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Thrombopoietin receptor agonists in ITP
TPO-RA using different generic and disease-specific ques- tionnaires. Unquestionably, ITP has a major negative impact on HRQoL.28,29
In general, short-term treatment with TPO-RA does not seem to affect HRQoL,19,22 while long-term studies with both agents show improvements in HRQoL.17,25 In the
open-label RCT comparing romiplostim to SoC, clinically significant improvement in seven scales of the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire (ITP-PAQ) was observed in both treatment arms at 52 weeks compared with baseline.17 However, the romiplostim group, and in particular the responders, had
Table 2. Summary of the randomized controlled trials performed in adult immune thrombocytopenia patients with romiplostim or eltrombopag.
Romiplostim
Bussel21
Kuter18
Kuter17
Shirasugi 88
Eltrombopag
Bussel22
Bussel19
Cheng25
Tomiyama89
Comparator Study Definition of the primary arm duration end point for efficacy
Placebo 6w Proportion of patients achieving platelet count
50-450x109/L
Primary end point
75% had platelet counts that reached or exceeded the targeted range vs. 25% in the placebo group
38% of splenectomized patients given romiplostim vs. 0% given placebo; P=0.0013, and 61% of non-splenectomized given romplostim vs. 5%; P<0.0001
11% in romiplostim arm
vs. 30% in SoC arm
(OR 0.31, 95% CI: 0.15-0.61; P<0.001)
Weekly responses occurred for a median of 11 weeks with romiplostim
vs. 0 weeks with
placebo; P<0.0001
Results
Any increase
in plate count
Overall platelet response rate was noted in 88%
of non-splenectomized and 79% of splenectomized patients given romiplostim compared with 14% of non-splenectomized and 0% splenectomized patients given placebo; P<0.0001
Between weeks 2 and 52
a 71-92% platelet response in the romiplostim group and 26-51% in the SoC
95% of romiplostim-treated patients achieved
platelet responses
Bleeding
Significant bleeding events were reported in 12% of the patients in the placebo group and 7% in the romiplostim group
Romiplostim group had significantly lower adjusted incidences of overall bleeding events (P=0.001) and bleeding events
of grade 3 or higher (P=0.02) vs.the SoC
Placebo 24w Proportion of patients achieving platelet count
≥50x109/L during ≥ 6 of the last 8 weeks of treatment
SoC 52w Incidences of treatment failure and splenectomy
Placebo Number of weeks with platelet response, defined
as a platelet count ≥50x109/L (not including the 4 weeks after administration of rescue medication)
Placebo 6w Proportion of patients achieving platelet counts
Not reported
Patients in the eltrombopag group also had significantly greater odds of responding at any point during the 6-week treatment period than did those in the placebo arm; OR 8.79, 95%CI: 3.54-21.86; P<0.0001
50x109/L ≥ at day 43 Placebo 6w Proportion of patients
59% in eltrombopag 16% in placebo arms,
OR 9.61, 95%CI: 3.31-27.86; P<0.0001
79% vs. 28%
OR 8·2, 95%CI: 3·59-18·73; P<0·0001
60% in eltrombopag-treated patients; 0% in placebo- treated patients
28-81% response
depending on
the dose vs. 11% in the placebo arm; P<0.001
achieving platelet counts 50x109/L ≥ at day 43
Placebo 6m OR of response defined as a platelet count of
50-400x109/L
Placebo 6w Platelet count of ≥50x109/L at week 6 of the 6-week cycle
38% of patients receiving
eltrombopag vs. 7% placebo
responded at 75% or more of assessments, OR 10·53, 95%CI: 3.48-31.91; P<0·0001
w: week; m:month; SoC: Standard of Care; OR: Odds Ratio; CI: Confidence Interval.
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