PMID- 36715850
OWN - NLM
STAT- MEDLINE
DCOM- 20230420
LR  - 20230420
IS  - 1434-9949 (Electronic)
IS  - 0770-3198 (Print)
IS  - 0770-3198 (Linking)
VI  - 42
IP  - 5
DP  - 2023 May
TI  - Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an 
      integrated safety analysis of the SELECT phase 3 clinical program.
PG  - 1249-1258
LID - 10.1007/s10067-023-06513-y [doi]
AB  - INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune 
      disease characterized by ongoing inflammation and degradation of synovial joints. 
      The oral JAK inhibitor, upadacitinib, is approved for RA. We conducted an 
      integrated safety analysis of upadacitinib 15 mg once daily (QD) in patients from 
      Latin America (LATAM) versus the rest of the world (RoW). METHODS: 
      Treatment-emergent adverse events (AEs) and laboratory data from six phase 3, 
      randomized controlled trials, adjusted for upadacitinib 15 mg QD use in RA, were 
      analyzed. RESULTS: Overall, 3209 patients received upadacitinib 15 mg QD for 7024 
      patient-years (PY). LATAM patients (n = 725) had a mean upadacitinib exposure of 
      1518 PY. Baseline characteristics were generally similar between LATAM and RoW 
      populations. AE rates (including serious/opportunistic infections, tuberculosis, 
      and herpes zoster) and deaths were comparable between populations. LATAM patients 
      had lower serious AE rates per 100 PY (9.4 vs 14.0 E/100 PY) and 
      discontinuation-related AEs (3.9 vs 6.0 E/100 PY) versus RoW. Rates of 
      cardiovascular events were low (</= 0.5 E/100 PY) and similar between populations. 
      Malignancies, excluding non-melanoma skin cancer, were less common in the LATAM 
      population versus RoW (0.2 vs 1.0 E/100 PY). Laboratory abnormalities were 
      similar between populations, with decreases in hemoglobin, lymphocyte, and 
      neutrophil counts, and elevations in liver enzymes and creatine phosphokinase. 
      Mean change from baseline in low- and high-density lipoprotein cholesterol was 
      generally comparable between LATAM and RoW populations. CONCLUSION: Upadacitinib 
      15 mg QD demonstrated a consistent safety profile across LATAM and RoW patient 
      populations, with no new safety risks observed. TRIAL REGISTRATION NUMBERS: 
      SELECT-EARLY, NCT02706873; SELECT-NEXT, NCT02675426; SELECT-COMPARE, NCT02629159; 
      SELECT-MONOTHERAPY, NCT02706951; SELECT-BEYOND, NCT02706847; SELECT-CHOICE, 
      NCT03086343.
CI  - (c) 2023. The Author(s).
FAU - Kakehasi, Adriana Maria
AU  - Kakehasi AM
AUID- ORCID: 0000-0001-9411-7493
AD  - Hospital das Clinicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 
      Brazil. amkakehasi@gmail.com.
FAU - Radominski, Sebastiao Cezar
AU  - Radominski SC
AD  - Universidade Federal Do Parana, Curitiba, PR, Brazil.
FAU - Baravalle, Marcos Daniel
AU  - Baravalle MD
AD  - Instituto Medico Strusberg, Cordoba, Argentina.
FAU - Palazuelos, Fedra Consuelo Irazoque
AU  - Palazuelos FCI
AD  - CINTRE (Centro de Investigacion y Tratamiento Reumatologico SC), Mexico City, 
      Mexico.
FAU - Garcia-Garcia, Conrado
AU  - Garcia-Garcia C
AD  - Rheumatology Unit, Hospital General de Mexico "Dr. Eduardo Liceaga", Mexico City, 
      Mexico.
FAU - Arruda, Maysa Silva
AU  - Arruda MS
AD  - AbbVie Farmaceutica Ltda, Sao Paulo, Brazil.
FAU - Curi, Marco
AU  - Curi M
AD  - AbbVie Farmaceutica Ltda, Sao Paulo, Brazil.
FAU - Liu, John
AU  - Liu J
AD  - AbbVie, North Chicago, IL, USA.
FAU - Qiao, Meihua
AU  - Qiao M
AD  - AbbVie, North Chicago, IL, USA.
FAU - Velez-Sanchez, Patricia
AU  - Velez-Sanchez P
AD  - Centro de Investigacion en Reumatologia Y Especialidades Medicas SAS (CIREEM 
      SAS), Bogota, Cundinamarca, Colombia.
FAU - Vargas, Juan Ignacio
AU  - Vargas JI
AD  - Quantum Research, Puerto Varas, Chile.
LA  - eng
SI  - ClinicalTrials.gov/NCT02629159
SI  - ClinicalTrials.gov/NCT02706847
SI  - ClinicalTrials.gov/NCT02675426
SI  - ClinicalTrials.gov/NCT03086343
SI  - ClinicalTrials.gov/NCT02706951
SI  - ClinicalTrials.gov/NCT02706873
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20230130
PL  - Germany
TA  - Clin Rheumatol
JT  - Clinical rheumatology
JID - 8211469
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 4RA0KN46E0 (upadacitinib)
SB  - IM
MH  - Humans
MH  - *Antirheumatic Agents/adverse effects
MH  - *Arthritis, Rheumatoid/drug therapy/chemically induced
MH  - Heterocyclic Compounds, 3-Ring/adverse effects
MH  - Latin America
MH  - Treatment Outcome
PMC - PMC9886207
OTO - NOTNLM
OT  - Janus kinase inhibitor
OT  - Latin America
OT  - Rheumatoid arthritis
OT  - Safety
OT  - Upadacitinib
COIS- AMK has received personal consulting and/or speaking fees from AbbVie, Amgen, Eli 
      Lilly, Janssen, Novartis, Pfizer, Sandoz, Roche, and UCB. SCR has received grants 
      for clinical studies from AbbVie, Bristol-Myers Squibb, and Lilly and speaker 
      fees from AbbVie, Amgen, Janssen, Pfizer, and UCB. MDB has received medical fees 
      as a Clinical Investigator from AbbVie, Galapagos, and GlaxoSmithKline. FCIP has 
      received speaker fees from AbbVie, Pfizer, Bristol-Myers Squibb, and Janssen; 
      consulting fees from AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and 
      Pfizer; and medical fees as a Principal Investigator from AbbVie, Bristol-Myers 
      Squibb, Celgene, Janssen, Pfizer, and Roche. CGG has received medical fees as a 
      Principal Investigator from AbbVie. MSA, MC, JL, and MQ are employees of AbbVie 
      and may own stock or options. PVS has received medical fees as a Principal 
      Investigator from AbbVie. JIV has received medical fees as a Principal 
      Investigator from AbbVie.
EDAT- 2023/01/31 06:00
MHDA- 2023/04/17 06:41
PMCR- 2023/01/30
CRDT- 2023/01/30 11:24
PHST- 2022/05/18 00:00 [received]
PHST- 2023/01/10 00:00 [accepted]
PHST- 2022/12/20 00:00 [revised]
PHST- 2023/04/17 06:41 [medline]
PHST- 2023/01/31 06:00 [pubmed]
PHST- 2023/01/30 11:24 [entrez]
PHST- 2023/01/30 00:00 [pmc-release]
AID - 10.1007/s10067-023-06513-y [pii]
AID - 6513 [pii]
AID - 10.1007/s10067-023-06513-y [doi]
PST - ppublish
SO  - Clin Rheumatol. 2023 May;42(5):1249-1258. doi: 10.1007/s10067-023-06513-y. Epub 
      2023 Jan 30.