Review Supports Eculizumab as Potential New Treatment for Lupus Nephritis

Stacy Grieve, PhD avatar

by Stacy Grieve, PhD |

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Eculizumab for lupus nephritis

A new study reports that eculizumab may be effective in the treatment of certain patients with systemic lupus erythematous (SLE) with renal (kidney) involvement, a condition called lupus nephritis (LN).

In the study, “Expanding the therapeutic options for renal involvement in lupus: eculizumab, available evidence,” published in the journal Rheumatology Internationalthe researchers conducted a review of published, peer-reviewed literature to identify reports on clinical experience using eculizumab in SLE patients with renal involvement.

Scientists believe the development of SLE is rooted in the dysregulation of the immune system. One part of the immune system that enhances, or complements, the ability of immune cells to clear foreign particles from the body is called the complement system. This system can also promote inflammation, and is believed to play a key role in the development of lupus nephritis (LN).

Eculizumab specifically inhibits certain components in the pathways linked to the action of the complement system. Although the drug has not been approved for the treatment of SLE, it has been FDA-approved to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). It’s sold by Alexion under the brand name Soliris.

Because of its role in inhibiting inflammation, eculizumab also shows promise for the treatment of other autoimmune diseases, as well as primary renal disease.

After searching available public and medical databases, six studies were included in the analysis. Each study reported on one patient with SLE with renal involvement.

Consistently, five of the six cases described the occurrence of thrombotic microangiopathy (TMA) in kidney biopsies of patients. TMA is a rare but serious medical condition that involves the smallest blood vessels (capillaries) in the kidney and impairs blood flow through the organ. Of those, three patients had histological characteristics consistent with lupus nephritis.

In the six SLE cases with renal involvement, eculizumab treatment was introduced because the current immunosuppressive agents were either ineffective or too toxic for the patients.

The reports from the six patients showed that treatment with eculizumab improved patient outcomes. In general, the patients showed a sustained improvement in kidney function and a normalization of the immune system function.

In three cases where eculizumab treatment was discontinued, renal flares were observed. After the patients were again treated with eculizumab, their renal function improved.

The team noted that the response to eculizumab was sustained in the follow-up period (a median of nine months).

Due to the low patient number represented in this study, limited conclusions can be drawn and the effectiveness and toxicity of eculizumab for the treatment of SLE remains to be determined.

However, the “available data are promising and provide preliminary support for targeting complement pathways in SLE,” the team concluded.

Conventional treatments for SLE are usually directed against the adaptive immune response. By targeting the complement pathway and consequently limiting the inflammatory response, eculizumab may represent an alternative treatment strategy for SLE patients.

“Future studies should evaluate whether eculizumab represents an additional therapeutic option in the treatment of selected cases of SLE with renal involvement, especially in the presence of TMA, or in patients with refractory LN,” the team added.