1. Managing Arthritis Flare-Ups Prof.Hisham Hamoud

2. Prevalence of Osteoarthritis  Arthritis is considered the most common joint disorders in the world.  Osteoarthritis is by far the most common form of arthritis occurring in practice and is a leading cause for chronic disability in elderly patients  The annual prevalence of knee pain associated with OA is 46% in those over age 50.  In those with knee pain, around 1 in 5 patients indicate problems at work. Arthritis Foundation. The facts about arthritis. Available at: www.arthritis.org/resources/gettingstarted/default.asp. Accessed September 8, 2006 Lawrence, et al. 1998; Woolf, et al. 2003 Deborah Symmons, Colin Mathers, Bruce Pfleger. Global burden of osteoarthritis in the year 2000. ww.who.int/entity/healthinfo/statistics/bod_osteoarthritis.pdf Adapted from Jinks C, Jordan K, Ong BN, Croft P. A brief screening tool for knee pain in primary care (KNEST). Wilkie R, Jordan K, Blagojevic, M, Croft P. What will happen if state pension age rises for people with joint pain? Impact

3.  PGE2 has important pro-inflammatory properties and contributes to vasodilation and pain in patients with OA 2  Chondrocytes isolated from patients with OA produce 50-fold more PGE2 than chondrocytes from patients without OA CLEVELAND CLINIC JOURNAL OF MEDICINE, VOLUME 69, SUPPLEMENT, SI-6 Pathophysiology 50 folds more PGE2 in osteoarthritis patients’ chondrocytes

4. Arthritis Flare-Ups

5. Definition of Arthritis Flare Ups  Some forms of arthritis go through cycles of getting better and worse 1  A flare-up means the disease is more active 1 Increased morning stiffness 1 More pain and swelling in the joints, 1 (the pain becomes more severe and responds less to rest, tending to become continuous) 2 Involvement of other joint 1 Increased tiredness and fatigue 1 1. M. Marty et al. / Joint Bone Spine 76 (2009) 268e272 2. Spector T, Hart DJ, Nandra D, et al. Arthritis Rheum 1997;40:723e7

6. Impact of Arthritis flare-ups & considerations Disability & sleep disorders are key symptoms associated with flare ups, proper management of flare-ups are crucial to avoid further damage  In patients with symptoms of OA flare-ups the following conditions are reported  Significant work disability  Reduced ability to deal with household duties  Sleep disorders  It's important to address arthritic flare-ups as soon as possible, because of the damage,the increased inflammation can do to already compromised joints Subjective impact of osteoarthritis flare-ups on patients' quality of life, Giuseppina Majani Health and Quality of Life Outcomes 2005, 3:14 http://www.ehow.com/about_4759080_arthritis-flare-up-symptoms.html

7. Diagnostic score for knee OA: KOFUS ( Knee Osteoarthritis Flare-Ups Score)

8. Diagnostic score for knee OA KOFUS ( Knee Osteoarthritis Flare-Ups Score)  Is to identify & validate a criteria for defining knee osteoarthritis flare-up, based on data from two large cross-sectional studies based on clinical features,NO blood tests or joint fluid studies were performed M. Marty et al. / Joint Bone Spine 76 (2009) 268e272 Objectives Clinical features associated with a flare-up were  Morning stiffness for longer than 20 min  Nocturnal awakenings due to knee pain  Limping  Swelling  Warmth  Joint effusion

9. Diagnostic score for knee OA: KOFUS ( Knee Osteoarthritis Flare-Ups Score) Patients with a score of 7 & above are diagnosed as flare-ups patients M. Marty et al. / Joint Bone Spine 76 (2009) 268e272 A score equal to or greater than 7 points indicates diagnosis of flare-up

10. Osteoarthritis Management

11. NSAIDs in Guidelines

12. To fully treat inflammation, a higher dose of NSAIDs must be taken on a regular basis for 2-4 weeks http://www.uptodate.com

13. Diclofenac in Arthritis Flare-Ups The recommended dose for arthritis flare-ups is, the full dose of Diclofenac which is 150 mg / day for 2 weeks. Voltaren Basic Prescribing Information http://www.merck.com/mmpe/lexicomp/diclofenac.html http://www.rxlist.com/voltaren-drug.htm

14. Fast Acting Oral NSAIDs at Maximum Doses are the Drugs of Choice in Patients with Arthritis for 1-2 Weeks

15. Nazli Conway et al,Diagnosis&Management of acute gout, Medicine&Health, vol.92, no 11, novemb. 2009

16. Full Dose of Diclofenac is Recommended for Management of Inflammation of Arthritis Nazli Conway et al,Diagnosis&Management of acute gout, Medicine&Health, vol.92, no 11, novemb. 2009

17. Arthrofast

18. What is Arthrofast Arthrofast is 150mg Diclofenac sodium in a modified release formulation. 1 Arthrofast is a once daily modified release 2 NSAID that provides fast & lasting 3 pain relief for patients suffering from flare-ups of both arthritis & spondylosis 2 through it’s bilayer technology. 1&4 1. Clinical Overview Diclofenac Modified Release Bi-Layer Tablets 75 and 150 mg Prepared by: Dr. Wilhelm Ackermann, September 2004, Hamburg. 2. Arthrofast basic prescribing information. 3. Adapted from Pharmacokinetic pilot study of a new diclofenac slow release formulation after single oral administration in six healthy male volunteers. Cephac Institute, Paris, 1994 4. Effective treatment of osteoarthritis with a 150 mg prolonged-release of diclofenac sodium, P. ARCANGELI, European Review for Medical and Plhannacological Sciences 1996; 18: 217-223

19. Mean + s.d. diclofenac plasma concentrations measured after single oral administration of 150 mg diclofenac as one slow-release tablet. 2 1. Clinical Overview Diclofenac Modified Release Bi-Layer Tablets 75 and 150 mg Prepared by: Dr. Wilhelm Ackermann, September 2004, Hamburg. 2. Pharmacokinetic pilot study of a new diclofenac slow release formulation after single oral administration in six healthy male volunteers. Cephac Institute, Paris, 1994 * Effective treatment of osteoarthritis with a 150 mg prolonged-release of diclofenac sodium, P. ARCANGELI, European Review for Medical and Plhannacological Sciences 1996; 18: 217-223 Arthrofast unique technology provide Immediate release within 15 minutes sustained effective concentration for 24 hours

20. A rthrofast® E fficacy & S afety in acute P ainful A ttacks of C hronic rh E umatic disorders

21. Arthrofast® Efficacy & Safety in Acute Painful attacks associated with chronic rheumatic disorders (AEROSPACE) 21 A 2 week treatment period, local, multicenter, open label, non-controlled, observational, non-interventional study to assess efficacy & safety of Arthrofast 150mg MR administered orally once daily for acute painful attacks in chronic Rheumatic Disorders like OA, back pain and gouty arthritis Novartis data on file

22. Arthrofast provides 65 % reduction of pain after 2 weeks Patient's pain intensity dropped from 7.24 in visit 1 to 2.55 in visit 2, where 0cm is very good and 10cm is very poor, with % change of -65% and Results are very highly statistically significant (p-value = 0.0000 <0.001 – T-test) Novartis data on file

23. Arthrofast provides 66% reduction in limitation of daily activity 23 Patient's Limitation of daily activity Patient's limitation of daily activity dropped from 6.42 in visit 1 to 2.16 in visit 2, where 0 is very good and 10 is very poor, with % change of -66% and Results are very highly statistically significant (p-value = 0.0000 <0.001 – T- test). Novartis data on file

24. Arthrofast provides 76 % improvement in joint tenderness 24 Tenderness of joints score dropped from 1.94 in visit 1 to 0.46 in visit 2, where 0 = No, 1 = Mild, 2 = Moderate and 3 = Sever, with % change of -317% and Results are very highly statistically significant (p-value = 0.0000 <0.001 – T-test, Chi-Square) Novartis data on file

25. 8 out of 10 patients treated with Arthrofast are relieved from swelling after 2 weeks 25 Swelling of joints dropped from 54.4% of patients in V1 to 11.4% of patients at V2 Novartis data on file

26. Almost 9 out of 10 patients are satisfied & extremely satisfied * with Arthrofast after 2 weeks 89.6 % of Patients are Satisfied and Extremely Satisfied 26 Novartis data on file

27. 93.8 % of Investigators are Satisfied and Extremely Satisfied 27 Novartis data on file

28. Safety Results 87% of Patients Have no Adverse Event 28 Patients and Investigators Satisfaction 87% of Patients Have no Adverse Event The safety information collected included adverse events (AE) and serious adverse events (SAE) reported Novartis data on file

29. Arthrofast Modified Release Formulation Provides  Immediate release starting in 15 minutes with sustained effective concentration lasting for 24 hours  65 % reduction of pain after 2 weeks  66% reduction in limitation of daily activity  76 % improvement in joint tenderness  8 out of 10 patients treated with Arthrofast are relieved from joint swelling after 2 weeks  Recommended dose for arthritis flare-ups 3&5