Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn’s Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis

Peyrin–Biroulet, Laurent; Danese, Silvio; Argollo, Marjorie; Pouillon, Lieven; Peppas, Spyros; González-Lorenzo, Marién; Lytras, Theodore; Bonovas, Stefanos

doi:10.1016/j.cgh.2018.06.026

Cited by 129 publications

(113 citation statements)

References 42 publications

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“…With low immunogenicity, and lack of clear data on target levels for mechanistic efficacy, the role of vedolizumab TDM in decision‐making (dose‐escalation or switching therapies) is adjunctive, and would require accounting for multiple clinical factors besides trough concentration. In a systematic review of 10 cohorts, pooled incidence rates of loss of response were 47.9 per 100 person‐years of follow‐up among patients with Crohn's disease and 39.8 per 100 person‐years of follow‐up in patients with ulcerative colitis; dose intensification was able to response to the drug in 53.8% patients with secondary nonresponders; TDM was not routinely performed in these cohorts . Since these data were not blinded or controlled data, it is possible that magnitude of benefit with empiric dose escalation may be overestimated; pivotal GEMINI trials did not identify any difference in efficacy of every 4 vs every 8 week dosing of vedolizumab.…”

Section: Discussionmentioning

confidence: 99%

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Singh

Dulai

Casteele

et al. 2019

Aliment Pharmacol Ther

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SUMMARY Background There has been limited evaluation of the association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases (IBD). Aim To perform a systematic review and meta‐analysis to evaluate the potential role of therapeutic drug monitoring (TDM) for vedolizumab. Methods Through a systematic literature search through 28 February 2019, we identified five cohort studies (558 patients, 42% with ulcerative colitis) reporting the association between vedolizumab trough concentration and clinical outcomes in patients with IBD. We calculated mean difference (MD) in vedolizumab trough concentration in patients achieving vs not achieving clinical outcomes, and qualitatively synthesized thresholds associated with favourable outcomes. Results In patients with UC, median vedolizumab trough concentrations were consistently higher in patients achieving clinical remission (median, 14.3 μg/mL vs 10.5 μg/mL; MD, 5.1 μg/mL, 95% CI, 2.8‐7.4) or endoscopic remission (median, 13.0 μg/mL vs 9.7; MD, 5.1 μg/mL, 95% CI, 2.2‐7.9). In patients with CD, there was no significant difference in median vedolizumab trough concentrations in patients achieving vs not achieving clinical remission (MD, 2.0 μg/mL; 95% CI, −0.5 to 4.5) or endoscopic remission (MD, 3.6 μg/mL; 95% CI, −1.4 to 8.6). In patients with UC, week 6 vedolizumab trough concentrations ≥18.5‐20.8 μg/mL, and maintenance trough concentrations ≥9.0‐12.6 μg/mL were associated with favourable clinical outcomes. Antibodies to vedolizumab were reported in 1.7%‐3.0% patients on maintenance therapy. Conclusion Based on meta‐analysis, patients with UC who achieve endoscopic and clinical remission have significantly higher vedolizumab trough concentration during maintenance therapy. Vedolizumab trough concentration >20 μg/mL at week 6, and >12 μg/mL during maintenance may be associated with better outcomes, though cause‐effect relationship remains unclear. Prospective studies on reactive and proactive therapeutic drug monitoring of vedolizumab (vs empiric dose escalation) are warranted.

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Section: Discussionmentioning

confidence: 99%

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Singh

Dulai

Casteele

et al. 2019

Aliment Pharmacol Ther

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“…For anti‐TNF drugs, primary and secondary nonresponse rates in patients with IBD have been reported to be 10–30% and 20–40%, respectively . Although real‐life data for the newer anti‐integrin and anti‐interleukin drugs is limited and quite variable, similar nonresponse rates as for the anti‐TNF drugs have been observed …”

Section: Therapeutic Drug Monitoringmentioning

confidence: 82%

Achieving Mucosal Healing in Inflammatory Bowel Diseases: Which Drug Concentrations Need to Be Targeted?

Berghe

Gils

Thomas

2019

Clin Pharma and Therapeutics

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Biologicals introduced a major shift in the treatment of patients suffering from inflammatory bowel diseases. Despite providing a tight disease control for many patients, a considerable proportion of patients will fail to respond favorably to treatment or will lose response over time. Therapeutic drug monitoring emerged as a valuable tool to guide clinical decision making as serum drug concentrations have been linked to outcomes. Focusing on mucosal healing as the ultimate treatment goal, different drug concentration thresholds to achieve this outcome have been identified in the literature and are summarized in this review. For therapeutic drug monitoring to be successful in guiding clinical decision making, the used assay, the sampling time point, and the outcome that is aimed for should be taken into account when interpreting drug concentration thresholds. Awareness of these essential aspects among clinicians will improve the implementation of therapeutic drug monitoring and aid in making an evidence‐based decision.

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“…Nevertheless, a significant proportion of patients show an inadequate response to these agents during the induction, while others may even relapse after an initial response . Recent data from a systematic review showed estimated pooled incidence rates of LOR to VDZ of 47.9 and 39.8 per 100 person‐years of follow‐up (95% CI, 26.3‐87.0) in patients with CD and UC, respectively . This fact appears to be progressive during the maintenance phase, with cumulative rates of 20% and 35% at 6 and 12 months, respectively, showing slightly lower rates in CD than in UC (15% vs 18% at 6 months and 30% vs 39% at 12 months, respectively; P = .03) .…”

Section: Discussionmentioning

confidence: 99%

“…This fact appears to be progressive during the maintenance phase, with cumulative rates of 20% and 35% at 6 and 12 months, respectively, showing slightly lower rates in CD than in UC (15% vs 18% at 6 months and 30% vs 39% at 12 months, respectively; P = .03) . In this setting, the strategy of VDZ intensification may restore the response to the drug, but only in around half (54%) of secondary nonresponders . This clinical scenario raises an important question concerning the medical options for patients with UC refractory to anti‐integrin therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, 20% to 35% of patients receiving VDZ can lose response (LOR) during the first 12 months of treatment . The intensification of VDZ can restore the response in some cases, but this strategy is only effective in approximately 54% of secondary nonresponders . These results show that a relevant proportion of patients failing anti‐integrin therapy still need alternative treatment options.…”

Section: Introductionmentioning

confidence: 99%

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The combination of granulocyte‐monocyte apheresis and vedolizumab: A new treatment option for ulcerative colitis?

Rodríguez‐Lago

Benítez

Sempere

et al. 2019

J of Clinical Apheresis

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Objectives To assess the effectiveness and safety of combining granulocyte‐monocyte apheresis (GMA) and vedolizumab (VDZ) in patients with refractory ulcerative colitis (UC). Methods This retrospective, multicentre pilot study included all UC patients receiving both GMA and VDZ. We recorded data on GMA sessions, demographic characteristics, and clinical response. Effectiveness was assessed 1 and 6 months after finishing the GMA using the partial Mayo score, C‐reactive protein, and fecal calprotectin levels. Data were also compiled on VDZ intensification, use of new immunomodulators and colectomy during follow‐up. Results Eight patients were included (mean age 46 years; 63% female; mean disease duration, 132 months; 50% E3). GMA was started after a loss of response to VDZ in all cases (25% primary nonresponse and 75% secondary loss of response). All had previously received anti‐TNF agents. VDZ was prescribed as the second‐, third‐, or fourth‐line biologic in 37%, 50%, and 13% of cases, respectively. Patients had a mean baseline partial Mayo score of 7.5 (SD 2.1) and received a median of 15 GMA sessions (range 5‐38). After a median follow‐up of 7.5 months (IQR 5‐12), partial Mayo score decreased after 1 and 6 months (P = .01 and .06, respectively). Three patients (38%) achieved steroid‐free clinical remission and five (63%) withdrew VDZ. Colectomy rate was 38%. No adverse events were observed during the combination therapy. Conclusions This small case series suggests that combining GMA with VDZ could be a treatment option in selected cases of UC with an inadequate response to this biologic agent.

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Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn’s Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis

Cited by 129 publications

References 42 publications

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Systematic review with meta‐analysis: association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases

Achieving Mucosal Healing in Inflammatory Bowel Diseases: Which Drug Concentrations Need to Be Targeted?

The combination of granulocyte‐monocyte apheresis and vedolizumab: A new treatment option for ulcerative colitis?

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