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

Abstract

ObjectiveTo report long-term safety from the completed extension trial of baricitinib, an oral selective Janus kinase inhibitor, in patients with active rheumatoid arthritis (RA).MethodsTreatment-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.Results3770 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.ConclusionsIn 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 numberNCT01185353, NCT00902486, NCT01469013, NCT01710358, NCT02265705, NCT01721044, NCT01721057, NCT01711359 and NCT01885078.

Persistent coxsackievirus B infection and pathogenesis of type 1 diabetes mellitus

“…Baricitinib, an oral inhibitor of the tyrosine protein kinases JAK1 and JAK2 approved by the FDA, has shown promising results in the treatment of rheumatoid arthritis in humans 227 . In a 2020 study, this molecule was able to substantially reduce in vitro hyperexpression of HLA class I molecules, ER stress and apoptosis of human β-cells and islets that was initiated by IFNα treatment 151 .…”

Application of Baricitinib in Dermatology

“…The IR of malignant tumours was 0.6 in the first 48 weeks, and remained stable thereafter (IR 1.0). 33 Clinical disease screening of patients before application of JAK inhibitors and continuous monitoring during application are essential. 34 Some experts believe that more targeted second-generation JAK inhibitors for only one subtype or topical application show better effects and lower adverse reactions.…”

Novel insights into the management of rheumatoid arthritis: one year in review 2022

“…Second, the interpretation of dose-effect on VTE is complicated because all patients on TOFA 10 mg were moved to the 5 mg dosage during the trial; still, their data continued to be analysed as part of the 10 mg cohort. (17). A second integrated analysis characterised the safety of filgotinib in RA from seven clinical trials that included 3,691 patients, 19% of whom aged ≥65 years, treated for a median of 1.6 years (maximum exposure, 5.6 years in <3% of patients) (21).…”

“…Reassuringly, neither observational data from real-life cohorts (14) nor long-term extension studies of randomised controlled trials detected safety signals with JAKis (17). • JAK inhibitors have been linked to an increased risk of HZ in patients with RA (17,22,23). Asian region and prior history of HZ may be associated with an increased risk of HZ infection (23,24).…”