4.6 Article

The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura

Journal

BRITISH JOURNAL OF HAEMATOLOGY
Volume 198, Issue 2, Pages 391-396

Publisher

WILEY
DOI: 10.1111/bjh.18192

Keywords

obinutuzumab; ofatumumab; relapse; rituximab; thrombotic thrombocytopenic purpura (TTP)

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Obinutuzumab and ofatumumab may be considered as alternative options to rituximab in the treatment of iTTP, with a comparable safety profile, absence of significant hypersensitivity reactions, and sustained normalization of ADAMTS13.
Rituximab, an anti-CD20 monoclonal antibody, can be used to treat immune thrombotic thrombocytopenic purpura (iTTP) during acute presentation or disease relapse. Undesirable side-effects include severe hypersensitivity reactions, particularly anaphylaxis and rituximab-induced serum sickness, with a minority not maintaining a response to treatment. Alternative humanised anti-CD20 treatments, obinutuzumab and ofatumumab, have been used. A review of the UK TTP Registry showed 15 patients received these drugs over 26 treatment episodes (eight obinutuzumab and 18 ofatumumab). Indications for alternative anti-CD20 treatment were severe infusion-related reactions, acute rituximab-induced serum sickness and a short duration of disease remission. All patients achieved disease remission (ADAMTS13 [A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13] activity >= 30 iu/dl) after a median 15 days and 92% of episodes achieved complete remission (>= 60 iu/dl). Seven patients required further treatment for disease relapse with a median relapse-free survival of 17.4 months. All patients continued to respond to re-treatment with the preceding drug when relapse occurred. There were four adverse events in 26 treatment episodes (15%) - two infections and two infusion reactions. These results suggest that obinutuzumab and ofatumumab may be considered as an alternative option to rituximab in the treatment of iTTP with a comparable safety profile, absence of significant hypersensitivity reactions and sustained normalisation of ADAMTS13.

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