A Vial Access Device for Facilitated Subcutaneous Immunoglobulin 10% Using Modular Innovation Principles and a Patient-Centric Design
Kimberly Duff, RN, BSN Clinical Sciences, R&D Takeda Development Center Americas, Inc. kimberly.duff@takeda.com
Stefan Holzner, PhD* Pharmaceutical Sciences, R&D Takeda Development Center Americas, Inc.
Madeleine Gibson, MSIE* Pharmaceutical Sciences, R&D Takeda Development Center Americas, Inc.
Seth Jones, BSc* Pharmaceutical Sciences, R&D Takeda Development Center Americas, Inc.
Scott Ariagno, MSc* Pharmaceutical Sciences, R&D Takeda Development Center Americas, Inc.
*Affiliation at the time of the study
Abstract
Introduction
Facilitated subcutaneous immunoglobulin 10% (fSCIG 10%) is packaged as a dual-vial unit of immunoglobulin G 10% (labelled ‘IG’) and recombinant human hyaluronidase (rHuPH20; labelled ‘HY’) for use as a prescribed immunoglobulin treatment for patients with primary or secondary immunodeficiency and chronic inflammatory demyelinating polyradiculoneuropathy. The current infusion process involves multiple steps that need repeating for patients requiring multiple dual-vial units per infusion. We hypothesized that the infusion process could be improved using patient-centric design and modular innovation principles.
Methods
Ethnographic research was conducted to understand patient and nurse experiences of administering fSCIG 10% to identify opportunities to improve the infusion process. Device design objectives were established based on feedback from 4 patients receiving fSCIG 10% for primary immunodeficiency (at-home observations and feedback sessions) and 4 nurses providing fSCIG 10% infusion training (interviews and mock training sessions). Design objectives included: simplifying steps for fSCIG 10% preparation and infusion, standardizing equipment and infusion stages and easing patient mobility during infusions. Formative usability evaluation research was conducted with 10 patients and 4 nurses to evaluate prototypes of a vial access device; observations were used to inform the modular design of the final device.
Results
The final vial access device is a base with numbered docking stations to accommodate up to 4 dual-vial units. Tubing underneath the docks separately combines the contents of multiple HY and IG vials, with separate color-coded connectors. The HY preparation process involves removing cover(s) from dock(s), inserting dual-vial units and drawing the total rHuPH20 dose into a single syringe from the HY connector attached to the device. To prepare IG, the pump tubing is attached to the IG connector on the device and primed. Following the delivery of HY, the pump tubing is attached to the same needle set; infusion administration remains similar to the current method. A device carrier, developed to hold the vial access device and a pump, enables patient mobility during the infusion. The vial access device is intended for single use and can be disposed of safely with the dual-vial units attached. Compared with the current fSCIG 10% infusion process, the vial access device simplified preparation, required fewer components and facilitated room-to- room patient mobility during infusion.
Conclusions
Patient-centric design and modular innovation principles were used to develop a vial access device to optimize the patient experience of fSCIG 10% infusion. Further research will assess its impact on patient quality of life.
Keywords
Chronic inflammatory demyelinating polyradiculoneuropathy, device, facilitated subcutaneous immunoglobulin, primary immunodeficiency, recombinant human hyaluronidase, secondary immunodeficiency
Introduction
Subcutaneous immune globulin (SCIG) therapy has emerged as an effective and patient-centered alternative to intravenous immune globulin (IVIG) for individuals requiring longterm immune globulin replacement. Traditionally, IVIG has been the primary route of administration; however, the complexity of venous access, patient discomfort, systemic side effects, and the demand for flexible, home-based therapies have driven the adoption of SCIG. SCIG allows for self-administration and improved treatment adherence, yet challenges persist, including variability in clinical practices, inconsistent equipment selection, and limited interdisciplinary collaboration.1-6 For vulnerable populations, such as the pediatric population, older adults, or those with mobility limitations, these challenges may exacerbate barriers to therapy and lead to suboptimal outcomes.6,7 This growing complexity necessitates a better understanding of the clinical, systemic, and patient-centered factors influencing SCIG therapy delivery.
Despite its advantages, SCIG therapy remains hindered by fragmented care delivery models and gaps in evidence-based practice guidelines.8,9 Current approaches to equipment selection, infusion site management, and patient education may be inconsistent and driven by institutional or health care provider preferences rather than standardized protocols.10,11 Specialty pharmacies and manufacturers frequently dictate the provision of supplies, with limited input from clinicians and patients, creating variability in the infusion experience. In some cases, clinicians may have inadequate training to guide patients in customizing their therapy to maximize comfort and adherence.
Objectives
- The objectives of the study were to:
- Identify areas of consensus and controversy on best practices in SCIG therapy, focusing on (a) infusion site selection and needle placement, (b) equipment use and troubleshooting, and (c) patient and caregiver education.
- Identify barriers to interdisciplinary collaboration in the delivery of SCIG therapy and inform strategies to enhance communication and decision-making among stakeholders.
- Prioritize innovations in equipment design and patient training to address challenges faced by patients with physical or cognitive limitations.
- Synthesize expert recommendations into a framework that promotes standardized, patient-centered care practices while allowing flexibility for individual needs.
This research aims to further inform the development of evidence-based practice guidelines for SCIG therapy, ensuring consistent, high-quality care for patients in both clinical and home-based settings. By addressing gaps in education, equipment usability, and interdisciplinary communication, the study seeks to optimize SCIG therapy outcomes and encourage broader adoption of this treatment modality.
Scope
The scope of this Delphi study encompasses SCIG therapy supply management practices for treatment in diverse patient populations and various infusion settings. Guided by the research question, “What are the best practice recommendations for the delivery, education, and interdisciplinary management of SCIG therapy supplies?” this study seeks to inform strategic approaches to improve patient outcomes, enhance safety, and standardize care. The study focuses on key aspects of SCIG therapy, including infusion site selection, equipment use, patient and caregiver education, and interdisciplinary collaboration.
Methods
Study Design
This study employed a 3-step modified Delphi method to identify areas of consensus and controversy on best practices in the administration of SCIG therapy. The Delphi method, well-suited for gathering expert opinions in a systematic and iterative process, was conducted electronically to accommodate geographically dispersed participants and ensure a transparent, structured approach to data collection and analysis.12
The Delphi process included qualitative and quantitative elements, allowing for both thematic exploration and prioritization of key issues. Participants included a multidisciplinary panel of pharmacists, infusion nurses, and prescribing providers, selected for their expertise and diverse practice settings. The iterative rounds were designed to identify and refine consensus on topics such as infusion site selection, equipment use, patient education, and interdisciplinary collaboration. This approach was chosen because it facilitates collective decision-making on complex issues that are not easily resolved through conventional analytical techniques but benefit from subjective judgments across specialties. The findings are intended to inform standardized, evidence-based recommendations that can be applied across clinical and home-based care settings.
Participants
The expert panel for this Delphi study was selected to ensure multidisciplinary representation, clinical expertise in SCIG therapy, and diversity in practice settings (Table 1). Participants included pharmacists, infusion nurses, and prescribing providers, all actively involved in the delivery or management of SCIG therapy in various infusion settings. To incorporate perspectives from key stakeholders, individuals were recruited through professional networks, academic affiliations, and referrals from relevant associations across the United States. Invitations were sent via email, accompanied by participant information and consent forms. Participants identified their disciplines from a prepopulated list which included the roles of Prescribing Provider, Pharmacist, Infusion Nurse, Case Manager, Nurse Navigator, Patient Advocate, or Other, in which case the respondent was able to self-identify their role in a free text field.
Inclusion criteria required participants to have: (a) recent (within 6 months) clinical experience prescribing, administering, or managing SCIG therapy, and/or (b) evidence of professional contributions, such as peer-reviewed publications, participation in scientific symposia, or teaching roles within this field. The aim was to recruit a panel of 6 to 10 experts, balancing representation from prescribers, pharmacists, and nurses to ensure a comprehensive range of perspectives. Recruitment relied on purposive and snowball sampling, targeting clinicians recognized as thought leaders or highly experienced in SCIG therapy. As this study prioritized health care professional perspectives, patients and the public were not directly involved in the design, conduct, or dissemination of this research.
Study Procedures
The initial open-ended questionnaire for this Delphi study was developed by a multidisciplinary research committee consisting of an infusion clinical specialist, a product development specialist, an epidemiologist, and a health economist. This committee drew on evidence from stakeholder interviews, a review of clinical guidelines (e.g., the Infusion Therapy Standards of Practice), and grey literature to ensure the framework was comprehensive and aligned with current practices and challenges in SCIG therapy. The research committee aimed to create a robust framework that addressed critical domains of supply characteristics, infusion site reaction mitigation, ease of use, SCIG administration, education and training, future research and innovation, cost considerations, and communication.
e-Delphi Survey Rounds
The study was conducted in iterative rounds. In the first round, an open-ended questionnaire invited the 9 participants to share their perspectives on challenges and best practices in SCIG therapy. The responses were thematically analyzed to generate key variables and structured response options for subsequent rounds. Open-ended survey responses were analyzed to capture qualitative insights to inform the development of closed-ended questions for the same 9 participants in the second round, allowing the panel to prioritize and refine recommendations, guidelines, and principles systematically. Thematic analysis was used to process and categorize the open-ended responses. The research team reviewed participant responses to identify recurring themes, patterns, and perspectives related to best practices for SCIG therapy and supply management. Responses were systematically coded into the categories of supply characteristics, infusion site reaction mitigation, ease of use, optimizing the infusion experience, supply availability, SCIG administration, training and education, new technologies, cost considerations, and communication. This qualitative feedback was integrated into the study design for subsequent rounds of the Delphi process. Additionally, the researchers integrated qualitative insights with the quantitative data to address discrepancies in consensus levels, refine the phrasing of areas of consensus or controversy, and introduce new items based on participant input. This structured and evidence-informed process ensured a rigorous approach to informing best practices in SCIG therapy supply management. Both survey rounds were administered electronically using Microsoft Forms to facilitate participation by geographically dispersed panel members. The first-round survey consisted of 10 open-ended questions (Table 2) designed to generate structured responses in the second-round survey (Supplementary, Appendix A). The second-round survey was divided into 8 sections corresponding to the coded themes identified during the first-round survey, reflecting key domains of SCIG therapy supply management: (a) supply characteristics, (b) infusion site reaction mitigation, (c) ease of use, (d) SCIG administration, (e) education and training, (f) future research and innovation, (g) cost considerations, and (h) communication. (Supplementary, Appendix B) Each survey contained embedded instructions and participation guidelines. Members of the expert panel were invited to participate via a web link sent to their provided email addresses.
During the second-round survey, panelists were asked to rate their agreement or assessment of each proposed practice recommendation, guideline, or principle. These responses were in the form of ratings using a 6-point forced-choice scale, a 10-point clinical impact scale, and ordered responses. Forced-choice scale items in this Delphi study were used to quantify levels of agreement with proposed statements related to SCIG therapy and supply management. The use of forced-choice response items instead of traditional Likert scales minimized the potential for response biases such as social desirability and acquiescence. Forced-choice formats require respondents to select options corresponding to the level of agreement or disagreement with a concept, topic, or practice without the ability to select a neutral option, thereby reducing the tendency to select socially desirable or indifferent responses, which is more common in Likert-type scales. Respondents may also tend to default to the middle option in longer surveys out of convenience or fatigue in a conscious or unconscious attempt to reduce the cognitive effort required to make a decision. Additionally, forced-choice items are advantageous in contexts where distinguishing the relative importance of various clinical practices is crucial, as they compel participants to prioritize specific practices over others, yielding clearer insights into expert consensus. By using this method, the study ensured a more nuanced and reliable assessment of expert priorities and preferences in clinical decision-making.13 These items were used to allow the researchers to measure the degree of positive or negative consensus on each statement abstracted from the round 1 survey. Response options included “strongly disagree” (0), “disagree” (1), “somewhat disagree” (2), “somewhat agree” (3), “agree” (4), “strongly agree” (5), and “I don’t know” (no score). The forced-choice scale responses were analyzed using median, mean, and interquartile range (IQR) to categorize the level and type of agreement (strong positive consensus, weak positive consensus, strong negative consensus, weak negative consensus, and disagreement). Forced-choice scale consensus thresholds are defined according to the criteria listed in Table 3.
Clinical impact scale items were rated on a scale of 1 to 10, with 1 indicating the lowest possible clinical impact to 10 indicating the highest possible clinical impact. This rating system was utilized to assess the perceived significance and practical relevance of each proposed recommendation or phenomenon in clinical settings. By assigning numerical values, panelists indicated the degree to which they believe a recommendation, principle, or circumstance will influence patient care, health care delivery, or outcomes. This scale provided a quantitative measure of the potential clinical importance of each statement, providing insights into how elements of patient care are both clinically meaningful and actionable. The results from the clinical impact scale guided the refinement of recommendations and clinical insights, ensuring that the final consensus reflects the most impactful and relevant practices for real-world application. The clinical impact rating responses were analyzed using median, mean, mode, and interquartile range (IQR) to categorize the level and type of agreement (strong consensus and moderate consensus). Clinical impact scale consensus thresholds are defined according to the criteria listed in Table 3.
Ordered response items were rated by allowing participants to drag-and-drop individual statements into a list ranking them in order of importance, with the first ordinal rank indicating the greatest importance and the last ordinal rank indicating the least importance. Open text fields were provided at the end of each section to allow participants to suggest modifications, provide rationale for their ratings, and propose new or excluded recommendations. The use of ordered response items in this Delphi study served to systematically capture and rank the priorities or preferences of the expert panel regarding specific recommendations or practices (Supplementary, Appendix B, items OR1-OR3). These items enabled participants to provide nuanced input by arranging options in order of perceived importance, relevance, or effectiveness, thereby offering insights into the relative value assigned to each item. This approach allowed the researchers to discern patterns in expert judgment, facilitating the identification of consensus on key priorities and areas requiring further deliberation or study. Additionally, ordered response items support the refinement of recommendations by highlighting areas of strong agreement or divergence, ensuring that the final consensus reflects both the collective expertise of the panel and the practical implications for clinical or operational contexts.
The round 2 survey included a total of 77 forced-choice scale items, 20 clinical impact rating items, and 3 ordered response items (Supplementary, Appendix B). While a third round of consensus via e-conference was initially planned to address unresolved discrepancies, it was deemed that individual interviews would be the most inclusive approach to identifying areas of consensus and controversy by offering panelists flexibility in participation and ensured that every participant had the opportunity to provide equal input during open-ended discussion. Efforts were made to identify and distinguish real clinical disagreements from those arising from fatigue or misunderstanding during one-on-one interviews. Four panelists opted to participate in this final interview stage. This iterative and inclusive approach ensured that the results reflected a broad range of expert perspectives while maintaining methodological rigor.
Consensus in this Delphi study was defined based on specific thresholds applied to the distribution of forced-choice scale responses, with metrics including the median, mean, and interquartile range (IQR). Strong positive consensus was defined as the median and mean ratings being between 4 and 5, with an IQR of ≤1, indicating high agreement and support for the recommendation, guideline, or principle. Moderate positive consensus was defined as median and mean being ≥3 and <4, with an IQR of <2, suggesting moderate agreement. Similarly, strong negative consensus was defined by median and mean ratings between 0 and 1, with an IQR of ≤1, reflecting strong opposition. Moderate negative consensus was defined as the median and mean falling between >1 and ≤2, with an IQR <2, indicating moderate disagreement. Disagreement, or lack of consensus, was defined as the IQR being ≥2, signifying significant variability in panelist responses and the absence of a clear collective opinion. These thresholds ensured a systematic and transparent evaluation of consensus levels for each recommendation.
Kendall’s W (Coefficient of Concordance) was employed to assess the level of agreement among experts when ranking ordered response survey items. Kendall’s W quantifies the degree of consensus by measuring the alignment of rankings provided by multiple respondents. It ranges from 0 (no agreement) to 1 (perfect agreement), making it a valuable tool for determining whether the panelists have a shared perspective on the relative importance or priority of survey items. A high Kendall’s W value indicates strong consensus, suggesting that the panelists are largely in agreement about the rankings of the items. Conversely, a low Kendall’s W value signifies a lack of consensus and variability in the rankings.14,15 By systematically applying Kendall’s W, the study ensures that agreement levels are objectively measured, guiding the iterative refinement process toward a cohesive, evidence-based set of recommendations.
A preliminary report detailing group responses, including qualitative feedback, was prepared and anonymized by the researchers and presented to participants who opted to participate in 1-on-1 interviews following the completion of the round 2 survey. The preliminary report consisted of the total number of respondents that selected each response option and mean score (forced-choice and clinical impact scale items), the rank sum and average rank (ordered response items), and open-ended responses.
Results
The areas of consensus derived from forced-choice scale survey items in this Delphi study highlight expert agreement on various aspects of SCIG therapy (Supplementary, Appendix A). Strong positive consensus was achieved on several clinical practices, including the importance of selecting appropriate needle length and placement based on individual patient factors, addressing infusion supply issues during initial assessments, and performing follow-up evaluations tailored to patient needs. There was also consensus on the clinical implications of needle length, optimal flow rates, and the influence of infusion system usability on training requirements. Cost considerations, such as the need to keep single-use supplies affordable, were also emphasized.
Moderate positive consensus was observed in areas related to patient comfort and practical aspects of infusion therapy, such as the role of adhesive dressings in skin irritation, the need for visual acuity assessments, and specific techniques for priming and needle insertion. Experts also agreed on the general principles guiding infusion rates, such as starting infusions slowly and adjusting based on patient tolerance, as well as the importance of education in mitigating supply inconsistencies.
In contrast, moderate negative consensus was reached on the feasibility of ensuring uniform supply distribution, such as guaranteeing a specific brand of pump for every patient. No items reached strong negative consensus, indicating minimal widespread disagreement among the panelists. Overall, the results reflect broad agreement on key clinical practices and supply management in SCIG therapy, while also highlighting areas where variability in practice persists.
Areas of consensus from the clinical impact survey items were categorized by the strength of agreement based on interquartile range (IQR) thresholds (Table 4). Strong consensus (IQR ≤ 2) was achieved on 2 items: the tendency of pumps/syringe drivers to break after more than 2 years of use and the potential for adhesive dressings to cause pain or discomfort during removal. These items had mean scores of 3.6 and 3.3, respectively, with median scores of 3, indicating moderate concern regarding their clinical impact.
Moderate consensus (IQR < 4) was observed for the statement that infusion site saturation can slow the infusion process and cause ulcerations. This item had a mean score of 4.9, a median of 5, and a mode of 5, suggesting a moderate to high perceived clinical impact. Overall, the results reflect a shared recognition of the potential complications associated with SCIG therapy equipment and infusion practices.
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.
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