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Acute Pain | Chronic Pain | General

NSAIDs for treating Osteoarthritis

Clinical bottom line:

NSAIDs effectively relieve pain by about half and increase mobility in about 60% of people with osteoarthritis. There is insufficient information to rank their effectiveness, but what information we have suggests that diclofenac (100-150 mg) and naproxen (500-750 mg) are more effective than low doses ibuprofen, and more effective than paracetamol.



Non-steroidal anti-inflammatory drugs (NSAIDs) have become the common choice for treating rheumatological conditions like osteoarthritis, rheumatoid arthritis and gout. About 25 million prescriptions are written in the UK every year and most general practitioners will write a number of prescriptions every day because these are common conditions. About 4% of all precriptions in the UK are for NSAIDs, and 70% of GP precriptions for analgesics are for NSAIDs.

Osteoarthritis is the most common form of arthritis and is associated with significant disability and impaired quality of life because of increasing pain, loss of mobility, and consequently loss of independence as people get older or the disease worsens. Osteoarthritis is probably the main reason why people have hip and knee replacement operations

Systematic review

Two Cochrane reviews on NSAIDs in OA of the hip and knee have been combined because there is no prior reason to suspect that they should be different in response to NSAIDs. In order to try to tease out more information in a very difficult area, the papers included in the original reviews have been obtained and re-analysed.

Reviews:

T Towheed, B Shea, G Wells, M Hochberg. Analgesia and non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the hip. Cochrane Library (May 21 1999).

MC Watson, ST Brookes, JR Kirwan, A Faulkner. Non-aspirin, non-steroidal anti-inflammatory drugs (NSAIDS) for osteoarthritis of the knee. Cochrane Library (May 21 1999).

Note: Four papers originally included have been omitted because they dealt with opioids, combination of NSAID with other compounds, suppositories (all others being oral), and naproxen/paracetamol combinations.

Date reviews completed: Nov 1996, August 1997

Number of trials: 29

Number of patients: 3,014

Control groups: Most studies compared two NSAIDs. Only a very few included a placebo.

Main outcomes: Studies used a variety of outcomes, and many gave only mean results without dispersion. For this summary, information has been taken from patient global evaluations available in dichotomous form and equivalent to at least 50% improvement or relief of pain. No statistical calculations were possible.

Inclusion criteria were randomised controlled trials of NSAIDs in patients with osteoarthritis of the hip and/or knee, compared with placebo, or other NSAID, or analgesic.

Trials

Despite extensive searching, only 29 trials were found which fulfilled these inclusion criteria; over 1,100 trials were originally identified by one of the reviews. The details of these trials are given in Table 1, from which relevant information has been extracted and tabulated. Note that no additional searching has been done to update these two reviews.

The trials were small, with 67 as the median number of patients as the total number of patients in the trials. Only five studies had more than 200 patients (Figure 1).

Figure 1: Total number of patients in NSAID RCTs in OA.

The trials were short, with 6 weeks as the median duration, either of the trial if parallel group or one treatment period if cross-over design. Only three trials lasted more than 10 weeks (Figure 2).

Figure 2: Duration of trials of NSAID RCTs in OA

Because the design of trials of NSAIDs in OA left much to be desired - they were small, short, and had poor reporting of results - the information on efficacy and harm that follows should be taken as indicative only.

Effectiveness of NSAIDs

A large number of different outcomes were used in the trials, but few were reported in detail. Pain at rest, pain on movement and patient and physician global evaluations were the most commonly used outcomes. Mobility was occasionally judged by walking times, and joint flexion and or tenderness were sometimes assessed.

Where results were reported, they were frequently given as mean values without dispersion. Many trials described 'improvement', but not one defined what improvement actually meant - though it was implied that this would be any improvement from baseline rather than a prior definition of what constituted sufficient quality of life or pain reductionfor the patient.

Almost all trials put patients on simple analgesics like paracetamol for one or two weeks before treatment, and some allowed paracetamol during treatment as additional analgesia. In these cases it was universally stated that paracetamol had to be discontinued before assessments were made.

The most commonly reported outcome with dichotomous information was the patient global evaluation of treatment. In Table 1 the actual figures are given for the trials, and these are shown graphically in Figure 3 where the results of global evaluations as good or better (equivalent to at least half pain relief) are given.

Figure 3: Global outcome equating to at least 50% pain relief in individual trials

Placebo, paracetamol and paracetamol/codeine, low dose ibuprofen (<1200 mg/day) and piroxicam were the least effective treatments with 20-40% of patients with at least 50% pain relief. Diclofenac 100-150 mg was the NSAID for which there was most data (four trials) and this showed consistently good responses of between 59% and 82% of patients with at least 50% pain relief.

Harm with NSAIDs

Most of the trials give information on harm at various levels. Table 2 contains the information collected from the trials for adverse effect discontinuations, which were essentially the same at below 10% across all treatments, including placebo. It is worth noting that very high adverse effect discontinuation rates were seen in the study comparing paracetamol and paracetamol plus codeine (Table 1).

Table 2: Overall reporting of measures of harm in RCTs of NSAIDs in OA

Drug Number of trials Number of patients Percent affected

Adverse effect discontinuations

 
Etodolac 400-800 mg

11

642

9

Diclofenac 100-150 mg

10

435

9

Naproxen 500-1000 mg

8

415

8

Piroxicam 20 mg

5

330

9

Nabumetone 1000-1500 mg

2

124

8

Flurbiprofen 100-150 mg

2

110

5

Placebo

3

185

10

Upper Gastrointestinal problems

 

Etodolac 400-800 mg

12

746

18

Diclofenac 100-150 mg

8

367

20

Naproxen 500-1000 mg

8

415

17

Piroxicam 20 mg

4

311

23

Placebo

4

291

9

Dyspepsia

Etodolac 400-800 mg

10

630

9

Piroxicam 20 mg

4

285

16

Naproxen 500-1000 mg

3

250

19

Placebo

3

185

11

Data calculated when at least 100 treated patients or two studies available. Upper GI problems includes dyspepsia, abdominal pain, nausea, vomiting etc

Upper gastrointestinal problems, including dyspepsia, abdominal pain, nausea, vomiting etc, were higher at about 20% with NSAIDs than the 9% recorded with placebo. For dyspepsia alone the distinction was less clear.

Bleeding episodes, including positive faecal occult bloods, melaena, ulcers and GI bleeding were reported in 21 patients. This is 0.7% of all patients in the 29 trials, including placebo, paracetamol, and non-NSAID treatments.

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