Summary of large RCTs assessing various combination therapies for treating newly diagnosed ITP (first line)
| Combination arm . | Monotherapy arm . | Study design . | Efficacy . | Remarks . |
|---|---|---|---|---|
| Rituximab (375 mg/m2 weekly for 4 weeks) + dexamethasone (1-6, 4-day cycle)5 | Dexamethasone (1-6, 4-day cycle) | Open-label RCT with 1:1 randomization, (n = 133) | Response rates at 6 months were 58% in the combination vs 37% in the dexamethasone groups, p = 0.02, with significantly longer time to relapse (p = 0.03) | Increased incidence of grade 3-4 adverse events in the combination group |
| Rituximab (375 mg/m2 weekly for 4 weeks) + dexamethasone (4-day cycle)6 | Dexamethasone (4-day cycle) | Open-label RCT with 1:1 randomization (n = 101) | Response rate at 6 months 63% vs 36%, p = 0.004 | Increased incidence of grade 3-4 adverse events in the combination group |
| Mycophenolate mofetil (MMF) (1-2 g daily) + prednisolone or dexamethasone.7 | Prednisolone or dexamethasone | Open-label RCT with 1:1 randomization (n = 120) | Rate of treatment failure was 22% in the MMF group vs 44% in the control group; HR = 0.41 (95% CI: 0.21-0.80; p = 0.008 | Patients in the MMF group reported worse HRQoL |
| Tacrolimus (initial dose 0.03 mg/kg/day for 12 weeks) + dexamethasone8 | Dexamethasone (1-2, 4-day cycles) | Phase 2, open-label RCT with 1:1 randomization (n = 140) | Sustained response in the combination group was 65% vs 43% in the monotherapy (p = 0.007), rates of treatment failure (19.4% vs 38.2%, p = 0.0014) | Published only in abstract form |
| rhTPO (300 ug/kg sc for up to 14 days) + dexamethasone (1-2, 4-day cycle)10 | Dexamethasone (1-2, 4-day cycle) | Open-label RCT with 1:1 randomization (n = 206) | The combination resulted in higher initial (89% vs 67%; p < 0.001) and durable response rates at 6 months (51% vs 36%; p = 0.02) compared with dexamethasone | Well-tolerated study drugs; only one thromboembolic event occurred in the combination; rhTPO is only available in certain countries in Asia |
| Oseltamivir (75 mg × 2/day for 10 days) + dexamethasone (1-2 4-day cycle)11 | Dexamethasone (1-2, 4-day cycle) | Phase 2 open-label, RCT with 1:1 randomization (n = 96) | Response at day 14 (86% vs 66%; p = 0.030) and at 6 month (53% vs 30%; p = 0.032) in the combination vs monotherapy groups | 19% suffered from gastrointestinal side effects in the combination group |
| ATRA (10 mg × 2/day for 12 weeks) + dexamethasone (14-day cycle)12 | Dexamethasone (1-2, 4-day cycle) | Phase 2 open-label, RCT with 1:1 randomization (n = 132) | Sustained* response rate at 6 months in the combination arm was 68% vs 41% in the monotherapy arm ( = R = 3, p = 0.0017) | Dry skin was reported in 48% of the patients treated with ATRA |
| Combination arm . | Monotherapy arm . | Study design . | Efficacy . | Remarks . |
|---|---|---|---|---|
| Rituximab (375 mg/m2 weekly for 4 weeks) + dexamethasone (1-6, 4-day cycle)5 | Dexamethasone (1-6, 4-day cycle) | Open-label RCT with 1:1 randomization, (n = 133) | Response rates at 6 months were 58% in the combination vs 37% in the dexamethasone groups, p = 0.02, with significantly longer time to relapse (p = 0.03) | Increased incidence of grade 3-4 adverse events in the combination group |
| Rituximab (375 mg/m2 weekly for 4 weeks) + dexamethasone (4-day cycle)6 | Dexamethasone (4-day cycle) | Open-label RCT with 1:1 randomization (n = 101) | Response rate at 6 months 63% vs 36%, p = 0.004 | Increased incidence of grade 3-4 adverse events in the combination group |
| Mycophenolate mofetil (MMF) (1-2 g daily) + prednisolone or dexamethasone.7 | Prednisolone or dexamethasone | Open-label RCT with 1:1 randomization (n = 120) | Rate of treatment failure was 22% in the MMF group vs 44% in the control group; HR = 0.41 (95% CI: 0.21-0.80; p = 0.008 | Patients in the MMF group reported worse HRQoL |
| Tacrolimus (initial dose 0.03 mg/kg/day for 12 weeks) + dexamethasone8 | Dexamethasone (1-2, 4-day cycles) | Phase 2, open-label RCT with 1:1 randomization (n = 140) | Sustained response in the combination group was 65% vs 43% in the monotherapy (p = 0.007), rates of treatment failure (19.4% vs 38.2%, p = 0.0014) | Published only in abstract form |
| rhTPO (300 ug/kg sc for up to 14 days) + dexamethasone (1-2, 4-day cycle)10 | Dexamethasone (1-2, 4-day cycle) | Open-label RCT with 1:1 randomization (n = 206) | The combination resulted in higher initial (89% vs 67%; p < 0.001) and durable response rates at 6 months (51% vs 36%; p = 0.02) compared with dexamethasone | Well-tolerated study drugs; only one thromboembolic event occurred in the combination; rhTPO is only available in certain countries in Asia |
| Oseltamivir (75 mg × 2/day for 10 days) + dexamethasone (1-2 4-day cycle)11 | Dexamethasone (1-2, 4-day cycle) | Phase 2 open-label, RCT with 1:1 randomization (n = 96) | Response at day 14 (86% vs 66%; p = 0.030) and at 6 month (53% vs 30%; p = 0.032) in the combination vs monotherapy groups | 19% suffered from gastrointestinal side effects in the combination group |
| ATRA (10 mg × 2/day for 12 weeks) + dexamethasone (14-day cycle)12 | Dexamethasone (1-2, 4-day cycle) | Phase 2 open-label, RCT with 1:1 randomization (n = 132) | Sustained* response rate at 6 months in the combination arm was 68% vs 41% in the monotherapy arm ( = R = 3, p = 0.0017) | Dry skin was reported in 48% of the patients treated with ATRA |
ATRA, all-trans retinoic acid; CI, confidence interval; HR, hazard ratios; HRQoL, health related qualty of life; MMF, mycophenolate mofetil; RCT, randomized controlled trial; rhTPO, recombinant thrombopoietin receptor agonist.