Baricitinib Safety for Events of Special Interest in Populations at Risk: Analysis from Randomised Trial Data Across Rheumatologic and Dermatologic Indications

Abstract

Introduction: Baricitinib, a Janus kinase (JAK) 1/2 inhibitor, is an approved treatment for rheumatoid arthritis (RA), atopic dermatitis (AD), and alopecia areata (AA). Further characterisation of adverse events of special interest (AESI) for JAK inhibitors in at-risk populations will improve benefit-risk assessment for individual patients and diseases.

Methods: Data were pooled from clinical trials and long-term extensions in moderate-to-severe active RA, moderate-to-severe AD, and severe AA. Incidence rates (IR) per 100 patient-years of major adverse cardiovascular event (MACE), malignancy, venous thromboembolism (VTE), serious infection, and mortality were calculated for patients with low risk (younger than 65 years with no specified risk factors), and patients at risk (≥ 1 of: aged 65 years or older, atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, current smoking, HDL cholesterol < 40 mg/dL, BMI ≥ 30 kg/m², poor mobility on EQ-5D, or history of malignancy).

Results: Datasets included baricitinib exposure up to 9.3 years with 14,744 person-years of exposure (PYE) (RA), 3.9 years with 4628 PYE (AD), and 3.1 years with 1868 PYE (AA). In patients with low risk (RA: 31%, AD: 48%, AA: 49%), IRs for MACE (0.05, 0.04, 0), malignancies (0.20, 0.13, 0), VTE (0.09, 0.04, 0), serious infection (1.73, 1.18, 0.6), and mortality (0.04, 0, 0) in the RA, AD, and AA datasets, respectively, were low. In patients at risk (RA: 69%, AD: 52%, AA: 51%), IRs were for MACE (0.70, 0.25, 0.10), malignancies (1.23, 0.45, 0.31), VTE (0.66, 0.12, 0.10), serious infection (2.95, 2.30, 1.05), and mortality (0.78, 0.16, 0) for RA, AD, and AA datasets, respectively.

Conclusion: Populations with low risk have low incidence of the examined JAK inhibitor-related AESI. In the dermatologic indications, incidence is also low for patients at risk. Considering individual disease burden, risk factors, and response to treatment is relevant to make informed decisions for individual patients treated with baricitinib.

Keywords: Adverse events; Baricitinib; JAK inhibitors; MACE; Malignancy; Mortality; Safety; Serious infection; VTE.

Fig. 1

Overview of occurrence of events of special interest in patients younger than 65 years without risk factors (low-risk) versus patients above 65 years and at least one pre-specified risk factor (at-risk) in integrated baricitinib clinical study datasets. A Number of patients in each risk group recording events of interest. B Incidence rate of events of interest per 100 patient-years of exposure for risk in each risk group. Abbreviations: AA alopecia areata; AD atopic dermatitis; BMI body mass index; CI confidence interval; EQ-5D EuroQol-5 dimension; HDL high-density lipoprotein; MACE major adverse cardiovascular event; MI myocardial infarction; N number of patients in the safety analysis set; n number of patients in the specified category; PYE patient-years of exposure; RA rheumatoid arthritis; VTE venous thromboembolic event. ^aFor MACE and MI in all-bari-RA: patients with low risk, n = 909; patients at-risk, n = 2342. For MACE, MI, and VTE in all-bari-AD: patients with low risk, n = 1231; patients at-risk, n = 1330. ^bExcluding non-melanoma skin cancer. ^cPatients without risk factors and < 65 years. ^dPatients ≥ 65 years or with at least one of the following risk factors: atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, current smoking (past smoking was not systematically documented in all trials), HDL < 40 mg/dL, BMI ≥ 30 kg/m², poor mobility on EQ-5D, and history of malignancy. Also including factors only documented in case narrative, such as past smoking