TY  - JOUR
AU  - Ross, David J.
AU  - Ardehali, Abbas
AU  - Natori, Christine
AU  - Belperio, John A.
PY  - 2019
DA  - 2019/11/07
TI  - Combination, Sequential Therapies Incorporating Tocilizumab Decrease the Progression of Chronic Lung Allograft Dysfunction (CLAD) after Lung Transplantation: Initial Clinical Experience
JO  - OBM Transplantation
SP  - 090
VL  - 03
IS  - 04
AB  - INTRODUCTION:  TH-17 and IL-6 interactions and detrimental biologic effects have been shown in rodent models of Chronic Lung Allograft Dysfunction (CLAD). Similarly, these pathways have been found to be upregulated in human CLAD.  Tocilizumab (TCZ), a humanized monoclonal antibody targets the IL-6 receptor subunit alpha and prevents binding of IL-6.  We herein report our preliminary experience with adjunctive TCZ therapy for human CLAD. 
METHODS:  We retrospectively reviewed our initial experience with TCZ given after other immunotherapies for CLAD  Linear Regression Slopes for Forced Expiratory Volume-1 sec (FEV-1/Month) (L/month), infection incidence, Single Antigen Flow Cytometry HLA Class I & II Donor-specific antibodies (DSA), Non-HLA Auto-antibodies (EC-1 & 2; AT1R) and adverse events.
RESULTS:  Nine LT recipients with CLAD Stages: BOS I (N=2), BOS II (N=4), BOS III (N=2), RAS (N=1) who received > 3 months treatment with TCZ (4-8 mg/Kg/month intravenous) in combination with Rabbit ATG (N=5), Rituximab (N=1) and IVIG (N=9) were analyzed. Median FEV-1/Month Slope PRE- therapy was -0.132+0.148 L/month and for POST-era this was -0.012+0.049 (P=0.011).   HLA DSA Class I & II decreased in 75% LT recipients while Non-HLA antibodies were unaffected by these therapies. Respiratory viral infection (N=2) and fatal cardiac event (N=1) occurred in this cohort. 
CONCLUSION:  Combination Sequential Immune modulation using Tocilizumab for CLAD after LT can ameliorate the Spirometric decline and would be appropriate for further Multi-Center, controlled clinical trials based on our knowledge of llo-immunologic pathobiology  and these pilot human data.
SN  - 2577-5820
UR  - https://doi.org/10.21926/obm.transplant.1904090
DO  - 10.21926/obm.transplant.1904090
ID  - Ross2019
ER  -