Robert Gilmore; Amrutha Murali; Amirah Etchegaray; Ei Swe; Yoon-Kyo An; Jakob Begun

doi:10.5217/ir.2024.00174

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Original Article Upadacitinib and vedolizumab combination therapy for the management of refractory ulcerative colitis and Crohn’s disease: Robert Gilmore^1,2, Amrutha Murali¹, Amirah Etchegaray¹, Ei Swe^1,2, Yoon-Kyo An^1,2, Jakob Begun^1,2,; DOI: https://doi.org/10.5217/ir.2024.00174
Published online: June 9, 2025

¹Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, Australia

²Mater Research Institute, The University of Queensland, South Brisbane, Australia

Correspondence to Jakob Begun, Department of Gastroenterology, Mater Hospital Brisbane, Raymond Terrace, South Brisbane, QLD 4101, Australia. E-mail: Jakob.begun@mater.uq.edu.au

• Received: October 22, 2024 • Revised: February 18, 2025 • Accepted: March 24, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
NOTES
REFERENCES

Abstract

Background/Aims
Inflammatory bowel disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract, and encompasses both ulcerative colitis (UC) and Crohn’s disease (CD). Refractory disease is common, a combination of advanced drug therapies may be required to obtain maximal efficacy. We describe the use of upadacitinib therapy in combination with vedolizumab therapy for the management of refractory UC and CD.
Methods
In this retrospective observational study, patients who received upadacitinib in combination with vedolizumab were identified at a tertiary IBD center between November 2022 and March 2024. Patients were followed for 6 months with clinical, biochemical, endoscopic and intestinal ultrasound outcomes.
Results
Sixteen patients (7 with UC, 9 with CD) were identified. Median age was 44 years (range, 25–58 years), 11 (69%) were male, and median number of prior biologic exposures was 3 (range, 2–5). Twelve patients (75%) achieved clinical response, clinical remission, biochemical remission, corticosteroid-free clinical remission, and transmural remission by intestinal ultrasound. Eleven patients (69%) achieved endoscopic remission, with 4 (25%) achieving histological remission. Adverse events were seen in 8 patients (50%), but the majority were mild and did not require interruption of therapy.
Conclusions
Upadacitinib in combination with vedolizumab may have a role in refractory UC and CD patients who have previously failed to respond to standard therapy, with a favorable safety profile. Prospective studies are required to determine the safety and efficacy of this combination in larger cohorts before routine use can be recommended.
Keywords: Upadacitinib; Vedolizumab; Combination therapy; Ulcerative colitis; Crohn disease

INTRODUCTION

Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic, relapsing conditions characterised by inflammation of the gastrointestinal tract, leading to significant physical and psychological morbidity and associated significant health care expenditure [1]. Despite advancement in the management of inflammatory bowel disease (IBD), a significant proportion of patients experience refractory disease that does not adequately respond to standard therapies. In such cases, advanced drug therapy (ADT) is typically required to achieve clinical remission and mucosal healing.

Recent advances in the treatment landscape of UC and CD have significantly expanded the repertoire of ADT, providing clinicians with a broader range of therapeutic options. These therapies encompass various mechanisms of action to downregulate pro-inflammatory signaling and reduce immune infiltrates in the gastrointestinal tract. Combination therapy using multiple ADTs may be considered for patients with severe disease that fail to respond to a single ADT to maximize therapeutic efficacy and to achieve sustained remission [2].

One promising class of IBD ADTs with rapid onset of clinical efficacy are the Janus kinase (JAK) inhibitors, which are orally available small molecules that inhibit cytokine signaling pathways dependent on signal transducer and activator of transcription factors [3]. Upadacitinib is a selective JAK1 inhibitor, and has been approved for the treatment of moderate to severe UC and CD. In phase 3 clinical trials for UC, upadacitinib 45 mg daily was significantly more effective than placebo for induction of remission with 26% to 34% of patients demonstrating clinical remission by week 8 [4]. In CD, upadacitinib achieved clinical remission rates of 38% to 49% at week 12. This significant benefit in clinical remission extended to 52 weeks with 48% of patients treated with 30 mg maintenance and 37% of patients on 15 mg maintenance achieving clinical remission [5].

Another ADT with favorable safety data used in IBD is vedolizumab, a fully humanized monoclonal antibody that selectively targets α4β7 integrin, inhibiting leukocyte migration into the inflamed gut mucosa [6]. Vedolizumab has been shown to be effective in both UC and CD, with clinical response rates in the phase 3 registration trials at week 6 of 47% and 31% respectively [7,8]. Due to its gut-selective mechanism of action, vedolizumab is considered one of the safer ADTs and is often preferred in combination regimens.

A number of case series have reported success rates of 60% to 85% with combination ADT, although adverse event rates vary widely [9]. The combination of vedolizumab with another ADT, such as upadacitinib, may offer an optimal balance of rapid efficacy and safety in the management of refractory IBD [10]. Currently, no studies have been published examining this combination.

METHODS

1. Study Design

Patients who initiated combination therapy with upadacitinib and vedolizumab following the failure of standard IBD therapies were identified from a prospectively maintained database at a tertiary IBD center (Table 1). Inclusion criteria required patients to have a lack of initial response or loss of response to at least 2 ADTs and have completed a minimum of 8 weeks of combination therapy, not merely an overlap while switching therapy. At least 24 weeks of complete follow-up data for each patient was required. Ethics approval for this study was approved by Mater Misericordiae Ltd Human Research Ethics Committee (HREC/MML/97196). The requirement for written informed consent was waived by the Ethics Committee.

Patients were considered for this off-label combination therapy after demonstrating an inadequate response to at least 2 ADT, including dose optimization and escalation as necessary for each agent. The decision to initiate combination therapy was made after multidisciplinary discussion, considering the efficacy data from clinical trials, real-world studies, and the safety profile of vedolizumab and upadacitinib. Immunomodulators were discontinued in relevant patients prior to the introduction of the second ADT, although 5-aminosalicylic acid was continued. De-escalation (to either upadacitinib or vedolizumab monotherapy) was initially planned after 16 weeks of combination therapy in all cases, but at the discretion of the treating physician and the multidisciplinary team, this was altered in cases of early response or treatment failure. Pneumocystis jirovecii prophylaxis was discussed with each patient, and recombinant varicella zoster vaccination was recommended.

2. Demographic and Clinical Data

Baseline demographic data, along with clinical, biochemical (fecal calprotectin [FCP] and C-reactive protein [CRP]), endoscopic and intestinal ultrasound (IUS) data, were collected for all patients. Follow-up was conducted for a minimum of 24 weeks from initiation of combination therapy.

3. Outcomes and Definitions

Clinical outcomes were defined using STRIDE II guidelines [11] using a Patient-Reported Outcome 2 (PRO2) score. The PRO2 criteria for UC include rectal bleeding and stool frequency, whereas the same criteria for CD include abdominal pain and stool frequency. The primary outcome was clinical response at week 8, 16, and 24. Outcomes for each patient were reported at all timepoints, regardless of whether they remained on combination therapy, using an intention-to-treat model. Clinical response was defined as a reduction of ≥50% in PRO2 from baseline in both UC and CD patients.

Secondary outcomes included the proportion of patients achieving the following endpoints at weeks 8, 16, and 24: (1) clinical remission, defined in UC as PRO2 score of ≤ 1 with a rectal bleeding subscore of 0, and in CD as PRO2 score of ≤ 2 with no abdominal pain; (2) corticosteroid-free clinical remission (CFCR), defined as clinical remission in patients who discontinued corticosteroid after baseline and at least 2 weeks before the clinical assessment; (3) biochemical remission, defined as normalization of CRP ( ≤ 5 mg/L) and FCP (<150 μg/ g) levels where at least one was abnormal at baseline; (4) endoscopic remission, defined as an Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score of ≤ 1 or Simple Endoscopic Score for Crohn’s Disease (SES-CD) of ≤3; and (5) transmural remission, assessed by IUS, defined as bowel wall thickness (BWT) <3 mm in all segments with a modified Doppler Limberg score of 0.

Safety outcomes included reported adverse events (AE) and serious AE (SAE), defined as AE leading to drug discontinuation or hospitalization at week 8, 16, and 24.

RESULTS

A total of 16 patients were identified and included in the study, as summarized in Table 1. The median age was 44 years (range, 23–58 years), and 12 (75%) were male. The 4 female patients (25%) received counselling on the risks of upadacitinib during pregnancy. All patients completed at least 8 weeks of combination therapy, with a median duration of 16 weeks (range, 8–24 weeks), and 24 weeks of follow-up data from the time of commencement were available for all patients. Upadacitinib was administered at a dose of 45 mg once daily for the first 16 weeks of combination therapy, then reduced to 30 mg once daily for the duration of therapy. Vedolizumab was administered via standard induction of 300 mg intravenous injection at weeks 0, 2, and 6 in the vedolizumabnaïve patients initiating combination therapy and continued at 4 weekly escalated intervals. Vedolizumab was continued as before in those patients who enrolled with prior vedolizumab exposure. As such, 300 mg intravenous 8-weekly was continued in 4 patients (25%), 108 mg subcutaneously 2-weekly continued in 4 patients (25%) and induction therapy with 300 mg intravenously at weeks 0, 2, and 6, followed by 4-weekly was started for 8 patients (50%).

1. Timing of Combination Therapy

Seven patients (44%) had UC, and 9 patients (56%) had CD. Baseline clinical characteristics are summarized in Tables 2 and 3 respectively. Secondary outcomes are summarized in Fig. 1. All patients had been exposed to at least 2 prior ADT (failed 2 =63%, failed 3 =24%, and failed 4 or more =13%). Six patients (38%) were on a weaning course of oral corticosteroid at the time of combination therapy initiation. Eight patients (50%) started upadacitinib and vedolizumab concurrently with a plan to withdraw upadacitinib after 16 weeks once clinical remission was achieved. The remaining 8 patients (50%) had started vedolizumab therapy first, with upadacitinib added after a median of 8 weeks (range, 8–48 weeks) due to partial therapeutic response in an attempt to induce remission.

2. Baseline Disease Severity

At the time of combination therapy initiation, the median PRO2 score was 4 (range, 3–5). For UC patients, the median Mayo endoscopic subscore was 2 (range, 2–3) and the median UCEIS was 5 (range, 3–7). For CD patients, the median SES-CD was 14 (range, 7–21). Baseline median FCP was 1,029 μg/mL and CRP was 11 mg/L. IUS showed a median BWT of 5.2 mm (range, 3.2–6.1 mm) in the most affected segment, with a median modified Limberg score of 2 (range, 1–3).

3. Clinical, Biochemical, Endoscopic and Sonographic Outcomes

At week 8, 11 patients (69%) met the criteria for clinical response, and 8 (50%) achieved both clinical and biochemical remission. The median PRO2 score decreased to 2 (range, 0–3). All patients discontinued corticosteroids, but only 3 (50%) met the criteria for CFCR. Endoscopic assessment within 8 weeks was performed in 5 patients, 2 (40%) achieving endoscopic remission. Transmural remission, as assessed by IUS, was seen in 4 patients (25%), with a median BWT reduction to 3.4 mm (range, 1.5–6.1 mm) and a median modified Limberg score reduction to 1 (range, 0–2). Four patients (25%) experienced AE. One patient (6%) who failed to respond to combination therapy was switched to infliximab in combination with thiopurine after week 8, and 1 patient (6%) who achieved clinical response and remission stepped down to vedolizumab monotherapy.

At week 16, 13 patients (81%) met criteria for clinical response, and 12 (75%) achieved both clinical and biochemical remission. The median PRO2 score further reduced to 1 (range, 0–3). CFCR was seen in 11 patients (69%). Endoscopic assessment within 16 weeks was performed in 11 patients, with 6 (55%) achieving endoscopic remission. Transmural remission was seen in 11 patients (69%), with a median BWT of 1.6 mm (range, 1.1–4.9 mm) and a median modified Limberg score of 0 (range, 0–3). Eight patients (50%) experienced AE during the first 16 weeks of follow-up, with 4 additional AE reported after week 8. One patient (8%) with UC who failed to respond underwent an uncomplicated colectomy. As originally planned, 7 patients (44%) stepped down to vedolizumab monotherapy, and 4 (25%) stepped down to upadacitinib monotherapy.

By week 24, 2 patients (13%) remained on combination therapy due to partial response at week 16, and both subsequently achieved clinical response and remission. Overall, 12 patients (75%) met criteria for clinical response, remission, biochemical remission, and CFCR by week 24. The median PRO2 score was 0 (range, 0–3). Endoscopic assessment within 24 weeks was performed in a total of 13 patients, with 9 (69%) of these achieving endoscopic remission. Of these 13 patients, 4 (31%) achieved endoscopic and histological remission consistent with disease clearance [12]. Transmural remission was observed in 11 patients (69%), with a median BWT of 1.5 mm (range, 1.1–4.3 mm) and a median modified Limberg score of 0 (range, 0–1). There was complete concordance between the 9 patients achieving endoscopic and transmural remission, having also attained biochemical and clinical remission. A total of 8 patients (50%) experienced AE during the first 24 weeks of follow-up, all occurring within the first 16 weeks, with no additional AE reported between week 16 and 24. Two patients (13%), who had achieved clinical remission and stepped down to monotherapy after week 16, required reinitiation of combination therapy after week 24 due to disease recurrence.

4. Safety and Adverse Events

Overall, 9 patients (56%) successfully stepped down to monotherapy and remained in clinical remission. AE were reported in 8 patients (50%), and included acne (n =5), herpes zoster infection (n=3) and headache (n=2). Eight patients (50%) were vaccinated with the recombinant herpes zoster vaccine at initiation of combination, and none of these patients experienced a case of herpes zoster. SAE’s included colectomy for refractory disease (n=1), and medical admission for infective colitis (n=1). No AE of special interest, including severe infection, major adverse cardiovascular events, venous thromboembolism, or malignancy were reported during the 24-week follow-up (Table 4).

DISCUSSION

This study is the first to explore the combination of upadacitinib, a selective JAK1 inhibitor, with vedolizumab, a gut-selective α4β7 integrin inhibitor, in patients with refractory UC and CD [13]. The combination of these ADT holds promise in managing difficult-to-treat cases where monotherapy or conventional treatment has failed as they target 2 distinct pathways driving inflammation in IBD. Our study investigated combination upadacitinib and vedolizumab treatment in a group of refractory patients who had failed 1 or more ADTs previously. In this cohort, 75% of patients achieved a clinical response, with significant proportions reaching clinical, biochemical, and CFCR, along with transmural remission as assessed by IUS. Endoscopic remission was achieved in 69% of patients by week 24, supporting the efficacy of this combination therapy in a refractory IBD population.

The rationale for combining upadacitinib with vedolizumab lies In the complementary mechanisms of action of these agents. Upadacitinib has a rapid onset of action due to its action on downstream cytokine signaling, leading to relatively rapid resolution of symptoms such as stool frequency and rectal bleeding. Vedolizumab, with a gut-selective mechanism of action, may take longer to achieve its maximal efficacy, but is associated with an excellent safety profile especially in terms of a lack of systemic immunosuppression. This combination quickly disrupts downstream cytokine signaling through JAK inhibition and upstream migration of pro-inflammatory immune cells into the gastrointestinal mucosa and lamina propria by blocking integrin mediated immune homing. This combination may therefore provide a strategy to rapidly induce a sustained clinical improvement, minimizing the need for prolonged corticosteroid use. After remission was achieved, ADT therapy was consolidated to a single agent in the majority of patients, although 12% flared after combination therapy was discontinued necessitating reintroduction.

However, combination therapy was associated with a relatively high rate of AE, with 50% of the cohort experiencing at least one AE during the 24-week follow-up period. The rates of acne (31%), varicella zoster (19%), and headache (12%) are comparable with the known safety profile from previous real-world data for upadacitinib monotherapy [14]. Only 2 patients required hospital admission, with one requiring an uncomplicated semi-elective colectomy for refractory disease, and another requiring an overnight admission for campylobacter enteritis treated with oral antibiotics. While AE were frequent, they were generally mild or moderate in severity, and no AE of special interest, such as major adverse cardiovascular events, malignancy or thromboembolism were reported.

The high rate of clinical response and remission in our study suggests that combination ADT may be an effective strategy for patients with aggressive disease or those who have experienced partial response to initial therapy. This approach has the potential to minimize steroid exposure, induce and sustain remission, and avoid the need for surgery. Additionally, early use of upadacitinib as a bridge to long- term therapy with vedolizumab is another viable strategy, given the rapid onset of action of upadacitinib. Such an approach has been reported previously with tofacitinib in combination with cyclosporin or vedolizumab [15,16].

While these results are promising, they should be interpreted with caution due to the small sample size and lack of a control group. An additional limitation in this study is the significant heterogeneity in dosage and delivery of vedolizumab employed. While dosing was standardized for patients initiating vedolizumab, given the retrospective nature of the study patients already receiving vedolizumab continued their prior dosage at the treating physicians’ discretion. Prospective, randomized controlled studies are needed to fully assess the safety and efficacy of this combination. One study is currently underway, aiming to evaluate the potential of upadacitinib and vedolizumab induction as a combination therapy for IBD in ADT naïve and exposed patients, followed by vedolizumab maintenance with results expected in 2026 (NCT06227910). These studies will provide more robust evidence to guide clinical practice and determine whether this combination should be added to the therapeutic armamentarium for refractory UC and CD.

Our preliminary data suggest that upadacitinib in combination with vedolizumab may be a viable treatment option for a select group of patients with refractory IBD, particularly those managed within specialized IBD referral centers. The combination appears to be effective in inducing clinical, biochemical, endoscopic, transmural and histological remission with a manageable safety profile. However, given the relatively high rate of AE, further prospective studies are required to confirm the safety and long-term efficacy of this combination therapy. Until then, this combination should considered be cautiously and used in highly selected patients where other therapeutic options have failed.

NOTES

Funding Source

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

An YK and Begun J have served as speakers, consultants, and advisory board members for AbbVie and Takeda. Except for that, no potential conflict of interest relevant to this article was reported.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Author Contributions

Conceptualization: Gilmore R, An YK, Begun J. Data curation: Murali A, Etchegaray A, Swe E. Formal analysis:Gilmore R, Etchegaray A, Swe E. Methodology: Gilmore R. Project administration: Gilmore R, Begun J. Supervision: An YK, Begun J. Writing - original draft: Gilmore R, Murali A, Etchegaray A, Swe E. Writing - review & editing: all authors. Approval of final manuscript: all authors.

Fig. 1.

Fecal calprotectin, bowel wall thickness by intestinal ultrasound, PRO-2 score, and CRP at baseline and after 16 weeks of combination therapy. PRO-2, Patient-Reported Outcome 2; CRP, C-reactive protein.

Table 1.

Baseline Cohort Demographics (n=16)

Demographics	No. (%)
Female sex	4 (25)
Age at time of combination (yr), median (IQR)	44 (23-58)
Disease duration (yr), median (IQR)	6 (4–13)
UC	7 (44)
UC Montreal classification–disease extent
E1–proctitis	1 (14)
E2–left-sided UC	3 (43)
E3–extensive UC	3 (43)
CD	9 (56)
CD Montreal classification–location
L1–ileal	2 (22)
L2–colonic	3 (33)
L3–ileocolonic	4 (45)
L4–isolated upper gastrointestinal	0
CD Montreal classification–behavior
B1–uncomplicated	3 (33)
B2–stricturing	3 (33)
B3–penetrating	2 (22)
Perianal fistulizing	1 (12)
History of extraintestinal manifestations	6 (38)
Current smoker	2 (13)
No. of prior advanced drug therapies
1	0
2	8 (50)
3	6 (38)
≥4	2 (12)
Prior advanced drug therapy
Infliximab	13 (81)
Ustekinumab	9 (56)
Adalimumab	5 (31)
Tofacitinib	1 (6)
Baseline concomitant medications
Oral corticosteroid	4 (25)

IQR, interquartile range; UC, ulcerative colitis; CD, Crohn’s disease.

Table 2.

Clinical, Biochemical, and Endoscopic Characteristics at Baseline in the Ulcerative Colitis Patients

Case No.	Age (yr)	Sex	Duration of disease (yr)	Extent of disease	Prior therapy	Vedolizumab dosage	FCP (μg/mL)	CRP (mg/L)	IUS BWT (mm)	mLS	MES	UCEIS	Partial Mayo Score
1	53	M	25	E2	Infliximab, etrasimod, vedolizumab	300 mg IV Q8w	936	47	5.2	2	2	4	9
2	44	F	5	E3	Infliximab, tofacitinib, vedolizumab	300 mg IV Q8w	6,000	19	6.0	2	3	6	7
3	53	M	30	E2	Infliximab, tofacitinib	300 mg IV Q4w	3,338	39	3.6	2	2	5	7
4	26	F	4	E1	Infliximab, guselkumab, vedolizumab	108 mg SC Q2w	2,989	122	5.2	2	2	4	8
5	44	M	5	E3	Infliximab, ustekinumab, vedolizumab	300 mg IV Q8w	1,355	5	6.1	3	3	6	7
6	41	F	11	E3	Infliximab, tofacitinib, etrasimod, vedolizumab	108 mg SC Q2w	564	19	4.2	1	3	7	7
7	49	M	15	E2	Infliximab, adalimumab	300 mg IV Q4w	1,219	6	5.1	2	2	5	7

FCP, fecal calprotectin; CRP, C-reactive protein; IUS, intestinal ultrasound; BWT, bowel wall thickness of most affected segment; mLS, modified Limberg score; MES, Mayo endoscopic score; UCEIS, Ulcerative Colitis Endoscopic Index of Severity; M, male; F, female; E1, proctitis; E2, left-sided UC; E3, extensive UC; IV, intravenous; SC, subcutaneous; Q2w, every 2 weeks; Q4w, every 4 weeks; Q8w, every 8 weeks.

Table 3.

Clinical, Biochemical, and Endoscopic Characteristics at Baseline in the Crohn’s Disease Patients

Case No.	Age (yr)	Sex	Duration of disease (yr)	Location of disease	Disease behavior	Prior therapy	Vedolizumab dosage	FCP (μg/mL)	CRP (mg/L)	IUS BWT (mm)	mLS	SES-CD	Prior surgery
8	58	M	27	L2	B1	Infliximab, adalimumab, ustekinumab	300 mg IV Q4w	> 2,300	19	5.3	2	12	No
9	28	M	9	L2	B1	Infliximab, ustekinumab, vedolizumab	108 mg SC Q2w	> 2,300	12	3.2	1	8	No
10	26	M	5	L1	B2	Infliximab, Adalimumab	300 mg IV Q4w	998	19	4.9	2	5	Yes
11	25	M	10	L2	B1	Infliximab, adalimumab, vedolizumab	300 mg IV Q8w	786	7	5.2	1	7	Yes
12	51	M	29	L3	B1p	Adalimumab, infliximab, gesulkumab, ustekinumab	300 mg IV Q4w	965	31	4.4	2	21	No
13	53	M	39	L3	B2p	Infliximab, adalimumab, ustekinumab	300 mg IV Q4w	3,218	21	5.3	2	19	Yes
14	23	M	6	L3	B1	Infliximab, adalimumab, ustekinumab, vedolizumab	108 mg SC Q2w	879	18	4.9	2	15	No
15	34	F	5	L3	B2	Ustekinumab, infliximab	300 mg IV Q4w	299	49	4.7	2	18	No
16	44	M	19	L1	B3	Ustekinumab, infliximab, adalimumab, guselkumab	300 mg IV Q4w	1,021	71	3.8	2	14	No

FCP, fecal calprotectin; CRP, C-reactive protein; IUS, intestinal ultrasound; BWT, bowel wall thickness of most affected segment; mLS, modified Limber Score; SES-CD, Simple Endoscopic Score for Crohn’s Disease; M, male; F, female; B1, uncomplicated; B2, stricturing; p, perianal disease; IV, intravenous; SC, subcutaneous; Q2w, every 2 weeks; Q4w, every 4 weeks; Q8w, every 8 weeks.

Table 4.

Adverse Events (n=16)

Adverse event	No. (%)
Overall adverse events	8 (50)
Acne	5 (31)
Herpes zoster infection	3 (19)
Headache	2 (13)
Serious adverse events	2 (13)
Severe infection	1 (6)
Colectomy	1 (6)
Patients with multiple adverse events	4 (25)
Major adverse cardiac event	0
Malignancy	0
Venous thromboembolism	0

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Upadacitinib and vedolizumab combination therapy for the management of refractory ulcerative colitis and Crohn’s disease

DOI: https://doi.org/10.5217/ir.2024.00174

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Figure

Upadacitinib and vedolizumab combination therapy for the management of refractory ulcerative colitis and Crohn’s disease

Fig. 1. Fecal calprotectin, bowel wall thickness by intestinal ultrasound, PRO-2 score, and CRP at baseline and after 16 weeks of combination therapy. PRO-2, Patient-Reported Outcome 2; CRP, C-reactive protein.

Fig. 1.

Upadacitinib and vedolizumab combination therapy for the management of refractory ulcerative colitis and Crohn’s disease

Demographics	No. (%)
Female sex	4 (25)
Age at time of combination (yr), median (IQR)	44 (23-58)
Disease duration (yr), median (IQR)	6 (4–13)
UC	7 (44)
UC Montreal classification–disease extent
E1–proctitis	1 (14)
E2–left-sided UC	3 (43)
E3–extensive UC	3 (43)
CD	9 (56)
CD Montreal classification–location
L1–ileal	2 (22)
L2–colonic	3 (33)
L3–ileocolonic	4 (45)
L4–isolated upper gastrointestinal	0
CD Montreal classification–behavior
B1–uncomplicated	3 (33)
B2–stricturing	3 (33)
B3–penetrating	2 (22)
Perianal fistulizing	1 (12)
History of extraintestinal manifestations	6 (38)
Current smoker	2 (13)
No. of prior advanced drug therapies
1	0
2	8 (50)
3	6 (38)
≥4	2 (12)
Prior advanced drug therapy
Infliximab	13 (81)
Ustekinumab	9 (56)
Adalimumab	5 (31)
Tofacitinib	1 (6)
Baseline concomitant medications
Oral corticosteroid	4 (25)

Case No.	Age (yr)	Sex	Duration of disease (yr)	Extent of disease	Prior therapy	Vedolizumab dosage	FCP (μg/mL)	CRP (mg/L)	IUS BWT (mm)	mLS	MES	UCEIS	Partial Mayo Score
1	53	M	25	E2	Infliximab, etrasimod, vedolizumab	300 mg IV Q8w	936	47	5.2	2	2	4	9
2	44	F	5	E3	Infliximab, tofacitinib, vedolizumab	300 mg IV Q8w	6,000	19	6.0	2	3	6	7
3	53	M	30	E2	Infliximab, tofacitinib	300 mg IV Q4w	3,338	39	3.6	2	2	5	7
4	26	F	4	E1	Infliximab, guselkumab, vedolizumab	108 mg SC Q2w	2,989	122	5.2	2	2	4	8
5	44	M	5	E3	Infliximab, ustekinumab, vedolizumab	300 mg IV Q8w	1,355	5	6.1	3	3	6	7
6	41	F	11	E3	Infliximab, tofacitinib, etrasimod, vedolizumab	108 mg SC Q2w	564	19	4.2	1	3	7	7
7	49	M	15	E2	Infliximab, adalimumab	300 mg IV Q4w	1,219	6	5.1	2	2	5	7

Case No.	Age (yr)	Sex	Duration of disease (yr)	Location of disease	Disease behavior	Prior therapy	Vedolizumab dosage	FCP (μg/mL)	CRP (mg/L)	IUS BWT (mm)	mLS	SES-CD	Prior surgery
8	58	M	27	L2	B1	Infliximab, adalimumab, ustekinumab	300 mg IV Q4w	> 2,300	19	5.3	2	12	No
9	28	M	9	L2	B1	Infliximab, ustekinumab, vedolizumab	108 mg SC Q2w	> 2,300	12	3.2	1	8	No
10	26	M	5	L1	B2	Infliximab, Adalimumab	300 mg IV Q4w	998	19	4.9	2	5	Yes
11	25	M	10	L2	B1	Infliximab, adalimumab, vedolizumab	300 mg IV Q8w	786	7	5.2	1	7	Yes
12	51	M	29	L3	B1p	Adalimumab, infliximab, gesulkumab, ustekinumab	300 mg IV Q4w	965	31	4.4	2	21	No
13	53	M	39	L3	B2p	Infliximab, adalimumab, ustekinumab	300 mg IV Q4w	3,218	21	5.3	2	19	Yes
14	23	M	6	L3	B1	Infliximab, adalimumab, ustekinumab, vedolizumab	108 mg SC Q2w	879	18	4.9	2	15	No
15	34	F	5	L3	B2	Ustekinumab, infliximab	300 mg IV Q4w	299	49	4.7	2	18	No
16	44	M	19	L1	B3	Ustekinumab, infliximab, adalimumab, guselkumab	300 mg IV Q4w	1,021	71	3.8	2	14	No

Adverse event	No. (%)
Overall adverse events	8 (50)
Acne	5 (31)
Herpes zoster infection	3 (19)
Headache	2 (13)
Serious adverse events	2 (13)
Severe infection	1 (6)
Colectomy	1 (6)
Patients with multiple adverse events	4 (25)
Major adverse cardiac event	0
Malignancy	0
Venous thromboembolism	0

Table 1. Baseline Cohort Demographics (n=16)

IQR, interquartile range; UC, ulcerative colitis; CD, Crohn’s disease.

Table 2. Clinical, Biochemical, and Endoscopic Characteristics at Baseline in the Ulcerative Colitis Patients

Table 3. Clinical, Biochemical, and Endoscopic Characteristics at Baseline in the Crohn’s Disease Patients