Rare Disease Report

Is Soliris Effective in aHUS with Complement-Amplifying Conditions?

DECEMBER 10, 2017
Jim Radke, PhD
At the 59th American Society of Hematology (ASH) Annual Meeting & Exposition in Atlanta, Julia M. Cunningham, MD of the Georgetown University Hospital in Washington D.C. presented data assessing the impact of Soliris (eculiuzmab) in a cohort of 52 atypical hemolytic uremic syndrome (aHUS) patients who received it between December 2011 and February 2017.

Julia M Cunningham, MD of presented results for 52 atypical hemolytic uremic syndrome (aHUS) patients who received Soliris (eculiuzmab) between December 2011 and February 2017 to assess the drug’s impact.

Soliris is the only orphan drug approved for treating aHUS patients, and acts as an antibody targeting the complement system. The only other currently-approved treatment option is plasma exchange.

aHUS is a rare condition with an estimated incidence of 1-2 cases per every million people. Genetic mutations result in chronic, uncontrolled activation of the alternative complement pathway leading to blood clots throughout the body. The glomerular capillaries in the kidneys are especially vulnerable, though, and if blood clots occur elsewhere, they can lead to organ failure.

Symptoms of aHUS most commonly include nausea and vomiting, dyspnea, fatigue, anemia, and thrombocytopenia.

Of particular interest to the investigators was whether the presence of Complement-amplifying conditions (CACs) in aHUS patients factored into the patients’ response to treatment.

CACs are known to put aHUS patients at increased risk for thrombotic microangiopathy (TMA). They include (but are not limited to):
 
  • Bacterial, viral and fungal infections
  • Atherosclerosis
  • Inflammatory bowel disease
  • Surgeries
  • Thyroiditis
  • Allergies and asthma
  • Anaphylactic shock
  • Malignant hypertension
  • Pregnancy
According to the data, CACs were present in 37 (71%) of the 52 patients while the remainder had de novo aHUS. A total of 47 patients (90%) received more than 1 month of treatment with Soliris and 21 patients (40%) remained on chronic Soliris therapy at the time of data cut-off (February 2017). Of the 21 patients on chronic therapy, 14 had CACs.

Of the 31 patients not currently being treated with Soliris, 19 discontinued treatment, 6 died, and the treatment status of 6 of the patients is unknown.  

CACs were associated with longer hospital time before Soliris treatment but not after treatment (Table 1).

Table 1.

Patient Demographics
Characteristic CAC positive
(n=37)
CAC negative
(n=15)
Chronic Soliris Use 14 7
Number of doses 38.86 ± 44.11 39.4 ± 37.75
Had Dialysis before Soliris 13 5
Hospital stay before Soliris 35.73 ± 48.60 days 14.92 ± 23.25 days
Hospital stay after Soliris 33.14 ± 38.12  days 27.50 ± 34.77 days

Additionally, the study noted that 18 patients began hemodialysis either before or at the start of Soliris treatment. Of those, 17 remained on hemodialysis 1 month after starting Soliris and 11 after more than 3 months of Soliris treatment.

Six patients died; 5 had CACs. The CACs observed in the patients who died included:
  • Non-renal solid organ transplant (n=2)
  • Renal transplant (n=1)
  • Rheumatoid arthritis (n=1)
  • Ulcerative colitis (n=1)
Based on the analysis, the authors concluded that aHUS paths, regardless of whether they have CACs, can be effectively treated with Soliris. Furthermore, it was speculated that the higher rate of death in CAC positive aHUS patients may be due to a longer time it may have taken those patients to get properly diagnosed.

Reference
Cunningham JM, Ahn J, Broome C. Outcomes for Atypical Hemolytic Uremic Syndrome (aHUS) Treated with Eculizumab: A Single Center Analysis. Presented at the 59th ASH Annual Meeting & Exposition, December 9-12, 2017; Atlanta GA. Abstract 2317. https://ash.confex.com/ash/2017/webprogram/Paper104380.html  
 

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