Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis

Cawson et al. BMC Musculoskeletal Disorders 2014, 15:26 http://www.biomedcentral.com/1471-2474/15/26 RESEARCH ARTICLE Open Access Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis Matthew Richard Cawson1, Stephen Andrew Mitchell2*, Chris Knight1, Henry Wildey1, Dean Spurden3, Alex Bird3 and Michelle Elaine Orme4 Abstract Background: An updated economic evaluation was conducted to compare the cost-effectiveness of the four tumour necrosis factor (TNF)-α inhibitors adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic arthritis (PsA) where response to standard treatment has been inadequate. Methods: A systematic review was conducted to identify relevant, recently published studies and the new trial data were synthesised, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). A previously developed economic model was updated with the new meta-analysis results and current cost data. The model was adapted to delineate patients by PASI 50%, 75% and 90% response rates to differentiate between psoriasis outcomes. Results: All four licensed TNF-α inhibitors were significantly more effective than placebo in achieving PsARC response in patients with active PsA. Adalimumab, etanercept and infliximab were significantly more effective than placebo in improving HAQ scores in patients who had achieved a PsARC response and in improving HAQ scores in PsARC non-responders. In an analysis using 1,000 model simulations, on average etanercept was the most cost-effective treatment and, at the National Institute for Health and Care Excellence willingness-to-pay threshold of between £20,000 to £30,000, etanercept is the preferred option. Conclusions: The economic analysis agrees with the conclusions from the previous models, in that biologics are shown to be cost-effective for treating patients with active PsA compared with the conventional management strategy. In particular, etanercept is cost-effective compared with the other biologic treatments. Background Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease characterised by joint involvement and several heterogeneous extra-articular manifestations, including enthesitis, dactylitis and dermatological involvement of the skin and nails (1). The broad involvement of articular and non-articular sites can have a significant impact on patients’ function and quality of life [2]. The presentation of PsA has been categorised into five overlapping clinical patterns; oligoarthritis (22% to 37% of patients); polyarthritis * Correspondence: 2 Abacus International, 6 Talisman Business Centre, Talisman Road, Bicester OX26 6HR, UK Full list of author information is available at the end of the article (36% to 41% of patients); arthritis of distal interphalangeal joints (up to 20% of patients); spondylitis (7% to 23% of patients); and arthritis mutilans (approximately 4%) [3,4]. The prevalence of PsA is greater among psoriasis patients, with a prevalence rate spanning a wide range from 7% to 26% [5]. Around seventy per cent of PsA patients develop joint complications usually around ten years after developing skin symptoms, whereas, 10-15% of patients suffer from joint damage before developing psoriasis, and in the remaining 10-15% of patients, these symptoms may manifest simultaneously [6]. There are a number of published recommendations for the management of PsA [7,8]. Treatment is dependent on the type and severity of the skin and joint involvement. Patients with mild-to-moderate PsA are frequently given © 2014 Cawson et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cawson et al. BMC Musculoskeletal Disorders 2014, 15:26 http://www.biomedcentral.com/1471-2474/15/26 non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular steroid injections. Patients with more severe PsA and persistent arthritis not responding to NSAIDs are treated with disease-modifying anti-rheumatic drug (DMARD) therapy. Methotrexate, sulphasalazine and cyclosporine-A are the commonly used DMARDs [9]. More recently, newer treatments targeting the inflammatory cascade and preventing disease progression have been introduced including tumour necrosis factor (TNF)α inhibitors. These drugs are used as monotherapy or in combination with the traditional nonbiologic DMARDs such as methotrexate. The combination regimen is used in patients with severe disease or with ongoing joint damage and disease progression [6]. While there is evidence to suggest that treatment with concomitant methotrexate is beneficial compared with TNF-α monotherapy (resulting from fewer withdrawals due to adverse events) [10], this has not been a universal finding [11]. There are currently no head-to-head randomised controlled trials (RCTs) comparing the TNF-α inhibitors to each other and therefore attempts to compare the relative efficacy and safety of these agents have relied upon a qualitative review of the published evidence or metaanalytic techniques [12]. A recently published metaanalysis assessing the relative efficacy of the currently available TNF-α inhibitors concluded that etanercept was the most efficacious treatment (as measured by American College of Rheumatology (ACR) response) compared with infliximab and adalimumab [13]. RCT data are also available for the TNF-α inhibitor golimumab [14] which has recently been recommended by the National Institute for Health and Care Excellence (NICE) as an option for the treatment of active and progressive PsA in adults, in the UK [15]. An economic evaluation developed for the NICE review concluded that etanercept, infliximab and adalimumab are costeffective versus palliative care [16,17]. However, it is unclear how cost-effective golimumab is compared with palliative care (conventional management strategy) and head-to-head with these three biologics. Therefore, this paper presents a new economic evaluation supported by an updated systematic review and metaanalysis that included recent data for golimumab, the objective being to determine the relative cost-effectiveness of all UK licensed biological disease-modifying antirheumatic drugs (bDMARDs) for the treatment of active, progressive PsA in patients with inadequate response to previous DMARDs. The paper presents the results from the updated meta-analysis for all clinical measures of efficacy used in the economic model (note that other clinical measures such as ACR response are reported elsewhere [18]). The meta- (...truncated)