Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study.
SLE
atacicept
low disease activity
lupus low disease activity state
remission
treat to target
Journal
Rheumatology (Oxford, England)
ISSN: 1462-0332
Titre abrégé: Rheumatology (Oxford)
Pays: England
ID NLM: 100883501
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
12
08
2019
revised:
16
12
2019
pubmed:
29
2
2020
medline:
23
1
2021
entrez:
29
2
2020
Statut:
ppublish
Résumé
Low disease activity (LDA) and remission are emerging treat-to-target (T2T) endpoints in SLE. However, the rates at which these endpoints are met in patients with high disease activity (HDA) are unknown. Atacicept, which targets B lymphocyte stimulator and a proliferation-inducing ligand, improved disease outcomes in SLE patients with HDA (SLEDAI-2K ≥10) at baseline in the phase 2b ADDRESS II study. This is a post hoc analysis of T2T endpoints in these patients. Patients received weekly atacicept (75 or 150 mg s.c.) or placebo for 24 weeks (1:1:1 randomization). Attainment of three T2T endpoints, LDA (SLEDAI-2K ≤ 2), Lupus Low Disease Activity State (LLDAS) and remission (clinical SLEDAI-2K = 0, prednisone-equivalent ≤5mg/day and Physician's Global Assessment <0.5), was assessed and compared with SLE Responder Index (SRI)-4 and SRI-6 response. Of 306 randomized patients, 158 (51.6%) had baseline HDA. At week 24, 37 (23.4%) HDA patients attained LDA, 25 (15.8%) LLDAS and 17 (10.8%) remission. Each of these endpoints was more stringent than SRI-4 (n = 87; 55.1%) and SRI-6 (n = 67; 42.4%). Compared with placebo (n = 52), at week 24, patients treated with atacicept 150 mg (n = 51) were more likely to attain LDA [odds ratio (OR) 3.82 (95% CI: 1.44, 10.15), P = 0.007], LLDAS [OR 5.03 (95% CI: 1.32, 19.06), P = 0.018] or remission [OR 3.98 (95% CI: 0.78, 20.15), P = 0.095]. At week 24, LDA, LLDAS and remission were more stringent than SRI-4 and SRI-6 response, were attainable in the HDA population and discriminated between treatment with atacicept 150 mg and placebo. These results suggest that T2T endpoints are robust outcome measures in SLE clinical trials and support further evaluation of atacicept in SLE. ClinicalTrials.gov, http://clinicaltrials.gov, NCT01972568.
Identifiants
pubmed: 32107560
pii: 5762650
doi: 10.1093/rheumatology/keaa029
pmc: PMC7516108
doi:
Substances chimiques
Placebos
0
Recombinant Fusion Proteins
0
TACI receptor-IgG Fc fragment fusion protein
K3D9A0ICQ3
Banques de données
ClinicalTrials.gov
['NCT01972568']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2930-2938Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.
Références
Arthritis Rheumatol. 2018 Nov;70(11):1790-1795
pubmed: 29806142
Arthritis Rheumatol. 2018 Feb;70(2):266-276
pubmed: 29073347
Ann Rheum Dis. 2015 Dec;74(12):2103-6
pubmed: 26511997
Lupus. 2010 Jul;19(8):949-56
pubmed: 20375124
Rheumatology (Oxford). 2012 Mar;51(3):491-8
pubmed: 22109798
Nat Rev Rheumatol. 2014 Jun;10(6):365-73
pubmed: 24614588
Arthritis Res Ther. 2017 Mar 20;19(1):62
pubmed: 28320433
Rheumatology (Oxford). 2011 Aug;50(8):1424-30
pubmed: 21415024
Ann Rheum Dis. 2016 Sep;75(9):1615-21
pubmed: 26458737
Nat Rev Rheumatol. 2014 Sep;10(9):567-71
pubmed: 25048762
Rheumatology (Oxford). 2013 Jul;52(7):1279-84
pubmed: 23479724
Ann Rheum Dis. 2018 May;77(5):706-713
pubmed: 29420200
Ann Rheum Dis. 2017 Sep;76(9):1575-1582
pubmed: 28450313
Ann Rheum Dis. 2015 Nov;74(11):2006-15
pubmed: 24951103
Semin Arthritis Rheum. 2017 Jun;46(6):798-803
pubmed: 28216192
Arthritis Rheum. 2009 Sep 15;61(9):1143-51
pubmed: 19714615
Ann Rheum Dis. 2019 May;78(5):629-633
pubmed: 30679152
Rheumatology (Oxford). 2017 Sep 1;56(9):1498-1509
pubmed: 28498975
Arthritis Care Res (Hoboken). 2016 Jul;68(7):981-7
pubmed: 26554745
Arthritis Res Ther. 2016 Nov 9;18(1):260
pubmed: 27829463
Lupus. 2013 Aug;22(9):873-84
pubmed: 23846230
Ann Rheum Dis. 2017 Mar;76(3):547-553
pubmed: 27558987
Ann Rheum Dis. 2014 Jun;73(6):958-67
pubmed: 24739325
Ann Rheum Dis. 2015 Dec;74(12):2117-22
pubmed: 26223434
Clin Immunol. 2010 Apr;135(1):118-24
pubmed: 20116334
J Immunol. 2001 Jan 1;166(1):6-10
pubmed: 11123269
Ann Rheum Dis. 2017 Mar;76(3):554-561
pubmed: 27884822
Nat Rev Rheumatol. 2016 Dec;12(12):696-698
pubmed: 27784893
Rheumatology (Oxford). 2018 Feb 1;57(2):337-344
pubmed: 29121273
Arthritis Rheum. 1997 Sep;40(9):1725
pubmed: 9324032
Lupus. 2016 May;25(6):582-92
pubmed: 26424128
J Rheumatol. 2002 Feb;29(2):288-91
pubmed: 11838846
Ann Rheum Dis. 2015 Sep;74(9):1706-13
pubmed: 24834926
Arthritis Res Ther. 2017 Nov 10;19(1):247
pubmed: 29126432
Ann Rheum Dis. 2014 Mar;73(3):492-509
pubmed: 24161836
Rheumatology (Oxford). 2017 Jan;56(1):121-128
pubmed: 27803306