COPD – Pharmacology Management - PowerPoint Presentation

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COPD – Pharmacology Management

West Suffolk Integrated Formulary

Dr Linda Pearce

Respiratory Consultant Nurse

West Suffolk Hospital NHS Foundation Trust

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Declaration

Linda Pearce has undertaken advisory board meetings, lectures and received support to attend educational meetings fromAstra ZenecaBoehringer Ingelheim Chiesi

NAPPPfizerTEVA

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Local formulary decision making

Meeting 4 Respiratory Medical Consultants1 Respiratory Nurse Consultant2 Specialist nursesWCCCG med management representative x2WSFT - Chief PharmacistReview of Evidence

Feedback from practice visitsApproval process - WSCCG

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Why LAMA and not LABA as monotherapy?

Clinical trials have shown a greater effect on exacerbations rates for LAMA vs LABA treatmentEvidence Reducing exacerbations - level A

Hospitalisation – level BVogelmeier et al. Tiotropium versus salmeterol for prevention of exacerbation of COPD. N Engl J Med 2011;364 (12):1093-103Decramer et al. Once daily indacaterol vs tiotropium for patients with severe COPD (Invigorate): a randomised blinded, parallel-group study. The Lancet Respiratory medicine 2013;1(7):524-33

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Rationale for combining long-acting

bronchodilators

Inhaled bronchodilators are the foundation of COPD treatmentMost patients with COPD improve with bronchodilation

Maximal bronchodilation is not achieved using clinically approved doses of one class of bronchodilator aloneThere could be synergistic interactions between 2-agonists and anticholinergics

Cazzola M, Molimard M.

Pulm Pharmacol Ther

2010;23:257-67

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Bronchodilator therapy – GOLD 2017

The SPARK study indicated that

Ultibro® was superior in reducing the risk of exacerbations versus long-acting bronchodilator monotherapy

The FLAME study confirmed that Ultibro® reduced the risk of exacerbations to a greater extent than LABA/ICS

The BLAZE study (in patients with moderate to severe COPD) confirmed that

Ultibro

®

was superior to placebo and

tiotropium

on patient reported dyspnoea

Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017.

http://goldcopd.org

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Rationale for FLAME: similar exacerbation rates were observed with SFC and tiotropium in INSPIRE

In INSPIRE, rates of exacerbations requiring antibiotics or systemic corticosteroids

at 2 years were similar between tiotropium and SFC treatment groups

1

Rate of exacerbations

r

equiring antibiotics

or systemic corticosteroids

per year

2.0

1.5

1.0

0.5

0.0

p=0.656 (ns)

Tiotropium

18

μ

g

o.d

. (n=665)

SFC 50/500

μ

g b.i.d. (n=658)

1.32

1.28

FLAME

2

was designed to evaluate LABA/LAMA versus LABA/ICS in patients with

a history of ≥1 exacerbation in the preceding year

INSPIRE = Investigating New Standards for Prophylaxis in Reducing Exacerbations; ns = not significant;

SFC = salmeterol/fluticasone propionate

1.Wedzicha JA, et al. Am J Crit Care Med 2008

2. Wedzicha JA, et al. N Engl J Med 2016

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Patients targeted by inclusion criteria

C

D

A

B

Patient population approximated to GOLD D

Inclusion criteria

Post-bronchodilator FEV

1

≥25 and <60%

of predicted normal

Symptomatic as

defined by mMRC ≥2

≥1 documented

COPD

exacerbation requiring

treatment with antibiotics and/or systemic corticosteroids

within 1 year of randomization

Primary

outcome

Rate of all COPD exacerbations (mild/moderate/severe) during

52 weeks of treatment

Primary objective

To demonstrate that

IND/GLY was at least

non-inferior to SFC

Secondary objective

If non-inferiority could be established, the secondary objective was to demonstrate that IND/GLY is

superior to SFC

Wedzicha JA, et al. N Engl J Med 2016

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Ultibro

®

Breezhaler® significantly reduced the rate of all (mild/moderate/severe) exacerbations versus SFC over 52 weeks

All exacerbations (annualized rate)

3.0

4.0

2.0

RR (95% CI)

0.89 (0.83, 0.96), p=0.003

1.0

0

11% reduction

IND/GLY 110/50

μ

g o.d. (n=1,518)

SFC 50/500

μ

g b.i.d. (n=1,544)

5.0

Wedzicha JA, et al. N Engl J Med 2016

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The incidence of pneumonia was significantly lower

with Ultibro

® Breezhaler® than with SFC

Preferred term, n (%)

IND/GLY

110/50

μ

g o.d.

(n=1,678)

SFC

50/500 μg b.i.d.

(n=1,680)

Patients with at least one AE

1,459 (86.9)

1,498 (89.2)

Adverse events ≥3% in any treatment group

 

 

Chronic obstructive pulmonary disease

1,299 (77.4)

1,374 (81.8)

Nasopharyngitis

197 (11.7)

195 (11.6)

Viral upper respiratory tract infection

132 (7.9)

138 (8.2)

Upper respiratory tract infection bacterial

125 (7.4)

168 (10.0)

Lower respiratory tract infection

82 (4.9)

98 (5.8)

Upper respiratory tract infection

81 (4.8)

83 (4.9)

Pneumonia

53 (3.2)

80 (4.8)

Cough

50 (3.0)

51 (3.0)

Dyspnea

49 (2.9)

51 (3.0)

Influenza

35 (2.1)

56 (3.3)

Oral candidiasis

20 (1.2)

71 (4.2)

SAE(s)

308 (18.4)

334 (19.9)

Death

24 (1.4)

24 (1.4)

Discontinuation due to AE(s)

126 (7.5)

143 (8.5)

Discontinuation due to SAE(s)

85 (5.1)

87 (5.2)

Discontinuation due to non-SAE(s)

49 (2.9)

70 (4.2)

Radiographic imaging was required to confirm pneumonia

AE = adverse event; SAE = serious adverse event

P=0.02

Wedzicha JA, et al. N Engl J Med 2016

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ICS use in COPD/side effects

Patients more vulnerable to side effectsOlderMore likely to receive oral prednisoloneHigher doses ICS used in COPDLife usePneumoniaIncreased risk fractures

Skin bruising/delayed healingTB – endemic areasDiabetesCataractsDysphonia & candidasis

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Inhaled corticosteroids

Regular treatment with ICS increases risk of pneumonia especially in those with severe diseaseEvidence level – ATriple therapy improves lung function, symptoms, health status

Evidence level – AAnd reduces exacerbationsEvidence level - BGOLD 2017

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Published Papers

Brusselle et al. The inevitable drift to triple therapy in COPD: an analysis of prescribing pathways in the UK. International Journal of COPD. 2015:10 2207-2217http://www.dovepress.com.dx.doi.org/10.21.47/COPD.S91694D’Urzo et al. A re-evaluation of the role of inhaled corticosteroids in the management of patients with chronic obstructive pulmonary disease

Journal Expert Opinion on Pharmacotherapy 2015:16, Issue 12. 1845-1860http://www.tandfonline.com/doi/full/10.1517/14656566.2015.1067682

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COPD - a complex and heterogeneous disease

several different pathophysiological mechanismsICS may have an effect on some components of the disease if airway inflammation is present.  COPD phenotypes appear to benefit from ICS ACO

Frequent exacerbators Eosinophilia

Inhaled corticosteroids in COPD: the clinical evidence. Ernst P, Saad N, Suissa S.Eur Respir J. 2015 Feb; 45(2):525-37.

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Summary of studies evaluating the withdrawal of ICS in patients with COPD

Alan G Kaplan. Applying the wisdom of stepping down inhaled corticosteroids in patients with COPD: a proposed algorithm for clinical practice. Int J Chron

Obstruct Pulmon Dis. 2015; 10: 2535–2548.

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Not superior to any other product

Dose equivalencePneumonia, fracture riskFluticasone furoate/Vilanterol -Relvar

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Barnes

PJ

. Chest. 2000; 117 (2 suppl

): 10S – 14SBarnes PJ. Am J

Respir

Crit

Care Med. 2000; 161:342-344

Keatings

VM

et al. Am J

Respir

Crit

Care Med. 1997;155: 542-548

Culpitt

SV

et al. Am J

Respir

Crit

Care Med. 1999; 160: 1635 - 1639

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COPD Placebo Inhaler device kit

Add own Spacer device

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What is on the Horizon?

More generic and branded generic productsTriple therapy – ICS, LAMA, LABA

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Questions?