Kidney function improvements seen only after long-term Soliris treatment: Study
Resolving disease requires long period of anti-C5 treatment, researchers said
The kidney function of a woman with atypical hemolytic uremic syndrome (aHUS) was completely rescued with Soliris (eculizumab), but only after more than a year of treatment, a case study reports.
“This case report supports the hypothesis that kidney pathological [disease] resolution in complement-mediated aHUS requires a long period of over [one] year after initiating anti-C5 monoclonal antibody treatment,” the researchers wrote.
The study, “Anti-C5 monoclonal antibody treatment showing pathological resolution of complement-mediated atypical hemolytic uremic syndrome: a case report,” was published in BMC Nephrology.
A rare disease driven by the overactivation of the complement system, a network of proteins that normally help defend the body against disease-causing microbes, aHUS features a a triad of symptoms: red blood cell destruction (hemolysis), low platelet counts (thrombocytopenia), and kidney injury.
Soliris and Ultomiris (ravulizumab) are approved to treat aHUS in the U.S. and Europe. Both work to keep the complement system in check by targeting C5, a complement protein. Soliris is infused into the bloodstream every other week, while Ultomiris is infused in intervals of up to two months. Both are used as first-line therapies for aHUS, but “no reports have compared the pathological kidney findings of a patient with complement-mediated aHUS before and after anti-C5 monoclonal antibody treatment,” the researchers wrote.
Improving kidney function with long-term Soliris
Here, the case of a 53-year-old woman with aHUS who underwent multiple kidney biopsies after starting Soliris is described.
Before being admitted to the hospital, the woman had gastroenteritis, a condition marked by inflammation of the stomach and intestine, for two weeks, followed by headaches, vomiting, and high blood pressure.
At the hospital, lab work revealed the presence of red blood cell fragments, or schistocytes, consistent with hemolysis, as well thrombocytopenia, and signs of kidney dysfunction. Complement activity, which is determined by measuring CH50 levels, was slightly elevated.
Fifteen days after her symptoms began, the woman’s platelet counts decreased even further and she completed a session of plasma exchange therapy. While her platelet counts recovered, blood work still showed signs of kidney dysfunction.
A kidney biopsy performed a month after the onset of her symptoms showed several alterations, including the presence of blood clots inside small blood vessels. The estimated glomerular filtration rate (eGFR), a measure of kidney function, confirmed the woman had severe kidney dysfunction. These signs suggested a diagnosis of aHUS, which was confirmed by a blood test.
On the 42nd day after the onset of her symptoms, the woman started Soliris. CH50 activity levels immediately dropped below the detection limit and she was discharged on day 68.
A month after starting treatment, the woman’s Soliris dose was changed from 900 mg per week to 1,200 mg every two weeks. Blood work revealed the presence of abnormally high levels of self-reactive antibodies against complement factor H (CFH), however, and she began treatment with prednisolone, a glucocorticoid.
A genetic analysis confirmed the presence of mutations in complement-related genes, including a known aHUS-causing mutation in the CFH gene.
While her kidney function gradually started to improve with Soliris, severe kidney dysfunction still persisted.
A second kidney biopsy was performed at the woman’s request three months after her symptoms began and two months after starting Soliris. Biopsy findings showed signs of improvement, even though some lesions persisted. Her doctors decided to gradually taper off steroids, but continue Soliris.
A third kidney biopsy conducted 17 months after the onset of the woman’s symptoms showed signs of improvements. Her kidney lesions were considered to be in remission and glucocorticoids were discontinued 18 months after her symptoms began.
The woman was monitored and treatment with Soliris was adjusted again, with dosing extended to 1,200 mg every four weeks after 34 months. Despite the extended interval, CH50 activity remained below detection, indicating a complete blockade of complement activity.
The woman’s eGFR continued to increase and at the latest follow up — 76 months, or 6.3 years after the onset of her symptoms — no signs of recurrence were observed. The patient was kept on Soliris to reduce that risk.
“We believe that this report is of great clinical importance, because it clarifies the long-term gradual kidney repair process of complement-mediated aHUS after anti-C5 monoclonal antibody treatment regardless of the quick improvement of [disease] biological markers,” the researchers wrote.
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