The study, “Atypical haemolytic uraemic syndrome in the eculizumab era: presentation, response to treatment and evaluation of an eculizumab withdrawal strategy,” was published in the British Journal of Haematology.
Soliris, an engineered monoclonal antibody developed and marketed by Alexion, works by specifically targeting a component (protein C5) of the complement system — a part of the immune system chronically and uncontrollably activated in aHUS patients.
Currently recommended as a first-line treatment for aHUS, Soliris prevents small blood vessel destruction and formation of blood clots, and consequent organ damage — all hallmark features of this rare disease.
While previous studies have shown the safety and effectiveness of Soliris in both adult and pediatric patients with aHUS, the best treatment duration and the safety of treatment withdrawal remain unclear.
Researchers in the U.K. evaluated the efficiency and safety of Soliris treatment, as well as the effects of a withdrawal strategy, in 22 aHUS patients treated with Soliris at a single center; they followed for up to six years.
They retrospectively analyzed patients’ genetic data, clinical symptoms, treatment responses, and long-term outcomes of a strategy of discontinuing Soliris after a patient had achieved a complete haematological (blood) response and a complete, or near-complete, kidney recovery.
Patients’ median age when they came to the clinic was 32 years, and 68% of them were women. Median duration of follow-up from beginning Soliris was 85 weeks, excluding a patient who died on day five.
More than half of the patients (64%) showed gastrointestinal problems, and 41% had neurological symptoms. Twenty-one patients showed abnormal kidney function and 14 patients (64%) required renal replacement therapy at presentation.
Mutations in disease-associated genes were present in 41% of the patients, but mutation status was not associated with an effect in disease severity.
Soliris treatment was begun after a median of six days of plasma exchange (PEX), and was given for a median of 11 weeks.
At the end of the study, all patients showed a haematological (blood parameters) recovery, and 81% achieved at least partial kidney recovery. Of the 14 patients who initially required renal replacement therapy, 10 became dialysis-independent.
More than half of patients (54.5%) had signs of normalized kidney function, 27% had chronic kidney disease, 14% were on dialysis, and 4.5% had died. No adverse side effects of Soliris treatment were reported.
Thirteen patients (59%) discontinued Soliris treatment following complete blood and kidney recovery. While 10 of them remained in disease remission, three (23%) relapsed within one year after treatment was discontinued. Re-starting Soliris after disease relapse led to a full recovery in all three patients, without needing PEX or renal replacement therapy.
“The withdrawal strategy therefore led to no long-term adverse effects for these patients, or on outcomes of the cohort as a whole, given that the overall outcomes were comparable to those of [a] Phase 2 trial, despite 59% of our cohort not receiving indefinite treatment,” the researchers wrote.
Researchers noted that treatment responses and relapse rates were consistent with results from previous clinical studies.
The results of this small study also showed that patients with disease-causative mutations had a significantly higher risk of relapse than those without those mutations, and a trend toward a higher relapse risk following shorter durations of initial therapy (median of two weeks) compared with longer treatment periods (median of 14 weeks).
“Our current approach is to give a minimum of 6 months’ therapy before considering withdrawal,” they wrote.
The research team emphasized that while the results suggest that Soliris withdrawal in selected cases is both safe and cost effective, randomized controlled clinical trials are required to confirm the results.
They noted, however, that “monitoring post-withdrawal, patient education regarding potential symptoms of relapse, and pathways to ensure timely re-initiation of eculizumab [Soliris] in the event of relapse, are all vital.”