Thrombopoietin Receptor Agonist Research Articles

Combination Therapy of Eltrombopag and Cyclosporine a Improves Hematopoiesis in Patients with Lower-Risk Myelodysplastic Syndrome

Objective: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid disorders characterized by ineffective hematopoiesis and cytopenias, with variable risks of progression to acute myelogenous leukemia (AML). Peripheral blood cytopenias are the major sources of morbidity and mortality for lower-risk MDS (LR-MDS) pts.The strategies guided by risk stratification tools are different for HR- and LR-MDS. The treatment options for cytopenias in IST non-responders, especially thrombocytopenia, are limited. Such pts are prone to a high risk of bleeding. Eltrombopag (EPAG) is an orally administered nonpeptide thrombopoietin (TPO) receptor agonist. The single-agent activity of EPAG was demonstrated in 44-47% of pts with LR-MDS . In this study, we investigated the efficacy and safety of the combination of EPAG and CysA in LR-MDS in a non-randomized phase II investigator-initiated trial. Method(s):Pts with a diagnosis of LR-MDS by WHO 2016 classification and IPSS-R as low to intermediate-risk group with hemoglobin (Hb) <9.0 g/dL, or RBC transfusion-dependence (at least four units of RBC at 8 weeks prior to enrollment); platelet count <20×109/L or platelet transfusion dependence; were enrolled. http://www.chictr.org.cn/ identifier: ChiCTR2000035473. The primary objective of this IIT was to evaluate the response to this regimen based on IWG-MDS 2006 criteria. Results All the 31 pts were evaluated for response at the primary endpoint. Among them, 21 (67.7%) pts achieved treatment response in at least one eligible lineage with an objective response rate (ORR), 4 (12.9%) pts achieved a CR, 5 (16.1%) pts achieved bi-lineage responses (HI-PE R), 11 (24.3%) pts achieved platelet lineage responses (HI-P R), and 1 (3.2%) patient achieved erythroid lineage response (HI-E R). ANC did not increase significantly at the primary endpoint compared to the baseline; however, altered ANC was a response of CR pts. The median time to response was 8 (range, 2-24) weeks, irrespective of whether the pts had a platelet or erythroid response.Of the 21 pts eligible for an erythroid lineage response,10 pts (47.6%) had responded by the endpoint and the platelet response rate was 64.5% (20/31). The median increase in Hb levels and platelets was from 60.4±18.2 g/L to 68.0±21.2 g/L (P=0.015) and from 12.3±11.2×109/L to 32.5±37.3×109/L (P=0.003) (Figure 1). The median DORs of HI-E and HI-P were not achieved, but the response rates of erythroid and platelet lineages in 20 months were 80.0% and 70.6%, respectively (Figure 2). The RBC and platelet transfusion-dependent rate decreased from 42.9% (9/21) to 28.6% (6/21) (P=0.334) and from 58.0% (18/31) to 25.8% (8/31)We also performed targeted next-generation exome sequencing of 80 genes associated with myeloid malignancies in 21 pts. Among them, 18 showed a total 19 somatic mutations (Figure 3). TET2,and ANKRD11 were detected in 3 responding pts,and KMT2D was detected in 3 responding pts. Pts with adverse prognostic genes, such as ASXL1, ARSR2, U2AF1, KIT, and ETV6, did not exhibit a hematological response. Somatic mutations in DHX9 and ROBO1 were associated with BM failure, as detected in responding pts. All 31 pts were evaluated for toxicity, and the treatment was found to be well-tolerated. The most commonly reported adverse events (AEs) of any grade were nausea (6/31,19.4%), elevated liver transaminases (4/31,12.9%), and headache (3/31,9.7%); no severe AEs had been reported until the cutoff date. One MDS-SLD patient who received CR at 3 weeks experienced deep venous thrombosis of the lower extremity after 9 months of medication, thereby requiring dose interruption. After anticoagulant therapy, the platelet count was still 65×109/L. One MDS-U case who received HI-P had increased BM blasts from 3.2% to 15.4% for 4 months. Another MDS-U case received HI-E and HI-P, and the chromosome was changed from normal karyotype to -7/del (20q) chimeric karyotype for 9 months after administration of the drugs. However, the hematological response was maintained for 16 months until the cutoff date for data collection. Conclusions: Our results indicated that the addition of Epag to CysA is well-tolerated and is an effective treatment for LR-MDS. These ORR are better than CysA monotherapy, especially HI-P. Also, the hematological responses are durable, although continued Epag administration might be necessary. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Eltrombopag Plus Diacerein Versus Eltrombopag in Adult Primary Immune Thrombocytopenia: Interim Analysis of a Multicenter, Randomized, Controlled, Phase 2 Trial

Background: Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. Eltrombopag is a preferred second-line treatment of ITP, but many patients still have no response or relapse due to unknown reasons. Our preclinical data indicate that rhein, the active metabolite of diacerein, can enhance megakaryocyte sensitivity to thrombopoietin receptor agonists, and promote megakaryocyte polyploidization and platelet formation in ITP. Thus, a prospective randomized controlled trial was conducted to compare the efficacy and safety of eltrombopag plus diacerein versus eltrombopag alone in adult ITP. Here we report the interim analysis of this study. Methods: This multicenter, open-label, randomized, phase 2 trial screened eltrombopag-inefficient or relapsed ITP patients from five tertiary medical hospitals in China. Eligible participants were randomly assigned into the combination arm (eltrombopag orally at an initial dose of 75 mg daily for 14 days, plus diacerein orally at an initial dose of 50 mg bid for 14 days) or the monotherapy arm (eltrombopag orally at an initial dose of 75 mg daily for 14 days) by masked statisticians. To maintain participants’ platelet counts at a safe range, individualized dosages were allowed to be adjusted by physicians according to the protocol. The primary outcome was initial response at day 15. Complete response was defined as a platelet count at or above 100×109/L and an absence of bleeding. Partial response was defined as a platelet count at or above 30×109/L but less than 100×109/L and at least a doubling of the baseline platelet count and an absence of bleeding. No response was defined as a platelet count of less than 30×109 cells per L, or less than two-times increase from baseline platelet count, or bleeding. Key secondary enpoints included response at day 28, time to response (TTR), duration of response, bleeding scores, health-related quality of life assessment and adverse events (AEs). This trial was registered with ClinicalTrials.gov (NCT04917679). Results: From September 2020 to December 2021, 90 patients were screened for eligibility, of whom 24 were ineligible, 66 were randomly assigned to receive either eltrombopag plus diacerein (n=32) or eltrombopag alone (n=34). Four patients did not receive allocated intervention and they were excluded from the analysis. Baseline characteristics were balanced between the two arms. The total population (female accounted for 51.6%) had a mean age of 42.6 years and a mean platelet count of 8.6 ×109/L. At day 15, a significantly higher proportion of participants in the eltrombopag plus diacerein arm (13 [43.3%] of 30) than in the eltrombopag monotherapy arm (5 [15.6%] of 32) had an initial response (p=0.0247). At day 28, the response rate in the combination arm was higher than that in the eltrombopag arm even though it did not reach statistical significance (10 [33.3%] of 30 vs 4 [12.5%] of 32, p=0.0699). There was no significant difference in median TTR between the two arms (p>0.05). During the follow-up period, the duration of response was longer in the eltrombopag plus diacerein arm than in the eltrombopag arm by the Kaplan Meier analysis (Hazard ratio 0.57, 95% CI 0.34-0.96, p=0.0178). Eltrombopag plus diacerein exhibited lower bleeding scores and better health-related quality of life scores than eltrombopag. Incidence of AEs was similar between the two arms. Most of AEs were mild and resolved spontaneously after treatment was completed. The incidence of gastrointestinal reactions in the combination arm was slightly higher, but no significant difference was observed. There were no grade 4 or 5 AEs. No treatment-related deaths occurred. Conclusions: In conclusion, our findings suggest that the addition of diacerein as a sensitizer to eltrombopag has improved initial response than eltrombopag alone for eltrombopag-inefficient or relapsed ITP patients. This oral combination therapy warrants further exploration. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Herombopag for Enhancement of Platelet Engraftment in Patients Undergoing Hematopoietic Stem Cell Transplantation

Abstract Background Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for many patients suffering from hematological malignancies. However, thrombocytopenia is a common and potentially severe complication of HSCT. A recent study found that the median time to platelet engraftment, defined as the first of 7 consecutive days of an unsupported platelet count of at least 20,000/μl, was more than 54 days. It was also reported that the incidence of mortality was significantly higher in patients with post-HSCT thrombocytopenia. We developed a clinical trial to facilitate platelet engraftment after HSCT using herombopag, an oral nonpeptide thrombopoietin receptor agonist. Herombopag is CFDA-approved for the treatment of chronic immune thrombocytopenia, and patients with severe aplastic anemia who do not respond well to immunosuppressive therapy in June 2021. From the pharmacological point of view, it functions by phosphorylating multiple downstream signaling proteins and has stronger effects than eltrombopag when used at the same dosages. Here we present the results of this prospective clinical trial. Methods: This is a phase I/II clinical trial. Eligible patients had: a platelet count before conditioning regimen≥ 50,000/μl, >18 years of age, ECOG ≤ 2, ALT ≤ 3 ULN (upper limit of normal), AST ≤ 3 ULN, total bilirubin ⩽ 1.5 ULN, creatinine ⩽ 1.5 ULN, the first HSCT and an expected survival period ≥ 3 months. The primary objective was to evaluate the safety and efficacy of herombopag for platelet engraftment after HSCT. After transplantation, oral herombopag (7.5 mg) was administered until platelet counts reached 50,000/μL for 7 consecutive days without platelet transfusions. The primary endpoints of this trial were the 21-day incidence of partial platelet engraftment (A platelet count exceeding 20,000/μl for 7 consecutive days without transfusion), and 50-day cumulative incidence of complete platelet engraftment (A platelet count exceeding 50,000/μl for 7 consecutive days without transfusion) after HSCT. We used Propensity Score Matching (PSM) to select matching subjects among other eligible subjects. Differences between groups were analyzed using Chi-squared tests. Results: Between February 2022 and June 2022, 17 patients with acute leukemia were enrolled (Table1). For partial and complete engraftment, the median time was 13 (range, 8-24) days, and 20 (range, 14-61) days. The median time to neutrophil engraftment was 11 (range, 9-19) days. We performed a comparison of engraftment data between our study cohort and a historical cohort comprised of 17 individuals. The 2 cohorts were matched in sex, age, ABO match, and transplantation type using the propensity score matching method (PSM). The incidence of partial and complete platelet engraftment was significantly higher in the study group (partial, 89% versus 59%, p=0.05; complete, 94% versus 65%, p=0.03). The median follow-up duration was 3 (range, 1-5) months. The median number of platelet transfusions required within 30 days after HSCT was 3 (range 1-9) U. The overall survival (OS) was 94%, and 1（6%）patient suffered from molecular recurrence. 1（6%）patient developed grade III aGVHD and died 3.4 months after transplantation. 5 (29%) developed grade I-II aGVHD and no grade IV aGVHD occurred. 3（18%）patients suffered cytomegalovirus (CMV) viremia. According to acute WHO side effects, 7 (41%) patients suffered grade I-II AEs of the digestive tract, and 1 (6%) patient suffered grade III. 3 (18%) patients suffered grade I-II AEs of fever, and no grade IV adverse events occurred. The AEs of the digestive tract included nausea (3/17, 18%), vomiting (2/17, 12%), oral ulcer (7/17, 41%), and diarrhea (3/17, 18%). Conclusions: Herombopag has a significant contribution to platelet engraftment in patients undergoing HSCT and the drug is very well-characterized and safe. While Further investigations for a longer period and more cases would be necessary next. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

COVID-19 Vaccination in Children and Young Adults with Pre-Existing Immune Thrombocytopenia (ITP): Preliminary Data from the Platelet Disorder Support Association (PDSA) Patient Registry

BACKGROUND AND AIMS Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder causing low platelet counts (PC) and an increased risk for bleeding. Some parents hesitate to vaccinate their children with ITP against SARS-CoV-2 fearing, based on data in adults, that it will trigger a PC decrease and exacerbate disease. We review how COVID-19 infections and vaccinations impact children and young adults with ITP in a small cohort. METHODS Data was collected using the COVID-19 & ITP survey in the ITP Natural History Study Registry. As of June 23, 2022, 21 parents of children with pre-existing ITP (< 18 years of age) and 9 young adults with pre-existing ITP (ages 18-21 years) completed the survey. Data was analyzed with descriptive statistics and chi-squared tests. RESULTS Most of the 30 participants were female (53%), under 18 (70%), and reported their diagnosis was primary ITP (90%) with no co-morbid conditions; 25% self-reported they were in remission, 50% had received ITP treatment within the last 6 months, and 1 patient reported having had a splenectomy. Viral disease: Eleven participants (37%) were diagnosed with SARS-CoV-2: 5 (46%) reported their PC did not change, in 4 (36%) their PC increased, and 2 (18%) did not provide counts. Summary: no PC decreases and no bleeding during or after infection. Recovery to baseline was reported in two of four patients who had a PC change with recovery within one month; 2 did not report their PC. There were no hospitalizations or deaths, or reports. Six participants who tested positive had received treatment for their ITP within the last six months, however only one of 6 had received immuno- suppressants, (a corticosteroid and mycophenolate mofetil), the latter in addition to a thrombopoietin receptor agonist. Vaccination impacts: 24/30 (72%) ITP patients reported receiving at least one vaccine dose at survey completion; 20/30 (61%) reported being fully vaccinated (2 doses): Pfizer (75%), Moderna (17%), and Johnson & Johnson (8%). Following the first vaccine dose (D1), 22/24 participants reported their PC: increases were seen by 8/22 (36%), decreases by 5/22 (23%), and 9/22 (41%) had no change. Of the 13 with a PC change following D1, 67% returned to baseline within one month. Of the 20 fully vaccinated participants, following dose two (D2), PC increases were reported by 2 (10%), PC decreases by 7 (35%) and 11 (55%) reported no change. A return to usual baseline occurred within 3 months in the 9 fully vaccinated individuals, in 6 within 4 weeks. One participant had been in remission for four years and then relapsed following D2 when their PC decreased by 30,000-50,000/µL. Four out of 5 (80%) children who reported a PC decrease following D1 also experienced a PC decrease following D2. Only 1/8 (13%) reported a PC increase following both D1 and D2. The majority (7/9) of participants who reported their PC remained the same after D1 experienced the same response following D2. Total changes in PC following receipt of D1 vs D2 were not statistically significant (X2 = 0.84, p = 0.36); however, there were notably more PC increases following D1 than D2 (X2 = 4.01, p = 0.045). Six participants had experienced a decrease in PC following a past non-COVID vaccine. Of these, five reported they were fully vaccinated for COVID-19, and reported they did not have a PC decrease following either D1 or D1. De novo ITP was reported in 3 children/young adults following receipt of D1. They were not included in the study. CONCLUSION These preliminary results in only 30 children nonetheless serve to reassure parents of children with ITP and young adults under age 21 years that the risk for platelet count decreases and worsening ITP due to either contracting the SARS-CoV-2 virus or receiving the COVID-19 vaccines appears to be quite low. In particular, even if the count decreases, it was almost always transient. Using the response to D1 is not reliable in predicting a PC change following D2. These findings should reduce vaccine hesitancy among ITP caregivers and young adults and encourage more to be vaccinated (and probably even boosted) whether or not they had problems with a previous vaccination.

Efficacy and Safety of Intravenous Efgartigimod in Adults with Primary Immune Thrombocytopenia: Results of a Phase 3, Multicenter, Double-Blinded, Placebo-Controlled, Randomized Clinical Trial (ADVANCE IV)

Background: In immune thrombocytopenia (ITP), immunoglobulin G (IgG) platelet autoantibodies accelerate platelet clearance and impair platelet production. IgG homeostasis is regulated by the neonatal Fc receptor (FcRn). Efgartigimod (EFG), a human IgG1 Fc-fragment, is a natural ligand of FcRn engineered to competitively bind to FcRn with high affinity and prevent recycling of endogenous IgG, but not albumin, thereby reducing IgG levels including IgG autoantibody levels. Methods: The efficacy and safety of intravenous (IV) EFG were evaluated in ADVANCE, a phase 3, multicenter, randomized, double-blinded, placebo (PBO)-controlled trial (NCT04188379) in adults with persistent or chronic ITP. Participants with an average of 2 platelet counts (PLTs) of <30×109/L during screening were randomized 2:1 to receive 10 mg/kg EFG or PBO for 24 weeks. Concurrent oral corticosteroids, oral immunosuppressants, dapsone, danazol, fostamatinib, and oral thrombopoietin receptor agonists (not romiplostim) were permitted but required to remain at the entry dosage and frequency. Participants received weekly dosing (weeks 1-4) followed by response-dependent weekly or every 2 weeks (q2w) dosing (weeks 5-16) and then maintained their dosing regimen from weeks 17-24. The primary and key secondary endpoints were tested in hierarchical order. The primary endpoint was the proportion of chronic ITP participants with a sustained PLT response (PLT of ≥50×109/L in ≥4 of 6 visits between weeks 19 and 24 without intercurrent events, e.g., rescue therapy at week 12 or later). Key secondary endpoints included extent of disease control (cumulative weeks with PLTs of ≥50×109/L) in the chronic population, proportion of participants in the overall population (chronic and persistent) with sustained PLT response, incidence of bleeding events, and a durable sustained platelet response (PLT of ≥50×109/L in ≥6 of 8 visits between weeks 17 and 24) in the overall population. Safety and pharmacodynamic measures were also evaluated. Results: 131 participants (118 chronic ITP, 13 persistent ITP; 86 EFG, 45 PBO) were randomized. Participants had long-standing, severe ITP (median time since diagnosis of 4.57 years; baseline median PLT of 17×109/L) and were heavily pretreated (67.2% had ≥3 prior ITP therapies). In chronic ITP participants, sustained PLT response was reached in more EFG-treated participants (21.8%; 17/78) than PBO (5.0%; 2/40; p=0.0316). EFG achieved all PLT-related secondary endpoints (Table1). Model-based mean changes from baseline in PLT levels over time showed a clear differentiation from PBO as of week 1, indicating an early onset of PLT response in the EFG group. A sustained PLT response was achieved in 90% (9/10) of participants who reached and maintained the q2w fixed dosing. EFG-treated participants responded better than PBO regardless of age, sex, severity of disease, time since diagnosis, prior ITP treatment, or background medication (Figure1). International working group (IWG) response (consecutive visits ≥7 days apart with PLTs of ≥30×109/L and 2-fold increase from baseline in the absence of bleeding events) was seen in 51.2% (44/86) of EFG treated participants compared to 20.0% (9/45) in the PBO group. Mean IgG levels in EFG-treated participants decreased steadily over the first 4 weeks of treatment, after which the mean maximum reductions from baseline remained greater than 60% throughout the trial. Mean IgG levels were similar in the group on q2w treatment. Adverse events (AEs) were reported in 93.0% (80/86) of participants in the EFG group and 95.6% (43/45) in the PBO group. Most frequent AEs included bruising, headache, hematuria, and petechiae. Serious AEs were reported in 8.1% (7/86) of participants in the EFG group and in 15.6% (7/45) in the PBO group, and none were treatment related. These included bleeding or events related to bleeding (n=5), infections (n=4), and worsening primary ITP (n=3). No deaths or increased risk of infection were observed. Conclusions: Compared to PBO, EFG showed an early PLT increase, higher sustained PLT response, and more weeks with PLT ≥50×109/L. EFG achieved the primary and all PLT-related secondary endpoints and also showed that 51.2% of participants on EFG achieved IWG response criteria versus 20% on PBO. EFG was well tolerated with no new safety signals. Long-term efficacy and safety data are being evaluated in the open-label extension trial (ADVANCE+; NCT04225156). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Eltrombopag in Pediatric Patients with Previously Untreated or Refractory/Relapsed Severe Aplastic Anemia: The Phase II Escalate Trial

Background: Severe aplastic anemia (SAA) is a rare, life-threatening disease characterized by pancytopenia and hypocellular bone marrow (BM). Immunosuppressive therapy (IST) is the standard of care for pediatric patients (pts) who lack a matched sibling donor. Approximately one-third of pts do not respond to IST or relapse following treatment. Therefore, effective and well-tolerated therapies are needed to improve outcomes of IST in pediatric pts with untreated or refractory/relapsed SAA. Aims: ESCALATE (CETB115E2201; NCT03025698) is a multi-institutional Phase II dose-escalation study to evaluate the pharmacokinetics (PK), safety, efficacy, and acceptability of the thrombopoietin receptor agonist eltrombopag (ETB) in pediatric pts who have refractory/relapsed SAA after IST for SAA (Cohort A) or who have previously untreated SAA (Cohort B). Methods: Patients (1 to <18 years [y] of age) received ETB as tablets or powder for oral suspension. Cohort A pts received ETB with IST (horse antithymocyte globulin [hATG] + cyclosporin A [CsA]) or ETB + CsA, based on investigator choice. Cohort B pts received ETB + hATG + CsA. The ETB starting dose was 50 mg/day (25 mg/day in pts aged <6 y) and was adjusted to achieve a target platelet count of 50-200×109/L. The maximum allowed daily dose was 150 mg. ETB was administered for 26 weeks and initiated together with CsA (duration of ≥104 weeks) +/- hATG (Days 1-4). Study follow-up included an additional 52 weeks during which ETB could be continued (data to Week 52 included here). ETB PK were the primary endpoint; secondary endpoints included safety/tolerability, overall response rate (ORR), BM cellularity, morphology, cytogenetics, paroxysmal nocturnal hemoglobinuria (PNH) clonal evolution, and acceptability/palatability (full data to be presented). ORR was defined as the proportion of pts with a complete (CR) or partial (PR) response (see Table 1 footnote). Results: Fifty-one pts (14 in Cohort A, 37 in Cohort B) were enrolled. The ORRs at Week 26 were 71% (95% CI 42-92) and 46% (30-63), respectively, for Cohorts A and B, and 57% (95% CI 29-82) and 51% (34-68) at Week 52 (Table 1). The most common ETB/hATG/CsA-related adverse events (AEs) (>20%) over the study period were increased bilirubin (43%), increased ALT (41%), increased creatinine (39%), increased AST (33%), hypertension (31%), hypomagnesemia (26%), and increased blood urea (24%). The most common serious AE was pyrexia (29%). Twenty-six pts discontinued ETB treatment, including 11 pts due to physician decision, 7 pts due to AEs (increased ALT/AST/blood bilirubin), 4 pts due to pt/guardian decision, 3 pts no longer requiring treatment, and 1 pt due to progressive disease. Two pts had BM chromosomal abnormalities post baseline (1 with 47XY+Y[2]/46XY[18] at Week 26 [normal at baseline and at Weeks 12 and 52]; 1 with 46,XY,t(2,3)(p23,q12)[2]/46,XY[18] at Week 182 [normal at baseline]). One pt evolved to PNH and 1 pt progressed to acute myeloid leukemia. Most pts reached the maximum daily dose of 150 mg regardless of age. The median dose intensity was 116.6 mg/day in pts aged <6 y and 94.8 mg/day in those aged 6 to <18 y. In pts who maintained the highest dose achieved for ≥14 days, the geometric mean (CV%) AUCtau was μg⋅h/mL (43%, n=8) and 733 μg⋅h/mL (63%, n=19) for pts aged 1 to <6 y and 6 to <18 y, respectively. Corresponding Cmax values were 71.6 μg/mL (33%, n=9) and 36.2 μg/mL (62%, n=22). Dose-adjusted (to 50 mg) geometric mean AUCtau was 447 μg⋅h/mL (54%, n=8) and 321 μg⋅h/mL (58%, n=19) for pts aged 1 to <6 y and 6 to <18 y, respectively. Corresponding Cmax values were 25.8 μg/mL (46%, n=9) and 16.6 μg/mL (52%, n=22). The higher ETB exposure in younger pts was a consequence of slower clearance: geometric mean CLss/F was 0.112 L/h (54%, n=8) and 0.156 L/h (58%, n=19) for pts aged 1 to <6 y and 6 to <18 y, respectively. This age effect on ETB PK is supported by data in adult SAA pts (dose-adjusted AUCtau and Cmax of 257 μg⋅h/mL and 13.4 μg/mL, respectively). Conclusion: The overall response rate to ETB in pediatric refractory/relapsed SAA pts was encouraging. ETB exposure was higher in pts aged 1 to <6 y than in those aged 6 to <18 y because of the age-related increase in ETB clearance. Despite the higher exposure in the younger pts, the daily dose achieved was generally 150 mg in both the 1 to <6 y and 6 to <18 y groups. The observed AEs reflected the disease itself and the safety profiles of hATG, CsA, and ETB. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Avatrombopag Added to Standard Immunosuppressive Therapy for Severe Aplastic Anemia

Acquired aplastic anemia is immune-mediated bone marrow failure disease. Antithymocyte globulin (ATG) and cyclosporine based immunosuppressive therapy (IST) is effective for severe aplastic anemia (SAA), but only 12-17% of patients achieve complete response at 6 months. Complete hematologic response predicts better survival of patients, so clinicians have been trying to further improve the complete response rate. Addition of eltrombopag improves both the overall response rate and complete response rate of SAA patients, but its hepatotoxicity is still worrying. Avatrombopag is a novel, oral, small-molecule thrombopoietin receptor agonist being developed to provide a predictable increase in platelet counts in immune thrombocytopenia and thrombocytopenia in patients with chronic liver disease. To date, there is no report on the effectiveness of avatrombopag in treating aplastic anemia. Here we enrolled 32 severe and very severe aplastic anemia (SAA/VSAA) patients who received ATG, cyclosporine and avatrombopag as first-line treatment between June 2021 and March 2022. Thirty-one patient received porcine ATG (20mg/kg.d for 5 consecutive days) and one patient received rabbit ATG (3mg/kg.d for 5 consecutive days). Avatrombopag was added within 3 months after ATG initiation at dose of 40-60mg per day and administered for at least 3 months. Cyclosporine was given orally at dose of 3.5-5mg/kg.d. There were 17 SAA patients and 15 VSAA patients. The median neutrophil count was 0.31 (range 0.01-1.01) ×109/L, median reticulocyte count was 8 (range 2-54) ×109/L, and median platelet count was 5 (range 1-16) ×109/L. All patients achieved the end-point of 3 months and 23 patients achieved end-point of 6 months. One patient with VSAA died at 1 month due to infections and was counted as no response at 3 months and 6 months. The rate of complete response was 15.6% and rate of overall response was 46.9% at 3 months. The rate of complete response at 6 months was 30.4% and rate of overall response was 65.2%. The complete response rate at 3 months and 6 months were both higher than historical results of standard IST (ATG and cyclosporine, 5.2% at 3 months and 14.6% at 6 months). Avatrombopag was safe, and there was no drug-related liver dysfunction. No patient discontinued avatrombopag due to adverse events. In conclusion, the addition of avatrombopag to IST was safe and associated with higher complete response rate among patients with SAA/VSAA.

The Safety and Efficacy of Fostamatinib in Patients with Chronic Immune Thrombocytopenic Purpura Treated in a Real-World Community Hematology Setting

Background: Chronic immune thrombocytopenia (ITP) in adults is a serious autoimmune disease in which platelets are prematurely destroyed, leaving the patient vulnerable to bruising and bleeding. Initial treatment with corticosteroids is intended to suppress the immune response and is effective in many patients but not sustainable. Fostamatinib is an approved therapy for adult patients with ITP who have had an insufficient response to a prior treatment. It is an oral small molecule that targets spleen tyrosine kinase (SYK), which has important roles in cellular proliferation, differentiation, and immune regulation. By blocking SYK, fostamatinib reduces the immune system's destruction of platelets, which allows the platelet (PLT) count to rise, thereby reducing the risk of bleeding in ITP patients. Two placebo-controlled randomized trials demonstrated that fostamatinib was well tolerated and able to induce meaningful platelet responses in heavily pretreated patients, as well as in earlier lines of therapy. The use of fostamatinib in a community hematology setting has not been evaluated. In this study, the real-world utilization and treatment patterns of fostamatinib in patients treated within the QCCA, a network of 17 community hematology clinics across the United States, is presented. Methods: The QCCA network real world database was reviewed for ITP patients who had received fostamatinib over the past 3 years. Data collection consisted of patient demographics, disease characteristics, duration of ITP, existing comorbidities, number and type of prior ITP treatments and PLT count at baseline prior to the start of fostamatinib. All of the information was collected via a standardized data collection form. From the first day until the end of treatment, data were collected on hemoglobin, white blood cells, absolute neutrophil counts, PLT counts, concomitant ITP therapies and the use of rescue IVIG. A meaningful increase in PLTs was defined as achievement of platelet counts ≥ 30 and ≥ 50 x 103/μL over the course of therapy. Results: The medical records of the 46 ITP patients who met the inclusion criteria and received fostamatinib were evaluated. Patients had a median age of 58 years, 65% were female and 35% had a splenectomy. All patients had prior exposure to corticosteroids and the median number of therapies before stating fostamatinib was two. In addition, 65% had received thrombopoietin receptor agonists and rituximab. All patients started therapy at a dose of 100 mg twice daily for a median duration of 2 months (interquartile range [IQR] = 1 to 15) and a mean duration of 6.7 months (95%CI: 3.5 to 9.9). When fostamatinib was started, the median PLT count was 19 x 103/μL (IQR = 3 to 70). From the start of therapy, the maximum increase in the median PLT count was 78 x 103/μL (IQR = 13 to 231), which was achieved after a median of 1.8 months. Over the course of therapy, 31 (67.4%) and 26 (56.5%) of 46 patients achieved or maintained PLT levels ≥ 30 and ≥ 50 x 103/μL respectively. Of note, prior to the start of fostamatinib, 9 and 7 patients respectively, already had PLT levels ≥ 30 and ≥50 x 103/μL. The percent of patients with at least a doubling of their baseline PLT count was 47.8% (95%CI: 32.9 to 63.0%). There were no serious bleeding events reported, and only one patient required the discontinuation of fostamatinib because of adverse events. Among the 46 patients, 16 received concomitant IVIG to increase PLT counts. Conclusions: In this real-world setting, the findings suggest that fostamatinib is safe and effective in patients with chronic ITP who had relapsed or had not responded to one or more prior treatments.

Treatment of Immune Thrombocytopenia (ITP) with Eltrombopag - Results of the 5th Interim Analysis of the Study RISA, with Special Consideration of Treatment Discontinuations

Background: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia due to increased platelet clearance and decreased megakaryopoiesis. Eltrombopag (EPAG) is an oral thrombopoietin-receptor agonist, which is proved to be effective and safe in the treatment of ITP. Here we present data from the 5th interim analysis of the RISA study, specially considering the reasons for treatment discontinuation and possible links to the safety profile of EPAG. Methods: RISA is a prospective multicenter non-interventional study in Germany. It started in December 2015, and it will continue until December 2023. Statistical analysis is solely descriptive. Results: Data cutoff for this 5th interim analysis was 11th Feb 2022. 313 patients with persistent or chronic primary ITP (pITP) were enrolled. 302 of them received at least one dose of EPAG and completed at least one post baseline visit. Mean duration of participation was 74.1 months. Mean±SD age was 62.8±17.4 years. 54.8% of the patients were female. Mean±SD duration of ITP at baseline was 5.4±7.5 years. Comorbidity was present in 245 (81.1%) patients. Mean±SD number of concomitant diseases was 2.9±3.0. 99 (32.8%) patients completed the entire treatment period of 24 months, which includes all scheduled visits before data cutoff. Median treatment duration was 14 months (minimum 1 day, maximum 6.1 years). Treatment with EPAG was carried out at a median dosage of 50 mg daily. Median platelet counts increased from baseline 34.0x109/L (N=292) to 91.5x109/L (N=262) within one month. From then and until the end of the two-year observation period, platelet counts remained stable above 90x109/L. The proportion of patients whose platelet count was at least 50x109/L increased from 30.1% at baseline to 74.4% after one month and to 85.6% after twelve months. The number of bleeding events per patient-year decreased, from 1.35 at baseline to 0.59 and 0.16 after one and two years, respectively. 128 (42%) patients discontinued treatment, 51 (40%) of them before day 92. Reasons for discontinuation (multiple answers possible) were insufficient effectiveness in 55 (43%) cases, adverse events (AE) in 36 (28%) cases, death in 20 (16%) cases, non-compliance in 16 (13%) cases, lost to follow up in 10 (8%) cases, cessation of therapy due to complete response in 15 (12%) cases and other reasons in 10 (8%) cases. Across the data set, most frequent AE classified as non-serious adverse drug reactions (nsADR) were fatigue (5.3%), thrombocytopenia (3.3%), thrombocytosis (2.3%), diarrhea (3.0%) and dizziness (2.0%). The most common AE leading to discontinuation of treatment and classified as nsADR were thrombocytosis (1.3%), diarrhea (1.7%), fatigue (1.0%) and arthralgia (1.0%). The most frequent serious AE that led to treatment discontinuation and was rated as serious adverse drug reaction was pulmonary embolism, which occurred in 2 (0.7%) patients. Comorbidity was present in 109 (85.2%) of all patients who discontinued treatment. In this subgroup, the mean±SD number of concomitant diseases was 3.4±3.3. Conclusions: We were able to confirm that EPAG therapy in ITP effectively increases platelet counts and reduces the risk of bleeding. For methodological reasons, we were unable to calculate the actual overall response rate. However, based on the proportion of total patients who were shown to discontinue treatment due to insufficient effectiveness (18%), one could assume that all other patients responded to EPAG at least temporarily. This would result in an overall response rate of 82%. This seems to be consistent with the results of the open extension study EXTEND [Wong RSM et al. Blood 2017; 130: 2527-36], in which a similarly high overall response rate (86%) was found. In general, treatment with EPAG was well tolerated, with no new safety signals from our data set. In view of the high discontinuation rate, it should be borne in mind that about one in eight (12%) of these patients responded so well to EPAG therapy that this was taken as an opportunity for a discontinuation attempt. Other factors that may have contributed to treatment discontinuation included age and comorbidity of patients. Notably, the percentage and number of comorbidities in the discontinuation subgroup were even higher than in the overall study population. However, since this is a non-interventional observational study, results are descriptive and need to be interpreted with caution.

Hematologic responses to avatrombopag switch in TPO-RA refractory aplastic anemia

Objective: Short-term efficacy and safety of afatrombopag conversion therapy in patients with aplastic anemia (AA) who were previously ineffectively treated with intense immunosuppressive therapy (IST) combined with TPO receptor Agonist (TPO-RA) or who were unable to tolerate the side effects of TPO-RA. Methods: Analysis of patients with severe aplastic anemia (SAA) treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 2021 to December 2021 who received IST combined with TPO-RA (eltrombopag/hatrombopag) for at least 6 months, but was ineffective for at least 3 months or patients who cannot continue to use TPO-RA due to side effects, and switched from TPO-RA to avatrombopag (APAG) , and treated for at least 6 months. This study analyzed its short-term efficacy and evaluated its safety. Results: The median age was 54 (14-68) years old among the 16 patients with AA (8 male and eight female) . A total of ten patients (refractory group) who did not respond to IST combined with TPO-RA were converted to APAG median therapy for 6 (6-10) months. Only seven patients (70% ) obtained trilineage HR [four cases of complete treatment response (CTR) , one case of good treatment response (GPR) , and two cases of partial treatment response (PR) ], all of which began to take effect at 3 months of APAG treatment. There were six patients with TPO-RA intolerance, and APAG was treated for 6 (2 to 8) months. About four patients (67% ) received HR (three GPR cases and one PR case) , of which two patients received PR at 3 months and four patients received HR at 6 months of APAG treatment. No APAG-related grade 2 or more adverse events occurred during the APAG therapy, no thrombotic events occurred, no fibrologic tissue hyperplasia was found in the bone marrow pathology reexamination at 6 months of treatment, and none of the patients discontinued the drug due to adverse events. Conclusion: APAG may be a better switching treatment option for patients with AA who are refractory or are intolerant to TPO-RA.

Evaluating the impact of thrombopoietin receptor agonist medications on patient outcomes and quality of life in paediatric immune thrombocytopenia through semi-structured interviews.

Over the last decade, treatment of immune thrombocytopenia (ITP) in children has advanced to include thrombopoietin receptor agonist (TPO-RA) medications. Concurrently, there has been an increased emphasis on patient-reported outcomes-especially quality of life-to guide treatment. Assessing the impact of TPO-RAs on quality of life in paediatric ITP is therefore a priority. In this single-centre integrative mixed-methods study, a cohort of children with ITP prescribed a TPO-RA was identified. These children and/or their caregivers were invited to participate in semi-structured interviews focussed on quality-of-life measures. Independently, a retrospective chart review collected ITP-related data (platelet count, bleeding events) and TPO-RA data (dosing, side effects). Among the 23 eligible patients, 20 were represented in interviews. On chart review, 11/20 patients responded to TPO-RA by meeting platelet count criteria of ≥50 × 109 /L for six or more weeks in the absence of rescue therapy. In interviews with these children and/or their parents, 19/20 expressed the TPO-RA had 'worked', with 11/20 reporting benefit to mood and 11/20 reporting increased participation in activities/sports. Concerns were raised in interviews about TPO-RA medication cost (17/20), medication administration (10/20) and potential side effects (10/20). In conclusion, this study suggests that TPO-RA use in children with ITP improves quality of life.

A single course of lusutrombopag for multiple invasive procedures in cirrhosis-associated thrombocytopenia: A case series.

Lusutrombopag is a thrombopoietin receptor agonist which reduces the need for platelet transfusions before planned invasive procedures. A post hoc analysis of data from the registration trials observed that lusutrombopag-treated patients who achieved a platelet count > 50 × 109/L (responder patients) did so in a median of 6 days and the effect on platelet count lasted for nearly 3 weeks in total. Since patients with cirrhosis often require repeat invasive procedures, this kind of response-time trend sheds light on the possibility of placing more than one invasive procedure within a single course of lusutrombopag treatment. Platelet transfusion represents the gold standard in this setting, but is limited by the risk of adverse events and limited availability. We describe our experience with lusutrombopag in three patients with severe cirrhosis-associated thrombocytopenia who underwent multiple invasive procedures after a single course of treatment. The treatment schedule is lusutrombopag orally 3 mg/daily for 7 days and then a time window of 6 days (day 9-14) for the elective invasive procedure. All three patients achieved good response to lusutrombopag treatment and were able to undergone more invasive procedures in the same course of treatment without need of platelet transfusion. our preliminary experience supports the safety and the effectiveness of lusutrombopag in patients with severe cirrhosis-associated thrombocytopenia who underwent multiple invasive elective procedures after a single course.

Management of patients with immune thrombocytopenia in the Moscow region

Background. Idiopathic thrombocytopenic purpura (ITp) is an autoimmune disease characterized by antibody-mediated platelets destruction and impairment of their production, which manifests itself as: isolated thrombocytopenia, risk of spontaneous hemorrhage and bleeding of varying severity. ITp is a hematological, orphan disease with an incidence of 1–4 cases per 100,000 population. In modern literature, primary and secondary immune thrombocytopenias are distinguished. primary immune thrombocytopenia is a diagnosis of exclusion. To verify it, a certain diagnostic search is required.Aim. To evaluate clinical characteristics and treatment efficacy in patients with a confirmed primary immune thrombocytopenia in the Moscow region.Materials and methods. This article presents the results of an analysis of more than 2,400 outpatient records of patients diagnosed with thrombocytopenia (for the period from 2010 to 2022). Of these, about 400 confirmed clinical cases of various ITp forms were included in the ITp registry of the Moscow Region. All patients live in the Moscow region, receive treatment and are observed at the Center for Orphan diseases of the M.f. vladimirskiy Moscow Regional Research Clinical Institute.Results. There are 415 patients with a verified diagnosis of ITp in the register of the Moscow Region Center for Orphan diseases of the M.f. vladimirskiy Moscow Regional Research Clinical Institute (71 % (n = 294) are female). In 69.8 % (n = 290) of patients at the time of disease manifestation, hemorrhagic syndrome was recorded. As a first-line therapy, 92.8 % (n = 385) of patients received corticosteroids (prednisolone, methylprednisolone, dexamethasone), in the second-line therapy, 82 % (n = 340) of patients were recommended therapy with thrombopoietin receptor agonists (romiplostim, eltrombopag). The options for third-line therapy in patients with ITp are rituximab monotherapy, splenectomy, and intravenous immunoglobulin. Splenectomy was performed in 3.37 % (n = 14) of patients.Conclusion. when evaluating this register, the highest efficiency of thrombopoietin receptor agonists (romiplostim, eltrombopag) is observed – 84.1 % of the objective response.

Eltrombopag modulates the phenotypic evolution and potential immunomodulatory roles of monocytes/macrophages in immune thrombocytopenia

Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease. Loss of immune tolerance plays a crucial role in the pathogenesis of ITP. Monocytes and macrophages play an indispensable role in the pathophysiology of hematopoietic malignancies and have been implicated as key players in platelet destruction. Approximately 80% of adult patients with ITP exhibit corticosteroid treatment failure or become dependent, requiring novel therapy. Thrombopoietin (TPO) receptor agonists (TPO-RAs) have been used clinically to manage ITP effectively, however, little is known about the effect of TPO-RAs on monocyte and macrophage modulation in adult ITP. In this study, we investigated the phenotypic evolution and potential immunomodulatory roles of monocytes/macrophages in ITP patients receiving eltrombopag therapy. Results showed that the peripheral monocyte count positively correlated with IFN-γ/IL-4 ratio in ITP patients. Moreover, numerous phenotype-associated genes in ITP macrophages exhibited diverse responses, and ITP macrophages exhibited more M1-related characteristics. After eltrombopag therapy, the peripheral monocyte count and IFN-γ/IL-4 ratio significantly decreased in ITP patients. M1-related characteristics of ITP macrophages were partially reversed by eltrombopag. Therefore, this study revealed eltrombopag restored the monocyte dynamics and the associated Th1/Th2 imbalance, and partially reversed the M1-related characteristics of the ITP macrophages, which suggest the potential vital roles of TPO-RAs in regulating the monocyte/macrophage plasticity in ITP.

Diagnosis and treatment of immune thrombocytopenia in Poland

Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by an isolated platelet count of less than 100,000/μL caused by destruction and reduced production of platelets. Systemic steroid therapy is a mainstay of first-line treatment; however, additional treatment lines are usually necessary due to the very high recurrence rate after therapy completion and steroid resistance. Standard treatment options for steroid resistance or steroid dependence include splenectomy, rituximab or thrombopoietin receptor agonists. The article presents current data on the diagnosics and therapy of ITP, considering the limited access to some forms of treatment in Poland.

Immune-mediated platelet transfusion refractoriness in a severely thrombocytopenic patient with myelodysplastic syndrome successfully treated with romiplostim

Immune-mediated platelet transfusion refractoriness due to anti-human leukocyte antigen (HLA) antibodies can occur in approximately 9% of patients with myelodysplastic syndromes (MDS) and can lead to an increased risk of clinically relevant bleeds and treatment delays. These patients are typically managed with frequent platelet transfusions; however, HLA-matched platelet transfusions are usually available only in large blood centers. For this reason, alloimunized thrombocytopenic MDS patients are notoriously difficult to manage. Here, we present a case of a MDS patient with an immune-mediated platelet transfusion refractoriness, severe thrombocytopenia and spontaneous subarachnoid hemorhage who we successfully treated with romiplostim, a thrombopoietin receptor agonist.

Perspectives of vitamin C upregulating regulatory T cells in the era of thrombopoietin receptor agonists for immune thrombocytopenia

Background Immune thrombocytopenia (ITP) is a rare disorder involving excessive peripheral destruction of platelets and inadequate bone marrow platelet production due to autoimmune reactions against megakaryocytes. Diagnosis is usually by the exclusion of primary causes; its rarity would only permit trial and error therapy experience. Historically, for ITP, oral ascorbic acid (AA) gave inconsistent results. However, unlike other nutrients, AA is found to have an exceptionally tight intestinal absorption restriction mandating intravenous delivery for any therapeutic purposes. Recently, as there is more pre-clinical evidence of AA restoring regulatory T cells (Tregs) by robust demethylation, the historical oral route was likely to be the “bottle neck” restricting effective blood levels. During this era of thrombopoietin receptor agonists (TPO-RAs), planned tapering is often required upon discontinuation but unplanned discontinuations, for example, due to side effects, are more problematic. Moreover, combinations with TPO-RAs are currently being tried using steroids and rituximab except rituximab is inappropriate during pandemics. Notably, with the indirect (but prognostically relevant) action of TPO-RAs on Tregs, boosting Treg functions by adding other Treg active agents, for example, steroids or AA, seems appropriate, especially if without added toxicity upon combining. Conclusions With updated pharmacokinetic concepts, it is timely to repeat AA clinical trials for ITP but using intravenous administration. Initially, this may be on compassionate grounds for its probable role as an adjunct to TPO-RAs for unsuccessful tapering and, especially, for all unplanned discontinuations of TPO-RAs. Such off-label usage of AA is justified because of AA's robust pre-clinical evidence on demethylation and initial clinical experience (despite the inappropriate administrative route). Moreover, moderate intravenous AA dosages have one of the best safety profiles, let alone its eminent affordability. Admittedly, after the initial clinical experience, more systematic trials on AA are required, especially for the most appropriate dosage range and its efficacy as monotherapy.

Diagnosis of disorders in the coagulation system, assessment of the risk of hemorrhagic complications in severe cirrhosis/liver diseases according to global screening tests of the hemostasis system and principles for their correction: guidelines

Hemostasis disorders in cirrhosis / severe liver disease are complex, as they affect both pro- and anticoagulant factors, as well as pro- and antifibrinolytic components. Most of the tests that are used in clinical practice to assess coagulation do not take into account the compensatory capabilities of this system as a whole. This document provides guidance for the optimal application and interpretation of global screening tests in the assessment of hemostasis in cirrhosis/severe liver disease, analysis of risk factor of spontaneous and perioperative hemorrhagic complications in these patients, and possible ways to correct them. Thrombocytopenia is one of the most common hematological abnormalities in cirrhosis/ severe liver disease. The frequency of thrombocytopenia in such patients at the stage of liver cirrhosis is 70%, at the pre-cirrhotic stage – 6%. The latest scientific data on the use of thrombopoietin receptor agonists in chronic liver diseases are presented: which patients are the best candidates for a such of therapy. The rationality and limitations in prescribing blood components to patients with liver cirrhosis/severe liver diseases are described. Emphasis is placed on the fact that a number of hemorrhagic complications develop for other non-coagulopathic reasons: decompensated portal hypertension, traumatization of a varicose vein with trophic wall disorders, etc. Data are presented on the use of viscoelastic tests to optimize the management of patients with liver cirrhosis, which simultaneously assess the four main known components of the hemostasis system: the coagulation cascade, platelets, anticoagulant mechanisms and the fibrinolysis system. These tests allow optimization of transfusion of blood components in such patients and should be further studied. Research in this very complex area of hepatology is ongoing and must continue.

Treatment, outcome and re-vaccination of patients with SARS-CoV-2 vaccine-associated immune thrombocytopenia

PurposeFollowing the emergency use authorization of BNT162b2 by the Food and Drug administration (FDA) in early December 2020, mRNA- and vector-based vaccines became an important means of reducing the spread and mortality of the COVID-19 pandemic. The European Medicines Agency labelled immune thrombocytopenia (ITP) as a rare adverse reaction of unknown frequency after vector-, but not mRNA-vaccination. Here, we report on the long-term outcome of 6 patients who were diagnosed with de-novo, vaccine-associated ITP (VA-ITP), and on the outcome of subsequent SARS-CoV-2 re-vaccinations.MethodsPatients were included after presenting to our emergency department. Therapy was applied according to ITP guidelines. Follow-up data were obtained from outpatient departments. Both mRNA- or vector-based vaccines were each used in 3 cases, respectively.ResultsIn all patients, the onset of symptoms occurred after the 1st dose of vaccine was applied. 5 patients required treatment, 3 of them 2nd line therapy. All patients showed a complete response eventually. After up to 359 days of follow-up, 2 patients were still under 2nd line therapy with thrombopoietin receptor agonists. 5 patients have been re-vaccinated with up to 3 consecutive doses of SARS-CoV-2 vaccines, 4 of them showing stable platelet counts hereafter.ConclusionThrombocytopenia after COVID-19 vaccination should trigger a diagnostic workup to exclude vaccine-induced immune thrombotic thrombocytopenia (VITT) and, if confirmed, VA-ITP should be treated according to current ITP guidelines. Re-vaccination of patients seems feasible under close monitoring of blood counts and using a vaccine that differs from the one triggering the initial episode of VA-ITP.

Clinical efficacy of avatrombopag and recombinant human thrombopoietin in the treatment of chronic liver disease-associated severe thrombocytopenia: A real-world study.

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD). Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias. Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ 2 = 1.659, p = 0.198; Waldχ 2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ 2 = 0.540, p = 0.910; Waldχ 2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05). Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.