Soliris Seen as Effective at Treating Lupus Nephritis Patients with TMA, Rare Disease of Small Vessels

Patients with lupus nephritis — a lupus-associated type of kidney inflammation — can sometimes develop a rare immune disorder, called thrombotic microangiopathy, as a consequence of excessive activation of the complement system. Using Soliris (eculizumab) to prevent over-activation is an effective way of treating these patients, a study found.

Outcomes in 11 lupus nephritis patients with thrombotic microangiopathy who were treated with complement inhibitors was described in “Complement-mediated thrombotic microangiopathy associated with lupus nephritis,” which was published in the journal Blood Advances.

Thrombotic microangiopathy (TMA) is a rare but severe medical condition that involves the capillaries and impairs blood flow, resulting in serious organ damage. The condition usually develops due to an abnormal activation of the complement system – a part of the immune system involved in fighting infections.

The complement system is also excessively active in lupus patients. As a consequence, roughly 17.5% of lupus nephritis patients develop TMA and progressive kidney failure, despite treatment with high-dose corticosteroids or aggressive immune-modulatory therapies.

Soliris, developed by Alexion, is an inhibitor of the complement system. While the medicine is not approved for lupus nephritis patients with TMA, its efficacy in other forms of TMA suggests it could also be a promising approach for lupus patients.

A research team at the University of Southern California retrospectively reviewed the clinical outcome of 11 patients (ages 22 to 59) diagnosed with lupus nephritis and TMA, who were followed between 2009 and 2018.

All patients showed signs of progressive renal insufficiency, systemic inflammation, anemia, and low platelet levels.

“In our cohort, treatment of the acute [lupus nephritis]-associated TMA with plasma exchange, corticosteroid, and immune modulation did not have a significant impact on recovery of the platelet count or renal function,” the researchers reported.

One patient died due to progressive TMA within 24 hours of receiving Soliris. An autopsy revealed extensive blockage of kidney capillaries and disseminated fungal infection, most likely due to prolonged high-dose corticosteroid treatment for lupus nephritis.

Ten patients were treated for a median of 63.5 weeks, and all showed improvements in kidney function, as well as increases in platelet and red blood cell count.

Seven were on dialysis before beginning to use Soliris, and four of these patients stopped dialysis within 60 days of starting treatment. One patient who remained on dialysis after discharge was able to stop peritoneal dialysis – another blood-filtering procedure – 36 weeks after starting Soliris.

Compared to other standard treatments, Soliris was significantly better at improving the low platelet levels and anemia, and at restoring kidney function in these patients, the study reports.

“Complement inhibition represents a paradigm shift in the treatment of this subset of patients with lupus nephritis and TMA,” the researchers concluded.