Does Belimumab Modify the Natural History of SLE? A Propensity Score-matched, Real-world Study

Overview

This will be a combined retrospective and prospective cohort study, that will evaluate the incidence of de novo Systemic Lupus Erythematosus major organ manifestations (defined as BILAG A flares) in patients receiving belimumab (Arm A) and compare it to 2 standard-of-care groups (SoC) (Arm B: patients on SoC; Arm C: patients on SoC followed-up up to May 1st 2014, the first date where belimumab was available in Greece). The investigators will utilize survival analysis methods (Kaplan-Meier survival curves and Cox regression) and mixed effects longitudinal analyses. Additionally, the investigators will employ propensity score matching and/or inverse probability of treatment weighting, to create balanced cohorts and reduce bias.

Detailed description

Belimumab (BEL) has been used for the treatment of SLE for over 10 years, with clear evidence for a beneficial effect in reduction of disease activity and frequency of flares, as well as prevention of damage accrual.

Whether BEL may also result in prevention of incident, major organ involvement in patients with SLE is less clear. A recent post-hoc analysis of the BLISS trials suggested that BEL (although at the low, rather than standard-dose) reduced the rate of de novo renal flares (defined by BILAG) compared to standard-of-care but real-life data are scarce. Importantly, data on the ability of belimumab to decrease major neuropsychiatric events in SLE such as strokes, seizures and cognitive dysfunction or other severe manifestations such as severe hematologic or cardiopulmonary disease is not known.

To this end, the investigators propose a propensity score-matched, real-world, with the use of longitudinal data from large patient cohorts and time-to-event analyses. Given the non-experimental setting of this study, the investigators will also employ propensity score matching (PSM), to create balanced cohorts of BEL-treated and non-BEL-treated patients and reduce bias in estimating treatment efficacy.

The study will consist of 3 arms, as follows: Arm A: patients on treatment with belimumab; Arm B: patients on standard-of-care (SoC) treatment from May 1st 2014 onwards; Arm C: a historical cohort of patients on SoC followed-up up to May 1st 2014, the first date where belimumab was available in Greece.

Primary outcome measures

• Bilag A flare [Time frame: From enrollment to the end of treatment (expected follow-up duration 1-4 years).]

Secondary outcome measures (1)

• SLICC/ACR Damage Index [Time frame: From enrollment to the end of treatment (expected follow-up duration 1-4 years).]

Eligibility criteria

Inclusion criteria

• Systemic lupus erythematosus classification according to the Systemic Lupus International Collaborating Clinics (SLICC) criteria
• Age ≥ 18 years old
• Time of follow-up ≥ 6 months
• Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ≥ 4
• Physician Global Assessment (PGA) visual analogue score > 1

Exclusion criteria

• Patients with incomplete medical records or missing key variables
• Patients with concomitant autoimmune disorders (excluding thyroid disease)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Greece · 1 center

• University Hospital 'Attikon' — Athens

Publications

• Fanouriakis A, Adamichou C, Koutsoviti S, Panopoulos S, Staveri C, Klagou A, Tsalapaki C, Pantazi L, Konsta S, Mavragani CP, Dimopoulou D, Ntali S, Katsikas G, Boki KA, Vassilopoulos D, Konstantopoulou P, Liossis SN, Elezoglou A, Tektonidou M, Sidiropoulos P, Erden A, Sfikakis PP, Bertsias G, Boumpas DT. Low disease activity-irrespective of serologic status at baseline-associated with reduction of PMID 29555348
• Nikoloudaki M, Nikolopoulos D, Koutsoviti S, Flouri I, Kapsala N, Repa A, Katsimbri P, Theotikos E, Pitsigavdaki S, Pateromichelaki K, Bertsias A, Elezoglou A, Sidiropoulos P, Fanouriakis A, Boumpas D, Bertsias G. Clinical response trajectories and drug persistence in systemic lupus erythematosus patients on belimumab treatment: A real-life, multicentre observational study. Front Immunol. 2023 Jan PMID 36685524
• Iaccarino L, Bettio S, Reggia R, Zen M, Frassi M, Andreoli L, Gatto M, Piantoni S, Nalotto L, Franceschini F, Larosa M, Fredi M, Punzi L, Tincani A, Doria A. Effects of Belimumab on Flare Rate and Expected Damage Progression in Patients With Active Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2017 Jan;69(1):115-123. doi: 10.1002/acr.22971. Epub 2016 Nov 18. PMID 27390293
• Bartels C, Bell C, Rosenthal A, Shinki K, Bridges A. Decline in rheumatoid vasculitis prevalence among US veterans: a retrospective cross-sectional study. Arthritis Rheum. 2009 Sep;60(9):2553-7. doi: 10.1002/art.24775. PMID 19714622
• van Vollenhoven R, Askanase AD, Bomback AS, Bruce IN, Carroll A, Dall'Era M, Daniels M, Levy RA, Schwarting A, Quasny HA, Urowitz MB, Zhao MH, Furie R. Conceptual framework for defining disease modification in systemic lupus erythematosus: a call for formal criteria. Lupus Sci Med. 2022 Mar;9(1):e000634. doi: 10.1136/lupus-2021-000634. PMID 35346982
• Fanouriakis A, Kostopoulou M, Andersen J, Aringer M, Arnaud L, Bae SC, Boletis J, Bruce IN, Cervera R, Doria A, Dorner T, Furie RA, Gladman DD, Houssiau FA, Ines LS, Jayne D, Kouloumas M, Kovacs L, Mok CC, Morand EF, Moroni G, Mosca M, Mucke J, Mukhtyar CB, Nagy G, Navarra S, Parodis I, Pego-Reigosa JM, Petri M, Pons-Estel BA, Schneider M, Smolen JS, Svenungsson E, Tanaka Y, Tektonidou MG, Teng YO PMID 37827694

Identifiers

NCT: NCT07056621 · 224080

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗