Excitement associated with FDA approval of Rinvoq in Crohn’s disease

On 18 May 2023, the FDA announced the approval of Rinvoq (upadacitinib), AbbVie’s Janus kinase inhibitor (JAKi), to treat adults with moderately to severely active Crohn’s disease (CD) who have had an inadequate response or intolerance to one or more tumour necrosis factor (TNF) blockers. The decision was based on data from two randomised induction trials, U-EXCEED (NCT03345836) and U-EXCEL (NCT03345849), and the subsequent maintenance study, U-ENDURE (NCT03345823). This newest indication continues AbbVie’s strategic push within the immunology marketplace to replace the diminishing revenues from its anti-TNF, Humira (adalimumab), following the asset’s loss of exclusivity and subsequent arrival of the adalimumab biosimilar, Amgen’s Amjevita in the US. As noted in the announcement, Rinvoq is the first approved oral product available to treat moderately to severely active CD, a significant point of distinction that will ultimately allow the therapy to be well positioned within the CD landscape.

Rinvoq is expected to have a rapid uptake in the CD market by healthcare providers (HCPs) due to the overall positive sentiment associated with this therapy. Primary research with US key opinion leaders (KOLs), conducted by GlobalData in February and March 2023, highlight this general impression, with one specialist stating Rinvoq is the “most promising agent” and equating it with “Goldilocks’ porridge,” achieving the proper balance of efficacy and safety. Additionally, the distinction of oral administration and the perceived preference by patients over the choices of intravenous (IV) and subcutaneous (subQ) administration with biologics will also supplement Rinvoq’s incorporation into the CD treatment landscape. As with other JAKis, Rinvoq is accompanied by a boxed warning of increased risk of cardiovascular events (CVEs) and serious infections. However, based on general assessment, as expressed by interviewed KOLs, this advisory is not expected to significantly affect the adoption of this therapy in practice.

In line with an ongoing trend by gastroenterologists to be more aggressive when treating CD to slow or prevent the progression of the disease, it is expected the prescribing patterns of Rinvoq by HCPs will follow this shift. It is also anticipated that AbbVie will position Rinvoq to align with this direction of disease management, evidenced by a sub-analysis of the U-EXCEED, U-EXCEL, and U-ENDURE trials presented at the Digestive Disease Week (DDW) 2023 meeting earlier in the month. This oral presentation showed Rinvoq at 30mg to be effective in treating CD patients regardless of prior treatment with biologics, comparable to responses at the lower 15mg dose in biologic-naïve patients. When asked about the findings during the Q&A portion, the presenter stated the overall clinical message from this analysis is that the high dose of Rinvoq is more effective than the low dose in the high-risk patients’ cohort, adding that he would treat aggressively with the high dose in high-risk patients and only consider reducing dosage when confident that the patient’s disease is stable. It should be noted that the lower 15mg maintenance dose is recommended to be first considered per the prescribing information (PI) insert.