Tips for searching:
• You have to select a product and type at least 2 words to activate the search
• Use only words that are specific to the information you are looking for
• Avoid typing questions or sentences
Please do not use this field to report adverse events or product complaints. Adverse events and product complaints should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow card in the Google play or Apple app store. Adverse events and product complaints should also be reported to Lilly: please call Lilly UK on 01256 315 000.
Olumiant ® (baricitinib)
This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).
What is the risk of malignancies in Olumiant® (baricitinib) patients with atopic dermatitis or alopecia areata?
In atopic dermatitis, the incidences of malignancy excluding NMSC and NMSC were 0.3 and 0.2 per 100 patient years, respectively. In alopecia areata, these incidences were 0.2 and 0.1. Malignancy is not listed as an adverse drug reaction.
Content Overview
- Special warnings and precautions regarding baricitinib and malignancies
- Incidence of malignancies in placebo-controlled trials and long-term exposure
- Incidence of malignancies based on real-world data
- Is baricitinib genotoxic or carcinogenic?
- References
- Appendix 1: Integrated safety datasets table atopic dermatitis clinical trials
- Appendix 2: Integrated safety datasets table alopecia areata clinical trials
Special warnings and precautions regarding baricitinib and malignancies
Immunomodulatory medicinal products may increase the risk of malignancies including lymphoma.1
Lymphoma and other malignancies have been reported in patients receiving JAK inhibitors, including baricitinib.1
In a large randomized active‑controlled study of tofacitinib (another JAK inhibitor) in rheumatoid arthritis patients 50 years and older with at least one additional cardiovascular risk factor, a higher rate of malignancies, particularly lung cancer, lymphoma and non-melanoma skin cancer (NMSC) was observed with tofacitinib compared to TNF inhibitors.1
In patients over 65 years of age, patients who are current or past long-time smokers, or with other malignancy risk factors (e.g. current malignancy or history of malignancy) baricitinib should only be used if no suitable treatment alternatives are available.1
Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.1
Incidence of malignancies in placebo-controlled trials and long-term exposure
Atopic dermatitis clinical trials
Baricitinib was evaluated for up to 4628 patient-years of exposure and up to 3.9 years to treat atopic dermatitis. Please find an overview of malignancies from the atopic dermatitis (AD) clinical trials in Malignancy and Nonmelanoma Skin Cancers in Atopic Dermatitis Clinical Trials. Appendix 1: Integrated safety datasets table atopic dermatitis clinical trials provides details about the corresponding studies.2,3
|
BARI 2 mg and 4 mg Extended |
All BARI AD |
||||
Placebo |
BARI 2 mg |
BARI 4 mg |
BARI 2 mg |
BARI 4 mg |
All doses |
|
Malignancy excluding NMSCc |
2d [0.66] |
0 |
0 |
2 [0.28] |
0 |
14 [0.30] |
NMSCe |
1f [0.68] |
0 |
0 |
1 [0.10] |
1 [0.12] |
11 [0.23] |
Abbreviations: AD = atopic dermatitis; adj = adjusted; BARI = baricitinib; IR = incidence rate; MedDRA SMQ = Medical Dictionary for Regulatory Activities query; NMSC = nonmelanoma skin cancer.
aData through 16-week placebo-controlled period.
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.
c1 uterine cancer, 1 testis cancer, 4 prostate cancers, 1 rectal cancer, 1 metatstatic small cell lung cancer, 1 lung adenocarcinoma, 1 diffuse large B-cell lymphoma, 1 anaplastic large cell lymphoma T and null cell types, 1 peripheral T-cell lymphoma unspecified, 1 follicular lymphoma, 1 Hodgkin’s disease
dbreast cancer n=1; papillary thyroid cancer n=1.
e6 events of basal cell carcinoma; 3 events of Bowen's disease; 2 events of squamous cell carcinoma, and 1 event of keratoacanthoma.
fBowen's disease n=1.
The majority (n= 6) had basal cell carcinoma (BCC) with two patients reporting squamous cell carcinoma (SCC). In this study, although only a small number of skin cancer events were identified, the BCC:SCC ratio was 3:1, in line with observations in the immunocompetent general population.4
The observed malignancy incidence rates (IRs) with baricitinib fall within the range of reported background rates for the atopic dermatitis population, which, according to published literature, is
- 0.12 to 0.85 per 100 patient-years of exposure (PYE) for malignancy excluding NMSC, and
- 0.04 to 1.12 per 100 PYE for NMSC.5-7
In the AD clinical trials, 1373 of the 2636 patients were considered patients at-risk, defined as ≥65 years, or with at least one of the following risk factors: atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, current smoking, high-density lipoprotein cholesterol less than 40 mg/dL, body mass index at least 30, poor mobility on EuroQol-5 Dimension, and history of malignancy.8
11 of 14 malignancies excluding NMSC were reported by patients at risk. 2 of those patients had lung cancer. Both were current or past smokers and 65 years or older.8
Alopecia areata clinical trials
Baricitinib was evaluated for up to 2218 patient-years of exposure for alopecia areata (AA). Please find an overview of malignancies from the alopecia areata (AA) clinical trials in Incidence of Malignancies From the 36-Week Placebo-Controlled Period, Extended, and All BARI Integrated Datasets. Appendix 2: Integrated safety datasets table alopecia areata clinical trials provides details about the corresponding studies.9,10
Event |
36-Week Placebo-Controlled BARI AA |
Extended BARI AA |
All BARI AA |
|||
Placebo |
BARI 2 mg |
BARI 4 mg |
BARI 2 mg |
BARI 4 mg |
All Doses |
|
Malignancies excluding NMSCa |
1 [0.4] |
0 |
1 [0.3] |
0 |
2 [0.2] |
4 [0.2] |
NMSCb |
0 |
0 |
0 |
1 [0.2] |
0 |
2 [0.1] |
Abbreviations: AA = alopecia areata; BARI = baricitinib; IR = incidence rate; NMSC = nonmelanoma skin cancer; PYE = patient-years of exposure;
aEvents: B-cell lymphoma, breast cancer, chronic lymphocytic leukemia, malignant melanoma in-situ, prostate cancer.
bEvents: basal cell carcinoma, squamous cell carcinoma.
All 4 cases of malignancy exluding NMSC were reported by patients at-risk.8
The association between AA and cancer has not been extensively studied and appears to vary based on the type of malignancy.
Published literature reported that AA was associated with an increased risk for thyroid cancer.12-15
Conversely, a minimal or rather negative association was found between AA and other malignancies.12-17
In the AA clinical trials, 659 of the 1303 patients were considered patients at-risk of adverse events of special interest (AESI).8
Incidence of malignancies based on real-world data
Best to our knowledge, there are no systematic real-world data in baricitinib patients with atopic dermatitis or alopecia areata.
Is baricitinib genotoxic or carcinogenic?
Baricitinib was not genotoxic in the
Baricitinib did not produce neoplastic changes in 2-year rat and 6-month transgenic mouse carcinogenicity studies.10,18
Non-clinical data reveal no special hazard for humans based on conventional studies of
- safety pharmacology,
- genotoxicity and
- carcinogenic potential.1
References
1Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Bieber 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.
3Bieber 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
4Bieber 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
5Arana A, Wentworth CE, Fernández-Vidaurre C, et al. Incidence of cancer in the general population and in patients with or without atopic dermatitis in the U.K. Br J Dermatol. 2010;163(5):1036-1043. https://dx.doi.org/10.1111/j.1365-2133.2010.09887.x
6Mansfield KE, Schmidt SAJ, Darvalics B, et al. Association between atopic eczema and cancer in England and Denmark. JAMA Dermatol. 2020;156(10):1086-1097. https://dx.doi.org/10.1001/jamadermatol.2020.1948
7Asgari MM, Tsai AL, Avalos L, et al. Association between topical calcineurin inhibitor use and keratinocyte carcinoma risk among adults with atopic dermatitis. JAMA Dermatol. 2020;156(10):1066-1073. https://dx.doi.org/10.1001/jamadermatol.2020.2240
8Taylor, P.C., Bieber, T., Alten, R. et al. Baricitinib Safety for Events of Special Interest in Populations at Risk: Analysis from Randomised Trial Data Across Rheumatologic and Dermatologic Indications. Adv Ther (2023). https://doi.org/10.1007/s12325-023-02445-w
9King 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
10Data on file, Eli Lilly and Company and/or one of its subsidiaries.
11King B, Mostaghimi A, Shimomura Y, et al. Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials. Poster presented at: Annual Meeting of the American Academy of Dermatology Association (AAD); March 25-29, 2022; Boston, MA. Accessed April 29, 2022. https://aad-eposters.s3.amazonaws.com/AM2022/poster/33966/Integrated+safety+analysis+of+baricitinib+in+adults+with+severe+alopecia+areata+from+two+randomized+clinical+trials.pdf
12Lee JH, Song Y, Do Han K, et al. Cancer risk by the subtype of alopecia. Sci Rep. 2018;8(1):9748. https://doi.org/10.1038/s41598-018-28142-1
13Lee S, Lee H, Lee CH, Lee WS. Comorbidities in alopecia areata: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80(2):466-477.e16. https://doi.org/10.1016/j.jaad.2018.07.013
14Seo HM, Han SS, Kim JS. Cancer risks among patients with alopecia areata: a population-based case-control study in Korea. J Am Acad Dermatol. 2018;78(1):209-211. https://doi.org/10.1016/j.jaad.2017.08.011
15Phan K, Smith SD. Alopecia areata and risk of cancer varies based on type of malignancy. J Am Acad Dermatol. 2021;85(suppl 3):AB25. https://dx.doi.org/10.1016/j.jaad.2021.06.126
16Conic RZ, Rambhia P, Atanaskova-Mesinkovska N, et al. Lack of an association between alopecia areata and visceral or hematopoietic cancers. J Am Acad Dermatol. 2017;77(5):981-982. https://doi.org/10.1016/j.jaad.2017.06.045
17Chen CC, Chang YT, Liu HN, Chen YJ. Cancer risk in patients with alopecia areata: a nationwide population-based matched cohort study. Cancer Med. 2018;7(5):2153-2159. https://doi.org/10.1002/cam4.1448
18Carfagna M, Cannady E, Ryan T, et al. Carcinogenicity assessment of baricitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. Regul Toxicol Pharmacol. 2018;92:458-471. https://www.ncbi.nlm.nih.gov/pubmed/29203403
19King B, Mostaghimi A, Shimomura Y, et al. Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials. Br J Dermatol. 2023;188(2):218-227. https://academic.oup.com/bjd/advance-article/doi/10.1093/bjd/ljac059/6821292
Appendix 1: Integrated safety datasets table atopic dermatitis clinical trials
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
Appendix 2: Integrated safety datasets table alopecia areata clinical trials
Analysis Set |
Description |
36-Week placebo-controlled BARI AA |
Assesses BARI 4 mg, BARI 2 mg, and placebo.
Evaluation time period included randomization to week 36. |
Extended BARI AA |
Assesses BARI 4 mg and BARI 2 mg including extended evaluations. Includes patients from the phase 2/3 BRAVE-AA1 and phase 3 BRAVE-AA2 studies who were randomized to
Evaluation time period included randomization up to data cutoff, May 10, 2022 for BRAVE-AA2 and May 24, 2022 for BRAVE-AA1. Data were censored after a patient was switched to another dose or treatment. |
All BARI AA |
No between-group assessments. Includes 1303 (total PYE=2217.9) patients from the phase 2/3 BRAVE-AA1 and phase 3 BRAVE-AA2 studies who were exposed to any BARI dose, including
Evaluation time period included any time points during the studies either from randomization or from switch or rescue from placebo. |
Abbreviations: AA = alopecia areata; BARI = baricitinib; PYE = patient-years of exposure.
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.
Date of Last Review: 05 June 2023