Predictors for Improvement in Patient-Reported Outcomes: Post-Hoc Analysis of a Phase 3 Randomized, Open-Label Study of Eculizumab and Ravulizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Background: Patients with PNH have uncontrolled terminal complement activation that can lead to thrombosis, organ damage, intravascular hemolysis (IVH), and clinical sequelae. It is also associated with debilitating patient-reported outcomes (PROs), such as fatigue, dyspnea, and pain that contribute...

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Published in:Blood 2021-11, Vol.138 (Supplement 1), p.2196-2196
Main Authors: Schrezenmeier, Hubert, Kulasekararaj, Austin G., Mitchell, Lindsay, Peffault De Latour, Regis, Devos, Timothy, Okamoto, Shinichiro, Wells, Richard, Johnston, Karissa, Popoff, Evan, Cheung, Antoinette, Wang, Jimmy, Gustovic, Philippe, Wang, Alice, Tomazos, Ioannis, Patel, Yogesh, Lee, Jong Wook
Format: Article
Language:English
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Summary:Background: Patients with PNH have uncontrolled terminal complement activation that can lead to thrombosis, organ damage, intravascular hemolysis (IVH), and clinical sequelae. It is also associated with debilitating patient-reported outcomes (PROs), such as fatigue, dyspnea, and pain that contribute to a poor quality of life (QoL). Whilst it is known that improvements in clinical outcomes are associated with C5 inhibitor (C5i) therapy in patients with PNH, evidence characterizing the relationship between clinical outcomes and fatigue or QoL are limited. Understanding key clinical drivers of improvements in QoL and fatigue during complement C5i therapy is vital for developing appropriate management strategies. Aims: To assess the relationship between clinical outcomes with fatigue and QoL, as measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Global Health (EORTC QLQ-C30 GH), in patients with PNH receiving C5i therapy. Methods: Post-hoc analyses were performed using data from a 26-week data cut of a randomized phase 3 study (NCT02946463) that assessed ravulizumab and eculizumab in complement inhibitor-naïve patients with PNH and high disease activity (defined as a lactate dehydrogenase [LDH] level ≥ 1.5 × upper limit of normal [ULN; 246 U/L] and ≥ 1 sign or symptom of PNH at screening). The PRO measures (PROMs) used were FACIT-F and EORTC QLQ-C30 GH. Clinical variables included LDH, hemoglobin (Hb), bone marrow disorders, transfusions, and hematological parameters such as reticulocyte, platelet, and neutrophil counts. Multivariable regressions were performed separately for each PROM to assess the effect of clinical variables on PROM score changes from baseline to day 183, controlling for demographic characteristics and baseline PROM scores. Multicollinearity between covariates was tested in each regression model and removed when present. Results: Data for 121 and 125 patients with PNH treated with eculizumab or ravulizumab were included, respectively. Trial data showed that reduced LDH levels at day 183 were associated with improvements in FACIT-F in both treatment groups; however, no equivalent association was observed with Hb levels (Figure 1). In the regression analyses, significant predictors of FACIT-F improvement included reductions in LDH levels from baseline to day 183 (p = 0.0024) and the interaction of both achie
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2021-144554