Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura

Abstract

Although steroids are routinely used as an adjunct to plasma exchange (PEX) therapy in the treatment of immune-mediated thrombotic thrombocytopenic purpura (iTTP), limited data regarding their efficacy or effect on ADAMTS13 biomarkers are available. We report the results of a prospective, randomized study that compared the effectiveness of prednisone or cyclosporine (CSA) as adjuncts to PEX in the treatment of iTTP. A total of 26 of the planned 72 subjects were enrolled and treated from November 2007 until February 2014 before the study was halted after a planned interim analysis. Fourteen patients were randomly assigned to the prednisone arm, and 12 to the CSA arm of the study. One patient died in each arm of the study, and 2 patients in the prednisone arm of the study failed to achieve a response and crossed over to the CSA arm, leaving 11 patients in each arm of the study evaluable for the primary end point of exacerbation. One of the 11 prednisone-treated subjects (9%) suffered an exacerbation, whereas 3 of the 11 (27%) patients in the CSA arm suffered an exacerbation. Although there was no significant difference in the exacerbation rate, suppression of the anti-ADAMTS13 antibodies and improvement in ADAMTS13 activity in the first month after stopping PEX were significantly better in the prednisone-treated subjects. Side effects were manageable and comparable in both arms of the study. These data demonstrate the superiority of prednisone over CSA as an adjunct to PEX in the suppression of the anti-ADAMTS13 antibodies and improvement in ADAMTS13 activity. This trial was registered at www.clinicaltrials.gov as #NCT00713193.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Graphical abstract

Figure 1.

Treatment plan and description of outcomes for enrolled subjects. (A) The eligibility and treatment schema for the study are shown. Eligible patients were randomly assigned to prednisone or CSA 1:1 in a prespecified manner. (B) The eligibility and treatment schema for the study are shown. A total of 11 subjects in each arm were evaluable for the primary outcome of exacerbation. Of the 18 subjects evaluable for long-term relapse rate, 3 subjects (1 in the prednisone arm, 2 in the CSA arm) elected to receive prophylactic therapy and were not evaluable for relapse.

Figure 2.

ADAMTS13 activity over the first month of follow-up after stopping PEX. The serial measurements of the median ADAMTS13 activity over the first month of follow-up after the last PEX procedure are shown. ADAMTS13 activity was significantly greater in the prednisone arm compared with the CSA arm beginning at week 3 of follow-up.

Figure 3.

Anti-ADMATS13 antibody levels over the first month of follow-up after stopping PEX. The serial measurements of the median anti-ADAMTS13 IgG and inhibitor titer levels over the first 4 weeks after stopping PEX are shown. The anti-ADAMTS13 IgG levels are significantly lower in the prednisone-treated patients beginning in week 2, corresponding well to the improvement in ADAMTS13 activity. There was no statistically significant difference in the inhibitor titers between the 2 arms of the study.

Figure 4.

ADAMTS13 activity and anti-ADAMTS13 antibody levels over the 6 months after stopping PEX. The measurements of the median ADAMTS13 activity (A) and anti-ADAMTS13 IgG concentration (B) are shown for both the prednisone- and CSA-treated patients. Patients that suffered an exacerbation or that crossed over from another treatment arm are not included in these graphs. In the prednisone arm of the study, all prednisone was tapered and stopped at the end of month 2, whereas the CSA-treated patients continued with the full-dose treatment throughout the 6-month time period shown.