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Baricitinib Lilly (baricitinib)

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Can baricitinib be used concomitantly with oral contraceptives in patients with rheumatoid arthritis?

Concomitant use of oral contraceptives was permitted in the baricitinib rheumatoid arthritis clinical trials. Subgroup analyses of efficacy and safety have not been conducted in patients with concomitant use of oral contraceptives.

UK_cFAQ_BAR305A_CONCOMITANT_ORAL_CONTRACEPTIVES_RA
UK_cFAQ_BAR305A_CONCOMITANT_ORAL_CONTRACEPTIVES_RAen-GB

Content overview

  • How to manage the risk of venous thromboembolism
  • Clinical trial criteria related to birth control  
  • Efficacy and safety of baricitinib in patients with concomitant oral contraceptives
  • Potential Drug-Drug Interactions
  • Clinical use of oral contraceptive therapy and baricitinib

How to manage the risk of venous thromboembolism

Baricitinib is contraindicated during pregnancy. Women of childbearing potential have to use effective contraception during and for at least 1 week after treatment. Please see section 4.6 of the Baricitinib Lilly Summary of Product Characteristics, for full prescribing information1

For full prescribing information relating to Deep vein thrombosis (DVT) and pulmonary embolism (PE), please see section 4.4 Venous thromboembolism and section 4.8 of the Summary of Product Characteristics.1

Safety Profile of Baricitinib for the Risk of Venous Thromboembolism

Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving baricitinib. In a retrospective observational study of baricitinib in rheumatoid arthritis (RA) patients, a higher rate of venous thromboembolic events was observed compared to patients treated with tumor necrosis factor (TNF) blockers. These events have been described with the use of other Janus kinase (JAK) inhibitors.2 

Baricitinib should be used with caution in patients with risk factors for DVT/PE. If clinical features of DVT/PE occur, interrupt baricitinib, evaluate promptly, and institute appropriate treatment.2 

Information regarding risk factors associated with DVT/PE is available in a separate response.

Rheumatoid Arthritis Baricitinib Pivotal Clinical Trials

Each of the 4 phase 3 studies in the clinical program evaluated a distinct treatment population of patients with moderate-to-severe RA.

  • RA-BEGIN compared baricitinib 4 mg monotherapy, baricitinib 4 mg plus methotrexate (MTX), and MTX monotherapy in patients who had limited or no prior treatment with MTX and were naïve to other disease-modifying antirheumatic drugs (DMARDs).3
  • RA-BEAM compared baricitinib 4 mg vs placebo or adalimumab, with background MTX, in patients with inadequate response to MTX.4 
  • RA-BUILD compared baricitinib 2 mg and 4 mg vs placebo, with background conventional synthetic DMARD (csDMARD) therapy, in patients with inadequate response to csDMARDs.5
  • RA-BEACON compared baricitinib 2 mg and 4 mg vs placebo, with background csDMARD therapy, in patients with an inadequate response to at least one TNF inhibitor, who may also have had an inadequate response to one or more non-TNF inhibitor biologic DMARDs.6

Clinical trial criteria related to birth control  

Patients were excluded from participating in baricitinib RA clinical studies if they were women of childbearing potential who did not agree to use 2 forms of highly effective birth control when engaging in sexual intercourse while enrolled in the study and for at least 28 days following the last dose of study treatment.2

For full information on baricitinib clinical trials in rheumatoid arthritis, please refer to the section 5.1 of the summary of product characteristics (SmPC).1

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Efficacy and safety of baricitinib in patients with concomitant oral contraceptives

Thorough subgroup analyses of the efficacy and safety of concomitant use of baricitinib and oral contraceptives have not been conducted.

Summary of Concomitant Hormone Modulators Used in Each Baricitinib Rheumatoid Arthritis Clinical Trials presents the percentages of patients with concomitant use of hormone modulators including contraceptives in the 4 pivotal phase 3 clinical trials in adults with RA.

Summary of Concomitant Hormone Modulators Used in Each Baricitinib Rheumatoid Arthritis Clinical Trials2,7,8

Sex Hormones and Modulators of the Genital Systemab

Treatment Arm

Treatment Arm

Treatment Arm

RA-BEGIN (N=584)

MTX
n=210

Baricitinib 4 mg
n=159

Baricitinib 4 mg plus MTX
n=215

Total, n (%)

15 (7.1)

18 (11.3)

20 (9.3)

Eugynon®c

3 (1.4)

3 (1.9)

4 (1.9)

Estradiol

0

1 (0.6)

3 (1.4)

Drospirenone

0

4 (2.5)

2 (0.9)

Drospirenone w/ ethinylestradiol

2 (1.0)

3 (1.9)

2 (0.9)

Ethinylestradiol

0

5 (3.1)

1 (0.5)

Diane®d

2 (1.0)

1 (0.6)

0

RA-BEAM (N=1305)

Placebo
n=488

Baricitinib 4 mg
n=487

Adalimumab
n=330

Total, n (%)

38 (7.8)

44 (9.0)

19 (5.8)

Drospirenone w/ ethinylestradiol

5 (1.0)

10 (2.1)

2 (0.6)

Eugynonc

8 (1.6)

6 (1.2)

3 (0.9)

Ethinylestradiol

3 (0.6)

4 (0.8)

0

RA-BUILD (N=684)

Placebo
n=228

Baricitinib 2 mg
n=229

Baricitinib 4 mg
n=227

Total, n (%)

19 (8.3)

21 (9.2)

19 (8.4)

Eugynonc

6 (2.6)

5 (2.2)

4 (1.8)

Drospirenone w/ethinylestradiol

2 (0.9)

0

2 (0.9)

Estradiol

1 (0.4)

4 (1.7)

1 (0.4)

RA-BEACON (N=527)

Placebo
n=176

Baricitinib 2 mg
n=174

Baricitinib 4 mg
n=177

Total, n (%)

15 (8.5)

9 (5.2)

16 (9.0)

Estradiol

4 (2.3)

3 (1.7)

5 (2.8)

Eugynonc

2 (1.1)

4 (2.3)

3 (1.7)

Medroxyprogesterone

1 (0.6)

0

2 (1.1)

Abbreviations: ATC = Anatomical Therapeutic Chemical; MTX = methotrexate.

aCategorized by Anatomical Therapeutic Chemical classification

bPresenting only preferred name medications totaling ≥0.5% across all the treatment arms.

cContains ethinylestradiol and norgestrel.

dContains cyproterone acetate and ethinylestradiol.

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Potential Drug-Drug Interactions

Based on clinical pharmacology studies, baricitinib had no effect on the pharmacokinetics of the components of Microgynon®, Bayer, United Kingdom (ethinyl estradiol and levonorgestrel), a cytochrome P450 (CYP) 3A substrate.9

In addition, no clinically relevant effects on baricitinib pharmacokinetics occurred with the co-administration of baricitinib and

  • a CYP 3A inhibitor
  • a CYP2C19/CYP2C9/CYP 3A inhibitor
  • a CYP 3A inducer, or
  • a P-glycoprotein (Pgp) inhibitor.9

For full information on interactions of baricitinib with other medicinal products please refer to the summary of product characteristics, section 4.5 and 5.2.

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Clinical use of oral contraceptive therapy and baricitinib

The treating physician may use the information provided, the patient’s prior medical history and other concomitant medications, and other individual factors, in formulating an assessment and approach. The treating physician should consider potential risks and benefits of treatment options and monitor appropriately.

References

1Baricitinib Lilly [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands (UK).

2Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol. 2017;69(3):506-517. http://dx.doi.org/10.1002/art.39953

4Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376(7):652-662. http://dx.doi.org/10.1056/NEJMoa1608345

5Dougados M, van der Heijde D, Chen YC, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis. 2017;76(1):88-95. http://dx.doi.org/10.1136/annrheumdis-2016-210094

6Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(13):1243-1252. http://dx.doi.org/10.1056/NEJMoa1507247

7Micromedex Solutions® Pharmaceutical Knowledge: Diane®. In: IBM Micromedex, Armonk, New York: IBM, Inc. http://www.Micromedex.com. Accessed February 8, 2024.

8Micromedex Solutions® Pharmaceutical Knowledge: Eugynon®. In: IBM Micromedex, Armonk, New York: IBM, Inc. http://www.Micromedex.com. Accessed February 8, 2024.

9Payne C, Zhang X, Shahri N, et al. Evaluation of potential drug-drug interactions with baricitinib. Ann Rheum Dis. 2015;74(suppl 2):1063. European League Against Rheumatism abstract AB0492. http://dx.doi.org/10.1136/annrheumdis-2015-eular.1627

Links to references and third-party websites are provided solely for your convenience and to facilitate easy access to the sources cited.

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Date of Last Review: 23 January 2024

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