Certolizumab pegol and secukinumab for treating active psoriatic arthritis following inadequate response to disease-modifying antirheumatic drugs: a systematic review and economic evaluation

Abstract

BackgroundSeveral biologic therapies are approved by the National Institute for Health and Care Excellence (NICE) for psoriatic arthritis (PsA) patients who have had an inadequate response to two or more synthetic disease-modifying antirheumatic drugs (DMARDs). NICE does not specifically recommend switching from one biologic to another, and only ustekinumab (UST; STELARA®, Janssen Pharmaceuticals, Inc., Horsham, PA, USA) is recommended after anti-tumour necrosis factor failure. Secukinumab (SEC; COSENTYX®, Novartis International AG, Basel, Switzerland) and certolizumab pegol (CZP; CIMZIA®, UCB Pharma, Brussels, Belgium) have not previously been appraised by NICE.ObjectiveTo determine the clinical effectiveness and cost-effectiveness of CZP and SEC for treating active PsA in adults in whom DMARDs have been inadequately effective.DesignSystematic review and economic model.Data sourcesFourteen databases (including MEDLINE and EMBASE) were searched for relevant studies from inception to April 2016 for CZP and SEC studies; update searches were run to identify new comparator studies.Review methodsClinical effectiveness data from randomised controlled trials (RCTs) were synthesised using Bayesian network meta-analysis (NMA) methods to investigate the relative efficacy of SEC and CZP compared with comparator therapies. A de novo model was developed to assess the cost-effectiveness of SEC and CZP compared with the other relevant comparators. The model was specified for three subpopulations, in accordance with the NICE scope (patients who have taken one prior DMARD, patients who have taken two or more prior DMARDs and biologic-experienced patients). The models were further classified according to the level of concomitant psoriasis.ResultsNineteen eligible RCTs were included in the systematic review of short-term efficacy. Most studies were well conducted and were rated as being at low risk of bias. Trials of SEC and CZP demonstrated clinically important efficacy in all key clinical outcomes. At 3 months, patients taking 150 mg of SEC [relative risk (RR) 6.27, 95% confidence interval (CI) 2.55 to 15.43] or CZP (RR 3.29, 95% CI 1.94 to 5.56) were more likely to be responders than patients taking placebo. The NMA results for the biologic-naive subpopulations indicated that the effectiveness of SEC and CZP relative to other biologics and each other was uncertain. Limited data were available for the biologic-experienced subpopulation. Longer-term evidence suggested that these newer biologics reduced disease progression, with the benefits being similar to those seen for older biologics. The de novo model generated incremental cost-effectiveness ratios (ICERs) for three subpopulations and three psoriasis subgroups. In subpopulation 1 (biologic-naive patients who had taken one prior DMARD), CZP was the optimal treatment in the moderate–severe psoriasis subgroup and 150 mg of SEC was optimal in the subgroups of patients with mild–moderate psoriasis or no concomitant psoriasis. In subpopulation 2 (biologic-naive patients who had taken two or more prior DMARDs), etanercept (ETN; ENBREL®, Pfizer Inc., New York City, NY, USA) is likely to be the optimal treatment in all subgroups. The ICERs for SEC and CZP versus best supportive care are in the region of £20,000–30,000 per quality-adjusted life-year (QALY). In subpopulation 3 (biologic-experienced patients or patients in whom biologics are contraindicated), UST is likely to be the optimal treatment (ICERs are in the region of £21,000–27,000 per QALY). The optimal treatment in subpopulation 2 was sensitive to the choice of evidence synthesis model. In subpopulations 2 and 3, results were sensitive to the algorithm for Health Assessment Questionnaire-Disability Index costs. The optimal treatment is not sensitive to the use of biosimilar prices for ETN and infliximab (REMICADE®, Merck Sharp & Dohme, Kenilworth, NJ, USA).ConclusionsSEC and CZP may be an effective use of NHS resources, depending on the subpopulation and subgroup of psoriasis severity. There are a number of limitations to this assessment, driven mainly by data availability.Future workTrials are needed to inform effectiveness of biologics in biologic-experienced populations.Study registrationThis study is registered as PROSPERO CRD42016033357.FundingThe National Institute for Health Research Health Technology Assessment programme.

Cost-Effectiveness Analysis of Sequential Biologic Therapy with Ixekizumab Versus Secukinumab in the Treatment of Active Psoriatic Arthritis with Concomitant Moderate-to-Severe Psoriasis in the UK

“…PsARC nonresponders and patients who ceased continuous therapy transitioned to the trial period of the next bDMARD treatment or BSC if they discontinued the last treatment in the sequence. An annual all-cause discontinuation rate of 16.5% was assumed for bDMARD continuous therapy, in accordance with previous models and consistent with recent NICE submissions [12,13]. In the absence of drug-specific data, this discontinuation rate was applied uniformly across all bDMARD comparators and treatment lines and assumed to be independent of Health Assessment Questionnaire (HAQ) and Psoriasis Area and Severity Index (PASI) scores.…”

“…The model includes four health states: bDMARD trial period, continuous bDMARD treatment, best supportive care (BSC) and death. The analysis used a lifetime horizon in the base case, in line with previous models [12,13,[16][17][18][19]. The model incorporated mortality data for the normal UK population [20] adjusted for an increased disease-specific mortality risk [21] regardless of whether patients respond to treatment.…”

“…Skin response might also play a greater role in combined dermatology/rheumatology clinics. The IL-17A antagonists and other recent bDMARDs have demonstrated robust efficacy with respect to PASI (in addition to PsARC) in PsA [13,[31][32][33]. While the model allows different levels of PASI response to be used (at least a 75%, 90% or 100% reduction in baseline PASI; i.e.…”

“…To address the lack of published cost-effectiveness analyses (CEAs) of ixekizumab in PsA in the UK, we conducted a CEA from the perspective of the UK National Health Service (NHS) using an adaptation of the economic framework of the most recent version of the York model, as the York model and updated versions of it are considered the 'gold standard' in this setting [11][12][13]. We aimed to assess the cost-effectiveness of ixekizumab versus secukinumab in patients with PsA and concomitant moderate-to-severe plaque psoriasis.…”

How to Appropriately Extrapolate Costs and Utilities in Cost-Effectiveness Analysis

“…Explicit consideration of any differences is not typically undertaken, and more often than not simple sensitivity analysis will instead be employed, for example increasing costs to a specified amount to reflect a more severe case mix modelled in the analysis. For example in a recent model developed as part of a NICE appraisal for psoriatic arthritis, health state costs for patients experiencing more extensive psoriasis were increased, under the expectation that they would utilise more expensive treatments [37].…”