Toxic interactions of Romiplostim and Rituximab in normal and thrombocytopenic Rats

Saeed H,Nahla S Kotb,Sayed H.M,Ramadan A

doi:10.21608/javs.2019.20470.1000

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immunologic destruction of normal platelets and insufficient production of platelets, as mediated by autoantibodies. Because of the progression of the disease and its multiple causes a combination of treatments used for management of ITP would be a point of interest. Co-administration of therapies may be useful in patients who are refractory to monotherapies and may result in a booster response because they target multiple mechanisms. Romiplostim is a potent drug used for the management of acute ITP and used in combination with other treatment options for ITP. The combination of Rituximab and Romiplostim may inhibit platelet destruction and at the same time increase platelet production. This combination can lead to a strong and a massive increase in platelet counts. In Preclinical studies of Romiplostim safety margins could not be reliably estimated. Although some clinical studies provided some information about the safety profile of this drug. The goal of this study is to investigate the safety of co-treatment of Romiplostim with Rituximab as compared to each of these drugs in normal and thrombocytopenic rats. The measured safety parameter was evaluated for the liver and kidney function in normal and diseased rats. The safety of this regimen should be taken in consideration, so that a balance between the harmful effects and beneficial response could be attained. Future studies are necessary to investigate the safety and efficacy balance of Romiplostim and Rituximab alone or in combination with each other for management of thrombocytopenia.

Highlights

The disease is most widely accepted the abbreviation, Immune thrombocytopenia (ITP), has variably been defined as “immune thrombocytopenic purpura”, “idiopathic thrombocytopenic purpura” and most recently “immune thrombocytopenia”
The measured safety parameters were evaluated for liver and kidney functions in normal and diseased groups of rats.The safety of this regimen should be taken in consideration, so that a balance between the harmful effects and beneficial response could be attained
Immune thrombocytopenia is associated with several chronic infections including Helicobacter pylori (HP), human immunodeficiency virus (HIV), autoimmune diseases, such as systemic lupus erythematosus (SLE) and hepatitis C virus (HCV)

Summary

Introduction

The disease is most widely accepted the abbreviation, ITP, has variably been defined as “immune thrombocytopenic purpura”, “idiopathic thrombocytopenic purpura” and most recently “immune thrombocytopenia”. It is an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets most commonly occurring in response to an unknown stimulus. ITP may occur in isolation (primary) or in association with other disorders (secondary).The International Working Group (IWG) defines ITP as newly diagnosed (diagnosis to 3 months), persistent (3 to 12 months from diagnosis), or chronic (lasting for more than 12 months) (Neunert et al, 2011). Immune thrombocytopenia is associated with several chronic infections including Helicobacter pylori (HP), human immunodeficiency virus (HIV), autoimmune diseases, such as systemic lupus erythematosus (SLE) and. The supposed mechanism is molecular mimicry, resulting in cross-reactive antibodies between bacterial and platelet antigens (Raj, 2017)

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