PMID- 38169057
OWN - NLM
STAT- MEDLINE
DCOM- 20240213
LR  - 20240314
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 41
IP  - 2
DP  - 2024 Feb
TI  - Safety of Upadacitinib in Immune-Mediated Inflammatory Diseases: Systematic 
      Literature Review of Indirect and Direct Treatment Comparisons of Randomized 
      Controlled Trials.
PG  - 567-597
LID - 10.1007/s12325-023-02732-6 [doi]
AB  - INTRODUCTION: Immune-mediated inflammatory diseases including rheumatoid 
      arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), 
      non-radiographic axial spondylarthritis (nr-axSpA), atopic dermatitis (AD), 
      ulcerative colitis (UC), and Crohn's disease (CD) pose a substantial burden on 
      patients and their quality of life. Upadacitinib is an orally administered, 
      selective, and reversible Janus kinase inhibitor indicated for seven conditions, 
      but data on its safety versus other active treatments are limited. A systematic 
      literature review of indirect and direct treatment comparisons of randomized 
      controlled trials (RCTs) was conducted to assess the safety profile of 
      upadacitinib. METHODS: MEDLINE, Embase, and Cochrane Library databases were 
      searched for indirect and direct treatment comparisons of RCTs that (1) included 
      licensed upadacitinib dosages; (2) studied any of the seven conditions; (3) 
      reported any adverse events (AEs), serious AEs (SAEs), AEs leading to 
      discontinuation, major adverse cardiovascular event, venous thromboembolism, 
      malignancies, infections or serious infections, and death; and (4) were published 
      between January 2018 and August 2022. RESULTS: A total of 25 studies were 
      eligible for inclusion. SAEs, AEs leading to discontinuation, and any AEs were 
      commonly studied. RA was the most studied condition, followed by AD and UC. Most 
      studies (16/25, 64%) reported no statistically significant difference in the 
      studied safety outcomes between upadacitinib and other active treatments (e.g., 
      tumor necrosis factor blockers, interleukin receptor antagonists, integrin 
      receptor antagonists, T cell co-stimulation modulator), or placebo 
      (placebo +/- methotrexate or topical corticosteroids). Other studies (9/25, 36%) 
      reported mixed results of no statistically significant difference and either 
      statistically higher (8/25, 32%) or lower rates (1/25, 4%) on upadacitinib. 
      CONCLUSION: Most studies suggested that upadacitinib has no statistically 
      significant difference in the studied safety outcomes compared to active 
      treatments or placebo in patients with RA, PsA, AS, AD, UC, and CD. A few studies 
      reported higher rates, but findings were inconsistent with limited 
      interpretation.
CI  - (c) 2023. The Author(s).
FAU - Mysler, Eduardo
AU  - Mysler E
AD  - Rheumatology, Organizacion Medica de Investigacion, Buenos Aires, Argentina.
FAU - Burmester, Gerd R
AU  - Burmester GR
AD  - Department of Rheumatology and Clinical Immunology, Charite Universitatsmedizin 
      Berlin, Berlin, Germany.
FAU - Saffore, Christopher D
AU  - Saffore CD
AD  - AbbVie Inc, North Chicago, IL, USA. christopher.saffore@abbvie.com.
FAU - Liu, John
AU  - Liu J
AD  - AbbVie Inc, North Chicago, IL, USA.
FAU - Wegrzyn, Lani
AU  - Wegrzyn L
AD  - AbbVie Inc, North Chicago, IL, USA.
FAU - Yang, Chelsey
AU  - Yang C
AD  - Analysis Group Inc., Beijing, China.
FAU - Betts, Keith A
AU  - Betts KA
AD  - Analysis Group Inc., Los Angeles, CA, USA.
FAU - Wang, Yan
AU  - Wang Y
AD  - Analysis Group Inc., Los Angeles, CA, USA.
FAU - Irvine, Alan D
AU  - Irvine AD
AD  - Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
AD  - Wellcome-HRB Clinical Research Facility, St. James' Hospital, Dublin, Ireland.
FAU - Panaccione, Remo
AU  - Panaccione R
AD  - Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Unit, 
      Cumming School of Medicine, University of Calgary, Calgary, Canada.
LA  - eng
PT  - Journal Article
PT  - Review
PT  - Systematic Review
DEP - 20240102
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - YL5FZ2Y5U1 (Methotrexate)
RN  - 4RA0KN46E0 (upadacitinib)
MH  - Humans
MH  - *Arthritis, Psoriatic/drug therapy
MH  - *Arthritis, Rheumatoid/drug therapy
MH  - *Colitis, Ulcerative/drug therapy
MH  - *Heterocyclic Compounds, 3-Ring/adverse effects
MH  - Methotrexate/therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - *Spondylitis, Ankylosing/drug therapy
PMC - PMC10838816
OTO - NOTNLM
OT  - Dermatology
OT  - Direct treatment comparison
OT  - Gastroenterology
OT  - Indirect treatment comparison
OT  - Rheumatology
OT  - Safety
OT  - Systematic literature review
OT  - Upadacitinib
COIS- Christopher Saffore, John Liu, and Lani Wegrzyn are employees of AbbVie, Inc. 
      Chelsey Yang, Keith A. Betts, and Yan Wang are employees of Analysis Group, Inc., 
      which received research funding from AbbVie, Inc. Eduardo Mysler received grants 
      and consulting fees from AbbVie, Amgen, AstraZeneca, Novartis, Lilly, Pfizer, 
      Roche, BMS, Sandoz, GSK, Janssen, Sanofi, Hi Bio Inc., Gemmene and Gema Biotech. 
      Gerd R. Burmester received honoraria for lectures and consulting fees from 
      AbbVie, Amgen, BMS, Lilly, Galapagos, Janssen, Novartis, Pfizer, Sanofi, Roche, 
      Celltrion, Chugai and MSD. Alan D. Irvine received grants or consulting fees or 
      advisory board honoraria from AbbVie, Almirall, Arena, Benevolent AI, Connect 
      Biopharma, Lilly, Janssen, LEO Pharma, Novartis, Pfizer, RAPT Therapeutics, 
      Regeneron, UCB, Sanofi. He is on the board of directors of the International 
      Eczema Council. Remo Panaccione received consulting fees from Abbott, AbbVie, 
      Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, 
      Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos 
      Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, 
      Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, 
      Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, 
      Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, 
      Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, 
      Trellus, Viatris, Ventyx, UCB; has received speaker's fees from AbbVie, Amgen, 
      Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, 
      Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, 
      Shire, Takeda Pharmaceuticals; and has served on advisory boards for AbbVie, 
      Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, 
      Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, 
      Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, 
      Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, 
      Progenity, Protagonist Therapeutics, Roche, SandozShire, Sublimity Therapeutics, 
      Takeda Pharmaceuticals, Ventyx.
EDAT- 2024/01/04 01:18
MHDA- 2024/02/06 06:42
PMCR- 2024/01/02
CRDT- 2024/01/03 11:13
PHST- 2023/08/27 00:00 [received]
PHST- 2023/11/07 00:00 [accepted]
PHST- 2024/02/06 06:42 [medline]
PHST- 2024/01/04 01:18 [pubmed]
PHST- 2024/01/03 11:13 [entrez]
PHST- 2024/01/02 00:00 [pmc-release]
AID - 10.1007/s12325-023-02732-6 [pii]
AID - 2732 [pii]
AID - 10.1007/s12325-023-02732-6 [doi]
PST - ppublish
SO  - Adv Ther. 2024 Feb;41(2):567-597. doi: 10.1007/s12325-023-02732-6. Epub 2024 Jan 
      2.