{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T18:12:52Z","timestamp":1773943972503,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012112","name":"Swedish Orphan Biovitrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012112","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012112","name":"Swedish Orphan Biovitrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012112","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra\u2010rare, acquired non\u2010malignant haematological disorder characterised by thrombosis risk, serious complications and debilitating symptoms in untreated patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This anchored indirect treatment comparison (ITC) evaluated efficacy data between proximal complement 3 inhibitor (C3i) pegcetacoplan and factor B inhibitor, iptacopan, in patients with PNH previously treated with complement 5 inhibitors (C5i; eculizumab, ravulizumab).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Respective pivotal studies provided patient\u2010level trial data for pegcetacoplan (16\u2010week PEGASUS [NCT03500549]) and published data for iptacopan (24\u2010week APPLY PNH [NCT04558918]). Differences in study design, duration and statistical methods between PEGASUS and APPLY PNH necessitated the comparative analyses to be conducted on secondary measures based on haemoglobin (Hb) levels, absolute reticulocyte count (ARC), lactate dehydrogenase (LDH) levels, and patient\u2010reported outcomes on the Functional Assessment of Chronic Illness Therapy\u2013Fatigue (FACIT\u2010Fatigue) scale scores. The availability of a common reference C5i treatment group in both PEGASUS and APPLY PNH studies allowed anchored ITC (Bucher method). Simulated treatment comparison (STC) assessed the robustness of the main analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, baseline characteristics of the populations in the PEGASUS and APPLY PNH studies were broadly comparable. Anchored ITC showed comparable outcomes (mean difference, [95% CI]) on change\u2010from\u2010baseline to end of study for pegcetacoplan versus C5i, and iptacopan versus C5i, respectively, across endpoints: Hb level\u2009(\n                      <jats:bold>\u2212<\/jats:bold>\n                      0.49\u2009g\/dL [\n                      <jats:bold>\u2212<\/jats:bold>\n                      1.78, 0.80]); ARC (\n                      <jats:bold>\u2013<\/jats:bold>\n                      34.41\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      \/L [\n                      <jats:bold>\u2212<\/jats:bold>\n                      90.02, 21.21]); LDH level (\n                      <jats:bold>\u2212<\/jats:bold>\n                      115.16\u2009U\/L [\n                      <jats:bold>\u2212<\/jats:bold>\n                      244.40, 14.01]); FACIT\u2010Fatigue score (3.57 [\n                      <jats:bold>\u2212<\/jats:bold>\n                      5.60, 12.73]). Finally, the STC produced results consistent with the main Bucher analyses across all clinical endpoints and patient\u2010reported fatigue, providing similar point estimates and confidence intervals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This anchored ITC, based on data from pivotal trials, did not indicate significant differences in clinical or patient\u2010reported outcomes between pegcetacoplan and iptacopan in PNH treatment. The findings suggest that PNH treatment decisions should also consider individualised disease\u2010 and patient\u2010related factors.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>ClinicalTrials.gov identifier: NCT03500549.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ejh.14422","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T02:43:11Z","timestamp":1745635391000},"page":"125-133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Anchored Indirect Treatment Comparison Finds Comparable Effects of Pegcetacoplan and Iptacopan in Paroxysmal Nocturnal Haemoglobinuria"],"prefix":"10.1111","volume":"115","author":[{"given":"Regis Peffault","family":"de Latour","sequence":"first","affiliation":[{"name":"French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-3570","authenticated-orcid":false,"given":"Austin","family":"Kulasekararaj","sequence":"additional","affiliation":[{"name":"Department of Haematological Medicine King's College Hospital, National Institute of Health Research\/Wellcome King's Clinical Research Facility  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Dingli","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine Mayo Clinic  Rochester USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koo","family":"Wilson","sequence":"additional","affiliation":[{"name":"Swedish Orphan Biovitrum AB (Sobi)  Stokholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Wojciechowski","sequence":"additional","affiliation":[{"name":"Clever\u2010Access  Krakow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zalmai","family":"Hakimi","sequence":"additional","affiliation":[{"name":"Swedish Orphan Biovitrum AB (Sobi)  Stokholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jameel","family":"Nazir","sequence":"additional","affiliation":[{"name":"Swedish Orphan Biovitrum AB (Sobi)  Stokholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Czech","sequence":"additional","affiliation":[{"name":"Swedish Orphan Biovitrum AB (Sobi)  Stokholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hillmen","sequence":"additional","affiliation":[{"name":"Apellis Pharmaceuticals  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff","family":"Szer","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology Peter MacCallum Cancer Centre &amp; Royal Melbourne Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/JBM.S431493"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2022.2109462"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199511093331904"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010148\u20108\u2010200804150\u201000003"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.14281"},{"key":"e_1_2_13_7_1","unstructured":"EMPAVELI\u2122 (pegcetacoplan) injection for subcutaneous use.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2021\/215014s000lbl.pdf."},{"key":"e_1_2_13_8_1","unstructured":"European Medicines Agency Aspaveli https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/aspaveli."},{"key":"e_1_2_13_9_1","unstructured":"Pegcetacoplan (Empaveli): CADTH Reimbursement Recommendation: Indication: For the Treatment of Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to or Are Intolerant of a C5 Inhibitor. 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