Emicizumab plasma levels after accelerated saturation in acquired haemophilia A
Bibliographic record
Abstract
Acquired haemophilia A (AHA) is a severe bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII).Treatment of AHA has traditionally consisted of control of acute bleeding episodes with bypassing agents such as recombinant porcine FVIII, activated prothrombin complex concentrates (APCC) and recombinant activated factor VII (rFVIIa).In addition, immunosuppressive therapy with agents such as prednisolone, cyclophosphamide, rituximab or mycophenolate mofetil is recommended for the eradication of the inhibitor.1 Inhibitor eradication can take several weeks 2,3 and an effective bleeding prophylaxis is warranted until remission is achieved.Approved treatment options like APCC result in high rates of breakthrough bleeding.4 Emicizumab is a bispecific antibody approved for bleeding prophylaxis in severe congenital haemophilia A (HA) with and without inhibitors as well as in moderate HA with severe bleeding phenotype.The use of emicizumab in AHA has been reported in several case reports and case series showing that various dosing regimens are efficacious in the prevention of bleeding.5 Recently, a prospective study from Japan (AGEHA, n = 12) 6 and the prospective GTH-AHA-EMI trial (n = 47) 7 reported favourable bleeding outcomes with emicizumab prophylaxis.As a result of these studies, consensus recommendations on the use of emicizumab in AHA were published by the GTH-AHA-study group, 8 and emicizumab has been approved for the treatment of AHA in some countries such as Japan and Canada.The AGEHA and the GTH-AHA-EMI-study included some patients who were actively bleeding at the time when emicizumab was initiated.Therefore, both studies proposed a therapeutic effect of emicizumab in contrast to congenital HA in which bleeding prophylaxis is the main treatment goal.To rapidly achieve effective and in that concept, therapeutic emicizumab plasma concentrations above 30 µg/mL, the AGEHA-and the GTH-AHA-EMI-trial used an accelerated emicizumab loading regimen consisting of 6 mg/kg on day 1 and 3 mg/kg on day 2 based on pharmacologic modelling.6 In the AGEHA study, emicizumab plasma levels were measured at day 1, day 2, day 4, and day 7. Emicizumab plasma levels showed a linear increase during saturation reaching a mean steady state concentration of 37.4 µg/mL (SD 14.3) on day 7.However, no individual data or the number of patients with available data is given in the manuscript.In the GTH-AHA-EMI study, emicizumab concentrations were only measured on day 7. Steady state concentrations were also reached after 7 days,
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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 | 0.001 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".