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P481 Efficacy of the sequential use of a second biologic agent for Crohn’s disease treatment in a non-academic tertiary centre

J. C. Silva*1, A. P. Silva1, A. Rodrigues1, C. Fernandes1, A. Ponte1, J. Rodrigues1, M. Sousa1, A. C. Gomes1, J. Carvalho1

1Centro Hospitalar Vila Nova de Gaia/Espinho, Gastroenterology, Vila Nova de Gaia, Portugal


One-third of Crohn’s disease (CD) patients, treated with anti-TNF agents do not respond to the drug (primary failure), and a relevant proportion from those who respond experiences loss of response (secondary failure) or intolerance over time. The aim was to investigate the efficacy of the sequential use of a second biologic agent after failing or developing intolerance to an anti-TNF drug as well as identify predictors of treatment failure.


Retrospective cohort-study, which included all CD patients who started anti-TNF between 2003–2017. The main outcome was the efficacy of a second biologic agent, measured by 12-week clinical remission (CR), 1-year CR and 1-year endoscopic (ER). When endoscopy could not adequately evaluate inflammation (small bowel CD), resolution of inflammation as assessed by cross-sectional imaging. Secondary outcomes includes identification of predictors to second-line biologic agents failure, time to treatment failure (defined as need to dose increase, switch biologic or surgery). Deep remission (DR) was defined as CR (as described in medical records), ER (absence of ulcers and erosions in endoscopy) and in ileal Crohn’s disease as absence of radiologic activity.


118 patients were included. Mean age was 39.8 years (SD 12.4) and 53.4% were females (n = 63). Anti-TNF therapy succeeded in 66.9% (n = 79), nonetheless dosing intensification was necessary in 46.8% (n = 37). Primary failure, loss of response and intolerance to anti-TNF occurred in 3.4% (n = 4), 25.4% (n = 30) and 4.2% (n = 5) respectively. A second biologic agent was started in 28.8% (n = 34). Treatment failure of a second biologic agent occurred in 67.7% (n = 23), and mean time to failure was 56.0 weeks (SD 62.3). Primary failure occurred in 20.6% (n = 7), and loss of response in 17.6% (n = 6). For a second agent 12-week CR rate was 52.9%, 1-year CR rate 71.4% and ER and/or absence of imagological activity 15.4%. Therapy was escalated to a third biologic agent in 9.3% (n = 11). There was an association between 1-year CR with anti-TNF and the need to escalate to a second biologic (p = 0.032). DP was associated with response to initial anti-TNF (p = 0.022). Failure of second biologic (primary failure or loss of response) was associated with absence oflong-term CR (p = 0.009). Failure of a second biologic agent was associated with age<40 at diagnosis (p = 0.012) and surgery for perianal disease (p = 0.004).


Sequential use of a second biologic agent failed in more than one third of patients, nonetheless clinical remission at 50 weeks was obtained in most patients. Younger age at diagnosis and surgery for perianal disease are potential predictors of failure of a second biologic agent.