Predictors of inhibitor eradication by primary immune tolerance induction in severe haemophilia A with high responding inhibitors. Issue 1 (2nd November 2021)

• Record Type: Journal Article
• Authors: Di Minno, Giovanni; Coppola, Antonio; Margaglione, Maurizio; Rocino, Angiola; Mancuso, Maria Elisa; Tagliaferri, Annarita; Linari, Silvia; Zanon, Ezio; Santoro, Cristina; Biasoli, Chiara; Castaman, Giancarlo; Santagostino, Elena; Mannucci, Pier Mannuccio
• Other Names: Scaraggi Francesco Antonio investigator.; Ettorre Cosimo Pietro investigator.; Marino Renato investigator.; Valdrè Lelia investigator.; Targhetta Roberto investigator.; Aru Anna Brigida investigator.; Musso Roberto investigator.; Cultrera Dorina investigator.; Santoro Rita Carlotta investigator.; Iannaccaro Piergiorgio investigator.; Tagariello Giuseppe investigator.; Sartori Roberto investigator.; Daniele Filomena investigator.; Morfini Massimo investigator.; Pedrazzi Paola investigator.; Schiavulli Michele investigator.; Brandolin Barbara investigator.; Mancuso Giacomo investigator.; Mansueto Francesca investigator.; Rivolta Gianna Franca investigator.; Di Perna Caterina investigator.; Iorio Alfonso investigator.; Marchesini Emanuela investigator.; Arbasi Maria Cristina investigator.; Latella Caterina investigator.; Mazzucconi Maria Gabriella investigator.; Grandone Elvira investigator.; Schinco Piercarla investigator.; Valeri Federica investigator.; Borchiellini Alessandra investigator.; Messina Maria investigator.; Feola Giulio investigator.; Gandini Giorgio investigator.; Giuffrida Anna Chiara investigator.;
• Is Part Of: Haemophilia. Volume 28:Issue 1(2022)
• Page Start: 55
• Page End: 64
• Publication Date: 2021-11-02
• Subjects: bleeding -- haemophilia A -- inhibitors -- ITI -- poor‐prognosis patients; Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.14431
• Languages: English
• ISSNs: 1351-8216

Abstract

Abstract: Background: Immune tolerance induction (ITI) is the only proven strategy to eradicate factor VIII inhibitors in patients with haemophilia A (HA). Aim: To identify patients and treatment options with the highest chance of inhibitor eradication by primary ITI. Patients and methods: In the frame of the Italian ITI Registry, carried out from 1995 to 2015 (last follow‐up 2018), 137 primary ITI courses in severe HA patients (90/137 with poor prognosis) were analysed for predictors of outcome (complete/partial response or failure). Sixty‐six of them (48%) were prospectively evaluated. Results: ITI was successful in 91/137 patients (66.4%) and 70 (51.1%) achieved complete response within 11 months (median). Historical peak titres ≤200 BU/ml ( P = .033), inhibitor titres ≤5 BU/ml at ITI start ( P = .001), peak titres ≤100 BU/ml during ITI ( P < .001) and missense mutations and small insertions/deletions of FVIII gene ( P = .027) predicted complete inhibitor eradication. A score that considers the cumulative number of these variables predicted complete response with positive predictive values up to .81 at ITI start and .91 during ITI, respectively. Patients who had no bleeding (OR, 3.45, 95% CI: 1.4–8.6) nor other adverse events (OR 2.6, 95%CI: 1.3–5.3) during ITI had higher chances of complete response. During the 120‐month follow‐up (median), 2/70 patients who had achieved complete response relapsed (2.9%). Conclusions: This Registry, with a centralized review of outcomes, homogeneous data collection (half of which prospective) and long‐term follow‐up, provides insights for optimizing ITI, with a rationale for further studies in the currently evolving scenario of inhibitor management in HA patients.