P573 Frequency and effectiveness of empirical anti-TNF dose intensification in inflammatory bowel disease: an on-going systematic review with meta-analysis

L. Guberna Blanco, O.P. Nyssen, M. Chaparro, J.P. Gisbert

Hospital Universitario de la Princesa, Gastroenterology and Hepatology, Madrid, Spain

Background

Loss of response to anti-TNF therapies in inflammatory bowel disease occurs in a high proportion of patients. However, the precise incidence of dose intensification (DI) and its effectiveness remain 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 until January 2019. Selection: prospective and retrospective studies assessing the 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. Exclusion criteria: Studies using anti-TNF as prophylaxis for postoperative recurrence in CD or those where DI was based on therapeutic drug monitoring. Data were analyzed by means of the inverse variance method using a random effect model and stratifying by medical baseline condition (UC vs. CD), anti-TNF drug and follow-up. Effectiveness was assessed by intention-to-treat analysis.

Results

Up to now, 107 studies (11,377 patients) were included. The overall rate of DI requirement for naïve patients after 12 and 36 months of follow-up was 35% (95% CI=26–45%, I2=95%, 15 studies) and 48% (41–55%, I2= 77%, 9 studies); respectively. Frequencies of DI requirement stratified by subgroup analysis are presented in the table (all patients being naïve except CD patients treated with adalimumab (ADA), including naïve and no naïve).

Anti-TNFUC/CDFollow-up time (months)DI requirement (%, 95% CI)I2 (%)Number of studies included
Infliximab (IFX)UC+CD1237 (26–48)9513
IFXUC+CD3648 (41–55)798
IFXUC1257 (48–65)735
IFXUC3652 (33–71)873
IFXCD1225 (16–44)898
IFXCD3646 (38–55)785
ADAUC+CD12 31 (24–38) 9111
ADAUC+CD3643 (36–49)444
ADAUC1225 (18–33)692
ADAUC3650 (34–66)Not applicable1
ADACD1233 (24–42)939
ADACD36 41 (35–48)463

The overall short-term response and remission rates to empirical DI were 67% (95% CI: 63–72%; I2=73%; 31 studies) and 45% (95% CI: 35–55%; I2=9%; 23 studies), respectively; subgroup analyses are summarised in the table.

Anti-TNFUC/CDRemission rate (%, 95% CI)I2 (%)Number of studies included
IFXUC+CD44 (29–59)8910
IFXUC51 (27–75)935
IFXCD36 (27–44)825
ADAUC+CD38 (22–54)898
ADAUC14 (3–24)573
ADACD55(33–77)825

Conclusion

Loss of response to anti-TNF agents and consequent DI occurs frequently in both UC and CD, with an overall rate of DI requirement of 35% at one year and 48% at 3 years. Empirical DI is a relatively effective therapeutic option. Further data extraction and analysis is necessary to confirm these findings.