Clinical SLEDAI-2K zero may be a pragmatic outcome measure in SLE studies

ABSTRACT

Objectives: Development of therapies for systemic lupus erythematosus (SLE) has in part been limited by the lack of suitable outcome measures in clinical trials. In the present post-hoc analysis of two clinical trials of belimumab, we investigated two potential outcomes, the Lupus Low Disease Activity State (LLDAS) and clinical SLE disease activity index 2000 (cSLEDAI-2K) zero, in relation to SLE responder index 4 (SRI-4).

Methods: A total of 1684 SLE patients from the BLISS-52 (n = 865) and BLISS-76 (n = 819) trials were surveyed. Physician’s Global Assessment (PGA) scores <0.5 (3-point scale) were used for comparisons. We used the chi-square test for comparisons and the phi coefficient for correlations.

Results: At week 52, LLDAS was achieved by 8.6% of patients, cSLEDAI-2K = 0 by 34.5% and SRI-4 by 45.1%. cSLEDAI-2K = 0 showed the strongest correlation with PGA <0.5 (r_φ = 0.36, P < 0.001). cSLEDAI-2K = 0 unveiled the superiority of belimumab 10 mg/kg over placebo (P = 0.003) with a magnitude which was comparable to that of SRI-4 (P < 0.001). LLDAS displayed a more moderate separation (P = 0.033).

Conclusions: LLDAS was a stringent measure. cSLEDAI-2K = 0 showed the strongest correlation with the clinician-based evaluation. Being based on the SLEDAI-2K only, cSLEDAI-2K = 0 may be considered a more pragmatic outcome measure in SLE studies compared with composite tools.

Trial registration: ClinicalTrials.gov identifier: NCT00424476.

Trial registration: ClinicalTrials.gov identifier: NCT00410384.

KEYWORDS:

• Systemic lupus erythematosus
• treatment
• outcome measures
• biologics
• belimumab

Acknowledgments

The authors would like to thank GlaxoSmithKline (Uxbridge, UK) for granting access to the data from the BLISS-52 and BLISS-76 trials (ClinicalTrials.gov identifiers NCT00424476 and NCT00410384, respectively).

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

Authors’ contributions

Study conception, design, and coordination: IP, IG, RV, KC

Acquisition of data: IP, SE, AG

Statistics: IP, SE, AG, KC

Interpretation of the results: IP, SE, AG, IG, RV, KC

Manuscript draft: IP, AG, KC

All authors read and critically revised the manuscript for intellectual content, approved its final version prior to submission, and agree to be accountable for all aspects of the work.

Declaration of interest

R van Vollenhoven has received honoraria from Amgen, Abbvie, BMS, Biotest, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, and Vertex; none of those was related to this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The study was supported by grants from the Swedish Research Council, Professor Nanna Svartz Foundation [Reference number: 2017-00213], Swedish Rheumatism Association, King Gustaf V’s 80-year Foundation, Ingegerd Johansson’s Fund, Stockholm County Council and Karolinska Institutet Foundations, and was independent of pharmaceutical sponsors.