TY - JOUR
T1 - Personalized medicine in rheumatoid arthritis
T2 - How immunogenicity impacts use of TNF inhibitors
AU - Bodio, Caterina
AU - Grossi, Claudia
AU - Pregnolato, Francesca
AU - Favalli, Ennio Giulio
AU - Biggioggero, Martina
AU - Marchesoni, Antonio
AU - Murgo, Antonella
AU - Filippini, Matteo
AU - Migliorini, Paola
AU - Caporali, Roberto
AU - Pellerito, Raffaele
AU - Ciccia, Francesco
AU - Sarzi-Puttini, Piercarlo
AU - Perosa, Federico
AU - Paolazzi, Giuseppe
AU - Hollan, Ivana
AU - Bendtzen, Klaus
AU - Meroni, Pier Luigi
AU - Borghi, Maria Orietta
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay – RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n = 67), adalimumab (ADL; n = 49) or etanercept (ETA; n = 47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.
AB - Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay – RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n = 67), adalimumab (ADL; n = 49) or etanercept (ETA; n = 47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.
KW - Anti-drug antibody
KW - Immunogenicity
KW - Inflammatory arthritides
KW - Precision medicine
KW - Tumor necrosis factor inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85081689943&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081689943&partnerID=8YFLogxK
U2 - 10.1016/j.autrev.2020.102509
DO - 10.1016/j.autrev.2020.102509
M3 - Review article
AN - SCOPUS:85081689943
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
SN - 1568-9972
M1 - 102509
ER -