Experimental drug iptacopan aids man with lupus-associated aHUS
Case report highlights combination of early-acting therapy and rituximab
After standard therapies failed, a 59-year-old man with lupus-related atypical hemolytic uremic syndrome (aHUS) improved when doctors gave him the oral medication iptacopan alongside one cycle of immunosuppressant rituximab, according to a case report from Italy.
Iptacopan, marketed as Fabhalta, is an oral therapy approved for other diseases driven by the overactivation of the complement system — a part of the immune system that normally helps fight infections — and is now being tested in a Phase 3 clinical trial (NCT04889430) for aHUS.
In this case, the therapy was made available under compassionate use, a pathway allowing people with serious or life-threatening conditions to access promising therapies not yet approved for their disease.
The case, “Iptacopan/LNP023 and rituximab as rescue therapy in a patient with systemic lupus erythematosus-associated atypical haemolytic uraemic syndrome,” was published in the Journal of Nephrology.
How lupus triggers the aHUS immune attack
aHUS is a disorder in which the complement system becomes overactive, triggering inflammation and clotting in small blood vessels. This can damage the kidneys and other organs, including the heart, lungs, and brain. Common symptoms include hemolytic anemia, where red blood cells are destroyed faster than they are produced; thrombocytopenia, or low levels of platelets that help the blood clot; and kidney failure.
Known triggers for complement overactivation include infections, pregnancy, and autoimmune diseases. Systemic lupus erythematosus (SLE) is one such disorder and the most common form of lupus. Although rarely associated with aHUS, the outcome is often poor, with a higher risk of multi-organ involvement and kidney failure.
Here, researchers detail the case of 59-year-old Caucasian man with a history of mild SLE who developed aHUS.
On Oct. 23, 2023, he arrived at a hospital in Vicenza, Italy, after a month of worsening symptoms, including persistent headaches, dizziness, tingling and numbness in his hands, swelling in his legs, and shortness of breath.
He had been diagnosed with SLE in 1990, but his disease remained mild and well-controlled with standard treatment, with no flares reported at his last rheumatological visit in May 2023.
On admission, his blood pressure was very high, his legs were swollen, and doctors heard crackling sounds in his lungs that suggested fluid build-up. They also observed tiny red spots under his fingernails, caused by bleeding from small blood vessels.
Initial tests revealed kidney stress, with high creatinine in the blood and traces of blood and protein in the urine, along with signs of heart strain, anemia, and thrombocytopenia. A brain scan showed small areas of damage caused by reduced blood flow, while chest imaging showed fluid buildup in the lungs and around the heart.
Follow-up testing revealed clear signs of hemolysis (red blood cell destruction), with high levels of lactate dehydrogenase — a marker of red blood cell destruction — and fragmented red blood cells in circulation. Worsening creatinine levels and urine findings also indicated kidney failure. Taken together with other tests, these findings supported an aHUS diagnosis secondary to lupus.
Novel combination proves beneficial
The man received high-dose glucocorticoids to reduce inflammation, immunosuppressive therapy to control his lupus, and Soliris (eculizumab) — an antibody-based therapy approved for aHUS that blocks complement activation.
His condition initially improved, but at the end of November, his platelets dropped again, and his kidney function worsened, leading doctors to begin plasma exchange therapy — a procedure that removes and replaces plasma, the non-cellular part of blood, to clear disease-driving immune components.
As his condition worsened, and his kidney function continued to deteriorate, he eventually began hemodialysis — a treatment that removes waste and excess fluid from the blood when the kidneys fail — three times a week. He received further courses of immunosuppressive therapy and plasma exchange, alongside a single cycle of rituximab.
Oral treatment with iptacopan also started under compassionate use. Unlike Soliris, which blocks complement activity at a later stage, iptacopan acts earlier in the complement cascade — potentially offering broader control of the overactive immune response driving aHUS.
Within 20 days, his blood markers normalized, his symptoms eased, and his health stabilized. Despite permanent damage that left him relying on dialysis, he requires no more plasma exchange or glucocorticoids and is being evaluated for a kidney transplant.
The researchers added that the co-administration of rituximab makes it difficult to attribute all improvements to iptacopan alone.
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