ASSOCIATION BETWEEN HEMOGLOBIN LEVELS AND END-ORGAN DAMAGE IN SICKLE CELL DISEASE: A RETROSPECTIVE LINKED PRIMARY AND SECONDARY CARE DATABASE ANALYSIS IN ENGLAND
Author(s): ,
Paul Telfer
Affiliations:
Queen Mary, University of London,London,Royaume-uni;Queen Mary, University of London,London,Vereinigtes Königreich;Queen Mary, University of London,London,Regno Unito;Queen Mary, University of London,London,United Kingdom;Queen Mary, University of London,London,Reino Unido;Queen Mary, University of London,London,Verenigd Koninkrijk;Queen Mary, University of London,London,Reino Unido;Queen Mary, Un
,
Sara Carvalho
Affiliations:
Health iQ, CorEvitas,London,Royaume-uni;Health iQ, CorEvitas,London,Vereinigtes Königreich;Health iQ, CorEvitas,London,Regno Unito;Health iQ, CorEvitas,London,United Kingdom;Health iQ, CorEvitas,London,Reino Unido;Health iQ, CorEvitas,London,Verenigd Koninkrijk;Health iQ, CorEvitas,London,Reino Unido;Health iQ, CorEvitas,London,Соединённое Королевство;Health iQ, CorEvitas,London,Storbritannien
,
Judith Ruzangi
Affiliations:
London School of Hygiene and Tropical Medicine,London,Royaume-uni;London School of Hygiene and Tropical Medicine,London,Vereinigtes Königreich;London School of Hygiene and Tropical Medicine,London,Regno Unito;London School of Hygiene and Tropical Medicine,London,United Kingdom;London School of Hygiene and Tropical Medicine,London,Reino Unido;London School of Hygiene and Tropical Medicine,London,Ve
,
Murat Arici
Affiliations:
Global Blood Therapeutics,South San Francisco,États-unis;Global Blood Therapeutics,South San Francisco,Vereinigte Staaten;Global Blood Therapeutics,South San Francisco,Stati Uniti;Global Blood Therapeutics,South San Francisco,United States;Global Blood Therapeutics,South San Francisco,Estados Unidos;Global Blood Therapeutics,South San Francisco,Verenigde Staten;Global Blood Therapeutics,South San
,
Matthew Binns
Affiliations:
Global Blood Therapeutics,South San Francisco,États-unis;Global Blood Therapeutics,South San Francisco,Vereinigte Staaten;Global Blood Therapeutics,South San Francisco,Stati Uniti;Global Blood Therapeutics,South San Francisco,United States;Global Blood Therapeutics,South San Francisco,Estados Unidos;Global Blood Therapeutics,South San Francisco,Verenigde Staten;Global Blood Therapeutics,South San
,
Anne Beaubrun
Affiliations:
Global Blood Therapeutics,South San Francisco,États-unis;Global Blood Therapeutics,South San Francisco,Vereinigte Staaten;Global Blood Therapeutics,South San Francisco,Stati Uniti;Global Blood Therapeutics,South San Francisco,United States;Global Blood Therapeutics,South San Francisco,Estados Unidos;Global Blood Therapeutics,South San Francisco,Verenigde Staten;Global Blood Therapeutics,South San
,
Caoimhe Rice
Affiliations:
Health iQ, CorEvitas,London,Royaume-uni;Health iQ, CorEvitas,London,Vereinigtes Königreich;Health iQ, CorEvitas,London,Regno Unito;Health iQ, CorEvitas,London,United Kingdom;Health iQ, CorEvitas,London,Reino Unido;Health iQ, CorEvitas,London,Verenigd Koninkrijk;Health iQ, CorEvitas,London,Reino Unido;Health iQ, CorEvitas,London,Соединённое Королевство;Health iQ, CorEvitas,London,Storbritannien
John J. Were
Affiliations:
Health iQ, CorEvitas,London,Royaume-uni;Health iQ, CorEvitas,London,Vereinigtes Königreich;Health iQ, CorEvitas,London,Regno Unito;Health iQ, CorEvitas,London,United Kingdom;Health iQ, CorEvitas,London,Reino Unido;Health iQ, CorEvitas,London,Verenigd Koninkrijk;Health iQ, CorEvitas,London,Reino Unido;Health iQ, CorEvitas,London,Соединённое Королевство;Health iQ, CorEvitas,London,Storbritannien
(Abstract release date: 05/12/22) EHA Library. Telfer P. 06/10/22; 358342; P1488
Paul Telfer
Paul Telfer
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1488

Type: Poster presentation

Session title: Sickle cell disease

Background
Sickle cell disease (SCD) is a chronic, multifaceted blood disorder that affects the oxygen-carrying protein hemoglobin (Hb). Along with chronic hemolysis and vaso-occlusion that often accompanies SCD, low Hb levels may contribute to downstream end-organ damage (EOD). Emerging evidence suggests an association between chronic hemolytic anemia in SCD and both short-term and long-term adverse outcomes, including EOD. Therefore, treatments that directly increase Hb may improve patients’ acute symptoms while reducing the risk for long-term disease-related effects known to contribute to morbidity and mortality.

Aims
This study aims to ascertain the association between Hb level variation and EOD and clinical conditions typically associated with SCD (stroke, pulmonary hypertension, chronic kidney disease [CKD], end-stage renal disease [ESRD], leg ulcers, and pneumonia) in a real-world data set.

Methods
The Clinical Practice Research Datalink (CPRD) and the Hospital Episode Statistics (HES) databases in England were used to retrospectively identify linked Hb data among patients with SCD (1 April 2007 to 31 March 2019). Recurring results in any 90-day period were averaged. Logistic regression adjusted with demographic and clinical variables was used to determine odds ratios (ORs) of developing each EOD outcome or clinical complication. ORs, P values, 95% confidence intervals (CIs), and areas under the receiver operating curve (AUC-ROCs) and corresponding 95% CIs were reported.

Results
Of 11,936 patients identified, 5379 (45%) had Hb results recorded in the CPRD. The logistic model for risk assessment of all outcomes studied indicated that an increase in Hb among patients with SCD was associated with a statistically significant (P<0.001) decrease in adjusted ORs per 1 g/dL increase in Hb (Table). Except for ESRD, leg ulcers, and pneumonia, the adjusted models showed statistically significant increases in AUC-ROC compared with the unadjusted models, signifying that the adjusted models were more robust and further verified a statistical OR after adjustment.

Increased Hb was associated with decreased risk of respiratory-related events. Pulmonary hypertension had the strongest effect with the most robust model (ORadjusted of 0.66). For pneumonia, ORadjusted was 0.77. For renal insufficiency, ORs for developing CKD or ESRD were significantly lower than 1 (ORadjusted=0.73 and ORadjusted=0.75, respectively). After adjusting for clinical and demographic factors, the model predicted a lower risk for stroke (ORadjusted=0.89). The estimated AUC-ROCs suggest that the adjusted model is more robust in stroke, hypertension, and CKD. These findings did not change when testing for other covariates such as deep vein thrombosis.

Conclusion
Among patients with SCD, an increase in Hb of 1 g/dL was associated with a statistically significant reduction in risk for 6 common EOD outcomes and clinical conditions. The results were more pronounced after adjusting for demographic and clinical covariates (based on clinical opinion and literature review) and further assessed with a bivariate analysis. The results were obtained from a representative real-world evidence dataset analyzed over a 12-year period, which was sufficient to observe EOD events, and are generalizable to the UK and similar populations. Our findings support the use of therapeutics that increase Hb in patients with SCD to protect against deleterious organ damage.

Keyword(s): Hemoglobin, Risk factor, Sickle cell disease

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1488

Type: Poster presentation

Session title: Sickle cell disease

Background
Sickle cell disease (SCD) is a chronic, multifaceted blood disorder that affects the oxygen-carrying protein hemoglobin (Hb). Along with chronic hemolysis and vaso-occlusion that often accompanies SCD, low Hb levels may contribute to downstream end-organ damage (EOD). Emerging evidence suggests an association between chronic hemolytic anemia in SCD and both short-term and long-term adverse outcomes, including EOD. Therefore, treatments that directly increase Hb may improve patients’ acute symptoms while reducing the risk for long-term disease-related effects known to contribute to morbidity and mortality.

Aims
This study aims to ascertain the association between Hb level variation and EOD and clinical conditions typically associated with SCD (stroke, pulmonary hypertension, chronic kidney disease [CKD], end-stage renal disease [ESRD], leg ulcers, and pneumonia) in a real-world data set.

Methods
The Clinical Practice Research Datalink (CPRD) and the Hospital Episode Statistics (HES) databases in England were used to retrospectively identify linked Hb data among patients with SCD (1 April 2007 to 31 March 2019). Recurring results in any 90-day period were averaged. Logistic regression adjusted with demographic and clinical variables was used to determine odds ratios (ORs) of developing each EOD outcome or clinical complication. ORs, P values, 95% confidence intervals (CIs), and areas under the receiver operating curve (AUC-ROCs) and corresponding 95% CIs were reported.

Results
Of 11,936 patients identified, 5379 (45%) had Hb results recorded in the CPRD. The logistic model for risk assessment of all outcomes studied indicated that an increase in Hb among patients with SCD was associated with a statistically significant (P<0.001) decrease in adjusted ORs per 1 g/dL increase in Hb (Table). Except for ESRD, leg ulcers, and pneumonia, the adjusted models showed statistically significant increases in AUC-ROC compared with the unadjusted models, signifying that the adjusted models were more robust and further verified a statistical OR after adjustment.

Increased Hb was associated with decreased risk of respiratory-related events. Pulmonary hypertension had the strongest effect with the most robust model (ORadjusted of 0.66). For pneumonia, ORadjusted was 0.77. For renal insufficiency, ORs for developing CKD or ESRD were significantly lower than 1 (ORadjusted=0.73 and ORadjusted=0.75, respectively). After adjusting for clinical and demographic factors, the model predicted a lower risk for stroke (ORadjusted=0.89). The estimated AUC-ROCs suggest that the adjusted model is more robust in stroke, hypertension, and CKD. These findings did not change when testing for other covariates such as deep vein thrombosis.

Conclusion
Among patients with SCD, an increase in Hb of 1 g/dL was associated with a statistically significant reduction in risk for 6 common EOD outcomes and clinical conditions. The results were more pronounced after adjusting for demographic and clinical covariates (based on clinical opinion and literature review) and further assessed with a bivariate analysis. The results were obtained from a representative real-world evidence dataset analyzed over a 12-year period, which was sufficient to observe EOD events, and are generalizable to the UK and similar populations. Our findings support the use of therapeutics that increase Hb in patients with SCD to protect against deleterious organ damage.

Keyword(s): Hemoglobin, Risk factor, Sickle cell disease

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