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

Patients and Methods

Study Population

From June to December 2014, 294 patients with IBD including 173 with CD and 121 with UC were enroled in a national multi-centre prospective cohort study (OBSERV-IBD cohort) conducted at 41 centres. Inclusion criteria before starting vedolizumab were active UC (partial Mayo score >4) or CD (Harvey-Bradshaw Index ≥6) and inadequate response to, lost response to, or intolerance to either conventional therapy or at least one anti-TNF agent.[16] Patients were treated with vedolizumab and followed from the first infusion at week 0 through week 162. Physicians were committed by the ANSM to collect effectiveness and safety information on a prospective basis independently from any commercial entity. The exclusion criteria included unclassified colitis, extraintestinal manifestation without significant IBD activity as the initial indication for vedolizumab, prevention of postoperative CD recurrence, ostomy and pregnancy or lactation. The protocol was approved by an ethics committee (CCTIRS N° 15.403). We herein present data on effectiveness and safety after week 54 through week 162. Effectiveness and safety results from week 6 to week 54 were previously published.[10,12] The patient demographic and clinical characteristics at week 0 are presented in Table S1.

Vedolizumab Induction Therapy

Vedolizumab induction therapy consisted of three intravenous infusions of 300 mg at week 0, 2 and 6. Thereafter, vedolizumab maintenance therapy consisted of an intravenous infusion of 300 mg every 8 weeks through week 54.[3–5] No recommended tapering schedule or stopping rules were defined for the concomitant administration of steroids and/or immunomodulators. The optimisation of vedolizumab therapy at a dose of 300 mg every 4 weeks in patients who did not have a sufficient response to vedolizumab therapy and de-escalation of vedolizumab therapy to a standard regimen in patients re-achieving steroid-free clinical remission after optimisation were also included at the investigator's discretion.

Follow-up

All of the patients were submitted to a standardised follow-up protocol consisting of a physical examination, calculation of HBI or partial Mayo clinic score for CD and UC patients, respectively, CRP (mg/L), haemoglobin (g/dL), leucocytes (/109/L) and platelet (/109/L) counts, and information about adverse events.[17,18] The evaluations were performed at week 81, 108, 135 and 162. Endoscopic evaluations were suggested between week 54 and 162 but were not mandatory.

Outcome Measures

The primary outcome measure was steroid-free clinical remission at week 162. Clinical remission was defined as HBI ≤4 for CD patients and a partial Mayo Clinic score <3 with a combined stool frequency and rectal bleeding subscore of ≤1 for UC.[16] The secondary outcomes were steroid-free clinical remission at weeks 81, 108, 135 and 162; clinical remission; clinical response; steroid-free clinical response rates at weeks 81, 108, 135 and 162; and safety through week 162. Clinical response was defined as a reduction in HBI of at least 3 points from the baseline score at week 0 for CD patients and as a reduction in the partial Mayo Clinic score from the baseline score at week 0 of at least 3 points and a decrease of at least 30%, with a decrease of at least 1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1 from the baseline score at week 0 for UC patients.[16] Steroid-free means the absence of any dose of any oral steroid (prednisone, prednisolone and/or budesonide) or rectal use of betamethasone. The Mayo Clinic endoscopic subscore and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were both used to assess endoscopic activity for UC patients. Mucosal healing was defined either as the absence of any ulcer for CD patients and as a Mayo Clinic endoscopic subscore of 0 or 1 for UC patients.[19,20] The rate of persistence of vedolizumab was assessed from week 0 to week 162 in the overall population. Safety was assessed by the physician in charge and retrospectively assessed from patient records. Severe adverse events were defined as treatment interruption, hospitalisation, persistent disability or damage, colectomy or death.

Statistical Analysis

All patients were evaluated from the week 54 visit through week 162. All analyses were performed in an intent-to-treat manner. Patients who discontinued vedolizumab therapy between week 54 and week 162 were considered nonresponders with the exception of patients who discontinued vedolizumab therapy in steroid-free clinical remission for pregnancy and by mutual agreement with the investigator. In the latter cases, patients were censured at the time of vedolizumab discontinuation. Qualitative data are expressed as a number (%) and quantitative data are expressed as a mean ± the standard deviation (SD) or median [interquartile range]. The proportions of patients with clinical remission and clinical response, limited to steroid-free or not, were compared to patients with CD and UC at every time point using Chi-square test without correction for multiple tests. The proportions of patients who met the criteria for the latter end points during the present follow-up of maintenance therapy were computed relative to the whole population included at week 0. The CRP level, the HBI and partial Mayo Clinic score were compared to week 0 for every other time point using Wilcoxon's matched pairs signed rank test. The persistence of vedolizumab was calculated using the Kaplan-Meier method from week 0 to week 162. The survival distributions were compared using the log-rank test. To identify the independent factors, two Cox proportional hazard models were adjusted separately for patients with CD and UC with an ascending stepwise procedure. Variables with P < 0.10 in univariate analysis were considered to be potential adjustment variables for the multivariate analysis. The continuous variables were converted to qualitative values using the dichotomy from the median value in two distinct groups of equal size. Variables with P < 0.10 in the univariate analysis were considered potential control variables for the multivariate analysis. All of the analyses were two-tailed, and p-values less than 0.05 were considered significant. All of the statistical evaluations were performed using SPSS statistical software (SPSS Inc, v17, Chicago, IL). All of the authors had access to the study data and reviewed and approved the final manuscript.

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