Immunoglobulin treatment and clinical outcomes: data from the Ontario Immunoglobulin Treatment program multicenter case registry

Abstract

Background:

The therapeutic use of immunoglobulin (IG) is increasing and accounts for the largest expenditure in the Canadian Blood Services budget. However, more granular data on IG utilization is limited.

Objective:

To describe IG treatment indications, dosing characteristics, and clinical outcomes in patients enrolled in the Ontario IG Treatment (ONIT) program, a government-funded pilot clinical program with a case registry.

Methods:

A longitudinal descriptive study was conducted on ONIT registry participants from June 1, 2020 to March 31, 2024.

Results:

Six hundred ninety-three consenting participants were included; 429 (61.9%) were female; median [Q1, Q3] age was 62 [47, 71] years; 47 (6.8%) passed away during the study period. Of 693, 658 (94.9%) were receiving IG treatment: 544 (82.7%) on SCIG and 114 (17.3%) on IVIG. Treatment indications were primary immune deficiency (PID) (299, 43.1%), secondary immune deficiency (SID) (348, 50.2%), and immune-mediated disease (IMD) (46, 6.7%). The median dose was 0.48 [0.42, 0.57] and 0.52 [0.44, 0.64] g/kg/4 weeks, for SCIG and IVIG, respectively. Seventy-three patients transitioned from IVIG to SCIG, with the dose adjusted to clinical response. The IVIG:SCIG conversion ratios were 1:1, 1:0.9, and 1:1.2 for PID, SID, and IMD, respectively. Only 33 (5.0%) stopped IG during the study. There was a 78.4% reduction in infections and over 90% reduction in emergency room visits and hospitalizations in PID and SID. Most patients (89.4%) reported improved health after starting IG therapy.

Conclusion:

The study provides insights into the current landscape of IG utilization, which may inform health system research and support healthcare delivery planning.

Introduction

Immunoglobulin (IG) therapy is a critical treatment modality for patients with immunodeficiencies and autoimmune conditions. It plays a vital role in enhancing immune function, reducing infection rates, and improving overall patient outcomes. ¹ Over time, the utilization of IG, the most extensively used product derived from human plasma, ² has broadened from treating individuals with immunodeficiencies to encompassing a wide array of illnesses, including hematologic, neurologic, rheumatologic, and dermatologic conditions, where it serves as an immune modulator. ³ Given the rising demand for IG across various medical specialties and the significant number of patients worldwide who remain without access to these treatments, there are increasing concerns about Canada’s long-term ability to ensure a continuous supply of IG for its citizens. ⁴ Canada has long been a significant consumer of IG, with per capita demand steadily increasing at a rapid pace. Currently, Canada ranks as the second-highest per capita user of IG globally. ⁴ Understanding the scope of patients receiving IG therapy is essential for understanding these trends, optimizing treatment protocols and addressing the specific needs of different patient populations. ⁵

Subcutaneous immunoglobulin (SCIG) has become increasingly popular due to its safety and tolerability, with a lower risk of systemic adverse reactions compared to intravenous immunoglobulin (IVIG). ⁶ In addition, SCIG provides consistent steady-state IgG trough levels without spikes in concentration, primarily because of the pharmacokinetic characteristics of subcutaneous administration, which include prolonged absorption over several days and an extended elimination half-life. ⁷ In an analysis of surveys from respondents in Canada with primary immune deficiency (PID) or secondary immune deficiency (SID), SCIG respondents had better treatment satisfaction, perceived effectiveness, and health outcomes than IVIG respondents. Specifically, SCIG users reported significantly shorter total times associated with infusion preparation, actual infusion, and post-infusion processes, even when accounting for the role of healthcare professionals in IVIG administration. These benefits were particularly notable among those new to SCIG therapy, suggesting that SCIG may offer greater convenience and a sense of empowerment for patients compared to IVIG. ⁸ With proper training, patients can self-administer SCIG at home, enhancing comfort, independence, and cost-effectiveness. ⁹

The Ontario Immunoglobulin Treatment (ONIT) program, first established at three tertiary care centers (Hamilton Health Sciences (HHS), St. Michael’s Hospital (SMH), and The Ottawa Hospital (TOH)) in Ontario in October 2019, with continuous funding from the Ontario Ministry of Health, has now expanded to a fourth center, Sault Area Hospital. This program is dedicated to enhancing healthcare delivery and supporting home-based SCIG therapy.

Integral to this program is the establishment of the ONIT case registry, a province-wide, multicenter clinical registry systematically collecting and monitoring data related to IG therapies, in June 2020. The primary objective of the ONIT registry is to improve patient care standards by organizing and analyzing data to answer research questions, identify treatment patterns, and monitor clinical outcomes.

Based on the first report from the ONIT registry, the use of IG therapy in patients with SID has shown remarkable efficacy in reducing healthcare utilization and infection rates. When comparing baseline data pre-IG with post-IG treatment data, it was found that IG treatment reduced the average annual number of infections by 82.6%, the average number of emergency room (ER) visits by 84.6%, and the average number of hospitalizations by 83.3%. ¹⁰ These findings suggest an association between IG treatment, particularly SCIG, and reductions in reported infections and the need for emergency and inpatient care in patients with SID, although causal interferences cannot be made due to the observational nature of the data.

This study provides a detailed report on the demographic and clinical profiles and IG treatment of patients enrolled in the ONIT registry in order to inform healthcare providers and policymakers on the current landscape of IG therapy.

Methods

The ONIT case registry is a comprehensive database that records patient demographics, clinical profile, indications for IG treatment, dosage, regimen, clinical outcomes such as infections, ER visits, hospitalizations, and patient-reported health outcomes. These data are collected prospectively during follow-up visits with physicians across multiple tertiary healthcare centers in Ontario. The study included patients enrolled between June 1, 2020 and March 31, 2024.

Follow-up visits generally included participants who were all adults (aged >18 years) with immunodeficiency or immune-mediated diseases who were previously or currently receiving IVIG or SCIG treatment, being considered for IG therapy, transitioning to SCIG, or starting IG therapy for the first time. Exclusion criteria were patients who had never received IG therapy during the study period. There were 47 (6.8%) patients who had passed away before the data extraction date, and the data closest to their time of death were included in the analysis.

At the start of study enrollment, patients completed a baseline questionnaire regarding infection rates, ER visits, hospitalizations, and their general state of health before and after receiving any IG treatment. During each follow-up visit, patients filled out questionnaires on infections, ER visits, hospitalizations, and their health status post-IG treatment. Patients were asked whether their overall health had remained the same, worsened, or improved compared to before starting IG treatment. Similar questions were posed to patients who switched their treatment modality from IVIG to SCIG or vice versa. The study-specific questionnaires were not validated instruments; they were developed internally to document trends in patient-reported outcomes (Supplemental Materials). Questionnaires were completed using a tablet, computer, pen, or paper. Patients were also instructed to maintain personal diaries, which are available for patients to log their weekly infusions, the LOT numbers of the product, infusion sites, and any adverse reactions.

IG dose usage was monitored and adjusted to achieve optimal response, including serum IgG level, rate of infection, and adverse events. The route of IG administration could be altered to patients’ needs. IVIG:SCIG dosage conversion ratio was typically 1:1, that is, the monthly IG dose was equivalent between both modalities. The conversion ratio was adjusted based on individual clinician’s judgment to obtain a comparable or better clinical response in the patient who had a change in route of IG administration.

All eligible participants in the ONIT registry during the study period were included in the analysis (N = 693). No formal sample size calculation was performed. Statistical analyses included descriptive statistics to summarize patient demographics, treatment modalities IVIG versus SCIG, and clinical outcomes, including infection rates, ER visits, hospitalizations, and patient-reported health status. Continuous variables such as IG doses and infusion times are presented as median [interquartile range] or mean ± standard deviation as appropriate. Categorical variables, including gender, disease type, and IG administration modality, are presented as counts and percentages. Changes in IG mode of delivery, follow-up intervals, discontinuation of therapy, and outcomes after dose adjustments were summarized descriptively. No formal hypothesis testing, subgroup analyses, or sensitivity analyses were conducted. Missing data are reported where available.

The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE; Supplemental Materials).

Results

Demographics and clinical profiles

The demographics of patients across three centers, HHS, SMH, and TOH, are presented in Table 1. A total of 693 participants were identified (264 male, 429 female) with a median age of 62 [Q1, Q3; 47, 71]. Of these patients, 658 were on IG treatment (94.9%), 544 were on SCIG (82.7% of the 658), and 114 were on IVIG (17.3% of the 658). A total of 35 patients (5.1% of the 693) had stopped IG therapy during the study period. Median study follow-up time was 12.0 [6.75, 18.0] months.

Table 1.

Demographics and clinical profiles of study participants.

Number of participants	693
Male:female	264:429
On IG	658 (94.9%)
IVIG:SCIG	114:544
Stopped IG	35 (5.1%)
PID	299 (43.1%)
CVID	181 (60.5%)
XLA	11 (3.7%)
Combined immunodeficiency	6 (2.0%)
Hyper IgM	5 (1.7%)
Hyper IgE	4 (1.3%)
Others, such as specific antibody deficiency, hypogammaglobulinemia with no known secondary causes	92 (30.8%)
PID patients tested for molecular genetic variants	69 (23.1%)
Pathogenic variants found	20 (29.0%)
SID	348 (50.2%)
Hematological malignancy	214 (61.5%)
CLL	77 (36.0%)
Lymphoma	64 (30.0%)
MM and other plasma cell dyscrasias	73 (34.0%)
Chronic or recurrent neutrophilic bronchitis with or without underlying lung diseases (asthma, COPD, bronchiectasis)	84 (24.1%)
Solid organ transplant	12 (3.5%)
HSCT	6 (1.7%)
Immunosuppression for RA, SLE, GPA, Crohn’s disease	29 (8.3%)
Other (chronic fatigue syndrome; severe malnutrition)	3 (0.9%)
IMD (ADEM; MG; CIDP; MMN; SFN)	46 (6.7%)

ADEM, acute disseminated encephalomyelitis; CIDP, chronic inflammatory demyelinating polyneuropathy; COPD, chronic obstructive pulmonary disease; CVID, common variable immunodeficiency; GPA, granulomatosis with polyangiitis; HSCT, hematopoietic stem cell transplant; IG, immunoglobulin; IMD, immune-mediated disease; MG, myasthenia gravis; MMN, multiple multifocal neuropathy; PID, primary immune deficiency; RA, rheumatoid arthritis; SFN, small fiber neuropathy; SID, secondary immune deficiency; SLE, systemic lupus erythematosus; XLA, X-linked agammaglobulinemia.

Indications for IG treatment

The most common indication was SID (348, 50.2%), followed by PID (299, 43.1%). Among SID, hematologic malignancies were the most prevalent, accounting for 61.5% of cases. CLL was the most common N = 77 (36.0%), followed by MM and other plasma cell dyscrasias N = 73 (34.0%), and lymphoma N = 64 (30.0%). Chronic or recurrent neutrophilic bronchitis, with or without underlying lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, or bronchiectasis, was observed in 24.1% of SID cases (N = 84).

CVID (60.5%) was the most common disease among PID. Molecular genetic testing was conducted on 69 patients (23.1%) with PID, identifying pathogenic variants in 20 (29.0%) of them. These variants were linked to specific PIDs, such as AICDA variants in hyper IgM syndrome and STAT3 variants in hyper IgE syndrome or Job’s syndrome. Additionally, 27 (9.0%) of PID patients reported having relative(s) with a diagnosed PID. Of 299, 117 (39.1%) had a comorbid lung disease such as asthma, COPD, or bronchiectasis, with 2 (0.7%) patients presenting with a complication of CVID, granulomatous lymphocytic interstitial lung disease. Twenty-eight (9.4%) PID patients had a concomitant hematologic malignancy, including lymphoma, CLL, and plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance or MM. Three (1.0%) patients had undergone hematopoietic stem cell transplant (HSCT). In addition, 30 (10.0%) patients had solid tumor, including thymoma, colon, kidney, breast, and skin cancers. Thirty (10.0%) patients also had organomegaly, such as splenomegaly.

Lastly, patients with immune-mediated diseases (IMD) such as acute demyelinating encephalomyelitis, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, multiple sclerosis, Sjogren’s syndrome, systemic lupus erythematosus, and others, where IG therapy is used for immune modulation rather than replacement, were also included in our registry. This group comprised a small proportion of patients, with 46 individuals (6.7%) across the three centers.

SCIG and IVIG administration

The median [Q1, Q3] dose of SCIG was 0.48 [0.42, 0.57] g/kg/4 weeks or 40 [32, 40] g/4 weeks (N = 544), while the median dose of IVIG was 0.52 [0.44, 0.64] g/kg/4 weeks or 40 [30, 50] g/4 weeks (N = 114). Among the SCIG patients, 517 (95.0%) used the 20% formulation, 24 patients (4.4%) used the 16.5% formulation, and 3 patients (0.6%) were on the 10% formulation of Gammagard.

For SCIG administration, 327 patients (60.1%) used the pump method, averaging 52.6 ± 26.4 min per infusion, while 217 patients (39.9%) used the push method, averaging 22.0 ± 18.1 min per infusion. Most patients self-administered their infusions without caregiver help: 206 (92.4%) of 223 PID patients, 225 (89.3%) of 252 SID patients, and 31 (96.9%) of 32 patients with diseases of immune dysregulation. A total of 505 patients (92.8%) were administered SCIG once a week. The mean weekly infusion time for SCIG was 40.7 ± 27.8 min or 162.9 ± 111.1 min per month, compared to the mean monthly IVIG infusion time of 197.0 ± 74.8 min.

Comparing the dosages utilized for different conditions, the median SCIG dose utilized for SID (N = 288) was 32 [32, 40] g/4 weeks and 0.46 [0.41, 0.53] g/kg/4 weeks, while the dose for PID (N = 224) was higher at 40 [32, 48] g/4 weeks and 0.50 [0.44, 0.60] g/kg/4 weeks. The highest dose required was for IMD (N = 32) with 44 [38, 80] g/4 weeks and 0.69 [0.44, 0.99] g/kg/4 weeks (Figure 1).

Figure 1.

Comparison of IG dosage between SCIG and IVIG for patients with different indications, PID, SID and IMD. The vertical axis represents the median dosage reported: (a) in g/kg/4 weeks and (b) in g/4 weeks.

PID, primary immune deficiency; SID, secondary immune deficiency

Changes in IG mode of delivery

Seventy-three (11.1%) patients switched from IVIG to SCIG, with dose adjustments based on clinical response. Median time from IVIG start to SCIG switch was 12.5 [4.75, 20.25] months. For patients with PID (N = 13), doses were adjusted at a 1:1 ratio, such that their IVIG and SCIG doses were equal in g/kg/4 weeks. By comparison, patients with SID (N = 45) had a slightly lower conversion rate of 1.0:0.9, resulting in reduced SCIG usage. Those with immune dysregulation disorders (N = 15) had the highest conversion rate of 1.0:1.2 to achieve comparable results between SCIG and IVIG.

Ten (1.5%) patients switched from SCIG to IVIG, 4 (40.0%) had PID, 4 (40.0%) had SID, and 2 (20.0%) had IMD. Median time from SCIG start to IVIG switch was 16 [11.5, 22.75] months. For PID, the average conversion rate was 1:1 (SCIG:IVIG). For SID, the average conversion rate was 1.0:0.9, while for IMD it was higher, with 1.0:1.1. The reasons for switching included poor symptom control on SCIG for one patient with IMD, while the remaining switches were due to patient preference or poor compliance with SCIG caused by needle phobia or lack of commitment.

Patient follow-up and dose adjustments

On average, 543 patients (78.4%) were seen once every 12 months. During the study, 115 patients on IG treatment (17.5%) had their doses adjusted. Of these, 11 patients (9.6%) were on IVIG, while 104 (90.4%) were on SCIG. Dose reductions were made for 45 patients (39.1%), with an average decrease of 10.9 ± 6.47 g/4 weeks. Most of these patients N = 33 (73.4%), had SID, 10 (22.2%) had PID, and 2 (4.4%) had immune dysregulation disorders. Dose reductions were made due to a decrease in body weight and clinical stability, patient request, physician assessment, or after rituximab discontinuation. Conversely, 70 patients (60.9%) had their doses increased, with an average increase of 12.0 ± 7.4 g/4 weeks. Among these, 32 (45.7%) had PID, 31 (44.3%) had SID, and 7 (10.0%) had immune dysregulation disorders. Dose increases were typically attributed to recurrent infections, low IgG trough levels, cyclical fatigue before injections were due, pregnancy and increase in body weight, and recurrent infections.

Clinical outcomes

Among 647 patients with PID and SID, 439 (67.9%) reported their average number of infections before and after starting IG therapy. There was a 78.4% decrease in the number of infections reported and a 78.8% decrease in treatments received for infections. In addition, there was a 90.1% reduction in ER visits and a 92.3% decrease in hospitalizations.

When asked about their health status after starting IG therapy, 442 patients (63.8%) responded, with 89.4% (N = 395) reporting improved health, 7.9% (N = 35) reporting no change, and 2.7% (N = 12) noting a decline. Patients who reported improved health attributed it to significantly fewer infections and increased energy levels. One participant described the change as “night and day” after starting IG therapy.

Participants who reported worse health attributed their decline to other comorbidities, such as chronic diseases and associated treatments, while others mentioned social isolation during COVID-19 as a contributing factor.

Discontinuation of IG therapy and patient outcomes

During the study, 14 (4.7%) patients with presumed PID discontinued IG therapy. Median time to discontinuation was 32 [12, 81] months. These patients had IgG subclass deficiencies and mild hypogammaglobulinemia, and the discontinuation allowed physicians to reassess their immunodeficiency. Of these, 7 (50.0%) showed improvement without IG therapy, leading to a complete cessation of treatment. The remaining patients had varied outcomes: 4 (28.6%) experienced worsening symptoms, including increased fatigue and recurrent upper respiratory tract infections, while 3 (21.4%) reported no change after an average of 6 months and continued to be monitored. In addition, one patient with Stevens-Johnson syndrome (SJS) discontinued treatment after being in remission from SJS eruptions for over a year, after intermittently receiving IG for approximately 10 years. Furthermore, 19 (5.5%) patients with SID ceased IG therapy following physician advice and were monitored post-interruption. Median time of IG therapy to discontinuation was 30 [15, 30] months. Of these SID patients, 8 (42.1%) had chronic neutrophilic bronchitis with or without underlying lung diseases, 5 (26.3%) had hematologic malignancies, 1 (5.3%) had undergone HSCT, 2 (10.5%) were post-kidney transplant, and 2 (10.5%) had received rituximab treatment for RA. Among the SID patients, 11 (57.9%), including those with conditions such as MM, Waldenström macroglobulinemia, CLL, and chronic neutrophilic bronchitis with or without underlying lung diseases, reported improved health and higher health scores after stopping treatment, likely due to recovered immunodeficiencies. Conversely, 5 (26.3%) reported no difference between being on and off treatment, and 3 (15.8%) reported worse health due to underlying conditions.

Discussion

The ONIT program offers insights through its registry, providing a comprehensive overview of patients receiving IG therapy at three academic centers in Ontario. This registry represents a significant advancement in understanding the diverse indications and patient characteristics related to IG therapy, helping to clarify the evolving trends in treatment.

In the evolving landscape of IG utilization, there has been a notable shift in indications, particularly toward an increased prevalence of SID cases. This trend aligns with findings from recent studies, such as the one by Keith et al., ¹¹ which reported a slightly higher proportion of SID 52.0% compared to 48.8% PID indications. Similarly, a large-scale noninterventional study by Bauhofer et al. in Germany found that SID accounted for 73.0% of IVIG recipients, compared to 15.0% of PID and 12.0% for other indications, highlighting the growing importance of SID as an indication for IG therapy. ¹²

The rising prevalence of SID is driven by patients with hematological malignancies. Over 60% of SID cases in our cohort are linked to CLL, MM and other plasma cell dyscrasias and lymphoma. Hypogammaglobulinemia, characterized by reduced circulating IgG levels, is commonly found in patients with B-cell malignancies such as CLL, MM, and non-Hodgkin lymphoma, and can also result from immunosuppressive therapies like B-cell depleting treatments. ¹³ Together, these factors significantly increase the risk of immune dysfunction, predisposing patients to recurrent and severe infections. ¹⁴ Infections are a leading cause of non-relapse mortality in up to 50% of CLL cases and up to 33% of non-Hodgkin lymphoma cases. ¹⁵ As the incidence of hematological malignancies continues to rise and immunosuppressive therapies become more advanced and widely used, improved survival rates are expected to coincide with a growing prevalence of SID.^16,17 This underscores the need for greater awareness, routine screening, and improved monitoring of at-risk patients across medical specialties to enable early identification and reduce infection-related morbidity and mortality in SID patients.

In this context, the first report from the ONIT registry demonstrated the clinical benefits of IG therapy in SID patients, including a marked reduction in infections and healthcare utilization. ¹⁰ These findings emphasize the potential of IG therapy, particularly SCIG, in mitigating the burden of infections and the need for emergency and inpatient care in SID patients. However, contrasting evidence from economic evaluations, such as the study by Carrillo de Albornoz et al., raises questions about the cost-effectiveness of IG therapy compared to prophylactic antibiotics. ¹⁸ While the clinical benefits of IG therapy are well-established, these economic concerns highlight the need for further research to understand its cost-effectiveness and inform clinical decision-making.

In addition to hematological malignancies, the ONIT program also highlights the increasing use of IG therapy for chronic or recurrent neutrophilic bronchitis, both with or without underlying lung diseases such as COPD, asthma, or bronchiectasis, reflecting growing awareness of its potential benefits in managing these conditions. Hypogammaglobulinemia has been associated with a higher risk of acute exacerbations of COPD (AECOPD) and hospitalizations. ¹⁹ Frequent AECOPD, occurring two or more times a year, contribute significantly to healthcare utilization and result in considerable morbidity and mortality. ²⁰ A retrospective study has shown significant reductions in the frequency of AECOPD with IG treatment, with marked decreases in both moderate and severe exacerbations that required hospitalizations. ²¹ Current guidelines recommend IG therapy for patients with recurrent bacterial respiratory infections, particularly when standard treatments fail, when laboratory evidence shows low IgG levels indicating inadequate antibody-mediated immunity, and when infections persist despite appropriate antibiotic prophylaxis. ²²

The conversion ratio between IVIG and SCIG remains a subject of ongoing research and debate, with significant variations observed across regulatory recommendations, clinical practice, and real-world data. Our study revealed varying SCIG:IVIG and IVIG:SCIG dose conversion ratios based on underlying conditions, diverging from standard approaches mentioned in other studies. While the US FDA recommends a 1.37:1 SCIG:IVIG ratio, our findings, along with other real-world studies, demonstrate that clinical practices often differ. ²³ For instance, Krishnarajah et al. found that an initial ratio of 1.14:1 stabilized to 1.05:1 after 4–6 months, aligning more closely with the 1:1 ratio approved by European regulatory bodies. ²⁴ The FDA’s initial higher ratio recommendations were based on area-under-curve pharmacokinetics of the earlier clinical trials. ²⁵ However, recent data suggest that target serum IgG concentrations can typically be achieved with lower ratios, closer to 1:1. ²⁶ Our study further reveals condition-specific conversion ratios: a 1:1 ratio for PID, 1.0:0.9 for SID, and a higher 1.0:1.2 ratio for immune dysregulation disorders. This nuanced approach contrasts with one-size-fits-all regulatory recommendations, emphasizing the importance of individualized treatment plans in IG therapy. The ability to fine-tune doses according to the underlying condition and route of administration not only improves patient outcomes but also reinforces the growing use of SCIG as a viable alternative to IVIG. This patient-centered approach, with dose adjustments tailored to everyone’s clinical response, underscores the evolving nature of IG therapy and the need for continued research in this field.

The ONIT program demonstrates significant cost-saving potential through its strategic emphasis on SCIG home-based therapy, leading to significant reductions in hospital and medical day care unit (MDCU) visits typically required for IVIG treatments. This shift to home-based care not only cuts direct costs associated with facility and staffing expenses but also alleviates pressure on healthcare resources. As the number of participants in the program grows, diverting patients from resource-intensive settings, such as the MDCU, enables a more efficient and equitable allocation of services, further optimizing cost management.

This study has several limitations. First, the program has an inherent bias toward SCIG as it is its primary objective and mandate. While SCIG is well-established in PID and SID treatments, it is less commonly used in IMD. Consequently, the lower proportion of these disorders as an IG indication in this report may not fully represent the overall IG utilization in the patient population. Second, information on infections, hospitalizations, and ER visits prior to IG therapy may be subject to recall bias, particularly for patients who started treatment long before the study, such as those with PID who have been on IG therapy since early childhood. Third, the classification of patients into PID, SID, and IMD categories may be subject to variability, especially in cases where patients have overlapping clinical features or complex presentations, which could potentially affect the accuracy of their categorization. Fourth, the facilitated SCIG became available in Canada only a few months before the study’s data extraction. As a result, no patients had started receiving it prior to this, which may influence the observed outcomes, particularly in terms of the adoption and clinical applications of SCIG. Lastly, as with most observational studies, the results may be influenced by selection bias, since patients with higher baseline infection rates may have been more likely to begin IG therapy and thus enroll in the study. Improvements in infection rates after IG therapy may also partially reflect regression to the mean, rather than solely the effect of IG therapy, which should be considered when interpreting these outcomes.

Despite these limitations, the ONIT registry’s detailed data provide a valuable resource for understanding the demographics, treatment patterns, and clinical outcomes associated with IG therapy across the three tertiary healthcare centers in Ontario. The findings highlight important trends and associations of IG utilization, particularly the increasing prevalence of SID and the variability in dosing strategies by indication. These data may help inform healthcare planning and resource allocation in the evolving landscape of IG therapy.

Conclusion

This study provides a comprehensive overview of IG therapy across three academic care centers in Ontario, revealing shifts in patient demographics, clinical profiles, and treatment indications. The findings underscore the increasing prevalence of SID and highlight the importance of tailored, individualized treatment regimens based on patient-specific clinical outcomes. While improvements in clinical outcomes were observed, these results should be interpreted with caution due to potential selection bias, regression to the mean, and limitations in follow-up data across multiple centers. Nevertheless, these insights into patient demographics, clinical profiles, treatment patterns, and dosing strategies remain valuable for informed healthcare planning and optimizing care delivery in the evolving landscape of IG therapy.