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M.D. Tarantino et al.
the anemia and had pre-existing intermittent neutropenia, which eventually resolved.
Efficacy
Median platelet counts remained >50x109/L from week 2 on and >100x109/L from weeks 24 to 260 (Figure 2C). Nearly all patients (94%) had ≥1 platelet response (platelet counts ≥50x109/L, excluding counts ≤4 weeks after rescue medication). Most patients (72%) had a platelet response ≥75% of the time and over half (58%) had a platelet response ≥90% of the time. Fifty-nine patients (91%) or their caregivers self-administered romiplostim at least once (i.e. administered at home, not at the clinic). In a post hoc analysis, self-administration started at a median study week of 7 (1-162) for a total duration of 112 weeks (range: 3-362 weeks). After patients started self-administration, they remained on self-administration (i.e. they did not interrupt it to receive romiplostim in the clinic for ≥4 weeks) for a median of 92% (range: 8-100%) of the time. Most subjects (45 of 59, 76%) remained on self-adminis- tration to the last non-zero dose of romiplostim. Twenty- three of 65 patients (35%) received rescue medications (Online Supplementary Table S3); usage was highest in the first few months of the study (Online Supplementary Figure S3A). At baseline, five patients were taking other ITP medications: aminocaproic acid, prednisolone, pred- nisone, and tranexamic acid. The rate of ITP medication use decreased during the study (Online Supplementary Figure S3B).
Treatment-free responses
Per the study dosing guidelines (Online Supplementary Figure S1), romiplostim doses were withheld if consecu- tive platelet counts were >200x109/L but <400x109/L and the current dose was 1 mg/kg/week; if the platelet count was ≥400x109/L at any dose of romiplostim; or if, in the investigator’s opinion, the patient could maintain accept- able platelet counts of ≥50x109/L without weekly romi- plostim treatment. Fifteen patients (23%) achieved a treat- ment-free response when romiplostim was withheld, and maintained platelet counts ≥50x109/L with no ITP medica- tions for ≥24 weeks (Table 4). All 15 patients also main- tained platelet counts >100x109/L for ≥24 weeks and the median time having platelet counts >100x109/L was 46 weeks (range: 25-109 weeks).
Platelet counts and romiplostim doses are shown in Online Supplementary Figure S4 for each patient with a treatment-free response. Among these patients, median platelet counts were 14 (1-44)x109/L at baseline and 299x109/L (range: 217-730x109/L) in the last few months before romiplostim was first withheld.
At the onset of treatment-free response (i.e. when romi- plostim was first withheld), these nine girls and six boys had had ITP for a median of 4 years (range: 1-12 years) and had received romiplostim for two years (range: 1-6 years) (Figure 3A). Three were from the phase I/II study and 12 were from the phase III study. Eleven received romi- plostim throughout and four received placebo in the phase III parent study. No patient with a treatment-free response
Figure 1. Study flow and patient disposition. Reasons for discontinuing romiplostim are provided. *Of the 21 patients who entered the first extension, one withdrew consent before treatment. †Of the 66 patients who enrolled on the second extension, one withdrew consent before treatment. ‡Of these three patients, two had treat- ment-free response and one had platelet counts <30x109/L despite ten weeks on 10 mg/kg. §Other reasons were that the study ended and treatment-free response. ¶Received romiplostim until study end January 2017 (12 months after the last patient enrolled). #: number of; PBO: placebo; Q1, Q3: 25th and 75th percentiles.
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