Eculizumab in recalcitrant antiphospholipid antibody syndrome
Bibliographic record
Abstract
Antiphospholipid syndrome (APS) is defined as the occurrence of venous or arterial thrombosis and/or pregnancy morbidity, in the presence of serological evidence of antiphospholipid antibodies (including IgM and IgG anticardiolipin antibodies, IgM and IgG anti-β 2 -glyoprotein I antibodies, or the lupus anticoagulant). Whereas most patients with focal thrombotic events respond to anticoagulation, occasional patients are refractory to standard therapeutic interventions and continue to have either focal or multifocal occlusive disease. For those with recalcitrant disease or those with the catastrophic antiphospholipid syndrome (CAPS), physicians resort to the addition of antiplatelet agents, steroids, immunosuppressives, IVIG, rituximab, or plasma exchange. Complement inhibition may be an effective way to prevent thrombosis associated with APS. Eculizumab, a monoclonal antibody that binds to complement protein C5 and prevents the conversion of C5 to C5a and C5b, may potentially be an effective treatment for patients with APS. First studied in patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, and idiopathic membranous nephropathy in the early 2000s, development of the drug for rheumatic diseases was abandoned in favor of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Given the experience of complement inhibition in animal models of APS as well as prior use of eculizumab several years ago in one of our refractory APS patients, we administered eculizumab to two patients with severe refractory APS. Two patients with antiphospholipid syndrome, unresponsive to conventional anticoagulant therapy, were treated with a loading dose of eculizumab followed by dosing every other week (atypical hemolytic uremic syndrome dosing schedule). It has been suggested that the platelet count may be used as a surrogate marker of APS activity. During therapy, both patients' platelet counts were monitored and any new thrombotic events documented. At the time of submission of this abstract, both patients are continuing treatment with eculizumab. At their lowest values, the patients had platelet counts of 35,000 and 22,000 (K/ml). One of the patients was steroid dependent in order to maintain her platelet count. After initiation of eculizumab, the patient was able to taper steroids as the platelet count has risen from a low of 35,000 to average counts of 100,000. The second patient's platelet count rose to over 200,000 from 22,000 within 10 days of receipt of eculizumab. For both patients the increases in platelet counts have been sustained other than during brief periods when therapy was delayed. During the treatment period (4 and 8 months), there were no new thrombotic events. See Figure 1 . APS patients treated with eculizumab: platelet counts . Eculizumab has shown promising results in our patients with refractory antiphospholipid syndrome. Longer follow-up of these patients will be needed in order to discern the effect on thrombosis. Controlled studies are needed to further assess the efficacy of eculizumab in this condition, as are mechanistic studies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".