Efficacy and Safety of Avatrombopag in Patients with Chronic Immune Thrombocytopenia: A Systematic Literature Review and Network Meta-Analysis

Abstract

Introduction: A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids. Methods: A systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2-4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs). Results: The NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2-4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed.

Avatrombopag: A Review in Thrombocytopenia

“…As such studies comparing avatrombopag to an active comparator would be of value. In the absence of such head-to-head studies, a network meta-analysis found that avatrombopag was associated with a significantly lower incidence of bleeding events than eltrombopag (incidence rate ratio 0.38 [95% credible interval 0.19, 0.75]) and romiplostim (incidence rate ratio 0.38 [95% credible interval 0.17, 0.86]), but not fostamatinib, in patients with chronic ITP and an inadequate response to corticosteroids [ 26 ]. In addition, a retrospective analysis has indicated that avatrombopag is effective in patients previously treated with eltrombopag or romiplostim [ 27 ], and a phase IV study evaluating treatment satisfaction in patients switching from eltrombopag or romiplostim to avatrombopag is currently underway [ 28 ].…”

Fostamatinib (Tavalisse)

“…Two indirect treatment comparison (ITC) studies were reviewed. The Wojciechowski et al 7 study was a systematic review and ITC comparing fostamatinib to 3 TPO-RAs (avatrombopag, eltrombopag, and romiplostim) among patients with chronic ITP who had inadequate response to previous therapy. The sponsor also submitted a systematic review and ITC 8 in which fostamatinib was compared to rituximab among patients with chronic or persistent ITP.…”

“…Utility values sourced from the literature were adjusted to the baseline age of 41 years using methods outlined in Ara and Brazier. 7 Utility values associated with platelet counts were sourced from Szende et al, 8 a UK study that estimated health-utility values associated with ITP using time trade-off (TTO) methods. Disutility due to disability after ICH for patients and caregivers was sourced from Dewilde et al, 9 a study in Belgium that used the EQ-5D 3-Levels questionnaire to elicit health-utility values.…”

“…Health-disutility values for severe bleed events and adverse events were sourced from published literature, which used a mix of TTO, EQ-5D, and standard gamble elicitation methods. 7,[10][11][12][13][14] Health-disutility values for severe bleed events were calculated by subtracting the baseline utility for ICH from the utility post-severe bleed event. The rate of adverse events for patients receiving fostamatinib or watch and rescue were sourced from the FIT trials.…”

“…Titles, abstracts, and full-text articles were screened for inclusion by 1 reviewer based on the population, intervention, comparator, and outcome criteria outlined in Table5.One sponsor-submitted ITC was included in this review 8. One relevant ITC by Wojciechowski et al was identified in the literature search 7.…”