Utilization and Tolerability of Crizanlizumab In Adult Alternate Infusion Site Patients: A Descriptive Retrospective Cohort Study
Kascha Brown PharmD, MS Option Care Health kascha.brown@optioncare.com
Maria Giannakos, PharmD, MBA, BCPS, BCSCP, FNHIA, Option Care Health
Christopher Roy PharmD, BCSCP Option Care Health
Annemarie Hocking PharmD Option Care Health
Abstract
Background
Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by vaso-occlusive crises (VOCs), leading to significant morbidity and health care utilization. Crizanlizumab, a P-selectin inhibitor, was approved in 2019 to reduce the frequency of VOCs. Limited data are available on the utilization and tolerability of crizanlizumab administered in home and alternate infusion site (AIS) settings.
Objective
To evaluate the utilization patterns and tolerability of crizanlizumab in patients with SCD receiving therapy in home and alternate infusion settings.
Methods
A retrospective, multi-center chart review was conducted to assess 52 months of data on patients aged 18 years and older with confirmed SCD who received at least one dispense of crizanlizumab during the 52-month study period. Data collected included demographics, payor type, site of administration, co-treatment, adherence, adverse events, and reasons for therapy discontinuation. Adherence was assessed via calculated dispense ratios. Add-on treatment efficacy was not assessed.
Results
Twenty-five patients were included, with 64% (n=16) receiving therapy in home or AIS settings. The mean patient age was 27.8 years (± 7.3), and 68.8% were male. Most patients (68.8%) had the HbSS genotype. Among patients treated outside of clinics, 56.3% discontinued therapy, primarily due to provider switches or non-adherence. No adverse drug reactions or anaphylaxis events were reported. Eight patients (50%) experienced VOC-related hospitalizations during the study. Co-treatment with hydroxyurea was common (81.3%). Adherence rates aligned closely with the FDA recommended dosing schedule after excluding outliers.
Conclusions
Crizanlizumab was safely administered in home and alternate infusion settings, supporting expanded access for SCD patients. However, the high discontinuation rate emphasizes the need for strategies to improve adherence and continuity of care. Further prospective studies are warranted to validate these findings and optimize patient outcomes in non-traditional infusion environments.
Keywords: Sickle cell disease, crizanlizumab, home infusion, adherence, patient outcomes
Background
Sickle cell disease (SCD) is an inheritable hemoglobinopathy that affects an estimated 100,000 people in the United States.1 Vaso-occlusive crises (VOCs) are a hallmark of sickle cell disease that often results in hospitalizations and can result in organ damage and complications such as acute chest syndrome, splenic sequestration crisis, venous thromboembolism, and priapism.2 The major clinical manifestation of VOCs are acute painful crises. Over three-fourths of SCD-related hospitalizations in 2016 involved a pain crisis.3 The number of hospital admissions for sickle cell pain crises increased from 2016 through 2020.4 Several new therapies have come to market in recent years to prevent the sickling of red blood cells, reduce VOCs, correct mutations in the gene encoding hemoglobin A, or induce expression of fetal hemoglobin.
Crizanlizumab was FDA approved in 2019 to reduce the frequency of VOCs in patients with SCD. Crizanlizumab is a humanized monoclonal antibody that inhibits P-selectin activity and works by binding to activated P-selectin on the surface of endothelial cells and platelets.5,6 This binding facilitates the inhibition of platelets, red blood cells, and leukocyte interactions thereby resulting in decreased platelet aggregation, increased blood flow, and decreased vaso-occlusion.
Despite having extensive health care needs, many patients with SCD have difficulty accessing appropriate care.1 Patients with SCD face barriers to timely care due to racial bias, rural residence, transportation challenges, and socioeconomic disadvantage. These factors contribute to higher rates of hospitalizations, readmissions, and emergency service use.7
Home infusion provides a level of convenience and can minimize geographic barriers to accessing treatment. While crizanlizumab has been shown to significantly reduce the rate of sickle cell-related pain crises with a low incidence of adverse events, limited data exists pertaining to the usage and tolerability of crizanlizumab in home and alternate infusion site settings.5
Purpose
This research provides evidence of the clinical utility and positive impact on patient access to SCD treatment in home and alternate infusion site setting. The primary objective of this study was to assess utilization of crizanlizumab in home and alternate site infusion patients. A secondary objective of this research was to assess patient tolerability of crizanlizumab in this patient population.
Methods
This retrospective, multicenter chart review was conducted across multiple dispensing pharmacies within a national home infusion company and evaluates data collected over a 52-month interval after FDA approval of crizanlizumab. Baseline characteristics, demographics, and adverse drug reactions were reviewed. This study was determined to be exempt by the Institutional Review Board.
Patients aged 18 and older with a confirmed diagnosis of SCD and at least 1 dispense of crizanlizumab (since its FDA approval) were included. Patients were excluded if they had no record of crizanlizumab dispensing during the study period, if there was insufficient documentation in the medical or pharmacy record to confirm treatment course, infusion setting, or outcomes, or if their medication was dispensed by a pharmacy in the study but administered by another provider or infusion center.
Data
Data collected includes:
- Number of patients that discontinued therapy (and reason)
- Frequency and types of adverse drug reactions (ADRs)
- Adherence to FDA-approved labeling (dose and schedule)
- Missed doses
- Payor type
- Characteristics of referral sources (physician specialty, local disease burden)
- Site of administration (home or alternate infusion setting)
- Use of other medications approved for SCD
- Frequency of VOC-related hospitalizations
Results
This study evaluated the utilization and tolerability of crizanlizumab in 16 patients with SCD across alternate infusion settings. Nine patients (36% of the total patients receiving crizanlizumab) received their infusions in a provider clinic setting and were excluded from further analysis. Among these 16 patients treated who met inclusion criteria, 11 (69%) received crizanlizumab at home, and 5 (31%) were treated in an AIS (Figure 1).
The patient sample consisted of 11 males (68.8%) and 5 females (31.2%), with an average age of 27.81 years (± 7.3) and a median age of 25.5 years at the first dispense (Table 1). Most patients were in the 18–34 year age range, with 7 patients (43.7%) aged 18–24 years and another 7 patients (43.7%) aged 25–34 years. Regarding payor types, 10 patients (62.5%) had commercial insurance, and 6 patients (37.5%) were covered by Medicaid. The predominant genotype amongst patients included in this study was HbSS (68.8%) whereas only 12.5% of patients presented with the HbSC genotype.
Key Terms and Definitions
Adherence: Defined in relation to the FDA-approved dosing schedule (every 4 weeks following the initial 2 loading doses). Adherence was assessed by comparing actual infusion intervals with the expected frequency outlined in the prescribing information. For this study, intervals of 28 ± 4 days (24–32 days) between infusions were considered adherent to account for minor real-world scheduling variability.
Adverse Drug Reaction (ADR): Defined as any documented infusion-related reaction, hypersensitivity event, or other adverse event attributed to crizanlizumab in provider notes, infusion records, or patient-reported outcomes.
Alternate Infusion Setting (AIS): For this study, AIS included home infusion and ambulatory infusion centers. Patients who received infusions in provider offices or hospital-based infusion centers were excluded.
Co-Treatment: Defined as concurrent use of 1 or more FDA-approved therapies for SCD (e.g., hydroxyurea, voxelotor, L-glutamine) during the study period while receiving crizanlizumab.
Days on Service: Defined as the total number of calendar days from the first recorded dispense of crizanlizumab to the last recorded dispense or discontinuation.
Dispense Ratio: Defined as the number of days on service divided by the number of dispenses for each patient. This metric was used to approximate adherence to the FDA-approved dosing schedule. Ratios corresponding to 28 ± 4 days (24–32 days) between infusions were considered adherent, while higher values indicate delayed or missed infusions, and lower values indicate early infusions. Outliers with substantially high ratios were identified as potential discontinuation, missed doses, or transitions between infusion providers.
Discontinuation: Defined as cessation of dispensing crizanlizumab by the pharmacy. Reasons included transfer to another infusion provider, prescriber cancellation of the order, patient request to stop therapy, or loss to follow-up due to non-adherence.
VOC-Related Hospitalization: Defined as an inpatient admission for vaso-occlusive crisis (VOC), identified through provider documentation, chart records, or reported hospitalization events in pharmacy records.
Patients received service for pharmacy services for an average of 416 days and a median of 343 days, indicating a positive skewed distribution. This might be attributed to the high discontinuation rate observed in the dataset. A dispense ratio was calculated in order to better quantify medication adherence (Table 2). Across the 16-patient cohort, 5 patients (31%) maintained dispense ratios of 24- 32 days, consistent with adherence to the FDA-approved crizanlizumab dosing schedule. The data of 3 patients can be perceived as outliers since their dispense ratios were 107, 178, and 290. Two of these patients were discharged for non-compliance and the third switched infusion providers due to issues with insurance authorizations. The outliers skew the dispense ratio to 63. Omitting the outliers reveals a mean ratio of 33.85 (SD 6.7) and a median of 32.44, values more in line with the FDA-approved dosing schedule of once every 28 days.
Geographically, the 16 patients receiving home or AIS treatments were distributed throughout the United States as follows: 10 patients (62.5%) were from the South region, 2 patients (12.5%) from the West region, and 2 patients (12.5%) from the Midwest region and 2 patients were from the Northeast region (Figures 2 and 3). Of the 16 patients treated outside a clinic, 9 (56.3%) discontinued therapy during the study period. The reasons for discontinuation were varied: 2 patients (12.5%) discontinued due to medication non-adherence, 5 patients (31.3%) switched to another infusion provider, 1 patient (6.3%) discontinued at their own choice, and 1 patient (6.3%) discontinued based on the provider’s discretion (Figure 4).
In terms of co-treatment for SCD, most patients were taking additional therapies alongside crizanlizumab (Table 1). Hydroxyurea was the most common concurrent medication, with 13 patients (81.3%) receiving it. Patients were also co-treated with folic acid (56.3%), voxelotor (25%), and L-glutamine (6.3%). Notably, no adverse drug reactions (ADRs) or use of anaphylaxis kits were reported during the study. The study also found that 8 patients (50%) had reported hospitalizations due to sickle cell crises during the study period. Amongst these patients, 1 was discharged for non-adherence, therapy was discontinued for another patient in favor of an oral agent, and a third patient switched infusion providers. Five of the patients with reported hospitalizations remained on service for subsequent infusions. This study did not evaluate the concurrent utilization of pain medication. While clinical documentation for some of the patients mentioned pain management regimens, it did not account for the frequency at which the patient was administering the medication. While clinical documentation for some of the patients mentioned pain management regimens, it did not account for the frequency at which the patient was administering the medication.
Discussion
This study aimed to evaluate the clinical utility of crizanlizumab in home and alternate infusion settings for patients with SCD. The findings suggest that crizanlizumab can be safely utilized outside of traditional clinic settings, with a substantial proportion of patients (64%) receiving their infusions at home or in alternative infusion suites without any reported adverse effects. However, the results also reveal a relatively high discontinuation rate, with 56.3% of patients in the home or alternate settings discontinuing therapy during the study period. Five of these 9 patients switched to a different infusion provider, leaving us unable to further assess their utilization (Fig. 4). Two of the remaining patients were discontinued due to medication nonadherence. One patient discontinued therapy at the prescriber’s discretion, in favor of an oral agent. One patient requested discontinuation, citing that the medication did not seem to be making a difference. There were no reported hospitalizations for this patient.
Findings in this report are consistent with previous studies that have explored factors contributing to the discontinuation of crizanlizumab. Non-adherence to scheduled infusion appointments was a significant reason for discontinuation in previous report, a factor that was also evident in this study where 2 patients discontinued due to medication non-adherence.5 A perceived lack of efficacy has also been reported as a reason for discontinuation and was also identified as a factor for some patients in this cohort where patients were still experiencing VOC-hospitalizations and pain crises.8
In their study, Cheplowitz et al. also report inability to adhere to scheduled appointments, lack of transportation, or increased pain as other reasons for crizanlizumab discontinuation. Only 65% of patients completed the SUSTAIN trial.5 The SUSTAIN investigators categorized the discontinuations as either lost to follow up, subject withdrawal, or “other.” Pregnancy, difficult venous access, and relocation were among the specified reasons for discontinuation in the SUSTAIN trial. Difficult venous access is not uncommon amongst patients with SCD. At least 1 patient in our cohort received their crizanlizumab infusions through an implanted port because of difficult peripheral venous access.
Our analysis of patients receiving crizanlizumab in alternate infusion settings found no reports of ADRs or infusion-related safety issues. Despite this favorable safety profile, 50% of patients experienced VOC-related hospitalizations while on therapy. This study was not designed to assess efficacy, but these findings provide real-world context consistent with the STAND study, which demonstrated that crizanlizumab is generally safe and well tolerated but did not show a significant difference in efficacy compared with placebo.9 Together, these results suggest that while crizanlizumab can be administered safely in alternate infusion settings, additional strategies may be needed to reduce hospitalizations and optimize clinical outcomes.
Analysis of medication adherence using dispense ratios revealed variability in crizanlizumab administration across 16 patients receiving therapy in home and alternate infusion settings. Five patients (31%) maintained ratios within the expected 28 ± 4 days (24–32 days) between infusions, indicating adherence to the FDA-approved schedule. When expanding the window to 28 ± 5 days (23–33 days), an additional 3 patients were captured, bringing the total within this broader adherence range to 8 patients (50%). Notably, 3 patients (19%) were extreme outliers with ratios exceeding 100 days. This data reflects interruptions in therapy, missed infusions, or transitions between infusion providers. Some patients were required to change infusion providers due to insurance carve-outs, which may have further contributed to interruptions and impacted overall adherence. The remaining 5 patients (31%) had moderate deviations from the expected infusion interval, which could reflect scheduling variability, minor logistical challenges, or clinical factors. Importantly, crizanlizumab is not administered in acute care settings, therefore patients who were hospitalized during their dosing window may have missed scheduled doses, further contributing to variability in adherence. These non-adherent cases highlight the challenges of maintaining consistent treatment in real-world settings, even when therapy is delivered safely outside of traditional infusion centers. Understanding the factors that contribute to missed doses or therapy discontinuation—including care coordination, patient engagement, hospitalization, and logistical or financial barriers—will be critical for optimizing treatment continuity and improving clinical outcomes.
Only 3 patients (Q, M, and P) initiated the full loading-dose phase of crizanlizumab (5 mg/kg every 2 weeks for 2 doses). Their dispense ratios highlight variability in early therapy adherence: Q maintained a ratio within the expected 28 ± 4 days (30.1), suggesting good adherence, while M (35.9) and P (47) experienced substantial delays between infusions. Both M and P had documented histories of cancelled appointments and delayed infusions, further contributing to variability in adherence. These data illustrate that even patients completing the loading phase can encounter realworld barriers—including hospitalization, scheduling challenges, and provider transitions—that impact early treatment adherence and overall therapy continuity.
Home and alternate infusion settings are uniquely positioned to provide consistent access to disease-modifying and supportive therapies for patients with SCD, helping to reduce treatment delays and prevent acute complications. Pharmacists practicing in these settings can play a pivotal role by ensuring safe and timely administration, monitoring for adherence and adverse events, and coordinating transitions of care between inpatient, outpatient, and specialty settings. In addition, pharmacists can address cost and insurance barriers, provide patient education, and collaborate with the multidisciplinary team to support individualized care plans that improve outcomes and reduce avoidable hospital utilization. Despite these advantages, maintaining long-term adherence to crizanlizumab therapy remains a challenge, underscoring the need to better understand the factors that contribute to treatment discontinuation, missed appointments, or transitions between infusion providers.
Limitations
This study is subject to several limitations. First, its retrospective design is an inherent limitation due to underreporting, potential information bias, and difficulty controlling confounding variables. We are unable to assess the role that underreporting of adverse events, emergency department visits, or infusion adherence may have had on the study results. This study could not capture the underlying reasons for missed doses, therapy discontinuations, or changes in infusion providers, limiting insight into patient-specific barriers to adherence. The small sample size is also a limitation; however, SCD is a rare disease. The generalizability of the findings to broader SCD populations or other home infusion practices are limited due to the small sample size. Because crizanlizumab is not administered in acute care settings, patients who were hospitalized during their scheduled dosing window would have missed doses. This likely contributed to some of the observed variability in dispense ratios and may overestimate nonadherence in the real-world setting.
Finally, this study did not include a comparator group, making it difficult to assess the relative effectiveness of crizanlizumab administered in the home versus traditional infusion center settings. Nevertheless, the study provides valuable insights into the utilization of crizanlizumab in real-world settings and underscores the potential benefits of expanding access to infusion therapy outside the clinic.
Future Directions
Future research should encompass an experimental design that allows investigators to better characterize predictors of adherence, long-term outcomes, and barriers to sustained use of crizanlizumab in home and alternate infusion settings. Studies comparing clinic-based and home-based administration directly could also provide valuable insights into optimizing site-of-care decisions for patients with SCD. Finally, development and evaluation of targeted patient support programs—including enhanced education, appointment reminders, and social support resources—may help to improve adherence and reduce discontinuation rates for home infusion therapies.
Conclusions
This study demonstrates that crizanlizumab can be utilized in home and alternate infusion settings for patients with sickle cell disease. However, the high discontinuation rate highlights the need for further research to identify barriers to treatment adherence and optimize care delivery in non-traditional settings. These findings contribute to the growing body of evidence supporting the use of home infusion therapies for chronic conditions like SCD, offering a potential model for improving patient access to care. Future studies with larger sample sizes and a prospective design are needed to confirm these findings and explore strategies to improve patient adherence and long-term outcomes. These findings support the feasibility of crizanlizumab administration in home and alternate infusion settings, while emphasizing the need for strategies to enhance patient adherence and optimize long-term treatment outcomes. Expanding access to crizanlizumab through home and alternate infusion settings is achievable, but targeted interventions are needed to improve adherence and maximize the therapy’s clinical benefits.
Disclosures: The authors have declared no potential conflicts of interest.
References
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