Predictors of Renal Flares in Systemic Lupus Erythematosus - European Medical Journal

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Predictors of Renal Flares in Systemic Lupus Erythematosus

1 Mins
Rheumatology
Authors:
Álvaro Gómez,1 Sandra Jägerback,1 *Ioannis Parodis1,2
  • 1. Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Sweden
  • 2. Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Sweden
*Correspondence to [email protected]
Disclosure:

Gómez and Jägerback have declared no conflicts of interest. Parodis has received grants or contracts from Amgen, Aurinia Pharmaceuticals, Eli Lilly and Company, GlaxoSmithKline (GSK), Hoffmann-La Roche, and Otsuka Pharmaceutical; and has received consulting fees from AstraZeneca, Janssen Pharmaceuticals, and Novartis.

Acknowledgements:

The authors would like to thank GSK (Uxbridge, UK) for providing data through the clinical study data request (CSDR) consortium.

Citation:
EMJ Rheumatol. ;10[1]:33-44. DOI/10.33590/emjrheumatol/10300344. https://doi.org/10.33590/emjrheumatol/10300344.
Keywords:
Biomarkers, lupus nephritis, monoclonal antibodies, systemic lupus erythematosus (SLE).

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

BACKGROUND AND AIMS

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a highly heterogenous clinical presentation that can affect almost any organ system.1 In patients with SLE, kidney disease is one of the most serious manifestations, as kidney failure may lead patients to require dialysis or a kidney transplant.2 Therefore, identification of patients at risk of developing renal flares despite immunosuppressant therapy is imperative to optimise management and improve outcomes.

In this study, the authors aimed to identify predictors of renal flares in patients receiving treatment for active extra-renal SLE.

MATERIALS AND METHODS

The authors analysed data from four randomised clinical trials of belimumab: BLISS-52,3 BLISS-76,4 BLISS Northeast Asia,5 and BLISS-SC.6 The trials included patients with SLE who had an active disease despite receiving standard therapy. In this population, the authors investigated several biomarkers that are routinely used in clinical practice as potential predictors of renal flares within 76 weeks.

RESULTS

Of the 3,225 patients enrolled in the clinical trials, 192 developed a renal flare. The factors that were more strongly associated with the development of renal flares were a history of renal involvement (hazard ratio [HR]: 9.4; 95% confidence interval [CI]: 5.0–17.7), baseline serum albumin (HR: 0.9; 95% CI: 0.9–0.9), levels of proteinuria (HR: 1.3; 95% CI: 1.2–1.4), and low complement component 3 levels (HR: 1.8; 95% CI: 1.3–2.5). All these factors predicted renal flares regardless of the treatment that patients received during the clinical trials.

However, the ability of some biomarkers to predict renal flares differed according to the treatment received by the patients, as positive levels of anti-Smith antibodies were associated with renal flares in the placebo (adjusted HR: 2.9; 95% CI: 1.5–5.6) but not in the belimumab subgroup. Anti-ribosomal P protein antibodies were associated with renal flare development only in patients treated with belimumab (HR: 2.8; 95% CI: 1.5–5.0).

CONCLUSION

In conclusion, the authors identified several biomarkers in blood and urine that are already accessible in the clinic, and may be useful tools to predict renal flares. While some of these biomarkers have an established role in disease monitoring, anti-Smith and anti-ribosomal P protein antibodies constitute novel and appealing candidates.

References
Kaul A et al. Systemic lupus erythematosus. Nat Rev Dis Primers. 2016;2:16039. Anders H-J et al. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7. Human Genome Sciences Inc. A study of belimumab in subjects with systemic lupus erythematosus (SLE) (BLISS-52). NCT00424476. https://clinicaltrials.gov/ct2/show/NCT00424476. Human Genome Sciences Inc. A study of belimumab in subjects with systemic lupus erythematosus (BLISS-76). NCT00410384. https://clinicaltrials.gov/ct2/show/NCT00410384. GlaxoSmithKline. GSK1550188 A 52 week study of belimumab versus placebo in the treatment of subjects with systemic lupus erythematosus (SLE) located in northeast Asia. NCT01345253. https://clinicaltrials.gov/ct2/show/NCT01345253. Human Genome Sciences Inc. A study of belimumab administered subcutaneously in subjects with systemic lupus erythematosus (SLE) (BLISS-SC). NCT01484496. https://clinicaltrials.gov/ct2/show/NCT01484496.

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