1. PACE (Psoriatic Arthritis Costs Evaluation Study) (Psoriatic Arthritis Costs Evaluation Study)

2. Razionale

3. Objective To evaluate costs, benefits and cost effectiveness of anti tumor necrosis factor (TNF) agents in psoriatic arthritis (PsA) patients with inadequate response to traditional standard treatment.

4. Methods Technique Prospective longitudinal cost and outcomes (clinical and Health Related Quality of Life) analysis SubjectsPatients enrolled from 9 centres participating to the prospective data collection PerspectiveNational Health Service (NHS) and societal CostsDirect healthcare costs (drugs, ambulatory care, day case treatments, hospitalizations) quantified using NHS tariffs and expressed in Euro 2003, and indirect cost (number of working days lost) quantified using human capital approach Time12 months

5. Cost-utility analysis Quality Adjusted Life Year

6. QALY (Quality Adjusted Life Year) QALY is a composite measure that takes into account both survival and quality of life. In the United Kingdom recent recommendations for the treatment by the National Institute of Clinical Excellence (NICE) seems to suggest a threshold of about £30,000 (€45,000) per QALY*. In the last few years, a threshold of € 60.000 per QALY gained has been proposed for Italy °. * National Institute for Clinical Excellence. Guide to the Methods of Technology Appaisal. (2004). Reference NO515. Available at http://www.nice.org.uk/TAP_Methods.pdfhttp://www.nice.org.uk/TAP_Methods.pdf ° Messori A, Santarlasci B, Trippoli S, Vaiani M. Controvalore economico del farmaco e beneficio clinico: stato dell’arte della metodologia e applicazione di un algoritmo farmacoeconomico. PharmacoEconomics – Italian Research Articles 2003; 5: 53-67

7. RESULTS

8. Clinical sub-set Axial n (%)19 (18.8%) Peripheral n (%)87 (81.3%) Peripheral entesitis n (%)1 (0.9%) Male patients Male patients n (%)51 (47.7%) Age (years) Age (years) mean (SD)49.68 (11.7) Years since diagnosis of PsA Years since diagnosis of PsA mean (SD)7.32 (7.4) VAS pain (patient) 62.83(21.10) VAS pain (physician) 60.15(13.33) HAQ1.14(0.57) PASI5.04(7.29) BASDAI5.95(1.82) BASFI43.37(24.49) EQ-5D VAS 47.17(66.58) Baseline characteristics (N=107)

9. Cost at baseline (6-months) MeanSt.dev Overall direct cost: 942.871,156.11 cost of drugs cost of drugs630.85963.20 cost to the NHS cost to the NHS883.091,148.65 In direct cost 576.301,565.11 Social cost 1,519.171,945.16

10. Change in clinical parameters (t12-t0) MeanSD 95% CI lower-upper t-test Pvalu e Reduction in VAS pain (patient) 31.1827.5625.88-36.4911.65P<0.0001 Reduction in VAS pain (physician) 33.8319.0630.04-37.6317.69P<0.0001 Reduction in VAS activity ( patient) 31.1824.4826.44-35.9113.05P<0.0001 Reduction in HAQ 0.480.660.35-0.627.19P<0.0001 Reduction in PASI score 3.757.032.40-5.105.50P<0.0001 Reduction in BASDAI score 2.722.392.26-3.1811.81P<0.0001 Reduction in BASFI score 17.7227.8912.38-23.076.57P<0.0001

11. anti-TNF therapy 144 individuals 144 individuals 107 received anti-TNF-a 107 received anti-TNF-a Etanercept: 93 Etanercept: 93 Infliximab: 15 Infliximab: 15 Adalimumab: 8 Adalimumab: 8 2 agents: 9 2 agents: 9

12. Changes in drugs utilization (t12-t0)

13. SF-36 results before and after treatment *=significant at the 0.0001 level §=non significant PF, physical functioning; RP, role-physical; BP, bodily pain; GH, general health; VT, energy/vitality; SF, social functioning; RE, role-emotional; MH, mental health; PCS, Physical Component Summary score and MCS, Mental Component Summary score

14. EQ-5D results before and after treatment p<0.0001

15. Change in 6-month cost (t12-t0) VariableMeanSD P Value Increase in overall direct cost 5,052.342,716.61P<0.0001 Increase in cost of drugs 5,189.972,686.59P<0.0001 Increase in overall direct cost to NHS 5,044.212,739.56P<0.0001 Decrease in overall indirect cost 413.341,574.09P=0.007 Increase in overall social cost 4,638.733,087.08P<0.0001 Increase in EQ-5D VAS 19.4025.00P<0.0001 Increase in EQ-5D utility 0.250.31P<0.0001

16. Variable Incremental cost (6 months) Utility gain (utility at final – utility at initial observations) QALY gain (6 months) COST/QALY Direct cost 5,052.340.250.1240,942.78 NHS cost 5,044.210.250.1240,876.90 Social cost 4,638.730.250.1237,591.01 ICER: incremental cost-utility ratio

17. High Impairment in HrQoL, lower than COCIS, higher than major depression High Impairment in HrQoL, lower than COCIS, higher than major depression Improvement in clinical and disability indices Improvement in clinical and disability indices 5 fold increase in cost 5 fold increase in cost Increase in cost almost completely attributable to the cost of anti-TNF, similar to Kobelt for RA Increase in cost almost completely attributable to the cost of anti-TNF, similar to Kobelt for RA Improvement in domains of HRQoL, particularly in physical domains Improvement in domains of HRQoL, particularly in physical domains Spectacular 0.25 gain in utility, similar to Kobelt for RA Spectacular 0.25 gain in utility, similar to Kobelt for RA CUA of approx. 37.000-40.000 /QALY, within CUA cut- offs for cost effectiveness, particularly in a rare disease CUA of approx. 37.000-40.000 /QALY, within CUA cut- offs for cost effectiveness, particularly in a rare disease Discussion