Lupuzor/P140 peptide in patients with systemic lupus erythematosus: A randomised, double-blind, placebo-controlled phase IIb clinical trial

Annals of the Rheumatic Diseases

Volumn 72, Issue 11, 2013, Pages 1830-1835

  Zimmer, Robert ^a   Scherbarth, Hugo R ^b   Rillo, Oscar Luis ^c   Gomez Reino, Juan Jesus ^d   Muller, Sylviane ^e  

^a ImmuPharma   (France)

^b Hospital Interzonal General de Agudos 'Dr Oscar Alende'   (Argentina)

^c Asociacion de Beneficencia Hospital Sirio Libanes Buenos Aires   (Argentina)

^d Instituto de Salud Carlos III   (Spain)

^e INSTITUT DE BIOLOGIE MOLÉCULAIRE ET CELLULAIRE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMALARIAL AGENT; AZATHIOPRINE; CORTICOSTEROID; FORIGERIMOD; METHOTREXATE; PLACEBO; IMMUNOLOGIC FACTOR; PEPTIDE FRAGMENT; SPLICEOSOMAL PEPTIDE P140;

ADULT; AGED; AMERICAN COLLEGE OF RHEUMATOLOGY SCORE; ARTICLE; BRITISH ISLES LUPUS ASSESSMENT GROUP 2004 SCALE; BRONCHITIS; COMPLEMENT SYSTEM; CONTROLLED STUDY; DIARRHEA; DISEASE SEVERITY; DIVERTICULITIS; DNA BINDING; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG FATALITY; DRUG WITHDRAWAL; FEMALE; GASTRITIS; HEADACHE; HUMAN; INJECTION SITE ERYTHEMA; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAMED INVENTORIES, QUESTIONNAIRES AND RATING SCALES; PHARYNGITIS; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SCORING SYSTEM; SLEDAI; SOFT TISSUE INFECTION; SYSTEMIC LUPUS ERYTHEMATOSUS; URINARY TRACT INFECTION; VIRUS PNEUMONIA; CLINICAL TRIAL; LUPUS ERYTHEMATOSUS, SYSTEMIC; MIDDLE AGED; TREATMENT OUTCOME; YOUNG ADULT;

ADULT; DOUBLE-BLIND METHOD; FEMALE; HUMANS; IMMUNOLOGIC FACTORS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MALE; MIDDLE AGED; PEPTIDE FRAGMENTS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84885182982     PISSN: 00034967     EISSN: 14682060     Source Type: Journal    
DOI: 10.1136/annrheumdis-2012-202460     Document Type: Article

References (25)

1. Rahman A, Isenberg DA, Systemic lupus erythematosus. N Engl J Med 2008;358:929-39.
2. Tsokos GC. Systemic lupus erythematosus. N Engl J Med 2011;365:2110-21.
3. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003;349:1526-33.
4. Gateva V, Sandling JK, Hom G, et al. A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009;41:1228-33.
5. Taylor KE, Chung SA, Graham RR, et al. Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes. PLoS Genet 2011;7:e1001311.
6. Merrill JT, Erkan D, Buyon JP. Challenge in bringing the bench to bedside in drug development for SLE. Nature Rev Drug Discov 2004;3:1036-46.
7. Steinman L, Merrill JT, McInnes IB, et al. Optimization of current and future therapy for autoimmune diseases. Nat Med 2012;18:59-65.
8. Lee SJ, Silverman E, Bargman JM. The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nat Rev Nephrol 2011;7:718-29.
9. Larche M, Wraith DC. Peptide-based therapeutic vaccines for allergic and autoimmune diseases. Nat Med 2005;11:S69-76.
10. Raz I, Elias D, Avron A, et al. Beta-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial. Lancet 2001;358:1749-53.
11. Monneaux F, Lozano JM, Patarroyo ME, et al. T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MR/lpr mice. Eur J Immunol 2003;33:287-96.
12. Monneaux F, Parietti V, Briand JP, et al. Intramolecular T cell spreading in unprimed MRL/lpr mice: importance of the U1-70K protein sequence 131-151. Arthritis Rheum 2004;50:3232-8.
13. Monneaux F, Hoebeke J, Sordet C, et al. Selective modulation of CD4+ T cells from lupus patients by a promiscuous, protective peptide analogue. J Immunol 2005;175:5839-47.
14. Monneaux F, Parietti V, Briand JP, et al. Importance of spliceosomal RNP1 motif for intermolecular T-B cell spreading and tolerance restoration in lupus. Arthritis Res Ther 2007;9:R111.
15. Page N, Schall N, Strub JM, et al. The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by γδ T cells. PloS ONE 2009;4:e5273.
16. Page N, Gros F, Schall N, et al. HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and endogenous MHCII presentation in murine lupus. Ann Rheum Dis 2011;70:837-43.
17. Muller S, Monneaux F, Schall N, et al. Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial. Arthritis Rheum 2008;58:3873-3.
18. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-7.
19. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725.
20. Isenberg DA, Rahman A, Allen E, et al. BILAG 2004. Development and initial validation of an updated version of the British Isles Lupus Assessment Group's disease activity index for patients with systemic lupus erythematosus. Rheumatology (Oxford) 2005;44:902-6.
21. Yee CS, Farewell V, Isenberg DA, et al. The BILAG-2004 index is sensitive to change for assessment of SLE disease activity. Rheumatology (Oxford) 2009;48:691-5.
22. Petri M. Postmenopausal estrogen replacement therapy and risk of developing systemic lupus erythematosus or discoid lupus. J Rheumatol 1999;26:752.
23. Furie R, Petri M, Zamani O, et al. BLISS-76 Study Group. 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.
24. Navarra SV, Guzmán RM, Gallacher AE, et al. BLISS-52 Study Group. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 2011;377:721-31.
25. van Vollenhoven RF, Petri MA, Cervera R, et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis 2012;71:1343-9.