Precision Medicine in LN: A Multicenter Proof-of-concept Study for Histopathological Biomarkers Analysis in Renal Biopsy

Summary

Lupus nephritis (LN) may affect approximately half of patients with Systemic Lupus Erythematosus (SLE). LN is a major cause of morbidity and the most important predictor of mortality in patients with SLE. Some 5-20% of patients with LN may develop end-stage renal disease within 10 years of follow-up from the time of diagnosis. Other studies have described progression to end-stage renal disease in 10-30% of patients with LN.

The European League Against Rheumatism, the European Renal Association and the European Dialysis and Transplant Association have recently updated their recommendations for the management of LN. These recommend the use of intravenous (IV) methylprednisolone boluses followed by lower doses of oral glucocorticoids (GC) and place mycophenolate mofetil (MMF) and the European regimen of cyclophosphamide (CYC) as the immunosuppressive drugs of first choice, with the IV CYC regimen for certain more aggressive cases. They also consider the use of "multitarget therapy" based on the combination of tacrolimus (TAC) and MMF and GC in patients with proteinuria in the nephrotic range who have not responded to the first line of treatment. For refractory active renal disease, they recommend as an alternative the use of rituximab (RTX) 1000 mg IV repeated after 15 days.

Belimumab has been shown to be significantly more effective than placebo in the treatment of patients with active LN. This finding will lead to positioning belimumab in the therapeutic algorithm for LN.

However, in clinical practice these immunosuppressive drugs are not always effective in the treatment of LN, and even one in 3 patients with an initial favorable response may experience renal recurrence.

The choice of the appropriate treatment for LN and its early initiation are key to improve the prognosis of these patients and to avoid progression to chronic renal failure.

The identification of biomarkers capable of predicting the response (or lack thereof) to one or another therapy at the time of LN diagnosis would allow to implement precision medicine, thus constituting a revolution in the treatment of patients with LN. Allows more targeted treatments with greater specificity to be established.

The objective of this project is to analyze histopathological biomarkers in the renal biopsy to predict the renal response to the different drugs used in the treatment of LN. This would contribute to a more specific and cost-effective therapeutic strategy.

Conditions

• Lupus Nephritis
• Systemic Lupus Erythematosus

Sponsors & Collaborators

• Hospital Universitario 12 de Octubre

  collaborator OTHER

• Germans Trias i Pujol Hospital

  collaborator OTHER

• Hospital del Mar

  collaborator OTHER

• Dr. Negrin University Hospital

  collaborator OTHER

• Hospital Universitario Araba

  collaborator OTHER

• Fundacin Biomedica Galicia Sur

  lead OTHER

Principal Investigators

• José María Pego-Reigosa, Dr · INSTITUTO DE INVESTIGACIÓN SANITARIA GALICIA SUR

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-10-15

Primary Completion

2022-07-15

Completion

2023-01-15

Countries

• Spain

Study Locations