P723 Therapeutic thresholds for golimumab serum concentrations during induction and maintenance: Results from the GO-LEVEL study

Abstract

Abstract Background The exposure–response relationship associated with the use of golimumab for UC has been previously demonstrated in the PURSUIT trial programme. A significant association between serum golimumab concentrations (SGC) and favourable outcomes was observed during both induction and maintenance therapy. However, data regarding the optimal therapeutic SGC threshold is limited. Methods GO-LEVEL was an open-label, phase IV, investigator initiated study (NCT03124121) which included a prospective cohort of UC patients commencing golimumab induction therapy, as well as a cross-sectional cohort receiving maintenance treatment (>18 weeks from initiation). Patients commencing induction therapy all had disease activity objectively confirmed and were evaluated at weeks 6, 10 and 14. Patients receiving maintenance therapy were recruited either at the point of flare, or during stable remission. Clinical disease activity was evaluated using SCCAI and PRO2, and biochemical activity using FC and CRP. Combined clinical-biochemical remission was defined as SCCAI<3 as well as FC<250ug/g. SGC and anti-golimumab antibodies (AGA) were measured using a drug-sensitive ELISA (LISATRACKER, Theradiag). Fishers exact or Mann–Whitney U were used to compare groups, ROC analysis to identify therapeutic thresholds and Spearman’s rank coefficient (rs) for correlations. Results Thirty-nine patients were included in the induction cohort, of whom 15 (38%) achieved combined remission at week 6. The median SGC of those in combined remission was significantly higher than those who were not (5.0 vs. 3.1 μg/ml, respectively, p = 0.03). ROC curve analysis demonstrates 3.8 μg/ml as the optimal therapeutic threshold to achieve combined remission at week 6 (sensitivity 0.71, specificity 0.65, AUC 0.72). Significant, inverse correlations were also observed between week 6 SGC and PRO2, CRP and FC (rs −0.41 (p = 0.01), −0.47 (p = 0.004) and −0.40 (p = 0.02), respectively). However, week 6 SGC did not predict outcomes at week 10 or 14. Sixty-four patients were included in the maintenance cohort; 32 (50%) were in combined remission, 32 were not. The median SGC of those in combined remission was significantly higher (3.0 vs. 2.1 μg/ml, respectively, p = 0.003). ROC curve analysis demonstrates 2.4 μg/ml as the optimal therapeutic threshold to achieve combined remission (sensitivity 0.73, specificity 0.66, AUC 0.71). No AGA were detected in either cohort. Conclusion GO-LEVEL offers further evidence of the exposure-response relationship with golimumab. Clinicians may consider using therapeutic drug monitoring to optimise golimumab dosing aiming to achieve our suggested SGC therapeutic thresholds of 3.8 μg/ml at week 6 and 2.4 μg/ml during maintenance.