Certolizumab Pegol for Treating Rheumatoid Arthritis Following Inadequate Response to a TNF-α Inhibitor: 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 (UCB Pharma) of certolizumab pegol (CZP;Cimzia®) to submit evidence of its clinical and cost-effectiveness for the treatment of rheumatoid arthritis (RA) following inadequate response to a tumour necrosis factor-alpha inhibitor (TNFi). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost-effectiveness of the technology, based upon the company's submission to NICE. The clinical effectiveness evidence in the company's submission for CZP was based predominantly on six randomised controlled trials (RCTs) comparing the efficacy of CZP against placebo. The clinical-effectiveness review identified no head to head evidence on the efficacy of CZP against the comparators within the scope; therefore the company performed a network meta-analysis (NMA). The company's NMA concluded that CZP had a similar efficacy to that of its comparators. The company submitted a Markov model that assessed the incremental cost effectiveness of CZP versus comparator biologic disease-modifying antirheumatic drugs (bDMARDs) for the treatment of RA from the perspective of the National Health Service for three decision problems each of which followed an inadequate response to a TNFi. These were (i) a comparison against rituximab (RTX) in combination with methotrexate (MTX); (ii) a comparison against bDMARDs when RTX was contraindicated or withdrawn due to an adverse event; and (iii) a comparison against bDMARDs when MTX was contraindicated or withdrawn due to an adverse event. Results from the company's economic evaluation showed that CZP resulted in similar number of QALYs produced at similar, or lower, costs as comparator bDMARDs. The commercial-in-2 confidence patient access schemes for abatacept and tocilizumab could not be incorporated by the company, but were incorporated by the ERG in a confidential appendix for the NICE Appraisal Committee (AC). The company estimated that the addition of CZP before RTX in a sequence for patients who could receive MTX, produced more quality-adjusted life years (QALYs) at an increased cost, with a cost per QALY of £33,222. Following a critique of the model, the ERG undertook exploratory analyses that did not change the conclusions reached based on the company's economic evaluation in relation to the comparison with bDMARDs. The ERG estimated that where CZP replaced RTX, CZP was dominated, as it produced less QALYs at an increased cost. The AC concluded that there was little difference in effectiveness between CZP and comparator bDMARDs and that equivalence among bDMARDs could be accepted. The AC consequently recommended CZP plus MTX for people for whom RTX is contraindicated or not tolerated and CZP monotherapy for people for whom MTX is contraindicated or not to...

Cost-utility analyses of targeted immunomodulators in rheumatoid arthritis: systematic review

“…Of the 31 models included in this review, 25 studies were published in peer-reviewed journals 5,[14][15][16][17][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] , five of them were NICE technology appraisals [11][12][13]40,41 , and two models were identified from the gray literature. 42,43 Table 1 provides an overview of each profiled publication.…”

“…With regard to geography, the majority of models were conducted from the US or UK perspectives, including nine UK models 5,[11][12][13][22][23][24]40,41 (includes five NICE HTAs [11][12][13]40,41 ) and nine US models. 14,15,[25][26][27][28][29]42,43 Of the US models, five of them were sponsored by pharmaceutical companies, two of them by academic consortia, and one each was sponsored by an HTA body or an analytics company.…”

“…All models focused on evaluating the CU of one or more new or previously-introduced interventions, with four models of tocilizumab, 22,29,34,38 four of tofacitinib, 13,14,16,17 three each of sarilumab, 12,15,26 and certolizumab, 30,39,41 two of adalimumab 5,33 and etanercept, 27,31 and one each of abatacept, 41 baricitinib, 11 and rituximab. 35 Six studies evaluated specific sequences of TIMs, 23,27,28,36,41,43 while four studies each evaluated multiple drugs within a class.…”

“…Framework selection is therefore a key factor in estimating the effectiveness of a given treatment over time. Of the 31 models included in this systematic review, 20 (65%) included a patient-level simulation component, with 11 (35%) structured with a single structure 5,14,17,22,25,29,[34][35][36]41,43 and 9 (23%) structured as two-stage simulation models. [11][12][13]15,23,24,26,27,40 The remaining 11 (35%) models were set up as Markov cohort models.…”

Systematic Review of Economic Evaluations of Cycling Versus Swapping Medications in Patients With Rheumatoid Arthritis After Failure to Respond to Tumor Necrosis Factor Inhibitors

“…The choice of comparator may be another source of bias: 11 of the 19 comparisons evaluated rituximab versus TNFi, which is interesting given that, at least in the US, 70% of patients who swap to an agent with other mechanisms of action switch to abatacept . Furthermore, although golimumab and certolizumab pegol have been on the market since 2009, only the latter was analyzed as an alternative to agents with other mechanisms of action ; however, new non‐TNFi drugs, tocilizumab (model excluded because the patients were TNFi‐naive at entry to the model ) and tofacitinib, have been explicitly considered. A recent analysis reported nonbiologic triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) to be cost‐effective in comparison to etanercept when used as first‐line therapy .…”