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P277 Frequency and effectiveness of empirical anti-TNF dose intensification in Inflammatory Bowel Disease: systematic review with meta-analysis

Guberna Blanco, L.(1);Nyssen, O.P.(1);Chaparro, M.(1);Gisbert, J.P.(1);

(1)Gastroenterology Unit- Hospital Universitario de La Princesa- Instituto de Investigación Sanitaria Princesa IIS-IP- Universidad Autónoma de Madrid UAM- and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBERehd, Gastroenterology Unit, Madrid, Spain

Background

Loss of response to anti-TNF (tumor necrosis factor) therapies in inflammatory bowel disease occurs in a high proportion of patients. However, the precise incidence of dose intensification (DI) and its effectiveness remains unclear. Our aims were: 1) To evaluate the need of DI of anti-TNF therapy either by increasing the dose or decreasing doses’ interval; 2) To evaluate possible variables influencing its requirement; 3) To assess the effectiveness of empirical DI.

Methods

Bibliographical searches were performed in Pubmed, Embase, the Cochrane Library and CINAHL. Selection: prospective and retrospective studies assessing loss of response to anti-TNF therapy, considered as the need of DI, in Crohn’s disease (CD) and ulcerative colitis (UC) patients treated for at least 12 weeks with an anti-TNF drug [infliximab (IFX), adalimumab (ADA), certolizumab or golimumab]. Exclusion criteria: studies using anti-TNF as prophylaxis for postoperative recurrence in CD or those where DI was based on therapeutic drug monitoring. Data synthesis: Effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (UC vs. CD), anti-TNF drug and follow-up. Subgroup analyses were performed to explore heterogeneity.

Results

In total, 174 studies (32,031 patients) were included. The overall rate of DI requirement after 12 months follow-up was 27% (95%CI 23-31, I2=96%, 51 studies) in naïve patients and 38% (95%CI 31-46, I2=87%, 18 studies) in non-naïve patients. The rate of DI requirement was higher in patients with prior anti-TNF exposure (c²=6.5, P=0.01) and in UC patients (c²=4.7, P=0.03). The rate of DI requirement in naïve patients after 36 months follow-up was 35% (95%CI 27-43%; I2=98%; 22 studies). The overall short-term response and remission rates to empirical DI in naïve patients were 66% (95%CI 61-71%; I2=81%; 35 studies) and 48% (95%CI 35-62%; I2=97%; 27 studies), respectively. Subgroup analyses are presented in the tables.

Anti-TNF UC/CD DI requirement (%, 95%CI) after 12 months I2 (%) Number of  included studies
IFX UC+CD 29 (23-36) 95 28
IFX UC 41 (26-55) 97 9
IFX CD 22 (15-28) 87 15
ADA UC+CD 27 (21-34) 93 17
ADA UC 29 (23-35) 86 7
ADA CD 24 (15-38) 95 10

Anti-TNF UC/CD Remission rate after DI (%, 95%CI) Number of included studies I2 (%)
IFX UC+CD 51 (40-61) 16 86
IFX UC 57 (35-78) 8 93
IFX CD 44 (35-54) 7 47
ADA UC+CD 44 (31-58) 10 86
ADA UC 17 (7-27) 1 NA
ADA CD 50 (36-64) 8 79

Conclusion

Loss of response to anti-TNF agents ―and consequent DI― occur frequently in IBD (approximately in 1/4 at one year and in 1/3 at 3 years). DI requirement is higher in UC patients and in those with prior anti-TNF exposure. Empirical DI is a relatively effective therapeutic option.

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