Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus

Department of Medicine/Rheumatology and Clinical Immunology, Charite Hospital, Berlin, Germany.
Arthritis research & therapy (Impact Factor: 4.12). 04/2006; 8(3):R74. DOI: 10.1186/ar1942
Source: PubMed

ABSTRACT B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE), so the safety and activity of anti-B cell immunotherapy with the humanized anti-CD22 antibody epratuzumab was evaluated in SLE patients. An open-label, single-center study of 14 patients with moderately active SLE (total British Isles Lupus Assessment Group (BILAG) score 6 to 12) was conducted. Patients received 360 mg/m2 epratuzumab intravenously every 2 weeks for 4 doses with analgesic/antihistamine premedication (but no steroids) prior to each dose. Evaluations at 6, 10, 18 and 32 weeks (6 months post-treatment) follow-up included safety, SLE activity (BILAG score), blood levels of epratuzumab, B and T cells, immunoglobulins, and human anti-epratuzumab antibody (HAHA) titers. Total BILAG scores decreased by > or = 50% in all 14 patients at some point during the study (including 77% with a > or = 50% decrease at 6 weeks), with 92% having decreases of various amounts continuing to at least 18 weeks (where 38% showed a >/= 50% decrease). Almost all patients (93%) experienced improvements in at least one BILAG B- or C-level disease activity at 6, 10 and 18 weeks. Additionally, 3 patients with multiple BILAG B involvement at baseline had completely resolved all B-level disease activities by 18 weeks. Epratuzumab was well tolerated, with a median infusion time of 32 minutes. Drug serum levels were measurable for at least 4 weeks post-treatment and detectable in most samples at 18 weeks. B cell levels decreased by an average of 35% at 18 weeks and remained depressed at 6 months post-treatment. Changes in routine safety laboratory tests were infrequent and without any consistent pattern, and there was no evidence of immunogenicity or significant changes in T cells, immunoglobulins, or autoantibody levels. In patients with mild to moderate active lupus, 360 mg/m2 epratuzumab was well tolerated, with evidence of clinical improvement after the first infusion and durable clinical benefit across most body systems. As such, multicenter controlled studies are being conducted in broader patient populations.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, characterized by impaired function of the exocrine glands. Many pSS patients also experience extraglandular symptoms. Effective therapeutic interventions for pSS patients are not yet approved. However, advances in understanding of the disease process have led to the development of promising therapeutic targets.Areas covered: This review provides an overview of current and presumed future strategies for the treatment of extraglandular symptoms in pSS patients, in relation to pathogenesis of the disease. In addition, future approaches for the evaluation of these symptoms in clinical trials will be discussed.Expert opinion: Of all clinical trials that have been conducted in pSS, only few evaluated the effect of treatment on extraglandular symptoms. This lack of data can be partially explained by: i) heterogeneity of extraglandular symptoms; ii) inclusion of patients with low systemic disease activity in clinical trials; and iii) the former lack of a validated outcome measure to evaluate the systemic disease activity. These methodological issues should be addressed in future clinical trials. The ultimate goal in the management of pSS is evidence-based and personalized treatment of the broad range of symptoms experienced by patients suffering from this disease, including extraglandular symptoms.
    02/2015; 3(2). DOI:10.1517/21678707.2015.1010510
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disorder with severe morbidity and mortality and diverse systemic involvement. Disease onset occurs during childhood in approximately 15 % of patients with SLE. It is important to treat the attacks adequately and prevent further flares for favorable long-term outcomes. The aim of effective disease management with early immunosuppression is to achieve symptomatic resolution and improvement in the quality of life by maintaining sustained remission and thereby preventing tissue damage. Adult literature on SLE management has evolved considerably over the past few decades based on observations from clinical studies investigating different immunosuppressive agents. We lack well-designed randomized controlled trials in children with SLE, thus we mainly depend on adult literature. Here, we review the literature for the current management of SLE in children and we present the recommendations and suggestions with the level of evidence.
    Current Rheumatology Reports 03/2015; 17(3):489. DOI:10.1007/s11926-014-0489-5 · 2.45 Impact Factor
  • 03/2009; 16(1):76-96. DOI:10.1016/S0121-8123(09)70120-3

Preview (3 Sources)

1 Download
Available from