Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database

Ann Rheum Dis. 2022 Mar;81(3):335-343. doi: 10.1136/annrheumdis-2021-221276. Epub 2021 Oct 27.

Abstract

Objective: To report long-term safety from the completed extension trial of baricitinib, an oral selective Janus kinase inhibitor, in patients with active rheumatoid arthritis (RA).

Methods: Treatment-emergent adverse events are summarised from an integrated database (9 phase III/II/Ib and 1 long-term extension) of patients who received any baricitinib dose (All-bari-RA). Standardised incidence ratio (SIR) for malignancy (excluding non-melanoma skin cancer (NMSC)) and standardised mortality ratio (SMR) were estimated. Additional analysis was done in a subset of patients who had ever taken 2 mg or 4 mg baricitinib.

Results: 3770 patients received baricitinib (14 744 patient-years of exposure (PYE)). All-bari-RA incidence rates (IRs) per 100 patient-years at risk were 2.6, 3.0 and 0.5 for serious infections, herpes zoster and major adverse cardiovascular events (MACE), respectively. In patients aged ≥50 with ≥1 cardiovascular risk factor, the IR for MACE was 0.77 (95% CI 0.56 to 1.04). The IR for malignancy (excluding NMSC) during the first 48 weeks was 0.6 and remained stable thereafter (IR 1.0). The SIR for malignancies excluding NMSC was 1.07 (95% CI 0.90 to 1.26) and the SMR was 0.74 (95% CI 0.59 to 0.92). All-bari-RA IRs for deep vein thrombosis (DVT)/pulmonary embolism (PE), DVT and PE were 0.5 (95% CI 0.38 to 0.61), 0.4 (95% CI 0.26 to 0.45) and 0.3 (95% CI 0.18 to 0.35), respectively. No clear dose differences were noted for exposure-adjusted IRs (per 100 PYE) for deaths, serious infections, DVT/PE and MACE.

Conclusions: In this integrated analysis including long-term data of baricitinib from 3770 patients (median 4.6 years, up to 9.3 years) with active RA, baricitinib maintained a similar safety profile to earlier analyses. No new safety signals were identified.

Trial registration number: NCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT02265705, NCT01721044, NCT01721057, NCT01711359 and NCT01885078.

Keywords: autoimmune diseases; biological therapy; rheumatoid arthritis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Azetidines / adverse effects
  • Azetidines / therapeutic use*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology
  • Databases, Factual
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Female
  • Follow-Up Studies
  • Herpes Zoster / chemically induced
  • Herpes Zoster / epidemiology
  • Humans
  • Incidence
  • Janus Kinase Inhibitors / adverse effects
  • Janus Kinase Inhibitors / therapeutic use*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neoplasms / chemically induced
  • Neoplasms / epidemiology
  • Pulmonary Embolism / chemically induced
  • Pulmonary Embolism / epidemiology
  • Purines / adverse effects
  • Purines / therapeutic use*
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Venous Thrombosis / chemically induced
  • Venous Thrombosis / epidemiology

Substances

  • Antirheumatic Agents
  • Azetidines
  • Janus Kinase Inhibitors
  • Purines
  • Pyrazoles
  • Sulfonamides
  • baricitinib

Associated data

  • ClinicalTrials.gov/NCT01469013
  • ClinicalTrials.gov/NCT01885078
  • ClinicalTrials.gov/NCT02265705
  • ClinicalTrials.gov/NCT01721057
  • ClinicalTrials.gov/NCT00902486
  • ClinicalTrials.gov/NCT01185353
  • ClinicalTrials.gov/NCT01710358
  • ClinicalTrials.gov/NCT01721044
  • ClinicalTrials.gov/NCT01711359