Baricitinib Maintains Established Safety Profile

Assorted trials and a long-term exposure study of 3770 patients with rheumatoid arthritis further demonstrate baricitinib’s previously recorded safety profile.

Mark C. Genovese

Baricitinib, an oral janus kinase (JAK) 1 and 2 inhibitor, maintained its previously demonstrated safety profile in an updated integrated analysis of patients with moderate to severe active rheumatoid arthritis (RA).

The study, which was divided into 9 randomized trials (5 phase 3; 3 phase 2; and 1 phase 1b) and 1 long-term exposure study (LTE), consisted of 3770 patients with RA. Maximum exposure time to baricitinib (dosage being either 2 mg or 4 mg) was 7 years. Mark C. Genovese, MD, professor of Medicine and director of the Rheumatology Clinic at Stanford University Medical Center, led the investigative team.

Up until week 24, investigators drew placebo comparisons against both 2 mg of baricitinib and 4 mg; dose responses were similarly evaluated in the 2 mg and 4 mg datasets from the phase 2 and 3 trials. All data was censored to account for rescue or dose change in patients that required an alteration in treatment during the study. Lastly, incidence rates were calculated per 100 patient-years (PY).

Fewer than 1% of patients experienced laboratory results abnormal enough to warrant discontinuation of the treatment. A 4 mg dose of baricitinib proved equivalent to a placebo regarding negligible rates of adverse events leading to an alteration or discontinuation of treatment, death, malignancy, serious infection, or major adverse cardiovascular events.

On the other hand, the incidence rate of herpes zoster was significantly higher for 4 mg of baricitinib (3.8) and 2 mg of baricitinib (3.1) when compared to placebo (0.9). Both dosages of baricitinib also exhibited similar incidence rates (both higher than the placebo) for deep vein thrombosis and pulmonary embolism. Additionally, rates of malignancy (excluding non-melanoma skin cancer) were .8 for a 2 mg baricitinib dose and 1.0 for a 4 mg dose in randomized analysis.

In summary, baricitinib achieved similar safety profile results to those achieved in prior studies, meeting broadly accepted standards for safety when weighed against its proven efficacy.

Baricitinib traveled a difficult road towards mainstream usage in the US. After receiving a Complete Response Letter (CRL) from the US Food and Drug Administration (FDA) in 2017, the drug received approval in 2018—though the FDA still recommended a 2 mg dose as opposed to a 4 mg dose due to safety and benefit-risk reasons.

Since its FDA approval, Baricitinib has indicated effectiveness and safety alike for treatment of atopic dermatitis in assorted phase 3 studies, as well as outperforming tocilizumab and adalimumab in a monotherapy trial designed to reduce pain and improve physical function. It also provided greater pain relief to patients with refractory rheumatoid arthritis when compared to a placebo in a phase 3 study.

Investigators presented the new study’s results at 2019’s Annual European Congress of Rheumatology in Madrid, Spain.