RESUMO
Acquired hemophilia A (AHA) is a rare but serious bleeding disorder. Randomized controlled trial (RCT) comparing the efficacy of immunosuppression therapy for AHA lacks. We conducted the first multicenter RCT aiming to establish whether the single-dose rituximab combination regimen was noninferior to the cyclophosphamide combination regimen. From 2017 to 2022, 63 patients with newly diagnosed AHA from five centers were randomly assigned 1:1 to receive glucocorticoid (methylprednisolone 0.8 mg/kg per day for the first 3 weeks and then tapered) plus single-dose rituximab (375 mg/m2 ; n = 31) or plus cyclophosphamide (2 mg/kg per day until inhibitor becomes negative, for a maximum of 5 weeks; n = 32). The primary outcome was complete remission (CR, defined as FVIII activity ≥50 IU/dL, FVIII inhibitor undetectable, immunosuppression tapered and no bleeding for 24 h without bypassing agents) rate measured within 8 weeks. The noninferiority margin was an absolute difference of 20%. Twenty-four (77.4%) patients in the rituximab group and 22 (68.8%) patients in the cyclophosphamide group achieved CR, which showed the noninferiority of the single-dose rituximab-based regimen (absolute difference = -8.67%, lower limit of the 95% confidence interval = -13.11%; Pnoninferiority = 0.005). No difference was found in the incidence of treatment-related adverse events. Single-dose rituximab plus glucocorticoid regimen showed similar efficacy and safety, without a reported risk of secondary malignancies or reproductive toxicity seen in cyclophosphamide, it might be recommended as a first-line therapy for AHA, especially in China where there is a young age trend in AHA patients. This trial was registered at ClinicalTrials.gov as #NCT03384277.
Assuntos
Glucocorticoides , Hemofilia A , Humanos , Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Hemofilia A/tratamento farmacológico , Metilprednisolona/uso terapêutico , Rituximab/uso terapêutico , Resultado do Tratamento , Quimioterapia Combinada/efeitos adversosRESUMO
Ruxolitinib has demonstrated efficacy in patients with myelofibrosis (MF). However, substantial number of patients may not respond after 3-6 months of treatment or develop resistance over time. In this phase 2 trial, patients with a current diagnosis of intermediate or high-risk MF who either had an inadequate splenic response or spleen regrowth after ruxolitinib treatment were enrolled. All patients received jaktinib 100 mg Bid. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR 35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profile. From July 6, 2021, to January 24, 2022, 34 ruxolitinib-refractory or relapsed patients were enrolled, 52.9% (18 of 34) were DIPSS intermediate 2 or high risk. SVR 35 at week 24 was 32.4% (11 of 34, 95% CI 19.1%-49.2%) in all patients and 33.3% (6 of 18, 95% CI 16.3%-56.3%) in the intermediate 2 or high-risk group. A total of 50% (8 of 16) transfusion-independent patients with hemoglobin (HGB) <100 g/L at baseline had HGB elevation ≥20 g/L within 24 weeks. Furthermore, 46.4% (13 of 28) of patients had a ≥ 50% decrease in the total symptom score (TSS 50) at week 24. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (32.4%), anemia (32.4%), and leukocytosis (20.6%). In total, 13 (38.2%) of 34 patients had serious adverse events (SAE), of which drug-related SAEs were found in 5 patients (14.7%). These results indicate that jaktinib can be a promising treatment option for patients with MF who have either become refractory to or relapsed after ruxolitinib treatment.
Assuntos
Inibidores de Janus Quinases , Mielofibrose Primária , Humanos , Inibidores de Janus Quinases/efeitos adversos , Mielofibrose Primária/diagnóstico , Pirimidinas/efeitos adversos , Nitrilas , Resultado do TratamentoRESUMO
Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.
Assuntos
Inibidores de Janus Quinases , Mielofibrose Primária , Humanos , Inibidores de Janus Quinases/efeitos adversos , Mielofibrose Primária/tratamento farmacológico , Nitrilas/uso terapêutico , Pirimidinas/uso terapêutico , Resultado do TratamentoRESUMO
Myelofibrosis (MF) is associated with several constitutional symptoms. Currently, there are few therapeutic options for MF. Jaktinib, a novel, small-molecule inhibitor of JAK, is currently being studied for its potential to treat MF. This phase 2 trial investigated efficacy and safety of jaktinib in the treatment of MF patients. The primary end point was the proportion of patients with ≥35% reduction in spleen volume (SVR35, proportion of patients with ≥35% reduction in spleen volume) at week 24. The secondary end points included improvement of anemia, rates of symptom response, and safety profile. Between January 8, 2019 and August 29, 2020, 118 patients were recruited and treated with either jaktinib 100 mg BID or 200 mg QD. At week 24, 54.8% (34/62) of patients in the 100 mg BID group and 31.3% (15/48) in the 200 mg QD group achieved SVR35 (p = .0199). Jaktinib treatment increased hemoglobin level to ≥20 g/L in 35.6% (21/59) of patients with hemoglobin ≤100 g/L at baseline. The proportion of patients who achieved a ≥50% improvement in total symptom score at week 24 was 69.6% (39/56) in the BID group and 57.5% (23/40) in the QD group. The most common ≥ grade 3 hematological treatment-emergent adverse events (TEAEs; ≥ 10%) were anemia (100 mg BID: 24.2%, 200 mg QD: 28.8%), thrombocytopenia (16.7%, 11.5%), and neutropenia (3.0%, 11.5%). All non-hematological TEAEs were mild. These results indicate that jaktinib can shrink the spleen, improve anemia, and other clinical symptoms with good tolerability.
Assuntos
Anemia , Inibidores de Janus Quinases , Mielofibrose Primária , Humanos , Mielofibrose Primária/diagnóstico , Inibidores de Janus Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Pirazóis/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Nitrilas/uso terapêutico , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Resultado do Tratamento , Janus Quinase 2Assuntos
Púrpura Trombocitopênica Idiopática , Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doença Crônica , Pirazinas/uso terapêutico , Pirazinas/efeitos adversos , Pirazinas/administração & dosagem , Adulto , Resultado do Tratamento , Benzamidas/uso terapêutico , Benzamidas/efeitos adversos , Piperidinas , PiridinasRESUMO
Romiplostim is approved for the treatment of immune thrombocytopenia (ITP). This study aimed to evaluate the pharmacokinetics, safety, and pharmacodynamics of romiplostim in Chinese patients with ITP. This multicenter, open-label, dose-escalation phase I/II trial enrolled ITP patients from 5 centers in China between October 2015 and August 2017. There were 2 cohorts: 1 µg/kg and 3 µg/kg weekly for 2 weeks. The end points included pharmacokinetics, platelet changes from baseline, hematological indicators, and adverse events (AEs). Sixteen participants, with 8 patients in each cohort, were enrolled. In the 1 µg/kg cohort, time to maximum concentration was 4.00 (4.00-7.83) hours, maximum serum drug concentration was 52.0 (16.0-228.0) pg/mL, and area under the serum drug concentration-time curve from time 0 to the last detectable time point was 389 (32.0-5400) pg · h/mL. In the 3 µg/kg cohort, time to maximum serum drug concentration was 11.91 (4.00-12.00) hours, maximum serum drug concentration was 105.0 (25.5-313.0) pg/mL, and half-life was 12.7 (8.2-23.6) hours. The absolute change of peak platelet count from baseline was 14 (3-40) and 72 (3-369) ×109 /L in the 1 and 3 µg/kg cohorts, respectively. Seven (87.5%) and eight (100%) participants had treatment-emergent AEs in 1 µg/kg cohort and 3 µg/kg cohort, respectively. No major AEs occurred in the 2 cohorts. Romiplostim (1 and 3 µg/kg) is safe and well tolerated in Chinese patients with ITP.
Assuntos
Púrpura Trombocitopênica Idiopática , Humanos , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão , Trombopoetina/efeitos adversos , Resultado do TratamentoRESUMO
Bacillus cereus YN917, obtained from a rice leaf with remarkable antifungal activity against Magnaporthe oryzae, was reported in our previous study. The present study deciphered the possible biocontrol properties. YN917 strain exhibits multiple plant growth-promoting and disease prevention traits, including production of indole-3-acetic acid (IAA), ACC deaminase, siderophores, protease, amylase, cellulase, and ß-1,3-glucanase, and harboring mineral phosphate decomposition activity. The effects of the strain YN917 on growth promotion and disease prevention were further evaluated under detached leaf and greenhouse conditions. The results revealed that B. cereus YN917 can promote seed germination and seedling plant growth. The growth status of rice plants was measured from the aspects of rice plumule, radicle lengths, plant height, stem width, root lengths, fresh weights, dry weights, and root activity when YN917 was used as inoculants. YN917 significantly reduced rice blast severity under detached leaf and greenhouse conditions. Genome analysis revealed the presence of gene clusters for biosynthesis of plant promotion and antifungal compounds, such as IAA, tryptophan, siderophores, and phenazine. In summary, YN917 can not only be used as biocontrol agents to minimize the use of chemical substances in rice blast control, but also can be developed as bio-fertilizers to promote the rice plant growth.
RESUMO
Electrochemical promotion of catalysis (EPOC) has been shown to accelerate the rate of many heterogeneous catalytic reactions; however, it has rarely been reported in low-temperature aqueous electrochemical reactions. Herein, we report a significant EPOC effect for the CO2 reduction to generate formate over Pd nanoparticles (NPs) in a 1 M KHCO3 aqueous solution. By applying a negative potential over differently-sized Pd NPs, the rate of formate production is greatly improved as compared to that at an open-circuit voltage, with a rate enhancement ratio ranging from 10 to 143. The thermocatalytic and electrocatalytic reduction of CO2 compete with each other and are promoted by the applied negative potential and H2 in the feeds, respectively. Inspired by the EPOC effect, a composite electrode containing Pd/C and Pt/C catalysts on different sides of a carbon paper was constructed for catalyzing the CO2 reduction without adding H2 to the feeds. Water electrolysis over Pt NPs generates H2, which then effectively promotes formate production over Pd NPs.
RESUMO
[This corrects the article DOI: 10.1039/C6SC04966D.].