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Immune Thrombocytopenic Purpura
Table 4: Incidence of Adverse Events
Outcome IV RhIG IVIG
t n MA% (95% CI) t n MA% (95% CI)
Total patients evaluated 36 1,030 – 85 2,092 –
Treatment discontinuations due to adverse events 2 1/28 4 (0–11) 15 15/288 3 (0–7)
Number of patients with:
Headache 7 28/137 14 (2–26)
*
23 151/594 27 (17–36)
Fever 9 23/137 10 (2–18)
*
21 75/524 13 (7–18)
*
Chills 5 25/122 19 (8–31)
*
4 16/172 11 (0–24)
*
Vomiting 7 0/28 0 (0–7) 7 28/266 11 (1.4–20)
*
Composite 6 7/118 5 (0–10)
*
12 56/259 21 (10–32)
*
Aseptic meningitis 3 0/86 0 (0–2) 8 9/256 3 (1–5)
Bleeding 7 2/152 1 (0–4) 13 73/296 14 (0.4–28)
*
Dyspnoea NR NR NR 3 4/61 7 (0.4–13)
Asthaenia 2 0/28 0 (0–7) 3 5/114 4 (0.5–8)
Post-treatment haemoglobin change (mg/dl) 12 462 -1 (-1.4 to -0.7)* 3 66 -0.5 (-0.9 to -0.1)
§
t = number of treatment groups; n = number of patients with characteristic/all patients evaluated; MA = meta-analysis; §(p<0.10) and *(p<0.01) indicate significant heterogeneity; composite includes
any combination of fever, nausea, vomiting or headache; NR = not reported; CI = confidence interval; IV = intravenous; RhIG = rhesus immune globulin; IVIG = intravenous immunoglobulin.
RhIG used in this study on day one was only 25mcg/kg, biasing the study study groups as the higher percentage of acute ITP patients in the IVIG
against immediate efficacy following IV RhIG. El Alfy et al.
16
concluded group may yield a better overall response. In addition, a greater
that single doses of both IV RhIG and low-dose IVIG effectively increased proportion of IV RhIG patients had HIV-related ITP and have received
PC in children with chronic ITP at risk of bleeding. In addition, repeated prior ITP treatment – factors that could potentially lead to lower
doses of IV RhIG could maintain PC above critical values or double baseline response rates as well. Furthermore, meta-analyses of continuous
counts in nearly two out of three of the patients showing good control of response outcomes (time to response and duration of response) were
bleeding. They, in contrast, used a low dose of IVIG, but this dose was planned but not performed due to the high variability of response
validated in children with acute ITP in a separate study.
20
Tarantino et al.
17
definition and lack of reporting of mean values and variances. Median
concluded that a single 75µg/kg dose of IV RhIG raised the platelet count values for continuous variables were often presented in these studies,
in children with newly diagnosed ITP more rapidly than standard-dose IV which on the one hand provide a better understanding of the
RhIG and as effectively as IVIG, with an acceptable safety profile. population means, but on the other hand are not useful for statistical
Therefore, the three studies with direct data comparisons in general testing in a meta-analytical context. Finally, at the time this study was
support approximately equivalent efficacy of IV RhIG and IVIG, while undertaken, the vast majority of studies were low-quality, non-
pointing out the dose dependency of the IV RhIG response. randomised, single-arm studies or retrospective chart reviews.
The limitations of the overall review include the variety of dosing Conclusion
regimens and the wide variation in the response definitions among We addressed the evidence gap regarding the efficacy and safety of IV RhIG
studies. The definition of response ranged from a small increase in and IVIG in ITP patients. This systematic review summarises the available
platelets from baseline to increases as high as 150x10
9
/l, and significant evidence published between 1985 and 2005. In the aggregate, data are
heterogeneity was detected among the studies analysed. Factors such based on 89 studies evaluating more than 3,100 patients. In acute ITP,
as study design, differences in ITP patient populations and disease where it is important to increase PC as quickly as possible, 53% of the
severity at baseline (acute and chronic, adults or children, treatment- patients in the IV RhIG group and 55% of those in the IVIG group responded
naïve or treatment-refractory, etc.), various treatment doses and within 24 hours of treatment. Similarly, in chronic ITP – where it is important
treatment duration all may have influenced the response rates. Some to keep the PC high for as long as possible – the mean duration of response
notable differences between the IV RhIG and IVIG groups were was eight weeks after IV RhIG and five weeks following IVIG treatment.
observed that may have potential influence on the study results. The Although limited safety information was available in these studies, both IV
majority of IVIG patients had acute ITP and were treated with high IVIG RhIG and IVIG appear to have similar safety profiles. Further direct
doses, while the majority of IV RhIG patients suffered from chronic ITP comparison in trials in similar patient populations, especially children with
and were predominantly treated with conventional or low doses of IV chronic ITP, would be valuable in further refining the comparative efficacy
RhIG. In acute ITP patients it is important to increase the PC as quickly and safety of IV RhIG versus IVIG in these patients. ■
as possible, and in chronic ITP patients it is important to maintain the
PC above a certain number, i.e. 20 or 30x10
9
/l. The proportion of Acknowledgement
acute to chronic patients may in part confound the results between This work was sponsored by Cangene Corporation.
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EUROPEAN HAEMATOLOGY 2007 43
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