{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:32:28Z","timestamp":1792798348706,"version":"4.5.0"},"reference-count":29,"publisher":"European Respiratory Society (ERS)","issue":"1","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,3,3]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Interleukin-33 may have a role in COPD pathobiology. FRONTIER-4 (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04631016\">NCT04631016<\/jats:ext-link>\n                      ) investigated tozorakimab (an anti-interleukin-33 monoclonal antibody) in patients with moderate-to-severe COPD with chronic bronchitis receiving dual or triple inhaled therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      FRONTIER-4 was a phase 2a, randomised, double-blind, placebo-controlled study. Patients received tozorakimab 600\u2005mg or placebo subcutaneously every 4\u2005weeks for 24\u2005weeks. The primary end\u2011point was change in pre-bronchodilator forced expiratory volume in 1\u2005s (FEV\n                      <jats:sub>1<\/jats:sub>\n                      ) from baseline to week 12. Secondary outcomes included post-bronchodilator FEV\n                      <jats:sub>1<\/jats:sub>\n                      , time-to-first COPD composite exacerbation event and safety.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The intent-to-treat population included 135 patients (tozorakimab, n=67; placebo, n=68). At week 12 in the intent-to-treat population, tozorakimab showed a greater increase, although nonsignificant, from baseline in pre-bronchodilator FEV\n                      <jats:sub>1<\/jats:sub>\n                      (least-squares mean difference (LSMD) 24\u2005mL, 80% confidence interval (CI) \u221215\u201363\u2005mL, p=0.216) and a significantly greater increase in post-bronchodilator FEV\n                      <jats:sub>1<\/jats:sub>\n                      (LSMD 67\u2005mL, 80% CI 17\u2013116\u2005mL, p=0.044) when compared with placebo. At week 12 in a prespecified subgroup of patients with at least two prior exacerbations, tozorakimab also showed improvements\n                      <jats:italic>versus<\/jats:italic>\n                      placebo in change from baseline in pre-bronchodilator FEV\n                      <jats:sub>1<\/jats:sub>\n                      (LSMD 69\u2005mL, 80% CI 9\u2013130\u2005mL, p=0.072) and post-bronchodilator FEV\n                      <jats:sub>1<\/jats:sub>\n                      (LSMD 124\u2005mL, 80% CI 47\u2013201\u2005mL, p=0.020). Tozorakimab did not significantly reduce the risk of COPD composite exacerbation events (hazard ratio 0.79, 80% CI 0.57\u20131.11, p=0.186) in the intent-to-treat population, although there were greater effects in patients with at least two prior exacerbations (hazard ratio 0.61, 80% CI 0.37\u20131.00). Results were similar in former and current smokers. Tozorakimab was well tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Although the primary end-point was not met in the intent-to-treat population, tozorakimab showed positive efficacy signals\n                      <jats:italic>versus<\/jats:italic>\n                      placebo in a subgroup of patients with COPD with a high risk of exacerbations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.02231-2024","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T06:15:17Z","timestamp":1743142517000},"page":"2402231","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":77,"title":["A phase 2a trial of the IL-33 monoclonal antibody tozorakimab in patients with COPD: 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