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Arthritis Res Ther. 2006; 8(4): R129.
Published online Jul 20, 2006. doi:  10.1186/ar2018
PMCID: PMC1779377
Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren's syndrome: an open-label phase I/II study
Serge D Steinfeld,corresponding author1 Laure Tant,1 Gerd R Burmester,2 Nick KW Teoh,3 William A Wegener,3 David M Goldenberg,3 and Olivier Pradier4
1Department of Rheumatology, Erasme University Hospital, 808 Route de Lennik, Brussels 1070, Belgium
2Department of Rheumatology, Charite Hospital, Schumannstr 20-21, Berlin D-10098, Germany
3Immunomedics, Inc., Morris Plains, 300 American Road, New Jersey 07950, USA
4Laboratory of Hematology, Erasme University Hospital, 808 Route de Lennik, Brussels 1070, Belgium
corresponding authorCorresponding author.
Serge D Steinfeld: ssteinfe/at/ulb.ac.be; Laure Tant: ltant/at/ulb.ac.be; Gerd R Burmester: gerd.burmester/at/charite.de; Nick KW Teoh: nteoh/at/immunomedics.com; William A Wegener: bwegener/at/immunomedics.com; David M Goldenberg: dmg/at/immunomedics.com; Olivier Pradier: opradier/at/ulb.ac.be
Received May 9, 2006; Revisions requested June 8, 2006; Revised June 16, 2006; Accepted July 20, 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/m2 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.
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