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CLINICALLY IMPORTANT CHANGE IN FACIT-FATIGUE SCORE FOR PATIENTS WITH COLD AGGLUTININ DISEASE: AN ANALYSIS USING THE PHASE 3 CARDINAL AND CADENZA STUDIES
Author(s): ,
Quentin A. Hill
Affiliations:
Department of Haematology,St James University Hospital,Leeds,United Kingdom
,
Alexander Röth
Affiliations:
Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen,University of Duisburg-Essen,Essen,Germany
,
Bernd Jilma
Affiliations:
Department of Clinical Pharmacology,Medical University of Vienna,Vienna,Austria
,
Catherine M. Broome
Affiliations:
Division of Hematology,MedStar Georgetown University Hospital,Washington, DC,United States
,
Sigbjørn Berentsen
Affiliations:
Department of Research and Innovation,Haugesund Hospital,Haugesund,Norway
,
Avery A. Rizio
Affiliations:
QualityMetric Incorporated LLC,Johnston, RI,United States
,
Florence Joly
Affiliations:
Sanofi,Chilly-Mazarin,France
,
Pronabesh DasMahapatra
Affiliations:
Sanofi,Cambridge, MA,United States
,
Xiaoyu Jiang
Affiliations:
Sanofi,Cambridge, MA,United States
,
Frank Shafer
Affiliations:
Sanofi,Cambridge, MA,United States
,
Melitza Iglesias-Rodriguez
Affiliations:
Sanofi,Cambridge, MA,United States
,
Jun Su
Affiliations:
Sanofi, Employee at time of study,Cambridge, MA,United States
,
Mark Kosinski
Affiliations:
QualityMetric Incorporated LLC,Johnston, RI,United States
David Cella
Affiliations:
Department of Medical Social Sciences,Northwestern University,Chicago, IL,United States
EHA Library. Hill Q. 06/09/21; 324900; EP1179
Quentin Hill
Quentin Hill
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1179

Type: E-Poster Presentation

Session title: Quality of life, palliative care, ethics and health economics

Background
Sutimlimab (formerly BIVV009) is a humanized monoclonal anti-C1s antibody with a clinical trial program to support its development as a treatment for cold agglutinin disease (CAD). CARDINAL (NCT03347396) and CADENZA (NCT03347422) are Phase 3 clinical trials for sutimlimab in patients with CAD. As fatigue is one of the most common symptoms of CAD (Su et al. ASH 2020; 2484), one of the secondary aims of CARDINAL and CADENZA was to examine treatment-related change in fatigue using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue outcome measure.

Aims
To estimate the clinically important change (CIC) for FACIT-Fatigue in patients with CAD using pooled data from CARDINAL and CADENZA. The CIC reflects the smallest score change that indicates a meaningful treatment benefit for individual patients.

Methods
CARDINAL is an open-label, single-arm, multicenter study in patients with CAD with a recent blood transfusion. CADENZA is a randomized, double-blinded, placebo-controlled study in patients with CAD without a recent blood transfusion. Data from the Part A, 26-week component of both studies were combined for these analyses. Anchor- and distribution-based analyses were performed to estimate the CIC. Anchor-based approaches (mean change and model-based) examined the relationship between change in FACIT-Fatigue scores and change in related anchor variables from baseline to Week 26. The independent variable was change in FACIT-Fatigue score and dependent variables were binary (improvement vs. no improvement). The anchor variables were change in self-assessed general health perceptions (as measured through change in response to the general health scale [GH01] of the Short Form 12-Item (version 2)® Health Survey [SF-12v2]), change in Patient Global Impression of (fatigue) Severity (PGI-S), Patient Global Impression of Change (PGIC), and change in hemoglobin levels.

Results
Fifty-five patients were included from CARDINAL (n=17) and CADENZA (n=38 [n=19 placebo, n=19 sutimlimab]). The median (range) age was 70 (46–88) years and 76% (n=42) were female. Mean FACIT-Fatigue score rose from 32.6 at baseline to 39.3 at Week 26, an improvement of 6.7 points. Correlations between FACIT-Fatigue scores and GH01, PGI-S, and PGIC exceeded 0.40, indicating moderately strong associations (Table 1). When using an anchor-based approach that evaluates mean change in FACIT-Fatigue score, CIC estimates ranged from 9.20 (PGIC) to 15.69 (PGI-S). Results from the two model-based anchor approaches that estimate CICs using receiver operating characteristic–based and logistic regression–based analyses ranged from 2 (hemoglobin) to 8.87 (GH01) (Table 2). CIC estimates generated from the anchor-based approaches ranged from 2 to 16 (interquartile range [IQR], 5–10). Distribution-based analyses determined the CIC to be 5.62 when based on one-half standard deviation of FACIT-Fatigue at baseline, and 2.78 when based on the standard error of the measure. The empirically determined CIC for patients with CAD for FACIT-Fatigue was 5, a median estimate produced by model-based analyses that falls within the IQR of all anchor-based analyses and converges with estimates produced by distribution-based analyses.

Conclusion
This study estimated a CIC of 5 for FACIT-Fatigue in patients with CAD, a CIC consistent with estimates for other disease areas (eg, rheumatoid arthritis, systemic lupus erythematosus, anemia related to cancer). This analysis demonstrated that the FACIT-Fatigue Scale may be an appropriate and interpretable assessment of fatigue among patients with CAD.

Keyword(s): Autoimmune hemolytic anemia (AIHA), Complement, Outcome, Quality of life

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1179

Type: E-Poster Presentation

Session title: Quality of life, palliative care, ethics and health economics

Background
Sutimlimab (formerly BIVV009) is a humanized monoclonal anti-C1s antibody with a clinical trial program to support its development as a treatment for cold agglutinin disease (CAD). CARDINAL (NCT03347396) and CADENZA (NCT03347422) are Phase 3 clinical trials for sutimlimab in patients with CAD. As fatigue is one of the most common symptoms of CAD (Su et al. ASH 2020; 2484), one of the secondary aims of CARDINAL and CADENZA was to examine treatment-related change in fatigue using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue outcome measure.

Aims
To estimate the clinically important change (CIC) for FACIT-Fatigue in patients with CAD using pooled data from CARDINAL and CADENZA. The CIC reflects the smallest score change that indicates a meaningful treatment benefit for individual patients.

Methods
CARDINAL is an open-label, single-arm, multicenter study in patients with CAD with a recent blood transfusion. CADENZA is a randomized, double-blinded, placebo-controlled study in patients with CAD without a recent blood transfusion. Data from the Part A, 26-week component of both studies were combined for these analyses. Anchor- and distribution-based analyses were performed to estimate the CIC. Anchor-based approaches (mean change and model-based) examined the relationship between change in FACIT-Fatigue scores and change in related anchor variables from baseline to Week 26. The independent variable was change in FACIT-Fatigue score and dependent variables were binary (improvement vs. no improvement). The anchor variables were change in self-assessed general health perceptions (as measured through change in response to the general health scale [GH01] of the Short Form 12-Item (version 2)® Health Survey [SF-12v2]), change in Patient Global Impression of (fatigue) Severity (PGI-S), Patient Global Impression of Change (PGIC), and change in hemoglobin levels.

Results
Fifty-five patients were included from CARDINAL (n=17) and CADENZA (n=38 [n=19 placebo, n=19 sutimlimab]). The median (range) age was 70 (46–88) years and 76% (n=42) were female. Mean FACIT-Fatigue score rose from 32.6 at baseline to 39.3 at Week 26, an improvement of 6.7 points. Correlations between FACIT-Fatigue scores and GH01, PGI-S, and PGIC exceeded 0.40, indicating moderately strong associations (Table 1). When using an anchor-based approach that evaluates mean change in FACIT-Fatigue score, CIC estimates ranged from 9.20 (PGIC) to 15.69 (PGI-S). Results from the two model-based anchor approaches that estimate CICs using receiver operating characteristic–based and logistic regression–based analyses ranged from 2 (hemoglobin) to 8.87 (GH01) (Table 2). CIC estimates generated from the anchor-based approaches ranged from 2 to 16 (interquartile range [IQR], 5–10). Distribution-based analyses determined the CIC to be 5.62 when based on one-half standard deviation of FACIT-Fatigue at baseline, and 2.78 when based on the standard error of the measure. The empirically determined CIC for patients with CAD for FACIT-Fatigue was 5, a median estimate produced by model-based analyses that falls within the IQR of all anchor-based analyses and converges with estimates produced by distribution-based analyses.

Conclusion
This study estimated a CIC of 5 for FACIT-Fatigue in patients with CAD, a CIC consistent with estimates for other disease areas (eg, rheumatoid arthritis, systemic lupus erythematosus, anemia related to cancer). This analysis demonstrated that the FACIT-Fatigue Scale may be an appropriate and interpretable assessment of fatigue among patients with CAD.

Keyword(s): Autoimmune hemolytic anemia (AIHA), Complement, Outcome, Quality of life

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