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Immune Thrombocytopenic Purpura
Table 2: Percentage of Patients with Platelet Response
Outcome Patients IV RhIG IVIG
t n MA% (95% CI) t n MA% (95% CI)
Overall platelet response All 34 761/995 79 (73–84)
¶
80 1,587/1,918 86 (83–89)
¶
Acute 12 234/300 78 (70–87)
¶
36 818/946 88 (85–92)
¶
Chronic 16 356/496 74 (67–81)
*
23 289/349 87 (81–92)
¶
Overall response at 24 hours All 10 109/222 50 (36–65)
¶
15 261/494 51 (37–64)
¶
Acute 8 93/179 53 (37–69)
¶
12 246/443 55 (41–70)
¶
Chronic 2 16/43 40 (0–80)
¶
1 9/14 64 (39–89)
Platelet response at 24 hours All 5 76/138 59 (39–79)
¶
9 230/358 65 (56–74)
¶
with PC
§
>20–30x10
9
/l Acute 5 76/138 59 (39–79)
¶
9 230/358 65 (56–74)
¶
Chronic NR NR NR NR NR NR
Overall response within seven days All 14 442/579 78 (71–85)
¶
40 825/974 88 (84–91)
¶
Acute 5 148/182 83 (75–91)
*
22 536/624 89 (85–94)
¶
Chronic 9 241/337 71 (61–81)
*
10 129/158 85 (76–93)
*
Platelet response at seven days All 8 291/448 77 (66–88)
¶
20 470/553 86 (82–90)
*
with PC >40–50x10
9
/l Acute 3 80/93 86 (79–93) 9 294/342 87 (83–91)
(or doubling of baseline PC) Chronic 4 71/94 77 (60–94)
¶
6 71/84 85 (77–93)
t = number of treatment groups; n = number of patients with characteristic/all patients evaluated; MA = meta-analysis; PC = platelet counts; *(p<0.10) and ¶(p<0.01) indicate significant
heterogeneity; NR = not reported; IV = intravenous; RhIG = rhesus immune globulin; IVIG = intravenous immunoglobulin; CI = confidence interval.
Table 3: Time to, Duration of and Magnitude of
capture did not need to be replicated. Due to the small number of
Platelet Response
randomised studies that directly compared IV RhIG and IVIG, a pooled meta-
analysis of IV RhIG and IVIG groups across all trials was conducted,
Outcome Patients IV RhIG IVIG
regardless of study type. t n Mean t n Mean
(range) (range)
Patients
Overall median All 7 240 3.5 (1–11) 10 244 2.4 (1–6)
time to platelet Acute 3 57 2.5 (1–11) 7 178 2.3 (1–6)
Patient characteristics at baseline for each treatment type are
response (days) Chronic 2 109 3.4 (3–7) 2 24 2.7 (2.5–3)
summarised in Table 1. The effect of IV RhIG treatment was evaluated in
Median time to All 3 112 3.0 (1–4) 6 175 1.9 (1–3)
1,027 patients, and IVIG treatment in 2,063 patients. Almost 70% of all
PC >20–30 Acute 2 52 1.7 (1–2) 5 133 1.5 (1–2)
ITP patients in these studies were children (age <16 years). The IV RhIG
x10
9
/l (days) Chronic 1 11 7 (NR) 2 24 2.7 (2.5–3)
and IVIG groups differed with regard to proportions of acute and chronic Mean duration All 8 106 6.6 (1.5–12.5) 12 207 4.7 (1.4–13.8)
ITP patients. Chronic ITP predominated in the IV RhIG group (62%),
of response Acute NR NR NR NR NR NR
whereas in the IVIG group the majority of patients were treated for acute
(weeks) Chronic 5 61 7.6 (4–12.5) 8 110 5.1 (1.4–8.8)
ITP (64%). The vast majority of patients had primary ITP (89%). However,
Median duration All 12 294 3.3 (1.3–6.6) 15 254 3.9 (1.3–12.3)
of response Acute 5 107 2.9 (1.3–6.6) 6 100 5.4 (1.3–12.3)
the prevalence of ITP secondary to HIV was approximately four times
(weeks) Chronic 4 144 3.5 (3–5.0) 7 98 2.7 (2.0–3.6)
higher in the IV RhIG group than in the IVIG group (17 versus 4%). In
Maximum PC All 11 182 148 (52–288) 31 446 183 (77–410)
studies reporting history of prior treatment, about 72% of IVIG-treated
(x10
9
/l) Acute 2 66 231 (177–288) 11 168 207
patients and 61% of patients in IV RhIG groups were treatment-naïve. In (144–410)
previously treated patients, steroids were the most common prior
Chronic 6 72 105 (70–165) 12 161 189 (89–295)
treatment. Approximately 17% of IV RhIG patients had previously t = number of treatment groups; n = number of patients evaluated; range = range of means
or medians; PC = platelet counts; NR = not reported; IV = intravenous; RhIG = rhesus
received IVIG.
immune globulin; IVIG = intravenous immunoglobulin.
Treatment response and duration of response. The overall response to IV RhIG
Dosing regimens were highly variable. Of the 1,031 IV RhIG-treated treatment in all ITP patients was 79%, while it was 86% in IVIG patients (see
patients, 9% were treated with high-dose IV RhIG (>50µg/kg), 11% Table 2). Interval responses were reported in a minority of studies, and the
received low-dose IV RhIG (<50µg/kg) and conventional doses were intervals varied. About 50% of patients in each treatment group with this
administered to 23% of patients. The remainder of patients (57%) information responded within 24 hours. Sixty-five per cent of IVIG patients
received a combination of different IV RhIG doses, or dosing information and 59% of IV RhIG patients had increased PC of >20–30x10
9
/l within 24
was not available. Slightly more than half of patients in the IVIG groups hours. Conversely, 33% of IVIG patients and 40% of IV RhIG patients
were treated with high-dose IVIG (53%), while only 10% of patients achieved platelet count recovery of greater than 40–50x10
9
/l within 24
received low-dose. Standard doses of IVIG were administered to only 3% hours. An overall response within seven days was achieved by 78% of IV
of patients, and 33% were given a combination of different doses or RhIG patients and by 88% of IVIG patients. PC increased to at least 40x10
9
/l
dosing information was not reported. within seven days in 77% of IV RhIG-treated patients, and in 86% of IVIG-
treated patients. In addition, significant heterogeneity was detected in these
Treatment Response meta-analyses, indicating high variability in response rates among individual
studies (p<0.01, test of heterogeneity). Pooled times to response, duration
All Immune Thrombocytopenic Purpura Patients of response and magnitude of platelet response are presented in Table 3.
The data were analysed with attention to overall platelet response, time to The overall median time to response was 3.5 days (mean four days)
EUROPEAN HAEMATOLOGY 2007 39
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