Journal Article

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

Takeuchi, Tsutomu, Durez, Patrick, Taylor, Peter C, Issa, Maher, Winthrop, Kevin L, Deberdt, Walter, Bello, Natalia, Smolen, Josef S, Burmester, Gerd R, Terres, Jorge Ross

2022

Overview

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

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited,BMJ Publishing Group
• Subject: Aged / Antirheumatic Agents - adverse effects / Antirheumatic Agents - therapeutic use / Arthritis, Rheumatoid - drug therapy / autoimmune diseases / Azetidines - adverse effects / Azetidines - therapeutic use / biological therapy / Cardiovascular diseases / Cardiovascular Diseases - chemically induced / Cardiovascular Diseases - epidemiology / Clinical trials / Databases, Factual / Drug dosages / Drug-Related Side Effects and Adverse Reactions - epidemiology / Drug-Related Side Effects and Adverse Reactions - etiology / Embolism / Enzyme inhibitors / Female / Follow-Up Studies / Herpes zoster / Herpes Zoster - chemically induced / Herpes Zoster - epidemiology / Humans / Incidence / Infections / Janus kinase / Janus Kinase Inhibitors - adverse effects / Janus Kinase Inhibitors - therapeutic use / Longitudinal Studies / Male / Malignancy / Melanoma / Middle Aged / Mortality / Neoplasms - chemically induced / Neoplasms - epidemiology / Patients / Population / Pulmonary Embolism - chemically induced / Pulmonary Embolism - epidemiology / Pulmonary embolisms / Purines - adverse effects / Purines - therapeutic use / Pyrazoles - adverse effects / Pyrazoles - therapeutic use / Randomized Controlled Trials as Topic / Rheumatoid Arthritis / Risk factors / Safety / Skin cancer / Sulfonamides - adverse effects / Sulfonamides - therapeutic use / Thromboembolism / Thrombosis / Treatment Outcome / Venous Thrombosis - chemically induced / Venous Thrombosis - epidemiology