Cost Effectiveness of Combined Spa–Exercise Therapy in Ankylosing Spondylitis: A Randomized Controlled Trial ASTRID VAN TUBERGEN, 1 ANNELIES BOONEN, 1 ROBERT LANDEWE ´ , 2 MAUREEN RUTTEN-VAN MO ¨ LKEN, 3 DE ´ SIRE ´ E VAN DER HEIJDE, 4 ALITA HIDDING, 5 AND SJEF VAN DER LINDEN 1 Objective. To evaluate the cost effectiveness and cost utility of a 3-week course of combined spa therapy and exercise therapy in addition to standard treatment consisting of antiinflammatory drugs and weekly group physical therapy in ankylosing spondylitis (AS) patients. Methods. A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 was treated in a spa resort in Bad Hofgastein, Austria; group 2 in a spa resort in Arcen, The Netherlands. The control group stayed at home and continued their usual activities and standard treatment during the intervention weeks. After the intervention, all patients followed weekly group physical therapy. The total study period was 40 weeks. Effectiveness of the intervention was assessed by functional ability using the Bath Ankylosing Spondylitis Function Index (BASFI). Utilities were measured with the EuroQoL (EQ-5D utility ). A time-integrated summary score defined the clinical effects (BASFI-area under the curve [AUC]) and utilities (EQ-5D utility -AUC) over time. Both direct (health care and non-health care) and indirect costs were included. Resource utilization and absence from work were registered weekly by the patients in a diary. All costs were calculated from a societal perspective. Results. A total of 111 patients completed the diary. The between-group difference for the BASFI-AUC was 1.0 (95% confidence interval [95% CI] 0.4 –1.6; P  0.001) for group 1 versus controls, and 0.6 (95% CI 0.1–1.1; P  0.020) for group 2 versus controls. The between-group difference for EQ-5D utility -AUC was 0.17 (95% CI 0.09 – 0.25; P < 0.001) for group 1 versus controls, and 0.08 (95% CI 0.00 – 0.15; P  0.04) for group 2 versus controls. The mean total costs per patient (including costs for spa therapy) in Euros (€) during the study period were €3,023 for group 1, €3,240 for group 2, and €1,754 for the control group. The incremental cost-effectiveness ratio per unit effect gained in functional ability (0 –10 scale) was €1,269 (95% CI 497–3,316) for group 1, and €2,477 (95% CI 601–12,098) for group 2. The costs per quality-adjusted life year gained were €7,465 (95% CI 3,294 –14,686) for group 1, and €18,575 (95% CI 3,678 –114,257) for group 2. Conclusion. Combined spa– exercise therapy besides standard treatment with drugs and weekly group physical therapy is more effective and shows favorable cost-effectiveness and cost-utility ratios compared with standard treatment alone in patients with AS. KEY WORDS. Cost-effectiveness analysis; Cost-utility analysis; Randomized clinical trial; Ankylosing spondylitis; Spa therapy. INTRODUCTION Treatment of ankylosing spondylitis (AS) is aimed at re- ducing symptoms and preventing, or at least minimizing, spinal deformity and disability. Standard treatment of ac- tive AS consists of nonsteroidal antiinflammatory drugs (NSAIDs), which reduce pain and stiffness, and physical therapy, which prevents deformity and improves or main- tains mobility, fitness, and strength (1). Patients are ad- vised to exercise daily and to follow weekly group physi- 1 Astrid van Tubergen, MD, Annelies Boonen, MD, Sjef van der Linden, MD, PhD: University Hospital Maastricht, Maastricht, The Netherlands; 2 Robert Landewe ´, MD, PhD: University Hospital Maastricht, Maastricht, and Atrium Medical Center, Heerlen, The Netherlands; 3 Maureen Rut- ten-van Mo ¨ lken, PhD: Erasmus University Rotterdam, Rot- terdam, The Netherlands; 4 De ´sire ´ e van der Heijde, MD, PhD: University Hospital Maastricht, Maastricht, The Nether- lands and University Center Diepenbeek, Diepenbeek, Bel- gium; 5 Alita Hidding, PT, MSc, PhD: Institute for Rehabili- tation Research, Hoensbroek, The Netherlands. Address correspondence to Astrid van Tubergen, MD, De- partment of Internal Medicine, Division of Rheumatology, University Hospital Maastricht, Post Office Box 5800, 6202 AZ Maastricht, The Netherlands. E-mail: avantubergen@yahoo.com. Submitted for publication May 9, 2001; accepted in re- vised form January 19, 2002. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 47, No. 5, October 15, 2002, pp 459 – 467 DOI 10.1002/art.10658 © 2002, American College of Rheumatology ORIGINAL ARTICLE 459