Avespa Study: Effectiveness and Safety of Avatrombopag in Immune Thrombocytopenia (ITP). a Real-World Study of the Spanish ITP Group (GEPTI)

Background

Thrombopoietin receptor analogues (TPO-RAs) are recommended as second-line treatment for immune thrombocytopenia (ITP). Avatrombopag (AVA) is the last oral AR-TPO approved for use in Spain and also recommended for second-line use, for which few real-life data are currently available. Our objective is to evaluate the effectiveness and safety of AVA in severe and moderate/mild ITP patients, including those who have not responded to other treatments; to explore AVA's potential to reduce concomitant immunosuppressive therapies and compare its efficacy and safety in newly diagnosed/persistent ITP patients with those with chronic ITP.

Methods

The AVESPA study was a national, multicenter, retrospective study conducted by The Spanish ITP Group (GEPTI) of the Spanish Society of Haematology and Haemotherapy (SEHH). The study enrolled patients diagnosed with chronic, persistent, newly diagnosed ITP who began treatment with AVA from July 2022 to January 2024. The study assessed rates and time to response (R) (>50x10⁹/L) and complete response (CR) (>100x10⁹/L), duration of response (DOR), loss of response (LOR), adverse events (AEs), and treatment withdrawal before the end of follow-up. The calculations were performed for the entire cohort and in patients who initially presented with severe (<50x10⁹/L), moderate (50-<100x10⁹/L) or mild (>100x10⁹/L) ITP. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Results

A total of 268 patients were recruited from 28 Spanish hospitals and were followed for a median of 47 months (interquartile range of 30.4-58.9 months). Median age was 59.3 years, and 57.8% patients were female. ITP primary was diagnosed in 227 patients (85,3%). When AVA treatment started, 193, 46 and 29 had severe (platelet count [PC] <50x10⁹/L), moderate (50-<100x10⁹/L) and mild (>100x10⁹/L) ITP, respectively. Prior to switching to AVA 197 (73%) and 106 (40%) patients had used >2 and >3 lines of treatment, respectively.

In the severe ITP group, 154/193 (79.8%) and 20/193 (10.4%) patients achieved complete response (CR, [PC>100x10⁹/L) and response (R, PC>50x10⁹/L), respectively. Among 129 severe ITP patients who were still on AVA at their last visit, 87(67.4%) and 26(20.1%) had CR and R, respectively.

Results were similar in the 104 severe ITP patients who switched to AVA due to previous treatment failure. Severe ITP patients reached R and CR in 13 (7-21) and 14 (9-35) days, respectively. Eighty-seven percent of moderate ITP patients reached CR while 93% of mild ITP patients showed PC >100x10⁹/L. LOR was always <10%, regardless of ITP severity. The duration of ITP did not significantly influence the response. Among the 147 severe ITP patients who switched to AVA due to previous treatment failure, age and sex did not significantly affect the response to AVA.. A significant, inverse correlation was observed between the number of previous treatment lines and the best response achieved (Rho = -0.230, P = .002). Accordingly, the proportion of patients reaching response or CR was decreasing as the number of previous treatment lines increased, and was significantly higher when patients had received less than 4 treatment lines

Ninety-one percent (39/43) of heavily pretreated (>4 lines) severe ITP patients who had previously failed treatment achieved a platelet count of >50x10⁹/L after switching to AVA.. Previous use of eltrombopag and/or romiplostim did not impact the response, regardless of whether the previous TPO-RA(s) treatment had succeeded or failed. In 80.0% of severe ITP patients, AVA allowed for the reduction or suspension of corticosteroid doses.

In terms of safety, 175/268 (65%) patients did not experience any AE, and 40/268 (15%) discontinued treatment after reaching counts >400x10⁹/L. Nine cases of thromboses were documented, none of which were fatal, and three occurred in patients who developed thrombocytosis. The remaining AEs were mild and transient. At the end of follow-up, 185/268 (69%) patients were still on AVA treatment.

Conclusion

AVESPA study included the largest cohort of patients treated with AVA in real life. Our findings were aligned with those of previous trials and real-world evidence. AVA can increase platelet counts above baseline in >90% of ITP patients, regardless of severity of the condition. This increase typically occurs within the first 2 weeks of treatment, while also maintaining a low rate of severe adverse events.