Short-Term Use of Upadacitinib in Combination With Biologic Therapy for Inducing Clinical Remission in Patients With Active Inflammatory Bowel Disease

Key Messages.

What is already known?

Upadacitinib is a small molecule Janus kinase inhibitor with the potential of rapid onset of action and therefore could have a role for short-term use.

What is new here?

In this case series, for the first time, we describe the outcomes of upadacitinib therapy intended for short-term (≤16 weeks) use in combination with biologic therapy to induce clinical remission in patients with active inflammatory bowel disease in the outpatient setting.

How can this study help patient care?

Shot-term use of upadacitinib may reduce the need for corticosteroids and offer a window for optimization of biologic therapy while avoiding a potentially premature therapy change in patients with active disease.

Upadacitinib is a small molecule Janus kinase inhibitor with a rapid onset of action.^1-3 It may therefore have a role for short-term use, either to avoid the need for corticosteroids or to bridge to effectiveness of a slower-to-onset therapy.

We retrospectively reviewed patients with inflammatory bowel disease (IBD) who were prescribed upadacitinib concurrently with a biologic therapy between September 2022 and September 2023. Patients with a documented plan for upadacitinib therapy for ≤16 weeks, regardless of the actual duration subsequently, were included. Patients who received upadacitinib intended as the next line of monotherapy were excluded. Reasons for initiating a short course of upadacitinib included minimizing steroid exposure during the induction phase of a new biologic therapy and bridging to effectiveness of dose optimization of a current biologic therapy, attempting to avoid a potentially premature therapy switch.

We identified 12 patients, 8 with ulcerative colitis (UC) and 4 with Crohn’s disease (CD). Clinical characteristics and outcomes are summarized in Table 1. Three (25%) patients were taking oral corticosteroids before initiation of upadacitinib. Median follow-up was 26 weeks (interquartile range [IQR], 21-34.5). Paired values were compared by Wilcoxon signed-rank test.

Table 1.

Patient characteristics and clinical outcomes.

UC
Age	Sex	Disease Extent	Disease Duration (Year)	Number of Advanced Therapies Prior to Initiation of Upadacitnib	Active Biologic Therapy at Initiation of Upadacitnib	Upadacitinib as Add-On Therapy Or Bridge Therapy	Chronic Use of Corticosteroids at Initiation of Upadacitinib	Partial Mayo Score		Fecal Calprotectin (FCP, μg/g)		C-Reactive Protein (CRP, mg/L)		Endoscopy Findings After Initiation of Upadacitinib	Adverse Events	Extended Use Beyond 16 Weeks	Reason For Extended Use	Follow- Up Time (Week)	Duration Of Upadacitinib (Week)	Active Therapy at the Last Follow-Up Visit
								pre*	post#	pre*	post#	pre*	post#
32	Male	Extensive	7	5	Vedolizumab	Add-on	—	6	2	—	939	34.3	11.5	—	—	Yes	Failure to achieve biochemical remission requiring further evaluation and adjustment of thearpy plan	24	>24†	Vedolizumab and Upadacitinib (45 mg daily)
44	Female	Extensive	7	3	Vedolizumab	Add-on	—	9	0	3519	523		0.4	—	—	Yes	Flare after discontinuation of upadacitinib	35	>22†	Upadacitinib (30 mg daily)
38	Female	Extensive	22	5	Ustekinumab	Add-on	—	5	0	7307	36	17.8	3.7	—	—	Yes	Patient’s preference	32	>32†	Ustekinumab and Upadacitinib (30 mg daily)
29	Male	Extensive	4	4	Vedolizumab	Add-on	Prednisone	8	0	5600	2760	13.1	—	Mayo 2	—	Yes	Failure to achieve biochemical remission requiring further evaluation and adjustment of thearpy plan	24	>24†	Upadacitinib (45 mg daily)
31	Male	Extensive	2	1	Vedolizumab	Bridge (to Infliximab)	—	3	0	—	1165	2.4	2.8	—	—	No	N/A	27	7	Infliximab
31	Male	Extensive	6	2	Adalimumab	Add-on	—	9	0	995	398	6	4.2	—	—	Yes	Flare after discontinuation of upadacitinib	61	>59†	Upadacitinib (30 mg daily)
35	Male	Left-sided	10	3	Ustekinumab	Add-on	—	3	0	43	—	11.7	—	Mayo 0	—	No	N/A	20	6	Ustekinumab
36	Female	Left-sided	15	3	Infliximab	Bridge (to Ustekinumab)	—	5	0	1109	54.9	0.4	0.4	Mayo 1	Influenza	No	N/A	57	8	Ustekinumab

CD
Age	Sex	Disease extent	Disease Duration (Year)	Number of Advanced Therapies Prior to Initiation of Upadacitnib	Active Biologic Therapy at Initiation of Upadacitnib	Upadacitinib as Add-On Therapy Or Bridge Therapy	Chronic Use of Corticosteroids at Initiation of Upadacitinib	Harvey- Bradshaw Index (HBI)		Fecal calprotectin (FCP, μg/g)		C-reactive protein (CRP, mg/L)		Endoscopy Findings After Initiation of Upadacitinib	Adverse Events	Extended Use Beyond 16 Weeks	Reason For Extended Use	Follow- Up Time (Week)	Duration Of Upadacitinib (Week)	Active Therapy at the Last Follow-Up Visit
								pre*	post#	pre*	post#	pre*	post#
20	Female	Ileocolonic and perianal	10	3	Ustekinumab	Add-on	Prednisone	6	2	2720	—	4.5	—	SES-CD 0	Acne	No	N/A	14	12	Ustekinumab
22	Male	Ileocolonic	6	5	Risankizumab	Add-on	—	2	2	547	311	13	2	SES-CD 0	—	No	N/A	33	16	Risankizumab
19	Male	Ileocolonic and perianal	4	1	Ustekinumab	Add-on	Budesonide	4	4	993	60	19	0.4	—	—	Yes	Flare after discontinuation of upadacitinib	25	>20†	Ustekinumab and Upadacitinib (30 mg daily)
45	Female	Ileocolonic	21	4	Risankizumab	Add-on	—	17	12	200	—	2.2	—	—	Acne	Yes	Patient’s preference	17	>17†	Risankizumab and Upadacitinib (30 mg daily)

Abbreviations: IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease; SES-CD, Simple Endoscopic Score for Crohn’s Disease.

^*Highest value between 24 weeks before and 1 week after initiation of upadacitinib;

^#Lowest value between 4 to 28 weeks after initiation of upadacitinib;

^†Ongoing use of upadacitinib at the last follow-up visit.

We observed a reduction in median partial Mayo (pMayo) score from 5.5 to 0 in UC patients (P = .008) and Harvey-Bradshaw index (HBI) from 5 to 3 in CD patients (P = .5). Nine of 11 (81.8%) patients who were not in steroid-free clinical remission (SFCR, defined as pMayo <2 or HBI <5 without receiving corticosteroids) achieved SFCR after initiation of upadacitinib. Paired fecal calprotectin and C-reactive protein decreased after upadacitinib therapy from medians of 1109 to 311 μg/g (P = .02) and 13 to 2.8 mg/L (P = .06), respectively.

Upadacitinib was discontinued within 16 weeks as originally planned in 8 patients. Of these, 5 continued a single biologic, whereas 3 experienced disease flare for which upadacitinib was resumed. In addition, 2 patients declined to discontinue upadacitinib due to concern for potential flare, and 2 patients were advised to extend upadacitinib, a change from the original plan, in view of their lack of biochemical remission, for which endoscopic evaluation was planned. Taken together, 7 patients (58.3%) required extended use of upadacitinib for over 16 weeks, all of which had ongoing use at the last follow-up. Minor adverse events were observed in 2 patients with acne and 1 with influenza infection.

In this novel case series, upadacitinib intended for short-term use in combination with biologic therapy appeared to be well-tolerated and effective in inducing SFCR in patients with active IBD. However, a substantial proportion of patients were not able to de-escalate their therapy in the short term as planned. Nevertheless, at least for some patients, the intended short-term use may reduce the need for corticosteroids and offer a window for optimization of biologic therapy while avoiding a potentially premature therapy change. Moreover, it allows the flexibility to extend upadacitinib as monotherapy or part of combination therapy with the benefit of already having assessed a patient’s clinical response to upadacitinib. Prospective studies are warranted to better define the role of upadacitinib as a short-term therapy.

Glossary

Abbreviations:

CD

Crohn’s disease

HBI

Harvey-Bradshaw index

IBD

inflammatory bowel disease

IQR

interquartile range

SFCR

steroid-free clinical remission

UC

ulcerative colitis

Author Contribution

J.Y.: data acquisition, manuscript drafting, manuscript revision

Y.E.N., N.C., M.J.T., and N.N.: data acquisition, manuscript revision

M.B. and E.B.: manuscript revision

D.I.F.: study concept, manuscript drafting, manuscript revision

Funding

None.

Conflicts of Interest

D.I.F. has served on advisory boards for Janssen, Fresenius Kabi, and Pfizer.

Other authors declare that there are no conflicts of interest in this study.