COPD

New evidence in COPD: is there consensus for clinical practice recommendations?

Industry Theater – American Thoracic Society 2018, May 18–23.

Chaired by Professor David Price (Singapore), with Professors Ken Chapman (Canada) and Dave Singh (UK). Click these links to view their biographies and introduction videos.

During this Novartis supported Industry Theater, a faculty of experts discuss the new evidence informing the role of LABA/LAMA and LABA/LAMA/ICS therapy in COPD management. The importance of personalized COPD management is discussed, including clinical considerations and consensus regarding use of ICS, and evidence-based approaches for ICS withdrawal.

Webinars

View footage from the COPD Spotlight Webinar on the 2019 GOLD update for COPD management and find out the responses to some of the FAQs from the COPD Spotlight Webinar entitled ‘Can we avoid ICS in COPD? Time for clarity’.

GOLD 2019 update for COPD management

Welcome to the COPD Spotlight Webinar on the 2019 GOLD update for COPD management. The webinar provides a concise review of the recommendations from GOLD 2019 and the implications for clinical practice. The review is followed by an interactive Q and A session with physicians from across the world.

Our expert faculty guiding us through GOLD 2019 are Professor Wisia Wedzicha, Professor of Respiratory Medicine, National Lung and Heart Institute, Imperial College, London, UK, and Dr Kai Beeh, Founder and Medical Director of insaf Respiratory Research Institute, Wiesbaden, Germany.

Welcome and introduction

Spotlight on the revised GOLD 2019 recommendations

Wisia Wedzicha, National Lung and Heart Institute, UK

Spotlight on the implications of GOLD 2019 for clinical practice

Kai Beeh, insaf Respiratory Research Institute, Wiesbaden, Germany

Global interactive Q & A session

Can we avoid ICS in COPD? Time for clarity

This section provides answers from Professor Wisia Wedzicha and Dr Kai Beeh to the FAQs from the COPD Spotlight Webinar entitled “Can we avoid ICS in COPD? Time for clarity”. 

FAQ - COPD Spotlight Webinar Can we avoid ICS in COPD? Time for clarity

Question 1

A patient receiving triple therapy moves from Global initiative for chronic Obstructive Lung Disease (GOLD) group D to B. Should we re-evaluate this patient every 12 months or leave him/her on triple therapy because inhaled corticosteroid (ICS) dependency was previously shown?

Wisia Wedzicha answers:

• If a patient receiving triple therapy moves from GOLD group D to B and has only one or no exacerbations over the past 12 months, I would try to withdraw the ICS.
• When withdrawing ICS, it is very important to warn patients that they may still get a cold and have an exacerbation (one moderately severe exacerbation over a 12 month period is GOLD B level), but this is not an indication for ICS therapy.¹  I would avoid withdrawing ICS directly over a winter period when the risk of exacerbations is much higher.
• It is also important to inform patients that when an ICS is withdrawn, they will experience some short-term withdrawal effects. While we would hope that with dual bronchodilator therapy some of these withdrawal effects will be reduced, patients may still experience some dyspnoea, cough or wheeze. Nonetheless, that is not an indication to go back on an ICS.

Kai Beeh answers:

• If a patient is exacerbating, treatment is escalated and the patient stabilizes, this indicates they are responding to and benefiting from receiving ICS, or triple combination therapy.
• On the other hand, we now have a de-escalation strategy for the management of COPD, as for asthma. For example, when treating patients with asthma, we step up therapy, reassess the stability of the patient and once we have reached clinical control, we step down therapy.²
• As such, although previous history suggests that this patient is an ICS responder, there is no reason why we cannot try to withdraw ICS and minimize exposure to this therapy after a period of monitoring.

**DISCLAIMER: Responses reflect the speakers’ opinions at the time of the webinar and may not necessarily reflect opinion of Novartis Pharma AG**

Question 2

If a patient is in Global initiative for chronic Obstructive Lung Disease (GOLD) group D and is stable on long acting β₂ agonist/long-acting muscarinic antagonist (LABA/LAMA), but their eosinophil level is above 300 cells/µL, should we escalate to triple therapy or not?

Wisia Wedzicha answers:

• My view is that if a GOLD group D patient is stable on a LABA/LAMA and not frequently exacerbating (i.e. with 0 or 1 exacerbation per year), but has an elevated eosinophil level, I would repeat the assessment of eosinophil levels and monitor them.
• If a patient has two exacerbations per year and a high eosinophil level, then that is an indication for inhaled corticosteroids (ICS), as identified in the WISDOM study.
  • In WISDOM, ICS withdrawal only increased exacerbation risk in patients with ≥2 exacerbations per year and blood eosinophils elevated at a level ≥400 cells/µL.³
• In patients with fewer than two exacerbations per year, an ICS-containing medication should not be used.¹

Kai Beeh answers:

• It is important to remember that we are not treating a biomarker. In this case, the biomarker of eosinophil levels helps us to identify patients with exacerbations who are likely to respond to treatment with an ICS.
• The indication for the use of ICS is exacerbation frequency, so if a patient is stable on a dual bronchodilator, I would not escalate to triple therapy, regardless of eosinophil count.

DISCLAIMER: Responses reflect the speakers’ opinions at the time of the webinar and may not necessarily reflect opinion of Novartis Pharma AG

Question 3

Is one long acting β₂ agonist/long-acting muscarinic antagonist (LABA/LAMA) combination superior to others and why?

Kai Beeh answers:

• Currently, we do not have head-to-head comparative evidence for LABA/LAMA combinations in terms of relevant outcomes.
• To date, one small study has been undertaken that assessed lung function markers⁴
  • In this randomised, two-period crossover open-label study, change from baseline in trough forced expiratory volume in 1 second (FEV₁) in symptomatic patients with COPD (N=236) was determined at Week 8, following treatment with umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO)
  • At Week 8, UMEC/VI was superior to TIO/OLO in terms of change in trough FEV₁
  • However, this study provided little data in relation to how LABA/LAMA combinations may differ in terms of efficacy/safety outcomes.
• For some LABA/LAMA combinations, such as indacaterol/glycopyrronium, there is an abundancy of consistent data. However, for other LABA/LAMA combinations, there is less evidence (e.g. in relation to exacerbation outcomes versus comparators). As a result, it is fair to consider the available evidence when it comes to choice of LABA/LAMA in clinical practice
  • When choosing a LABA/LAMA, it is important to remember that the effects observed may not apply to all LABA/LAMAs.

Wisia Wedzicha answers:

• In terms of the extent to which FEV₁ has been studied, there is likely to be not much difference between LABA/LAMA combinations, but other efficacy outcomes have been studied to a much greater extent in some compounds compared with others.
• A study comparing the effects of two different LABA/LAMA combinations on exacerbation outcomes is unlikely to be undertaken. As such, in my opinion, we should consider the available evidence and our experience with the compounds when choosing a LABA/LAMA combination. 

DISCLAIMER: Responses reflect the speakers’ opinions at the time of the webinar and may not necessarily reflect opinion of Novartis Pharma AG

Question 4

Does a high eosinophil count indicate asthma-COPD overlap (ACO)?

Wisia Wedzicha answers:

• Currently, we have little real knowledge about the cause(s) of high blood eosinophil counts in patients with COPD and their significance.
• We do know that blood eosinophils and sputum eosinophils are quite different.
  • In one study, a weak correlation was reported between blood and sputum eosinophil levels, and blood eosinophil % did not predict sputum eosinophil %.⁵
• We do not understand what a high blood eosinophil level really means, but an association between high blood eosinophils and risk of exacerbations has been reported.
  • In a recent study, the rates of COPD exacerbations during 1-year follow-up were significantly greater for patients with blood eosinophil counts of ≥300 cells/mm³, ≥400 cells/mm³ and ≥500 cells/mm³, compared with patients with eosinophil levels lower than these cut-offs.⁶
• I think that high eosinophil counts could indicate a move into the ACO territory, but there is limited evidence available. It should be noted that patients should not be treated based on a high eosinophil count, but on their exacerbation history.¹

Kai Beeh answers:

• Some recent COPD studies included patients with a prior history or current diagnosis of asthma. In these studies, higher levels of eosinophils were reported (on average), which could signify ACO.^7,8

DISCLAIMER: Responses reflect the speakers’ opinions at the time of the webinar and may not necessarily reflect opinion of Novartis Pharma AG

Question 5

Would you measure blood eosinophils in non-frequently exacerbating patients? If yes, would you make a distinction between patients with 0 and 1 exacerbation in your approach?

Wisia Wedzicha answers:

• Data from exacerbation studies inform us that exacerbation events are not very frequent and that a patient may experience one exacerbation one year, but then may not have an exacerbation over the next few years.
  • In the ECLIPSE study, the majority of patients reporting 0 or 1 exacerbation in the year before enrolment went on to have infrequent exacerbations in the first year of the study (negative predictive value 79%).⁹
  • Similarly, infrequent exacerbations in Years 1 and 2 predicted infrequent exacerbations in Years 2 and 3 of the study, respectively (with corresponding negative predictive values of 83% and 84%).⁹
• In terms of measuring blood eosinophils in infrequent exacerbators, I would do this, as it is very useful to obtain a baseline reading.
  • If blood eosinophils are elevated and the patient is not exacerbating, I would repeat the assessment and monitor eosinophil levels but not make any immediate change to therapy.

Kai Beeh answers:

• I think that determining eosinophil levels may be useful to characterize patients. However, for infrequent exacerbators, the eosinophil level (whether high or low) does not modify management decisions, which should be based on exacerbation history.¹

DISCLAIMER: Responses reflect the speakers’ opinions at the time of the webinar and may not necessarily reflect opinion of Novartis Pharma AG

FAQ References

Educational slides

A number of educational slide decks are available to view and download from this section.