Publications by authors named "Nishimura Ji"
Aims: Crovalimab is a novel C5 inhibitor administered first intravenously and then subcutaneously in patients with paroxysmal nocturnal haemoglobinuria (PNH) naive to complement inhibition or switching from eculizumab or ravulizumab. Crovalimab showed efficacy and safety comparable to eculizumab in the pivotal COMMODORE 2 and supporting studies.
Methods: We characterized crovalimab pharmacokinetics and the relationship between exposure pharmacokinetic parameters and pharmacodynamic biomarkers, efficacy and safety endpoints using pooled data (healthy volunteers [n = 9], naive [n = 210] and switched [n = 211] patients).
Complement C5 inhibitor treatment with ravulizumab or eculizumab for paroxysmal nocturnal hemoglobinuria (PNH) improves outcomes and survival. Some patients remain anemic due to clinically significant extravascular hemolysis (cs-EVH: hemoglobin [Hgb] ≤9.5 g/dL and absolute reticulocyte count [ARC] ≥120×109/L).
View Article and Find Full Text PDFParoxysmal nocturnal hemoglobinuria (PNH) is an acquired, rare, life-threatening hematopoietic stem cell disorder that causes stem cell-derived cells to be vulnerable to complement-mediated lysis and manifests as hemolytic anemia, thrombosis, and peripheral blood cytopenias. C5 inhibitors, eculizumab, and ravulizumab, are recognized as the current standard of care for PNH treatment in countries where they are available. Crovalimab (PiaSky®), which is approved for the treatment of PNH, is a novel anti-C5 inhibitor with an every-4-weeks, low-volume, subcutaneous maintenance dosing regimen with the possibility for self-administration.
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- Sutimlimab, a new treatment approved in Japan for cold agglutinin disease (CAD), showed positive safety and efficacy results in Japanese patients from a global phase 3 clinical trial and an open-label extension study.
- In the studies, most patients were female with a median age of 70, and a notable percentage experienced mild adverse effects like injection site reactions and infections.
- Overall, sutimlimab was well tolerated over an average treatment duration of nearly 3.8 years, with improvements in hemoglobin and bilirubin levels observed during treatment, and no new safety issues arose during retreatment.
Article Synopsis
- Paroxysmal nocturnal haemoglobinuria (PNH) is a rare blood disorder causing serious issues due to chronic hemolysis and can significantly affect patients' quality of life.
- A post hoc analysis evaluated the effectiveness of pegcetacoplan, a targeted complement C3 inhibitor, in PNH patients with poor bone marrow function from the PEGASUS and PRINCE studies.
- Results showed that while normalisation of certain health parameters was challenging, a significant percentage of patients experienced clinically meaningful improvements in hemoglobin, LDH levels, and fatigue after treatment with pegcetacoplan.
Article Synopsis
- Cold agglutinin disease (CAD) is a rare autoimmune condition causing anemia, and sutimlimab, which inhibits a key part of the immune system, showed effectiveness in reducing symptoms like hemolysis and fatigue in the CADENZA Part A study.
- In Part B of the CADENZA study, 32 out of 39 patients continued treatment for about 99 weeks, showing sustained improvements in hemoglobin, bilirubin levels, and quality of life measures, with no severe adverse effects reported.
- Despite the promising results, stopping sutimlimab led to a return of disease symptoms, indicating that while the treatment is effective, continuous management is necessary to maintain its benefits.
Article Synopsis
- - Crovalimab is a new treatment for paroxysmal nocturnal hemoglobinuria that allows for easy self-administration every four weeks and is shown to be as effective as the existing treatment eculizumab in maintaining hemolysis control and avoiding transfusions.
- - The COMMODORE 2 trial involved 204 patients and compared the effects of crovalimab with eculizumab over 24 weeks, finding similar outcomes for key health measures, including hemoglobin stabilization and fatigue reduction.
- - Both treatments were safe, with no cases of meningococcal infections reported, and many patients preferred crovalimab after switching from eculizumab, showcasing its favorable benefit-risk profile.
Article Synopsis
- The study evaluates the safety and effectiveness of danicopan, an oral complement factor D inhibitor, as an add-on treatment for patients with paroxysmal nocturnal haemoglobinuria (PNH) experiencing extravascular haemolysis while on C5 inhibitors (ravulizumab or eculizumab).
- It is an ongoing, phase 3 trial called ALPHA, which randomly assigns eligible adult patients to receive danicopan or a placebo alongside their current PNH treatment for 12 weeks.
- The primary goal of the study is to measure changes in haemoglobin concentration from baseline to week 12, with interim analysis conducted once around 75% of participants completed the trial up to that point.
Article Synopsis
- Various diseases linked to abnormalities in complement molecules (complementopathies) are being targeted by new therapies called anti-complement agents.
- Paroxysmal nocturnal hemoglobinuria (PNH) is a specific condition caused by a lack of complement regulatory factors, making it a main focus for these treatments; eculizumab, the first anti-complement agent, was approved for PNH in 2007.
- New anti-complement agents are currently in development for PNH and other diseases, including the recently approved sutimlimab for cold agglutinin disease, an autoimmune hemolytic anemia.
Article Synopsis
- A nationwide study involving 2402 patients investigated the prevalence of glycosylphosphatidylinositol-anchored protein-deficient (GPI[-]) cells, specifically PNH-type cells, in individuals with acquired aplastic anaemia (AA) and myelodysplastic syndrome (MDS) using high-sensitivity flow cytometry.
- PNH-type cells were found in 52.6% of AA patients and 13.7% of MDS patients, while none were present in patients with refractory anaemia having ringed sideroblasts or excess blasts.
- The study concluded that PNH-type granulocyte levels can change over time in patients with AA and highlighted that having ≥1% PNH-type granul
Eculizumab is a C5 inhibitor approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR + gMG) in Japan. We report integrated safety data from post-marketing surveillance in these three indications, focusing on commonly occurring adverse events (AEs) and infection-related AEs. Of 1219 patients registered, 1055 (PNH: 780; aHUS: 192; AChR + gMG: 83) had available safety data.
View Article and Find Full Text PDFRavulizumab is a long-acting C5 inhibitor available for treating paroxysmal nocturnal hemoglobinuria (PNH). Post-marketing surveillance (PMS) was implemented following its approval in September 2019 in Japan. We report safety data obtained through to December 2021 for 218 patients and effectiveness data for 194 patients (182 switched from eculizumab and 12 complement inhibitor-naïve).
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- Eculizumab was the first anti-complement drug approved in 2007 to help treat a blood disorder called PNH, and now it can help with other diseases too.
- An improved version, called ravulizumab, allows patients to get treatment every 2 to 8 weeks instead of more often, making life easier.
- New treatments like pegcetacoplan, iptacopan, danicopan, and sutimlimab are being developed or approved to help with different types of blood issues, focusing on hemolytic anemia.
Article Synopsis
- The study examined the long-term effects of crovalimab in patients with paroxysmal nocturnal hemoglobinuria as an extension of the COMPOSER trial, focusing on safety and drug effects.
- Out of 44 patients, 43 participated in the open-label extension (OLE) phase, with 32% experiencing treatment-related side effects, but overall, crovalimab's effectiveness was maintained.
- Findings indicated significant success in managing blood-related issues, such as haemoglobin stabilization and avoiding transfusions, confirming crovalimab's long-term tolerability and efficacy over a median treatment period of three years.
Article Synopsis
- Ravulizumab is the first long-acting complement inhibitor approved for treating paroxysmal nocturnal hemoglobinuria (PNH), with a focus on Japanese adults.
- In a study evaluating patient preferences between ravulizumab and eculizumab, 82.6% of participants favored ravulizumab due to its lower infusion frequency (every 8 weeks) compared to eculizumab (every 2 weeks).
- The preference for ravulizumab suggests it enhances treatment convenience and quality of life for PNH patients, offering valuable insights for treatment decision-making.
Article Synopsis
- Drug-target-drug complexes (DTDCs) were observed in patients transitioning from eculizumab to crovalimab for treating paroxysmal nocturnal hemoglobinuria (PNH), due to the different ways these drugs bind to C5.
- In a phase I/II study, patients experienced transient reductions in crovalimab levels and the formation of DTDCs, with some mild hypersensitivity reactions noted.
- A mathematical model helped optimize crovalimab dosing, resulting in over a 50% reduction of large DTDCs and improved safety, showing that careful dosing can enhance treatment outcomes for patients using new antibody therapies.
Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by uncontrolled activation of the terminal complement pathway, leading to intravascular hemolysis (IVH) and a prothrombotic state. Treatment with terminal complement (C5) inhibitors, the current standard of care, suppresses IVH and reduces the risk of thrombosis and the associated morbidity and mortality. Opportunities exist to further improve care by alternative modes of administration and the reduction of clinically significant anemia and transfusion dependence caused by extravascular hemolysis in some patients.
View Article and Find Full Text PDFTwo Case Studies on Inferior Mesenteric Artery Embolization for Primary Postpartum Hemorrhage.
Interv Radiol (Higashimatsuyama)
March 2022
Postpartum hemorrhage (PPH) remains a leading cause of maternal mortality. Transcatheter arterial embolization (TAE) is an effective treatment option for PPH. Among the vessels embolized, the inferior mesenteric artery (IMA) is usually not the first choice for TAE, because it is a rare source of bleeding in PPH.
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- * The study found that 73% of patients receiving sutimlimab met the primary effectiveness criteria, significantly improving hemoglobin levels and reducing symptoms compared to only 15% of those on placebo.
- * While sutimlimab showed promising results, some patients experienced more side effects, including headaches and hypertension, highlighting the need for careful monitoring in clinical use.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic hematologic disorder associated with inappropriate terminal complement activity on blood cells that can result in intravascular hemolysis (IVH), thromboembolic events (TEs), and organ damage. Untreated individuals with PNH have an increased risk of morbidity and mortality. Patients with PNH experiencing IVH often present with an elevated lactate dehydrogenase (LDH; ⩾ 1.
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- - The study evaluated the long-term effects of ravulizumab, a C5 inhibitor, on patients with paroxysmal nocturnal hemoglobinuria (PNH) over a period from 27 weeks to 2 years after initial treatment.
- - Results showed sustained improvements in key health indicators such as lactate dehydrogenase (LDH) levels and a significant rate of transfusion avoidance, with 81.9% to 85.6% of patients avoiding transfusions.
- - Overall, ravulizumab was well tolerated during this extended period, with a low incidence of serious adverse events, confirming its effectiveness and safety as a primary treatment option for PNH.
All Japanese patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab were enrolled in post-marketing surveillance (PMS) between June 2010 and August 2019 to assess the long-term effectiveness and safety of eculizumab. The reduction in intravascular hemolysis, the change in hemoglobin (Hb) level, and the change in renal function were assessed to determine the effectiveness of eculizumab. The types and frequencies of adverse events (AEs) were assessed to determine its safety.
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