Abrocitinib , tralokinumab or upadacitinib for treating moderate to severe atopic dermatitis

Abrocitinib, tralokinumab or upadacitinib for treating moderate to severe atopic dermatitis

NICE state (1):

Abrocitinib and upadacitinib are recommended as options for treating moderate to severe atopic dermatitis that is suitable for systemic treatment in adults and young people 12 years and over, only if:

• the disease has not responded to at least 1 systemic immunosuppressant, or these are not suitable
• the companies provide abrocitinib and upadacitinib according to the commercial arrangement

Tralokinumab is recommended as an option for treating moderate to severe atopic dermatitis that is suitable for systemic treatment in adults, only if:

• the disease has not responded to at least 1 systemic immunosuppressant, or these are not suitable
• the company provides tralokinumab according to the commercial arrangement

Stop abrocitinib, upadacitinib or tralokinumab at 16 weeks if the atopic dermatitis has not responded adequately. An adequate response is:

• at least a 50% reduction in the Eczema Area and Severity Index score (EASI 50) from when treatment started and
• at least a 4-point reduction in the Dermatology Life Quality Index (DLQI) from when treatment started

For full details then consult NICE (August 2022). Abrocitinib, tralokinumab or upadacitinib for treating moderate to severe atopic dermatitis

The NICE committee state (1):

• standard treatment for moderate to severe atopic dermatitis (eczema) includes topical treatments such as emollients and corticosteroids
  • if these treatments are not effective, systemic immunosuppressants such as methotrexate and ciclosporin can be added
  • dupilumab and baricitinib are used if systemic immunosuppressants are not effective
  • the clinical trial evidence shows that abrocitinib, tralokinumab and upadacitinib all reduce symptoms of atopic dermatitis compared with placebo
    • abrocitinib and upadacitinib were indirectly compared with ciclosporin, but the results are highly uncertain
    • abrocitinib, upadacitinib and tralokinumab were each directly or indirectly compared with dupilumab and baricitinib for use after systemic immunosuppressants, but the results are uncertain

Notes:

• Janus kinase-1 (JAK) inhibitors [part of the DMARDs (disease-modifying antirheumatic drugs) family, with the JAK-1, JAK-2, JAK-3 and tyrosine kinase-2 - TYK-2 molecules] which (from a pharmacological viewpoint) are small molecular (synthetic) compounds that inhibit the intracellular transduction of the signal derived from the cell's cytokine receptors
  • cytokines such as IL-1, 2, 4, 5, 13, 22, 31, stromal thymic lymphopoietin, interferon-gamma are involved in atopic disease (atopic dermatitis)'s pathologic process; JAK inhibitors exert their activity by cytokine receptor phosphorylation (an inhibiting action), which in turn modifies the immune response (by decreasing it)
• abrocitinib is part of the JAK-1 inhibitor class, currently being investigated for the use in cases of moderate-to-severe AD, which did not have a proper response to the use of topical treatment (2)
• upadacitinib is an oral, reversible, small molecule JAK inhibitor engineered to have increased selectivity for JAK1 vs JAK2, JAK3, and tyrosine kinase 2, with the intention of improving efficacy and safety for an improved benefit-risk profile compared with other, less-selective JAK inhibitors (3)
• tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds with high affinity to IL-13 alone, preventing its interaction with the receptor and subsequent downstream signalling (4)
• in an analysis (n=2285) of tralokinumab in adult patients with moderate-to-severe atopic dermatitis
  • safety profile during prolonged treatment was consistent with that during initial treatment period and frequency of events did not increase over time (any adverse event [AE]: 65.7% vs. 67.2% placebo and serious AEs in 2.1% vs 2.8%, respectively) (5)

Reference:

• NICE (August 2022). Abrocitinib, tralokinumab or upadacitinib for treating moderate to severe atopic dermatitis
• Niculet E, Bobeica C, Stefanopol IA, Pelin AM, Nechifor A, Onisor C, Tatu AL. Once-Daily Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults and Adolescents Aged 12 Years and Over: A Short Review of Current Clinical Perspectives. Ther Clin Risk Manag. 2022 Apr 13;18:399-407.
• Parmentier JM, Voss J, Graff C, et al.. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. 2018;2:23. doi: 10.1186/s41927-018-0031-x
• Wollenberg A et al; ECZTRA 1 and ECZTRA 2 study investigators. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J Dermatol. 2021 Mar;184(3):437-449.
• Simpson EL, Merola JF, Silverberg JI, Reich K, Warren RB, Staumont-Sallé D, Girolomoni G, Papp K, de Bruin-Weller M, Thyssen JP, Zachariae R, Olsen CK, Wollenberg A. Safety of tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomized, double-blind, placebo-controlled phase II and phase III trials. Br J Dermatol. 2022 Sep 9.