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Clinical trials and drug discovery
Clinical response beyond the Systemic Lupus Erythematosus Responder Index: post-hoc analysis of the BLISS-SC study
  1. Ronald F van Vollenhoven1,
  2. William Stohl2,
  3. Richard A Furie3,
  4. Norma Lynn Fox4,
  5. James G Groark5,
  6. Damon Bass6,
  7. Milena Kurtinecz7,
  8. Bonnie F Pobiner8,
  9. William J Eastman9,
  10. Tania Gonzalez‑Rivera10 and
  11. David Gordon4
  1. 1 Department of Rheumatology, Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, The Netherlands
  2. 2 University of Southern California Keck School of Medicine, Los Angeles, California, USA
  3. 3 Northwell Health, Great Neck, New York, USA
  4. 4 GSK, Clinical Development – Immuno-Inflammation, Rockville, Maryland, USA (at the time of the study)
  5. 5 GSK, Clinical Development – Immuno-Inflammation, Philadelphia, Pennsylvania, USA
  6. 6 GSK, Immuno-Inflammation and Future Pipeline, Collegeville, Pennsylvania, USA
  7. 7 GSK, Biostatistics, Immuno-Inflammation, Collegeville, Pennsylvania, USA
  8. 8 GSK, Medical Affairs, Research Triangle Park, North Carolina, USA
  9. 9 GSK, Medical Affairs – Immuno-Inflammation, Research Triangle Park, North Carolina, USA (at the time of the study)
  10. 10 GSK, Medical Affairs, Rockville, Maryland, USA
  1. Correspondence to Professor Ronald F van Vollenhoven; r.f.vanvollenhoven{at}amc.uva.nl

Abstract

Objective The Systemic Lupus Erythematosus (SLE) Responder Index (SRI), developed as a primary outcome measure for use in clinical trials, captures improvement in SLE disease activity without concomitant worsening in disease manifestations. This study investigated the relationships between the SRI and clinical/laboratory correlates of SRI response in patients with SLE.

Methods This was a post-hoc analysis of the phase III, double-blind, placebo-controlled study of subcutaneous BeLimumab in Subjects with Systemic lupus erythematosus - SubCutaneous (BLISS-SC). Patients were randomised to weekly belimumab 200 mg subcutaneously or placebo, plus standard SLE therapy. Changes from baseline to week 52 in clinical and laboratory parameters were compared among SRI responders and non-responders, irrespective of the treatment received.

Results SRI responders (n=475) had significantly better (p<0.0001) outcomes compared with non-responders (n=358), including (by definition) higher proportions achieving ≥4-point improvement in Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (100.0% vs 2.0%), no worsening in British Isles Lupus Assessment Group (BILAG; 0 new BILAG A or ≤1 new BILAG B score; 100.0 % vs 50.3%) and no worsening (<0.3-point increase) in Physician’s Global Assessment score (100.0% vs 49.7%). Among patients receiving >7.5  mg/day corticosteroids at baseline, significantly more SRI responders had reductions in prednisone dose to ≤7.5 mg/day than non-responders. SRI responders reported lower flare rates and improvements in serological markers and Functional Assessment of Chronic Illness Therapy-Fatigue score than non-responders.

Conclusion SRI response is associated with improvements in clinical and laboratory measures, strengthening its value as a clinically meaningful primary endpoint in clinical trials.

  • belimumab
  • corticosteroids
  • FACIT-fatigue
  • systemic lupus erythematosus
  • SLE responder index

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/lupus-2018-000288

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    Footnotes

    • Contributors RFvV, DB and DG were involved in the study design, and in data analysis and interpretation. WS was involved in the acquisition of data and in data analysis and interpretation. RAF was involved in the study design, acquisition of data, and in data analysis and interpretation. NLF, JGG, MK, BFP, WJE and TG-R were involved in data analysis and interpretation. All authors contributed to the writing of this manuscript and approved the final version.

    • Funding This study was funded by GlaxoSmithKline (GSK; study number: BEL112341).

    • Competing interests RFvV has received consulting fees and/or honoraria from AbbVie, Biotest, Bristol-Myers Squibb, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB and Vertex; research grants from AbbVie, Bristol-Myers Squibb, GSK, Pfizer, Roche and UCB; and is Editor-in-chief of Lupus Science & Medicine. WS has received consulting fees from Akros Pharma, Janssen and Sanofi, and clinical trials support from GSK and Pfizer. RAF has received consulting fees, research grants and clinical trials support from GSK. NLF, WJE and DG were employees of GSK and held shares in GSK at the time of the study. JGG, DB, MK, BFP and TG-R are employees of GSK and hold shares in the company.

    • Patient consent All patients provided written informed consent prior to enrollment.

    • Ethics approval The study and all protocols were approved by the Institutional Review Board and the study was conducted in accordance with the Declaration of Helsinki 2008.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Anonymized individual participant data and study documents can be requested for further research from "http://www.clinicalstudydatarequest.com"