Study of the Golimumab Exposure-Response Relationship Using Serum Trough Levels (GO-LEVEL)

The purpose of this study is to gain insight into the exposure-response relationship of golimumab in moderate-to-severe Ulcerative Colitis (UC). Patients commencing induction therapy with golimumab will be enrolled into a prospective study and evaluated at three time-points (weeks 6, 10 and 14) for clinical and biochemical UC disease activity as well as serum golimumab concentrations and the presence of anti-golimumab antibodies. Patients already established on stable golimumab maintenance therapy will be enrolled into a cross-sectional study with the same evaluations taken at a single time point.

The study will involve two study groups designed to offer insights into the pharmacokinetics of golimumab during induction and maintenance therapy: Cohort 1: Patients commencing golimumab induction therapy will be included in a prospective, observational study. Cohort 2: Patients receiving golimumab maintenance therapy will be included in a cross-sectional, observational study. Primary objective: To define a week 6 serum golimumab concentration that predicts response at week 14. Secondary objective: To define serum golimumab concentrations at weeks 6, 10 and 14 that predict response at each time point, respectively and at week 14. Exploratory objectives: Correlations between serum golimumab concentrations and novel disease activity indices (PRO2), biochemical markers of disease activity (CRP, faecal calprotectin) and quality of life indices (IBD-Q and IBD-Control). Correlations between the presence of anti-golimumab antibodies, serum golimumab concentrations and UC disease activity. This study will also generate data that can be used to validate a commercially available golimumab assay as well as a novel patient reported outcome (PRO) assessment of clinical UC disease activity.

Serum protein marker with higher values associated with increasing inflammatory activity and lower serum levels of anti-TNF agents (such as golimumab)

Evaluated using Patient Reported Outcome 2 (PRO2). PRO2 ranges from 0-5 with higher scores denoting increasing clinical disease activity.

Evaluated using IBD-Control questionnaires. IBD-Control scores range from 0-16 with higher scores denoting better quality of life.

At any study time point during induction therapy (weeks 6, 10 or 14) and at the point if study entry during maintenance

Inclusion Criteria for cohort 1: Aged 18 years or over Moderate-to-severe UC, defined as: SCCAI > 5 and, i. A raised fecal calprotectin (> 59 μg/g) or, ii. A raised CRP (> 5 mg/L) or, iii. Endoscopic disease activity Mayo 2 or above, Evaluated within 4 weeks of study enrollment Commencing golimumab treatment Written informed consent to participate Sufficient English language skills to understand the patient information sheet and consent form Inclusion Criteria for cohort 2: Aged 18 years or over Receiving golimumab treatment for UC for over 18 weeks (6 injections) Written informed consent to participate Sufficient English language skills to understand the patient information sheet and consent form Exclusion Criteria (cohort 1 only): Contra-indication to golimumab: tuberculosis or severe infections Imminent need for colectomy (i.e. colectomy is being planned) Previous primary non-response to anti-TNF therapy in the opinion of the investigator Previous treatment with more than one anti-TNF therapy (excluding golimumab)

Samaan MA, Cunningham G, Tamilarasan AG, Beltran L, Pavlidis P, Ray S, Mawdsley J, Anderson SH, Sanderson JD, Arkir Z, Irving PM. Therapeutic thresholds for golimumab serum concentrations during induction and maintenance therapy in ulcerative colitis: results from the GO-LEVEL study. Aliment Pharmacol Ther. 2020 Jul;52(2):292-302. doi: 10.1111/apt.15808. Epub 2020 Jun 7.