PMID- 32413933 OWN - NLM STAT- MEDLINE DCOM- 20200911 LR - 20220924 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 5 IP - 5 DP - 2020 May 16 TI - Adalimumab for maintenance of remission in Crohn's disease. PG - CD012877 LID - 10.1002/14651858.CD012877.pub2 [doi] LID - CD012877 AB - BACKGROUND: Conventional medications for Crohn's disease (CD) include anti-inflammatory drugs, immunosuppressants and corticosteroids. If an individual does not respond, or loses response to first-line treatments, then biologic therapies such as tumour necrosis factor-alpha (TNF-alpha) antagonists such as adalimumab are considered for treating CD. Maintenance of remission of CD is a clinically important goal, as disease relapse can negatively affect quality of life. OBJECTIVES: To assess the efficacy and safety of adalimumab for maintenance of remission in people with quiescent CD. SEARCH METHODS: We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, and clinicaltrials.gov from inception to April 2019. SELECTION CRITERIA: We considered for inclusion randomized controlled trials (RCTs) comparing adalimumab to placebo or to an active comparator. DATA COLLECTION AND ANALYSIS: We analyzed data on an intention-to-treat basis. We calculated risk ratios (RRs) and corresponding 95% confidence intervals (95% CI) for dichotomous outcomes. The primary outcome was failure to maintain clinical remission. We define clinical remission as a Crohn's Disease Activity Index (CDAI) score of < 150. Secondary outcomes were failure to maintain clinical response, endoscopic remission, endoscopic response, histological remission and adverse events (AEs). We assessed biases using the Cochrane 'Risk of bias' tool. We used GRADE to assess the overall certainty of evidence supporting the primary outcome. MAIN RESULTS: We included six RCTs (1158 participants). We rated four trials at low risk of bias and two trials at unclear risk of bias. All participants had moderate-to-severe CD that was in clinical remission. Four studies were placebo-controlled (1012 participants). Two studies (70 participants) compared adalimumab to active medication (azathioprine, mesalamine or 6-mercaptopurine) in participants who had an ileocolic resection prior to study enrolment. Adalimumab versus placebo Fifty-nine per cent (252/430) of participants treated with adalimumab failed to maintain clinical remission at 52 to 56 weeks, compared with 86% (217/253) of participants receiving placebo (RR 0.70, 95% CI 0.64 to 0.77; 3 studies, 683 participants; high-certainty evidence). Among those who received prior TNF-alpha antagonist therapy, 69% (129/186) of adalimumab participants failed to maintain clinical or endoscopic response at 52 to 56 weeks, compared with 93% (108/116) of participants who received placebo (RR 0.76, 95% CI 0.68 to 0.85; 2 studies, 302 participants; moderate-certainty evidence). Fifty-one per cent (192/374) of participants who received adalimumab failed to maintain clinical remission at 24 to 26 weeks, compared with 79% (149/188) of those who received placebo (RR 0.66, 95% CI 0.52 to 0.83; 2 studies, 554 participants; moderate-certainty evidence). Eighty-seven per cent (561/643) of participants who received adalimumab reported an AE compared with 85% (315/369) of participants who received placebo (RR 1.01, 95% CI 0.94 to 1.09; 4 studies, 1012 participants; high-certainty evidence). Serious adverse events were seen in 8% (52/643) of participants who received adalimumab and 14% (53/369) of participants who received placebo (RR 0.56, 95% CI 0.39 to 0.80; 4 studies, 1012 participants; moderate-certainty evidence) and withdrawal due to AEs was reported in 7% (45/643) of adalimumab participants compared to 13% (48/369) of placebo participants (RR 0.59, 95% CI 0.38 to 0.91; 4 studies, 1012 participants; moderate-certainty evidence). Commonly-reported AEs included CD aggravation, arthralgia, nasopharyngitis, urinary tract infections, headache, nausea, fatigue and abdominal pain. Adalimumab versus active comparators No studies reported failure to maintain clinical remission. One study reported on failure to maintain clinical response and endoscopic remission at 104 weeks in ileocolic resection participants who received either adalimumab, azathioprine or mesalamine as post-surgical maintenance therapy. Thirteen per cent (2/16) of adalimumab participants failed to maintain clinical response compared with 54% (19/35) of azathioprine or mesalamine participants (RR 0.23, 95% CI 0.06 to 0.87; 51 participants). Six per cent (1/16) of participants who received adalimumab failed to maintain endoscopic remission, compared with 57% (20/35) of participants who received azathioprine or mesalamine (RR 0.11, 95% CI 0.02 to 0.75; 51 participants; very low-certainty evidence). One study reported on failure to maintain endoscopic response at 24 weeks in ileocolic resection participants who received either adalimumab or 6-mercaptopurine (6-MP) as post-surgical maintenance therapy. Nine per cent (1/11) of adalimumab participants failed to maintain endoscopic remission compared with 50% (4/8) of 6-MP participants (RR 0.18, 95% CI 0.02 to 1.33; 19 participants). AUTHORS' CONCLUSIONS: Adalimumab is an effective therapy for maintenance of clinical remission in people with quiescent CD. Adalimumab is also effective in those who have previously been treated with TNF-alpha antagonists. The effect of adalimumab in the post-surgical setting is uncertain. More research is needed in people with recent bowel surgery for CD to better determine treatment plans following surgery. Future research should continue to explore factors that influence initial and subsequent biologic selection for people with moderate-to-severe CD. Studies comparing adalimumab to other active medications are needed, to help determine the optimal maintenance therapy for CD. CI - Copyright (c) 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Townsend, Cassandra M AU - Townsend CM AD - Department of Medicine, University of Western Ontario, London, Canada. FAU - Nguyen, Tran M AU - Nguyen TM AD - Robarts Clinical Trials, London, Canada. FAU - Cepek, Jeremy AU - Cepek J AD - Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada. FAU - Abbass, Mohamad AU - Abbass M AD - Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada. FAU - Parker, Claire E AU - Parker CE AD - Robarts Clinical Trials, London, Canada. FAU - MacDonald, John K AU - MacDonald JK AD - Department of Medicine, University of Western Ontario, London, Canada. FAU - Khanna, Reena AU - Khanna R AD - Department of Medicine, University of Western Ontario, London, Canada. AD - Robarts Clinical Trials, London, Canada. FAU - Jairath, Vipul AU - Jairath V AD - Department of Medicine, University of Western Ontario, London, Canada. AD - Robarts Clinical Trials, London, Canada. AD - Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada. FAU - Feagan, Brian G AU - Feagan BG AD - Department of Medicine, University of Western Ontario, London, Canada. AD - Robarts Clinical Trials, London, Canada. AD - Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20200516 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Immunosuppressive Agents) RN - 0 (Placebos) RN - 0 (Tumor Necrosis Factor-alpha) RN - 4Q81I59GXC (Mesalamine) RN - E7WED276I5 (Mercaptopurine) RN - FYS6T7F842 (Adalimumab) RN - MRK240IY2L (Azathioprine) SB - IM UOF - doi: 10.1002/14651858.CD012877 MH - Adalimumab/adverse effects/*therapeutic use MH - Adolescent MH - Adult MH - Aged MH - Anti-Inflammatory Agents/adverse effects/*therapeutic use MH - Azathioprine/therapeutic use MH - Crohn Disease/*drug therapy MH - Drug Administration Schedule MH - Humans MH - Immunosuppressive Agents/therapeutic use MH - Maintenance Chemotherapy/*methods/statistics & numerical data MH - Mercaptopurine/therapeutic use MH - Mesalamine/therapeutic use MH - Middle Aged MH - Patient Dropouts/statistics & numerical data MH - Placebos/therapeutic use MH - Randomized Controlled Trials as Topic MH - Time Factors MH - Treatment Outcome MH - Tumor Necrosis Factor-alpha/antagonists & inhibitors MH - Young Adult PMC - PMC7386457 COIS- Cassandra Townsend: None known Tran M Nguyen: None known Jeremy Cepek: None known Mohamad Abbass: None known Claire E Parker: None known John K MacDonald: None known Reena Khanna: Reena Khanna has been a speaker advisory board member, and or clinical investigator for AbbVie, Encycle, Gilead, Innomar, Janssen, Lilly, Merck, Pfizer, Pendopharm, Robarts Clinical Trials, Roche/Genetec, Shire, Takeda. Vipul Jairath: Dr Jairath has received consulting fees from Abbvie, Sandoz, Takeda, Pfizer, and Janssen; and Lecture fees from Takeda, Ferring, Janssen, and Shire. All of these activities are outside the submitted work. Brian G 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. EDAT- 2020/05/16 06:00 MHDA- 2020/09/12 06:00 PMCR- 2021/05/16 CRDT- 2020/05/16 06:00 PHST- 2020/05/16 06:00 [entrez] PHST- 2020/05/16 06:00 [pubmed] PHST- 2020/09/12 06:00 [medline] PHST- 2021/05/16 00:00 [pmc-release] AID - CD012877.pub2 [pii] AID - 10.1002/14651858.CD012877.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2020 May 16;5(5):CD012877. doi: 10.1002/14651858.CD012877.pub2.