Golimumab for the Treatment of Psoriatic Arthritis
- First Online:
The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of golimumab (Schering-Plough/Centocor) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of active and progressive psoriatic arthritis (PsA) in patients who have responded inadequately to previous disease-modifying anti-rheumatic drugs (DMARDs). The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG) to critically appraise the evidence presented by the manufacturer. This article provides a description of the company submission, the ERG review and the resulting NICE guidance. The ERG critically reviewed the evidence presented in the manufacturer’s submission and identified areas requiring clarification, for which the manufacturer provided additional evidence.
The main clinical effectiveness data were derived from a single phase III randomized controlled trial (GO-REVEAL) that compared golimumab with placebo for the treatment of active and progressive patients who were symptomatic despite the use of previous DMARDs or NSAIDs. The 14-week data showed that, compared with placebo, golimumab 50 mg significantly improved joint disease response as measured by American College of Rheumatology (ACR) 20 (relative risk [RR] 5.73, 95%CI 3.24, 10.56) and Psoriatic Arthritis Response Criteria (PsARC) [RR 3.45, 95% CI 2.49, 4.87], and significantly improved skin disease response as measured by Psoriasis Area and Severity Index (PASI) 75 (RR 15.95, 95% CI 4.62, 59.11). The 24-week absolute data showed that these treatment benefits were maintained. There was a significant improvement in patients’ functional status as measured by Health Assessment Questionnaire change from baseline at 24 weeks (−0.33; p < 0.001). The open-label extension data showed that these beneficial effects were also maintained at 52 and 104 weeks. The ERG identified several issues relating to the clinical effectiveness results. Analyses of the 24-week data were less robust, failing to adjust for treatment contamination due to patient crossover at week 16. It was also unclear if these results were generalizable to clinical practice.
No randomized controlled trial compared the effectiveness of different biologic therapies head-to-head. To compare the effectiveness of the biologics etanercept, infliximab, adalimumab and golimumab, the manufacturer conducted a network meta-analysis, including the comparator palliative care (usual care including use of NSAIDs or DMARDs). The ERG considered the assumption of exchangeability between the trials for the purpose of the network meta-analysis to be acceptable and the statistical approach to be reliable. The results indicated somewhat lower efficacy with golimumab than with comparator biologics.
The ERG identified a number of issues relating to the cost-effectiveness results. The manufacturer calculated incremental cost-effectiveness ratios (ICERs) incorrectly by comparing golimumab with palliative care instead of the most cost-effective alternative (etanercept). Despite the manufacturer’s claim that golimumab was a cost-effective treatment option, the manufacturer’s own model showed that golimumab was unlikely to be cost effective, relative to currently accepted thresholds, when the ICERs were correctly calculated using an incremental analysis (i.e. comparing each treatment to the next best alternative). None of the sensitivity analyses carried out by the manufacturer or the ERG regarding uncertainty in the estimates of clinical effectiveness, the acquisition and administration cost of drugs, the cost of treating psoriasis and the utility functions estimated to generate health outcomes changed this conclusion.
However, a key area in determining the cost effectiveness of biologics was whether they should be treated as a class. The ERG concluded that if all biologics were considered equally effective, then etanercept, adalimumab and golimumab had almost equal costs and equal QALYs, and all had an ICER of about £15 000 per QALY versus palliative care, whilst infliximab, with a higher acquisition cost, was dominated by the other biologics.
The Appraisal Committee altered its position between the Appraisal Consultation Document and the Final Appraisal Determination. It ultimately recommended that golimumab be provided as an option for the treatment of active and progressive PsA in adults only if (i) it is used as described for other tumour necrosis factor inhibitor treatments in ‘Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis’ (NICE clinical guideline 199); and (ii) the manufacturer provides the 100mg dose of golimumab at the same cost as the 50mg dose.
- 1.National Institute for Health and Clinical Excellence. Guide to the methods of technology appraisal. London: NICE, 2008Google Scholar
- 3.Yang H, Epstein D, Bojke L, et al. Evidence Review Group’s report: golimumab for the treatment of psoriatic arthritis. London: NIHR HTA, 2010Google Scholar
- 4.National Institute for Health and Clinical Excellence. Guide to the single technology appraisal (STA) process. London: NICE, 2006Google Scholar
- 10.Dickson R, Bagust A, Boland A, et al. Erlotinib monotherapy for the maintenance treatment of non-small cell lung cancer after previous platinum-containing chemotherapy: a NICE single technology appraisal. Pharmacoeconomics 29 (12): 1051–62Google Scholar
- 11.McKenna C, Maund E, Sarowar M, et al. Dronedarone for the treatment of atrial fibrillation: a NICE single technology appraisal. Pharmacoeconomics. In pressGoogle Scholar
- 12.Holmes M, Carroll C, Papaioannou D. Dabigatran etexilate for the prevention of venous thromboembolism in patients undergoing elective hip and knee surgery: a NICE single technology appraisal. Pharmacoeconomics. In pressGoogle Scholar
- 13.Boyers D, Jia X, Jenkinson D, et al. Eltrombopag for the treatment of chronic idiopathic (immune) thrombocytopenic purpura: a NICE single technology appraisal. Pharmacoeconomics. In pressGoogle Scholar
- 14.Burch J, Griffin S, McKenna C, et al. Omalizumab for severe and persistent asthma in children aged 6 to 11 years: a NICE single technology appraisal. Pharmacoeconomics. In pressGoogle Scholar
- 15.Whyte S, Pandor A, Stevenson M. Bevacizumab for metastatic colorectal cancer: a NICE single technology appraisal. Pharmacoeconomics. In pressGoogle Scholar
- 16.Kilonzo M, Hislop J, Elders A. Pazopanib for the first-line treatment of patients with advanced and/or metastatic renal cell carcinoma: a NICE single technology appraisal. PharmacoEconomics. In pressGoogle Scholar
- 17.National Institute for Health and Clinical Excellence. Golimumab for the treatment of psoriatic arthritis: NICE technology appraisal guidance 220. London: NICE, 2011 [online]. Available from URL: http://guidance.nice.org.uk/TA220 [Accessed 2011 Jun 1]
- 18.Gladman DD, Antoni C, Mease P, et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 2005; 64 Suppl. 2: ii14–7Google Scholar
- 20.Kay LJ, Parry-James JE, Walker DJ. The prevalence and impact of psoriasis and psoriatic arthritis in the primary care population in North East England. Arthritis Rheum 1999; 42 Suppl.: s299Google Scholar
- 22.National Institute for Health and Clinical Excellence. Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis [guide no. 199]. London: NICE, 2010 [online]. Available from URL: http://guidance.nice.org.uk/TA199/Guidance/pdf/English [Accessed 2010 Sep 17]
- 23.Centocor Ltd. A multicenter, randomized, double-blind, placebo-controlled trial of golimumab, a fully human anti-TNFα monoclonal antibody, administered subcutaneously in subjects with active psoriatic arthritis. Malvern (PA): Centocor, 2007 OctGoogle Scholar
- 24.Kavanaugh A, McInnes I, Mease P, et al. Golimumab, a new human tumor necrosis factor antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis twenty-four–week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum 2009; 60 (4): 976–86PubMedCrossRefGoogle Scholar
- 25.Mease P, Ganguly R, Wanke L, et al. How much improvement in functional status is considered important by patients with active psoriatic arthritis: applying the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) group guidelines. Ann Rheum Dis 2004; 63 Suppl. 1: 391Google Scholar
- 27.Joint Formulary Committee. British national formulary. 59th rev. ed. London: Pharmaceutical Press, 2010 MarGoogle Scholar
- 28.National Institute for Health and Clinical Excellence. Appraisal consultation document: golimumab for the treatment of psoriatic arthritis. London: NICE, 2010Google Scholar
- 31.van der Heijde D, Kavanaugh A, Gladman DD, et al. Infliximab inhibits progression of radiographic damage in patients with active psoriatic arthritis through one year of treatment: results from the induction and maintenance psoriatic arthritis clinical trial 2. Arthritis Rheum 2007 Aug; 56 (8): 2698–707PubMedCrossRefGoogle Scholar
- 32.National Institute for Health and Clinical Excellence. Final appraisal determination: golimumab for the treatment of psoriatic arthritis. London: NICE, 2011 [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/12411/53514/53514.pdf [Accessed 2011 Jun 1]
- 33.Clegg DO, Reda DJ, Mejias E, et al. Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. a Department of Veterans Affairs Cooperative Study. Arthritis Rheum 1996; 39 (12): 2013–20Google Scholar