Table 2.
Medical treatment of AE-IPF other than high-dose intravenous corticosteroids mono therapy.
| Treatment | Reference | Study design | Number of patients | Treatment/intervention | Clinical outcome |
|---|---|---|---|---|---|
| Tacrolimus | Horita et al. (82) | Single-center, retrospective study | 15 | Steroids mono versus combination steroids plus tacrolimus | Significantly better survival in tacrolimus-group |
| Cyclosporine | Inase et al. (102) | Single-center, retrospective study | 14 | Steroids mono versus steroids followed by cyclosporine | Cyclosporine seemed to prevent re-exacerbation and improve survival (no data on significance level) |
| Homma et al. (103) | Retrospective study | 44 | Effect of treatment with steroids mono versus steroids plus cyclosporine before AE-IPF | Significantly better survival in cyclosporine-group | |
| Sakamoto et al. (104) | Single-center, retrospective study | 22 | Steroids mono versus combination of steroids plus cyclosporine | Significantly better survival in cyclosporine-group | |
| Rituximab | Donahoe et al. (105) | Pilot- phase I/II-study; historical controls | 31 | Steroids mono versus combination of steroids plus rituximab/therapeutic plasma exchanges and IVIG in severely ill IPF | Significantly better 1-year survival in rituximab group |
| PMX | Seo et al. (99) | Open-label pilot trial | 6 | Combination of steroids plus PMX | Potential beneficial effect of treatment with PMX |
| Abe et al. (106) | Multi-center, retrospective study | 160 | Combination of steroids plus PMX | PMX improved oxygenation and may improve survival in IP patients with AE | |
| Abe et al. (107) | Single-center, retrospective study | 45 | Steroids mono versus combination of steroids plus PMX | PMX treatment significantly improved oxygenation | |
| Oishi et al. (108) | Single-center, retrospective study | 50 | Steroids mono versus combination of steroids plus PMX | Significantly better 1-year survival in PMX group | |
| Oishi et al. (109) | Single-center, retrospective study | 26 | Stable IPF and healthy controls versus combination of steroids plus PMX in AE-IPF | PMX treatment significantly improved oxygenation | |
| Thrombomodulin i.v. | Isshiki et al. (110) | Single-center, retrospective study | 41 | Steroids mono versus combination of steroids plus recombinant human soluble thrombomodulin | Thrombomodulin treatment significantly improved 3-month survival |
| Kataoka et al. (112) | Single-center, retrospective study | 40 | Combination of steroids and cyclosporine versus combination of steroids and cyclosporin plus recombinant human soluble thrombomodulin | Thrombomodulin treatment significantly improved 3-month survival | |
| Tsushima et al. (111) | Single-center, combined prospective and retrospective study | 20 | Combination of steroids plus recombinant human soluble thrombomodulin | Thrombomodulin treatment significantly improved oxygenation | |
| Hayakawa et al. (113) | Single arm, non-randomized prospective clinical trial; historical controls | 23 | Steroids mono versus combination of steroids plus recombinant human soluble thrombomodulin | Thrombomodulin plus steroid pulse therapy improved oxygenation and may improve overall survival | |
| Abe et al. (114) | Single-center, prospective, non-randomized study | 22 | Steroids mono versus combination of steroids plus recombinant human soluble thrombomodulin | Thrombomodulin treatment significantly improved 3-month survival | |
| Procalcitonin-guided antibiotic therapy | Ding et al. (115) | Single-center, prospective, randomized study | 68 | Clinically guided versus procalcitonin-guided antibiotic therapy | Procalcitonin-guided antibiotic therapy had no benefits on survival |
| Cyclophosphamide | Akira et at (20) | Single-center, retrospective study | 58 | Steroids mono and combination of steroids mono plus cyclophosphamid | No data on treatment-related outcome |
| Fujimoto et al. (21) | Multi-institutional, retrospective study | 60 | Steroids plus cyclophosphamide and steroids plus cyclosporine | No data on treatment-related outcome | |
| Yokoyama et al. (116) | Single-center, retrospective study | 11 | Steroids mono and combination of steroids mono plus cyclophosphamide and combination of steroids mono plus cyclosporine | No data on treatment-related outcome | |
AE-IPF, acute exacerbation of idiopathic pulmonary fibrosis; IPF, idiopathic pulmonary fibrosis; i.v., intravenous; IVIG, intravenous immunoglobulin; PMX, polymyxin B-immobilized fiber column.