Olumiant Adverse Reactions

Summary of the safety profile: The most commonly reported adverse reactions with baricitinib are increased LDL cholesterol (26.0%), upper respiratory tract infections (16.9%), headache (5.2%), herpes simplex (3.2%), and urinary tract infections (2.9%). Serious pneumonia and serious herpes zoster occurred uncommonly in patients with rheumatoid arthritis.
Tabulated list of adverse reactions: Frequency estimate: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000). The frequencies in Table 9 are based on integrated data from clinical trials and/or post-marketing setting across rheumatoid arthritis, atopic dermatitis, and alopecia areata indications unless stated otherwise; where notable differences in frequency between indications are observed, these are presented in the footnotes following the table. (See Table 9.)

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Description of selected adverse reactions: Gastrointestinal disorders: In rheumatoid arthritis clinical studies, in treatment-naïve patients, through 52 weeks, the frequency of nausea was greater for the combination treatment of methotrexate and baricitinib (9.3%) compared to methotrexate alone (6.2%) or baricitinib alone (4.4%). In the integrated data from rheumatoid arthritis, atopic dermatitis and alopecia areata clinical trials, nausea was most frequent during the first 2 weeks of treatment.
Cases of abdominal pain were usually mild, transient, not associated with infectious or inflammatory gastrointestinal disorders, and did not lead to treatment interruption.
Infections: In the integrated data from rheumatoid arthritis, atopic dermatitis and alopecia areata clinical trials, most infections were mild to moderate in severity. In studies which included both doses, infections were reported in 31.0%, 25.7% and 26.7% of patients in the 4 mg, 2 mg and placebo groups, respectively. In rheumatoid arthritis clinical studies, combination with methotrexate resulted in increased frequency of infections compared to baricitinib monotherapy. Frequency of herpes zoster was common in rheumatoid arthritis, very rare in atopic dermatitis and uncommon in alopecia areata. In atopic dermatitis clinical trials, there were less skin infections requiring antibiotic treatment with baricitinib than with placebo.
The incidence of serious infections with baricitinib was similar to placebo. The incidence of serious infections remained stable during long-term exposure. The overall incidence rate of serious infections in the clinical trial programme was 3.2 per 100 patient-years in rheumatoid arthritis, 2.1 in atopic dermatitis and 0.8 in alopecia areata. Serious pneumonia and serious herpes zoster occurred uncommonly in patients with rheumatoid arthritis.
Hepatic transaminase elevations: Dose-dependent increases in blood ALT and AST activity were reported in studies extended over week 16. Elevations in mean ALT/AST remained stable over time. Most cases of hepatic transaminase elevations ≥ 3 x ULN were asymptomatic and transient.
In patients with rheumatoid arthritis, the combination of baricitinib with potentially hepatotoxic medicinal products, such as methotrexate, resulted in increased frequency of these elevations.
Lipid elevations: In the integrated data from rheumatoid arthritis, atopic dermatitis and alopecia areata clinical trials, baricitinib treatment was associated with dose-dependent increases in lipid parameters including total cholesterol, LDL cholesterol, and high density lipoprotein (HDL) cholesterol. There was no change in the LDL/HDL ratio. Elevations were observed at 12 weeks and remained stable thereafter at a higher value than baseline including in the long-term extension study in rheumatoid arthritis. Mean total and LDL cholesterol increased through week 52 in patients with atopic dermatitis and alopecia areata. In rheumatoid arthritis clinical trials, baricitinib treatment was associated with dose-dependent increases in triglycerides. There was no increase in triglycerides levels in atopic dermatitis and alopecia areata clinical trials.
Elevations in LDL cholesterol decreased to pre-treatment levels in response to statin therapy.
Creatine phosphokinase (CPK): Baricitinib treatment was associated with dose-dependent increases in CPK. Mean CPK was increased at week 4 and remained at a higher value than baseline thereafter. Across indications, most cases of CPK elevations > 5 x ULN were transient and did not require treatment discontinuation.
In clinical trials, there were no confirmed cases of rhabdomyolysis.
Neutropaenia: Mean neutrophil counts decreased at 4 weeks and remained stable at a lower value than baseline over time. There was no clear relationship between neutropaenia and the occurrence of serious infections. However, in clinical studies, treatment was interrupted in response to ANC < 1 x 10⁹ cells/L.
Thrombocytosis: Dose-dependent increases in mean platelet counts were observed and remained stable at a higher value than baseline over time.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to the Drug Office, Department of Health.