A. Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation: a real-life study on the appropriateness of treatment in moderate COPD patients (OPTIMO). Respir Res 2014b. 15:77

Rossi 2014a; Rossi 2014b; Magnussen 2014 Withdrawal of ICS only increases exacerbation rates in patient with both raised eosinophils and a history of frequent exacerbations

Calverley P. 2017 Et al Eosinophilia, Frequent Exacerbations, and Steroid Response in Chronic Obstructive Pulmonary Disease

Rossi A, van der Molen T, del Olmo R, Papi A, Wehbe L, et al. INSTEAD: a randomised switch trial of indacaterol versus salmeterol/ fluticasone in moderate COPD. Eur Respir J 2014a;44(6):1548–56

Magnussen H, Disse B, Rodriguez-Roisin R, Kirsten A, Watz H, et al; WISDOM Investigators. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med 2014;371(14):1285–94

Suissa S, Coulombe J, Ernst P. Discontinuation of Inhaled Corticosteroids in COPD and the Risk Reduction of Pneumonia. Chest 2015;148(5): 1177–83

Suissa S, Patenaude V , Lapi F , Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax 2013;68:1029–36

Brusselle G, Pavord ID, Landis S, Pascoe S, Lettis S, Morjaria N, Barnes N, Hilton E. Blood eosinophil levels as a biomarker in COPD. Respir Med. 2018 May;138:21-31. doi: 10.1016/j.rmed.2018.03.016

Vedel-Krogh S, Nielsen SF, Lange P, Vestbo J, Nordestgaard BG. Blood eosinophils and exacerbations in chronic obstructive pulmonary disease: The copenhagen general population study. Am J Respir Crit Care Med. 2016;193(9):965-974. doi:10.1164/rccm.201509-1869OC

Triple therapy inhaler options for patients reviewed and require ICS/LABA/LAMA treatment:

Trimbow® (MDI) 2 puffs BD (Beclometasone 87mcg/Formoterol 5mcg/Glycopyrronium 9mcg) (equivalent to 1000mcg BDP /Clenil Modulite®)

OR

Trelegy Ellipta® (DPI) 1 puff daily (Fluticasone Furoate 92mcg/Vilanterol 22mcg/Umeclidinium 55mcg) (equivalent to 1000mcg BDP /Clenil Modulite®)

Thanks to Primary Care Respiratory Society (PCRS), BCCG/LCCG & Leicestershire & Rutland for sharing Guidance on ICS withdrawal

Primary Care Respiratory Society https://www.pcrs-uk.org/sites/pcrs-uk.org/files/SteppingDownICS_FINAL5.pdf

BCCG LCCG Inhaled Corticosteroid Review Protocol in COPD Sept19

Leicestershire and Rutland Respiratory Prescribing Group – Stepping Down ICS in COPD Feb19

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