Systemic Lupus Erythematosus (SLE) Responder Index response is associated with global benefit for patients with SLE

Abstract

A post-hoc analysis of pooled data from two Phase IIb trials (sifalimumab; NCT01283139, anifrolumab; NCT01438489) assessed the clinical significance of a Systemic Lupus Erythematosus (SLE) Responder Index (SRI(4)) response (Week 52) for 736 patients with moderate to severe SLE disease activity (study entry). SRI(4) responders achieved significantly greater improvements in clinical outcome measures (including percentages of patients with a ≥ 7-point reduction in SLE Disease Activity Index (SLEDAI)–2000 (2K), British Isles Lupus Assessment Group “A” or “2B” flare rate, and oral corticosteroid reduction to ≤7.5 mg/day; change from baseline in Physician’s Global Assessment; and numbers of SLEDAI–2K organ domains with improvement), as well as in patient-reported outcomes (Patient’s Global Assessment, Functional Assessment of Chronic Illness Therapy−Fatigue; Short-Form 36 Health Survey Physical Component Summary, Mental Component Summary, Vitality domain scores) vs. nonresponders. Of patients with abnormal serologies, SRI(4) responders had numerically greater improvements (baseline to Week 52) in anti-double-stranded DNA concentrations vs. nonresponders (p = 0.051), but there were no differences in C3/C4 concentration changes between the two groups. These results confirm previous findings in a different cohort, indicating that an SRI(4) response is associated with global clinical benefit.

Keywords

Anifrolumab randomized controlled trial clinical outcomes disease activity sifalimumab SLE Responder Index

Get full access to this article

View all access options for this article.

References

Kaul

Gordon

Crow

et al.

Systemic lupus erythematosus. Nat Rev Dis Primers 2016; 2: 16039–16039.

Bengtsson

Rönnblom

. Systemic lupus erythematosus: Still a challenge for physicians. J Intern Med 2017; 281: 52–64.

Tsokos

Costa Reis

Sullivan

. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol 2016; 12: 716–730.

Jordan

D’Cruz

. Current and emerging treatment options in the management of lupus. Immunotargets Ther 2016; 5: 9–20.

Oon

Wilson

Wicks

. Targeted therapeutics in SLE: Emerging strategies to modulate the interferon pathway. Clin Transl Immunology 2016; 5: e79–e79.

Peng

Oganesyan

Dall’Acqua

Damschroder

. Molecular basis for antagonistic activity of anifrolumab, an anti-interferon-α receptor 1 antibody. MAbs 2015; 7: 428–439.

Merrill

Wallace

Petri

et al.

Safety profile and clinical activity of sifalimumab, a fully human anti-interferon α monoclonal antibody, in systemic lupus erythematosus: A phase I, multicentre, double-blind randomised study. Ann Rheum Dis 2011; 70: 1905–1913.

Petri

Wallace

Spindler

et al.

Sifalimumab, a human anti-interferon-alpha monoclonal antibody, in systemic lupus erythematosus: A phase I randomized, controlled, dose-escalation study. Arthritis Rheum 2013; 65: 1011–1021.

Lauwerys

Ducreux

Houssiau

. Type I interferon blockade in systemic lupus erythematosus: Where do we stand? Rheumatology (Oxford) 2014; 53: 1369–1376.

10.

Crow

Olferiev

Kirou

. Targeting of type I interferon in systemic autoimmune diseases. Transl Res 2015; 165: 296–305.

11.

Crow

. Type I interferon in the pathogenesis of lupus. J Immunol 2014; 192: 5459–5468.

12.

Rönnblom

Alm

Eloranta

. The type I interferon system in the development of lupus. Semin Immunol 2011; 23: 113–121.

13.

Furie

Khamashta

Merrill

et al.

Anifrolumab, an anti-interferon-α receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol 2017; 69: 376–386.

14.

Khamashta

Merrill

Werth

et al.

Sifalimumab, an anti-interferon-alpha monoclonal antibody, in moderate to severe systemic lupus erythematosus: A randomised, double-blind, placebo-controlled study. Ann Rheum Dis 2016; 75: 1909–1916.

15.

Goldberg

Geppert

Schiopu

et al.

Dose-escalation of human anti-interferon-α receptor monoclonal antibody MEDI-546 in subjects with systemic sclerosis: A phase 1, multicenter, open label study. Arthritis Res Ther 2014; 16: R57–R57.

16.

Furie

Petri

Wallace

et al.

Novel evidence-based systemic lupus erythematosus responder index. Arthritis Rheum 2009; 61: 1143–1151.

17.

Food and Drug Administration. Guidance for Industry Systemic Lupus Erythematosus—Developing medical products for treatment. Available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072063.pdf (2010, accessed 30 May 2017).

18.

Bertsias

Gordon

Boumpas

. Clinical trials in systemic lupus erythematosus (SLE): Lessons from the past as we proceed to the future—the EULAR recommendations for the management of SLE and the use of end-points in clinical trials. Lupus 2008; 17: 437–442.

19.

Smolen

Strand

Cardiel

et al.

Randomized clinical trials and longitudinal observational studies in systemic lupus erythematosus: Consensus on a preliminary core set of outcome domains. J Rheumatol 1999; 26: 504–507.

20.

Castrejón

Tani

Jolly

Huang

Mosca

. Indices to assess patients with systemic lupus erythematosus in clinical trials, long-term observational studies, and clinical care. Clin Exp Rheumatol 2014; 32(Suppl 85): S85–S95.

21.

Navarra

Guzmán

Gallacher

et al.

Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: A randomised, placebo-controlled, phase 3 trial. Lancet 2011; 377: 721–731.

22.

Furie

Petri

Zamani

et al.

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: 3918–3930.

23.

Furie

Petri

Strand

et al.

Clinical, laboratory and health-related quality of life correlates of Systemic Lupus Erythematosus Responder Index response: A post hoc analysis of the phase 3 belimumab trials. Lupus Sci Med 2014; 1: e000031–e000031.

24.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

25.

Tan

Cohen

Fries

et al.

The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

26.

Gladman

Ibañez

Urowitz

. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol 2002; 29: 288–291.

27.

Isenberg

Rahman

Allen

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: 902–906.

28.

Yee

Cresswell

Farewell

et al.

Numerical scoring for the BILAG-2004 index. Rheumatology (Oxford) 2010; 49: 1665–1669.

29.

Lam

Petri

. Assessment of systemic lupus erythematosus. Clin Exp Rheumatol 2005; 23(Suppl 39): S120–S132.

30.

Albrecht

Taylor

Berlin

et al.

The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): An outcome instrument for cutaneous lupus erythematosus. J Invest Dermatol 2005; 125: 889–894.

31.

Klein

Moghadam-Kia

LoMonico

et al.

Development of the CLASI as a tool to measure disease severity and responsiveness to therapy in cutaneous lupus erythematosus. Arch Dermatol 2011; 147: 203–208.

32.

Smith

Lai

Cella

. Building a measure of fatigue: The functional assessment of Chronic Illness Therapy Fatigue Scale. PM R 2010; 2: 359–363.

33.

Biesen

Dähnrich

Rosemann

et al.

Anti-dsDNA-NcX ELISA: dsDNA-loaded nucleosomes improve diagnosis and monitoring of disease activity in systemic lupus erythematosus. Arthritis Res Ther 2011; 13: R26–R26.

34.

Subasic

Karamehic

Delic-Sarac

et al.

Monitoring of disease biomarkers activity and immunophenotyping as important factors in SLE clinical management. Med Arch 2012; 66: 336–339.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.14 MB