PMID- 38541765
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240330
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 13
IP  - 6
DP  - 2024 Mar 7
TI  - Association between Ustekinumab Trough Levels, Serum IL-22, and Oncostatin M 
      Levels and Clinical and Biochemical Outcomes in Patients with Crohn's Disease.
LID - 10.3390/jcm13061539 [doi]
LID - 1539
AB  - Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients 
      with Crohn's disease. Monitoring treatment response can improve disease 
      management and reduce healthcare costs. We investigated whether UST trough levels 
      (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of 
      non-response by analysing their correlation with clinical and biochemical 
      outcomes in CD. Methods: Patients with CD initiating UST treatment from October 
      2018 to September 2020 were enrolled at six Italian centres for inflammatory 
      bowel disease (IBD). Clinical and biochemical data were collected at four time 
      points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. 
      TLs were measured during maintenance, at the second SC dose, and at the fourth SC 
      dose. IL-22 and OSM serum levels were assessed at baseline and the second SC 
      dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated 
      with clinical response, clinical remission, biochemical remission, and endoscopic 
      remission using the appropriate statistical tests. Results: Out of eighty-four 
      initially enrolled patients, five were lost to follow-up, and eleven discontinued 
      the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical 
      remission based on faecal calprotectin levels, and 61.8% achieved clinical 
      remission. TLs at the second SC dose significantly correlated with biochemical 
      remission at the same time point (p = 0.011). However, TLs did not correlate with 
      clinical remission. Baseline OSM levels did not correlate with biochemical or 
      clinical remission or response. IL22 levels notably decreased during UST therapy 
      (p = 0.000), but its values did not correlate with biochemical or clinical 
      remission. Conclusions: UST is an effective therapy for patients with CD. TLs 
      measured at the second SC dose significantly correlated with biochemical 
      remission, emphasising their potential role in treatment monitoring. Levels of 
      OSM and IL-22, despite a significant decrease in the latter during therapy, did 
      not exhibit correlations with clinical or biochemical outcomes in our study. 
      Further studies are needed to confirm these findings.
FAU - Bertin, Luisa
AU  - Bertin L
AUID- ORCID: 0009-0001-9816-4171
AD  - Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, 
      Azienda Ospedale Universita Padova, 35128 Padova, Italy.
FAU - Barberio, Brigida
AU  - Barberio B
AD  - Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, 
      Azienda Ospedale Universita Padova, 35128 Padova, Italy.
FAU - Gubbiotti, Alessandro
AU  - Gubbiotti A
AUID- ORCID: 0000-0002-0174-8729
AD  - Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, 
      Azienda Ospedale Universita Padova, 35128 Padova, Italy.
FAU - Bertani, Lorenzo
AU  - Bertani L
AUID- ORCID: 0000-0001-8653-1790
AD  - Department of General Surgery and Gastroenterology, Tuscany Northwest 
      ASL-Pontedera Hospital, 56025 Pontedera, Italy.
FAU - Costa, Francesco
AU  - Costa F
AUID- ORCID: 0000-0002-9150-3345
AD  - IBD Unit, Department of General Surgery, Pisa University Hospital, 56124 Pisa, 
      Italy.
FAU - Ceccarelli, Linda
AU  - Ceccarelli L
AD  - IBD Unit, Department of General Surgery, Pisa University Hospital, 56124 Pisa, 
      Italy.
FAU - Visaggi, Pierfrancesco
AU  - Visaggi P
AUID- ORCID: 0000-0002-6985-5301
AD  - IBD Unit, Department of General Surgery, Pisa University Hospital, 56124 Pisa, 
      Italy.
FAU - Bodini, Giorgia
AU  - Bodini G
AD  - Gastrointestinal Unit, Department of Internal Medicine, University of Genoa, 
      16132 Genoa, Italy.
FAU - Pasta, Andrea
AU  - Pasta A
AUID- ORCID: 0000-0003-1791-4506
AD  - Gastrointestinal Unit, Department of Internal Medicine, University of Genoa, 
      16132 Genoa, Italy.
FAU - Sablich, Renato
AU  - Sablich R
AD  - Gastroenterology Unit, Santa Maria Degli Angeli Hospital, 33170 Pordenone, Italy.
FAU - Urbano, Maria Teresa
AU  - Urbano MT
AD  - Gastroenterology Unit, Santa Maria Degli Angeli Hospital, 33170 Pordenone, Italy.
FAU - Ferronato, Antonio
AU  - Ferronato A
AD  - Endoscopy Unit, Department of Medicine, ULSS7 "Pedemontana", "Alto Vicentino" 
      Hospital, 36014 Santorso, Italy.
FAU - Buda, Andrea
AU  - Buda A
AD  - Gastroenterology Unit, Department of Gastrointestinal Oncological Surgery, S. 
      Maria del Prato Hospital, 32032 Feltre, Italy.
FAU - De Bona, Manuela
AU  - De Bona M
AD  - Gastroenterology Unit, Department of Gastrointestinal Oncological Surgery, S. 
      Maria del Prato Hospital, 32032 Feltre, Italy.
FAU - Del Corso, Giulio
AU  - Del Corso G
AUID- ORCID: 0000-0003-4604-2006
AD  - Institute of Information Science and Technologies "A. Faedo", National Research 
      Council of Italy (CNR), 56124 Pisa, Italy.
FAU - Massano, Alessandro
AU  - Massano A
AUID- ORCID: 0000-0002-9064-3434
AD  - Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, 
      Azienda Ospedale Universita Padova, 35128 Padova, Italy.
FAU - Angriman, Imerio
AU  - Angriman I
AUID- ORCID: 0000-0001-5873-5833
AD  - Third Surgical Clinic Section, Department of Surgical, Oncological and 
      Gastroenterological Sciences, Azienda Ospedale Universita Padova, 35128 Padova, 
      Italy.
FAU - Scarpa, Marco
AU  - Scarpa M
AD  - Third Surgical Clinic Section, Department of Surgical, Oncological and 
      Gastroenterological Sciences, Azienda Ospedale Universita Padova, 35128 Padova, 
      Italy.
FAU - Zingone, Fabiana
AU  - Zingone F
AUID- ORCID: 0000-0003-1133-1502
AD  - Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, 
      Azienda Ospedale Universita Padova, 35128 Padova, Italy.
FAU - Savarino, Edoardo Vincenzo
AU  - Savarino EV
AUID- ORCID: 0000-0002-3187-2894
AD  - Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, 
      Azienda Ospedale Universita Padova, 35128 Padova, Italy.
LA  - eng
PT  - Journal Article
DEP - 20240307
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC10971511
OTO - NOTNLM
OT  - Crohn's disease
OT  - IL-22
OT  - Oncostatin M
OT  - inflammatory bowel disease
OT  - ustekinumab
OT  - ustekinumab trough levels
COIS- Edoardo Vincenzo Savarino has served as speaker for Abbvie, Agave, AGPharma, 
      Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr. Falk, EG Stada Group, Fenix 
      Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, 
      Innovamedica/Adacyte, Malesci, MayolyBiohealth, Omega Pharma, Pfizer, Reckitt 
      Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, and Unifarco; has served as a 
      consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, 
      DiademaFarmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB 
      Pharmaceuticals, Merck & Co, Nestle, Reckitt Benckiser, Regeneron, Sanofi, SILA, 
      Sofar, Synformulas GmbH, Takeda, and Unifarco; he has received research support 
      from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. Fabiana 
      Zingone has served as a speaker for EG Stada Group, Fresenius Kabi, Janssen, 
      Pfizer, Takeda, Unifarco, Malesci, and Kedrion; and has served as a consultant 
      for Galapagos. Brigida Barberio has served as a speaker for Abbvie, Agave, 
      Alfasigma, AGpharma, Janssen, MSD, Procise, Sofar, Takeda, and Unifarco. Giorgia 
      Bodini has served as a speaker for Abbvie, Lilly, Sandoz, Janssen, and Takeda. 
      Lorenzo Bertani has received lecture fees, consultancy fees, or advisory board 
      honoraria from Abbvie, Aliveda, Janssen, Noos, Pfizer, Pharmanutra, Takeda, and 
      Zambon. Alessandro Gubbiotti: none. Francesco Costa has served as speaker for 
      Abbvie, Biogen, Diasorin, Eurospital, Ferring, Galapagos, Janssen, Pfizer, 
      Takeda, Thermo-Fisher, and Zambon; has served as a consultant for Abbvie, Amgen, 
      Biogen, Eurospital, Ferring, Fresenius Kabi, Galapagos, Janssen, MSD, Pfizer, and 
      Takeda. Linda Ceccarelli: none; Pierfrancesco Visaggi: none; Andrea Pasta: none; 
      Renato Sablich: none; Maria Teresa Urbano: none; Antonio Ferronato: none; Andrea 
      Buda: none; Manuela De Bona: none; Giulio del Corso: none; Imerio Angriman: none; 
      Marco Scarpa: none; Alessandro Massano: none.
EDAT- 2024/03/28 06:45
MHDA- 2024/03/28 06:46
PMCR- 2024/03/07
CRDT- 2024/03/28 01:15
PHST- 2024/01/23 00:00 [received]
PHST- 2024/02/26 00:00 [revised]
PHST- 2024/03/03 00:00 [accepted]
PHST- 2024/03/28 06:46 [medline]
PHST- 2024/03/28 06:45 [pubmed]
PHST- 2024/03/28 01:15 [entrez]
PHST- 2024/03/07 00:00 [pmc-release]
AID - jcm13061539 [pii]
AID - jcm-13-01539 [pii]
AID - 10.3390/jcm13061539 [doi]
PST - epublish
SO  - J Clin Med. 2024 Mar 7;13(6):1539. doi: 10.3390/jcm13061539.