EFFICACY OF EARLY ANTI-TUMOR NECROSIS FACTOR TREATMENT IN ADULT AND PEDIATRIC PATIENTS WITH CROHN'S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Ungaro R.1, Aggarwal S.2, Topaloglu O.2, Lee W.-J.3, Clark R.3, Colombel J.-F.1 1Icahn School of Medicine at Mount Sinai, New York, United States, 2NOVEL Health Strategies, Bethesda, United States, 3AbbVie Inc., Health Economics and Outcomes Research, North Chicago, United States

Introduction: There is an increasing body of evidence supporting earlier use of anti-tumor necrosis factor (anti-TNF) agents to improve outcomes and change the natural course of Crohn's disease (CD). The objective of this study was to perform a meta-analysis to assess the impact of early anti-TNF use in the treatment of CD

Aims & Methods: The PubMed and Embase databases were searched for English language papers and conference abstracts published through 31 December 2017. Studies were selected for inclusion if patients initiated anti-TNFs within 2 years of a CD diagnosis or if anti-TNFs were used before or with immunosuppressants (top-down) in clinical trials and retrospective observational studies based on PRISMA guidelines. Random-effects meta-analyses were conducted to compare clinical remission (including steroid-free remission), disease relapse and endoscopic healing rates with early anti-TNF treatment (< 2 years of disease duration or top-down treatment strategy) to late/conventional treatment (defined as biologic use after >2 years of disease duration or conventional step-up treatment strategy in recently diagnosed patients).

Results: A total of 3,061 records were identified, of which 39 references met the selection criteria for systematic review. The meta-analysis included 14 studies that reported comparative remission, relapse and endoscopic healing rates for early vs late/conventional anti-TNF treatment. Early vs. late/conventional anti-TNF use was more likely to result in clinical remission or steroid-free remission, with an odds-ratio (OR) of 2.11 (95% CI: 1.66-2.68, n=2,113, P< 0.001). The positive results were observed in both adult (OR 1.97 at week 26 [95% CI: 1.53-2.53, n=803, P< 0.001]) and pediatric subgroups (OR 3.07 at week 52 [95% CI: 1.59-5.94, n=217, P< 0.001]). Conversely, early treatment with anti-TNFs was associated with reduced risk of relapse compared to late/conventional treatment, with an OR of 0.31 (95% CI: 0.14-0.68, n=596, P=0.003). A subgroup analysis for adults was not feasible, however in the pediatric patient subgroup, the OR for relapse with early treatment was 0.18 (95% CI: 0.07-0.43, n=105, P< 0.001). Early anti-TNF treatment was also more likely to result in endoscopic healing compared to late/conventional treatment (OR 2.06 [95% CI: 1.35-3.15, n=454, P< 0.001]). A subgroup analysis for pediatrics was not feasible, but in the adult patient subgroup, the OR for endoscopic healing with early treatment was 2.21 (95% CI: 1.34-3.64, n=424, P=0.002).

a Early treatment is defined as anti-TNF use <2 years of disease duration or top-down treatment strategy; late/conventional treatment is defined as anti-TNF use after >2 years of disease duration or conventional step-up treatment strategy b Definition of clinical remission: 3 studies used CDAI<150; 1 study used CDAI<150 plus no bowel resection and no steroid use; 2 studies used PCDAI≤10; 1 study used corticosteroid free remission c Definition of disease relapse: 1 study used increase in CDAI≥70 and an absolute CDAI>220; 3 studies used PCDAI>10 d Definition of endoscopic healing: 2 studies used SES-CD=0; 1 study used CDEIS<4 and absence of deep ulcers; 1 study used absence of any mucosal ulcers (including aphthous ulcers); 1 study used absence of mucosal ulceration; 1 study used disappearance of ulcerations, multiple erosions, bleeding and friability (grade 0 or 1) CDAI: Crohn´s Disease Activity Index; PCDAI: Pediatric Crohn´s Disease Activity Index; SES-CD: Simple Endoscopic Score for Crohn´s Disease; CDEIS: Crohn´s Disease Endoscopic Index of Severity

Conclusion: Early use of anti-TNF in CD patients is associated with improved outcomes in clinical remission, disease relapse, and endoscopic healing compared to late/conventional treatment.

Disclosure: Jean-Frederic Colombel: Has served as a consultant or advisory board member for AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, Celltrion, Enterome, Ferring, Genentech, Janssen and Janssen, Medimmune, Merck & Co., Pfizer, Protagonist, Second Genome, Seres, Shire, Takeda, Theradiag; a speaker for AbbVie, Ferring; speaker's bureau for Amgen. Dr. Colombel has received research grants from Takeda, Janssen and Janssen, and is a stockholder of Intestinal Biotech Development and Genefit. Ryan Ungaro: Consultant or advisory board member for Takeda, Janssen, and Pfizer. Research support from Pfizer and Abbvie. Saurabh Aggarwal and Ozlem Topaloglu: are employees of NOVEL Health Strategies, which received payment from AbbVie to conduct the study. Ryan Clark and Wan-Ju Lee are employees of AbbVie and may hold AbbVie stock. Funding Statement Financial support for the study was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. All authors contributed to the development of the publication and maintained control over the final content. Acknowledgement: Medical writing support was provided by Sushil Kumar, of NOVEL Health Strategies, Columbia, MD, USA; this support was funded by AbbVie

Link to conference website