Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost-effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost-effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from the GEMINI1 trial, which is a Phase III, multicentre, randomised, doubleblind, placebo-controlled trial designed to evaluate the efficacy and safety of vedolizumab as an induction and maintenance treatment in patients with moderate-to-severe active UC who had an inadequate response to, loss of response to, or intolerance to conventional therapy or anti-Tumour necrosis factor-alpha (TNF-). The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post-hoc subgroup analyses, patients with or without prior anti-TNF-therapy, vedolizumab performed better then placebo (p-value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab and the frequency and types of adverse events were similar between the vedolizumab and placebo group but the evidence was limited to shortterm follow-up. There were a number of limitations and uncertainties in the clinical evidence base which warrant caution in its interpretation. In particular, the post-hoc subgroup analyses and high dropout rates in the maintenance phase of the GEMINI1 trial. The company also presented a network meta-analysis of vedolizumab versus other biologics therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects since fixed effects models were Key Points for Decision Makers Vedolizumab appears to be more effective in both the induction and maintenance phase compared with placebo in patients with moderate-to-severe active ulcerative colitis who have had an inadequate response to, loss of response to, or intolerance to conventional therapy or TNF-inhibitor. However, the subgroup analyses for patients with or without prior TNF-inhibitor therapy were post-hoc and the study was not powered for these assessments.  The findings of the network meta-analysis of vedolizumab versus TNF-inhibitor are limited due to a number of uncertainties in treatment effects. In addition, there is currently no head-to-head randomised 3 controlled trial comparing vedolizumab to other biologic therapies indicated for moderate-to-severe ulcerative colitis.  The National Institute for Health and Care Excellence (NICE) Appraisal Committee recommended vedolizumab within its licence indication but only if the company provides vedolizumab with the discount agr...

Cost-Effectiveness Analysis of Vedolizumab Compared with Other Biologics in Anti-TNF-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan

“…Second, previous cost-effectiveness analyses have characterized disease severity during the maintenance phase using three health states, defined by patients' Mayo score: remission (Mayo score 0-2), mild UC (Mayo score 3-5), and moderate-to-severe UC (Mayo score 6-12) [17,18,60]. This approach has been criticized by an independent Evidence Review Group (ERG) during a NICE single technology appraisal of VDZ for the treatment of patients with moderate-to-severe UC in the UK, as this approach ignored that patients in the mild and moderate-to-severe UC health states can include both patients with and without response [61]. The ERG suggested that this issue could have been addressed by modeling the maintenance phase transitions between moderate-to-severe UC, response, and remission health states, using the patient-level data from the GEMINI I clinical trial [15,61].…”

“…This approach has been criticized by an independent Evidence Review Group (ERG) during a NICE single technology appraisal of VDZ for the treatment of patients with moderate-to-severe UC in the UK, as this approach ignored that patients in the mild and moderate-to-severe UC health states can include both patients with and without response [61]. The ERG suggested that this issue could have been addressed by modeling the maintenance phase transitions between moderate-to-severe UC, response, and remission health states, using the patient-level data from the GEMINI I clinical trial [15,61]. We followed the ERG's recommendation, and the model structure is in line with previous models [62].…”

Pharmacologic therapies for severe steroid refractory hospitalized ulcerative colitis: A network meta‐analysis

“…Several studies have performed network meta‐analyses assessing the efficacy of various anti‐tumor necrosis factor (TNF)‐α agents for the treatment of UC . Essat et al found eight studies among four anti‐TNF‐α agents and have shown that infliximab was superior to other agents for clinical response, remission, and mucosal healing among anti‐TNF‐α naive patients in the induction phase . Thorlund et al and Stidham et al found comparable efficacy between three anti‐TNF‐α agents .…”

“…36,38 Essat et al found eight studies among four anti-TNF-α agents and have shown that infliximab was superior to other agents for clinical response, remission, and mucosal healing among anti-TNF-α naive patients in the induction phase. 36 Thorlund et al and Stidham et al found comparable efficacy between three anti-TNF-α agents. 37,38 These studies did not include any loop in the network and lacked assessment of the inconsistency factor making it difficult to interpret the strength of evidence.…”

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

“…209 210 Although nasopharyngitis and arthritis have been reported as side effects of vedolizumab, 211 212 extensive clinical experience over the past eight years has amply validated the safety and effectiveness of vedolizumab for the induction and maintenance of remission in patients with Crohn's disease and ulcerative colitis. [213][214][215][216][217][218] Progressive multifocal leukoencephalopathy has not been reported with vedolizumab and JC virus does not need to be checked before starting treatment. 219 Whenever a new agent shows efficacy and safety, the question arises whether to use it as the primary biologic treatment, to reserve it for rescue when anti-TNF therapy is ineffective, or to introduce it for maintenance of remission induced by another drug that is too toxic to use long term (for example, steroids, ciclosporin).…”