For the treatment of moderate to severe hidradenitis suppurativa (HS) in patients 12 years of age and older
TARGETING TNF-α IN HS
Overexpression of cytokines, including TNF-α, plays a key role in fueling inflammation2,3
Moderate to severe HS is a chronic immune-mediated skin disease that can be progressive and debilitating.2,4-7
- Hair follicles become plugged with keratin, then rupture, leaking contents into connective tissue.3,8
- An inflammatory response follows, fueled by TNF-α and other proinflammatory cytokines, and an inflammatory nodule or abscess forms.2,3
- The wound heals, but the process becomes chronic, which may lead to sinus tracts and hypertrophic scars.8
The relationship between these pharmacodynamic activities and the mechanism(s) by which HUMIRA exerts its clinical effects is unknown.1
MECHANISM OF ACTION IN HS
Explore how HUMIRA works to help target and block TNF-α in HS and disrupt the chronic cycle of inflammation.
HS is a chronic, inflammatory skin condition characterized by recurrent nodules, abscesses, and fistulas in the apocrine gland-bearing regions of the body. HS severity may be determined by the Hurley Staging System, a widely used classification. Current research suggests TNF-α is involved in the pathogenesis of HS. TNF-α is elevated in HS lesions and plays an important role in both the preclinical and chronic inflammatory stages of the disease.
HS begins in the hair follicles, and is thought to result from a combination of environmental and genetic factors. In response to bacteria or injury, T cells and mast cells produce cytokines, including TNF-α and IL-1beta that stimulate epidermal psoriasiform hyperplasia and keratosis in the follicular infundibulum as part of an inflammatory response.
These factors contribute to follicular plugging and accumulation of bacteria. The plugged follicle eventually ruptures, spreading keratin fibers and epithelial strands into the dermis. Follicular rupture fuels activation of keratinocytes and macrophages, which produce TNF-α and additional pro-inflammatory and anti-inflammatory cytokines. The resulting inflammation promotes abscessing inflammation, neutrophilic infiltration, and follicular plugging in the surrounding skin. Inflammatory cytokines incite proliferation of epithelial strands leading to epithelialized fistulas.
These fistulas provide a direct route for bacteria to invade deep in the dermis, aggravating inflammation. Subsequently, keratin fibers present in the dermis are phagocytosed by macrophages, forming multinucleated giant cells. Inflammation develops, leading to spread of follicular plugging to surrounding non-lesional skin, rupture, and further spread of inflammation. Disease progression is marked by subsequent healing, which produces scarring, sinus tracts, and contractures. TNF-α and other cytokines perpetuate the cycle of chronic inflammation.
HUMIRA (adalimumab) specifically targets TNF-α, a key driver of systemic inflammation in HS. HUMIRA was found to be effective for the treatment of adults with moderate to severe HS. The relationship between these pharmacodynamic activities and the mechanism(s) by which HUMIRA exerts its clinical effects is unknown. In clinical trials, many patients with Hurley stage II and III disease achieved at least a 50% reduction in total abscess and inflammatory nodule count with no increase in abscesses and draining fistulas at week 12 relative to baseline.
HUMIRA is indicated for the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older.
Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.
Patients treated with HUMIRA also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.
Please see additional Important Safety Information, including BOXED WARNING on Serious Infections and Malignancy, on the page below.
Please see full Prescribing Information by clicking the link at the top of this page.
MOA=mechanism of action; TNF-α=tumor necrosis factor alpha