P144 Therapeutic thresholds for golimumab serum concentrations during induction and maintenance: results from the GO-LEVEL study

Introduction The exposure-response relationship associated with the use of golimumab for UC was demonstrated in the PURSUIT trial. Significant associations between serum golimumab concentrations (SGC) and favourable outcomes were observed during both induction and maintenance therapy. However, data regarding the optimal therapeutic SGC threshold is limited and therefore, recent AGA guidance made no recommendation in this regard. 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 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 less than 3 and FC less than 250 ug/g. SGC and anti-golimumab antibodies (ADA) were measured using a drug sensitive ELISA (LISATRACKER, Theradiag). Mann-Whitney U was used to compare groups, ROC curve analysis to identify therapeutic thresholds, Spearman’s rank coefficient (rs) for correlations and Cochrane-Armitage test for quartile data. 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 ug/ml, respectively, p=0.03). ROC curve analysis demonstrates 3.8 ug/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 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). 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 ug/ml, respectively, p=0.003). ROC curve analysis demonstrates 2.4 ug/ml as the optimal therapeutic threshold to achieve combined remission (sensitivity 0.73, specificity 0.66, AUC 0.71). SGC quartile analyses (figure 1) demonstrated significant trends to higher rates of combined remission with greater exposure during both induction (p=0.01) and maintenance (p=0.01). No AGA were detected in either cohort. Conclusions 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 ug/ml at week 6 and 2.4 ug/ml during maintenance.