Abstract
Introduction:
ADAMTS13, a cleaving protease, deficiency/relapse during thrombotic thrombocytopenic purpura (TTP) remission is associated with an increased risk of recurrent TTP. Rituximab is currently being used in TTP patients with suboptimal response to plasma exchange. We aim to explore outcomes with Rituximab as a preventive agent in patients with TTP remission and ADAMTS13 deficiency/relapse.
Methods:
Following PRISMA guidelines, a comprehensive search of PubMed, Cochrane, Embase, and ClinicalTrials.gov (inception to July 2025) was conducted using MeSH terms for “Rituximab” and “ADAMTS13.” After screening 1013 references and excluding review articles, meta-analyses, and studies without clinical outcomes of interest, two prospective clinical trials reporting the outcomes of Rituximab as a preventive agent in patients with TTP remission and low ADAMTS13 levels were included. Data on patient demographics, clinical presentation, disease stage, treatment, and survival outcomes were systematically reviewed and summarized.
Results:
A total of 137 patients from two prospective trials were included in this review. Jestin et al reported 92 patients with clinical and hematological remission who received preemptive Rituximab for ADAMTS <10%. The median age was 42 years (33.3-51), and 73% (n = 67) were females. 50% had received Rituximab during the previous acute phase. The median anti-ADAMTS13 IgG antibody titer was 28 U/mL (16-48). Patients received 1 (n = 42), 2 (n = 15), or three or more (n = 35) Rituximab infusions. During the follow-up period of 35.8 months (23.3-68), Rituximab significantly reduced the median number of TTP relapses (0, range, 0-4) and the median cumulative incidence (0 episodes per year, IQR 0-1.32, P < 0.001). At 3 months, ADAMTS13 activity level was normal in 56% (n = 42/76), moderately decreased in 30% (n = 23/76), and still undetectable in 14% (n = 11/76). ADAMTS13 activity progressively increased until 6 months posttransfusion, declined afterwards, and increased again with retreatment. Thirty-four patients (37%) sustained ADATMS13 recovery after a single infusion and did not experience any clinical relapse. A total of 14 (15%) patients suffered relapse (median follow-up of 37.8 months), all with persistent severe ADAMTS13 deficiency, with death reported in 2 patients. Adverse events were reported in 21% (n = 19) of the patients; all were low grades, and none led to drug interruption. No high-grade infections were reported. Westwood et al. administered preemptive Rituximab in 76 patient episodes to 45 patients. Among these 45 patients, 31% had one previous TTP episode and 69% had 2-6 episodes. The median age was 43.5 years (18-78), and 79% (n = 60) were female. The median platelet count was 268 x109/L (83-443) and the median ADAMTS13 activity was 5% (<5-17). After the transfusion, complete ADAMTS13 recovery was documented in 60 (79%) patient episodes, with CR >60%. Additionally, 13% had partial recovery of ADAMTS13 to at least 30%. Of the remaining patient episodes, three had no response to ADAMTS13. With a median follow-up of 15 months (range, 1-141 months), 3 (3.9%) relapses were reported, with 2/3 of the episodes being subacute relapses. Adverse events were reported in 30% (n = 23) patient episodes, with only 2 being high-grade reactions. No increase in infections or significant liver injury was reported.
Conclusions:
Preventive Rituximab infusion in patients with clinical remission and low ADAMTS13 activity leads to a sustained, prolonged increase in ADAMTS13 activity, a significantly decreased relapse rate, and a lower mortality rate. The safety profile was excellent with no high-grade infections. Given these encouraging findings, larger randomized trials are needed to confirm and consolidate these results.
