Three-year Effectiveness and Safety of Vedolizumab Therapy for Inflammatory Bowel Disease

A Prospective Multi-centre Cohort Study

Aurelien Amiot; Melanie Serrero; Laurent Peyrin-Biroulet; Jerome Filippi; Benjamin Pariente; Xavier Roblin; Anthony Buisson; Carmen Stefanescu; Caroline Trang-Poisson; Romain Altwegg; Philippe Marteau; Thibaud Vaysse; Anne Bourrier; Stephane Nancey; David Laharie; Matthieu Allez; Guillaume Savoye; Jacques Moreau; Lucine Vuitton; Stephanie Viennot; Guillaume Bouguen; Vered Abitbol; Mathurin Fumery; Charlotte Gagniere; Yoram Bouhnik; on the behalf of the OBSERV-IBD study group, the GETAID

Disclosures

Aliment Pharmacol Ther. 2019;50(1):40-53. 

In This Article

Results

Study Population

Among the 294 patients enrolled in the OBSERV-IBD cohort, 166 (56.5%) were evaluated while on VDZ therapy at week 54, including 94 (54.3%) patients with CD and 72 (59.5%) with UC (Table 1), whereas 128 (43.5%) had discontinued vedolizumab. Seventeen patients discontinued vedolizumab immediately following the week 54 visit, including 17 patients with CD and one with UC (lack of efficacy and switch to another treatment in 16 cases and pregnancy in one). The demographic and clinical characteristics and medication history at week 54 in the 149 (50.7%) patients who were evaluated from week 54 to week 162 are listed in Table 1.

A total of 92 (31.3%) patients completed the 162-week maintenance period, including 43 (24.9%) in the CD group and 49 (40.5%) in the UC group (Figure S1). Fifty-seven patients discontinued vedolizumab therapy between week 54 and week 162 (34 for lack of efficacy and switch to another treatment, one for pregnancy, eleven were referred for surgery, eight for adverse events and three who discontinued vedolizumab therapy in clinical remission by mutual agreement with their physician), including 35 in the CD group and 22 in the UC group. After the week 162 visit, 10 additional patients discontinued vedolizumab therapy (four for lack of clinical efficacy and switch to another treatment, three for adverse events and two who were referred for surgery and one discontinued vedolizumab therapy in clinical remission by mutual agreement with their physician), including nine with CD and one with UC (Figure 1).

Figure 1.

Flow chart of patient disposition throughout the OBSERV-IBD study. The grey portion indicates the week 0 to week 54 period, the results of which have been published previously10, 12

Steroid-free Clinical Remission Through Week 162

At week 162, 34 (19.9%) and 43 (36.1%) patients were in steroid-free clinical remission in the CD and the UC groups, respectively (Table 2). The rates of clinical remission, clinical response and steroid-free clinical response are presented in Table 2. Among the 149 patients still treated after the week 54 visit, 62.3% of patients with UC and 44.7% of patients with CD were still in steroid-free clinical remission at week 162 (Table S2).

In the CD group, among the 47 patients in steroid-free clinical remission at week 54, 26 (55.3%) were still in steroid-free clinical remission at week 162 (Figure 2A). One additional patient was still in steroid-free clinical remission at week 162 while discontinuing vedolizumab therapy after the week 135 visit by mutual agreement with the physician in charge. Two patients presented with a clinical response without steroid-free clinical remission at week 162 but continued vedolizumab therapy. Eighteen patients discontinued vedolizumab therapy between week 108 and week 162 for insufficient response in 17 cases and for adverse events in one. Among the 31 patients without steroid-free clinical remission at week 54, 8 (25.8%) achieved steroid-free clinical remission at week 162. One additional patient was still in steroid-free clinical remission at week 162 while discontinuing vedolizumab therapy after the week 135 visit by mutual agreement with the physician in charge. One patient presented with a clinical response without steroid-free clinical remission at week 162 and discontinued vedolizumab therapy after the week 162 visit. Twenty-two patients discontinued vedolizumab therapy for insufficient response to vedolizumab therapy between week 81 and week 162.

Figure 2.

Flow chart of patient with ulcerative colitis (panel A) and Crohn's disease (panel B) achieving steroid-free clinical remission (SFCR) throughout the OBSERV-IBD study

In the UC group, among the 49 patients with UC in steroid-free clinical remission at week 54, 34 (69.4%) was still in steroid-free clinical remission at week 162 (Figure 2B). Two additional patients were still in steroid-free clinical remission at week 162 while having discontinued vedolizumab therapy after the week 135 visit for ongoing pregnancy in one case and by mutual agreement with the physician in charge. Four patients presented with a clinical response without steroid-free clinical remission at week 162 and subsequently discontinued vedolizumab therapy. The nine remaining patients discontinued vedolizumab therapy for insufficient response to vedolizumab therapy between week 81 and week 162. Among the 22 patients with UC without steroid-free clinical remission at week 54, nine (40.9%) achieved steroid-free clinical remission at week 162. Additionally, 13 patients discontinued vedolizumab therapy for insufficient response to vedolizumab therapy between week 81 and week 162.

Vedolizumab Therapy Optimisation

The optimisation of vedolizumab therapy at a dose of 300 mg every 4 weeks was at the investigator's discretion. In the CD group, vedolizumab therapy was optimised in 54 (69.2%) patients at week 54 including 29 without steroid-free clinical remission and 25 with steroid-free clinical remission but persistence of elevated CRP. Among the 54 patients with CD with optimisation of vedolizumab therapy at week 54, 29 (53.7%) discontinued vedolizumab therapy during follow-up, 15 were still treated with an optimised regimen at week 162 and 10 were de-escalated to a standard regimen every 8 weeks without relapse. Among the 24 patients with CD with no optimisation of vedolizumab therapy at week 54, vedolizumab was optimised in eight (33.3%) patients, including six who discontinued vedolizumab during follow-up and 16 were still treated at week 162 with standard regimen. In the UC group, vedolizumab therapy was optimised in 37 (52.1%) patients at week 54, of whom 20 out of 49 (40.8%) were in steroid-free clinical remission and 17 out of 22 (77.3%) were not. Among the 37 patients with UC with optimisation of vedolizumab therapy at week 54, 17 (45.9%) discontinued vedolizumab therapy during follow-up, 12 were still treated with an optimised regimen at week 162 and eight were de-escalated to a standard regimen every 8 weeks without relapse. Among the 34 patients with CD with no optimisation of vedolizumab therapy at week 54, vedolizumab was optimised in 13 (38.2%) patients, including five who discontinued vedolizumab during follow-up, and 19 were still treated at week 162 with a standard regimen and two discontinued vedolizumab for long-term steroid-free clinical remission.

Endoscopic Activity

Among the 78 patients with CD still being treated with vedolizumab after the week 54 visit, 34 (43.6%) were assessed for mucosal healing. Mucosal healing occurred in 11 (32.4%) patients with CD. Among the 71 patients with UC still being treated with vedolizumab after the week 54 visit, 60 (84.5%) were assessed for mucosal healing. According to the Mayo Clinic endoscopic subscore (0 or 1), mucosal healing occurred in 32 (53.3%) patients. The UCEIS score was ≤2 in 32 (53.3%) patients, between 3 and 4 in 11 (18.3%) patients and >4 in 17 (28.3%) patients. Mucosal healing was significantly higher in patients with UC who achieved steroid-free clinical remission at week 162 (66.6% vs. 7.70%, P < 0.001).

Persistence of Vedolizumab

In the CD group, the rate of persistence of vedolizumab was 48.5%, 31.4% and 26.3% at 1, 2 and 3 years, respectively (Figure 3). In multivariate analysis, the rate of persistence of vedolizumab was significantly decreased in patients with history of perianal disease (HR = 0.62, 95% CI [0.43-0.90], P = 0.01) and increased in patients with an age at induction of vedolizumab therapy >35 years (HR = 1.47, 95% CI [1.01-2.13], P = 0.005) (Supplementary Table S3).

Figure 3.

Kaplan-Meier curves of 173 patients with Crohn's disease and 121 patients with ulcerative colitis treated with vedolizumab to assess the persistence of vedolizumab therapy

In the UC group, the rate of persistence of vedolizumab was 61.0%, 49.9% and 42.9% at 1, 2 and 3 years, respectively (Figure 3). In multivariate analysis, the persistence of vedolizumab was significantly decreased in patients with partial Mayo Clinic score >6 at week 0 (HR = 0.43, 95% CI [0.25-0.74], P = 0.003) and in patients with UCEIS >5 at week 0 (HR = 0.55, 95% CI [0.32-0.94], P = 0.03) (Supplementary Table S4).

Persistence of Vedolizumab in Patients Still Treated After the Week 54 Visit

In the CD group, the rate of persistence of vedolizumab was 82.9%, 77.1% and 71.3% at 12, 18 and 24 months, respectively (Figure S1). In multivariate analysis, the rate of persistence of vedolizumab was significantly decreased in case of vedolizumab optimisation every 4 weeks at week 54 (HR = 0.17, 95% CI [0.05-0.54], P = 0.003) (Supplementary Table S5).

In the UC group, the rate of persistence of vedolizumab was 71.6%, 62.5% and 57.1% at 12, 18 and 24 months, respectively (Figure S1). In multivariate analysis, the rate of persistence of vedolizumab was significantly decreased in case of vedolizumab optimisation every 4 weeks at week 54 (HR = 0.21, 95% CI [0.07-0.62], P = 0.005) (Supplementary Table S6).

Safety

The analysis of adverse events was performed for all patients who received at least one dose of vedolizumab after the week 54 visit. Adverse events occurred in 68 (45.6%) out of 149 patients (Table 3). Serious adverse events occurred in 24 (16.1%) patients and were mainly related to severe IBD flare in 15 cases out of 23 IBD flares reported. Infection was the most commonly reported adverse event in 35 (23.5%) patients, accounting for 45 events. Infections included rhinopharyngitis in 12 cases, gastrointestinal infection in nine, upper respiratory tract infection in nine, flu or flu-like infection in three, sinusitis in two, pharyngitis in two and miscellaneous in nine. Three patients experienced dermatological complication of unknown significance that could be related to vedolizumab therapy or infectious. The other commonly reported adverse events were arthralgia in seven cases, headache in four cases and paraesthesia in one case. One localised prostate adenocarcinoma was observed during the study period in a 58.3-year-old patient who was treated with external radiotherapy and hormone therapy, who achieved complete remission with no subsequent recurrence and vedolizumab therapy was continued.

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