An Updated Integrated Safety Analysis of Baricitinib for the Treatment of Moderate-to-Severe RA

In clinical trials, the JAK1/2 inhibitor baricitinib (bari) has shown significant efficacy and an acceptable safety profile for patients with moderate-to-severe rheumatoid arthritis (RA). The current study reported on updated integrated safety data from 8 randomized trials that further described the safety profile for up to 5.5 years of baricitinib in adult patients with moderately to severely active RA.

Three sets of data analyses were conducted, for the all-bari-RA, bari-2-mg-4-mg-extended, and placebo-bari-4-mg subgroups. The all-bari-RA subgroup included all patients exposed to any baricitinib dose from 8 randomized trials, including 4 phase 3 trials, 3 phase 2 trials, 1 phase 1b trial, and an ongoing long-term extension (LTE) study. The 2-mg-4-mg-extended dataset is based on the 4 phase 2/3 trials in which patients were randomized to 2 or 4 mg, and includes data from the LTE. The placebo-bari-4-mg dataset includes patients from the 6 phase 2/3 trials that were randomized to baricitinib 4 mg or placebo to week 24.

As of September 1, 2016, the total patient-years of exposure to any dose of baricitinib were 6637 (n = 3492)—baricitinib 2 mg (n = 479), baricitinib 4 mg (n = 1476), and placebo (n = 1070)—with maximum exposure of 5.5 years. The baseline patient demographics and disease severity were similar in the 3 analysis sets. The majority were female (80%), with mean RA diagnosis of about 9 years. Patients had moderately to severely active RA as indicated by mean Clinical Disease Activity Index of about 37 and mean swollen joint count of about 15.

In the all-bari-RA dataset, the incidence rates (IRs) were 2.9 for infections, 3.2 for herpes zoster, 0.8 for malignancy (excluding nonmelanoma skin cancer), 0.09 for lymphoma, 0.05 for gastrointestinal perforation, and 0.15 for tuberculosis. In the placebo-bari-4-mg analysis, there were no differences between bari 4 mg and placebo in terms of adverse events (AEs) leading to permanent study drug discontinuation, death, malignancy, serious infection, or major adverse cardiovascular event (MACE). In terms of AEs of special interest, the IR of herpes zoster infection was significantly higher with baricitinib 4 mg than with placebo (4.3 vs 1.0). In the bari-2-mg-4-mg-extended analysis set, no significant differences between baricitinib 2 mg and 4 mg were reported in AEs leading to discontinuation, death, serious infection, herpes zoster infection, or MACE. IRs for malignancy (excluding nonmelanoma skin cancer) were 0.5 for 2 mg and 1.3 for 4 mg baricitinib. The IRs for these AEs in all datasets were similar to those previously reported.

Taken as a whole, the current updated integrated safety analysis showed that baricitinib treatment for up to 5.5 years in patients with moderately to severely active RA maintained a safety profile that was similar to that previously reported, and proved acceptable in the context of demonstrated efficacy.

Genovese MC, et al. ACR 2017. Abstract 511.

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