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What has the ongoing development of biologics taught us about COPD so far?

Presented by Lowie Vanfleteren, Sweden

Oppsummering

Med de første biologiske legemidlene til behandling av alvorlig KOLS som antagelig er nær godkjenning, står vi på kanten av en ny æra. Som med alvorlig astma, har utviklingen av biologiske legemidler mot KOLS lært oss noe viktig om sykdomsmekanismer og fenotyper ved sykdommen. Hvordan ser personen med KOLS ut, som kan ha positiv effekt av behandling med biologiske legemidler?

Reduce risk, as well as symptoms

During his lecture, Lowie Vanfleteren did not only elegantly summarise the data generated during the clinical development programs of biologics in COPD, but importantly, he also shared his current expert understanding on which emerging patient characteristics will be in focus to select the individuals with best chances for good treatment responses.

He reminded us of the two goals of COPD treatment: to reduce symptoms for the individual, and to reduce the risk for both, exacerbations and progression of the disease. Basically, all persons living with COPD will sooner or later exacerbate.

Key considerations: prior exacerbations and eosinophils

Two recognized risks factors are prior exacerbations and elevated blood eosinophil counts. The treatment effect of inhaled corticosteroids relates to the extent of blood eosinophils present1. As shown by Bafadhel et al 2011, eosinophilic inflammation is present in ca 28% of COPD exacerbations2. Vanfleteren shows us the schematic overview of Type 2 inflammation in the lung that we all recognize from lectures on severe asthma. He points us to the fact that there are triggers of Type 2 inflammation that we sometimes tend to overlook, eg. cigarette smoking leading to the induction of cytokines and alarmins such as IL-33, TSLP, IL-4, IL-5 and IL-13. All these cytokines display valid targets for biologics in COPD, surely for the overlapping phenotypes of asthma and COPD.

Know the type of exacerbation

The clinical development programs for these antibodies found that efficacy is again related to the level of eosinophil counts. Thus, to define a threshold to predict beneficial effects is very important. Even though the fraction of exhaled nitric oxide (FeNO) is comparable low in COPD, biologics have shown to reduce the FeNO levels. It crystallizes more and more that biologics can become powerful tools to reduce OCS-sensitive exacerbations, but less so exacerbations that would need treatment with antibiotics. Vanfleteren mentions a disease-label free, treatable traits approach for the use of biologics in severely diseased persons: it is important to identify the right medicine for the person you try to help.  

Barbara Fuchs
Medical Manager, Chiesi Nordics


References:

  1. Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord ID. Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials. Lancet Respir Med. 2015 Jun;3(6):435-42. doi: 10.1016/S2213-2600(15)00106-X. Epub 2015 Apr 12. Erratum in: Lancet Respir Med. 2015 Jun;3(6):e19. PMID: 25878028.
  2. Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, McCormick M, Haldar K, Kebadze T, Duvoix A, Lindblad K, Patel H, Rugman P, Dodson P, Jenkins M, Saunders M, Newbold P, Green RH, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011 Sep 15;184(6):662-71. doi: 10.1164/rccm.201104-0597OC. PMID: 21680942.

8659-18.06.2024