The MOA of RINVOQ
DISRUPT
THE SIGNAL WITH JAK INHIBITION
RINVOQ: a JAK Inhibitor Targeting the JAK-STAT Pathway
RINVOQ is an oral small molecule that inhibits the signaling of the
JAK-STAT pathway, utilized by proinflammatory cytokines.1-4
Atopic Dermatitis (AD):
A CHRONIC AND COMPLEX SKIN DISEASE
AD is a heterogeneous, chronic, inflammatory
skin disease driven by complex pathology and
characterized by itch, rash, and eczematous lesions.5-7
Cytokines in AD
Several key cytokines are thought to use signaling networks such as the JAK-STAT pathway.1,3,5,8
Overexpression of these key cytokines can lead to excess inflammation and may contribute to the signs and symptoms of AD.1,3,5,8
AD=atopic dermatitis; JAK=Janus kinase; STAT=signal transducer and activator of transcription.
Proinflammatory Cytokines Involved in AD Pathogenesis5,8,9
The proinflammatory cytokines shown here are thought to play a role in skin barrier
dysfunction, itch, epidermal hyperplasia, and keratinocyte apoptosis.
IL-4
IL-4
IL-13
IL-31
TSLP
IL-22
IFNγ
AD=atopic dermatitis; IFN=interferon; IL=interleukin; TSLP=thymic stromal lymphopoietin.
Proinflammatory Cytokines Involved in AD Pathogenesis1,5,8
Many cytokines signal through pairs of JAKs (JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, JAK2/TYK2).
The proinflammatory cytokines shown here all signal through the JAK-STAT pathway.
The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.
IL-4
IL-4
IL-13
IL-31
TSLP
IL-22
IFNγ
JAK1
JAK3
JAK1
JAK2
TYK2
JAK1
JAK2
JAK1
JAK2
JAK1
TYK2
JAK1
JAK2
IFN=interferon; IL=interleukin; JAK=Janus kinase; STAT=signal transducer and activator of transcription; TSLP=thymic stromal lymphopoietin; TYK=tyrosine kinase.
The Role of the
JAK-STAT Pathway3-5,10-12
Proinflammatory cytokines utilize signaling pathways—such as the JAK-STAT pathway—to communicate with the cell nucleus.
The cytokine binds to a specific receptor on the cell surface.
JAK=Janus kinase; STAT=signal transducer and activator of transcription.
The Role of the
JAK-STAT Pathway3-5,10-12
JAK activation is triggered from inside the cell.
JAK=Janus kinase; STAT=signal transducer and activator of transcription.
The Role of the
JAK-STAT Pathway3-5,10-12
The activated JAKs then mobilize STATs, which transmit the signal into the cell nucleus.
JAK=Janus kinase; STAT=signal transducer and activator of transcription.
The Role of the
JAK-STAT Pathway3-5,10-12
This signaling is responsible for initiating the inflammatory response in AD.
AD=atopic dermatitis; JAK=Janus kinase; STAT=signal transducer and activator of transcription.
How RINVOQ Works
RINVOQ targets JAK, affecting the
JAK-STAT pathway inside the cell, which is linked to the signaling of proinflammatory cytokines.1,3,5
STRATEGICALLY DESIGNED
Demonstrated greater inhibitory potency for JAK1 and JAK2 vs JAK3 and TYK2 via cell-free enzymatic assays.1
The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.
VISUALIZE
INHIBITORY
POTENCY FOR JAK1
JAK=Janus kinase; STAT=signal transducer and activator of transcription; TYK=tyrosine kinase.
How RINVOQ Works
By binding to JAK, RINVOQ is thought to block the phosphorylation and activation of STATs, disrupting the proinflammatory cytokine signaling cascade.1,4
The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.1
JAK=Janus kinase; STAT=signal transducer and activator of transcription.
In clinical trials, RINVOQ has been shown to provide significant skin clearance and itch relief in patients with moderate to severe AD.1
The recommended dosage of RINVOQ is 15 mg once daily. For adults <65 years and pediatric patients 12+ years weighing at least 40 kg (88 lb), initiate treatment with 15 mg orally once daily in pediatric patients (≥12 years, ≥40 kg) and adults <65 years of age. If an adequate response is not achieved, consider increasing the dosage to 30 mg once daily. Discontinue RINVOQ if an adequate response is not achieved with the 30 mg dose. Use the lowest effective dose needed to maintain response. For patients ≥65 years of age, patients receiving strong CYP3A4 inhibitors, and patients with severe renal impairment, the recommended dose of RINVOQ is 15 mg once-daily. Coadministration of RINVOQ with strong CYP3A4 inducers is not recommended.1
