TABLE 1.
Studies for therapy of chronic antibody-mediated rejection.
| Tx | Study design (no. of Ptx) | Diagnostic criteria | Treatment | ISAs | Time after CAMR | Graft loss | Graft function | Ref |
|---|---|---|---|---|---|---|---|---|
| PE and IVIG | Retrospective cohort study (123) | Chronic active ABMR | Steroids, IVIG, PE, RTX, or ATG vs no Tx | All ptx received CNIs | 4.3 years | Steroids + IVIG | NR | Redfield et al. (2016) |
| −BANFF 2013 | −HR 0.38 for graft loss (in unadjusted analysis) | |||||||
| No additional benefit of rituximab or ATG to CS/IVIG | ||||||||
| Retrospective cohort study (69) | Chronic active ABMR | IVIG + CS | Variable | 6.3 years | Graft survival at 1, 3 and 5 years after chronic active ABMR diagnosis | ΔeGFR | Sablik et al., (2019) | |
| -BANFF classification | -Responders: 100, 75 and 59% | −9.8/yr prior to tx | ||||||
| -Non-responders: 89, 57 and 20% | −6.3/yr after tx (p < 0.05) | |||||||
| RTX | Prospective cohort study (20 pediatric ptx) | Chronic ABMR | All ptx received IVIG RTX | All ptx received CS MMF TAC or CsA | 2 years | 20% | ΔeGFR from −7.6 during 6 months prior to tx to −2.1 during 6months after tx (p < 0.05) | Billing et al. (2012) |
| -BANFF 2005 | ||||||||
| Retrospective cohort study (59) | Chronic ABMR | IVIG RTX CS vs CS | All ptx received CNIs | >2 years | IVIG RTX + CS | ΔeGFR 0.2/month in RTX group (p < 0.05 compared to the pre-6 months ΔeGFR) | Chung et al. (2014) | |
| -BANFF 2005 | −HR 0.24 for graft loss | ΔeGFR −1.4/month in control group (p = NS compared to the pre-6 months ΔeGFR) | ||||||
| Retrospective cohort study (21) | Chronic ABMR with TG | IVIG CS + RTX vs no IVIG RTX | CNIs | 2 years | 53% in RTX group | NR | Bachelet et al. (2015) | |
| -BANFF 2013 | 95% in RTX group | 60% in control group | ||||||
| 80% in control group | ||||||||
| Retrospective cohort study (62) | Chronic active ABMR with TG | IVIG PE + RTX vs no Tx | Variable | 27 months | NS | NS | Piñeiro et al. (2018) | |
| -BANFF 2017 | ||||||||
| Placebo-controlled RCT (25) | Chronic ABMR: TG ± C4d in ptc; anti-HLA DSA | IVIG RTX vs placebo | All ptx received TAC MMF | 1 year | 8% in RTX group | ΔeGFR | Moreso et al. (2018) | |
| 8% in placebo group | −4.2 in RTX group | |||||||
| −6.6 in placebo group (p = NS) | ||||||||
| Bortezomib | Prospective cohort study (30) | Early acute ABMR (13 ptx) and late acute ABMR (17 ptx) | All pts received PE RTX bortezomib | All ptx received TAC MMF | 7 months | 10% in early ABMR | eGFR from 40 prior to tx to 66 after tx in early ABMR (p < 0.05) | Walsh et al. (2011) |
| -BANFF 2007 | 20% in late ABMR | eGFR from 27 prior to tx to 37 after tx in late ABMR (p < 0.05) | ||||||
| Placebo-controlled RCT (44) | Late ABMR | Bortezomib vs placebo | All ptx received CS MMF TAC or CsA | 2 years | 19% in bortezomib group | eGFR slope | Eskandary et al. (2018b) | |
| BANFF 2013 (28 ptx: chronic active ABMR) | 4% in placebo group (p = NS) | −4.7/year in bortezobmib group −5.2/year in placebo group (p = NS) | ||||||
| Eculizumab | Nonblinded RCT (20) | Chronic ABMR: DSA >MFI 1100; 20% reduction in eGFR; no severe fibrosis | Eculizumab vs control | CNIs or rapamycin | 1 year | NR | NS | Kulkarni et al. (2017) |
| C1 inhibitor | Prospective phase 1 study (10) | Late ABMR | All ptx received C-INH (BIVV009) | All ptx received CS MMF + CNIs (9 ptx – TAC, 1 ptx - CsA) | 50 days | NR | Stable | Eskandary et al. (2018a) |
| -BANFF 2013 (9 ptx: chronic active ABMR) | ||||||||
| IL-6 Tocilizumab | Prospective cohort study (36) | Chronic ABMR with TG - BANFF 2013 | All ptx received tocilizumab | All ptx received CS MMF + TAC | 3.3 years | 11.1% | Stable | Choi et al. (2017) |
| Clazakizumab | Randomized, placebo controlled, parallel-group phase 2 trial (20) | Late active or chronic active ABMR ≥ 365 days post-transplantation with a molecular pattern of ABMR | Clazakizumab vs palcebo | 18 ptx received CNIs or mTOR inhibitor-based triple therapy, 2 ptx received dual therapy without steroids | 52 weeks | 1 ptx at 3 months after last visit | eGFR slope −0.96/month in clazakizumab group | Doberer et al. (2020) |
| −2.43/month in placebo group (p < 0.05) | ||||||||
| Improvement of eGFR slope in pts switched from placebo to clazakizumab (p < 0.05) |
eGFR is reported as mL/min/1.73 m2.
ATG, rabbit antithymocyte globulin; CAMR, chronic antibody-mediated rejection; CNIs, calcineurin inhibitors; CS, corticosteroid; CsA, cyclosporin A; DSA, donor-specific antibodies; eGFR, estimated glomerular filtration rate; HR, hazard ratio; ISA, immunosuppressive agent; IVIG, intravenous immunoglobulin; MMF, mycophenolate mofetil; NR, not reported; NS, non-significant; PE, plasma exchange; ptc, peritubular capillary; Ptx, patient; RCT, randomized controlled trial; Ref., reference; RTX, rituximab; TAC, tacrolimus; TG, transplant glomerulopathy; Tx, treatment; Δ, change in.