Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study

Eric F Morand; David A Isenberg; Daniel J Wallace; Amy H Kao; Cristina Vazquez-Mateo; Peter Chang; Kishore Pudota; Cynthia Aranow; Joan T Merrill

doi:10.1093/rheumatology/keaa029

Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study

Rheumatology (Oxford). 2020 Oct 1;59(10):2930-2938. doi: 10.1093/rheumatology/keaa029.

Authors

Eric F Morand¹, David A Isenberg², Daniel J Wallace³, Amy H Kao⁴, Cristina Vazquez-Mateo⁴, Peter Chang⁴, Kishore Pudota⁴, Cynthia Aranow⁵, Joan T Merrill⁶

Affiliations

¹ Centre for Inflammatory Disease, Monash University, Melbourne, Australia.
² Centre for Rheumatology, University College London, London, UK.
³ Division of Rheumatology, Cedars-Sinai Medical Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
⁴ EMD Serono Research & Development Institute, Inc. (A Business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA.
⁵ Institute of Molecular Medicine, Feinstein Institute for Medical Research, Manhasset, NY, USA.
⁶ Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

Abstract

Objective: 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.

Methods: 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.

Results: 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].

Conclusion: 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.

Trail registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01972568.

Keywords: SLE; atacicept; low disease activity; lupus low disease activity state; remission; treat to target.

Publication types

Clinical Trial, Phase II
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Double-Blind Method
Female
Humans
Lupus Erythematosus, Systemic / drug therapy*
Male
Odds Ratio
Placebos / therapeutic use
Recombinant Fusion Proteins / administration & dosage
Recombinant Fusion Proteins / therapeutic use*
Remission Induction
Treatment Outcome

Substances

Placebos
Recombinant Fusion Proteins
TACI receptor-IgG Fc fragment fusion protein

Associated data

ClinicalTrials.gov/NCT01972568