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Markov model into the cost-utility over five years of etanercept and infliximab compared with usual care in patients with active ankylosing spondylitis

A Boonen¹, D van der Heijde², J L Severens³, A Boendermaker⁴, R Landewé⁸, J Braun⁵, J Brandt⁶, J Sieper⁷, Sj van der Linden⁹

¹ Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht, Netherlands
² Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht and Caphri Research Institute
³ Department of Health Organisation, Policy and Economics, University of Maastricht
⁴ University of Maastricht
⁵ Rheumatology Medical Centre Ruhrgebiet, Herne, and Benjamin Franklin Free University of Berlin, Department of Rheumatology, Berlin, Germany
⁶ Rheumatology Medical Centre Ruhrgebiet, Herne Germany
⁷ Benjamin Franklin Free University of Berlin, Department of Rheumatology, Berlin, Germany
⁸ Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht
⁹ Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht

Correspondence to:
Dr Annelies Boonen
Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, Netherlands; aboo{at}sint.azm.nl

Objective: To estimate the incremental cost-utility of etanercept and infliximab compared with usual care in active ankylosing spondylitis.

Methods: A Markov model over five years with cycle times of three months was computed. Patients included all had active disease, defined as Bath ankylosing spondylitis disease activity index (BASDAI) 4 and could reach low disease activity, defined as BASDAI <4. Non-response to tumour necrosis factor (TNF) inhibitors was always followed by cessation of treatment. Response to TNF inhibitors could be followed at any time by either relapse to BASDAI 4, leading to cessation of treatment, or toxicity, leading to cessation of treatment if major. Probabilities for efficacy, relapse, and toxicity were derived from two European randomised controlled trials. Utilities and costs assigned to the BASDAI disease states were derived from a two year observational Dutch cohort. In sensitivity analyses probabilities of effectiveness, toxicity, costs, and utilities were varied.

Results: Over five years the total quality adjusted life years varied from 2.57 to 2.89 for usual care, compared with 3.13 to 3.42 and 3.07 to 3.35 for etanercept or infliximab. Cumulative costs were between 49 555 to 69 982 for usual care compared with 59 574 to 91 183 or 28 3330 to 106 775 for etanercept and infliximab. This resulted in incremental cost-utility ratios varying between 42 914 and 123 761 per QALY for etanercept compared with usual care and 67 207 to 237 010 for infliximab. The model was sensitive to drug prices.

Conclusion: Etanercept and infliximab have large clinical effects in ankylosing spondylitis. The present model suggests the high drug costs restricts efficient use in all patients who have a BASDAI >4. The validity of the model is limited by insufficient insight in the natural course of the disease and long term effectiveness and toxicity of TNF inhibitors.

Abbreviations: BASDAI, Bath ankylosing spondylitis disease activity index; BASFI, Bath ankylosing spondylitis functional index; ICER, incremental cost-effectiveness ratio; ICUR, incremental cost-utility ratio; NSAID, non-steroidal anti-inflammatory drug; QALY, quality adjusted life year; RCT, randomised controlled trial

Keywords: ankylosing spondylitis; etanercept; infliximab; TNF inhibitors; cost-effectiveness

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