Cyclosporine and Plasma Exchange Is Superior to Corticosteroids and Plasma Exchange as Initial Therapy of TTP.
Authors: Cataland Spero R. , Jin Ming , Ferketich Amy K. , Kraut Eric H. , George James N. , Wu Haifeng M. 
Published: April 2020

Patients with a clinical diagnosis of TTP presenting to The Ohio State University between April 2003 and July 2005 were enrolled and treated on one of two consecutive, prospective clinical trials. The first study treated patients with concurrent corticosteroids and plasma exchange(PE), with the second study using concurrent cyclosporine(CSA) and PE as initial therapy.

Patients: Eleven patients categorized as idiopathic TTP were enrolled on the corticosteroid/PE study and 5 patients (4 idiopathic, 1 SLE associated) have been enrolled to date on the concurrent CSA/PE study. Complete demographic data for both study populations is shown in Table 1.

Table 1. Demographic Information Corticosteroids/Plasma Exchange Cyclosporine/Plasma Exchange N 11 5 Sex Male 4 1 Female 7 4 Race Caucasian 7 4 African American 4 1 Previous Treatment for TTP 6/11 4/5

Methods: Patients treated on the corticosteroid/PE study received prednisone (1 mg/kg/day) concurrent with daily plasma exchange therapy until remission was achieved. After remission, patients tapered the corticosteroids over 4 weeks. Patients enrolled on the CSA/PE study received CSA (2–3 mg/kg/day) concurrent with PE until remission was achieved. CSA was then continued for a total of 6 months of therapy and discontinued. Serial measurements of ADAMTS13 activity and inhibitors were obtained prior to therapy, after remission was achieved and PE discontinued, and serially throughout follow-up.

Results: Nine of 11 patients achieved remission with concurrent corticosteroids and PE, with 2 patients refractory to therapy.

Clinical Response and Laboratory Data Corticosteroids/PE Cyclosporine/PE * p= 0.05 Clinical Data Remission 9/11 5/5 Median Days to Remission 7 (range, 5 to 9) 6 (range, 5 to 9) &lt; 30-Day Recurrence 6/9 0/5 &gt; 30-Day recurrence 1/9 1/5 Laboratory Data Median Pre-Treatment ADAMTS13% 1 (range, 0 to 5) 8 (range, 0 to 60) Median Pre-Treatment Inhibitor (ug/ml) 338 (range 188 to 1,950) 2,325 (range, 223 to 2,594) Median Remission Inhibitor* (ug/ml) 1,550* (range 144 to 5,704) 1,265* (range, 127 to 2,150)

Six of the 9 patients achieving remission suffered a recurrence of TTP within 30 days of tapering PE, and while still taking corticosteroids. In contrast, all 5 patients treated with concurrent CSA/PE achieved a remission with no patients suffering a recurrence within 30 days of tapering PE. More importantly, patients treated with concurrent corticosteroids/PE had an increase in median inhibitor titer (338 ug/ml to 1550 ug/ml) after successful treatment with corticosteroids/PE, in contrast to the CSA/PE treated patients that had a significant decrease in median inhibitor titer (2325 ug/ml to 1265 ug/ml) after therapy. This decrease in ADAMTS13 inhibitors after CSA/PE treatment compared to the corticosteroids/PE treated patients was found to be statistically significant (p=0.05) by the exact Wilcoxon Rank Sum Test.

Conclusions: The CSA/PE treated patients compared to the corticosteroid/PE treated patients had a statistically significant decrease in the inhibitor titer. This may in part explain the improvement in remission rate and 30-day recurrence rate seen with the CSA/PE treated patients.