Baricitinib

Baricitinib is an oral selective Janus kinase 1 and Janus kinase 2 inhibitor(JAK inhibitor). The active substance was investigated in a Phase 2 and several Phase 3 studies in adults with moderate to severe AD at a dose of 1 mg, 2 mg and 4 mg once daily compared to placebo. This showed a significant improvement in the EASI score from baseline to 16 weeks, particularly at the two higher doses, 2 mg daily (mean difference -5.6 points; CI 95%: 0.4-10.9 and 4 mg daily (mean difference -5.2 points; CI 95%: 0.1-10.4 (Drucker AM et al. (2020). Like all JAK inhibitors, baricitinib is a fast-acting drug.

Baricitinib can be used in adult patients with moderate to severe atopic dermatitis for whom systemic therapy is an option. After a response to therapy, a dose reduction can be considered according to the individual benefit/risk assessment and the clinical course. Baricitinib should be used in particular in patients with AD for whom systemic therapy is an option and with concomitant alopecia areata or concomitant rheumatoid arthritis.

Further approvals:

Rheumatoid arthritis Baricitinib is used for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have had an inadequate response or intolerance to previous treatment with one or more disease-modifying antirheumatic drugs (DMARDs). Baricitinib can be used as monotherapy or in combination with methotrexate.

Alopecia areata: Baricitinib is used for the treatment of severe alopecia areata in adult patients.

Juvenile idiopathic art hritis: Baricitinib is used for the treatment of active juvenile idiopathic arthritis in patients 2 years of age and older who have previously had an inadequate response or intolerance to one or more conventional synthetic or biologic DMARDs:

- Polyarticular juvenile idiopathic arthritis (polyarticular rheumatoid factor positive [RF+] or negative [RF-], extended oligoarticular),

- enthesitis-associated arthritis,

and

- Juvenile psoriatic arthritis.

Baricitinib can be used as monotherapy or in combination with methotrexate.

Atopic dermatitis: Acute flare, short-term, long-term treatment Baricitinib is approved at a daily dose of 2 mg and 4 mg. Currently, data on baricitinib are available for a follow-up period of up to 52 weeks (Silverberg JI et al. 2021), demonstrating sustained efficacy.

Combination with other therapies: No studies have yet been published investigating the use of baricitinib with other systemic therapies in AD patients, but the combination therapy of baricitinib with methotrexate is a proven combination regimen for the treatment of rheumatoid arthritis

The most common side effects of baricitinib observed in clinical trials include an increase in LDL cholesterol, upper respiratory tract infections, acne and headaches. Infections associated with baricitinib include herpes simplex, eczema herpeticum, erysipelas and pneumonia (Bieber T et al. 2020). Short-term CPK increases are possible, especially after intensive physical exertion. Even though the clinical studies did not show any significant incidences of baricitinib, it should be used with caution in patients with an increased risk of deep vein thrombosis or pulmonary embolism due to a possible class effect with other JAK inibitors (such as tofacitinib).

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1. Bieber T et al. (2020) Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. J Eur Acad Dermatol Venereol doi:10.1111/jdv.16948
2. BREEZE-ADPEDS (2021) A Study of Baricitinib (LY3009104) in Children and Adolescents With Atopic Dermatitis (BREEZE-ADPEDS). 02.11.2021, 02.11.2021. https://clinicaltrials.gov/ct2/show/NCT03952559
3. Drucker AM et al. (2020) Systemic Immunomodulatory Treatments for Patients With Atopic Dermatitis: A Systematic Review and Network Meta-analysis. JAMA Dermatol 156:659-667.
4. King B et al. (2022) BRAVE-AA Investigators. Two Phase 3 Trials of Baricitinib for Alopecia Areata. N Engl J Med 386: 1687-1699.
5. Reich K et al. (2020) Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol 156:1333-1343.
6. Silverberg JI et al. (2021) Long-term Efficacy of Baricitinib in Adults With Moderate to Severe Atopic Dermatitis Who Were Treatment Responders or Partial Responders: An Extension Study of 2 Randomized Clinical Trials. JAMA Dermatol 157:691-699.
7. Traves PG et al. (2021) JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signaling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis 80:865-875.