Skin pain improvements and improved quality of life in atopic dermatitis

Baricitinib rapidly improves skin pain resulting in improved quality of life for patients with atopic dermatitis: analyses from BREEZE-AD1, 2 and 7

Thyssen JP, Buhl T, Fernández-Peñas P, Kabashima K, Chen S, Lu N, et al. Dermatol Ther (Heidelb). 2021;11:1599–1611.

Skin pain is one of the most frequently reported symptoms of atopic dermatitis, after itch, but its importance has been under-recognised by dermatologists and treatment guidelines¹

Skin pain, often described by patients as discomfort or soreness, can markedly affect quality of life^1,2, but may not be adequately controlled by current topical or systemic immunomodulatory treatments³.

Baricitinib, an oral inhibitor of Janus kinase (JAK) 1 and 2, is approved in the European Union and Japan for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are eligible for systemic therapy. Baricitinib is also under investigation for this indication in the US and other countries⁴.

The safety and efficacy of baricitinib for the treatment of AD is being evaluated in the BREEZE-AD program, which consists of seven phase 3 multicentre, randomised, double-blind, placebo-controlled clinical trials^5,6. Four of these trials, BREEZE-AD1, 2, 5 and 7 have now been completed and the main outcomes published^7-9.

BREEZE-AD 1, 2 and 7 were global trials that included patients with moderate-to-severe AD who had inadequate responses to available topical therapies. Data collected in these trials included participant-recorded questionnaires for Itch Numerical Rating Scale (NRS), Skin Pain NRS, AD Sleep Scale and the Dermatology Life Quality Index (DLQI)^7,8. A post hoc analysis showed that baricitinib rapidly reduced itch and improved sleep quality, as reported by participants¹⁰. Thyssen and colleagues conducted a subsequent analysis of these three trials to examine the effect of baricitinib on participant-reported skin pain and associated quality of life (QoL)³.

How did the investigators conduct the trials?

Thyssen and colleagues analysed Skin Pain NRS and DLQI data from BREEZE-AD1, 2 and 7 to examine the effect of several doses of baricitinib (1 mg, 2 mg, 4 mg) on skin pain and quality of life (Table 1).

Table 1. Design of BREEZE-AD1, 2 and 7 clinical trials. DLQI, Dermatology Life Quality Index; NRS, Numerical Rating Scale; TCS, topical corticosteroids. *All participants were patients with moderate-to-severe atopic dermatitis with inadequate response to topical therapies.

What did the investigators find?

Skin pain

In all three trials:

• Significant changes from baseline in the Skin Pain NRS were seen in all baricitinib treatment groups, compared with placebo, at Day 2 (Table 2)
• Significant changes in least squares mean (LSM) change from baseline were seen in all baricitinib groups, compared with placebo, after 1 week of treatment (Table 2)
• At week 1, a significantly higher proportion of participants in the 4 mg baricitinib group achieved at least a 4-point improvement in Skin Pain NRS, compared with placebo (BREEZE-AD1: 3.3%, P=0.043; BREEZE-AD2: 5.3%, P=0.028; BREEZE-AD7: 11.6%, P=0.027)

Table 2. Changes from baseline in Skin Pain Numerical Rating Scale. LSM, least squares mean

The improvements increased with treatment duration and plateaued at 3–5 weeks.

At week 16:

• Improvements in Skin Pain NRS were maintained in the 1 mg and 4 mg groups in BREEZE-AD1, and the 2 mg and 4 mg groups in BREEZE-AD2 and 7.
• A significantly higher proportion of participants in the 4 mg baricitinib group in all three trials and the 2 mg groups in BREEZE-AD2 and 7 achieved a clinically meaningful response of at least a 4-point improvement in Skin Pain NRS (responders), compared with those in the placebo groups (BREEZE-AD1, 4 mg: 25.3% P<0.001; BREEZE-AD2, 4 mg: 20.0%, P<0.001; 2 mg: 19.0%, P<0.001; BREEZE-AD7 4 mg: 48.8%, P<0.001; 2 mg: 45.2%, P=0.004)

Quality of life

At week 16, a significantly higher proportion of responders achieved at least a 4-point improvement in the Dermatology Quality of Life Index, compared with non-responders (Figure 1). This result indicates that improved skin pain is related to increased QoL, although numbers in this analysis were limited.

Figure 1. Improvement in DLQI at week 16 (Adapted³). Bars represent the percentage of Skin Pain NRS responders and non-responders who achieved at least a 4-point improvement in DLQI score in (A) BREEZE-AD1, (B) BREEZE-AD2 and C) BREEZE-AD7. ***P<0.0001. CI, confidence intervals DLQI, Dermatology Life Quality Index; NRS, numerical rating scale.

The BREEZE-AD1, 2 and 7 trials showed that baricitinib can reduce skin pain within 24 hours of treatment and this is accompanied by a significant improvement in quality of life for patients with moderate-to-severe atopic dermatitis

References

1. Ständer S, Simpson EL, Guttman-Yassky E, Thyssen JP, Kabashima K, Ball SG, et al. Clinical Relevance of Skin Pain in Atopic Dermatitis. J Drugs Dermatol. 2020;19(10):921-926.
2. Vakharia PP, Chopra R, Sacotte R, Patel KR, Singam V, Patel N, et al. Burden of skin pain in atopic dermatitis. Ann Allergy Asthma Immunol. 2017;119(6):548-552.e543.
3. Thyssen JP, Buhl T, Fernández-Peñas P, Kabashima K, Chen S, Lu N, et al. Baricitinib Rapidly Improves Skin Pain Resulting in Improved Quality of Life for Patients with Atopic Dermatitis: Analyses from BREEZE-AD1, 2, and 7. Dermatol Ther (Heidelb). 2021;11(5):1599-1611.
4. Silverberg JI, Boguniewicz M, Waibel J, Weisman J, Strowd L, Sun L, et al. Clinical Tailoring of Baricitinib 2 mg in Atopic Dermatitis: Baseline Body Surface Area and Rapid Onset of Action Identifies Response at Week 16. Dermatol Ther (Heidelb). 2022;12(1):137-148.
5. Radi G, Simonetti O, Rizzetto G, Diotallevi F, Molinelli E, Offidani A. Baricitinib: The First Jak Inhibitor Approved in Europe for the Treatment of Moderate to Severe Atopic Dermatitis in Adult Patients. Healthcare (Basel). 2021;9(11).
6. Hoy SM. Baricitinib: A Review in Moderate to Severe Atopic Dermatitis. Am J Clin Dermatol. 2022;23(3):409-420.
7. Simpson EL, Lacour JP, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, et al. 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. 2020;183(2):242-255.
8. Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, et al. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020;156(12):1333-1343.
9. Simpson EL, Forman S, Silverberg JI, Zirwas M, Maverakis E, Han G, et al. 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. 2021;85(1):62-70.
10. Buhl T, Rosmarin D, Serra-Baldrich E, Fernandez-Peñas P, Igarashi A, Konstantinou MP, et al. Itch and Sleep Improvements with Baricitinib in Patients with Atopic Dermatitis: A Post Hoc Analysis of 3 Phase 3 Studies. Dermatol Ther (Heidelb). 2021;11(3):971-982.