Eculizumab in recalcitrant antiphospholipid antibody syndrome
Notice bibliographique
Résumé
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.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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