Caplacizumab Added to Plasma Exchange and Immunosuppression Accelerates Recovery and Improves Survival in Immune-Mediated TTP: an International Real-World Study of the IWG-TTP (The Capla 1000+Project)
Bibliographic record
Abstract
Introduction: Immune thrombotic thrombocytopenic purpura (iTTP) results from antibody-mediated severe deficiency of ADAMTS13, the Von Willebrand factor (VWF)-cleaving protease. The anti-VWF nanobody caplacizumab is licensed for adults with iTTP. Prospective controlled trials and national real-world studies have provided evidence that caplacizumab improved outcome of the acute phase of the disease. However, whether caplacizumab decreases mortality, and the optimal timing of caplacizumab initiation, remain to be determined. To address these questions, an international survey, the Capla 1000+project, has been conducted. Method: In this international, multicenter retrospective cohort study, 1015 patients were treated with daily therapeutic plasma exchange (TPE), immunosuppression with corticosteroids±rituximab, and caplacizumab (caplacizumab group), which was compared to historic controls treated with TPE and corticosteroids±rituximab (control group, N=510). Caplacizumab initiation was classified as early (within 3 days; 76% of cases) or delayed (³4 days from first TPE). Results: Three-month survival rate in the caplacizumab group was 98.5%, compared with 94% in controls (p<0.0001). Three-month mortality rate was 4.2-fold higher in controls than in caplacizumab-treated patients (95%CI: 2.22-7.7, p<0.0001), regardless of rituximab use. Death in the caplacizumab group was observed primarily in elderly patients, and age was the prognostic factor most associated with 3-month mortality. Patients receiving caplacizumab showed reduced refractoriness, exacerbations, and required fewer TPE sessions to achieve clinical response versus controls (p<0.0001 all). Time to clinical response in the caplacizumab group was shorter than in controls, and even shorter in patients with early caplacizumab initiation (p<0.0001 both). Caplacizumab-related adverse events were observed in 21% of patients, with major bleeding in 2.4%, which was more common in elderly patients. Clinically relevant non-major bleeding (3.7%), non-clinically relevant non-major bleeding (14%), and inflammatory reaction at the injection site (4.5%) were also reported. Conclusion: This international academic effort provides convincing evidence that Caplacizumab added to TPE and immunosuppression significantly reduces unfavorable outcomes during iTTP, including death, and alleviates the burden of care at the potential expense of bleeding events. Advanced age, however, remains an adverse prognostic factor for survival. Publication History Article published online: 13 February 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".