Emicizumab in children: bleeding episodes and outcome before and after transition to Emicizumab

Abstract

Purpose Real-world data and study data regarding therapy with Emicizumab in pediatric cohorts with haemophilia A is scarce. Especially, data on previously untreated pediatric patients (PUPs) and minimally treated patients (MTPs) are missing. Methods Thirteen pediatric patients with haemophilia A and treatment with Emicizumab were retrospectively evaluated for Annual Bleeding Rates (ABR) pre-and post-Emicizumab treatment. Safety data and data on management of minor surgery as well as laboratory results were collected. Additionally, we describe the clinical features of two PUPs and one MTP that are included in our cohort. Results Median age at initiation of Emicizumab was 5.3 (range: 0.26–17.5) years, three patients were younger than one year at initiation of treatment with Emicizumab. Median follow-up time on Emicizumab was 23.8 (range: 0.7–40) months. Total ABR (p = 0.009) as well as spontaneous (p = 0.018), traumatic (p = 0.018), and joint (p = 0.027) ABR reduced significantly post-Emicizumab transition. Safety profile was favourable as only one local site reaction occurred; no cessation of treatment was necessary. Surgery was successfully performed in three patients receiving rFVlla pre- and post-surgery. Emicizumab trough levels showed a median of 43.2 μg/ml (range: 23.9–56.8) after three doses of 3 mg/kg and 51.9 μg/ml (range: 30.4–75) at first follow-up with 1.5 mg/kg. Conclusion Emicizumab is safe and efficient in pediatric patients with and without inhibitors. More data on larger multicenter cohorts and especially on PUPs/MTPs are still needed.

Single centre experience of the use of emicizumab in previously untreated and minimally treated patients under 18 months of age

“…The decision to start emicizumab was made after discussions with parents, considering the advantages and potential risks associated with its initiation at an early age. Although evidence is limited on emicizumab use in infants, there are emerging data from real‐world experience and observational studies that provide reassuring insights 1,7–14 . Moreover, the preliminary findings from the HAVEN 7 trial (NCT04431726) showed that emicizumab was well tolerated, safe and effective in infants with SHA ≤12 months without FVIII inhibitors 15 …”

“…Although evidence is limited on emicizumab use in infants, there are emerging data from real-world experience and observational studies that provide reassuring insights. 1,[7][8][9][10][11][12][13][14] Moreover, the preliminary findings from the HAVEN 7 trial (NCT04431726) showed that emicizumab was well tolerated, safe and effective in infants with SHA ≤12 months without FVIII inhibitors. 15 Despite the early promising indications about the benefits of starting emicizumab prophylaxis at a young age, there is a need for understanding the full implications of its long-term use, particularly in terms of the risk of inhibitor development.…”

Orthopedic surgical procedures in people with hemophilia

“…When hematologic prophylaxis and conservative measures are not successful [e.g., analgesics (paracetamol), cyclooxygenase-2 (COX-2) inhibitors, intraarticular injections of hyaluronic acid and corticosteroids, Physical and Rehabilitation Medicine, orthoses, chemical synovectomy, radiosynovectomy], and joint-preserving surgery (e.g., arthroscopic synovectomy to control synovitis at any joint, removal of the distal tibia osteophyte by open surgery or by arthroscopic surgery at the ankle, ankle joint distraction, joint debridement by arthroscopic surgery at the knee and ankle), the only surgical solution will be ankle arthrodesis or total ankle arthroplasty at the ankle joint, and total joint arthroplasty at the elbow, knee and hip joints [14]. Table 1 summarizes the main orthopedic surgery techniques used in PWH and their indications [12–51].…”

“…Several authors have reported that surgery can be successfully carried out in PWH with inhibitors who are being treated with emicizumab, and that bypassing drugs (recombinant Factor VII activated -rFVIIa and activated prothrombin complex concentrates -aPCCs) can be utilized concomitantly both in adults and in children [49][50][51]. In the study of Kruse-Jarres et al 215 minor surgical procedures (including minor joint procedures) were performed in 115 PWH A (64 with FVIII inhibitors), and 18 major surgeries (including arthroplasty and synovectomy) in 18 PWH A (10 with Facto VIII inhibitors).…”

Emicizumab: the hemophilia A game changer

“…The reader is referred to a very thoughtful and comprehensive discussion of the debate on immune tolerance induction and treatment decision-making pertinent to previously untreated or minimally treated patients in the era of emicizumab. 47 …”