Baricitinib-TCS combo therapy clinically benefits adult patients with moderate to severe atopic dermatitis

30 Dec 2020

Topical corticosteroid (TCS) therapy has been used in the management of atopic dermatitis (AD) for more than 60 years and has remained as the current mainstay of anti-inflammatory therapy in clinical practice.1 In a recently published phase 3 BREEZE-AD7 study, baricitinib, a new oral selective Janus kinase (JAK) 1 and JAK2 inhibitor, in combination with TCS have significantly reduced the signs and symptoms of AD in adult patients with moderate to severe AD when compared to placebo.

AD, a disease affecting 2.1% to 4.9% of adults in developed countries, is associated with a multidimensional burden of illness that includes not only skin symptoms but also sleep disturbances, mental health impairments, quality of life, and reduced work productivity.2 For patients with moderate to severe AD whose burden cannot be eased effectively with TCS, the addition of phototherapy and/or systemic treatment is recommended.3 As these alternative treatment options have raised safety concerns in long-term therapy with limited efficacy, more targeted therapies have recently been developed based on the molecular pathogenesis of AD.3,4

Among these targeted therapies is baricitinib which inhibits several cytokines in AD pathogenesis such as thymic stromal lymphopoietin, interleukin (IL)-4, IL-5, IL-13, IL-22, and IL-31.3 In the previous phase 3 BREEZE-AD1 and BREEZE-AD2 trials, baricitinib 2mg and 4mg once-daily oral monotherapy have demonstrated superiority to placebo in improving the clinical signs and symptoms of AD with a satisfactory safety profile in patients with moderate to severe AD who had insufficient response to TCSs.3 To further this success, promising results have been recently published from the BREEZE-AD7 study, the first 16-week phase 3 trial which evaluated the combined therapy of baricitinib with TCS. This novel regimen closely mirrors clinical practice and will provide a new hope to patients who had an inadequate response to TCS therapy.3

BREEZE-AD7 is a multicenter, double-blind, placebo-controlled, parallelarm, 16-week, phase 3 randomized clinical trial involving patients from 68 centers across 10 countries in Asia, Australia, Europe, and South Africa.3 From 2018 to 2019, 329 patients with mean age of 33.8 years, score of 3 (moderate) to 4 (severe) AD as evaluated by the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), and insufficient responses to TCSs within the last 6 months were randomized 1:1:1 to baricitinib 4mg daily (n=111), baricitinib 2mg daily (n=109), or placebo (n=109) for 16 weeks.3 All patients also received moderate and/or low-potency TCSs such as 0.1% triamcinolone cream and 2.5% hydrocortisone ointment, respectively, for active lesions.3

Based on the results, the efficacy of 4mg baricitinib-TCS was significantly superior to that of 2mg baricitinib-TCS and placebo. At week 16, 31% of patients receiving 4mg baricitinib-TCS and 24% of patients receiving 2mg baricitinib-TCS reached a vIGA-AD score of 0 (clear) or 1 (almost clear), compared to only 15% of patients receiving placebo (OR, 4mg and 2mg vs. placebo=2.8 and 1.9; 95% CI: 1.4-5.6 and 0.9-3.9; p=0.004 and 0.08, respectively).3 Additionally, patients receiving 4mg baricitinib- TCS had demonstrated significant improvement in the proportion of patients who achieved 75% improvement in Eczema Area and Severity Index (EASI) score (48% vs. 23%; p<0.001) and a 4-point or greater improvement on the Itch Numeric Rating Scale (NRS) (44% vs. 20%; p<0.001) when compared to those receiving placebo.3

In terms of safety, a higher proportion of patients in the two baricitinib- TCS groups reported treatment-associated adverse events (AEs) than in the placebo group (58%, 56% and 38% in the 4mg baricitinib- TCS, 2mg baricitinib-TCS, and placebo group, respectively).3 The most prevalent AEs were nasopharyngitis, folliculitis, oral herpes, upper respiratory tract infection, acne, diarrhea, and back pain.3 However, the overall safety profile for baricitinib-TCS was consistent with previous phase 3 baricitinib monotherapy AD trials.3

In conclusion, BREEZE-AD7 demonstrated that combining a dose of baricitinib 4mg with a background of TCS therapy was efficient in improving the signs and symptoms of moderate to severe AD in adults who had insufficient response to TCSs when compared to placebo. The study further suggests that this combination has a comparable safety profile to baricitinib monotherapy. As such, the combination of baricitinib-TCS may be a novel oral regimen option for patients who have inadequate response to TCSs.

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