Effects of Rapamycin Combined with Low Dose Prednisone in Patients with Chronic Immune Thrombocytopenia

Abstract

We conducted this randomized trial to investigate the efficacy and safety of rapamycin treatment in adults with chronic immune thrombocytopenia (ITP). Eighty-eight patients were separated into the control (cyclosporine A plus prednisone) and experimental (rapamycin plus prednisone) groups. The CD4+CD25+CD127low regulatory T (Treg) cells level, Foxp3 mRNA expression, and the relevant cytokines levels were measured before and after treatment. The overall response (OR) was similar in both groups (experimental group versus control group: 58% versus 62%, P = 0.70). However, sustained response (SR) was more pronounced in the experimental group than in the control group (68% versus 39%, P < 0.05). Both groups showed similar incidence of adverse events (7% versus 11%, P = 0.51). As expected, the low pretreatment baseline level of Treg cells was seen in all patients (P < 0.001); however, the experimental group experienced a significant rise in Treg cell level, and there was a strong correlation between the levels of Treg cells and TGF-beta after the treatment. In addition, the upregulation maintained a stable level during the follow-up phase. Thus, rapamycin plus low dose prednisone could provide a new promising option for therapy of ITP.

Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study

“…Li et al (23) demonstrated that treatment with rapamycin plus prednisone can increase PLT number in chronic ITP patients; increased PLT number was associated with a significant increase in Treg cell levels and TGF-beta in patient plasma after treatment. Consistent with this observation, levels of Treg cells were lower in ITP patients compared with healthy donors prior to treatment in our cohort study.…”

State of the art – how I manage immune thrombocytopenia

“…Combining immunosuppressive treatments with TPO‐RAs show the most promise (Mahévas et al , ). Additional immunosuppressive agents can be useful, including cyclophosphamide (Verlin et al , ; Reiner et al , ), rapamycin (Li et al , ), and anti‐TNF agents (McMinn et al , ; Litton, ). However some patients remain refractory to all medications, intermittently using IVIG and steroids for acute episodes.…”

Combination therapy in relapsed or refractory chronic immune thrombocytopenia: a case report and literature review

“…GCs, rituximab and CsA were the most frequently used agents in Group A, with an overall response rate (ORR) of 58–100%, complete remission (CR) rates of 30–64% and sustained CR rates of 10–70%. This group includes one randomized clinical trial (RCT), with 88 patients (all steroid‐refractory) randomized between corticosteroids with either sirolimus or CsA . There were no significant differences between the groups in ORR (58% vs. 62%, respectively) and CR rate (35% vs. 38%, respectively).…”

“…A total of 14 studies were eligible [10][11][12][13][14][15][16][17][18][19][20][21][22][23] (Table 1). According to the classification presented above, 8 studies used approaches (i) alone (Group A), 2 used approaches (i) and (ii) combined (Group B), 3 used approaches (i) and (iii) combined (Group C) and 1 used approaches (ii) and (iii) combined (Group D).…”

“…This group includes one randomized clinical trial (RCT), with 88 patients (all steroid-refractory) randomized between corticosteroids with either sirolimus or CsA. 18 There were no significant differences between the groups in ORR (58% vs. 62%, respectively) and CR rate (35% vs. 38%, respectively). Although sustained response (defined in the study as platelet count ≥50 9 10 9 /L during follow-up) seemed to be higher in the sirolimus group (68% vs. 39%, respectively), the P value was not reported.…”