Epratuzumab humanised anti-CD22 antibody in primary Sjögrens syndrome: an open-label phase I-II studyReportar como inadecuado




Epratuzumab humanised anti-CD22 antibody in primary Sjögrens syndrome: an open-label phase I-II study - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 8:R129

First Online: 20 July 2006Received: 09 May 2006Revised: 16 June 2006Accepted: 20 July 2006

Abstract

This open-label, phase I-II study investigated the safety and efficacy of epratuzumab, a humanised anti-CD22 monoclonal antibody, in the treatment of patients with active primary Sjögren-s syndrome pSS. Sixteen Caucasian patients 14 females-2 males, 33–72 years were to receive 4 infusions of 360 mg-m epratuzumab once every 2 weeks, with 6 months of follow-up. A composite endpoint involving the Schirmer-I test, unstimulated whole salivary flow, fatigue, erythrocyte sedimentation rate ESR, and immunoglobulin G IgG was devised to provide a clinically meaningful assessment of response, defined as a ≥20% improvement in at least two of the aforementioned parameters, with ≥20% reduction in ESR and-or IgG considered as a single combined criterion. Fourteen patients received all infusions without significant reactions, 1 patient received 3, and another was discontinued due to a mild acute reaction after receiving a partial infusion. Three patients showed moderately elevated levels of Human anti-human epratuzumab antibody not associated with clinical manifestations. B-cell levels had mean reductions of 54% and 39% at 6 and 18 weeks, respectively, but T-cell levels, immunoglobulins, and routine safety laboratory tests did not change significantly. Fifty-three percent achieved a clinical response at ≥20% improvement level at 6 weeks, with 53%, 47%, and 67% responding at 10, 18, and 32 weeks, respectively. Approximately 40%–50% responded at the ≥30% level, while 10%–45% responded at the ≥50% level for 10–32 weeks. Additionally, statistically significant improvements were observed in fatigue, and patient and physician global assessments. Further, we determined that pSS patients have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy. Thus, epratuzumab appears to be a promising therapy in active pSS, suggesting that further studies be conducted.

AbbreviationsACR= American College of Rheumatology

AE= adverse event

ANA= antinuclear antibody

APC= allophycocyanin

AT= artificial tear

BCR= B-cell antigen receptor

CRP= C-reactive protein

CTC= National Cancer Institute Common Toxicity Criteria

ELISA= enzyme-linked immunosorbent assay

ESR= erythrocyte sedimentation rate

HACA= human anti-chimeric antibody

HAHA= human anti-human epratuzumab antibody

Ig= immunoglobulin

NHL= non-Hodgkin-s lymphoma

PE= phycoerythrin

pSS= primary Sjögren-s syndrome

RF= rheumatoid factor

SD= standard deviation

SLE= systemic lupus erythematosus

USF= unstimulated whole salivary flow

VAS= visual analogue scale.

Electronic supplementary materialThe online version of this article doi:10.1186-ar2018 contains supplementary material, which is available to authorized users.

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Autor: Serge D Steinfeld - Laure Tant - Gerd R Burmester - Nick KW Teoh - William A Wegener - David M Goldenberg - Olivier Pr

Fuente: https://link.springer.com/







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