Guidelines for Treating Crohn's Disease with Rinvoq (Upadacitinib)

Indications and Positioning

Upadacitinib is conditionally recommended for induction and maintenance therapy in patients with moderate to severe Crohn's disease, particularly in those who have had an inadequate response or intolerance to anti-TNF therapy 1, 2, 3
It is particularly valuable as it is the first oral agent shown to be effective and safe in both inducing and maintaining remission in Crohn's disease 1, 3

Before initiating treatment, update immunizations 1
Before initiating treatment, screen for active and latent tuberculosis 2
Before initiating treatment, evaluate for viral hepatitis 1
Monitor for laboratory abnormalities, including interrupting treatment if absolute neutrophil count is less than 1000 cells/mm³ 1
Monitor for laboratory abnormalities, including interrupting treatment if absolute lymphocyte count is less than 500 cells/mm³ 1
Key safety concerns include black box warnings for venous thromboembolism (VTE) and major adverse cardiovascular events (MACE) in higher-risk patients 1

Avoid initiation or interrupt treatment if absolute lymphocyte count is less than 500 cells/mm³ 1
Avoid initiation or interrupt treatment if absolute neutrophil count is less than 1000 cells/mm³ 1

The European Crohn's and Colitis Organisation (ECCO) strongly recommends upadacitinib as induction therapy in moderate-to-severe Crohn's disease with high-quality evidence 4, 5
Upadacitinib 45mg daily for 12 weeks was significantly superior to placebo for induction of remission in moderate-to-severe Crohn's disease, with clinical remission rates of 44.4% vs 25.1% (p<0.001) 6, 4
Endoscopic response was also significantly higher with upadacitinib 45mg compared to placebo (40.2% vs 8.4%, p<0.001) 4

Herpes zoster infection was reported in 4.0-7.2% of patients on maintenance therapy 4
Hepatic disorders and neutropenia were more frequent with the 30mg dose 7, 8
Gastrointestinal perforations were rare but reported in clinical trials 7, 8
The European Medicines Agency cautions about use in patients with increased risk of cardiovascular problems, VTE, or cancer 9

The FDA and European Medicines Agency labeling restrict JAK inhibitors, such as upadacitinib, to patients who have failed or are intolerant to TNF antagonists, as stated by the Gastroenterology journal 10

In biologic-exposed Crohn's disease patients, risankizumab and upadacitinib are favored over ustekinumab, adalimumab, and vedolizumab, with no demonstrated superiority between risankizumab and upadacitinib, according to the Gastroenterology journal 10

The FDA and European Medicines Agency advise that JAK inhibitors, such as upadacitinib, should not be used as first-line therapy in biologic-naïve patients, and should only be used if no suitable alternatives exist in patients with increased cardiovascular risk, as stated by the Gastroenterology journal 10