PMID- 31742665 OWN - NLM STAT- MEDLINE DCOM- 20200416 LR - 20220223 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 2019 IP - 11 DP - 2019 Nov 14 TI - Adalimumab for induction of remission in Crohn's disease. LID - 10.1002/14651858.CD012878.pub2 [doi] LID - CD012878 AB - BACKGROUND: Adalimumab is an IgG1 monoclonal antibody that targets and blocks tumor necrosis factor-alpha, a pro-inflammatory cytokine involved in the pathogenesis of Crohn's disease (CD). A significant proportion of people with CD fail conventional therapy or therapy with biologics or develop significant adverse events. Adalimumab may be an effective alternative for these individuals. OBJECTIVES: The objectives of this review were to assess the efficacy and safety of adalimumab for the induction of remission in CD. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register, ClinicalTrials.Gov and the World Health Organization trial registry (ICTRP) from inception to 16 April 2019. References and conference abstracts were searched to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing any dose of adalimumab to placebo or an active comparator in participants with active CD were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies, extracted data and assessed bias using the Cochrane 'Risk of bias' tool. The primary outcome was the failure to achieve clinical remission, as defined by the original studies. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of less than 150 points. Secondary outcomes included failure to achieve clinical response (defined as a decrease in CDAI of > 100 points or > 70 points from baseline), failure to achieve endoscopic remission and response, failure to achieve histological remission and response, failure to achieve steroid withdrawal, adverse events (AEs) and serious adverse events (SAEs), withdrawal from study due to AEs and quality of life measured by a validated instrument. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes. Data were pooled for analysis if the participants, interventions, outcomes and time frame were similar. Data were analyzed on an intention-to-treat basis. The overall certainty of the evidence was assessed using GRADE. MAIN RESULTS: Three placebo-controlled RCTs (714 adult participants) were included. The participants had moderate to severely active CD (CDAI 220 to 450). Two studies were rated as at low risk of bias and one study was rated as at unclear risk of bias. Seventy-six per cent (342/451) of adalimumab participants failed to achieve clinical remission at four weeks compared to 91% (240/263) of placebo participants (RR 0.85, 95% CI 0.79 to 0.90; high-certainty evidence). Forty-four per cent (197/451) of adalimumab participants compared to 66% (173/263) of placebo participants failed to achieve a 70-point clinical response at four weeks (RR 0.68, 95% CI 0.59 to 0.79; high-certainty evidence). At four weeks, 57% (257/451) of adalimumab participants failed to achieve a 100-point clinical response compared to 76% (199/263) of placebo participants (RR 0.77, 95% CI 0.69 to 0.86; high-certainty evidence). Sixty-two per cent (165/268) of adalimumab participants experienced an AE compared to 72% (188/263) of participants in the placebo group (RR 0.90, 95% CI 0.74 to 1.09; moderate-certainty evidence). Two percent (6/268) of adalimumab participants experienced a SAE compared to 5% (13/263) of participants in the placebo group (RR 0.44, 95% CI 0.17 to 1.15; low-certainty evidence). Lastly, 1% (3/268) of adalimumab participants withdrew due to AEs compared to 3% (8/268) of participants in the placebo group (RR 0.38, 95% CI 0.11 to 1.30; low-certainty evidence). Commonly reported adverse events included injection site reactions, abdominal pain, fatigue, worsening CD and nausea. Quality of life data did not allow for meta-analysis. Three studies reported better quality of life at four weeks with adalimumab (measured with either Inflammatory Bowel Disease Questionnaire or Short-Form 36; moderate-certainty evidence). Endoscopic remission and response, histologic remission and response, and steroid withdrawal were not reported in the included studies. AUTHORS' CONCLUSIONS: High-certainty evidence suggests that adalimumab is superior to placebo for induction of clinical remission and clinical response in people with moderate to severely active CD. Although the rates of AEs, SAEs and withdrawals due to AEs were lower in adalimumab participants compared to placebo, we are uncertain about the effect of adalimumab on AEs due to the low number of events. Therefore, no firm conclusions can be drawn regarding the safety of adalimumab in CD. Futher studies are required to look at the long-term effectiveness and safety of using adalimumab in participants with CD. CI - Copyright (c) 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Abbass, Mohamad AU - Abbass M AD - University of Western Ontario, Schulich School of Medicine & Dentistry, London, Ontario, Canada. FAU - Cepek, Jeremy AU - Cepek J AD - University of Western Ontario, Schulich School of Medicine & Dentistry, London, Ontario, Canada. FAU - Parker, Claire E AU - Parker CE AD - Robarts Clinical Trials, 100 Dundas Street, Suite 200, London, ON, Canada, N6A 5B6. FAU - Nguyen, Tran M AU - Nguyen TM AD - Robarts Clinical Trials, 100 Dundas Street, Suite 200, London, ON, Canada, N6A 5B6. FAU - MacDonald, John K AU - MacDonald JK AD - University of Western Ontario, Department of Medicine, London, ON, Canada. FAU - Feagan, Brian G AU - Feagan BG AD - Robarts Clinical Trials, 100 Dundas Street, Suite 200, London, ON, Canada, N6A 5B6. AD - University of Western Ontario, Department of Medicine, London, ON, Canada. AD - University of Western Ontario, Department of Epidemiology and Biostatistics, London, ON, Canada. FAU - Khanna, Reena AU - Khanna R AD - Robarts Clinical Trials, 100 Dundas Street, Suite 200, London, ON, Canada, N6A 5B6. AD - University of Western Ontario, Department of Medicine, London, ON, Canada. FAU - Jairath, Vipul AU - Jairath V AD - Robarts Clinical Trials, 100 Dundas Street, Suite 200, London, ON, Canada, N6A 5B6. AD - University of Western Ontario, Department of Medicine, London, ON, Canada. AD - University of Western Ontario, Department of Epidemiology and Biostatistics, London, ON, Canada. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20191114 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Antibodies, Monoclonal, Humanized) RN - FYS6T7F842 (Adalimumab) SB - IM UOF - doi: 10.1002/14651858.CD012878 MH - Adalimumab/*therapeutic use MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Crohn Disease/*therapy MH - Humans MH - Quality of Life MH - Randomized Controlled Trials as Topic MH - Remission Induction MH - Treatment Outcome PMC - PMC6953260 COIS- Mohamad Abbass: None known Jeremy Cepek: None known Claire E Parker: None known Tran M Nguyen: None known John K MacDonald: None known Brian Feagan has received fee(s) from Abbott/AbbVie, Amgen, Astra Zeneca, Avaxia Biologics Inc., Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Ferring, JnJ/Janssen, Merck, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, Tillotts Pharma AG, UCB Pharma for Board membership; fee(s) from Abbott/AbbVie, Actogenix, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Axcan, Baxter Healthcare Corp., Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma, Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Merck, Millennium, Nektar, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, Tillotts, UCB Pharma, Vertex Pharma, Warner-Chilcott, Wyeth, Zealand, and Zyngenia for consultancy; and lecture fee(s) from: Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-Chilcott, and UCB Pharma. All of these activities are outside the submitted work. Reena Khanna: Dr. Khanna has received honoraria from AbbVie, Encycle, Merck, Genetech/Roche, Pendopharm, Robarts Clinical Trials, Jansen, Pfizer, Shire, and Takeda for consultancy. All of these activities are outside the submitted work. Vipul Jairath: Dr. Jairath has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena Pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, Celltrion; and speaker's fees from Takeda, Janssen, Shire, Ferring, Abbvie, Pfizer. EDAT- 2019/11/20 06:00 MHDA- 2020/04/17 06:00 PMCR- 2020/11/14 CRDT- 2019/11/20 06:00 PHST- 2019/11/20 06:00 [entrez] PHST- 2019/11/20 06:00 [pubmed] PHST- 2020/04/17 06:00 [medline] PHST- 2020/11/14 00:00 [pmc-release] AID - CD012878.pub2 [pii] AID - 10.1002/14651858.CD012878.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2019 Nov 14;2019(11):CD012878. doi: 10.1002/14651858.CD012878.pub2.