Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a phase IIb, randomised, placebo-controlled trial

Annals of the Rheumatic Diseases

Volumn 77, Issue 4, 2018, Pages 495-499

  Van Vollenhoven, Ronald F ^a   Keystone, Edward Clark ^b   Strand, Vibeke ^c   Pacheco Tena, Cesar ^d   Vencovský, Jiří ^e   Behrens, Frank ^f   Racewicz, Arthur ^g   Zipp, Daniela ^h   Rharbaoui, Faiza ^h   Wolter, Ralf ^h   Knierim, Luise ^h   Schmeidl, Rainer ^h   Zhou, Xuefei ^h   Aigner, Silke ^h   Dälken, Benjamin ^h   Wartenberg Demand, Andrea ^h  

^a The Amsterdam Rheumatology and Immunology Center ARC   (Netherlands)

^b MOUNT SINAI HOSPITAL   (Canada)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d Investigacion y Biomedicina de Chihuahua   (Mexico)

^e INSTITUTE OF RHEUMATOLOGY   (Czech Republic)

^f GOETHE UNIVERSITY   (Germany)

^g ZDROWIE Osteo Medic   (Poland)

^h BIOTEST AG   (Germany)

Author keywords

autoimmune diseases; Dmards (biologic); rheumatoid arthritis; t cells

Indexed keywords

METHOTREXATE; PLACEBO; TREGALIZUMAB; ANTIRHEUMATIC AGENT; CD4 ANTIGEN; IMMUNOGLOBULIN G; MONOCLONAL ANTIBODY;

ADVERSE EVENT; ANTIGENIC MODULATION; ARTICLE; BIOLOGICAL ACTIVITY; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ENDOCRINE DISEASE; GASTROINTESTINAL DISEASE; HEMATOLOGIC DISEASE; HUMAN; INFECTION; INJECTION SITE REACTION; INJURY; INTOXICATION; MAJOR CLINICAL STUDY; MULTICENTER STUDY; MUSCULOSKELETAL DISEASE; NEUROLOGIC DISEASE; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; SIDE EFFECT; SKIN DISEASE; VASCULAR DISEASE; ADOLESCENT; ADULT; AGED; CLINICAL TRIAL; DRUG EFFECT; FEMALE; IMMUNOLOGY; IMMUNOMODULATION; MALE; MIDDLE AGED; SEVERITY OF ILLNESS INDEX; SUBCUTANEOUS DRUG ADMINISTRATION; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; CD4 ANTIGENS; DOUBLE-BLIND METHOD; FEMALE; HUMANS; IMMUNOGLOBULIN G; IMMUNOMODULATION; INJECTIONS, SUBCUTANEOUS; MALE; METHOTREXATE; MIDDLE AGED; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME; YOUNG ADULT;

EID: 85044241799     PISSN: 00034967     EISSN: 14682060     Source Type: Journal    
DOI: 10.1136/annrheumdis-2017-212478     Document Type: Article

References (20)

1. Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis. Lancet 2009;373:659-72.
2. McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet 2017;389:2328-37.
3. E hrenstein MR, Evans JG, Singh A, et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med 2004;200:277-85.
4. Cribbs AP, Kennedy A, Penn H, et al. Methotrexate restores regulatory T Cell function through demethylation of the FoxP3 upstream enhancer in patients with rheumatoid arthritis. Arthritis Rheumatol 2015;67:1182-92.
5. Álvarez-Quiroga C, Abud-Mendoza C, Doníz-Padilla L, et al. CTLA-4-Ig therapy diminishes the frequency but enhances the function of Treg cells in patients with rheumatoid arthritis. J Clin Immunol 2011;31:588-95.
6. Bonelli M, Göschl L, Blüml S, et al. Abatacept (CTLA-4Ig) treatment reduces T cell apoptosis and regulatory T cell suppression in patients with rheumatoid arthritis. Rheumatology 2016;55:710-20.
7. P icchianti Diamanti A, Rosado MM, Scarsella M, et al. Abatacept (cytotoxic T lymphocyte antigen 4-immunoglobulin) improves B cell function and regulatory T cell inhibitory capacity in rheumatoid arthritis patients non-responding to anti-tumour necrosis factor-agents. Clin Exp Immunol 2014;177:630-40.
8. McGovern JL, Nguyen DX, Notley CA, et al. Th17 cells are restrained by Treg cells via the inhibition of interleukin-6 in patients with rheumatoid arthritis responding to antitumor necrosis factor antibody therapy. Arthritis Rheum 2012;64:3129-38.
9. T hiolat A, Semerano L, Pers YM, et al. Interleukin-6 receptor blockade enhances CD39+ regulatory T cell development in rheumatoid arthritis and in experimental arthritis. Arthritis Rheumatol 2014;66:273-83.
10. P ericolini E, Gabrielli E, Alunno A, et al. Functional improvement of regulatory T cells from rheumatoid arthritis subjects induced by capsular polysaccharide glucuronoxylomannogalactan. PLoS One 2014;9:e111163.
11. König M, Rharbaoui F, Aigner S, et al. Tregalizumab-a monoclonal antibody to target regulatory T cells. Front Immunol 2016;7:11.
12. Humblet-Baron S, Baron F. Tregalizumab (BT-061) increases regulatory T cell function. Boosting regulatory T-cell function with the humanized CD4-specific humanized monoclonal antibody Tregalizumab (BT-061). Immunol Cell Biol 2015;93:321-2.
13. Helling B, König M, Dälken B, et al. A specific CD4 epitope bound by tregalizumab mediates activation of regulatory T cells by a unique signaling pathway. Immunol Cell Biol 2015;93:396-405.
14. Felson DT, Anderson JJ, Boers M, et al. American College of rheumatology. preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727-35.
15. Fransen J, Creemers MC, Van Riel PL. Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria. Rheumatology 2004;43:1252-5.
16. S molen JS, Aletaha D. Scores for all seasons: SDAI and CDAI. Clin Exp Rheumatol 2014;32.
17. Walter GJ, Fleskens V, Frederiksen KS, et al. Phenotypic, functional, and gene expression profiling of peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127(low) treg cells in patients with chronic rheumatoid arthritis. Arthritis Rheumatol 2016;68:103-16.
18. R apetti L, Chavele KM, Evans CM, et al. B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by regulatory T cells in rheumatoid arthritis. Ann Rheum Dis 2015;74:294-302.
19. Heim K, Dälken B, Faust S, et al. High thioredoxin-1 levels in rheumatoid arthritis patients diminish binding and signalling of the monoclonal antibody Tregalizumab. Clin Transl Immunology 2016;5:e121.
20. Abufarag A, Aigner S, Czeloth N, et al. Selective activation of naturally occurring regulatory T cells (Tregs) by the monoclonal antibody BT-061 as a novel therapeutic opportunity in psoriasis: early clinical results after single doses. J Invest Dermatol 2010;130:S64.