BACKGROUND: Several 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.
OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of CZP 
and SEC for treating active PsA in adults in whom DMARDs have been inadequately 
effective.
DESIGN: Systematic review and economic model.
DATA SOURCES: Fourteen 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 METHODS: Clinical 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.
RESULTS: Nineteen 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).
CONCLUSIONS: SEC 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 WORK: Trials are needed to inform effectiveness of biologics in 
biologic-experienced populations.
STUDY REGISTRATION: This study is registered as PROSPERO CRD42016033357.
FUNDING: The National Institute for Health Research Health Technology Assessment 
programme.