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ABSTRACT Objectives Methods Results Conclusions To evaluate the tolerability of crovalimab versus eculizumab in C5 inhibitor (C5i)‐naive and ‐experienced patients with PNH from COMMODORE 2, 3 and 1 (NCT04434092, NCT04654468 and NCT04432584).Pooled safety data were assessed in the total crovalimab and eculizumab populations and by C5i‐naive versus C5i‐switched status in patients receiving crovalimab. Analyses include 6.5 months of additional follow‐up from the COMMODORE 2 and 1 primary analyses.COMMODORE safety data (crovalimab, 393 patients [naive, 192 patients; switched, 201 patients]; eculizumab, 111 patients) were analysed. The total patient years (PY) were 503.9 and 51.1 in the total crovalimab and eculizumab populations, respectively, with 471 and 581 adverse events (AEs) per 100 PY. Serious infection rates were 8.9 and 13.7 AEs per 100 PY, respectively; no meningococcal infections were reported. Fatal AEs occurred in eight (2%) patients receiving crovalimab (naive, six patients; switched, two patients) and one (1%) receiving eculizumab, all treatment unrelated. In C5i‐switched patients, 39 (19%) had transient immune complex reactions (risk when switching between C5i and crovalimab); the majority were Grades 1–2 arthralgia and rash, and 16 (8%) had Grade 3 events.Crovalimab's safety profile was consistent with eculizumab's and was generally comparable between C5i‐naive and C5i‐switched patients. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the tolerability of crovalimab versus eculizumab in C5 inhibitor (C5i)-naive and -experienced patients with PNH from COMMODORE 2, 3 and 1 (NCT04434092, NCT04654468 and NCT04432584)., Methods: Pooled safety data were assessed in the total crovalimab and eculizumab populations and by C5i-naive versus C5i-switched status in patients receiving crovalimab. Analyses include 6.5 months of additional follow-up from the COMMODORE 2 and 1 primary analyses., Results: COMMODORE safety data (crovalimab, 393 patients [naive, 192 patients; switched, 201 patients]; eculizumab, 111 patients) were analysed. The total patient years (PY) were 503.9 and 51.1 in the total crovalimab and eculizumab populations, respectively, with 471 and 581 adverse events (AEs) per 100 PY. Serious infection rates were 8.9 and 13.7 AEs per 100 PY, respectively; no meningococcal infections were reported. Fatal AEs occurred in eight (2%) patients receiving crovalimab (naive, six patients; switched, two patients) and one (1%) receiving eculizumab, all treatment unrelated. In C5i-switched patients, 39 (19%) had transient immune complex reactions (risk when switching between C5i and crovalimab); the majority were Grades 1-2 arthralgia and rash, and 16 (8%) had Grade 3 events., Conclusions: Crovalimab's safety profile was consistent with eculizumab's and was generally comparable between C5i-naive and C5i-switched patients., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Objectives: This study reports long-term outcomes from the open-label extension (OLE) period of the Phase I/II COMPOSER trial (NCT03157635) that evaluated crovalimab in patients with paroxysmal nocturnal haemoglobinuria, who were treatment-naive or switched from eculizumab at enrolment., Methods: COMPOSER consists of four sequential parts followed by the OLE. The primary OLE objective was to assess long-term crovalimab safety, with a secondary objective to assess crovalimab pharmacokinetics and pharmacodynamics. Exploratory efficacy endpoints included change in lactate dehydrogenase (LDH), transfusion avoidance, haemoglobin stabilisation and breakthrough haemolysis (BTH)., Results: A total 43 of 44 patients entered the OLE after completing the primary treatment period. Overall, 14 of 44 (32%) experienced treatment-related adverse events. Steady state exposure levels of crovalimab and terminal complement inhibition were maintained over the OLE. During the OLE, mean normalised LDH was generally maintained at ≤1.5× upper limit of normal, transfusion avoidance was achieved in 83%-92% of patients and haemoglobin stabilisation was reached in 79%-88% of patients across each 24-week interval. Five BTH events occurred with none leading to withdrawal., Conclusions: Over a 3-year median treatment duration, crovalimab was well tolerated and sustained C5 inhibition was achieved. Intravascular haemolysis control, haemoglobin stabilisation and transfusion avoidance were maintained, signifying long-term crovalimab efficacy., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

We study and compare several variants of random forests tailored to prognostic models for ordinal outcomes. Models of the conditional odds function are employed to understand the various random forest flavours. Existing random forest variants for ordinal outcomes, such as Ordinal Forests and Conditional Inference Forests, are evaluated in the presence of a non-proportional odds impact of prognostic variables. We propose two novel random forest variants in the model-based transformation forest family, only one of which explicitly assumes proportional odds. These two novel transformation forests differ in the specification of the split procedures for the underlying ordinal trees. One of these split criteria is able to detect changes in non-proportional odds situations and the other one focuses on finding proportional-odds signals. We empirically evaluate the performance of the existing and proposed methods using a simulation study and illustrate the practical aspects of the procedures by a re-analysis of the respiratory sub-item in functional rating scales of patients suffering from Amyotrophic Lateral Sclerosis (ALS).