Elsevier

Autoimmunity Reviews

Volume 12, Issue 11, September 2013, Pages 1085-1090
Autoimmunity Reviews

Review
Rituximab use in the catastrophic antiphospholipid syndrome: Descriptive analysis of the CAPS registry patients receiving rituximab

https://doi.org/10.1016/j.autrev.2013.05.004Get rights and content

Abstract

The catastrophic variant of the antiphospholipid syndrome (APS) is characterized by thrombosis in multiple organs developing over a short period of time. First-line treatment for the catastrophic APS is the combination of anticoagulation plus corticosteroids plus plasma exchange and/or intravenous immunoglobulin. Despite this regimen, the mortality remains high and new treatment options are needed. By a systematic review of the Catastrophic APS Registry (CAPS Registry), we identified 20 patients treated with rituximab. The purpose of this study is to describe the clinical manifestations, laboratory features, and outcomes of rituximab-treated CAPS patients. In addition, the rationale for using rituximab in catastrophic APS is discussed.

Introduction

The antiphospholipid syndrome (APS) is characterized by venous and arterial thrombosis and/or pregnancy morbidity occurring in patients with persistently positive antiphospholipid (aPL) antibodies [1]. The catastrophic variant of the APS is characterized by thrombosis in multiple organs developing over a short period of time [2].

Unfortunately, the current knowledge of the pathogenic mechanisms of this variant of APS is scarce in part due to the lack of studies on the pathophysiological mechanisms of catastrophic APS. In this context, it has been hypothesized that some of the features of catastrophic APS may be due to the development of systemic inflammatory response syndrome (SIRS), which are presumed to be due to excessive cytokine release from injured tissues [3].

Besides identification and treatment of any precipitating factor, the current treatment of catastrophic APS is based on two underlying pathophysiologic events, thrombosis and SIRS. First line therapies include the combination of anticoagulation (AC) against thrombosis plus glucocorticoids (GCs) against manifestations of SIRS plus plasma exchange (PE) and/or intravenous immunoglobulins (IVIGs) against both aPL and SIRS [4]. Our group demonstrated that the combined treatment of AC plus GC plus PE followed by AC plus GC plus PE and/or IVIG achieved the higher recovery rate [5].

Despite this reduction of mortality from 53% in patients diagnosed before 2001 to 33% in those diagnosed between 2001 and February 2005 (p < 0.005), refractory patients who die despite first-line treatments or those suffering from recurrent episodes of catastrophic APS exist. Due to the existence of these refractory cases, other medications such as rituximab have been used together with conventional combined therapy [6].

Rituximab is a chimeric monoclonal antibody against a surface antigen expressed by the B cells named CD20. Rituximab is approved for relapsed or refractory CD20+, B-cell non-Hodgkin lymphoma and rheumatoid arthritis [7] and it may play a role in the treatment of autoimmune diseases. Although, two randomized controlled trials failed to demonstrate its effectiveness as add-on therapy in SLE [8], [9], the global analysis of all cases reported to date supports the off-label use of rituximab in severe, refractory SLE cases, whereas its use as a first-line therapy or in patients with a predominantly mild form of the disease is not advised [10].

Regarding APS, a recent open label phase II trial has shown the safety of rituximab use in patients with APS and some benefits in controlling non-criteria manifestations such as thrombocytopenia, skin ulcers, nephropathy, and cognitive dysfunction [11]. Moreover, Erre et al. [12] described 12 patients with primary and SLE-associated APS who were treated with rituximab.

The aim of this review is to describe the clinical manifestations, laboratory features, and outcome of patients with catastrophic APS treated with rituximab. In addition, the rationale for using rituximab in catastrophic APS is discussed.

Section snippets

Data collection

We reviewed the web-based international Catastrophic APS Registry (“CAPS Registry”) for rituximab-treated patients. This registry was created by the European Forum on Antiphospholipid Antibodies, a study group devoted to the development of multicenter projects with large populations of APS patients. The source of information for the CAPS Registry is: a) periodic Medline search of published CAPS reports; and b) personal communication with physicians of CAPS patients for the unpublished cases

General characteristics

Of the 441 patients included in the “CAPS Registry” as of May 2013, 20 (4.6%) were treated with rituximab. Ten patients were previously published [13], [14], [15], [16], [17], [18], [19], [20], [21] and 10 additional patients were identified based on personal communications. The main demographic features, precipitating factors, and clinical manifestations are depicted in Table 1. In 6 (30%) patients, the catastrophic event was the first manifestation of APS.

In nine (45%) patients, precipitating

Discussion

Based on our review of the CAPS-registry, rituximab may have a role in the management of catastrophic APS patients; however, the study design and the limited number of patients included did not allow us to complete a detailed effectiveness and safety analysis.

In SLE patients, rituximab substantially reduces CD20+ B-cell levels in peripheral blood within days to weeks for up to 6 months. In fact, the effect of rituximab in SLE patients was closely associated with a reduction in anti-dsDNA and

Take-home messages

  • The combined treatment of anticoagulation plus glucocorticoids plus plasma exchange and/or intravenous immunoglobulins achieves the higher recovery rate in patients with catastrophic APS.

  • Despite the reduction of mortality, there are some refractory patients, such as those who die despite first-line treatments or those suffering from recurrent episodes of catastrophic APS.

  • In this review, 20 patients with catastrophic APS treated with rituximab were described.

  • Regarding the effectiveness of

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  • Cited by (185)

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    See complete list of members of the CAPS Registry at the end of the article.

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