Olumiant ® (baricitinib)

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Were concomitant corticosteroid treatments permitted in the baricitinib alopecia areata clinical program?

In the BRAVE-AA1 and BRAVE-AA2 clinical studies, patients who required systemic, intralesional, or topical corticosteroids to treat alopecia areata on the scalp, eyebrows, or eyelids were discontinued from the study.

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Overview of BRAVE-AA phase 3 placebo-controlled clinical trials

The efficacy and safety of baricitinib (BARI) have been evaluated in the following pivotal, phase 3, placebo-controlled trials in adult patients with severe alopecia areata (AA)

  • BRAVE-AA1 (N=654) compared BARI 2 mg or 4 mg to placebo in adult patients with ≥50% scalp hair loss, and
  • BRAVE-AA2 (N=546) compared BARI 2 mg or 4 mg to placebo in adult patients with ≥50% scalp hair loss.1

Concomitant medication use criteria in the BRAVE-AA phase 3 placebo-controlled clinical studies

Exclusion criteria related to corticosteroid use

Patients were excluded from participation in the BRAVE-AA1 and BRAVE-AA2 clinical studies if they had

  • any serious concomitant illness that was anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring, or
  • received
    • topical corticosteroids applied to the scalp or eyebrows within 1 week prior to randomization
    • systemic corticosteroids within 8 weeks prior to randomization
    • an intralesional corticosteroid injection for treatment of AA within 8 weeks prior to randomization, or
    • an intraarticular corticosteroid injection within 8 weeks prior to randomization.1

Permitted concomitant corticosteroid medications for non-AA related conditions

In the BRAVE-AA1 and BRAVE-AA2 clinical studies, permitted concomitant corticosteroid medications included

  • topical corticosteroids except on the scalp, eyebrows, and eyelids
  • intranasal, ophthalmic, or inhaled steroids
  • a maximum of 2 intraarticular or soft tissue (bursa, tendon, and/or ligament) corticosteroid injections up until the 36-week primary endpoint and after 36 weeks, and
  • systemic corticosteroids for the treatment of an AE (ie, worsening of an existing condition, such as an asthma flare). If used for ≥30 days, sponsor approval was required to restart investigational medication.1

Efficacy and safety of baricitinib in patients with concomitant corticosteroid treatments

Subgroup analyses of efficacy and safety have not been conducted in patients with concomitant use of corticosteroid treatments. In the BRAVE-AA1 and BRAVE-AA2 clinical studies, patients who required systemic, intralesional, or topical corticosteroids for treatment of AA on the scalp, eyebrows, or eyelids were discontinued from the study.2

Summary of Concomitant Medications in the Combined Analysis of the Pivotal Phase 3 BRAVE-AA1 and BRAVE-AA2 Trials (Integrated Analysis Set Population) presents the percentages of patients with concomitant use of corticosteroid treatments that were permitted in the BRAVE-AA placebo-controlled clinical trials.


Summary of Concomitant Medications in the Combined Analysis of the Pivotal Phase 3 BRAVE-AA1 and BRAVE-AA2 Trials (Integrated Analysis Set Populationa)2

Categorized by ATC Level 2 Classification, n (%)

Placebo (n=345)

BARI 2 mg (n=340)

BARI 4 mg (n=515)

Corticosteroids, dermatological preparationsb

46 (13.3)

29 (8.5)

36 (7.0)

Mometasone

9 (2.6)

4 (1.2)

7 (1.4)

Betamethasone

5 (1.4)

3 (0.9)

6 (1.2)

Clobetasol

8 (2.3)

9 (2.6)

5 (1.0)

Triamcinolone

5 (1.4)

3 (0.9)

5 (1.0)

Clobetasone

1 (0.3)

0

3 (0.6)

Desonide

6 (1.7)

3 (0.9)

3 (0.6)

Hydrocortisone

8 (2.3)

2 (0.6)

3 (0.6)

Methylprednisolone

4 (1.2)

2 (0.6)

3 (0.6)

Prednicarbate

2 (0.6)

1 (0.3)

3 (0.6)

Dexamethasone

0

2 (0.6)

2 (0.4)

Difluprednate

0

0

2 (0.4)

Fluocinonide

2 (0.6)

1 (0.3)

2 (0.4)

Prednisolone

4 (1.2)

1 (0.3)

2 (0.4)

Alclometasone

0

0

1 (0.2)

Betamethasone; clotrimazole; gentamicin

0

0

1 (0.2)

Betamethasone; gentamicin; miconazole

0

0

1 (0.2)

Clotrimazole; dexamethasone; neomycin

0

0

1 (0.2)

Fluocinolone acetonide

0

0

1 (0.2)

Fluocinolone acetonide; neomycin

0

0

1 (0.2)

Betamethasone; gentamicin

1 (0.3)

0

0

Clocortolone

1 (0.3)

0

0

Desoximetasone

2 (0.6)

0

0

Diflucortolone

1 (0.3)

1 (0.3)

0

Hydrocortisone; hydroquinone; tretinoin

0

1 (0.3)

0

Ulobetasol

0

1 (0.3)

0

Corticosteroids, systemic useb

11 (3.2)

12 (3.5)

18 (3.5)

Prednisone

4 (1.2)

4 (1.2)

8 (1.6)

Dexamethasone

4 (1.2)

3 (0.9)

3 (0.6)

Methylprednisolone

3 (0.9)

4 (1.2)

2 (0.4)

Prednisolone

1 (0.3)

0

2 (0.4)

Triamcinolone

0

2 (0.6)

2 (0.4)

Beclometasone

0

0

1 (0.2)

Corticosteroid, NOS

0

1 (0.3)

1 (0.2)

Cortisone

0

0

1 (0.2)

Fludrocortisone

0

0

1 (0.2)

Hydrocortisone

0

0

1 (0.2)

Betamethasone

0

1 (0.3)

0

Deflazacort

1 (0.3)

0

0

Other corticosteroidsb

Nasal preparations

Fluticasone

5 (1.4)

6 (1.8)

10 (1.9)

Budesonide

1 (0.3)

0

1 (0.2)

Mometasone

0

0

1 (0.2)

Azelastine; fluticasone

0

1 (0.3)

0

Triamcinolone

1 (0.3)

0

0

Ophthalmologic preparations

Dexamethasone; neomycin; polymyxin B

0

0

2 (0.4)

Fluorometholone

0

2 (0.6)

2 (0.4)

Prednisolone

0

0

1 (0.2)

Dexamethasone

1 (0.3)

0

0

Inhaled preparations

Budesonide; formoterol

6 (1.7)

2 (0.6)

6 (1.2)

Fluticasone; salmeterol

0

1 (0.3)

5 (1.0)

Budesonide

0

0

3 (0.6)

Fluticasone

3 (0.9)

1 (0.3)

2 (0.4)

Fluticasone; vilanterol

1 (0.3)

1 (0.3)

2 (0.4)

Beclomethasone; formoterol

0

1 (0.3)

1 (0.2)

Ciclesonide

0

1 (0.3)

1 (0.2)

Beclomethasone

1 (0.3)

0

0

Formoterol; mometasone

1 (0.3)

1 (0.3)

0

Otological preparations

Dexamethasone; neomycin; polymyxin B

0

1 (0.3)

0

Hydrocortisone; neomycin; polymyxin B

0

1 (0.3)

0

Abbreviations: AA = alopecia areata; ATC = Anatomical Therapeutic Chemical; BARI = baricitinib; NOS = not otherwise specified.

aBased on the pooled week-36 efficacy population.

bSpecified as treatment for non-AA conditions.

Drug–drug interactions with baricitinib and concomitant corticosteroids

Potential for drug-drug interactions with baricitinib based on PK studies

Pharmacokinetic substrate studies

There were no clinically relevant effects on BARI PK when BARI was coadministered with

  • a CYP3A inhibitor (ketoconazole)
  • a CYP2C19/CYP2C9/CYP3A inhibitor (fluconazole)
  • a CYP3A inducer (rifampicin)
  • a Pgp inhibitor (cyclosporine), or
  • MTX.3

Coadministration with BARI had no clinically relevant effects on the PK of

  • a CYP3A substrate (simvastatin or Microgynon®)
  • a OATP1B1 substrate (simvastatin acid)
  • a Pgp substrate (digoxin), or
  • an OAT1, OAT3, and BCRP substrate (MTX).2,3

Coadministration of baricitinib with ciclosporin (Pgp/BCRP inhibitor) or methotrexate (substrate of several transporters including OATP1B1, OAT1, OAT3, BCRP, MRP2, MRP3, and MRP4) resulted in no clinically meaningful effects on baricitinib exposure.4

Metabolism and elimination

Baricitinib metabolism is mediated by CYP3A4, with less than 10 % of the dose identified as undergoing biotransformation.4

No metabolites were quantifiable in plasma. In a clinical pharmacology study, baricitinib was excreted predominately as the unchanged active substance in urine (69 %) and faeces (15 %) and only 4 minor oxidative metabolites were identified (3 in urine; 1 in faeces) constituting approximately 5 % and 1 % of the dose, respectively.4

Renal elimination is the principal mechanism for baricitinib’s clearance through glomerular filtration and active secretion via

  • OAT3,
  • Pgp,
  • BCRP and
  • MATE2-K.4

In a clinical pharmacology study, approximately 75 % of the administered dose was eliminated in the urine, while about 20 % of the dose was eliminated in the faeces.4

Clinical use of corticosteroids 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

1King B, Ohyama M, Kwon O, et al; BRAVE-AA investigators. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. https://doi.org/10.1056/nejmoa2110343

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

3Payne 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

4Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

Date of Last Review: 29 April 2022


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