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Therapeutics Letter, issue 4, February 1995

Should We Be Using NSAIDs for the Treatment of Osteoarthritis and "Rheumatism"?


It is essential that we prescribe non-steroidal anti-inflammatory drugs (NSAIDs) with knowledge and care; inappropriate prescribing puts our patients unnecessarily at risk of morbidity and mortality. There are many different NSAIDs available for prescription in British Columbia. The large number of drugs and formulations makes it difficult for the primary care physician to choose the best drug for his/her patient. The choice can be markedly simplified by a review of the published evidence on effectiveness and safety and by taking into consideration the cost of the drug. Using these principles most patients can probably be treated with the use of four drugs. 

Is there evidence of differences in effectiveness of the different NSAIDS?

There are relatively few clinical trials comparing the effectiveness of different NSAIDs. These trials have not demonstrated any consistent superiority of one NSAID over another. Differences that have been published can often be explained by the failure to use equivalent doses.(1)

What is the treatment of choice for osteoarthritis?

The long term use of NSAIDs for osteoarthritis in the elderly is common, however, the drug of first choice in these patients is acetaminophen 500 mg TID titrated to a maximum dose of 1 gram QID. Acetaminophen is safer, less expensive, and as effective as NSAIDs in approximately 50% of patients, particularly in those where arthralgia is the primary manifestation.(2),(3) If acetaminophen is ineffective in relieving symptoms enteric coated acetylsalicylic acid (ECASA), ibuprofen or naproxen can be tried.

Is ketorolac (Toradol) a more effective analgesic than other NSAIDS?

All of the NSAIDs have analgesic properties, usually at doses lower than the effective antiinflammatory doses. This is also true of keforolac which is chemically similar to tolmetin. There is no convincing evidence that ketorolac is a better analgesic than the other NSAIDS.

 Is there evidence that NSAIDs have a disease-modifying effect?

There is no evidence that NSAIDs alter the natural course of osteoarthritis. The patient should be made aware that NSAIDs represent symptomatic therapy, and that the therapy is associated with some risks. 

What are the major risks of NSAIDs in my patients?

The major risk is gastrointestinal ulceration associated with bleeding or perforation, both of which can be fatal.(4),(5) This risk is increased with higher dose and longer duration of therapy and is increased in the elderly. The relative risk of this complication has been studied in a practice setting(4),(5), and differs between the different NSAIDs (Table 1). Another common adverse consequence is the capacity of NSAIDs to elevate blood pressure; in a recent meta-analysis the magnitude of this effect was estimated to be 5 mm Hg.(6) In patients on long term therapy this would lead to a significantly increased risk of hypertension-related morbidity. NSAIDs can also cause salt and water retention and may precipitate congestive heart failure in susceptible patients.

How can I minimize the risk of NSAIDs in my patients?

The best way to minimize the risks is to use the simple analgesic, acetaminophen, whenever possible. When an NSAID is essential for control of symptoms prescribe the safest NSAID in the lowest effective dose for the shortest period of time (e.g. ibuprofen 200 mg TID for 1 to 2 weeks). Patients in whom chronic therapy is found to be necessary should be reassessed by decreasing the NSAID dose and/or stopping it at 3 to 6 month intervals. Administration of misoprostol (Cytotec) during NSAID therapy has been shown to reduce the incidence of significant GI events by 0.38% from 0.95% to 0.57% (unpublished MUCOSA Study). Unfortunately misoprostol also causes side effects, e.g. diarrhea, average incidence 11.9%.

What are the least expensive NSAIDs?

The doses and daily ingredient costs of the various NSAIDs available in B.C. are shown in Table 2. The three least expensive NSAIDs are ECASA, ibuprofen, and naproxen. Fortunately these are also amongst the safest.

Table 1: Rank According to Risk of Gastrointestinal Toxicity * 4,5

Safest

 

  Salsalate

 

  Ibuprofen

 

  ECASA

 

  Diclofenac

 

  Naproxen

 

  Sulindac

 

  Tolmetin

 

  Ketoprofen

 

  Indomethacin

 

  Piroxicam
Most Toxic

Table 2: Dosing and Cost for Selected NSAIDs

Drug Name Trade Name Dosage Range Daily Cost*
ASA Enteric Coated ASA 325-975 mg QID $0.06-$0.17
Celecoxib Celebrex 100- 200 mg BID $1.37-$2.71
Diclofenac generic, Voltaren 25-50 mg TID $0.60-$1.26
Diclofenac/Misoprostol Arthrotec 50/200 mg TID $1.79
Diflunisal generic, Dolobid 250-500 mg BID $0.79-$1.08
Etodolac Ultradol 200-400 mg BID $1.79-$3.58
Fenoprofen Nalfon 300-600 mg TID $0.85-$1.71
Floctafenine Idarac 200-400 mg TID $1.17-$1.96
Flurbiprofen generic, Ansaid, Froben 50-100 mg TID $0.84-$1.14
Ibuprofen generic 200-600 mg TID $0.11-$0.16
Indomethacin generic, Indocid 25-50 mg TID $0.29-$0.51
Ketoprofen generic, Rhodis, Orudis 50-100 mg TID $0.55-$0.99
Ketorolac Toradol 10 mg QID $2.06
Mefenamic Ponstan 250 mg QID $1.52
Meloxicam Mobicox 7.5- 15 mg daily $0.83-$0.99
Nabumetone Relafen 1-2 g daily $1.17-$2.34
Naproxen generic, Naprosyn 125-500 mg BID $0.12-$0.46
Naproxen sodium generic, Anaprox 275-550 mg BID $0.74-$1.47
Piroxicam generic, Feldene 10-20 mg daily $0.45-$0.78
Rofecoxib Vioxx 12.5- 25 mg daily $1.34
Salsalate Disalcid 0.75-1.75 g BID $0.70-$1.70
Sulindac generic, Clinoril 150-200 mg BID $0.80-$1.00
Tenoxicam Mobiflex 20 mg daily $1.04
Tiaprofenic acid Surgam 300 mg BID $0.91
Tolmetin Tolectin 200-600 mg TID $1.34-$2.67

* least expensive available formulation in BC, 2000


References

  1. Rochon PA, Gurwitz JH, Simms RW, Fortin PR, Felson DT, Minaker KL, Chalmers TC. A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of artbritis. Arch Intern Med, 1994; 154:157-163.

  2. Bradley JD, Brandt KD, Katz BP, Kalasinski LA, Ryan SI. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med, 1991; 325:87-91.

  3. March L, Irwig L, Schwarz J, Simpson J, Chock C, Brooks P. N of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis. BMJ, 1994, 309:1041-6.

  4. Fries JF, Williams CA, Ramey D, Bloch DA. The relative toxicity of disease modifying antirheumatic drugs. Arthritis and Rheumatism, 1993; 36:297-30.

  5. Langman KS, Well J, Wainwright P, Lawson DH, Rawlins MD, Logan RFA, Murphy M, Vessey MP, Collin-Jones DG. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs, Lancet, 1994; 343:1075-78.

  6. Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? Ann Intern Med 1994; 121:289-300.


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