Baricitinib

Baricitinib (2 mg/4 mg Filmtbl.) a Jak inhibitor approved since 2017 for the treatment of rheumatoid arthritis, is now also approved in adults with atopic dermatitis for whom topical medications have not resulted in adequate disease control.Baricitinib inhibits the Janus kinases JAK1 and JAK2, whose activation leads to the release of inflammatory cytokines in tissues. An advantage over biologics is that baricitinib is orally available (Calabrese L et al 2020).

Baricitinib has a targeted inhibitory effect on the activity of JAK1 and JAK2 in the cell, competing with ATP. This reversibly blocks the signal transduction of several cytokines.

The CHMP's recommendation for approval in atopic dermatitis was based on the results of 3 randomized phase 3 studies. The BREEZE-AD1 and BREEZE-AD2 studies enrolled 1,239 patients whose skin condition had been rated by physicians prior to the start of the study at 4 points on the vIGA-AD scale ("Validated Investigator Global Assessment for Atopic Dermatitis"), which ranges from 0 (healed) to 4 points (severe atopic dermatitis) for approximately half (Simpson EL et al. 2020). Patients were treated with baricitinib at 3 doses or placebo for 16 weeks. At the end, under dosing of 1 mg/day, 11.8% in BREEZE-AD1 and 8.8% in BREEZE-AD2 had achieved a score of 0 or 1 on the vIGA-AD scale (primary endpoint of the study) versus 4.8% and 4.5%, respectively, in the placebo groups. The success rate increased to 11.4% and 10.6% at the 2 mg/day dose and to 16.8% and 13.8% at the 4 mg/day dose, respectively.

In addition to atopic dermatitis, the following additional indications are provided:

• Treatment of moderate to severe active rheumatoid arthritis (RA) in adults who have had an inadequate response to, or have been intolerant of, previous treatment with one or more disease-modifying anti-rheumatic drugs(DMARDs). Use as monotherapy or in combination with methotrexate possible.
• Since October 2020, the European Medicines Agency (EMA) has granted a marketing authorization extension for the treatment of adult patients with moderate to severe atopic dermatitis .

• In the European Union in the United States and Japan, baricitinib was approved for the treatment of adults with severe alopecia areata. The dosage was 2m/4mg/day.

Dosage 4 mg/day, from the age of 75 2 mg/day, also in chronic infections 2 mg/day. Under the highest dosage of 4 mg/day, significantly better results were also achieved in all secondary endpoints than in the placebo group, including also in the scores EASI 75, EASI 90 as well as in itching, sleep disturbances, skin pain and in the quality of life (Reich K et al. 2020).

Control: in the absence of response after 8 weeks, discontinuation of therapy.

Upper respiratory tract infections, zoster, nasopharyngitis, headaches and acne are the most common (King B et al. 2023). A higher prevalence of oral herpes simplex infections was reported compared to a control group.

Olumiant®

1. Calabrese L et al. (2020) Baricitinib: therapeutic potential for moderate to severe atopic dermatitis. Expert Opin Investig Drugs 29:1089-1098.

2. King B et al. (2023) Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials. Br J Dermatol 188:218-227.

3. 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.

4. Reich K et al. (2020) Baricitinib improves symptoms in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: patient-reported outcomes from two randomized monotherapy phase III trials. J Dermatolog Treat 22:1-10.

5. Simpson EL et al. (2020) Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol 183:242-255.

6. Simpson EL et al (2021) Baricitinib in patients with moderate-to-severe atopic dermatitis: results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5). J Am Acad Dermatol S0190-9622(21)00353-4. epub ahead of print. PMID: 3360091