Introduction

Vedolizumab (VDZ) is a gut-selective humanised monoclonal anti-α₄β₇ integrin antibody for treatment of ulcerative colitis (UC) and Crohn’s disease (CD). The GEMINI Long-Term Safety (LTS) study demonstrated the durable efficacy and safety of vedolizumab for inflammatory bowel disease (IBD) treatment. Patients experiencing clinical benefit from vedolizumab in GEMINI LTS (NCT00790933) or VERSIFY (NCT02425111) studies could continue treatment in the vedolizumab extended access programme (XAP).

Aims & Methods

​​​​​​The XAP study was a phase 3b/4, prospective, open-label, multinational, interventional study (NCT02743806)^1,2 conducted from Aug 2016 to Jan 2023 to investigate long-term treatment persistence and safety of vedolizumab 300mg IV every 4 weeks (Q4W) or every 8 weeks (Q8W) in adults with UC or CD.

Results

The study enrolled 331 patients (UC=142; CD=189) including 20 rolling over from VERSIFY and 311 patients from GEMINI LTS. Patients treated with vedolizumab in the XAP study had either dose frequency reduction Q4W to Q8W or were maintained on their current Q8W or Q4W dosing; 297 patients started the XAP study on Q8W dosing, of which 295 received at least one dose of vedolizumab in XAP. At XAP study baseline, mean (SD) disease duration was 13.9 (6.8) and 13.2 (6.8) yrs for patients with UC and CD, respectively; most patients were in clinical remission (Table 1). In total, 283/295 patients (95.9%) were persistent on Q8W dosing for ≥6 months without relapse (UC: 129/132 [97.7%] and CD: 154/163 [94.5%]). Median (range) duration of vedolizumab treatment in the XAP study was UC: 3.8 (0–6) and CD: 4.2 (0–6) yrs. Only 27 patients (9.2%) were re-escalated from Q8W to Q4W dosing during the study (UC: 11/132 [8.3%] and CD: 16/163 [9.8%]); median (range) duration from last dose in the qualifying study to dose escalation in XAP was 1.5 (0.6–3.0) and 1.2 (0.2–5.2) yrs for UC and CD groups, respectively; the corresponding duration from last dose in the qualifying study to relapse was 1.4 (0.4–4.0) and 1.2 (0.06–5.4) yrs. Adverse events (AEs) after enrolment into XAP occurred in 61.3% of patients with UC and 62.4% with CD (treatment-related in 2.1% UC and 4.2% CD) but only 4.2% UC and 1.6% CD had AEs leading to study discontinuation (treatment-related: 0.7% UC, 0.5% CD); 13.4% UC and 16.4% CD had serious AEs (treatment-related: 0.7% UC, 0.5% CD). Severe infections occurred in 2 patients with UC (1.4% including 1 patient with COVID-19) and in 1 patient with CD (0.6%), none were considered treatment-related. There was 1 death from COPD reported during the study.

Conclusion

This long-term, prospective study reported high patient persistence on vedolizumab Q8W after the reduction of dosing frequency, together with low rates of dose frequency escalation to Q4W and relapse. Safety results were consistent with the known safety profile of vedolizumab; no new safety signal was identified.

References

1. Vermeire S, et al. J Crohns Colitis 2020;14(8):1066-73.
2. Danese S, et al. Aliment Pharmacol Ther 2021;53(2):265-72.

Disclosure

Silvio Danese: Lecture fees: AbbVie, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer Inc, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, Boehringer Ingelheim; Consultancy: AbbVie, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer Inc, Tigenix, UCB Pharma, Vifor, Biogen, Celgene, Allergan, Celltrion, Sandoz, Boehringer Ingelheim. Grazyna Rydzewska: Lecture fees: AbbVie, Ferring, Johnson & Johnson, Takeda, Pfizer Inc, Celltrion, Sandoz, Boehringer Ingelheim; Alfa Sigma, ProMed, Biocodex, Sanprobi; Consultancy: AbbVie, Ferring, Johnson & Johnson, Takeda, Pfizer Inc, Celltrion, Sandoz, Sobi, ProMed. Stephen Jones: consultant to Takeda. Shashi Adsul and Dirk Lindner: employees of Takeda and hold Takeda stock/stock options; medical writing support was provided by Excel Medical Affairs and funded by Takeda. Séverine Vermeire: Grants: AbbVie, Galapagos, Johnson & Johnson, Pfizer, Takeda; consulting/and or speaker fees: AbbVie, AbolerIS, AgomAb, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Cytoki, Dr Falk, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, Johnson & Johnson, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots, Zealand.

Introduction

Only a small number of trials have been conducted on the use of SC Infliximab in IBD with a lack of data to directly compare with IV Infliximab. These trials have focused upon patients newly started on Infliximab. There has been an under representation of patients who have been established on IV Infliximab for a longer period of time and then undergone SC switch as well as higher risk patient groups including those with Perianal Disease and Escalated Dosing Regimens of IV Infliximab. We conducted the largest study completed so far in the UK comparing the efficacy, pharmacokinetics and safety of SC with IV Infliximab in IBD .The novelty of SC Infliximab use in the UK combined with the scarcity of units currently using this treatment and critical study outcomes at 1 year only becoming available in May 2023 have prompted us to submit this as a late breaking abstract.

Aims & Methods

Retrospective cohort study of 306 patients in established clinical remission receiving Infliximab at an IBD centre in the UK during May 2023. Efficacy was assessed using objective biomarkers (CRP, FCP), clinical disease activity scores (HBI/SCCAI) at Baseline, 3-6, 12-15 months and treatment persistence. Pharmacokinetics was assessed through treatment discontinuation secondary to Anti-Drug Antibody formation and changes in serum drug levels. Safety was assessed through the frequency of treatment related side effects. Statistical analyses included; Descriptive, Wilcoxon, ANOVA, Regression, KMC/Log Rank and MWU Test. Ethical approval was not required.

Results

199 patients were on SC Infliximab and 107 patients on IV Infliximab. The Efficacy of SC Infliximab was demonstrated through no significant change in the CRP and FCP from baseline when compared to values at 3-6 months and 12-15 months (CRP (p = 0.344)) (FCP (p = 0.301)). Higher rates of treatment persistence were reported on SC Infliximab when compared to the IV group (87% SC vs 35% IV, p < .001). This difference persisted when escalation of the IV dose was excluded as the reason for the failure of treatment persistence (87% SC vs 76% IV, p = .001). An increase in drug levels on treatment was found to be a significant factor for treatment persistence in the SC group (p = .001) (OR 31.77). However, perianal disease and the dosing of IV Infliximab prior to SC switch were not significant factors for treatment persistence in the SC group (Perianal Disease ((p= .757) (OR 1.2)) (Dosing of IV Infliximab (p = .513) (OR 0.67)). There were significant differences between the SC and IV Infliximab group when comparing drug levels on treatment (p=<.001), the CRP at 3-6/12 (p=<.001) and the FCP at 3-6/12 (p=<.001). Those on SC Infliximab had a significant increase in drug levels on treatment not observed in the IV group with higher drug levels and more frequent increase in drug levels (SC (p = <.001) (Median 6 Before, Median 14 After) (83.2%)), (IV (p = .085) (Median 3.1 1^st, Median 4.8 2^nd) (54.4%)). Furthermore, Anti-Drug Antibody (ADA) formation leading to treatment discontinuation was less frequently observed on SC Infliximab (2% SC vs 20% IV). Treatment discontinuation due to side effects was less frequent in those on SC Infliximab (3% SC vs 13% IV).

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Conclusion

SC switch should be considered in patients who are in established clinical remission on IV Infliximab as offering an effective and safe alternative, even in higher risk patients, with an increase in serum drug levels predictive of treatment success. The SC route displays different pharmacokinetic properties to IV which are favourable given the lower rates of treatment discontinuation.

References

Peyrin-Biroulet, L. et al. (2022) ‘Comparative efficacy and safety of infliximab and vedolizumab therapy in patients with inflammatory bowel disease: A systematic review and meta-analysis’, BMC Gastroenterology, 22(1). doi: 10.1186/s12876-022-02347-1.
Bots, S.J. et al. (2021) ‘Anti-drug antibody formation against biologic agents in inflammatory bowel disease: A systematic review and meta-analysis’, BioDrugs, 35(6), pp. 715–733. doi:10.1007/s40259-021-00507-5.
Haar, G.S. et al. (2021) ‘Assessing adherence to infusion-based biologic therapies in patients with inflammatory bowel disease’, Research in Social and Administrative Pharmacy, 17(8), pp. 1420–1425. doi:10.1016/j.sapharm.2020.10.011.
Schreiber, S. et al. (2021) ‘Randomized controlled trial: Subcutaneous vs intravenous infliximab CT-P13 maintenance in inflammatory bowel disease’, Gastroenterology, 160(7), pp. 2340–2353. doi:10.1053/j.gastro.2021.02.068.
Buisson, A. et al. (2022) ‘Effectiveness of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases: The REMSWITCH study’, Clinical Gastroenterology and Hepatology [Preprint]. doi:10.1016/j.cgh.2022.08.011.
Smith, P.J. et al. (2022) ‘Efficacy and safety of elective switching from intravenous to subcutaneous infliximab [CT-P13]: A multicentre cohort study’, Journal of Crohn’s and Colitis, 16(9), pp. 1436–1446. doi:10.1093/ecco-jcc/jjac053.