Introduction

Vedolizumab (VDZ) is a gut-selective anti–lymphocyte trafficking drug used to treat ulcerative colitis and Crohn’s disease (CD), lifelong conditions with unknown aetiology. In the POLONEZ II study, we evaluated the real-world effectiveness, including patient-reported outcomes (PROs), and safety of VDZ therapy in patients with CD treated in the National Drug Programme in Poland. Previously, we reported interim results at week (wk) 14.¹

Aims & Methods

We describe long-term outcomes after 54 wks of VDZ treatment. POLONEZ II was a multicentre, observational, prospective study in patients with moderately to severely active CD eligible for reimbursed treatment with VDZ in 10 centres in Poland between April 2020 and November 2021. The primary endpoints at wk 54 were clinical response (≥70-point reduction in the Crohn's Disease Activity Index [CDAI] and >25% versus wk 14), remission rate (CDAI ≤150) and steroid-free remission (CDAI ≤150 in patients with steroid use at baseline but not at the time of assessment). Secondary endpoints at wk 54 included changes from baseline in PROs: quality of life (QoL; Inflammatory Bowel Disease Questionnaire [IBDQ]) and fatigue (Inflammatory Bowel Disease-Fatigue Self-assessment Scale [IBD-F]). Safety outcomes included adverse events (AEs) coded from Medical Dictionary for Regulatory Activities (v25.0).

Results

A total of 98 patients (55 men; mean [standard deviation] age: 35.1 [12.2] years) with CD were enrolled in the study. At wk 54, 63 (64.3%) patients had continued VDZ treatment. Primary reason for discontinuation was lack or loss of response (n=23/35, 65.7%). The most common disease location was ileocolonic (n=71/98, 72.4%), and 67.3% (n=66/98) of patients had received previous biologic therapy. At wk 54, clinical response was observed in 63.3% (n=62/98), clinical remission in 48% (n=47/98) and steroid-free remission in 36% (n=18/50) of patients (Table 1). The median CDAI score significantly decreased from 336.5 at baseline to 110.0 (P<0.001) at wk 54. Of the responders with corticosteroid dose reduction, 73.3% (n=22/30) of patients had a 100% reduction in dose at wk 54 (corticosteroid-free). At wk 54, median changes from baseline scores on the IBDQ (total and all subscales) were statistically significant (P<0.001) and maintained from wk 14. Significant improvements were maintained from wk 14 in IBD-F fatigue severity and frequency (P<0.05) and fatigue impact on daily activities (P<0.001). Overall, 11 (11.2%) patients experienced 15 non-serious AEs (none VDZ-related) and 6 (6.1%) patients experienced 9 serious AEs (one VDZ-related). One (1.0%) patient experienced rash as a VDZ-related serious AE (1.3 per 100 patient-years).

Table 1. Clinical response and remission at week 54 (full analysis set)

Conclusion

The results elucidate the real-world use of VDZ in patients with moderately to severely active CD treated for 54 wks in the Polish National Drug Programme. VDZ was effective in maintaining clinical remission in approximately half of the patients, with benefits on disease activity and PROs (QoL and fatigue) and was generally well tolerated.

References

A Liebert, M Kłopocka, H Cichoż-Lach, A Michalak, R Talar-Wojnarowska, D Domżał-Magrowska, et al. P421: Real-world effectiveness and safety of vedolizumab induction therapy for Crohn’s disease in Poland – a prospective, observational POLONEZ II study considering patients reported outcomes. Journal of Crohn's and Colitis 2023;17(Supplement_1).

Disclosure

The study and medical writing support were funded by Takeda Pharma Sp. z o.o.

Agata Michalak received lectures fees from Takeda.
Maria Kłopocka received payment for lectures from Janssen, Takeda, Ferring, Alfasigma and Pharmabest and travel/accommodation/meeting expenses from Ferring, Janssen, Takeda, Alfasigma and Pharmabest.
Ariel Liebert received payment for lectures from Janssen, Takeda, Egis, AbbVie and Pharmabest and travel/accommodation/meeting expenses from Janssen, Takeda, Egis and AbbVie.
Renata Talar-Wojnarowska received lecture fees and/or travel grants from AbbVie, Astellas, Ferring, Janssen and Takeda.
Aleksandra Filipiuk received payment for lectures from Janssen and Pfizer and travel/accommodation/meeting expenses from Takeda and Janssen.
Kamila Stawczyk-Eder received travel grants and lecture fees from Janssen, Pfizer and Takeda.
Katarzyna Waszak received payment for travel/accommodation/meeting expenses from Janssen-Cilag, Pfizer, Pro.Med.CS, Samsung Bioepis and Takeda.
Piotr Eder received lecture fees and/or travel grants from Takeda, Ferring, Astellas, Pfizer and Janssen.
Edyta Zagórowicz received lecture fees from Janssen, Sandoz, Ferring and Pfizer; consultancy fees from Pfizer, Janssen and Takeda and other compensations from Takeda and Janssen.
Krzysztof Skrobot received lecture fees and/or travel grants from Promed and Biocodex.
Szymon Drygała is a permanent employee of Takeda Pharma Sp. z o.o.
Krzysztof Wojciechowski is a former employee of Takeda Pharma Sp. z o.o. and currently an invited external lecturer for Takeda. He is now an employee of Independent Public Health Care Center in Tarczyn, Warszawska 42, Tarczyn, Poland.
Danuta Domżał-Magrowska, Łukasz Konecki, Michał Krogulecki, Maria Kopertowska-Majchrzak and Izabela Smoła declare no conflicts of interest.

Introduction

Vedolizumab (VDZ) is approved for moderate-to-severe inflammatory bowel disease (IBD; ulcerative colitis [UC] & Crohn’s disease [CD]).^1,2 While the subcutaneous (SC) formulation of VDZ is effective as maintenance treatment (mTx) in patients (pts) responding to intravenous (IV) VDZ induction treatment (Tx),^1,3 real-world data on Tx patterns of pts switching mTx from VDZ IV to SC or initiating mTx VDZ SC after IV induction are limited.

Aims & Methods

This prospective, non-interventional, multicentre (NCT05384080) study (conducted under the umbrella VARIETY protocol) enrolled adults with UC or CD initiating/undergoing induction with VDZ IV or continuing VDZ IV mTx, with the option to switch to VDZ SC mTx. The primary endpoint was real-world Tx patterns with VDZ, including Tx persistence. Additional endpoints assessed pt characteristics, pt-reported outcomes, and safety (adverse events [AEs]). Data were descriptively analysed.

Results

Overall, 162 enrolled pts (August 2022–June 2023; UC, n=103; CD, n=59) were included in the interim analysis. At enrolment, 127 (78.4%) received VDZ mTx (UC, n=78; CD, n=49) and 35 (21.6%), VDZ induction (UC, n=25; CD, n=10). The mean (SD) age was 38.2 (12.3) yrs, and time since IBD diagnosis was 10.7 (11.1) yrs. Majority of pts were male (96 [59.3%]), currently employed (124 [76.5%]), had never smoked (109 [67.3%]), and reported previous biologic therapy (95 [58.6%]). Demographic and IBD Tx history data were consistent across cohorts. At baseline, in pts with UC, the mean (SD) partial Mayo score was 1.8 (2.7); in pts with CD, the mean (SD) Crohn’s Disease Activity Index (CDAI) score was 90.6 (70.1). During the 1-yr study period, 20.0% (n=7; UC, n=2; CD, n=5) of pts in the induction and 51.2% (n=65; UC, n=40; CD, n=25) in the mTx cohort switched to VDZ SC. At week (W) 52, Tx persistence was 40.0% (n=14; UC, n=11; CD, n=3) and 77.2% (n=98; UC, n=61; CD, n=37) in the induction and mTx cohorts, respectively, and highest overall in mTx pts who switched to VDZ SC (86.2%; n=56; Table). The most common reason for Tx discontinuation was investigator decision (64.7%; n=33). For VDZ IV and SC, the mean (SD) number of doses per pt was 10.5 (7.6) and 23.8 (15.0), respectively. The median time from VDZ Tx initiation to SC Tx was 383 days (induction: 98 days; mTx: 434 days). In the induction cohort, the mean (SD) Work Productivity & Activity Impairment (WPAI) scores improved from 32.7 (24.1) at baseline (n=21) to 21.5 (31.2) at W52 (n=11), and the Short IBD Questionnaire (SIBDQ) scores improved from 44.1 (10.0) at baseline (n=34) to 51.0 (12.9) at W52 (n=15). In the mTx cohort, WPAI and SIBDQ results remained consistent over time. Fifty-three AEs were reported, including 4 serious AEs (malignancy, IBD flare requiring hospitalization, abdominal abscess, and unconsciousness). One AE of special interest (hypersensitivity reaction) was considered VDZ-related.

Conclusion

In this Polish real-world study, high Tx persistence was reported, especially in pts who switched to VDZ SC. No new safety signals were noted. Overall, the results were consistent with those from other VARIETY cohorts,⁴ although lower persistence was observed during induction. The small size of the induction cohort was a limitation of this study.

References

1. Sandborn WJ, et al. Gastroenterology. 2020;158:562–72.e12.
2. Loftus EV Jr, et al. Aliment Pharmacol Ther. 2020;52:1353–65.
3. Vermeire S, et al. J Crohns Colitis. 2022;16:27–38.
4. Novacek G, et al. J Crohns Colitis. 2024;18(suppl 1):i1506–7

Disclosure

Conflicts of interest: Agata Michalak received lectures fees and/or travel grants from AbbVie, Bayer, Biocodex and Takeda. Katarzyna Karłowicz received lecture fees, consultancy fees or travel educational grants from Bristol Myers Squibb, AbbVie, Polpharma, Takeda and Pfizer. Renata Talar-Wojnarowska received lecture fees and/or travel grants from AbbVie, Astellas, Ferring, Janssen and Takeda. Adam Fabisiak received fees and/or travel grants from Bristol Myers Squibb, Pro. Med. CS, Pfizer and Polpharma. Magdalena Achtenberg received lecture fees from Ferring. Piotr Eder received lecture fees and/or travel grants from Takeda, Ferring, Astellas, Pfizer and Janssen. Maria Kłopocka received payment for lectures from Janssen, Takeda, Ferring, Alfasigma and Pharmabest and travel/accommodation/meeting expenses from Ferring, Janssen, Takeda, Alfasigma and Pharmabest. Maciej Gonciarz received compensation and/or research/educational grants from Pfizer, Polfarma, Abbvie, BMS, Ewoppharma, Ferring, Astellas, Takeda, Jansen-Cilag, Celtrion, Johnson & Johnson, and Sanofi. Grażyna Rydzewska received speaker and consultant fees from AbbVie, AlfaSigma, AstraZeneca, Bayer, Biocodex, Bristol Myers Squibb, Ferring, Janssen, Lilly, Pro. Med. Pl., Recordati, Sanprobi, SOBI and Takeda and travel/accommodation meeting expenses from AbbVie, Ferring and Takeda. Eliza Majewska is a permanent employee of Takeda Pharma Sp. z o.o. Maria Kopertowska-Majchrzak, Tomasz Romańczyk, Halina Cichoż-Lach, Małgorzata Zwolińska-Wcisło, and Elżbieta Poniewierka declare no conflicts of interest.
Funding: The study was funded by Takeda Pharma Sp. z o.o.
Acknowledgements: Medical writing support was provided by Michelle Rebello, PhD, of Cactus Life Sciences (part of Cactus Communications) and funded by Takeda Pharma Sp. z o.o.

Introduction

Resolution of pain, fatigue and other symptoms are key treatment goals for many patients (pts) with Crohn’s disease (CD);^1,2 however, time to symptomatic improvement in pts treated with vedolizumab (VDZ) has not been formally evaluated.

Aims & Methods

VOICE (NCT06249555) is a prospective, observational study in pts with CD aged ≥18 years initiating VDZ or anti-IL-23 antagonist treatment (tx) per product labelling as part of standard of care, with the main objective to explore the time course of response to VDZ as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) domain Short Form (SF) scores. Inclusion criteria include baseline PROMIS Pain Interference (PI)-SF T-score ≥55 (0.5 SD above general population). We enrolled pts via Takeda pt support program in Canada, with additional pts enrolled at US and Canada sites. Planned sample size is 300 pts (VDZ, 200; anti-IL-23 antagonist [reference group not for formal comparison], 100); planned follow-up is 52 weeks (wks), with PROMIS PI data reported weekly for the first 14 wks. The primary endpoint is time to the first meaningful clinical improvement in PROMIS PI-SF T-score, defined as ≥2-point decrease in PROMIS PI-SF T-score from baseline. We also collect data on improvement in 7 PROMIS domains with clinical improvement defined as 5-point (0.5 SD)³ change in T-score from baseline, Short Inflammatory Bowel Disease Questionnaire (SIBDQ; including SIBDQ improvement [≥9 point increase from baseline] and SIBDQ remission [score of ≥60]) and safety. Here, we report the results from pts with ≥1 VDZ dose and ≥1 post-baseline PI assessment included in the interim analysis (IA; prespecified to occur after 50 pts from VDZ group completed or discontinued before the wk 14 assessment to provide an early evaluation of tx response and safety).

Results

Overall, 64 pts with ≥1 VDZ dose and ≥1 post-baseline PROMIS PI assessment (mean±SD age, 43.1±17.0 years, 35.9% male, 92.2% White) were included in the IA. Disease duration (mean±SD) was 6.4±12.1 years; 84.4% of pts were anti-TNF-naïve. Data collection is ongoing for 57 pts (49 with and 8 without completed wk 14 PROMIS PI questionnaire); 7 pts discontinued from the study. The median time to achieve the first ≥2_-point decrease in PROMIS PI-SF T-score (in n=56 pts) was 12 days (95% CI, 6-13). Baseline PROMIS domain scores indicated notable impairment; by wk 14, improvements in mean PROMIS scores from baseline were observed in all 7 measured domains, with ≥5-point improvements in 4/7 domains (Table). At wk 14, 37.5% (24/64) and 7.8% (5/64) pts achieved SIBDQ improvement and remission, respectively. One pt had serious adverse events of appendicitis and diverticulitis, and another pt had a fatal event; none of these were related to VDZ tx.

Table. Summary of PROMIS domain T-scores

Conclusion

The IA results through wk 14 show an early improvement across multiple symptom domains and quality of life in pts with CD starting VDZ tx. Time to first ≥2-point decrease in PROMIS PI-SF T-score was short, with a benefit observed after 12 days from VDZ initiation. Study recruitment and data collection are ongoing.

References

1. Keefer L, et al. Gastroenterology. 2022;162(5):1439-1451.
2. Kitchen H, et al. Crohns Colitis 360. 2020;2(2):otaa033
3. Cella D, et al. Value Health. 2019;22(5):537-544.
4. Shaw BE, et al. Cancer. 2018;124(4):841-849.

Disclosure

This study was sponsored by Alimentiv, Inc.
V. Jairath reports consulting/advisory board fees from AbbVie, Alimentiv, Anaptyis Bio, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ensho, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, MRM Health, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Spyre, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Tillotts and Fresenius Kabi.
M. Long reports consulting fees from AbbVie, Alimentiv, Bristol Myers Squibb, Intercept, Janssen, Lilly, Pfizer, Prometheus, Roivant, Syneos Health and Takeda; and research support from Lilly, Pfizer and Takeda.
M.D. Kappelman reports being a consultant to Eli Lilly and Takeda.
G. Radulescu and N. Li are employees of Alimentiv.
J.J. Wu, I. Romo Bautista, A. Insogna and C. Agboton are employees of Takeda and hold stock and/or share options in Takeda.
N. Narula has received advisory board/consulting honoraria from Abbvie, Amgen, Eli Lilly and Company, Ferring, Fresinius Kabi, Innomar Strategies, Iterative Health, Janssen, Novartis, Organon, Pfizer, Sandoz and Takeda.

Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking agent, was approved in Europe and the USA for the treatment of moderate-to-severe Crohn’s disease (CD) in 2014. Real-world evidence is essential for understanding the effectiveness and benefit–risk profile of VDZ for CD outside clinical trial settings. A systematic literature review and meta-analysis published in 2018 confirmed the real-world effectiveness and positive benefit–risk profile of VDZ treatment for up to 12 months in patients with inflammatory bowel disease.¹ However, there are limited real-world evidence on the long-term (> 12 months) effectiveness of VDZ in patients with CD.

Aims & Methods

A systematic literature review was performed using MEDLINE, MEDLINE In-Process, Embase, Cochrane Library, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform to identify relevant studies published from May 2014 to July 2022. In addition, if the congress abstracts were not indexed in Embase, key congresses from 2015 to July 2022 were hand-searched. Data from adults (aged ≥ 18 years) with CD treated with VDZ in a real-world setting were extracted for meta-analysis. Depending on data availability, the analysis was conducted using the DerSimonian-Laird random-effects model to obtain weighted mean rates (percentage of patients) and the corresponding 95% confidence interval (CI) for each outcome of interest, as per the 2018 meta-analysis.¹ The aims of the current analysis were to evaluate the rates of treatment persistence at 12 and 24 months and mucosal healing at 12 months (overall and stratified by biologic-naïve versus biologic-experienced patients) to address the paucity of long-term data available on these outcomes.

Results

Overall, data from 78 studies of 30 158 patients with CD had at least one outcome of interest for analysis. Using the reported number of patients as the weight, the baseline weighted mean age was 39.3 years (standard error [SE] 2.7; 15 studies), weighted mean disease duration was 12.5 years (SE 0.5; 8 studies), weighted mean CD activity index score was 177 (SE 4.3; 3 studies), and weighted mean Harvey-Bradshaw index score was 7.9 (SE 0.7; 5 studies). In the 32 and 13 studies that assessed treatment persistence at 12 and 24 months, respectively, the rates of treatment persistence were 62.8% (95% CI 56.6–68.9) and 54.9% (95% CI 44.3–65.4), and were higher in biologic-naïve patients than biologic-experienced patients at both time points (Table). The rate of mucosal healing at 12 months (assessed in 20 studies) was 38.4% (95% CI 30.2–46.5) and was higher in biologic-naïve patients than biologic-experienced patients at both time points (Table).

Conclusion

This meta-analysis of real-world studies of VDZ demonstrated high rates of robust, long-term treatment persistence and mucosal healing in patients with CD, particularly in biologic-naïve versus biologic-experienced patients. Over a third of patients achieved mucosal healing at 12 months, confirming the effectiveness of VDZ for achieving this important treatment outcome.

References

1. Schreiber S et al. J Gastroenterol 2018;53:1048–64.

Disclosure

This study was funded by Takeda Pharmaceuticals International AG. Medical writing services were provided by Matthew Reynolds, of Oxford PharmaGenesis, and funded by Takeda Pharmaceuticals International AG.
SS: Personal fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr. Falk Pharma, Fresenius, Galapagos/Gilead, Hikma, I-Mab, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, ProventionBio, Takeda and Theravance Biopharma.
PB: Employee and stockholder of Takeda Pharmaceuticals International AG, Zurich, Switzerland.
RJB: Employee of PHMR Ltd., who received funding for this study from Takeda Pharmaceuticals International AG.
MN: Employee and stockholder of Takeda Pharmaceuticals International AG, Zurich, Switzerland.
SW: Employee and stockholder of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
AA Advisory board/lecture fees from AbbVie, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda.

Introduction

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking drug indicated for Crohn's disease (CD), is administered intravenously at Weeks 0, 2, and 6, then every 8 weeks (Q8W). Dose escalation to every 4 weeks (Q4W) may recapture response to treatment in ~50% of patients with inadequate/loss of response. Factors associated with VDZ dose escalation from Q8W to Q4W and real-world outcomes remain underexplored.

Aims & Methods

Adults with moderate to severe CD initiating VDZ Q8W maintenance therapy were prospectively followed in a Canadian patient support program (2015-2023). Two cohorts were included: 1) patients escalated to Q4W during maintenance therapy any time after week 14 infusion (Q8W>Q4W maintenance) and 2) patients maintained on Q8W treatment for ≥2 years without dose escalation (Q8W maintenance). Baseline characteristics were summarized as median (range) and frequency (%) and compared between cohorts. Rates of clinical remission (Harvey-Bradshaw Index [HBI]<5) were described stratifying by prior biologic experience. Associations between baseline factors and clinical remission 3 months after Q4W dose escalation were assessed using Wilcoxon rank sum test and Fisher’s exact test. Treatment persistence at 12 and 24 months after treatment initiation and dose escalation were evaluated in the Q8W>Q4W cohort using Kaplan-Meier survival analysis.

Results

250 patients were included in the Q8W>Q4W maintenance cohort (39% bio-naïve), and 116 in the Q8W maintenance cohort (51% bio-naïve). In both cohorts, median age at treatment initiation was 50 years and baseline HBI score was 10. In the Q8W>Q4W maintenance cohort, median disease duration prior to initiation of treatment was 14 years (0-69) and median follow-up duration was 22 months (7-60). In the Q8W cohort, median disease and follow-up duration were 8 years (0-50) and 35 months (27-46), respectively. At 14 weeks post-treatment initiation, rates of remission in the Q8W>Q4W maintenance cohort were 47% (bio-naïve) and 22% (bio-experienced), and in the Q8W cohort 61% (bio-naïve) and 48% (bio-experienced) (Table 1). Among patients in the Q8W>Q4W maintenance cohort not in remission at the time of dose escalating, 33% achieved remission 3 months after dose escalation to Q4W. Disease duration at baseline was shorter in these patients than in those who did not achieve remission (8 months [0-52] vs. 16 months [0-69], p=0.007). In the Q8W>Q4W maintenance cohort, 12- and 24-month treatment persistence after treatment initiation was 91% and 64% (bio-naïve) and 94% and 67% (bio-experienced), respectively. After dose escalation, 12- and 24-month treatment persistence was 66% and 59% (bio-naïve) and 69% and 53% (bio-experienced) (Table 1).

Conclusion

Patients with CD who underwent VDZ Q8W>Q4W dose escalation achieved lower rates of clinical remission than those remaining on Q8W treatment, and one third achieved clinical remission 3 months after dose escalating. Baseline disease duration was significantly associated with remission among those escalating to Q4W.

References

N/A

Disclosure

AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
EJB: Participation in advisory boards or speaker services: Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, Eli Lilly, BMS, Grant/Research: Janssen, Abbvie, Any other investment or relationship that could be judged by a reasonable and knowledgeable participant to have the potential to influence the content of the training activity, Abbvie, Janssen, Takeda, Pfizer, Merck, Amgen, Pendopharm, Jamp, Fresenius, Kabi, Bausch Health, Celltrion, BMS.
JFL: AbbVie, BMS, Janssen, Frenesius-Kabi, Pfizer, Sandoz, Takeda. AHS: Advisory Board Membership/Consultant: Abbvie, Amgen, BioJAMP, BMS, Celltrion, Fresenius Kabi, Janssen, McKesson, Mylan Pharmaceuticals, Organon, Pendopharm, Roche, Pfizer, Sandoz, Takeda, Viatris, Speakers’ Bureau: Abbvie, Amgen, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer, Sandoz, Takeda, Research Grants: Abbvie, Arena, Celgene/BMS, Genentech, Janssen, Roche, Takeda.
PW: Personal fees from AbbVie, Ferring, Biogen, and Janssen
MJA, AW, RW: were employees of Takeda Canada Inc. at the time of the study.
RM, JW, CP: were employees of Pentavere Research Group Inc. at the time of the study.
LPB: Consulting from AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HACPharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, and Vectivbio; grants from Takeda, Fresenius Kabi, and Celltrion; and lecture fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, and Medac.
BB: Advisor/Speaker: Ferring, Janssen, Abbvie, Takeda, Pfizer, BMS, Merck, Sandoz, Organon, Lifelabs, Celltrion. Advisor: Alimentiv, Gilead, Iterative Health, AMT, Celgene, Merck, Amgen, Pendopharm, Eli Lilly, BMS, Fresenius Kabi, Mylan, Viatris, Bausch Health, Celltrion Healthcare, BioJamp Pharma, Eupraxia. Research support: Janssen, Abbvie, GSK, BMS, Amgen, Genentech, Merck. Stock Options: Qu Biologic.

Introduction

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of digestive tract, and anti-inflammatory drugs, such as vedolizumab, have central role in their treatment. Intravenous form of vedolizumab is approved for induction and maintenance of remission in patients with CD and UC. Recently, subcutaneous form of vedolizumab was approved as a maintenance therapy after the induction with, at least, two intravenous doses.

Aims & Methods

The aim of this study was to show how the switch from intravenous to subcutaneous vedolizumab in a real-life setting in inflammatory bowel disease (IBD) patients on stable maintenance therapy affects vedolizumab serum concentration and clinical outcomes. IBD patients treated with intravenous vedolizumab and planned to switch to subcutaneous vedolizumab at the Department of Gastroenterology and Hepatology in the University Hospital Centre Osijek were included in the study. Patients were in remission at the time of transition (based on clinical symptoms, fecal calprotectin level or endoscopy scores). Data on vedolizumab serum trough concentration and clinical outcomes (remission rate, fecal calprotectin level, clinical scores, hospitalization rate, rate of surgical procedures, change of therapy, and adverse events) were collected prior to and after the switch from intravenous to subcutaneous vedolizumab.

Results

In total, 31 patients, 17 with CD and 14 with UC, were included in final analysis. Median follow up was 12 months (interquartile range, IQR 9-12). Median duration of therapy with intravenous vedolizumab prior to switch was 14 months (IQR 6-32). Mean serum trough concentration of intravenous vedolizumab was significantly lower than mean serum trough concentration of subcutaneous vedolizumab (25.62 mg/L±14.29 vs. 34.93±14.59 mg/L; p=0.002). This rise in vedolizumab serum concentration after the switch to subcutaneous drug, was more evident in CD (Δ11.8 mg/L) than in UC (Δ5.79 mg/L) patients. There was no significant difference between fecal calprotectin level in all patients, as well as fecal calprotectin and Harvey–Bradshaw index in CD patients prior to or after the transition to subcutaneous vedolizumab. In UC patients, fecal calprotectin and Partial Mayo score were significantly higher (p= 0.011 and p=0.018, respectively) after the switch to subcutaneous vedolizumab, although this difference was not clinically significant. There was a significant difference in remission rate before and after the transition to subcutaneous vedolizumab in all patients (100% vs 71%; p=0.004), and in UC patients (100% vs. 57.1%; p=0.031). During the follow up, one (3.2%) CD patient was hospitalized and had a surgical procedure due to IBD. In 7 (22.6%) patients, the therapy was discontinued during the follow-up period with a median of 8 months. In all patients, therapy was discontinued due to loss of response. In total, 27 adverse events were reported by 17 patients, and the most common adverse event was COVID-19. One serious adverse event was reported (a patient was hospitalized for subileus).

Conclusion

Despite the rise in serum vedolizumab trough concentration after the switch from intravenous to subcutaneous vedolizumab, total remission rate was significantly lower in all patients and in the subgroup of UC patients. No new safety signals were observed in patients after the switch to subcutaneous vedolizumab.

Disclosure

Vlasta Oršić Frič has received speaker honoraria from Takeda, Janssen, Merck Sharp & Dohme, Sandoz, Ferring, Oktal Pharma, Abbvie, Viatris-Mylan and has been a member of advisory board for Janssen. Vladimir Borzan has received speaker honoraria from Takeda, Janssen, Sandoz, Merck Sharp & Dohme, Abbvie, Oktal Pharma, Viatris-Mylan, Ferring and has been a member of advisory board for Takeda, Sandoz, Abbvie, Viatris-Mylan, Merck Sharp & Dohme. Other authors declare no conflict of interest.

Introduction

Vedolizumab (VDZ) is a monoclonal antibody therapy approved in China in 2020 for the treatment of patients with inflammatory bowel disease (IBD; Crohn's disease [CD] and ulcerative colitis [UC])² who were intolerant to conventional therapies.¹ VDZ has a unique, gut-selective, anti-lymphocyte trafficking (GSALT) mechanism of action.³ However, data on the efficacy and safety of VDZ in Chinese patients with IBD in the real-world setting are limited.⁴ This study evaluated the safety of VDZ in adult patients with IBD.

Aims & Methods

VALUE (NCT04872491) was a multicenter, single-arm, prospective, observational study to evaluate the safety of VDZ in adult Chinese patients with IBD (N=500) over a maximum observation period of 72 weeks. Incidence of adverse events (AEs), serious AEs (SAEs), treatment-related adverse drug reactions (ADRs), and AEs of special interest (AESIs) was evaluated. This was the final analysis of the VALUE study conducted in patients with IBD.

Results

A total of 500 patients (UC: n=409; CD: n=91) received VDZ 300 mg. Mean (±standard deviation) age of patients was 44.3 (±15.2) years, and 61.4% (n=307) were male. The mean duration for VDZ exposure was 414 days (UC: 416 days; CD:407 days). A total of 500 patients developed 674 AEs (Table), and the most frequent AEs were infections and infestations (I&I; UC: 115 [28.1%]; CD: 24 [26.4%]), followed by gastrointestinal disorders (GIDS; UC: 87 [21.3%]; CD: 18 [19.8%]). Incidence rates of AEs (/patient-years) were 1.2 and 1.0 in patients with UC and CD, respectively. Overall, 13 (3.2%) patients with UC and 10 (11.0%) with CD had AEs leading to study discontinuation. SAEs were observed in 78 patients with UC and 18 with CD (Table). A total of 19 AESIs were reported by patients with UC and 9 AESIs by those with CD, with the most common AESIs being I&I (UC: 13 [3.2%]; CD: 4 [4.4%]) and malignancy (UC: 3 [0.7%], CD: 2 [2.2%]). The most common I&I disorders reported by patients with UC and CD were Clostridium difficileinfection (4 [1.0%]) and pneumonia (1 [1.1%]), respectively. Overall, 17 (4.2%) patients with UC and 7 (7.7%) with CD had at least 1 AESI. A total of 91 and 15 treatment-related ADRs were observed in patients with UC and CD, respectively; I&I were the most frequently documented ADRs to VDZ treatment (Table). A total of 10 (UC: 5 [1.2%]; CD: 5 [5.5%]) patients treated under concomitant IBD advanced therapy (CIBDAT) experienced a total of 16 AEs (UC: 9; CD: 7), with the most common AEs being I&I (UC: 1 [20.0%]; CD: 2 [40.0%]) and GIDS (UC: 3 [60.0%]; CD: 1 [20.0%]) with CIBDAT. No deaths were reported during the study.

Conclusion

The VALUE study indicated that VDZ was well tolerated in Chinese patients with IBD, with no new safety concerns.

References

1. Scribano ML. World J Gastroenterol. 2018; 24: 2457-2467.
2. Yamamoto S et al., Cureus. 2024;16: e59691.
3. Soler D et al. J Pharmacol Exp Ther. 2009; 330: 864-875.
4. Baili C et al. Am J Gastroenterol. 2023; 118: S213-S214.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Li Li, Haiyan Zhang, Chengxia Liu, and Xiaomei Sun have no conflicts of interest. Xiaoyu Qian and Fang Zhou are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.
Medical writing support for the development of this abstract under the direction of the authors was provided by Vibhuti Singh, Ph.D., of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd.