ABSTRACT
Caplacizumab is an anti-von Willebrand factor humanized single-variable-domain immunoglobulin fragment whose efficacy and safety in immune-mediated thrombotic thrombocytopenia purpura (iTTP) have been demonstrated in international studies. This prospective, open-label phase 2/3 study evaluated caplacizumab 10 mg administered daily during plasma exchange and for 30 days afterward, in combination with immunosuppressive treatment, in Japanese adults with a clinical diagnosis of iTTP (new or recurrent). The primary endpoint was prevention of iTTP recurrence; key secondary endpoints included time to platelet count response, time to organ damage normalization, and safety. Among 21 treated patients, 1 of 15 (6.7%) evaluable patients developed iTTP recurrence. Median time to normalization was 2.79 days for platelet count and 2.65 days for organ damage markers (n = 15). Treatment-emergent adverse events (TEAEs) were mostly mild to moderate in severity; the most frequently reported caplacizumab-related TEAEs were increased alanine aminotransferase, epistaxis, and gastrointestinal hemorrhage (all in 9.5% of patients). At least one bleeding event was reported in 7 of 21 patients (33%). Caplacizumab was effective in Japanese patients with iTTP, with a low rate of iTTP recurrence, rapid normalization of platelet counts and organ damage markers, and no unexpected TEAEs. Trial registration: ClinicalTrials.gov identifier, NCT04074187.
Subject(s)
Purpura, Thrombotic Thrombocytopenic , Single-Domain Antibodies , Adult , Humans , East Asian People , Prospective Studies , ADAMTS13 Protein , Single-Domain Antibodies/therapeutic use , Plasma Exchange , Gastrointestinal HemorrhageABSTRACT
Objective: We report a case of additional carotid artery stenting (CAS) for plaque protrusion occurring after initial CAS for radiation-induced common carotid artery (CCA) stenosis. Case Presentation: A 69-year-old man with a history of radiotherapy for laryngeal cancer presented to our hospital with sudden-onset right hemiparesis. Since vulnerable plaque of the left CCA was considered the embolic source for ischemic stroke, CAS was performed for left CCA stenosis. No perioperative complications were observed and the patient was discharged with a modified Rankin Scale score of 0. However, 1 month after CAS, cerebral embolism recurred. As protruding plaque was found on CTA, additional endovascular treatment was performed with intravascular ultrasonography. He was discharged without complications and showed a good outcome at 3 months. Conclusion: In CCA stenosis after radiotherapy, accelerated arteriosclerosis may cause drug-resistant cerebral embolism and plaque protrusion after CAS, making determination of the treatment strategy difficult. Appropriate treatment options need to be based on individual underlying diseases and plaque instability.
ABSTRACT
AIMS: Many parasitic helminths are known to alter host immune responses and consequently affect the progression of autoimmune and allergic diseases. The parasitic nematode Trichinella sp has been reported to suppress several experimental diseases in rodents, including experimental autoimmune encephalomyelitis, type 1 diabetes, colitis, airway inflammation and autoimmune arthritis. We tried to clarify requirement of Th2 cytokines in the anti-arthritic effects of Trichinella spiralis (Ts) against collagen-induced arthritis (CIA). METHODS AND RESULTS: We infected Ts and then induced CIA in STAT6KO DBA/1 mice, comparing the disease progression with that in wild-type (WT) DBA/1 mice, Ts significantly mitigated arthritis in WT mice, in addition to the impairment of anti-type II collagen (IIC) IgG production in a subclass-independent manner. The genetic absence of STAT6 in the mice did not abrogate the anti-arthritic effects of Ts. Alteration of splenic cytokines was not related to the anti-arthritic effects of the parasite. Moreover, lack of IL-10 did not abrogate the anti-arthritic effects of Ts. CONCLUSION: Our results suggest that the anti-arthritic effects of Ts do not require host Th2 signals.
