S853 SUCCESSOR: A MULTICENTER RETROSPECTIVE NONINTERVENTIONAL FOLLOW‐UP STUDY IN PATIENTS WITH SICKLE CELL PAIN CRISES WHO PREVIOUSLY PARTICIPATED IN THE SUSTAIN TRIAL IN THE UNITED STATES
Authors: Liles D. , Shah N. , Scullin B. , Gordeuk V. , Smith W. , Kanter J. , Achebe M. , Boccia R. , Crary S. , Kraft W. , Archer N. , Cataldo V. , Hardesty B. , Idowu M. , Desai P. , Ikeda A. , Puthenveetil G. , Hassell K. , Sarnaik S. , Paulose J. , Lainé D. , Purkayastha D. , Nandal S. , Kutlar A. 
Published: June 2019

Background:

SUCCESSOR (SUSTAIN Chart‐review of Crizanlizumab to Evaluate Sickle‐cell Study One‐year Retrospective) reviewed medical records of patients who completed the SUSTAIN study at US sites to assess subsequent cases of significant pain crisis events and generate real‐world data on treatment patterns and health care resource utilization upon completion of crizanlizumab treatment. SUSTAIN was a phase 2, randomized, double‐blind, placebo‐controlled, 52‐week study that compared the effect of crizanlizumab, a P‐selectin inhibitor, versus placebo on the frequency of sickle cell pain crises (SCPCs, or vaso‐occlusive crises [VOCs] leading to a health care visit) in patients with any genotype of sickle cell disease (SCD).

Aims:

To determine the 52‐week post‐SUSTAIN occurrence of VOCs, time to first VOC, frequency of blood transfusions, and use of opioids and hydroxyurea in patients after withdrawal of treatment with crizanlizumab or placebo.

Methods:

SUCCESSOR is a multicenter, retrospective cohort study of patients (≥18 years old) who participated in SUSTAIN to evaluate SCD‐related outcomes up to 52 weeks following trial completion. SUCCESSOR included the SUSTAIN per‐protocol population who received at least 12 of the 14 study drug doses, completed a visit at least 14 days after the final dose, and had no major protocol deviations that impacted efficacy assessments. The study period was from September 2015 to March 2017 and patients’ data were obtained from medical records. Crizanlizumab was not administered in the 52 weeks post‐SUSTAIN. An exploratory analysis was conducted to evaluate outcomes in the retrospective SUCCESSOR study using a subset of SUSTAIN patients. Patient consent was obtained prior to data collection if required by local and/or central research ethics review.

Results:

In SUCCESSOR, data for 48 patients were analyzed (15, 18, and 15 patients who were previously randomized in SUSTAIN to receive crizanlizumab 5 mg/kg, crizanlizumab 2.5 mg/kg, and placebo, respectively). The median age was 31.5 years (range 19–65 years) and 69% were female. One patient had HbSβ+, 4 had HbSβ0, 10 had HbSC, 1 had HbS‐Lepore disease; all remaining patients had HbSS. In the 52 weeks post‐SUSTAIN, VOCs were reported by 73% of patients who previously received crizanlizumab 5 mg/kg, 83% of patients who previously received crizanlizumab 2.5 mg/kg, and 80% of patients previously treated with placebo. The mean annual rate of VOCs was 2.7, 3.9, and 5.4 in patients previously on crizanlizumab 5 mg/kg, 2.5 mg/kg, and placebo, respectively. Median time to first VOC post‐SUSTAIN was 6.1, 2.7, and 2.6 months in patients previously on crizanlizumab 5 mg/kg, 2.5 mg/kg, and placebo, respectively, similar to differences observed for the same patients during SUSTAIN (6.9, 2.2, and 1.4 months for crizanlizumab 5 mg/kg, 2.5 mg/kg, and placebo, respectively). In SUCCESSOR, all but 1 patient utilized opioids, and 79% did not require blood transfusions. Hydroxyurea was used by 60%, 50%, and 80% of patients previously on crizanlizumab 5 mg/kg, 2.5 mg/kg, and placebo, respectively. There were no deaths.

Summary/Conclusion:

In SUCCESSOR across all patient groups, 80% of patients experienced a VOC in the 52 weeks post‐SUSTAIN. This retrospective cohort study indicates that after withdrawal of crizanlizumab, patients previously treated with 5 mg/kg maintained a similar time to first VOC compared with time to first VOC while on treatment in SUSTAIN. Further research is needed to establish whether these findings are due to a prolonged effect of crizanlizumab or to other factors.

image