Volume 4, Issue 3 | November / December 2025

Optimizing Subcutaneous Immunoglobulin Therapy: A Modified Delphi Study on Supply Management and Best Practices in the U.S. Health Care System

Devin Wall, RN KORU Medical Systems dwall@korumedical.com
Elizabeth M. Younger, CRNP, PhD Johns Hopkins University School of Medicine
Kelvin Shaw, MD Allergy and ENT Associates
Chris Pratt, PharmD CVS
Suzanne Strasters, FNP-C GC Biopharma
Sam Mihelich, PharmD NuFactor Specialty Pharmacy
Will Holland, PharmD Realo Specialty Care Sarah
Taylor, RN Realo Specialty Care
Kolleen Casey, BSN KH Nursing Services
Nicole Graves, RN RxCrossroads

https://doi.org/10.70776/ZJVE7679

Abstract

Introduction
Subcutaneous immune globulin (SCIG) therapy is a flexible, patient-centered alternative to intravenous immune globulin (IVIG). While increasingly popular in home and specialty infusion care, managing the ancillary supplies for SCIG therapy remains complex. Current literature offers general guidance on SCIG administration but lacks detailed consensus on best practices for supply management, infusion site selection, and training requirements. This gap contributes to variability in practice and challenges for both patients and providers. The purpose of this Delphi study was to leverage multidisciplinary expertise to identify consensus in SCIG supply management, aiming to inform best practices, improve care consistency, and support the growing demand for SCIG therapy in home-based settings.

Methods
Nine multidisciplinary experts were recruited, representing prescribing providers, pharmacists, and infusion nurses with either recent or extensive experience in supporting, managing, or administering SCIG therapy in the clinical setting. The study consisted of multiple Delphi rounds. In the first round, participants answered 10 open-ended questions about best practices for ancillary supply management for patients receiving SCIG therapy. For the second Delphi round, responses and statements collected during the first round were categorized by theme and organized into forced-choice scale (77 items), ranked response (3 items), and rated response (20 items) questionnaire items. Participants reviewed, commented on, and ranked responses to identify consensus and areas of controversy. Participants were given the opportunity to clarify responses, achieve greater understanding, and explore opportunities for future research during optional individual interviews during a third and final Delphi round. Four out of the 9 original panelists opted to participate in individual interviews. The results of Delphi rounds were de-identified, clustered, and compared with existing literature surrounding best practices for SCIG infusion.

Results
The Delphi process identified several key findings: individualized approaches to needle selection, infusion site management, and flow rate adjustments are critical for minimizing adverse reactions and optimizing patient comfort. Additionally, the ease of use of infusion systems significantly impacts patient adherence and the need for clinical support, while ongoing education and follow-up are essential for addressing infusion-related challenges. The study also highlighted the importance of interdisciplinary collaboration and cost considerations in ensuring effective and patient-centered SCIG therapy delivery.

Consensus Areas:
Consensus emerged among the 9 participants within the domains of shared decision-making, selecting needle length and infusion site locations based on individual anatomical variation rather than bodyweight alone, and prioritizing patient-centered approaches (Somewhat Agree 11.1%; Agree up to 44.4%; Strongly Agree 56%). A simple infusion system with fewer steps was preferred over complex systems due to reduced training and education demands (Somewhat Agree 11.1%; Agree 55.6%; Strongly Agree 22.2%).

Disciplinary Variations:
Different priorities were noted across the disciplines of nursing, pharmacy, and prescribing providers, particularly in achieving optimal infusion rates for patients. These variations primarily emerged in the ordered response items, with Kendall’s W values between 0.24 and 0.38.

Conclusions
The study’s emphasis on individualized infusion practices and simplified systems aligns with the broader health care trend toward patient-centric approaches and home-based care. By establishing expert consensus and addressing gaps in current practices, the findings support the development of clearer guidelines and future innovations.

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.

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

^1. Centers for Disease Control and Prevention (CDC). Data and Statistics on Sickle Cell Disease. Sickle Cell Disease (SCD). Published May 6, 2024. https://www.cdc.gov/sickle-cell/data/index.html.

^2. Borhade MB, Patel P, Kondamudi NP. Sickle Cell Crisis. [Updated 2024 Feb 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526064/. Accessed August 26, 2024.

^3. Fingar KR, Owens PL, et al. Characteristics of Inpatient Hospital Stays Involving Sickle Cell Disease, 2000-2016. HCUP Statistical Brief #251. September 2019. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb251-Sickle-Cell-Disease-Stays-2016.pdf. Accessed August 24, 2024.

^4. Chennapragada SS, Thevuthasan S, Savani S, Goyal S, Singh V, Ramphul K, et al. Characteristics and Trends of Hospitalizations for Sickle-Cell Related Complications. Blood. 2023;142 (Supplement 1):2305-. doi: 10.1182/ blood-2023-187511.

^5. Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, et al. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. New England Journal of Medicine. 2017;376(5):429-39. doi: 10.1056/ NEJMoa1611770.

^6. Adakveo [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2024.

^7. Khan H, Krull M, Hankins JS, Wang WC, Porter JS. Sickle cell disease and social determinants of health: A scoping review. Pediatric Blood & Cancer. 2022;70(2). doi: 10.1002/pbc.30089.

^8. Cheplowitz H, Block S, Groesbeck J, Sacknoff S, Nguyen AL, Gopal S. Real-World Data of Crizanlizumab in Sickle Cell Disease: A Single-Center Analysis. Journal of Hematology. 2023;12(3):105-8. doi: 10.14740/jh1127.

^9. Abboud MR, Cançado RD, De Montalembert M, Smith WR, Rimawi H, Voskaridou E, et al. Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebocontrolled, randomised, double-blind, phase 3 trial. The Lancet Haematology. 2025;12(4):e248-e57. doi: 10.1016/s2352-3026(24)00384-3.

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