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Background 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. Methods 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). Results 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. Conclusion 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.

Background We aimed to describe the long-term impact of achieving endoscopic and deep remission among participants in the effect of tight control management on CD (CALM) trial. Methods We analysed medical records from patients with follow-up data since end of CALM. Patients were stratified by outcomes in CALM at 1 year: clinical remission (Crohn’s disease activity index, CDAI Results One hundred twenty-two patients with median age 29 years (IQR 22.5–37) and median disease duration 0.2 years (IQR 0.1–0.8) were included. Median follow-up time from end of CALM was 3.02 years (range 0.05–6.26 years). Fifty per cent were randomised to the tight control arm. There were no significant differences in baseline characteristics in patients with follow-up data and those lost to follow-up with the exception of a slightly higher CDEIS score in patients lost to follow-up (14.6 vs. 12.9, p = 0.04). Thirty-four patients (27.9%) had a major adverse outcome during follow-up. Patients in clinical remission at 1 year did not have significantly lower rates of the composite endpoint (log-rank p = 0.15). Patients in endoscopic and deep remission at the end of CALM were significantly less likely to have a major adverse event over time (Figures 1 and 2). After adjusting for age, disease duration, prior surgery, prior stricture, and randomisation arm, endoscopic remission (aHR 0.44, 95% CI 0.20–0.96, p = 0.038) and deep remission (aHR 0.25, 95% CI 0.09–0.72, p = 0.01) were significantly associated with lower risk of major adverse events. Conclusions Early CD patients who achieve endoscopic or deep remission after 1 year of intensive treatment are less likely to have disease progression over a median of 3 years.

BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD). METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period. RESULTS: Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome. CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy. ispartof: GASTROENTEROLOGY vol:159 issue:1 pages:139-147 ispartof: location:United States status: published