Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program

Clin Rheumatol. 2023 May;42(5):1249-1258. doi: 10.1007/s10067-023-06513-y. Epub 2023 Jan 30.

Abstract

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.

Keywords: Janus kinase inhibitor; Latin America; Rheumatoid arthritis; Safety; Upadacitinib.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Antirheumatic Agents* / adverse effects
  • Arthritis, Rheumatoid* / chemically induced
  • Arthritis, Rheumatoid* / drug therapy
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Humans
  • Latin America
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Heterocyclic Compounds, 3-Ring
  • upadacitinib

Associated data

  • ClinicalTrials.gov/NCT02629159
  • ClinicalTrials.gov/NCT02706847
  • ClinicalTrials.gov/NCT02675426
  • ClinicalTrials.gov/NCT03086343
  • ClinicalTrials.gov/NCT02706951
  • ClinicalTrials.gov/NCT02706873