Tag: atopic dermatitis

Categories : New Compounds and Treatments Skin ConditionsTags :

New JAK1 Inhibitor Abrocitinib Effective in Atopic Dermatitis

On By ModernMedia

A phase III trial showed that a new oral Janus kinase 1 (JAK1) inhibitor, abrocitinib, bettered placebo, at higher doses, also outperformed dupilumab in treating signs and symptoms of atopic dermatitis.

More patients on the higher dose of abrocitinib had an Eczema Area and Severity Index 75 (EASI-75) response (75% improvement from baseline) as compared with the other three randomised groups, reported Hernan Valdez, MD, of Pfizer in New York City, and colleagues.

“In the JADE COMPARE trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo on the basis of IGA and EASI-75 responses at weeks 12 and 16,” the authors stated. “The 100-mg dose of abrocitinib was not significantly different from dupilumab with respect to the three key secondary endpoints of the trial.”

“The 200-mg dose of abrocitinib was superior to dupilumab with respect to itch response at week 2 but not to an EASI-75 response at week 16; no conclusion could be drawn regarding the difference between the 200-mg dose of abrocitinib and dupilumab with respect to an IGA response… . Longer and larger trials are necessary to determine the efficacy and safety of abrocitinib and to compare it with other JAK inhibitors and with biologic agents used for the treatment of atopic dermatitis,” they added.

Several oral JAK inhibitors besides abrocitinib being clinically evaluatied for AD. According to the authors, targeting JAK1 results in inhibition of signaling by interleukin (IL)-4, IL-13, and other cytokines involved in AD. However, there is a lack of data on head-to-head trials of JAK inhibitors.

Despite the very positive reception of JAK inhibitors for the treatment of AD, there have been some studies which raised safety concerns. Tofacitinib, for example, has been associated with a higher rate of malignancies and major adverse cardiovascular events.

In this phase III trial, 838 patients with moderate or severe AD were randomised to abrocitinib 100 mg or 200 mg, dupilumab, or placebo. The trial had two primary endpoints: investigator’s global assessment (IGA) response at week 12 and EASI-75 response at week 12. Both endpoints were compared versus placebo. Secondary analyses included comparisons of itch response at week 2 versus placebo and dupilumab and IGA and EASI-75 responses versus placebo at week 16.

More patients on either of the two doses of abrocitinib had IGA responses at week 12 compared to placebo. The proportion of patients with an EASI-75 response at 12 weeks was 70.3% with abrocitinib 200mg, 58.7% for abrocitinib 100mg, 58.1% for dupilumab, and 27.1% for placebo. All treatment groups performed significantly better than placebo.

At week 2, 49.1% of patients had itch response with the higher dose of abrocitinib, 31.8% with the lower dose, 26.4% with dupilumab, and 13.8% with placebo. The 200-mg abrocitinib group was superior to dupilumab. 

Adverse events (AEs) occurred more often with 200-mg abrocitinib as compared with the other three groups (61.9% vs 50.0% to 53.4%), the most common of which was nausea.

Source: MedPage Today

Journal information:  Bieber T, et al “Abrocitinib versus placebo or dupilumab for atopic dermatitis” N Engl J Med 2021; DOI: 10.1056/NEJM0a2019380.

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

New Bacteria-based Atopic Dermatitis Treatment Proves Effective

On By ModernMedia

A skin bacteria-based treatment for atopic dermatitis (AD) was successful in clinical trials, with no serious adverse effects and indications that it reduces eczema symptoms as well.

Atopic dermatitis (AD) is a common, chronic skin disorder which can have great impacts on the lives of sufferers. The disorder seems to result from the complex interplay between the skin, environmental effects and the immune system. Treatment involves a multifaceted approach that involves education, optimal skin care practices, anti-inflammatory treatment with topical corticosteroids and/or topical calcineurin inhibitors, the management of pruritus, and the treatment of skin infections. Severe flare-ups or more difficult-to-control disease may be treated with systemic immunosuppressive agents. Topical corticosteroids are the first-line treatment of choice, and seem to be prophylactic against flareups.

AD is associated with S. aureus colonisation, which induces a proteolytic breakdown of the epidermal barrier and dermal immune dysregulation. Inflammation results in further dysregulation of the skin microbial system. Commensal, coagulase-negative staphylococci (CoNS) were observed to produce bacteriocins which inhibit bacteria such as S. aureus, and these were not seen in the skin of most patients with AD. They hypothesised that reintroduction of CoNS would improve AD in patients.

Patients treated with MSB-0221, which incorporated the naturally occurring skin bacteria S. hominis (ShA9), had fewer AD-related adverse events (AEs) as compared with patients treated with a topical placebo, reported Richard L Gallo, MD, PhD, of the University of California San Diego and co-founder of the company developing MSB-0221.

“Besides its effect on decreasing the redness and itch in a subset of patients, and dramatically and rapidly decreasing the colonisation by Staph aureus, one of the unique aspects of this is that it’s specific for this organism,” said Dr Gallo. “It was not detrimental to other members of the microbiome that could help restore balance.”

Applying MSB-0221 to 54 adults, they found a reduction in S. Areus, which was associated with a significant decrease in AD symptoms compared to placebo.

The next step would be a larger, 150 patient clinical trial over 12 weeks.

“We don’t fully understand all of the ramifications, but there seems to be at least a subset of patients with atopic dermatitis whose disease is influenced and exacerbated by certain bacteria, such as Staph aureus,” said Bruce Brod, MD, of the University of Pennsylvania. “There is still sort of a chicken-and-egg aspect to the relationship. Did the skin inflammation come first or the Staph aureus?“

“This is a proof-of-concept study that provides some evidence that shifting the balance of another bacteria that’s not pathogenic might have some therapeutic benefit in some patients with atopic dermatitis,” he added. “It provides support for larger studies looking at safe bacteria to shift the flora to a more favourable environment. At this point, it’s just another piece of a puzzle that could one day lead to different therapies. It’s probably not the whole picture, but in some patients, it may play a significant role.”

Source: MedPage Today

Journal information: Nakatsuji T, et al “Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase I randomized clinical trial” Nature Med 2021; DOI: 10.1038/s41591-021-01256-2.