THE CLINICAL EFFECTIVENESS AND COST EFFECTIVENESS OF CELECOXIB, ROFECOXIB, MELOXICAM AND ETODOLAC (COX-II INHIBITORS) FOR RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS. On behalf of: The National Institute for Clinical Excellence Report prepared by: NICE Appraisal Team A number of unpublished studies were submitted as commerical in confidence. These data have been removed from this version of the assessment report to enable publication on the website. The Appraisal Committee had full access to these data prior to their meeting of 26th October 2000. 1 November 2000 TABLE OF CONTENTS Executive Summary……………………………………………………………….5 Abbreviations……………………………………………………………………….8 1. Introduction ........................................................................................ 9 1.1. Aim of the review ...............................................................................9 1.2. Background........................................................................................9 Description of underlying health problem ............................................. 9 1.3. Osteoarthritis (OA).............................................................................9 Diagnosis and Classification............................................................... 10 Epidemiology of osteoarthritis ............................................................ 10 Clinical Presentation........................................................................... 11 Management of OA ............................................................................ 11 Outcome Measures ............................................................................ 12 1.4. Rheumatoid arthritis (RA) ................................................................12 Diagnosis and Classification............................................................... 12 Epidemiology...................................................................................... 13 Clinical Presentation........................................................................... 13 Management of RA............................................................................. 13 Outcome Measures ............................................................................ 14 1.5. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) ...........................14 Mechanism of Action .......................................................................... 14 Side effects......................................................................................... 14 Risk factors for NSAID related GI events ........................................... 15 Use of Gastroprotective Agents (GPAs)............................................. 15 1.6. Cox-II inhibitors................................................................................16 Assessment of COX-2 selectivity........................................................ 17 Classification ...................................................................................... 18 1.7. Financial Implications.......................................................................18 Economic Burden of Musculoskeletal Disorders ................................ 18 Economic Burden of NSAID Related Side Effects.............................. 19 2. Methods............................................................................................. 20 2.1. Search Strategy And Bibliographic Databases Used.......................20 2.2. Inclusion and exclusion criteria ........................................................20 Interventions....................................................................................... 20 Participants......................................................................................... 21 Study design....................................................................................... 21 Comparators....................................................................................... 21 Outcomes........................................................................................... 21 Data extraction strategy...................................................................... 21 2 2.3. Assessment of study quality ............................................................21 2.4. Data presentation ............................................................................21 Effectiveness ...................................................................................... 21 Adverse events................................................................................... 22 Data pooling............................................................................................................................. 22 3. Results: effectiveness of Cox-II inhibitors ..................................... 23 3.1. Literature searches ..........................................................................23 3.2. Included studies...............................................................................24 3.3. Effectiveness results: beneficial effects ...........................................51 Celecoxib............................................................................................ 51 Efficacy in rheumatoid arthritis................................................................................................. 51 Efficacy in osteoarthritis ........................................................................................................... 51 Rofecoxib ........................................................................................... 51 Efficacy in rheumatoid arthritis................................................................................................. 51 Efficacy in osteoarthritis ........................................................................................................... 51 Meloxicam .......................................................................................... 52 Efficacy in rheumatoid arthritis................................................................................................. 52 Efficacy in osteoarthritis ........................................................................................................... 52 Etodolac ............................................................................................. 52 Efficacy in rheumatoid arthritis................................................................................................. 52 Efficacy in osteoarthritis ........................................................................................................... 53 3.4. Effectiveness results: adverse events..............................................53 Celecoxib............................................................................................ 53 Rofecoxib ........................................................................................... 56 Meloxicam .......................................................................................... 58 Sub group analyses............................................................................ 62 4. Economic Evaluation of Cox-II inhibitors....................................... 63 4.1. Results.............................................................................................63 Literature searches............................................................................. 63 Included studies ................................................................................. 63 Merck Sharp & Dohme submission (Rofecoxib) ...................................................................... 64 Pfizer & Searle joint submission (Celecoxib) ........................................................................... 65 Boehringer Ingelheim submission (Meloxicam)....................................................................... 66 Shire submission (Etodolac) .................................................................................................... 67 CCOHTA Study........................................................................................................................ 68 Analysis of the economic evaluations................................................. 68 Variations in Event Rates......................................................................................................... 71 Variation in Cost Estimates...................................................................................................... 73 Estimate of Budgetary Impact ............................................................ 74 5. Discussion ........................................................................................ 82 5.1. Summary of effectiveness evidence ................................................82 5.2. Summary of the economic evidence................................................83 5.3. Limitations of the evidence base......................................................85 3 References…..…………………………………………………………………….86 Appendices Appendix A: Epidemiology of arthritis ...................................................................................... 97 Appendix B: Revised ARA criteria for the classification of rheumatoid arthritis, 2000 ............ 98 Appendix C: Full list of NSAIDs from BNF 40: September 2000 (9)........................................ 99 Appendix D: Search strategies ............................................................................................. 101 Appendix E: Abstract selection form.....................................................................................