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Current status of biologics in COPD

In Professor Alberto Papi’s comprehensive lecture on the evolving landscape of biological treatment in COPD, he emphasized the proven efficacy of triple therapy in reducing the annual exacerbation rate. Despite these advancements, challenges persist as some patients continue to experience exacerbations even with optimized triple therapy. This underscores the urgency for novel and individualized treatment approaches. 

Navigating potential molecular targets in COPD

The complex task of navigating potential molecular targets poses a considerable challenge in this field. While exploring the non-type 2 inflammatory response, known for its involvement in exacerbations, studies on non-type 2 mediators like TNF and IL-17A have yielded inconclusive results (1, 2). Contrary to this, asthma has seen success with antibody treatments targeting type 2 inflammatory mediators, prompting exploration of their applicability in COPD. 

Specifically, antibodies targeting IL-5 signaling, effective in certain asthma phenotypes, raise intriguing questions about their potential role in COPD. However, Prof. Papi shared conflicting findings regarding the impact of anti-IL-5 in COPD, emphasizing the need for more targeted studies in specific patient subgroups (3). 

Blocking IL-4 and IL-13 – a potential breakthrough

An encouraging breakthrough emerged in the form of blocking IL-4 and IL-13 signaling, showing a promising 30% reduction in the annual exacerbation rate in a subgroup of COPD patients characterized by specific criteria (4). This development marks a significant leap forward, especially for individuals on triple therapy still experiencing exacerbations. 

Alarmins may recall history of smoking

Diving further into the exploration of alarmins’ influence on COPD, studies on IL-33 inhibition revealed nuanced results. While there was no significant change in the overall exacerbation rate, a subgroup analysis showed a substantial reduction in frequency among former smokers (5). Ongoing research is dedicated exclusively to this population, promising deeper insights. 

Work in progress

Prof. Papi concludes that while treatments for type 2 inflammatory mediators in COPD have progressed, addressing non-type 2 inflammation remains a work in progress. With hope, future research will unveil treatments for non-type 2 inflammation in COPD, given that it represents the majority of cases. 

Recommended reading

Agusti A. Biologics for COPD – Finally Here. N Engl J Med. 2023 Jul 20;389(3):274-275. doi: 10.1056/NEJMe2305752. PMID: 37467502. 

Written by

Ingvild Bjellmo Johnsen

Medical Advisor Respiratory, Chiesi Nordic

References

  1. Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, Korenblat P, Smith W, Kaye M, Mandel M, Andrews C, Prabhu R, Donohue JF, Watt R, Lo KH, Schlenker-Herceg R, Barnathan ES, Murray J; COPD Investigators. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007 May 1;175(9):926-34. doi: 10.1164/rccm.200607-995OC. Epub 2007 Feb 8. PMID: 17290043. 
  2. Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, Liam CK, Kuo PH, Hou Y, Xiao J, Branigan P, O’Brien CD. A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic Obstructive Pulmonary Disease. COPD. 2017 Oct;14(5):476-483. doi: 10.1080/15412555.2017.1335697. Epub 2017 Jul 28. PMID: 28753067. 
  3. Pavord ID, Chanez P, Criner GJ, Kerstjens HAM, Korn S, Lugogo N, Martinot JB, Sagara H, Albers FC, Bradford ES, Harris SS, Mayer B, Rubin DB, Yancey SW, Sciurba FC. Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017 Oct 26;377(17):1613-1629. doi: 10.1056/NEJMoa1708208. Epub 2017 Sep 11. PMID: 28893134. 
  4. Bhatt SP, Rabe KF, Hanania NA, Vogelmeier CF, Cole J, Bafadhel M, Christenson SA, Papi A, Singh D, Laws E, Mannent LP, Patel N, Staudinger HW, Yancopoulos GD, Mortensen ER, Akinlade B, Maloney J, Lu X, Bauer D, Bansal A, Robinson LB, Abdulai RM; BOREAS Investigators. Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts. N Engl J Med. 2023 Jul 20;389(3):205-214. doi: 10.1056/NEJMoa2303951. Epub 2023 May 21. PMID: 37272521. 
  5. Rabe KF, Celli BR, Wechsler ME, Abdulai RM, Luo X, Boomsma MM, Staudinger H, Horowitz JE, Baras A, Ferreira MA, Ruddy MK, Nivens MC, Amin N, Weinreich DM, Yancopoulos GD, Goulaouic H. Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial. Lancet Respir Med. 2021 Nov;9(11):1288-1298. doi: 10.1016/S2213-2600(21)00167-3. Epub 2021 Jul 21. PMID: 34302758. 

ID 7361-11.03.2024