Non-steroidal anti-inflammatory drugs for acute low back pain

Key Points

1. Non-steroidal anti-inflammatory medications (NSAIDs) are commonly used for acute low back pain (LBP).
2. NSAIDs for pain relief and improvement of disability are only slightly more effective than placebo in acute LBP management.
3. Four of 8 National Practice Guidelines recommend use of NSAIDs, in contrast to the remaining 4 recommending paracetamol as first line analgesia for acute LBP.

BACKGROUND & OBJECTIVE

This massive and statistically impressive Cochrane Review is the latest part in a series on the effect of NSAIDs for LBP which commenced in 2000 (1). The 2008 review looked at the efficacy of NSAIDs for acute and chronic LBP plus sciatica, in which a small but significant effect was found in favour of NSAIDs over placebo for short-term pain reduction and global improvement in participants with acute LBP (2). Due to the high number of included trials and the response to NSAIDs differing between acute and chronic LBP plus sciatica, the 2016 updates were separated into chronic LBP (3) and sciatica (4). This 2020 update assessed the effects of NSAIDs compared to placebo and other comparison treatments for acute LBP.

Low back pain is a leading cause of disability world-wide.

The magnitude of effect of NSAIDs on acute LBP was found to be slight and probably not clinically relevant.

METHODS

Acute LBP was defined as the experience of symptoms for less than 12 weeks. Extensive searches had been repeated annually between 2012 -2020 on NSAID use in acute LBP studies, following which analysis involved:

• Risk of bias
• Measures of treatment effect
• Unit of analysis issues
• Dealing with missing data
• Assessment of heterogeneity and reporting of biases
• Quality of evidence was assessed using the GRADE approach
• Summary of findings tables
• Subgroup analysis
• Sensitivity analysis

Outcome measures included:

1. Pain intensity (e.g. Visual Analogue Scale (VAS) or Numerical Rating Scale (NRS))
2. Back pain-specific functional status (e.g. Roland Morris Disability Questionnaire (RMDQ), Oswestry Disability Index (ODI))
3. Global measure (e.g. overall improvement, proportion of participants recovered)
4. Adverse events (proportion of participants experiencing adverse events)
5. Return to work (e.g. return to work status, number of days off work).

RESULTS

32 world-wide trials encompassing 5356 participants (aged 16-78yrs) were included. Follow-up ranged from 1 day to 6 months. Only 7 studies were at a low risk of bias and future high quality research may change the estimates of effect.

In Relation to NSAIDs High Quality Evidence:

NSAIDs are slightly more effective for short-term improvement in disability (RMDQ) than placebo (MD -2.02; 95% CI -2.89 to -1.15; 2 RCTs; N = 471). The magnitude of these effects is small and probably not clinically relevant. Moderate Quality Evidence:

NSAIDs are slightly more effective in short-term (≤ 3 weeks) reduction of pain intensity (VAS) than placebo (MD -7.29; 95% CI -10.98 to -3.61; 4 RCTs; N = 815). Low Quality Evidence:

NSAIDs are slightly more effective for short-term global improvement than placebo (RR 1.40; 95% CI 1.12 to 1.75; 5 RCTs; N = 1201), but there was substantial heterogeneity between studies. Very Low Quality Evidence:

No clear difference in the proportion of participants experiencing adverse events when using NSAIDs compared to placebo (RR 0.86; 95% CI 0.63 to 1.18; 6 RCTs; N = 1394).

No clear difference between the proportion of participants who could return to work after seven days between those who used NSAIDs and those who used placebo (RR 1.48; 95% CI 0.98 to 2.23; 1 RCT; N = 266).

In Relation to COX Inhibitors vs Non-Selective NSAIDs Moderate Quality Evidence:

Conflicting results for short-term disability improvement between groups (2 RCTs; N = 437). Low Quality Evidence:

No clear difference in short-term reduction of pain intensity between those who took selective COX-2 inhibitor NSAIDs compared to non-selective NSAIDs (MD -2.60; 95% CI -9.23 to 4.03; 2 RCTs; N = 437).

One trial (N = 333) reported no clear difference between groups in the proportion of participants experiencing global improvement. Very Low Quality Evidence:

No clear difference in the proportion of participants experiencing adverse events between those who took COX-2 inhibitors and non-selective NSAIDs (RR 0.97; 95% CI 0.63 to 1.50; 2 RCTs; N = 444).

No data were reported for return to work.

LIMITATIONS

There is a risk of publication bias due to the low number of trials included in the meta-analysis. Furthermore, almost half of the included studies were by pharmaceutical manufacturers, so risk of industry bias is also present.

CLINICAL IMPLICATIONS

The magnitude of effect of NSAIDs on acute LBP was found to be slight and probably not clinically relevant, yet the prescription and over the counter sale of NSAIDs for acute LBP is a massive multi-billion dollar enterprise, with many GPs prescribing NSAIDs almost routinely to LBP patients (5). The slight pain relief and disability reduction benefit is concerning when potential gastro-intestinal and cardiovascular adverse effects of NSAIDs are considered.

Eight current national guidelines for the management of acute LBP are moving away from pharmacotherapy with a focus on:

• Early and gradual return to activity
• Patient education
• Minimal bed rest
• Psycho-social interventions to help prevent chronicity
• Analgesic medication for short periods in acute LBP

Change is slow in relation to medication, with 4 guidelines advocating paracetamol, despite it being found to be no better than placebo for LBP (6,7). The other 4 guidelines suggest NSAIDs could be used carefully in the short term as support to stay active (8). Considering the poor results highlighted in The Lancet LBP series paper, we may need a total rethink on how we manage acute (and all) LBP, and of course the use of opioids would be part of that process.

+STUDY REFERENCE

van der Gaag WH, Roelofs PDDM, Enthoven WTM, van Tulder MW, Koes BW (2020) Non-steroidal anti-inflammatory drugs for acute low back pain. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD013581. DOI: 10.1002/14651858.CD013581.

SUPPORTING REFERENCE

1. Tulder MW, Scholten RJ, Koes BW, Deyo RA. (2000). Non‐steroidal anti‐inflammatory drugs for low back pain. Cochrane Database of Systematic Reviews, Issue 2. [DOI: 10.1002/14651858.CD000396; CD000396; PUBMED: PMID: 10796356]
2. Roelofs PDDM, Deyo RA, Koes BW, Scholten RJPM,van Tulder MW.(2008). Non-steroidal anti-inflammatory drugs for lowback pain. Cochrane Database of Systematic Reviews, Issue1. [DOI: 10.1002/14651858.CD000396.pub3]
3. Enthoven WTM, Roelofs PDDM, Deyo RA, van Tulder MW, Koes BW. (2016). Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database of Systematic Reviews, Issue 2. [DOI: 10.1002/14651858.CD012087]
4. Rasmussen-Barr E, Held U, Grooten WJA, Roelofs PDDM, Koes BW, van Tulder MW, et al. (2016). Non-steroidal anti-inflammatory drugs for sciatica. Cochrane Database of Systematic Reviews, Issue 10. [DOI: 10.1002/14651858.CD012382
5. Machado GC, Maher CG, Ferreira PH, Day RO, Pinheiro MB, Ferreira ML. (2017). Non-steroidal anti-inflammatory drugs for spinal pain: a systematic review and meta-analysis. Annals of the Rheumatic Diseases;76:1269-78. [DOI: 10.1136/ annrheumdis-2016
6. Schreijenberg M, Koes BW, Lin CWC. (2019). Guideline recommendations on the pharmacological management of non-specific low back pain in primary care – is there a need to change? Expert Review of Clinical Pharmacology;12(2):145-57. [DOI: 10.1080/17512433.2019.1565992]
7. Saragiotto BT, Machado GC, Ferreira ML. Pinheiro MB, Abdel Shaheed C, Maher CG. (2016). Paracetamol for low back pain. Cochrane Database of Systematic Reviews, Issue 6. [DOI: 10.1002/14651858.CD012230]
8. Oliveira CB, Maher CG, Pinto RZ, Traeger AC, Lin CC, Chenot JF, et al.(2018). Clinical practice guidelines for the management of nonspecific low back pain in primary care: an updated overview. European Spine Journal Nov;27(11):2791-2803. [DOI: 10.1007/s00586-018-5673-2]