ACR Congress Review 2019

Update on JAK inhibitor safety data
Upadacitinib
Upadacitinib safety in the SELECT clinical program
Findings from an integrated analysis of the upadacitinib safety profile from the SELECT Phase 3 clinical
program were presented in three posters.
Cohen and colleagues presented exposure-adjusted event rates (EAERs) and key safety data. Across
the five Phase 3 trials, 3834 patients received one or more dose of upadacitinib 15 (n=2630) or 30 mg
QD (n=1204). The EAERs of overall SAEs and AEs leading to discontinuation on upadacitinib 15 mg
were comparable to adalimumab; while the rates of both were higher on upadacitinib 30 versus
upadacitinib 15 mg and MTX. Rates of deaths were comparable across the treatment groups. Serious
infection rates were comparable between upadacitinib 15 mg and adalimumab, while higher on
upadacitinib compared with MTX. Rates of herpes zoster were higher in both upadacitinib groups versus
MTX and adalimumab. The rates of serious infections and herpes zoster were higher on upadacitinib 30
versus 15 mg. Rates of VTE, MACE, and malignancy were comparable with that observed in the MTX
and adalimumab groups while also being consistent with reported rates in the RA population [509*].
Choy and colleagues presented an analysis focusing on MACE and VTE. The EAERs of MACE and
VTE in the upadacitinib groups were comparable to placebo, MTX and adalimumab. Approximately 40%
of MACEs and 1 PE event (upadacitinib 15 mg) were fatal. All patients with a MACE or VTE event had
one or more CV risk factors (hypertension, diabetes, dyslipidaemia) or one or more VTE risk factor (prior
history of thrombotic event, obesity, or hypertension) at baseline, respectively. Treatment with
upadacitinib increased the levels of LDL-C and HDL-C, however, their ratio remained constant over time
and there was no association of LDL‐C increases and MACE occurrences. No dose‐response or pattern
of time-to-VTE-onset was observed with either upadacitinib dose [846*].
An integrated, long-term safety analysis of upadacitinib in Japanese patients was presented by
Yamaoka and colleagues. The analysis included a total of 371 Japanese patients who received
upadacitinib 7.5 (n=121), 15 (n=126), or 30 mg QD (n=124) in one of three clinical studies (SELECT-
SUNRISE, SELECT-EARLY or SELECT-MONOTHERAPY). Among the Japanese population, EAERs
were consistently higher in the 30 mg group compared with the 15 mg and 7.5 mg groups. EAERs in the
15 mg and 7.5 mg groups were comparable. In comparison with the global population, EAERs in the 15
mg and 30 mg groups was higher in the Japanese population. The EAER of infections (including herpes
zoster) was also higher in the Japanese population compared with the global population. In contrast,
EAERs of AESI (including malignancies, cardiovascular disorders, hepatic disorders, and laboratory
abnormalities) were comparable between the Japanese and global populations [2407].
Baricitinib
Long-term baricitinib safety in RA
The long-term safety and efficacy profile for baricitinib up to 7 years was presented by Genovese et al.
The analysis included 3770 patients with RA (10,127 patient-years of exposure) from 9 randomised trials
and an ongoing open-label, long-term extension study. No significant differences were seen for
baricitinib 4 mg versus placebo in AEs leading to permanent drug discontinuation, death, malignancy,
serious infection, or MACE. The incidence rate of herpes zoster was significantly higher for baricitinib
4 mg versus placebo (3.8 versus 0.9) and numerically higher for baricitinib 2 mg (3.1). Incidence rates
for DVT/PE were numerically higher in baricitinib 4 mg versus placebo. Malignancy (excluding
*Chairman’s Pick