Real-world Data on Switching From Intravenous to Subcutaneous Vedolizumab Treatment in Patients With Inflammatory Bowel Disease

Viktoria Bergqvist; Johanna Holmgren; Daniel Klintman; Jan Marsal

Disclosures

Aliment Pharmacol Ther. 2022;55(11):1389-1401. 

In This Article

Results

Eighty-nine patients (48 patients with CD, 41 patients with UC and no patients with IBD-unclassified) were included in the study. In total, 102 patients were approached regarding participation. Twelve patients declined participation, and one patient did not meet the inclusion criteria (Figure 1). Baseline patient characteristics, clinical disease activity scores, laboratory biomarkers, concomitant IBD treatment and time on IV vedolizumab are presented in Table 2. Details on previous IBD treatments and changes during follow-up are presented in Table S2. The median time on IV vedolizumab before the switch was 26.1 months (IQR 9.5–52.9). The wide IQR illustrates heterogeneity in terms of previous exposure time to vedolizumab. At baseline, four patients received low dose oral prednisolone (1.25–10 mg daily), and three patients received oral budesonide. Prednisolone could be discontinued in one of these patients. Results refer to 6 months follow-up, unless otherwise specified.

Figure 1.

Flow chart of study design, enrollment of consecutive patients, patients discontinued and reasons for discontinuation during the primary observational follow-up period of 6 months. Abbreviations: EIM, extraintestinal manifestations; n, number of patients

Changes in Disease Activity and Remission Rates 6 Months After the Switch

For the cohort as a whole and the subgroup of CD patients, significant decreases in faecal calprotectin median levels were observed following the switch, whereas no change was seen in UC patients (Figure 2A). The remission rates as defined by faecal calprotectin remained stable for all three groups (Figure 2B). A subgroup analysis of faecal calprotectin levels in patients with limited ileal CD showed a median of 145 μg/g (IQR 48–281) at baseline and 94 μg/g (IQR 50.0–175.5) at follow-up. The corresponding values for the entire CD group were 64.0 (IQR 12.5–238.5) μg/g and 49.0 μg/g (IQR 12.5–161.8), respectively. Analyses of plasma CRP levels did not show any significant changes before compared with after switch for the cohort as a whole, nor in the CD and UC subgroups (data not shown).

Figure 2.

Analysis of faecal calprotectin levels and remission rates defined by faecal calprotectin at baseline and 6 months after the switch from IV to SC vedolizumab treatment. (A) Faecal calprotectin levels presented as median values with IQR. (B) Proportions of patients in remission as defined by a faecal calprotectin level of <150 μg/g. Abbreviations: CD, Crohn's disease; IQR, interquartile range; IV, intravenous; M, months; SC, subcutaneous; UC, ulcerative colitis. *p < 0.05

Clinical disease activity in patients with CD, as measured by average patient-based HBI and PRO2-CD scores, remained unchanged (Figure 3A). Patients with UC displayed a statistically significant improvement in clinical symptoms according to the SCCAI although the median score remained unchanged, while the PRO2-UC score did not show a significant change (Figure 3C). There were no statistically significant changes in the proportions of patients displaying clinical remission, as defined by patient-based HBI ≤4 or PRO2-CD ≤11 for patients with CD, and by SCCAI ≤2 or PRO2-UC = 0 for patients with UC (Figure 3B,D).

Figure 3.

Analysis of clinical disease activity index score levels and remission rates at baseline and 6 months after the switch from IV to SC vedolizumab treatment. (A) Patient-based HBI and PRO2-CD scores for CD patients presented as median values with IQR. (B) Proportions of CD patients in remission as defined by a patient-based HBI ≤4 or PRO2-CD ≤11. (C) SCCAI and PRO2-UC scores for UC patients presented as median values with IQR. (D) Proportions of UC patients in remission as defined by an SCCAI ≤2 or PRO2-UC = 0. Abbreviations: CD, Crohn's disease; IQR, interquartile range; IV, intravenous; M, months; pHBI, patient-based Harvey Bradshaw index; PRO2-CD, Crohn's Disease Activity Index-based patient-reported outcomes-2; PRO2-UC, Mayo-based patient-reported outcomes-2; SC, subcutaneous; SCCAI, simple clinical colitis activity index; UC, ulcerative colitis. *p < 0.05

At baseline, 10 patients had a diagnosis of perianal CD. Three of these had active perianal disease at baseline, and at follow-up, this number was two.

Subgroup Analyses of Patients on Optimised and Standard Dosing of IV Vedolizumab

Twenty patients were on optimised IV vedolizumab dosing at baseline. At follow-up, there was no significant change in their faecal calprotectin levels, whereas the 69 patients that had been on standard IV vedolizumab dosing showed a small but significant decrease (Figure 4A). Faecal calprotectin remission rates (Figure 4A) and plasma CRP median values (data not shown) remained unchanged in both groups. Clinical remission rates remained stable at follow-up (Figure 4B,C) except for the PRO2-UC remission rate for UC patients that had been on standard IV vedolizumab dosing, where a statistically significant improvement was seen (Figure 4C).

Figure 4.

Subgroup analysis of faecal calprotectin and clinical disease activity levels at baseline and 6 months after the switch from IV to SC vedolizumab treatment for patients on standard versus optimised dosing of IV vedolizumab. (A) Faecal calprotectin levels presented as median values with IQR, and proportions of patients in remission as defined by a faecal calprotectin level of <150 μg/g, respectively. (B) Proportions of CD patients in remission as defined by a patient-based HBI ≤4 or PRO2-CD ≤11. (C) Proportions of UC patients in remission as defined by an SCCAI ≤2 or PRO2-UC = 0. Abbreviations: CD, Crohn's disease; IQR, interquartile range; IV, intravenous; M, months; pHBI, patient-based Harvey Bradshaw index; PRO2-CD, Crohn's disease activity index-based patient-reported outcomes-2; PRO2-UC, Mayo-based patient-reported outcomes-2; SC, subcutaneous; SCCAI, simple clinical colitis activity index; UC, ulcerative colitis. *p < 0.05

SC Vedolizumab Dose Optimization

Dose optimization of SC vedolizumab to 108 mg weekly was deemed indicated in 10.1% of patients (6 CD, 3 UC). Three of these (1 CD, 2 UC) belonged to the subgroup of 20 patients (22.5%) that had been on intensified IV vedolizumab dosing before the switch, whereas the other 17 (85%) remained on standard SC dosing. All patients with perianal CD (n = 10) remained on treatment, but 3/10 were dose optimised to SC vedolizumab 108 mg weekly. No patient required hospitalisation or IV corticosteroid treatment due to disease worsening during the study.

Drug Persistence and Biomarker Levels at 12 Months After the Switch

A subset of patients was evaluated at 12 months after the switch, in addition to the more comprehensive evaluation after the primary follow-up period of 6 months. Drug persistence at 6 and 12 months were 95.5% (85/89) and 88.5% (69/78), respectively, for the whole cohort (Figure 5). Reasons for drug discontinuation (n = 9) were disease worsening in five patients, change in treatment regimen due to extraintestinal manifestations (present before the switch) in one patient, local injection reaction in one patient and adverse events in two patients (headache and repeated infections). There were no statistically significant changes in plasma CRP levels for the whole cohort (n = 50), CD (n = 27) or UC (n = 23); or in faecal calprotectin levels for the whole cohort (n = 20), CD (n = 10) or UC (n = 10), at 12 months (data not shown).

Figure 5.

Kaplan–Meier survival curve for drug persistence after the switch from IV to SC vedolizumab treatment. Events refer to treatment discontinuation. Censored points refer to patients that have not yet completed 12 months of follow-up

Serum Vedolizumab Concentrations Before and After the Switch

Median serum vedolizumab trough levels at steady state on IV treatment (i.e. at baseline) were 8.1 μg/ml (IQR 5.2–14 μg/ml) for the whole cohort, 8.7 μg/ml (IQR 4.9–14.0 μg/ml) in CD patients, and 7.9 μg/ml (IQR 5.3–12.5 μg/ml) in UC patients. Median serum vedolizumab trough levels at steady state on SC treatment (i.e. at 6 months follow-up) were 19.0 μg/ml (IQR 13.0–23.0 μg/ml) for the whole cohort, 19.0 μg/ml (IQR 12.0–22.8 μg/ml) in CD patients, and 18.5 μg/ml (IQR 15.0–23.8 μg/ml) in UC patients. When patients were on IV treatment, we found significantly higher faecal calprotectin levels, primarily among CD patients, in the quartiles with the lowest serum vedolizumab trough levels compared to those with higher serum vedolizumab trough levels (Figure 6A). This relationship was not observed after patients had been on SC treatment for 6 months (Figure 6B).

Figure 6.

Associations between serum vedolizumab trough concentration quartiles (Q1 lowest; Q4 highest) and faecal calprotectin levels during IV and SC treatment for the entire cohort (all patients), and for the subgroups of CD and UC patients. (A) IV vedolizumab treatment. (B) SC vedolizumab treatment. Data are presented as median values with IQR (box), 1.5 × IQR (whiskers) and outliers. Abbreviations: CD, Crohn's disease; IQR, interquartile range; IV, intravenous; Q, quartile; SC, subcutaneous; UC, ulcerative colitis. *p < 0.05

Quality-of-life and Patient Satisfaction Regarding the Switch and Injector pen

We observed no differences in the SHS composite score or separate SHS items (Figure S1). Patient satisfaction with the injector pen (all eight categories; see Table S1 for details) was high with 94.1%–100% of patients responding "strongly agree", "agree" or "agree to some extent" (Figure 7A). Overall satisfaction with the injection experience was generally high with 96.4% of the patients reporting being satisfied or very satisfied (Figure 7B). Generally, patients favoured SC administration over IV (Figure 7C). Only 2.4–9.4% of patients reported a slight preference for IV treatment over SC. Conversely, 55.3% of patients experienced SC treatment as slightly or clearly more effective, and 85.9% slightly or clearly more convenient (Figure 7C). Regarding overall feeling of security, no preference was the most frequent response (58.8%) and a slight preference for IV treatment was reported by 9.4% of patients (Figure 7C). Taking all aspects that follow with the given route of administration into account, 83.3% of patients reported a preference for SC over IV treatment, whereas the opposite was true for 2.4% of patients (Figure 7C).

Figure 7.

Patient satisfaction regarding various aspects of handling the vedolizumab injector pen, overall satisfaction with the injection experience, and patient preference comparing various aspects of IV versus SC vedolizumab treatment, based on questionnaires (Table S1). Data are presented for all patients (entire IBD cohort) collectively. (A) Aspects of handling the vedolizumab injector pen are perceived as easy or difficult to varying degrees. Data are presented as proportions of patients reporting a specific response option ranging from easy to difficult. (B) Satisfaction with the injection experience presented as proportions of patients reporting a specific response option ranging from very satisfied to very dissatisfied. (C) Patient preference comparing IV versus SC treatment in terms of patient-perceived therapeutic effect, overall convenience, overall feeling of security and patient preference overall. Data are presented as proportions of patients reporting a specific response option ranging from clear preference for SC treatment to clear preference for IV treatment, with slight preference or no preference as response options in-between. Abbreviations: IBD, inflammatory bowel disease; IV, intravenous, SC, subcutaneous

Adverse Events Experienced on IV and SC Vedolizumab Treatment

All reported adverse events are presented in Table 1. Adverse events, excluding local injection reactions, occurred in 15 (31.3%) of CD patients and 10 (24.4%) of UC patients. The corresponding rates for IV treatment were 27.1% and 22.0%, respectively. Some patients reported several side effects. The most common complaint was fatigue, followed by headache, nausea and rash. No serious adverse events were reported. Data on local skin reactions including discomfort, pain, burning sensation and erythema are presented in Table 1. The vast majority experienced none or only mild local injection reactions (88.0%–94.0% of patients, depending on the type of local injection reaction). Similar numbers were seen among CD and UC patients. Severe local symptoms were reported in only 1.2% of patients for the various subcategories. There was one case of drug discontinuation due to local injection reactions at 12 months of follow-up, but none during the first 6 months.

Annualised Costs Related to SC as Compared With IV Vedolizumab Treatment

In Sweden, the current fee for a visit to a registered nurse for administration of an IV infusion is approximately €290; the annual drug cost for IV vedolizumab (standard dosing) is approximately €13,700; and the annual drug cost for SC vedolizumab (standard dosing) is approximately €13,800. During IV vedolizumab treatment, 22.5% of patients required dose optimization (one infusion of 300 mg every 4–7 weeks or 600 mg every 8 weeks), and during SC vedolizumab treatment 10.1% were dose optimised to 108 mg of SC vedolizumab once weekly. Taking these factors into account, the annualised cost of maintenance treatment with SC vedolizumab was 15.0% lower than for maintenance treatment with IV vedolizumab.

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