Efficacy and safety of belimumab in patients with rheumatoid arthritis: A phase II, randomized, double-blind, placebo-controlled, dose-ranging study

Journal of Rheumatology

Volumn 40, Issue 5, 2013, Pages 579-589

  Stohl, William ^a   Merrill, Joan T ^b   McKay, James D ^c   Lisse, Jeffrey R ^d   Zhong, Z John ^e   Freimuth, William W ^e   Genovese, Mark C ^e  

^a LAC USC MEDICAL CENTER   (United States)

^b OKLAHOMA MEDICAL RESEARCH FOUNDATION   (United States)

^c Oklahoma Center for Arthritis Therapy and Research   (United States)

^d UNIVERSITY OF ARIZONA   (United States)

^e STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Autoimmune diseases; B lymphocyte stimulator; Belimumab; Rheumatoid arthritis

Indexed keywords

BELIMUMAB; C REACTIVE PROTEIN; CYCLIC CITRULLINATED PEPTIDE ANTIBODY; DISEASE MODIFYING ANTIRHEUMATIC DRUG; IMMUNOGLOBULIN A; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; NONSTEROID ANTIINFLAMMATORY AGENT; PLACEBO; PREDNISONE; RHEUMATOID FACTOR; TUMOR NECROSIS FACTOR INHIBITOR;

ADULT; ANGIONEUROTIC EDEMA; ARTHRALGIA; ARTICLE; B LYMPHOCYTE; BREAST CANCER; CONNECTIVE TISSUE DISEASE; CONTROLLED STUDY; DISEASE ACTIVITY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG FATALITY; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; ERYTHEMA; FACE EDEMA; FEMALE; FLUSHING; HUMAN; HYPERGLYCEMIA; IMMUNOGLOBULIN BLOOD LEVEL; INFECTION; INFUSION RELATED REACTION; LUNG SQUAMOUS CELL CARCINOMA; LYMPHOCYTE; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; MULTICENTER STUDY; MUSCULOSKELETAL DISEASE; NON MELANOMA SKIN CANCER; OPEN STUDY; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; SCORING SYSTEM; SIDE EFFECT; SKIN CARCINOMA; SOLID TUMOR; UNSPECIFIED SIDE EFFECT; UPPER RESPIRATORY TRACT INFECTION; URTICARIA; VULVA CANCER;

AUTOIMMUNE DISEASES; B LYMPHOCYTE STIMULATOR; BELIMUMAB; RHEUMATOID ARTHRITIS;

ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SUBSTITUTION; FEMALE; HUMANS; JOINTS; MALE; MIDDLE AGED; SYMPTOM ASSESSMENT; TREATMENT OUTCOME;

EID: 84876889502     PISSN: 0315162X     EISSN: 14992752     Source Type: Journal    
DOI: 10.3899/jrheum.120886     Document Type: Article

References (41)

1. Nam JL, Winthrop KL, van Vollenhoven RF, Pavelka K, Valesini G, Hensor EM, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: A systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis 2010;69:976-86.
2. Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet 2010;376:1094-108.
3. Smolen JS, Landewé R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010;69:964-75.
4. Morgan C, Lunt M, Brightwell H, Bradburn P, Fallow W, Lay M, et al. Contribution of patient related differences to multidrug resistance in rheumatoid arthritis. Ann Rheum Dis 2003;62:15-9. (Pubitemid 36005789)
5. Weyand CM, Seyler TM, Goronzy JJ. B cells in rheumatoid synovitis. Arthritis Res Ther 2005;7 Suppl 3:S9-12.
6. Berglin E, Johansson T, Sundin U, Jidell E, Wadell G, Hallmans G, et al. Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset. Ann Rheum Dis 2006;65:453-8.
7. Bukhari M, Lunt M, Harrison BJ, Scott DG, Symmons DP, Silman AJ. Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis: Results from the Norfolk Arthritis Register Study, a large inception cohort. Arthritis Rheum 2002;46:906-12. (Pubitemid 34303801)
8. Meyer O, Labarre C, Dougados M, Goupille P, Cantagrel A, Dubois A, et al. Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage. Ann Rheum Dis 2003;62:120-6. (Pubitemid 36135386)
9. Rantapää-Dahlqvist S, de Jong BAW, Berglin E, Hallmans G, Wadell G, Stenlund H, et al. Antibodies against citric citrullinated peptide (CCP) and immunoglobulin-A rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 2003;10:2741-9. (Pubitemid 37280601)
10. Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, et al; for the REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006;54:2793-806. (Pubitemid 44497758)
11. Cohen SB, Keystone E, Genovese MC, Emery P, Peterfy C, Tak PP, et al. Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate. Ann Rheum Dis 2010;69:1158-61.
12. Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science 1999;285:260-3. (Pubitemid 29330000)
13. Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med 1999;189:1747-56. (Pubitemid 29272691)
14. Laabi Y, Gras M-P, Brouet J-C, Berger R, Larsen C-J, Tsapis A. The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed. Nucleic Acids Res 1994;22:1147-54. (Pubitemid 24162116)
15. Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, et al. BAFF-R, a novel TNF receptor that specifically interacts with BAFF. Science 2001;293:2108-11. (Pubitemid 32848062)
16. von Bülow G-U, Bram RJ. NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily. Science 1997;278:138-41. (Pubitemid 27446295)
17. Yan M, Brady JR, Chan B, Lee WP, Hsu B, Harless S, et al. Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency. Curr Biol 2001;11:1547-52. (Pubitemid 32931019)
18. Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum 2001;44:1313-9. (Pubitemid 32537529)
19. Tan SM, Xu D, Roschke V, Perry JW, Arkfeld DG, Ehresmann GR, et al. Local production of B-lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis. Arthritis Rheum 2003;48:982-92. (Pubitemid 36418240)
20. Zhang J, Roschke V, Baker K, Wang Z, Alarcón GS, Fessler BJ, et al. Cutting edge: A role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol 2001;166:6-10. (Pubitemid 32038409)
21. Bosello S, Youinou P, Daridon C, Tolusso B, Bendaoud B, Pietrapertosa D, et al. Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis. J Rheumatol 2008;35:1256-64. (Pubitemid 352000768)
22. La DT, Collins CE, Yang H-T, Migone T-S, Stohl W. B lymphocyte stimulator expression in patients with rheumatoid arthritis treated with tumour necrosis factor α antagonists: Differential effects between good and poor clinical responders. Ann Rheum Dis 2008;67:1132-8.
23. Gross J, Dillon S, Mudri S, Johnston J, Littau A, Roque R, et al. TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. Impaired B cell maturation in mice lacking BLyS. Immunity 2001;15:289-302. (Pubitemid 32816877)
24. Wang H, Marsters SA, Baker T, Chan B, Lee WP, Fu L, et al. TACI-ligand interactions are required for T cell activation and collagen-induced arthritis in mice. Nat Immunol 2001;2:632-7. (Pubitemid 32677631)
25. Cancro MP. Signalling crosstalk in B-cells: Managing worth and need. Nat Rev Immunol 2009;9:657-61.
26. Baker KP, Edwards BM, Main SH, Choi GH, Wager RE, Halpern WG, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum 2003;48:3253-65. (Pubitemid 37409340)
27. Furie R, Stohl W, Ginzler EM, Becker M, Mishra N, Chatham W, et al. Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: A phase I trial in patients with systemic lupus erythematosus. Arthritis Res Ther 2008;10:R109.
28. Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum 2011;63:3918-30.
29. Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: A randomised, placebo-controlled, phase 3 trial. Lancet 2011;377:721-31.
30. Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT, et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum 2009;61:1168-78.
31. Stohl W, Hiepe F, Latinis KM, Thomas M, Scheinberg MA, Clarke A, et al. Belimumab reduces autoantibodies, normalizes low complement, and reduces select B-cell populations in patients with systemic lupus erythematosus. Arthritis Rheum 2012;64:2328-37.
32. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology. Preliminary definitions of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727-35.
33. Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44-8.
34. van Riel PL, van Gestel AM, van de Putte LB. Development and validation of response criteria in rheumatoid arthritis: Steps towards an international consensus on prognostic markers. Br J Rheumatol 1996;35 Suppl 2:4-7.
35. Genant HK, Jiang Y, Peterfy C, Lu Y, Redei J, Countryman PJ. Assessment of rheumatoid arthritis using a modified scoring method on digitized and original radiographs. Arthritis Rheum 1998;41:1583-90. (Pubitemid 28459916)
36. National Institute of Allergy and Infectious Diseases. Adult toxicity tables. Bethesda, MD: Division of Microbiology and Infectious Diseases (DMID); 2001. [Internet. Accessed Feb 1, 2013.] Available from: www.niaid.nih.gov/ labsandresources/resources/dmidclinrsrch/pages/toxtables.aspx
37. Van Gestel AM, Haagsma CJ, van Riel PLCM. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 1998;41:1845-50. (Pubitemid 28465539)
38. Carter RH, Zhao H, Liu X, Pelletier M, Chatham W, Kimberly R, et al. Expression and occupancy of BAFF-R on B cells in systemic lupus erythematosus. Arthritis Rheum 2005;52:3943-54. (Pubitemid 41798234)
39. van Vollenhoven RF, Petri MA, Cervera R, Roth DA, Ji BN, Kleoudis CS, et al. Belimumab in the treatment of systemic lupus erythematosus: High disease activity predictors of response. Ann Rheum Dis 2012;71:1343-9.
40. Lai Kwan Lam Q, King Hung Ko O, Zheng BJ, Lu L. Local BAFF gene silencing suppresses Th17-cell generation and ameliorates autoimmune arthritis. Proc Natl Acad Sci USA 2008;105:14993-8.
41. Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: The ARMADA trial. Arthritis Rheum 2003;48:35-45. (Pubitemid 36091645)