Management of acute breakthrough hemolysis with intensive pegcetacoplan dosing in patients with PNH.
Morag GriffinRichard J KellyJens Peter PanseCarlos de CastroJeffrey SzerRegina HorneffLisa TanMichael YehRégis Peffault de LatourPublished in: Blood advances (2024)
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated intravascular hemolysis leading to anemia, fatigue, and potentially life-threatening thrombotic complications. Breakthrough hemolysis (BTH) was first described in patients with PNH treated with terminal complement C5 inhibitors when intravascular hemolysis reoccurred despite treatment. Pegcetacoplan, the first proximal complement C3 inhibitor, offers broad hemolysis control in patients with PNH. While experience of managing BTH on C5 inhibitors is documented, very limited guidance exists for proximal complement inhibitors. This interim analysis assessed the effect of intensive treatment with pegcetacoplan following an acute BTH event in a subset of patients enrolled in the ongoing open-label extension study of pegcetacoplan in PNH. Thirteen patients with acute BTH included in the analysis received either a single IV dose of 1080 mg (n = 4) or 1080 mg subcutaneous (SC) dosing on 3 consecutive days (n = 9). A potential, clinically-relevant complement-amplifying condition, such as infection or vaccination, was reported in approximately half of the patients experiencing an acute BTH. Lactate dehydrogenase (LDH) levels decreased between day 1 and day 2 in 8 of 12 evaluable patients and in all 13 patients at day 7 to 12. Nine of 13 patients (69%) achieved LDH <2× the upper limit of normal by day 14 to 19. All adverse events associated with the acute BTH event were considered resolved by the investigators. Overall, intensive treatment with pegcetacoplan was safe and well tolerated. These novel data support effective management of acute BTH events in patients on pegcetacoplan with intensive IV or SC pegcetacoplan dosing. This trial was registered at www.clinicaltrials.gov as #NCT03531255.
Keyphrases
- end stage renal disease
- chronic kidney disease
- newly diagnosed
- ejection fraction
- liver failure
- prognostic factors
- peritoneal dialysis
- randomized controlled trial
- open label
- clinical trial
- blood pressure
- squamous cell carcinoma
- coronary artery
- machine learning
- drug induced
- radiation therapy
- climate change
- electronic health record
- obstructive sleep apnea
- sleep quality
- aortic dissection
- combination therapy
- atrial fibrillation
- big data
- artificial intelligence
- deep learning
- double blind
- phase ii study