scholarly journals Caplacizumab Is Effective in Treating Immune-Mediated Thrombotic Thrombocytopenic Purpura in Real-World Scenarios and May Lower Mortality: An Aggregative Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1019-1019
Author(s):  
Linus A. Völker ◽  
Gesa Balduin ◽  
Lucas Kühne ◽  
Jessica Kaufeld ◽  
Ulf Schönermarck ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Real World ◽  
Prospective Trial ◽  
Patient Centered ◽  
Thrombocytopenic Purpura ◽  
Aggregated Data ◽  
Immune Mediated ◽  
Life Saving ◽  
The Uk ◽  
Historical Controls

Abstract Introduction: The treatment of acquired thrombotic thrombocytopenic purpura has been a subject to change lately due to the introduction of caplacizumab as a novel, and potentially life-saving agent. Here, we compare patient-centered outcomes of a historic cohort of 119 aTTP-patients and an extended real-world caplacizumab-treated cohort of 113 aTTP-patients from Germany and Austria in the context of multiple recently published international cohorts of aTTP patients. Methods: From October 2018 until May 2021, data from German and Austrian patients presenting with an acute episode of aTTP as defined by an ADAMTS13 activity below 10 % treated with caplacizumab were gathered retrospectively. We aggregated data from two published randomized controlled trials (TITAN, HERCULES), one single-arm prospective trial and two retrospective cohorts with a historical control cohort. In total, we report 846 aTTP cases, 396 of those treated with caplacizumab and 450 without. For data analysis, placebo groups from randomized trials and historical controls from retrospective analyses were combined. Results: All cohorts combined reported 30 aTTP-related deaths, predominantly in the non-caplacizumab cohort. Mortality in the caplacizumab-cohort (8 cases total) was mainly driven by 5 reported deaths in the UK-cohort, which have been ascribed to a delayed use of caplacizumab by the authors. The number of daily PEX was significantly less in the caplacizumab-treated cohort (7.2 vs 10.2 days). In line, the number of hospital (14.0 vs 18.1) and ICU (4.7 vs 8.9) days differed significantly. Exacerbations (14% vs 39%) were significantly reduced in the caplacizumab-group. In view of all treatment-related outcomes, the data presented herein argues strongly in favor of an early and consistent use of caplacizumab in all instances of aTTP. Disclosures Völker: Sanofi-Genzyme: Honoraria, Other: counselling fees.

scholarly journals Real-World Evidence of Caplacizumab Use in the Management of Acute TTP

Blood ◽  
2020 ◽  
Author(s):  
Tina Dutt ◽  
Rebecca J Shaw ◽  
Matthew James Stubbs ◽  
Jun Yong ◽  
Benjamin Bailiff ◽  
...  
Keyword(s):  
Platelet Count ◽  
Real World ◽  
Patient Characteristics ◽  
Patient Access Scheme ◽  
Fda Approval ◽  
Immune Mediated ◽  
Real World Evidence ◽  
Life Saving ◽  
The Uk ◽  
Von Willebrand

The cornerstone of life-saving therapy in immune mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody, trialled in two multicentre, randomised-placebo-controlled trials leading to EU and FDA approval, has been available in the UK through a patient-access scheme. Data was collected retrospectively from 2018-2020 for 85 patients receiving caplacizumab, including 4 children, from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial endpoints and historical outcomes in the pre-caplacizumab era. 84/85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalisation (3 days), duration of PEX (7 days) and hospital stay (12 days) was comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalisation was favourable compared with historical outcomes (p<0.05). TTP recurrence occurred in 5/85 patients; all with persistent ADAMTS13 activity <5iu/dL. Of 31 adverse events in 26 patients, 17/31 (55%) were bleeding episodes and 5/31 (16%) were thrombotic events (two unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4/5 deaths caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients receiving caplacizumab outside clinical trials, including paediatric patients. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.

Dasatinib-induced immune mediated-thrombotic thrombocytopenic purpura

2018 ◽  
Vol 57 (2) ◽  
pp. 222-224 ◽  
Author(s):  
Esra Terzi Demirsoy ◽  
Ozgur Mehtap ◽  
Elif Birtas Atesoglu ◽  
Pinar Tarkun ◽  
Necmi Eren ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated

scholarly journals The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians

2020 ◽  
Vol 9 (10) ◽  
pp. 3379
Author(s):  
Ilaria Mancini ◽  
Elisa Giacomini ◽  
Silvia Pontiggia ◽  
Andrea Artoni ◽  
Barbara Ferrari ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Risk Allele ◽  
Absolute Risk ◽  
Disease Onset ◽  
Close Monitoring ◽  
Reference Allele ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
The Impact ◽  
Risk Of Relapse

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) deficiency, recurring in 30–50% of patients. The common human leukocyte antigen (HLA) variant rs6903608 was found to be associated with prevalent iTTP, but whether this variant is associated with disease relapse is unknown. To estimate the impact of rs6903608 on iTTP onset and relapse, we performed a case-control and cohort study in 161 Italian patients with a first iTTP episode between 2002 and 2018, and in 456 Italian controls. Variation in rs6903608 was strongly associated with iTTP onset (homozygotes odds ratio (OR) 4.68 (95% confidence interval (CI) 2.67 to 8.23); heterozygotes OR 1.64 (95%CI 0.95 to 2.83)), which occurred over three years earlier for each extra risk allele (β −3.34, 95%CI −6.69 to 0.02). Of 153 survivors (median follow-up 4.9 years (95%CI 3.7 to 6.1)), 44 (29%) relapsed. The risk allele homozygotes had a 46% (95%CI 36 to 57%) absolute risk of relapse by year 6, which was significantly higher than both heterozygotes (22% (95%CI 16 to 29%)) and reference allele homozygotes (30% (95%CI 23 to 39%)). In conclusion, HLA variant rs6903608 is a risk factor for both iTTP onset and relapse. This newly identified biomarker may help with recognizing patients at high risk of relapse, who would benefit from close monitoring or intensified immunosuppressive therapy.

scholarly journals Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura

Blood ◽  
2017 ◽  
Vol 130 (4) ◽  
pp. 466-471 ◽  
Author(s):  
Ferras Alwan ◽  
Chiara Vendramin ◽  
Karen Vanhoorelbeke ◽  
Katy Langley ◽  
Vickie McDonald ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Fold Increase ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
Key Points

Key Points High anti-ADAMTS13 antibody and low ADAMTS13 antigen levels adversely affect outcome in immune-mediated TTP with greater mortality seen. A raised troponin at presentation confers a sixfold increase and reduced GCS a nine-fold increase in mortality in acute TTP.

Treatment of Thrombotic Thrombocytopenic Purpura Using Solvent Detergent Treated Plasma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3989-3989
Author(s):  
Gail Rock ◽  
David Anderson ◽  
Barrett Benny ◽  
William Clark ◽  
Pierre Leblond ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Therapeutic Option ◽  
Statistical Significance ◽  
Prospective Trial ◽  
Thrombocytopenic Purpura ◽  
Number Of Patients ◽  
Normal Enzyme ◽  
Randomized Prospective Trial ◽  
To Receive ◽  
Insufficient Number

Abstract Background: Patients with Thrombotic Thrombocytopenic Purpura require immediate therapy with large volumes of plasma. They have been reported to respond well to plasma exchange (PE) with FFP (78%)1 and CSP (95%)2. We initiated a randomized prospective trial with CSP and solvent detergent treated plasma (SDP) intended to show non inferiority. Methods: Patients were randomized to receive either of the exchange fluids at 1.5 PV x 3 days then 1 PV x 4–6 days. Laboratory values were followed with ADAMTS-13 levels measured according to Furlan3. The primary end point was survival at 6 months. Results: A total of 62 of the required 280 patients entered the study then the supply of SDP was discontinued. 3/35 patients receiving CSP and 1/27 on SDP died before 1 month. These values are not significant but the study is underpowered so statistical analysis is not possible. FVIII and vWF levels were elevated in all patients at entry. 34/50 patients tested also had antibodies to CD36. 9 patients had no ADAMTS-3 at entry, 19 had between 5–50%, 9 patients had 50–100% and 15/62 patients tested had normal levels. Inhibitors were present at between 5–50% levels in 22/50 patients tested whereas 9 patients had complete inhibition of ADAMTS-13 and 18 had normal enzyme activity. Conclusions: Patients with TTP appear to respond well to SDP thereby offering a relatively safer therapeutic option for PE. An insufficient number of patients were entered to achieve statistical significance. Both the ADAMTS-13 and the inhibitor levels show great variation and are not prognostic.

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