Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Selective Activation of Naturally Occurring Regulatory T Cells (Tregs) by the Monoclonal Antibody (mAb) BT-061. Markers of Clinical Activity and Early Phase II Results in Patients with Rheumatoid Arthritis (RA).

Rudnev1,  Anatoliy, Ragavan6,  Sukanya, Trollmo6,  Christina, Malmstroem6,  Vivianne, Becker5,  Christian, Jonuleit5,  Helmut, Strand7,  Vibeke

Biotest AG, Dreieich, Germany
Botkin Clinical Hospital, Moscow, Russian Federation
City Clinical Hospital Nr. 23 n.a. Medsantrud, Moscow, Russian Federation
Clinical Hospital for Emergency Medical Care, Yaroslavl, Russian Federation
Johannes-Gutenberg University, Mainz, Germany
Karolinska Institute, Stockholm, Sweden
Stanford University, Portola Valley, CA

Naturally occurring Tregs are essential for maintaining normal immune homeostasis in healthy individuals. In patients with autoimmune diseases reduced numbers or functional impairment of Tregs has been observed. A humanized agonistic mAb, BT-061 selectively activates Tregs. It binds to a unique epitope of the CD4 molecule, leading to induction of Treg specific signaling events. While freshly isolated and resting Tregs do not inhibit T cell proliferation, pre-treatment of Tregs with BT-061 leads to suppression of CD4 and CD8 T effector cell proliferation, reduction of pro-inflammatory cytokines and a moderate increase in the anti-inflammatory cytokine TGF-beta.

To further assess the potential of BT-061 to modulate immune responses, in vitro studies with synovial fluid derived mononuclear cells from patients with active RA were performed. Addition of BT-061 at concentrations between 0.01 and 50 micro g/mL to isolated CD4-positive cells derived from the highly inflammatory milieu of RA synovial fluid suppressed proliferation as well as IFN-gamma production following antigen-specific stimulation.

In a Phase I/IIa trial in patients with psoriasis, a single dose of BT-061 resulted in PASI 50/75 responses for up to 90 days at doses of 0.5, 2.5, 10, 20 mg iv and 12.5, 25 mg sc. A Phase IIa, multicenter, randomized placebo-controlled trial with BT-061 monotherapy was performed in 96 patients with active RA and inadequate responses to one or more traditional DMARD despite 3 months or more of treatment. Patients were randomized to 12 treatment groups: from 1.25 – 100 mg sc, or 0.5 – 25 mg iv, once weekly for 6 weeks: 6 patients received BT-061 and 2 received placebo in each group.

Initial data analysis confirmed the clinical activity of BT-061 by ACR20/50/70 responses in a meaningful proportion of patients despite the short duration of therapy. No major safety signals were identified. Final analyses of safety and efficacy data are ongoing and will be presented.

Phase II multiple dose trials with BT-061 are underway to further evaluate the clinical benefit of BT-061 in patients with RA and psoriasis.

To cite this abstract, please use the following information:
Rudnev, Anatoliy, Ragavan, Sukanya, Trollmo, Christina, Malmstroem, Vivianne, Becker, Christian, Jonuleit, Helmut, et al; Selective Activation of Naturally Occurring Regulatory T Cells (Tregs) by the Monoclonal Antibody (mAb) BT-061. Markers of Clinical Activity and Early Phase II Results in Patients with Rheumatoid Arthritis (RA). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1125
DOI: 10.1002/art.28892

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