Effectiveness of Adjunctive Caplacizumab Treatment in Immune Thrombotic Thrombocytopenic Purpura in Real-Life Setting. Retrospective Monocentric Cohort

Caplacizumab Therapy in Immune Thrombotic Thrombocytopenic Purpura

Effect of Caplacizumab in the Recovery of ADAMTS13 Level in Patients with Autoimmune Thrombotic Thrombocytopenic Purpura. Analysis from the Spanish Registry (REPTT)

A Phase 3 Study to Evaluate the Efficacy and Safety of Caplacizumab without First-Line Therapeutic Plasma Exchange in Adults with Immune-Mediated Thrombotic Thrombocytopenic Purpura

Metformin for patients with metastatic prostate cancer starting androgen deprivation therapy: a randomised phase 3 trial of the STAMPEDE platform protocol.

LONG-TERM OUTCOMES OF PATIENTS TREATED WITH CAPLACIZUMAB FOR IMMUNE-MEDIATED THROMBOTIC THROMBOCYTOPENIC PURPURA (ITTP): THE POST-HERCULES STUDY

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura

BackgroundSevere deficiency in ADAMTS-13 (<10%) and the loss of von Willebrand factor–cleaving function can precipitate microvascular thrombosis associated with thrombotic thrombocytopenic purpura (TTP). Patients with immune-mediated TTP (iTTP) have anti-ADAMTS-13 immunoglobulin G antibodies that inhibit ADAMTS-13 function and/or increase ADAMTS-13 clearance. Patients with iTTP are treated primarily by plasma exchange (PEX), often in combination with adjunct therapies that target either the von Willebrand factor-dependent microvascular thrombotic processes (caplacizumab) or the autoimmune components (steroids or rituximab) of the disease. ObjectivesTo investigate the contributions of autoantibody-mediated ADAMTS-13 clearance and inhibition in patients with iTTP at presentation and through the course of the PEX therapy. Patients/MethodsAnti-ADAMTS-13 immunoglobulin G antibodies, ADAMTS-13 antigen, and activity were measured before and after each PEX in 17 patients with iTTP and 20 acute TTP episodes. ResultsAt presentation, 14 out of 15 patients with iTTP had ADAMTS-13 antigen levels of <10%, suggesting a major contribution of ADAMTS-13 clearance to the deficiency state. After the first PEX, both ADAMTS-13 antigen and activity levels increased similarly, and the anti-ADAMTS-13 autoantibody titer decreased in all patients, revealing ADAMTS-13 inhibition to be a modest modifier of the ADAMTS-13 function in iTTP. Analysis of ADAMTS-13 antigen levels between consecutive PEX treatments revealed that the rate of ADAMTS-13 clearance in 9 out of 14 patients analyzed was 4- to 10-fold faster than the estimated normal rate of clearance. ConclusionThese data reveal, both at presentation and during PEX treatment, that antibody-mediated clearance of ADAMTS-13 is the major pathogenic mechanism that causes ADAMTS-13 deficiency in iTTP. Understanding the kinetics of ADAMTS-13 clearance in iTTP may now enable further optimization of treatment of patients with iTTP.

To determine the effectiveness of green banana in the home management of acute (<7 days) or prolonged (≥ 7 days) diarrhoea at the community level. A cluster randomized field trial was conducted among 2968 Bangladeshi rural children 6-36 months old. Wards (villages) were randomly assigned to either a standard care group or a standard care plus green banana group where mothers were instructed to add cooked green banana to the diets of diarrhoeal children. Through a village-based surveillance system, diarrhoeal morbidity data (severity, duration, compliance) were collected for 14 days. Treatment effects were determined by analysing cumulative probability of cure by testing Cox proportional hazards models and relative risk (RR). The cumulative probability of cure was significantly (P < 0.001) different in children receiving GB for both acute [hazard ratio (HR) = 0.63 (95% CI: 0.56-0.67)] and prolonged diarrhoea [HR = 0.38 (95% CI: 0.26-0.59)]. The recovery rates of children with acute diarrhoea receiving GB (vs. control) were significantly more by day 3: 79.9%vs. 53.3% [(RR) = 0.47, 95% CI: 0.41-0.55], (P < 0.001) and day 7: 96.6%vs. 89.1% (RR = 0.32; 0.22-0.46), (P < 0.001). Children with prolonged diarrhoea receiving green banana had significantly higher recovery rates by day 10: 79.8%vs. 51.9% (RR = 0.42; 0.23-0.73), (P < 0.001) and day 14: 93.6%vs. 67.2% (RR = 0.22; 0.08-0.54), (P < 0.001). A green banana-supplemented diet hastened recovery of acute and prolonged childhood diarrhoea managed at home in rural Bangladesh.

Treatment Patterns and Real World Outcomes with Clinical Trials for Patients with Follicular Lymphoma across Lines of Therapy

Delays in the Emergent Management of Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura: A Ten-Year Retrospective Study

Pegylated Liposomal Doxorubicin (PLD) in Combination with Bortezomib (B) May Provide Therapeutic Advantage for High-Risk Multiple Myeloma Patients Relapsing within 12 Months of Stem Cell Transplant.

Caplacizumab for pediatric immune thrombotic thrombocytopenic purpura: A scoping review of current evidence

Immune-mediated thrombotic thrombocytopenic purpura is a rare and challenging hematological disease caused by the antibody anti-ADAMTS13. Though the mortality rate has decreased considerably in recent years, fatalities still remain unacceptable. This study aimed at further adding to the existing knowledge of this medical challenge. We enrolled 89 consecutive patients observed in six Italian centers (from 8 August 2013 to 28 May 2021) with a diagnosis of immune-mediated thrombotic thrombocytopenic purpura. Clinical information and blood parameters were collected for all patients. We describe clinical manifestations and laboratory data, possible risk factors and the therapeutic management of first episodes or relapses. A total of 74 first episodes and 19 relapses (median 3 years (interquartile range (IQR): 2–7)) were recorded. Seventy percent of patients enrolled at the first episode showed neurological signs and/or symptoms. All the patients enrolled at the first episode were treated with plasma exchange (median = 12; IQR: 8–19.5) and methylprednisolone (1 mg/kg/day). Rituximab (375 mg/m2 weekly for four weeks) and caplacizumab were given to 15 (20.2%) and 2 patients (2.6%), respectively. We observed an overall mortality of 5.4% in the follow-up (median 60 months; IQR: 36.0–103.5). All fatalities occurred after a diagnostic delay. Present data point to the importance of the early detection of factors mostly associated with poor outcomes. It is likely that use of caplacizumab could improve the prognosis in those patients.

Effectiveness of hydroxychloroquine against SARS-CoV-2 has been highly controversial. In our research, we aimed to investigate the effects of hydroxychloroquine on disease outcomes in hospitalized patients with COVID-19. A total of 393 hospitalized patients with COVID-19 were retrospectively assigned to the standard of care therapy group (n = 180) or the standard of care plus hydroxychloroquine group (n = 213). The standard of care therapy comprised favipiravir, low molecular weight heparin, acetylsalicylic acid. Status of oxygenation at baseline and on the seventh day, laboratory tests at baseline and at discharge were recorded. Length of hospital stay, administration of anti-inflammatory treatment, admission to the intensive care unit and 28th day mortality were set as primary endpoints. There were no statistically significant differences between groups in terms of oxygen delivery route and mortality after seven days of treatment (p = 0.592). C-reactive protein levels of the standard of care plus hydroxychloroquine group were significantly lower than that of the standard of care group at discharge (p = 0.034). Patients in the standard of care plus hydroxychloroquine group had shorter hospital stay (p = 0.007). The standard of care plus hydroxychloroquine group was favored over standard of care group in terms of rate of intensive care unit admissions (21.7% vs. 10.8%; relative risk with 95% CI = 0.49 [0.31-0.80], p = 0.003). Hydroxychloroquine in addition to standard of care was associated with less intensive care unit admissions, early discharge and greater C-reactive protein reduction. There was no difference in 28-day mortality.

Caplacizumab As New Paradigm-Changing Therapy for Patients with Autoimmune Thrombotic Thrombocytopenic Purpura (aTTP): Real-World Data from TTP Spanish Registry