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Abstract
Objectives To evaluate the utilisation of intravenous immunoglobulin (IVIG) at Tawam Hospital, a tertiary care teaching hospital, over a 1-year period.
Methods Patients who received IVIG from March 2010 to April 2011 at Tawam Hospital were identified retrospectively using the hospital computer system. Their charts were subsequently reviewed and data were collected on patients' demographics, indication, dose regimen, adverse drug reactions and physician specialty. Indications were placed into three main categories: US Food and Drug Administration (FDA) labelled; off-label indications with evidence favouring IVIG efficacy; and off-label indications with lack of evidence for efficacy.
Results A total of 134 patients (74 paediatric and 60 adult) were identified. In 39%of paediatric versus 46% of adult patients, IVIG was dispensed for appropriate indications (US FDA labelled and off-label with support for use). However, 61%of paediatric patients and 54% of adult patients received IVIG for inappropriate indications (off-label use without support). The estimated annual cost of IVIG is US$1.25 million, of which US$0.7 million was considered as inappropriate use.
Conclusions A significant amount of IVIG was prescribed for inappropriate indications, resulting in a large financial burden on the institution.
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Introduction
Intravenous immunoglobulin (IVIG) is a plasma product prepared from pooled plasma from 3000–10 000 or more healthy blood donors1 ,2 and is primarily composed of IgG. IVIG has become an important treatment option for a range of medical conditions beyond its use in treating immune deficiencies, particularly autoimmune and acute inflammatory diseases. The use of IVIG has grown steadily and has overtaken albumin (human) in commercial importance among fractionated plasma products.3 This has been attributed to the expanding list of clinical conditions for which IVIG may be used.4 However, there are only a limited number of approved indications by well recognised licensing agencies. For example, there are only six indications approved by the US Food and Drug Administration (FDA): primary immunodeficiency; secondary immunodeficiency due to chronic lymphocytic leukaemia; paediatric HIV infection; prevention of graft versus host disease and infection in bone marrow transplantation; immune thrombocytopenic purpura; and Kawasaki syndrome. However, in the USA and Canada, more than half of IVIG use is for off-label indications,4,–,7 most of which have supporting evidence and/or expert opinion favouring efficacy.
The large number of donors increases the possibility of contamination by viruses, but this is rare.8 IVIG is also an expensive medication. In our institution the estimated cost per gram ranges from US$66 to 75. In one major hospital in the USA, the annual acquisition cost of infused IVIG was estimated to be US$4 million, making it the most expensive blood product dispensed in that institution.9 We evaluated the utilisation of IVIG in Tawam Hospital, a tertiary care teaching hospital in Al Ain, Abu Dhabi, United Arab Emirates.
Methods
This is a retrospective chart review study. The medical records of all paediatric and adult patients who received IVIG from March 2010 to April 2011 were identified using the hospital computer system. Patients' demographics, indication of IVIG, dose regimen, monitoring criteria, adverse effects and prescribers' specialties were recorded. Identified indications were placed into three different categories based on IVIG efficacy, as defined by Thomson Reuters10:
▶ Group A (which includes the US FDA labelled indications): evidence and/or expert opinion suggests that IVIG for a specific indication is effective.
▶ Group B: evidence and/or expert opinion is conflicting as to whether IVIG is effective, but the weight of evidence and/or expert opinion favours efficacy.
▶ Group C: evidence and/or expert opinion argues against IVIG efficacy or suggests that IVIG is ineffective.
Results
A total of 134 patients (74 paediatric and 60 adult) were identified who received IVIG in our institution during a 1-year period. Among adult patients, there were 24 men and 36 women (40% vs 60%), whereas among paediatric patients, there were 41 boys and 33 girls (55 vs 45%).
Table 1 and table 2 show the distribution of indications within each category and the number of patients receiving IVIG for each indication in paediatric patients and adult patients, respectively.
Distribution of indications within each category and the number of patients receiving intravenous immunoglobulin for each indication in paediatric patients
Distribution of indications within each category and the number of patients receiving intravenous immunoglobulin for each indication in adult patients
The brands of IVIG used in our hospital during the study period were Intraglobin (Intraglobin F, Biotest Pharma GmbH, Dreieich, Germany) and Gamunex (Gamunex-c, Talecris Biotherapeutics, Inc., Research Triangle Park, NC 27709 USA).The average cost per gram was US$73.4 for Intraglobin and US$66 for Gamunex.
There were more patients receiving IVIG for off-label indications without support (category C) than any other category. In 39% of paediatric and 46% of adult patients, IVIG was dispensed for appropriate indications. However, 61% of paediatric patients and 54% of adult patients received IVIG for inappropriate indications. This corresponded to more than half of the amount of IVIG dispensed, with a total cost of nearly US$0.7 million. Among various paediatric subspecialties, paediatric intensivists prescribed IVIG the most often (31%) followed by paediatric haematologists (30%), neonatologists (26%), immunologists (5%), cardiologists (4%), neurologists (3%) and nephrologists (1%). Among adult subspecialties, adult haematologists prescribed IVIG the most often (71%), followed by intensivists (8%), neurologists and obstetricians (7% each), rheumatologists (3%), and nephrologists and internal medicine (2% each).
Among the 24 paediatric patients who received IVIG in group A, 18 were found to respond to IVIG (75%). In group B, four out of five patients responded to IVIG (75%), and in group C, 12 out of 45 patients responded to IVIG (26%). Among adult patients, 17 out of 25 patients were found to respond to IVIG in group A (68%), three out of three in group B (100%) and 10 out of 32 in group C (31%).
The most common adverse drug reactions in adult patients were anaemia (20%), renal impairment and headache (8% each), vomiting (7%), shortness of breath, fever, tachycardia, hypotension and paraproteinaemia (5% each). In paediatric patients tachycardia was the most commonly encountered adverse reaction (9%), followed by headache and anaemia (7% each), vomiting (5%), paraproteinaemia (4%), renal impairment, hypotension and leucopenia (3% each).
In our institution, the total cost of IVIG used during the study period was US$1.25 million.
Discussion
IVIG is an essential blood product that is used to treat an increasing number of conditions.1 ,11 ,12 Thus, there is an increasing demand on this product every year.
In many institutions, policies have been developed to monitor and control the dispensing process of IVIG.9 ,12 At our institution IVIG was mostly dispensed on physician's prescription, however there was a lack of approved guidelines controlling its use. This partly explains why IVIG was prescribed unnecessarily for many conditions. In comparison with other reports,11,–,15 the number of conditions for which IVIG was inappropriately used at our institution is unacceptably high, with only minimal response rate (26% in paediatric and 31% in adult patients). This is clearly reflected in the high cost of IVIG dispensed for those conditions.
In a study by Pendergrast et al on IVIG prescribing patterns from 1995 to 2000 in four teaching hospitals in Toronto, over 80% of the 429 patients in the study were determined to receive IVIG for appropriate reasons.15
Another study from Spain by Badia et al,12 which looked at IVIG use from 2000 to 2004, reported that of the total 1332 IVIG courses recorded in 5 years, 86% were for labelled indications, 10% were for off-label but scientifically supported indications, and only 4% were for off-label unsupported indications.
One of the main reasons many of the above-mentioned reports demonstrate that most IVIG was dispensed for appropriate reasons is the existence of a strict approval system for IVIG prescriptions for off-label indications, or at least those that are not supported by sound scientific evidence.9 ,12 ,16 ,17 ,22
Our study is one of very few to touch on this important subject in the Middle East. Despite being limited by its retrospective nature, we believe that our study included a good number of patients who received IVIG for a wide variety of indications in a tertiary academic centre. At the time we wrote this article, IVIG use for neonatal sepsis had already been stopped in our institution.
Soon after completing this study, we introduced a clinical practice guideline for the use of IVIG. We are planning to perform a year-by-year analysis to see if there is any change in IVIG use after implementation of the guideline.
In conclusion, we have shown that there is a relatively high amount of IVIG dispensed at our institution for inappropriate indications. This has a huge cost burden on the hospital and may reflect similar practices in many other institutions in the area. Implementing a guideline for the approved indications of IVIG in our institution will have a significant impact on the use of this expensive, yet life-saving product. Moreover, the requirement to obtain expert permission to use IVIG for off-label indications, especially when the scientific evidence is limited or not conclusive, may limit this practice as well.
Key messages
– A large number of IVIG is dispensed for inappropriate indications, resulting in a large, unnecessary financial burden on the institution.
– There is a strong need to restrict IVIG use to approved indications through implementation of prescribing guidelines.
References
Footnotes
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Competing interests None.
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Ethics approval Al Ain District Research Ethics Committee.
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Provenance and peer review Not commissioned; externally peer reviewed.