According to researchers, this suggests that CH50 may be a useful measure for monitoring Soliris’ efficacy in treating the progressive autoimmune disease, which typically affects the optic nerve. However, further studies are needed to confirm these findings.
The study, “CH50 as a putative biomarker of eculizumab treatment in neuromyelitis optica spectrum disorder,” was published in the journal Heliyon.
Developed by Alexion Pharmaceuticals, Soliris is approved in the U.S., Canada, Europe, and Japan to treat adults with NMOSD who test positive for aquaporin-4 antibodies (AQP4). These so-called autoantibodies target and damage nerve cells called astrocytes by triggering the immune system’s complement pathway, causing inflammation.
The therapy is composed of an antibody that blocks the action of a complement pathway protein known as C5, which, in turn, suppresses complement activation, inflammation, and astrocyte damage.
Serum 50% hemolytic complement (CH50) activity is commonly used as a marker for complement pathway activity, which measures the total amount of complement proteins in the blood.
Although the CH50 marker has been used to monitor the efficacy of Soliris in people with other autoimmune conditions, there are no reports of this marker being used in NMOSD patients following Soliris therapy.
Now, investigators based at the Tohoku University Graduate School of Medicine, in Japan, describe three cases of AQP4-positive NMOSD adults who were successfully treated with Soliris and monitored for CH50, as well as the specific complement proteins C3 and C4, before and after the therapy.
All three patients participated in the Phase 3 PREVENT trial (NCT01892345), which evaluated the efficacy of Soliris compared with a placebo. Each patient received 900 mg of Soliris weekly for the first four doses, followed by 1,200 mg biweekly.
The first case was a 53-year-old woman who initially sought treatment after experiencing inflammation of the optic nerve (optic neuritis). She had been diagnosed with AQP4-positive NMOSD. Despite treatment with the oral immunosuppressants prednisolone and azathioprine, she experienced eight attacks during the first four years after onset.
At age 57, she entered the PREVENT trial with an Expanded Disability Status Scale (EDSS) score of 7.0. The EDSS is a measure of disability ranging from 0 to 10, with higher scores representing worse disability.
According to the trial protocol, she continued taking prednisone, but azathioprine was stopped. She did not experience a relapse during the trial, but Soliris was suspended for four weeks due to bacterial pneumonia more than four years later.
Although her C3 and C4 levels remained unchanged, her serum CH50 levels decreased to below normal levels (10 Units (U)/mL) throughout the trial and even during the Soliris interruption. Her EDSS score did not change during Soliris treatment.
The second case involved a woman who experienced neck and arm pain at age 46. MRI scans of her brain revealed lesions (damage) in her brain stem. She was diagnosed with AQP4 antibody-positive NMOSD. Oral prednisone was started, but after five months, she experienced a relapse.
She entered the trial while continuing prednisone, with an EDSS score of 2.0. This patient had no relapses throughout the trial. Again, no change was seen in C3 and C4 levels, but the serum CH50 level declined to normal levels below 10 U/mL. Soliris treatment did not impact her EDSS score.
In the third case, a 28-year-old woman developed optic neuritis and was found to be AQP4-positive. She was diagnosed with NMOSD and treated with prednisone but experienced a relapse after seven months with acute inflammation of the spinal cord.
She joined PREVENT with an EDSS score of 3.5 while continuing prednisone. She did not experience a relapse during the trial period, and her EDSS score was unaffected without clinical worsening. However, her serum CH50 level decreased to below 10 U/mL without affecting C3 and C4 markers.
“Serum CH50 activity measurement can be useful for assessing efficacy of [Soliris] treatment in NMOSD patients,” the researchers concluded.
However, they added that further data is needed “to check the reliability of CH50 as a drug monitoring marker.”
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