P465 Is golimumab serum level predictive of clinical remission after intensification for loss of response in patients with ulcerative colitis?
Fumery, M.(1);Nancey, S.(2);Filippi, J.(3);Altwegg, R.(4);Hebuterne, X.(3);Boschetti, G.(2);Veyrard , P.(5);Yzet, C.(1);Paul, S.(6);Roblin, X.(5);
(1)Amiens University Hospital, Gastroenterology, Amiens Cedex 1, France;(2)Lyon University Hospital, Gastroenterology, Lyon, France;(3)Nice University Hospital, Gastroenterology, Nice, France;(4)Montpellier University Hospital, Gastroenterology, Montpellier, France;(5)Saint Etienne University Hospital, Gastroenterology, Saint Etienne, France;(6)Saint Etienne University Hospital, Immunology, Saint Etienne, France; GOLILOR Study group
Loss of response to golimumab occurs in nearly 40% of patients with ulcerative colitis (UC). Unlike others anti-TNF, no study has reported a correlation between serum golimumab level and response to drug intensification. The objective of this study was therefore to determine a threshold of serum golimumab before intensification predictive of clinical remission after optimization.
We included consecutive patients with UC and loss of response to golimumab (Mayo score between 6 and 12 and an endoscopic Mayo sub-score> 1) in a prospective multicentric cohort. Patients with loss of response at 50 mg / 4 weeks (W) and 100 mg / 4W underwent therapeutic intensification at 100 mg / 4W and 100 mg / 2W, respectively. Patients were followed prospectively with a first evaluation between weeks 2 and 4 (visit 2) and between weeks 4 and 8 (visit 3) after intensification. Clinical remission was defined by partial Mayo score ≤ 1. Serum level and anti-golimumab antibodies were evaluated at each visit (Lisa Tracker, Theradiag France).
A total of 47 patients (female, 50%; median age, 39 years (IQR, 27-52) treated with golimumab for a median of 20.4 weeks (IQR, 10.7-38.3) were included. The median partial Mayo score was 6 (IQR, 5-7) and the endoscopic Mayo score was 3 (IQR, 2-3). The median golimumab serum level before intensification was 2.23 µg / mL (IQR, 1.02-3.96) and only three patients (6.2%) had anti-drug antibodies. After a total of 50 drug intensification, 23 (48.9%) patients had clinical response (100 mg / 4W: 14/25 (58.3%) ; 100 mg / 2W: 9/25 (36%)), 10 (21%) clinical remission and 18 (39%) endoscopic response. The median golimumab levels before intensification were respectively 2.17 µg / mL (IQR, 0.97-3.25) and 2.47 (IQR, 1.10-4.05) in responders and non-responders (p = 0.66), and 1.11 µg / mL (IQR, 0.59-2.29) and 2.47 µg / mL (IQR, 1.21-3.83) in patients with and without clinical remission after intensification (p = 0.054). In multivariate analysis, intensification to golimumab 100 mg / 2W (vs 100 mg / 4W) (OR, 0.11 [95%CI, 0.01 - 0.87], p=0.037) and change of golimumab level between V1 and V2 (OR, 1.48 [95%CI, 1.02 - 2.14], p=0.037) were significantly associated with clinical remission after intensification. Only one serious adverse event (infection) was reported during the 24-week follow-up.
In this prospective multicentric study, half of patients recaptured response following golimumab intensification in UC. Change of golimumab level was predictive of clinical remission after intensification.