What is Hidradenitis Suppurativa?
Hidradenitis suppurativa (HS) is a debilitating, painful, chronic autoinflammatory disease affecting the apocrine gland-bearing skin. HS occurs after puberty and typically manifests as painful inflammatory nodules in the armpits, genital area, groin, breasts, and buttocks/anus. Sustained inflammation in the area contributes to the formation of abscesses, fistulas, and sinus tracks (tunnels under the skin) . Disease progression from mild to severe (Hurley stage I to III) can span years. The exact pathology of HS is unknown but involves an autoinflammatory response and microbial dysbiosis resulting in the local recruitment of T-helper-17 cells and neutrophils and the production of proinflammatory cytokines.
How common is HS?
HS is a relatively common disease with an estimated prevalence of 0.5-3% . Patients with HS have significantly impaired quality of life due to both physical and psychological discomfort associated with the disease (e.g., pain, suppuration, social isolation due to embarrassment, and the off-putting smell of lesions and work disability). Depression and anxiety are common comorbidities in patients with HS . HS affects three times as many women as men, and there is a positive family association.
HS has a positive association with smoking and obesity. A meta-analysis that included data from over 90,000 participants found that patients with HS have a 5.6-fold increase of inflammatory bowel disease (IBD) compared with controls, suggesting that some of the underlying pathology between these diseases is similar.
What options are there for pateints with HS?
There is no cure for HS and current treatment options, which are primarily based on the stage of the disease, remain suboptimal. Treatment is further complicated by an estimated average 7-year delay between onset of disease and diagnosis. Treatment guidelines for HS, as outlined by the European Academy of Dermatology and Venerology and the European Dermatology Forum, recommend mild-to-moderate disease be treated with topical (clindamycin) or systemic (e.g., tetracycline, clindamycin, rifampin) antibiotics, other topical agents (e.g., resorcinol), and anti-inflammatory medications. Intralesional corticosteroids are used with flares. Surgical procedures, medications that regulate hormones, and laser treatments are also sometimes used. For more severe cases, systemic corticosteroids and biologics (adalimumab, infliximab, etanercept) have been used with variable efficacy . Adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor, is the only approved treatment for HS in the United States, European Union, Australia, and other regions and is only indicated for patients with moderate-to-severe disease. In the pivotal phase 3 trials, treatment with adalimumab (40 mg weekly by subcutaneous injection), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks (41.8% vs 26.0%; 58.9% vs 27.6%;).
There is no currently approved treatment for mild-to-moderate HS. A topical medication that is effective with a favorable safety profile would fulfill an important unmet medical need.
AT-193 for HS
AT-193 is a topical investigational drug in clinical trials for the treatment of HS. AT-193 contains a potent AhR agonist and is made by Azora Therapeutics. AhR agonists have shown efficacy in a number inflammatory diseases but have not be studied clinically in the treatment of HS.
AT-193 is currently being studied in pateints with mild to moderate HS. The study is entitled "A Randomized, Double-Blind, Placebo-Controlled Phase 1b Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of AT193 in the Treatment of Patients With Hidradenitis Suppurativa".
If you would like to find out more about the study please go to ClinicalTrials.gov.
Resources for HS
The Hidradenitis Suppurativa Foundation is a non-profit organization improving the lives of people affected by HS through advocacy, education and research.
The goals of the Canadian HS Foundation are to:
Communicate the latest HS management techniques
Establish cross-specialty dialogue to improve HS patient outcomes
Collaborate with international HS foundations to optimize research, education and patient care
The goals of the European HS Foundation are to:
Promote science and research in field of the disease hidradenitis suppurativa
Raise funds for the promotion of research projects in the field of the disease hidradenitis suppurativa
Train physicians, patients and laypersons