1. A Survey of Pediatric Rheumatologists to Determine Usage and Experience with Celebrex FDA Arthritis Advisory Committee November 29, 2006 Gloria C. Higgins, PhD, MD Associate Professor of Pediatrics The Ohio State University Division of Rheumatology Columbus Children’s Hospital

2. Methods: Independently generated and unsubsidized on-line survey using “Survey Monkey” service, conducted November ‘06 15 questions (drop-down or open-ended response) Anonymous or signed (responder’s choice) Responses solicited from US participants on Pediatric Rheumatology list-server, and sent individually by e-mail to all US pediatric rheumatologists in 2006 ACR directory Number of recipients unknown (> 150)

3. Responders: Board-eligible Pediatric Rheumatologists 11 Board-certified Pediatric Rheumatologists 86 Non-board eligible or certified 6 Total103 Years in practice: Mean 14.6 Range 0 – 43 (“0” years for 2 fellows) Total 1504 physician-years Distribution: 35 States, 1 US Territory

4. Question:YesNo Cox-II important drugs for JRA? 958 Ever used Celebrex for JRA?958 Advantages of COX-2 ? (>1 response possible) None 8 Fewer adverse effects85 Easier dosing27 Increased efficacy 5 Other (GI, hemostasis)16

5. Source of information? Chart review 2 Estimate91 Number of patients treated with Celebrex? Responders = 94 0 - 9 patients35(37%) 10 - 2535(37%) 26 - 5018(19%) > 50 6( 6%) Total Celebrex exposures (estimated): 1118-2390patients

6. Average duration of Celebrex treatment? Responders = 82 < 1 mo 1 1 - 6 mo17 7 - 12 mo26 13 - 18 mo15 > 18 mo23 “Median” range 7- 18 mo

7. When have you chosen Celebrex? Responders = 95 (> 1 answer possible) Preferred NSAID 2 If toxicity develops with other NSAID67 If patient/family requests14 Past success with other COX-225 After failure with 1 other NSAID20 After failure with >1 other NSAID48* Other:23 Patients with GI disorders (ex; gastritis, IBD) thrombocytopenia, coagulation deficits, asthma. * Restrictions on insurance coverage cited

8. Have you seen significant adverse effects or toxicities with Celebrex ? Responders = 95 No83(87%) Yes12(13%) Do the adverse effects or toxicities with Celebrex differ from other NSAIDs ? Responders = 75 No63(84%) Yes12(16%)* *Less GI toxicity, less bruising.

9. Have you seen any vascular thromboses or cardiovascular toxicities in JRA patients treated… With traditional NSAIDS ? Responders = 95 No94 Yes 1 * * 1 patient with thoracic outlet syndrome developed a deep vein thrombosis With Celebrex ? Responders = 94 No94 Yes 0

10. Summary (1)COX-2 inhibitory drugs are perceived by most pediatric rheumatologists as important for the treatment of JRA. Celebrex is used mainly in cases of treatment failure, or toxicity with other NSAIDs. (2) Celebrex is typically used for relatively short periods for treatment of JRA. (3)Celebrex appears to have similar adverse effects or toxicity in children as other NSAIDS, and may be associated with less GI toxicity and bruising. NSAIDs are frequently used in the treatment of JRA. The results of this practice-based survey indicate: