title: Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren's syndrome: an open-label phase I/II study.
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 > or = 20% improvement in at least two of the aforementioned parameters, with > or = 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 > or = 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 > or = 30% level, while 10%-45% responded at the > or = 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.
authors.affiliation: Department of Rheumatology, Erasme University Hospital, 808 Route de Lennik, Brussels 1070, Belgium. ssteinfe@ulb.ac.be
authors.forename: Serge D
authors.initials: SD
authors.lastname: Steinfeld
authors.forename: Laure
authors.initials: L
authors.lastname: Tant
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Nick K W
authors.initials: NK
authors.lastname: Teoh
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Olivier
authors.initials: O
authors.lastname: Pradier
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001799:Blood Sedimentation; D015536:Down-Regulation; D004334:Drug Administration Schedule; D005221:Fatigue / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007262:Infusions, Intravenous; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D051918:Sialic Acid Binding Ig-like Lectin 2; C448700:epratuzumab