Abstract
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) that can lead to end organ damage and death without treatment. The ability to rapidly distinguish aHUS from other forms of TMA is key for optimal patient management. The PLASMIC Score was developed to identify individuals with thrombotic thrombocytopenic purpura (TTP), a TMA subtype characterized by severe ADAMTS13 deficiency (< 10%), using 7 commonly available laboratory variables and aspects of the patient's medical history. This study aimed to assess the distribution of PLASMIC Scores in patients with known aHUS, and evaluate the utility of the PLASMIC Score in the diagnostic pathway of aHUS in patients with confirmed TMA. METHODS: Data from eculizumab (NCT01194973) and ravulizumab (NCT02949128) clinical trials were utilized to calculate and evaluate PLASMIC Score distribution in aHUS patients. Real-world patient-level data from the PINC AI™ Healthcare Database (PHD) were used to evaluate the performance of the PLASMIC Score in identifying aHUS in patients with documented TMA diagnoses and renal impairment (primary analysis population; n = 110), and subsequent sensitivity analyses were performed in alternative populations. RESULTS: A total of 94 aHUS patients from the eculizumab and ravulizumab clinical trials dataset were evaluated; 18/36 (50.0%) and 27/58 (46.6%) patients in the eculizumab and ravulizumab trials, respectively, had a PLASMIC Score of 4, and most patients (~ 85%) had PLASMIC Scores ≤ 5 (range: 3-5), which were distributed similarly between the trials. Among the 110 patients with undifferentiated TMA (primary analysis) from the PHD, a PLASMIC Score cutoff of ≤ 5 yielded sensitivity, specificity and positive predictive value (PPV) and negative predictive values (NPV) of 86.5%, 71.4%, 92.8% and 55.6%, respectively, for identifying probable aHUS. Similar diagnostic performance was observed at a cutoff value of ≤ 5 in further sensitivity analyses. A cutoff value of ≤ 4 yielded a lower PPV (62.9%), yet a higher NPV (85.7%), with only 3 patients misclassified as TTP. CONCLUSION: Application of the PLASMIC Score in the aHUS diagnostic pathway may support clinical judgement and ascertain confidence in the earlier identification and subsequent treatment of patients with aHUS, thereby improving patient outcomes.