Ann Rheum Dis. 2017 (Jul); 76 (7): 1269–1278 ~ FULL TEXT
Gustavo C Machado, Chris G Maher, Paulo H Ferreira,
Richard O Day, Marina B Pinheiro, Manuela L Ferreira
The George Institute for Global Health,
Sydney Medical School,
University of Sydney,
Sydney, New South Wales, Australia.
BACKGROUND: While it is now clear that paracetamol is ineffective for spinal pain, there is not consensus on the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) for this condition. We performed a systematic review with meta-analysis to determine the efficacy and safety of NSAIDs for spinal pain.
METHODS: We searched MEDLINE, EMBASE, CINAHL, CENTRAL and LILACS for randomised controlled trials comparing the efficacy and safety of NSAIDs with placebo for spinal pain. Reviewers extracted data, assessed risk of bias and evaluated the quality of evidence using the Grade of Recommendations Assessment, Development and Evaluation approach. A between-group difference of 10 points (on a 0-100 scale) was used for pain and disability as the smallest worthwhile effect, as well as to calculate numbers needed to treat. Random-effects models were used to calculate mean differences or risk ratios with 95% CIs.
RESULTS: We included 35 randomised placebo-controlled trials. NSAIDs reduced pain and disability, but provided clinically unimportant effects over placebo. Six participants (95% CI 4 to 10) needed to be treated with NSAIDs, rather than placebo, for one additional participant to achieve clinically important pain reduction. When looking at different types of spinal pain, outcomes or time points, in only 3 of the 14 analyses were the pooled treatment effects marginally above our threshold for clinical importance. NSAIDs increased the risk of gastrointestinal reactions by 2.5 times (95% CI 1.2 to 5.2), although the median duration of included trials was 7 days.
CONCLUSIONS: NSAIDs are effective for spinal pain, but the magnitude of the difference in outcomes between the intervention and placebo groups is not clinically important. At present, there are no simple analgesics that provide clinically important effects for spinal pain over placebo. There is an urgent need to develop new drug therapies for this condition.
KEYWORDS: Analgesics; Low Back Pain; NSAIDs
Commonly used non-steroidal anti-inflammatory drugs used to treat back pain provide little benefit and may make things worse according to new research from The George Institute for Global Health.
The findings of the systematic review, published in the Annals of the Rheumatic Diseases, reveal only one in six patients treated with the pills, also known as NSAIDs, achieve any significant reduction in pain.
The study is the latest work from The George Institute questioning the effectiveness of existing medicines for treating back pain. Earlier research has already demonstrated
paracetamol does not speed recovery or reduce pain for acute low back pain, and opioids provide minimal benefit over placebo.
Lead author Associate Professor Manuela Ferreira says the study highlights an urgent need to develop new therapies to treat back pain which affects 80 per cent of Australians during their lifetime.
A/Prof Ferreira, Senior Research Fellow at The George Institute and at the Institute of Bone and Joint Research, said: “Back pain is the leading cause of disability worldwide and is commonly managed by prescribing medicines such as anti-inflammatories. But our results show anti-inflammatory drugs actually only provide very limited short term pain relief. They do reduce the level of pain, but only very slightly, and arguably not of any clinical significance.”
A/Prof Ferreira added: “When you factor in the side effects which are very common, it becomes clear that these drugs are not the answer to providing pain relief to the many millions of Australians who suffer from this debilitating condition every year.”
The team at The George Institute, which examined 35 trials involving more than 6,000 people, also found patients taking anti-inflammatories were 2.5 times more likely to suffer from gastro-intestinal problems such as stomach ulcers and bleeding.
Research Fellow Gustavo Machado, of The George Institute and the School of Medicine at the University of Sydney, said: “Millions of Australians are taking drugs that not only don’t work very well, they’re causing harm. We need treatments that will actually provide substantial relief of these people’s symptoms.
“Better still we need a stronger focus on preventing back pain in the first place. We know that education and exercise programs can substantially reduce the risk of developing low back pain.”
Most clinical guidelines currently recommend NSAIDs as the second line analgesics after paracetamol, with opioids coming at third choice.
From the FULL TEXT Article:
Spinal pain (neck or low back pain) is the leading
cause of disability worldwide, [1, 2] and commonly
managed in general practice by prescription of
medicines. [3, 4] Clinical guidelines recommend nonsteroidal
anti-inflammatory drugs (NSAIDs) as a
second-line analgesic after paracetamol, with third
choice being opioids.  However, recent
meta-analyses have shown that paracetamol is ineffective, [6, 7]
and opioids appear only to offer small
benefits for this condition.  Thus, although the use
of NSAIDs has fallen in the past decade,  their use
could rapidly rise, given the lack of efficacy of paracetamol
and increased awareness of risks associated
with opioid use. [10, 11]
There is still not consensus on the efficacy of
NSAIDs for spinal pain. The most recent
meta-analysis excluded participants with acute low
back pain or neck pain,  and to date no reviews
have investigated NSAID injections or topical formulations
in this population. Furthermore, previous
meta-analyses have reported standardised mean differences
(MD) as effect sizes, which are nonintuitive
and difficult to interpret;  thus better
measures of treatment effects, such as numbers
needed to treat (NNT), are likely to enhance interpretability
for the clinician. There is also concern
about the cardiovascular safety of cyclo-oxygenase-2
(COX-2) inhibitors, while serious gastrointestinal
adverse reactions are more closely linked to nonselective
NSAIDs,  although all NSAIDs have been
associated with cardiovascular and gastrointestinal
risks.  Thus, there is far greater need to understand
the efficacy and safety of this medicine for spinal
Therefore, the aim of this systematic review was
to investigate the efficacy and safety of NSAIDs
compared with placebo in patients with spinal pain,
with or without radicular pain. We also aimed to
evaluate whether trial characteristics or methods
are associated with estimates of treatment effect.
Our review of 35 randomised placebo-controlled trials demonstrates
that NSAIDs are effective in reducing pain and disability in
patients with spinal pain, although treatment effects above those
of placebo are small and arguably not clinically important. For
every six patients treated with NSAIDs, rather than placebo, only
one additional patient would benefit considering a between-group
difference of 10 points for clinical importance in the short-term.
Furthermore, when looking at different spinal pain, outcomes or
time points in only 3 of the 14 analyses were the pooled effects
only marginally above our 10-point threshold for clinical relevance.
NSAIDs were associated with higher number of patients
reporting gastrointestinal adverse effects in the short-term
follow-up (ie, <14 days). No data on safety at medium-term or
long-term follow-ups were provided by included trials.
The strengths of our review include that it was prospectively
registered and followed the PRISMA recommendations, including
the use of GRADE to appraise the quality of the evidence.
We were able to identify a significantly larger number of trials
than past reviews, [12, 62–70]
which have often limited their inclusion
criteria to a specific language, population or type of
NSAID. Including more studies (35 randomised placebocontrolled
trials) enabled us to conduct a more thorough evaluation
of the effects of NSAIDs for various forms of spinal pain,
and to include a range of forms of drug administration. We have
also provided valuable information on pooled treatment effects
for specific populations, including neck pain, acute/chronic low
back pain and sciatica. Furthermore, we have provided clinically
interpretable estimates on a 0–100 scale, and compared our
effect sizes with a predetermined smallest worthwhile effect of
10 points, which reflects the smallest effect of the intervention
on outcomes compared with placebo that patients would consider
meaningful or important.22 Given physicians often find
the interpretation of effect sizes reported in meta-analysis challenging, 
we have also presented our results on pain reduction
as the NNT for a clinically significant effect of NSAIDs over
placebo. Moreover, potential factors that could have influenced
our treatment effects, such as risk of bias judegments, class of
NSAIDs and route of administration, were investigated through
meta-regression analyses. Although COX-2 inhibitors showed
larger effects than non-selective NSAIDs on pain reduction, the
size of the difference is of arguable clinical relevance. COX-2
inhibitors trials included in our review were fairly recent (all
were conducted after 2003) and substantially larger (mean
sample size of 280). They were also more likely to report safety
outcomes than older trials.
Our review has some limitations. First, we did not find any
trials investigating the efficacy and safety of celecoxib versus
placebo, a commonly used COX-2 selective drug. Second,
some of the trials included in our meta-analysis used drugs that
are discontinued or are no longer commercialised in major
markets (eg, rofecoxib and valdecoxib), but our
meta-regression revealed that this was not a factor that influenced our estimates; discontinued drugs (MD –8.9, 95% CI
–10.8 to –7.0) had similar effects as currently marketed
NSAIDs (MD –9.3, 95% CI –12.1 to –6.5). Third, there is no
evidence on the long-term effects and safety of NSAIDs, as the
median follow-up time was 1 week in included trials, with
some treatment schedules lasting <1 day. Fourth, our overall
pooled estimates resulted in substantial between-trial heterogeneity
(I2 ranged from 59% to 87%), which, however, was
found considerably reduced in the stratified meta-analyses
according to the type of spinal pain (ie, neck pain, acute/
chronic low back pain, or sciatica). Finally, another limitation
of our study is that there were very few trials on neck pain,
and none on whiplash.
We provide sound evidence that NSAIDs are effective, but do
not offer clinically important benefits for spinal pain above
those attributable to placebo, given overall pooled estimated differences
were <10 points. This is crucially important because
we now know paracetamol is ineffective, [6, 7] and opioids only
offer small benefits for spinal pain.  Thus, given our results and
evidence from these recent high-quality meta-analyses, it seems
that there are no analgesics with clinically important effects over
placebo for spinal pain. This is a problem, as current guidelines
for spinal pain endorse these three medicines.  For instance, the
National Institute for Health and Care Excellence (NICE) guidance
on low back pain and sciatica now recommends NSAIDs as
first analgesic option and suggests the use of opioids with paracetamol
to treat spinal pain. In our review, even when the
effects of NSAIDs were analysed for different spinal pain strata
(ie, neck pain, acute/chronic low back pain or sciatica), only 3
of the 14 analyses revealed effects that were marginally above
our threshold for clinical relevance. The effects observed in
trials including participants with neck pain were unexpected,
particularly because these trials investigated topical NSAIDs
only. Our safety analysis revealed that NSAIDs increased the risk
of gastrointestinal adverse effects by 2.5 times compared with
placebo, although safety data were limited to trials that used
non-selective NSAIDs. However, it is established that all
NSAIDs, including COX-2 inhibitors, have been linked to
gastrointestinal harms. [15, 72] Our safety results should be interpreted
with caution given the short duration of exposure to
NSAIDs in included trials.
In summary, compared with placebo, NSAIDs do not provide
a clinically important effect on spinal pain, and six patients
must be treated with NSAIDs for one patient to achieve a clinically
important benefit in the short-term. When this result is
taken together with those from recent reviews on paracetamol
and opioids, it is now clear that the three most widely used, and
guideline-recommended medicines for spinal pain do not
provide clinically important effects over placebo. There is an
urgent need to develop new analgesics for spinal pain.
Refer to the Full-Text Article