# Presentation: 836897

## CONCLUSION

**Richard Kent, MD**
**Chief Medical Officer**
**Glaxo Wellcome **

## Conclusion

**Significant disease burden**

**Consistently effective**
**Comparable magnitude of benefit**

## Efficacy of Celecoxib

- *

- *

- *

- *

**Percent Responders**

**Efficacy of Celecoxib**

- Simon L et al., *JAMA* 282:1921-1928 (1999).

## Global Improvement Responder

**Global Improvement Responder**

**Month**

*** p<0.05**

-   *****

**  *******

**  **

**     *******

**% Responders**

## Has the Safety Profile Changed?

**Hepatic abnormalities**
**No**
**Ischemic colitis**
**No**
**Constipation**
**Rare serious sequelae**

## Extensive Risk Management Program

**Appropriate labeling**
**Actively and effectively communicate new messages**
**Evaluate reception of new messages**

## NSAID Complications

**Endoscopic Ulcers:****	****	****   12 -25%**
**Serious GI Complications:   0.1-2.0%**
**Hospitalizations:****	****	****   >70,000/yr**
**Deaths:****	****	****	****	****   10,000-20,000/yr**
**Schoenfeld P, et al. Aliment Pharmacol Ther 1999;13:1273-1285**

## NSAID WARNING

**80% of patients who develop a serious upper GI adverse event on NSAID therapy are asymptomatic**
**Ulcer, gross bleeding, or perforation caused by NSAIDs occurs in 2-4% of patients after 12 months of therapy**

## GI AE’s in Labeling

**Constipation: **
**94 drugs have a >3% incidence (3-46%)**
**Other GI AE’s of these drugs:**
**Colitis****	****	****	****	****25**
**Intestinal obstruction****	****	****14**
**Perforation****	****	****	****	****10**
**Paralytic ileus****	****	****	****6**
**Ileus****	****	****	****	****	****5**
**Fecal impaction****	****	****	****4**
**No bolded warnings or black boxes**

## Postmarketing Safety of Sildenafil

**130 Deaths (March-November 1998)**
**77 Cardiovascular Events**
**16 received concomitant nitrates**
**Contraindications:**
**Concomitant nitrate use**
**Warnings:**
**Cardiac risk for sexual activity**
**Major patient subgroups not studied**

##   “We believe that these contraindications statements adequately advise against the use of Viagra in patients taking nitrates to control chest pain. Therefore, the agency does not believe that a boxed warning is necessary at this time.”
				Janet Woodcock, MD
				Director
				Center for Drug Evaluation and Research
				February 28, 2000 letter to Robert P. Brady, Esq.

**	****	****	****	****Janet Woodcock, MD**
**	****	****	****	****Director**
**	****	****	****	****Center for Drug Evaluation and Research**
**	****	****	****	****February 28, 2000 letter to Robert P. Brady, Esq.**

## Summary

**Significant burden of illness**
**Positive benefit-risk profile**
**Integrated and targeted risk management program**

## Consultants

**Martha Bayliss, MSc****	****QualityMetric**
**Lawrence Brandt, MD****	****Montefiore Medical Center**
**William Chey, MD****	****University of Rochester**
**Rosemarie Fisher, MD****	****Yale University**
**Ian Gralnek, MD****	****UCLA**
**John Lennard-Jones, MD****	****St. Marks Hospital**
**Rona Levy, Ph.D.****	****University of Washington**
**James McGill, MD****	****Indiana University**
**Louis Morris, Ph.D.****	****SCP Communications**
**Kay Washington, MD****	****Vanderbilt University**