Adverse events of special interest1
Data are presented as n(events per 100 PY).
With baricitinib 4 mg (not an approved dose):
- During the 16-week treatment period, serious infections were reported in 11 patients (3.7 events per 100 PY). During 0 to 52 week exposure, serious infections were reported in 32 patients (3.5 events per 100 PY)
- During the 16-week treatment period, no events of TB were reported. During 0 to 52 week exposure, events of TB were reported in 1 patient (0.1 per 100 PY)§
- During the 16-week treatment period, opportunistic infections were reported in 2 patients (0.7 per 100 PY). During 0 to 52 week exposure, opportunistic infections were reported in 5 patients (0.6 per 100 PY)
- During the 16-week treatment period, malignancies excluding non-melanoma skin cancers (NMSC) were reported in 1 patient (0.3 per 100 PY). During the 0 to 52 week treatment period, malignancies excluding NMSC were reported in 6 patients (0.7 per 100 PY)
- During the 16-week treatment period, arterial thromboses were reported in 2 patients (0.7 per 100 PY). During the 0 to 52 week treatment period, arterial thromboses were reported in 3 patients (0.3 per 100 PY)
- During the 16-week treatment period, venous thromboses (deep vein thrombosis or pulmonary embolism) were reported in 5 patients (1.7 per 100 PY). During the 0 to 52 week treatment period, venous thromboses were reported in 7 patients (0.8 per 100 PY)
Lilly is conducting long-term safety studies, including post-marketing studies, to continue to evaluate the safety of Olumiant. Certain adverse events, such as malignancy, require longer observation periods and larger patient exposure to ascertain risk.
*In the 0 to 52 week exposure population, most commonly reported serious infections were pneumonia, herpes zoster, and urinary tract infection.
§Cases of disseminated TB were also reported.
An extended safety analysis: adverse events of special interest3-5
Extended safety analysis
Extended safety of baricitinib includes all patients with active RA (including non-indicated patient populations) exposed to any baricitinib dose (including non-approved doses) pooled from 9 RA clinical trials (one completed phase 1, three completed phase 2, four completed phase 3 and data through April 1, 2017, from one ongoing phase 3 long-term extension study). As of April 1, 2017, 3492 patients received baricitinib for 7860 total PY. Of these, 2723 (78.0%) were treated for at least 52 weeks and 1788 (51.2%) were treated for at least 130 weeks. The majority of patients were exposed to baricitinib 4 mg. Baricitinib 4 mg is not an approved dose.
Incidence rates (IR) were calculated as the number of unique patients with an event per 100 PY.
In this extended safety analysis, 3 patients treated with baricitinib had a confirmed gastrointestinal perforation event. The IR in this data set is 0.04 per 100 PY.
Limitations of analysis
Some patients do not qualify or choose not to enroll, and some are ineligible due to prior events such as malignancies.
Some patients discontinue from the extended study for a range of possible reasons, including AEs. Information on AEs is limited to the time that patients are taking the study drug and up to approximately 4 weeks after discontinuation; information on AEs that occur more than 4 weeks after discontinuation is often not available.
Patient numbers and total exposure vary across the extended study time points as a function of patients entering or leaving the extended study, and/or changing their dosing.
Rates are subject to change depending on the timing of the data analysis.
†Includes multidermatomal herpes zoster.
References: 1. Olumiant [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018. 2. Data on file. Lilly USA, LLC. DOF-BA-US-0004. 3. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 6 years: an updated integrated safety analysis [abstract]. Arthritis Rheumatol. 2018;70(suppl 10). 4. Taylor PC, Weinblatt ME, Burmester GR, et al. Cardiovascular safety during treatment with baricitinib in rheumatoid arthritis. Arthritis Rheumatol. Published Online: January 21, 2019 (doi: 10.1002/art.40841). 5. Data on file. Lilly USA, LLC. DOF-BA-US-0008.