![Dose-response study of anakinra in a mouse model of TTP; survival curve at the selected dose of 100 mg/kg. (A) Protocol for dose-response study. (B) PS-100b levels at day 3 among the 6 dosage groups. One-way analysis of variance (ANOVA): P < .001. Multiple comparisons with Dunn correction: 100 mg/kg per day: 1570 (1280-1880) ng/mL vs 10 mg/kg per day: 2750 (2340-2930) ng/mL, P = .04, and 1mg/kg per day: 3125 (3060-3190) ng/mL, P = .02. (C) Plasma troponin I levels at day 3 among the 6 dosage groups. One-way ANOVA: P < .001. Multiple comparisons with Dunn correction: 100 mg/kg per day: 2.4 (2.1-4.5) ng/mL; 50 mg/kg per day: 11.0 (10.3-12.3) ng/mL, P = .00; 25 mg/kg per day: 11.6 (10.7-12.7) ng/mL, P = .003; 10 mg/kg per day: 19.9 (14.7-25.6) ng/mL, P < .001; and 1 mg/kg per day: 27.5 (26.5-28.5) ng/mL, P <.001. (D) Probability of survival of the 6 dosage groups. Log-rank test: P = .07. (Not significant [ns]: P > .05; ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001). (E) Probability of survival of the 4 groups of mice: TTP (VWF + placebo, n = 28), TTP + anakinra (VWF + anakinra, 100 g/kg, n = 14), and 2 control groups (control [vehicle + placebo], n = 5; and anakinra [vehicle + anakinra] 100 mg/kg, n = 5; ∗∗∗P < .001). The curves for the 2 control groups overlap (no deaths in either group).](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/143/26/10.1182_blood.2023021974/3/blood_bld-2023-021974-gr2.jpeg?Expires=1754060744&Signature=qFE79Ikg~x~etwSJKPAcqs9rRb5PGFyuEH1JLpdaneGLlgIL8PvUVoqnMyV1lGsgpNsHGfhEbICEdCGK5yNDWSwj1DL3gxUo8tpk4Txsdlu~l1Sdgxsle8sqgK9hCoW7-eX7xIPVQvIDsTGte8t3AJRDko-F74z2FG0a0VMgrO7LFsIf6aljqBbr09nLR9zs7pF6-pImZSW3B5TN0andB1hyJ6t8Vl88YdS0ccYc1ucqNM80i671fHdw26watvHtmIXGBarGGTmR-O2qWR9WpSS1ryDDw1G27isLMOsDFb8iS1GeaHhgpY6Rk6NE7~3E59Q~E8bjK2XUA24MfuaTZw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Dose-response study of anakinra in a mouse model of TTP; survival curve at the selected dose of 100 mg/kg. (A) Protocol for dose-response study. (B) PS-100b levels at day 3 among the 6 dosage groups. One-way analysis of variance (ANOVA): P < .001. Multiple comparisons with Dunn correction: 100 mg/kg per day: 1570 (1280-1880) ng/mL vs 10 mg/kg per day: 2750 (2340-2930) ng/mL, P = .04, and 1mg/kg per day: 3125 (3060-3190) ng/mL, P = .02. (C) Plasma troponin I levels at day 3 among the 6 dosage groups. One-way ANOVA: P < .001. Multiple comparisons with Dunn correction: 100 mg/kg per day: 2.4 (2.1-4.5) ng/mL; 50 mg/kg per day: 11.0 (10.3-12.3) ng/mL, P = .00; 25 mg/kg per day: 11.6 (10.7-12.7) ng/mL, P = .003; 10 mg/kg per day: 19.9 (14.7-25.6) ng/mL, P < .001; and 1 mg/kg per day: 27.5 (26.5-28.5) ng/mL, P <.001. (D) Probability of survival of the 6 dosage groups. Log-rank test: P = .07. (Not significant [ns]: P > .05; ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001). (E) Probability of survival of the 4 groups of mice: TTP (VWF + placebo, n = 28), TTP + anakinra (VWF + anakinra, 100 g/kg, n = 14), and 2 control groups (control [vehicle + placebo], n = 5; and anakinra [vehicle + anakinra] 100 mg/kg, n = 5; ∗∗∗P < .001). The curves for the 2 control groups overlap (no deaths in either group).
