Effectiveness of vedolizumab dose intensification to achieve inflammatory bowel disease control in cases of suboptimal response

Abstract

BackgroundDespite the proven efficacy of vedolizumab (VDZ) for ulcerative colitis (UC) and Crohn’s disease (CD), suboptimal response is commonly encountered. However, data regarding the effectiveness of dose intensification (by interval shortening) to achieve response are limited.ObjectivesWe evaluated the effectiveness of dose intensification at achieving response in patients with a previously suboptimal response to VDZ. Additionally, we aimed to identify predictors of response to this strategy.MethodsWe performed a retrospective cohort study of patients who underwent VDZ dose intensification for suboptimal response. Clinical disease activity was evaluated at the point of dose intensification (baseline) and at weeks 12 and 24. Response was defined as Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) reduction of ≥3, and remission as HBI <5 or SCCAI <3.ResultsA total of 36 patients received dose intensification to 4-weekly infusions: 18 CD, 14 UC and 4 inflammatory bowel disease-unclassified (analysed in the UC group). Median SCCAI scores fell from 6 (range 0–11) at baseline to 4 (0–6, p=0.008) at week 24, while HBI scores did not change significantly (4 (0–27) and 3 (0–8), p=0.092). Overall median C reactive protein (CRP) fell from 6 mg/L (1–23) to 2 mg/L (1–17, p=0.011). Of 20 patients with clinically active disease at baseline, 10 (50%) responded, of whom 4 (20%) achieved remission at week 24. Univariate analysis demonstrated low baseline CRP (p=0.045) and response at week 12 (0.020) were associated with week 24 response.ConclusionsOur findings demonstrate VDZ dose intensification to be effective at achieving clinical response in half of patients. Low baseline CRP and response at week 12 are potential predictors of week 24 response.

Vedolizumab Dose Escalation: In for a Penny, in for a Pound?

“…These findings are broadly in keeping with a metanalysis of 4 studies (comprising 2 full articles and 2 abstracts), with a combined cohort of 111 patients with IBD, that demonstrated a random-effects pooled efficacy rate of 53.8% [2]. They are also in keeping with our own published cohort of 36 dose-escalated patients (18 Crohn's disease (CD), 18 UC), in which a 50% response rate was observed [3]. Moreover, rates of week 28 response to dose intensification for CD and UC reported as part of the GEMINI longterm extension were also similar at 17/32 (54%) and 31/57 (53%), respectively.…”

“…Given the financial implications of such a strategy, it would clearly be desirable to identify patients most likely to respond to escalation, thus allowing for a more personalised approach to treatment adjustment and judicious use of a high-cost drug. For example, there are some data that suggest that a lower CRP at the point of escalation may be favourable [3]. Nevertheless, more and more specific predictors and biomarkers are badly needed.…”

Editorial: vedolizumab in inflammatory bowel diseases—less is more? Authors’ reply

“…As noted by Drs. Townsend and Subramanian, there is a place for Q4W dosing in clinical practice, as data from multiple studies show that responses can be re‐captured with dose escalations in cases of suboptimal response or loss of response 4‐6 . The current study was not able to determine patient or disease characteristics that may predict loss of adequate response after de‐escalation of dosing from Q4W to Q8W given the low number of relapses in this population (11.6%).…”

Putting Crohn’s on the MAP: Five Common Questions on the Contribution of Mycobacterium avium subspecies paratuberculosis to the Pathophysiology of Crohn’s Disease

“…104 weeks—RX: 31/102 (16/111) p < 0.005 Borody et al [ 79 ] Anti-mycobacterial therapy in Crohn’s disease heals mucosa with longitudinal scars 52 Endoscopic ulcer healing in 56% of patients at 12 months follow-up colonoscopy (22/39) Gui et al [ 76 ] Two-year-outcomes analysis of Crohn’s disease treated with rifabutin and macrolide antibiotics 52 (6 dropped out and 46 analyzed) A reduction in the Harvey–Bradshaw Crohn’s disease activity index An improvement in inflammatory parameters observed at 18 months compared with pre-treatment levels An increase in serum albumin at 12 months At 6 months ( p = 0.004) At 24 months ( p < 0.001). Reduction in ESR ( p = 0.009) and C-reactive protein ( p = 0.03) ( p = 0.04) Honap et al [ 83 ] Anti-Mycobacterium paratuberculosis (MAP) therapy for Crohn’s disease: an overview and update 41 Symptomatic benefit in 46% of patients. − 63% of these patients had improved biochemical markers, radiological or endoscopic indices p = 0.04 Agrawal et al [ 30 ] Targeted Combination Antibiotic Therapy Induces Remission in Treatment-Naïve Crohn’s disease: A Case Series 8 Clinical remission (CDAI < 150) Improvement in inflammatory markers in all 8 patients receiving AMAT as sole therapy by 6 weeks Median CDAI score decreased from 289 prior to treatment to 62 at the 12-month follow-up ( p < 0.001).…”