HPE 91 – March 2019 | Page 4

p1_hpe92_cover_v3.indd 1 18/06/2019 14:00
Figure reproduced with permission from IQVIA Institute
*Asthmatic features/features suggesting steroid responsiveness in this context include any previous secure diagnosis of asthma or atopy, a higher blood
eosinophil count, substantial variation in FEV1 over time (at least 400 ml) or substantial diurnal variation in peak expiratory flow (at least 20%)
This is a summary of the recommendations on non-pharmacological management of chronic obstructive pulmonary disease and use of inhaled therapies
in people over 16. The guideline also covers diagnosis and other areas of management.
See www.nice.org.uk/guidance/NG115
© NICE 2018. All rights reserved. Subject to Notice of rights.
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Issue 92 | 2019
hospitalpharmacyeurope.com
Updated COPD NICE guidelines P12
Quality care with biosimilars P22
Intravenous ibuprofen P26
REVIEW
COPD: overview of updated
NICE guidance
The guidance addresses many current clinically relevant issues in the diagnosis and management
of patients with COPD but acknowledges that evidence is still lacking or unclear in some areas,
leading to recommendations for research
FIGURE 1
Chronic obstructive pulmonary disease in over 16s: non-pharmacological management
and use of inhaled therapies
Fundamentals of COPD care
Confirmed
•Offer treatment and support to stop smoking
diagnosis
•Offer pneumococcal and influenza vaccinations
•Offer pulmonary rehabilitation if indicated
of COPD
•Co-develop a personalised self-management plan
•Optimise treatment for comorbidities
These treatments and plans should be
revisited at every review
Ravijyot Saggu
BPharm MRPharmS
Clin Dip IP
Senior Clinical
Pharmacist, University
College Hospital London
NHS Foundation Trust,
London, UK
In December ember 2018, the National Institute for
Health
and Care Excellence (NICE) published
its long-awaited update
to the 2010 guideline on
chronic obstructive pulmonary disease (COPD) in
over the update and previous guideline, and other
16-year-olds. -olds. A long time had elapsed between
guidance, such as that
produced (and updated more
frequently) by the Global initiative for chronic
Obstructive Lung Disease (GOLD), has been useful in
the interim to individualise treatment for patients.
This article will outline
the significant changes in
the NICE guidance.
COPD is a progressive long-term condition and
leading cause
of death
and disability; it has an
estimated cost to the National Health Service over
£800 million
pounds per year. The mortality rate in
England is roughly 23,000 deaths each year (around
one person every 20 minutes). 1
COPD is associated with current or history of
smoking and/or biomass fuel/noxious particle
exposure and
usually affecting people over the
age of 35 years (and often diagnosed in their 50’s).
The ageing population
is living for longer, often
with a poorer quality of life, which itself presents
P8
a challenge to the healthcare system. Current
generations may have
started smoking from
a younger age than previous, resulting in earlier
onset of poor
health. Prevalence is associated with
geographical
levels of deprivation and is increasing;
many millions remain
undiagnosed and by 2020,
COPD will be
the third
leading cause of death
globally. 1,2
COPD is characterised by breathlessness
and cough. Patients will typically experience
exacerbations (some patients more so) which
negatively impacts disease progression, rates of
hospitalisation on and readmission and health status.
The number
of exacerbations in the year prior is the
strongest predictor of a
patient’s future exacerbation
frequency. 3 The rate of lung function decline is faster
in the earlier
r stages of
the disease, which can be
modified by
treatment. 1
The new guideline specifically acknowledges the
need for a secure diagnosis, made using signs and
symptoms and confirmed through spirometry by
appropriately trained healthcare workers (who have
up to date skills and are competent in interpreting
results). This
includes noting exacerbation history,
excluding conditions such as asthma/cancer and
consideration n of alternative diagnoses such as
alpha-1 antitrypsin trypsin disease. Diagnosis should also be
considered in symptomatic individuals with normal
spirometry. Oral steroids should not be used for
reversibility testing or
to predict response to inhaled
corticosteroid id (ICS) in individuals. 2
Pharmacogenomics
Key opinion leaders and emerging research
suggest that there are disease phenotypes (frequent
exacerbator or persistent symptomatic patient). 3
Start inhaled therapies only if:
However, SPONSORED the place of inhaled triple therapy (where
access to quality medicines, efficient use of
While the analytical characterisation phase of
•all the above interventions have been offered
‘triple therapy’ refers to use of long-acting beta
healthcare budgets, and healthy levels of supply and
biosimilar development aims to match both the
(if appropriate), and
agonist (LABA), long-acting anti-muscarinic agent
competition.
•inhaled therapies are needed to relieve
(LAMA) and ICS together), asthma–COPD quality overlap patient care
3 Ultimately, it must meet the needs
structure and function of the candidate biosimilar to
Upholding of all stakeholders including patients, healthcare
the reference product, minor structural differences
breathlessness or exercise limitation
management, role of eosinophils 3 and role of
professionals/providers, payers and manufacturers
are acceptable provided they do not impact
macrolide antibiotics in disease management are
(Figure 1).
also important considerations biosimilars
3
function. 19,20 If structural comparisons leave residual
with (which the guideline
uncertainties, functional studies are the first step in
attempts to address) but require longer term data
Pathway to the pharmacy: critical quality
addressing these. Dr McBride presented an example
to further The role inform of biosimilars future practice. in upholding Updates quality in this patient care was explored during an Amgen Europe-
attributes
of a candidate biosimilar product which fell outside
Inhaled therapies
guideline sponsored have been satellite made symposium on the following: at the 2 24th Congress of the European Association of Hospital
D r Helen McBride began by summarising the
of the defined glycosylation quality range during
•Investigations, including incidental findings differences between biologics and chemically
structural analysis. However, functional testing
Pharmacists (EAHP), Barcelona, Spain on 28 March 2019
Offer SABA or SAMA to use if needed
CT scans – primary care review, advice for patients
synthesised generic drugs, biologics being larger
associated with glycosylation showed that the
to return if respiratory symptoms appear, offering
and structurally more complex. 7–9 The complexity
biosimilar remained within the defined functional
smoking cessation and discussing the potential risk
of biologics, particularly monoclonal antibodies,
quality range. 20 Another challenge that biosimilar
of lung cancer
is reflected in the potential for post-translational
manufacturers may face is an observed shift in the
Person still breathless or has exacerbations despite treatment?
•Prognosis – to avoid use of a multidimensional
modifications that can, in turn, affect mechanism
structure and/or function of the reference product,
index such as BODE to assess prognosis
of action, bioavailability, clearance, immunogenicity,
for example due to manufacturing changes. This was
•Inhaled therapies – to discuss risk of pneumonia
effector function and binding. 10,11 Manufacturing
encountered during the development of rituximab
and ICS use with patients. Minimising the number
of biological products is a proprietary multistep
and trastuzumab biosimilars. 21,22
No asthmatic features/features suggesting steroid Asthmatic features/features
and types Dr of Gunar inhalers Stemer patients (Vienna use and General ensuring Hospital,
they of treatment) and release funds for new medicines
process, with each manufacturer using proprietary
Dr McBride concluded that analytical
responsiveness*
suggesting steroid responsiveness*
are trained Vienna) on use
opened and chaired the symposium,
as they come to market. 2–4 While biosimilars can
techniques and unique cell lines. 10,12 Posttranslational
modifications can be influenced
establishing similarity in CQAs for the biosimilar
characterisation, including identifying and
•Oral with phosphodiesterase presentations from 4 inhibitors Dr Helen are McBride mentioned (Amgen help to mitigate the explosion in cancer care costs,
in line Biosimilars, with the USA), associated Professor 2017 João technology Gonçalves appraisal education is needed to correct any misperception of
by the manufacturing process (for example, cell Analytical testing candidate and reference product, forms the
•Prophylactic (University antibiotics of Lisbon, Portugal) – recommendations and Mr Simon made inferior quality compared with originator medicines
type and culture conditions, purification, and raw forms the strong foundation of biosimilar development. However, it
Offer LABA + LAMA
Consider LABA + ICS
on (unlicensed) Cheesman (University use of azithromycin College London Hospitals and, therefore, support acceptance and maximum
materials) 13,14 and hence the manufacturing process basis of
must be considered as part of the whole totality of
•Oxygen NHS Foundation therapy – eligibility Trust, UK).
of patients for
uptake. 5
must be tightly controlled to ensure product
evidence – comprising analytical characterisation,
establishing the
and risks of prescription (including short burst
When selecting a biosimilar and evaluating which
consistency and quality over time. 13,15,16
non-clinical studies and clinical studies (PK/
and Supporting ambulatory use) sustainable and consideration quality care
for use
product offers the best value, criteria to consider
Biosimilar development is performed via a fact you have pharmacodynamics [PD], efficacy and safety) −
For ALL inhaled therapies:
Person still breathless or has exacerbations despite
in pulmonary Global spending hypertension medicines (noting is this increasing is not and the include: production process/manufacturer; product
stepwise approach to demonstrate biosimilarity and a biosimilar
in order to justify and confirm biosimilarity and
Train people in correct inhaler technique, and
further treatment?
a treatment cost of biological for breathlessness medicines and is a not major effective driver for this specifications; clinical efficacy; and clinical safety
bioequivalence to the reference product. 10,12 The goal
clinical equivalence. 16–18
review medication and assess inhaler technique and
isolated increase: nocturnal 1 the overall hypoxaemia global costs caused of by medicines COPD) are and tolerability. 6 For pharmacists in particular,
of biosimilar development is to demonstrate clinical
adherence regularly
•Managing projected pulmonary to exceed US hypertension $1.5 trillion and by cor
2023. 1
further considerations include: ease of use/route
equivalence, not to independently re-establish safety
Monoclonal antibodies in the pharmacy:
pulmonale Dr Gunar – advice Stemer on described optimised three therapies potential
of administration, vial size, storage considerations
and efficacy Offer which have already been extensively
practical considerations
•Lung approaches volume reduction to achieve (LVR) sustainability surgery and
in the face of (including packaging and stability), supply chain
studied in clinical LAMA trials + LABA of + the ICSreference product
Professor João Gonçalves started his presentation
procedures limited healthcare – updated advice resources: to increase increase uptake/access
healthcare
reliability, support/education, reimbursement and
(Figure 2). 16–18 Analytical characterisation forms the
by noting how the extensive analytical and
•Self-management/exacerbation budgets, improve efficiency, and/or plans – limit developed the medical price. 6 Dr Stemer explained that in respect to the
foundation of biosimilar development, establishing
quality characterisation that is required during
in collaboration offering. Of these with options, patients improving and carers. efficiency is tendering process for biosimilars, a multi-tender/
similarity of both structure and function to that of
biosimilar development has not only given
These the most supplement attractive. the existing recommendations multiple ‘winner’ model may be preferable to
the reference product. 16–18 Biosimilar manufacturers
confidence in biosimilar use but has also provided
on:
Biosimilar medicines can play an important role a single tender/single ‘winner’ model in terms of
start with limited knowledge of the reference
important insights that can be applied to biologics
•diagnosing in improving COPD efficiency using symptoms, by driving spirometry cost savings
and overall cost (competition keeps price Explore down) further and, treatment options if needed (see product; guideline) therefore, biosimilars are developed
more broadly. Such insights have influenced
other and tests
reducing ‘wasteful’ spending on more costly therefore, sustainability. 3
based on information from testing the reference
the European Medicine Agency’s ‘Guideline on
•managing alternatives. stable 2 As COPD such, using the potential nebulisers, savings oral from Dr Stemer concluded by highlighting the role of
product and establishing a list of critical quality
good pharmacovigilance practices’. 23 During the
therapy biosimilars and pulmonary – in addition rehabilitation to generic drugs
– represent hospital pharmacists in supporting sustainability of
attributes (CQAs) that need to be matched within
development of a trastuzumab biosimilar, for
•multidisciplinary an important tool management for achieving of efficient stable COPD,
and
care by ensuring responsible, criteria-based product
an expected quality range (Figure 3). 12,16–19 CQAs
example, shifts in antibody-dependent cellular
including sustainable physiotherapy, healthcare occupational systems. 2,3 The therapy, availability of selection, providing education, and safeguarding
are specific attributes that can impact biologic
toxicity (ADCC) were observed in the trastuzumab
nutrition biosimilars and palliative also has the carepotential to increase patient the onboarding of biosimilars. Sustainable care
activity, such as potency, pharmacokinetics (PK)
reference product; these shifts were associated
•managing access to exacerbations biological medicines of COPD (by in reducing primary care the cost encompasses multiple factors including patient
and immunogenicity. 12
with manufacturing changes, highlighting
and in hospital.
NICE FIGURE has produced 1 a visual summary alongside
FIGURE 2
the guidance, covering non-pharmacological
A multi-stakeholder definition of sustainability for the biosimilars
Biosimilar development: a stepwise approach to demonstrating bioequivalence and
management and use of inhaled therapies (Figure
1). They marketplace also published concurrent 3
antimicrobial
biosimilarity to the reference product 16–18
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Originator development 18
Demonstrate safety and effectiveness with adequate and
well-controlled substantial evidence for a new product
Clinical studies
(efficacy and safety)
(PK/PD)
With the use of
biosimilars, the
costs go down
and you can
generate cost
savings in the
overall healthcare
budget
Non-clinical studies
Analytical testing
Biosimilar development 16–18
Demonstrate clinical equivalence (efficacy, safety and
immunogenicity) to the reference product, but not
independently re-establish safety and efficacy
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