Chronic paint r.gunadi pain update 22june2013 malang

389 views

Published on

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
389
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
18
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Chronic paint r.gunadi pain update 22june2013 malang

  1. 1. Efficacy & risk evaluation for long term therapy
  2. 2. Rheumatic pain 2
  3. 3. Symptoms  Joint pain  Joint swelling  Morning stiffness  Fatigue  Weight loss  Flu-like symptoms 3
  4. 4. Symptomatic Treatments  Education/support  Rest/relaxation  Joint protection  Physiotherapy  Analgesics  Anti-inflammatory drugs  Steroids  Joint injections  Pain Management Clinics 4
  5. 5. Symptomatic Treatments  Education/support  Rest/relaxation  Joint protection  Physiotherapy  Analgesics  Anti-inflammatory drugs  Steroids  Joint injections  Pain Management Clinics 5
  6. 6. Key questions regarding NSAIDs*  What are the benefits and risks from NSAIDs?  How do I reduce the GI risks?  How do I reduce the CV risks?  Are there specific safety concerns with etoricoxib ?  What does the prescribing data Iook like? *Note by NSAIDs we mean traditional NSAIDs (e.g. diclofenac, naproxen, ibuprofen); etodolac, meloxicam, or coxibs (e.g. celecoxib, etoricoxib)
  7. 7. What are the benefits and risks of NSAIDs?
  8. 8. NICE Full Clinical Guideline 59: Osteoarthritis. Feb 2008 Benefits and risks of NSAIDs
  9. 9. Estimate of hospital-related admissions due to NSAID adverse reactions Bandolier 2000;79:6–8 Event due to NSAID Estimated number of cases per year per primary care group (PCG) Upper GI bleed 18 Acute renal failure 10 Congestive heart failure 22 Information based on an average PCG of 100,000 patients where 3,800 patients aged over 65 years take NSAIDs
  10. 10. NSAIDs: Renal risks MHRA DSU. May 2009 Renal risk
  11. 11. How do I reduce the GI risks of NSAIDs?
  12. 12.  No strong evidence to suggest NSAIDs have a consistent benefit over paracetamol, although some patients obtain greater symptom relief from NSAIDs  Clinicians should consider offering paracetamol for pain relief in addition to core treatment; regular dosing may be required  Paracetamol (and/or topical NSAIDs) should be considered ahead of oral NSAIDs, COX-2 inhibitors or opioids Paracetamol>< NSAIDs ? NICE Full Guideline 59: Osteoarthritis, Feb 2008 NICE Full Clinical Guideline 59: Osteoarthritis. Feb 2008
  13. 13. Using Paracetamol ? Pincus T, et al. J Rheumatol 2000;27:1020–1027 Wolfe F, et al. Arthritis Rheumatol 2000;43:378–385
  14. 14. Risk of upper GI ulcer bleeding Lanas A, et al. Gut 2006;55:1731–38 Hospital-based, case-control study in Spain 2777 consecutive patients with endoscopy-proved major upper GI bleeding (peptic lesions) and 5532 matched controls Use of NSAIDs increased risk (RR 5.3;95%CI 4.5 to 6.2) No increased risk for NSAIDs + PPI (RR 0.9, 95%CI 0.7 to 1.3) Rofecoxib increased the risk (RR 2.1; 95%CI 1.1 to 4.0) No increased risk with celecoxib (RR 1.0; 95%CI 0.4 to 1.6) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Control Aceclofenac Diclofenac IbuprofenNaproxen Lornoxicam Ketoprofen Indomethacin MeloxicamKetorolac CelecoxibRofecoxib Paracetamol AdjustedRR
  15. 15. NSAIDs: GI risks  Ibuprofen offers the lowest GI risk; Coxibs are associated with reduced GI risk relative to most NSAIDs at equivalent doses MeReC Extra 30. November 2007  When offering treatment with an oral NSAID/coxib inhibitor, the first choice should be either a standard NSAID or a coxib (other than etoricoxib 60mg). In either case, these should be co-prescribed with a proton pump inhibitor (PPI), choosing the one with the lowest acquisition cost. NICE. Osteoarthritis Guideline CG59. February 2008
  16. 16. How do I reduce the CV risks of NSAIDs?
  17. 17. Coxibs and cardiovascular risk MHRA. Safety of selective and non-selective NSAIDs October 2006  Coxibs are associated with an increased thrombotic risk.  Risk varies according to underlying patient risk factors  Population risk is about 3 additional events (mainly MI) per 1000 patients per year compared with placebo.  Dose-related adverse effects may manifest early and the risk may persist throughout treatment
  18. 18. Traditional NSAIDs and CV risk MHRA. Safety of selective and non-selective NSAIDs. October 2006  Diclofenac 150mg daily has a similar excess thrombotic risk to that of etoricoxib▼ and possibly other coxibs  Naproxen 1000mg daily may be associated with a lower risk of thrombotic events than coxibs. Although some risk with naproxen cannot be entirely ruled out, epidemiological evidence suggests that naproxen is not associated with an excess risk of MI  Ibuprofen may be associated with a small thrombotic risk at high doses (e.g. 2400mg daily), whereas at low doses (e.g. 1200mg daily) evidence does not suggest an increased thrombotic risk in the short term
  19. 19. CV Issues With COX-2 Selective and Traditional NSAIDs In placebo-controlled randomized trials, COX-2 selective NSAIDs ↑’ed the risk of thrombotic CV events  Observational studies suggest ↑ CV risk for some traditional NSAIDs  CV risk of high-dose naproxen may be different:  Meta-analysis of randomized trials: CV risk of high- dose naproxen appears lower than COX-2 inhibitors  2005-6 FDA and European regulatory agencies added a warning of an increased thrombotic CV risk for all NSAIDs (both COX-2 selective and traditional) 20 Kearney et al. BMJ. 2006;332:1302; Solomon et al. NEJM. 2005;352:1071; Bresalier et al. NEJM 2005;352:1092; FDA. At: http://www.fda.gov/bbs/topics/news/2005/NEW01171.html. Accessed October 2006; CHMP. At: http://www.emea.eu.int/pdfs/human/opiniongen/nsaids.pdf. Accessed October 2006.
  20. 20. Questions arising with COX-2 selective and traditional NSAID therapies These studies raise many questions: 1. Does greater COX-2 selectivity increase CV risk vs. traditional NSAID? 2. Is high-dose naproxen, with its sustained antiplatelet effect, different? 3. Would use of aspirin attenuate the increased risk seen with NSAIDs? Need large randomized trials comparing CV outcomes between different NSAID agents 21
  21. 21. Primary Endpoint: Cumulative Incidence of Thrombotic CV Events 22 Etoricoxib (320 events) Diclofenac (323 events) Months No. of patients at risk* Etoricoxib Diclofenac 16,819 16,483 13,359 10,733 8277 6427 4024 805 81538326213790110,14212,800 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 6 12 18 24 30 36 420 Cumulativeincidence(%)with95%CI Etoricoxib vs diclofenac HR = 0.95 95% CI = (0.81-1.11) *Per protocol population.
  22. 22. 23 Cumulative Incidence of Confirmed Upper GI Events (Perforations, Ulcers, and Bleeds)* POBs† MonthsNo. of patients at risk Etoricoxib Diclofenac 17412 17289 13704 10972 8400 6509 4063 821 8203867630680271039613190 3.0 2.5 2.0 1.5 1.0 0.5 0 6 12 18 24 30 36 420 Cumulativeincidence(%)with95%CI Etoricoxib vs diclofenac HR = 0.69 95% CI = (0.57-0.83) *ITT (14 days) population. 50.6% of patients were on gastroprotective agents. Etoricoxib (176 events) Diclofenac (246 events) †No significant difference in perforations, obstructions, or major bleeds.
  23. 23. 24 “Our results show that patients with arthritis treated with the COX-2 selective NSAID etoricoxib and those given the traditional NSAID diclofenac have nearly identical rates of thrombotic cardiovascular events.” Cannon CP, Curtis S, FitzGerald GA, et al. Lancet. 2006:368 (published online) www.thelancet.com Dr. Loren Laine is presenting preliminary GI subgroup data at Am. Coll. Rheumatology in Wash DC today For the lower risk upper GI clinical events with etoricoxib:  Generally consistent benefit in ASA and PPI subgroups
  24. 24. 25
  25. 25. Etoricoxib and blood pressure MHRA. DSU July 2008  EMA review of etoricoxib  Patients whose BP is persistently above 140/90 mmHg and inadequately controlled must not receive etoricoxib  High BP should be controlled before starting treatment, and should be monitored for 2 weeks after the start of treatment and regularly thereafter
  26. 26. Key messages  All NSAIDS (both coxibs and traditional NSAIDs) are associated with CV, renal and GI side effects  Where NSAIDs are required, base prescribing on the safety profiles of individual NSAIDs taking into account individual patient risk factors  Generally, prescribe NSAIDS at the lowest effective dose and for the shortest period of time necessary to control symptoms. Review prescribing regularly.
  27. 27. Key messages  The risks of CV side effects with diclofenac and coxibs are similar  Low-dose ibuprofen and naproxen are associated with the lowest CV risk  Consider co-prescribing a PPI with an NSAID, especially to those at high risk of GI side effects, and when used for long-periods of time
  28. 28. Have an enjoyable learning

×