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Olumiant ® (baricitinib)
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What is the effect of Olumiant® (baricitinib) on lipids in patients with atopic dermatitis?
With baricitinib, increases of lipid parameters have been reported. Lipid parameters should be assessed 12 weeks after treatment initiation.
Baricitinib label information related to lipids
Warnings and precautions
Dose dependent increases in blood lipid parameters were reported in patients treated with baricitinib.1
- Elevations in low density lipoprotein (LDL) cholesterol decreased to pre- treatment levels in response to statin therapy.
- Lipid parameters should be assessed approximately 12 weeks following initiation of therapy and thereafter patients should be managed according to international clinical guidelines for hyperlipidaemia.
Adverse drug reactions
The frequencies of adverse reactions are based on integrated data from clinical trials and/or postmarketing setting across
- rheumatoid arthritis,
- atopic dermatitis, and
- alopecia areata
indications unless stated otherwise.1
Increased LDL cholesterol (26.0 %) was among the most commonly reported adverse drug reactions with baricitinib. 1
Hypercholesterolaemia is a known side effect of baricitinib, the reported frequency is very common (≥ 1/10). 1
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.1
- 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.
Elevations in LDL cholesterol decreased to pre-treatment levels in response to statin therapy.1
Lipid changes in the baricitinib atopic dermatitis development program
The effects of baricitinib on lipid analytes are consistent with a pharmacologic effect of janus kinase (JAK) inhibition, which may be explained, in part, by the inhibition of interleukin-6 signaling.2,3 Data from the baricitinib rheumatoid arthritis clinical development program demonstrated that patients with significant increases in low-density lipoprotein cholesterol (LDL-C) responded to statin treatment.4
In the baricitinib atopic dermatitis (AD) BREEZE-AD trials, assessment of lipids included
- mean changes from baseline
- shifts in analytes according to National Cholesterol Education Program (NCEP) criteria, and
- review of treatment-emergent adverse event (TEAEs) potentially related to hyperlipidemia.2,5,6
The integrated datasets used to evaluate lipid analytes are described in Integrated Analysis Datasets Used to Evaluate Safety in Atopic Dermatitis Clinical Trials.
Mean Change From Baseline in Lipid Analytes
In patients in the BREEZE-AD program, mean LDL-C and high-density lipoprotein cholesterol (HDL-C) were elevated for baricitinib treated patients in the placebo-controlled period and remained elevated during the extended period. No clinical relevant changes were observed through 120 weeks.6,7
Change from baseline in LDL-C and HDL-C in the AD clinical trials are presented in Change From Baseline in Low-density Lipoprotein Cholesterol (A) and High-density Lipoprotein Cholesterol (B) in the Atopic Dermatitis Trials.
Figure 1 Description: In the atopic dermatitis trials, mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were elevated in baricitinib-treated patients in the 16-week placebo-controlled period and remained elevated during the extended period through week 120.
Abbreviations: LDL-C: high-density lipoprotein cholesterol; HDL-C = high-density lipoprotein cholesterol.
Treatment-Emergent Changes in Lipids from Baseline
The proportion of patients who had a categorical increase (according to NCEP criteria) was higher in the baricitinib treatment groups compared to the placebo group for total cholesterol, LDL-C, and HDL-C.2,6
Categorical increases for triglycerides were similar between the baricitinib treatment groups and placebo groups (see Treatment-Emergent Shifts in Total Cholesterol, LDL-C, HDL-C, and Triglycerides).2,6
Total Cholesterol ≥200 mg/dL |
LDL-C ≥130 mg/dL |
HDL-C ≥60 mg/dL |
Triglycerides ≥500 mg/dL |
|
Placebo-Controlled (to week 16) |
||||
Placebo, n=743 |
47/469 (10.0) |
34/542 (6.3) |
65/442 (14.7) |
5/662 (0.8) |
BARI 2 mg, n=576 |
77/386 (19.9) |
52/435 (12.0) |
70/360 (19.4) |
3/510 (0.6) |
BARI 4 mg, n=489 |
66/319 (20.7)a |
48/363 (13.2)b |
75/297 (25.3)a |
3/437 (0.7) |
Extended BARI 2 mg vs 4 mg (up to 3.9 years) |
||||
BARI 2 mg, n=584 |
143/394 (36.3) |
118/443 (26.6) |
117/368 (31.8) |
8/520 (1.5) |
BARI 4 mg, n=497 |
138/328 (42.1) |
114/372 (30.6) |
120/306 (39.2)c |
13/448 (2.9) |
All BARI AD (up to 3.9 years) |
||||
All doses, N=2636 |
694/1691 (41.0) |
595/1958 (30.4) |
575/1582 (36.3) |
52/2390 (2.2) |
Abbreviations: AD = atopic dermatitis; BARI = baricitinib; HDL-C = high-density lipoprotein-cholesterol; LDL-C = low-density lipoprotein-cholesterol; NAR = number at risk.
ap<.001 BARI 4 mg vs placebo.
bp<.01 BARI 4 mg vs placebo.
cp<.05 BARI 2 mg vs BARI 4 mg.
Treatment Emergent Adverse Events Related to Hyperlipidemia
There were no clinically meaningful differences in the integrated safety datasets for lipid-related TEAEs (see Treatment Emergent Adverse Events Related to Hyperlipidemia in the Atopic Dermatitis Clinical Trials).2
|
Placebo-Controlled |
Extended BARI 2 mg vs 4 mg |
All BARI AD |
|||
Placebo |
BARI 2 mg |
BARI 4 mg |
BARI 2 mg |
BARI 4 mg |
All doses |
|
>1 lipid-related TEAE |
9 (1.0) |
14 (1.9) |
7 (1.3) |
24 (3.4) [3.3] |
28 (5.0) [3.5] |
131 [2.9] |
Blood cholesterol increased |
1 (0.1) |
5 (0.5) |
2 (0.3) |
6 (0.7) [0.7] |
4 (0.7) [0.5] |
20 [0.4] |
Hypercholesterolaemia |
3 (0.3) |
4 (0.6) |
1 (0.2) |
9 (1.4) [1.3] |
6 (1.1) [0.8] |
43 [0.9] |
Hypertriglyceridaemia |
4 (0.4) |
5 (0.8) |
2 (0.4) |
8 (1.1) [1.0] |
5 (0.9) [0.5] |
25 [0.5] |
Blood triglycerides increased |
2 (0.3) |
2 (0.2) |
2 (0.4) |
5 (0.7) [0.7] |
3 (0.6) [0.4] |
14 [0.3] |
LDL-C Increased |
1 (0.1) |
3 (0.3) |
2 (0.3) |
3 (0.3) [0.3] |
2 (0.3) [0.3] |
7 [0.1] |
Dyslipidaemia |
0 |
2 (0.3) |
0 |
5 (0.8) [0.7] |
2 (0.4) [0.2] |
20 [0.4] |
Hyperlipidemia |
0 |
0 |
1 (0.2) |
0 |
9 (1.6) [1.1]d |
24 [0.5] |
Lipids Increased |
1 (0.1) |
0 |
0 |
0 |
1 (0.1) [0.1] |
3 [0.1] |
Lipids Abnormal |
NA |
NA |
NA |
0 |
1 (0.2) [0.1] |
1 [<0.1] |
Lipoprotein increased |
NA |
NA |
NA |
0 |
0 |
1 [<0.1] |
Abbreviations: AD = atopic dermatitis; adj = adjusted; BARI = baricitinib; IR = incidence rate; LDL-C = low-density lipoprotein-cholesterol; MedDRA = Medical Dictionary for Regulatory Activities; SMQ = Standardized MedDRA Query; TEAE = treatment emergent adverse event.
aTreatment-emergent adverse events related to hyperlipidemia were reported based on Lilly-defined MedDRA preferred terms SMQ.
bFor the integrated controlled analysis sets where the randomized ratio of patients receiving BARI to placebo or BARI to active control is not the same across all the integrated studies (example 2:1:1:1 vs 1:1:1:1), the study-size adjusted percentages were calculated for the adverse events to provide appropriate direct comparisons between treatment groups.
cFor the integrated controlled analysis sets where the randomized ratio of patients receiving BARI to placebo or BARI to active control is not the same across all the integrated studies (example 2:1:1:1 vs 1:1:1:1), the study-size adjusted percentages were calculated for the adverse events to provide appropriate direct comparisons between treatment groups.
dp<.01.
Integrated safety datasets table
Analysis Set |
Description |
16-Week Placebo-Controlled BARI AD Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE-AD4, and BREEZE-AD7 |
Compares BARI 2 mg, BARI 4 mg and placebo. Includes patients with AD from 1 phase 2 and 4 phase 3 studies who were randomized to
Treated for 0 to 16 weeks during the placebo-controlled period. |
BARI 2 mg and 4 mg Extended ADa Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE-AD4, BREEZE-AD7, and extension study BREEZE-AD3 |
Compares BARI 2 mg vs BARI 4 mg including extended evaluations Includes patients with AD from 1 phase 2 and 4 phase 3 studies and any further exposure for those patients in the phase 3 extension study, BREEZE-AD3, who were randomized to
Data censored at dose or treatment change (rescue, dose switch, or re-randomization to a different BARI dose or placebo) for BREEZE-AD4 and BREEZE-AD3. |
All BARI AD Studies: JAHG, BREEZE-AD1, BREEZE-AD2, BREEZE-AD4, BREEZE-AD5, BREEZE-AD7, and extension studies BREEZE-AD3, BREEZE-AD6a |
No between-group comparisons Includes 2636 (total PYE=4628.4) patients with AD from 1 phase 2, 5 phase 3, and 2 phase 3 extension studies who received BARI at a variety of doses, including
Includes all patients who were exposed to any BARI dose at any time during the studies, either from randomization or from switch or rescue from placebo. No censoring of data at dose change. |
Abbreviations: AD = atopic dermatitis; BARI = baricitinib; PYE = patient-years of exposure.
aData cut as of November 3, 2021 for BREEZE-AD3 and December 15, 2021 for BREEZE-AD4
Note: BARI 1 mg was studied in pivotal trials, however it is not approved. Please refer to section 4.2 of the Olumiant Summary of Product Characteristics for approved dosage.
References
1Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3Charles-Schoeman C, Gonzalez-Gay MA, Kaplan I, et al. Effects of tofacitinib and other DMARDs on lipid profiles in rheumatoid arthritis: implications for the rheumatologist. Semin Arthritis Rheum. 2016;46(1):71-80. https://doi.org/10.1016/j.semarthrit.2016.03.004
4Taylor PC, Kremer JM, Emery P, et al. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis. 2018;77(7):988-995. http://dx.doi.org/10.1136/annrheumdis-2017-212461
5National Cholesterol Education Program (NCEP). Third report of the NCEP expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. National Heart, Lung, and Blood Institute, National Institutes of Health, NIH Publication No. 02-5215. September 2002. Accessed March 4, 2022. https://www.nhlbi.nih.gov/files/docs/resources/heart/atp-3-cholesterol-full-report.pdf
6Bieber T, Thyssen JP, Reich K, et al. Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. J Eur Acad Dermatol Venereol. 2021;35(2):476-485. https://doi.org/10.1111/jdv.16948
7Bieber T, Katoh N, Simpson EL, et al. Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 years and up to 3.9 years of treatment: an updated integrated analysis of eight clinical trials. J Dermatolog Treat. 2023;34(1):2161812. https://doi.org/10.1080/09546634.2022.2161812
8King B, Maari C, Lain E, et al. Extended safety analysis of baricitinib 2 mg in adult patients with atopic dermatitis: an integrated analysis from eight randomized clinical trials. Am J Clin Dermatol. 2021;22(3):395-405. https://doi.org/10.1007/s40257-021-00602-x
9Bieber T, Katoh N, Simpson EL, et al. Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 and up to 3.9 years treatment: an updated integrated analysis of 8 clinical trials. Poster presented at: 31st Annual European Academy of Dermatology and Venereology Congress; September 7-10, 2022; Milan, Italy.
Date of Last Review: 23 November 2022