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RINVOQ IS A SELECTIVE AND REVERSIBLE JAK INHIBITOR1
The pathology of Crohn's disease is driven by multiple proinflammatory cytokines (including IL-6, IL-7, IL-15, and IFN-γ) that transduce signals via the JAK1 pathway1
JAKs are intracellular enzymes that transmit these proinflammatory cytokine signals1
Inhibiting JAK1 with RINVOQ reduces the signaling of many mediators which drive the signs and symptoms of CD1
In human cellular assays, RINVOQ preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.1
(RINVOQ's JAK inhibition is represented by X)
*In vitro potency in engineered cellular assays. Fold selectivity is indicative of how much more selective RINVOQ is to JAK1 over other JAKs.
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APS: abdominal pain score; JAK: Janus kinase; IL: interleukin; SES-CD: simple endoscopic activity score for Crohn’s disease; SF: stool frequency.
Study designs: the U-EXCEL and U-EXCEED induction studies were both multicenter, double-blind, placebo-controlled clinical studies. In U-EXCEL (N=526 [287 bio-naive, 239 biologic failures]) and U-EXCEED (N=495 biologic failures only), patients were randomized to RINVOQ 45 mg Q or placebo for 12 weeks with a 2:1 treatment allocation ratio and included in the efficacy analysis. In both studies, induction nonresponders were allowed to enter an additional 12-week open-label extended treatment period. All enrolled patients had moderately to severely active CD defined as SF ≥4 and/or APS ≥2, plus an SES-CD ≥6 (≥4 for patients with isolated ileal disease) excluding the narrowing component. U-ENDURE maintenance was a multicenter, double-blind, placebo-controlled clinical study with 502 patients who achieved clinical response (≥30% decrease in average daily SF and/or in APS, neither worse than baseline) to 12 weeks of RINVOQ 45 mg QD induction treatment. These patients were rerandomized 1:1:1 to receive either RINVOQ 15 mg QD, 30 mg QD, or placebo.1
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REFERENCES
- RINVOQ [Summary of Product Characteristics]. AbbVie Deutschland GmbH & Co. KG; April 2023.
- Parmentier JM, Voss J, Graff C, et al. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. 2018;2:23. doi:10.1186/s41927-018-0031-x