Clinical Review & Education

JAMA Clinical Evidence Synopsis

NSAIDs for Chronic Low Back Pain

Wendy T. M. Enthoven, MD, PhD; Pepijn D. Roelofs, PhD; Bart W. Koes, PhD

CLINICAL QUESTION Arenonsteroidalanti-inflammatorydrugs(NSAIDs)associatedwithgreaterpain

relief than placebo, other drugs, and nondrug treatments for patients with chronic low back pain?

BOTTOM LINE Compared with placebo, NSAIDs are associated with a small but significant
improvement in pain and disability in patients with chronic low back pain, although this
difference became nonsignificant when studies with high risk for bias were excluded. The
associated benefits were smaller than the minimal clinically important difference.

Introduction
Chroniclowbackpain(lasting>3months)isacommonhealthproblem.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most
prescribedmedicationsandarefrequentlyusedbypatientswithchronic
lowbackpain.1,2 Clinicalpracticeguidelinesrecommendshort-termuse
ofNSAIDsforpainreliefinpatientswithchroniclowbackpain,buttheir
efficacy is still unclear.3,4 This JAMA Clinical Evidence Synopsis summa-
rizes a Cochrane review5 on the association of NSAIDs with pain relief
and adverse events for patients with chronic low back pain.
Summary of Findings
Sixofthe13studiescomparedNSAIDswithplacebo(n = 1354)(Figure).
There was low-quality evidence based on the Grades of Recommen-
dation, Assessment, Development and Evaluation assessment6 that
NSAIDswereassociatedwithstatisticallysignificantgreaterbenefitthan
placeboforpainintensity.Themeandifferencefrombaselinewas−6.97
(95% CI, −10.74 to −3.19) on a 0-to-100 visual analog scale and the
median follow-up was 56 days (interquartile range, 13 to 91 days). For
patientswithchronicbackpain,theminimalclinicallyimportantchange
was at least 20 mm.7 Four studies measured disability. There was
low-quality evidence that NSAIDs were associated with greater ben-
efit than placebo for the outcome of disability. The mean difference
from baseline was −0.85 (95% CI, −1.30 to −0.40) on a 0-to-24 visual
analog scale. The minimal clinically important change was 3.5 points.7
Six studies reported adverse events. NSAIDs were not associ-
ated with higher rates of adverse events vs placebo (735 vs 619 events;
relative risk [RR], 1.04, 95% CI, 0.92 to 1.17). When randomized clini-
cal trials (RCTs) with high risk of bias were excluded, the associated
benefits were smaller and the difference was not statistically signifi-
cant (pain: −5.03 [95% CI, −10.37 to 0.32]; disability: −0.41 [95% CI,
−1.04 to 0.23]). Three studies comparing different types of NSAIDs
and studies comparing NSAIDs with paracetamol (acetaminophen)
(n = 30) and pregabalin (n = 36) were too heterogeneous for a
quantitative meta-analysis. All reported no associated differences in
pain and disability. One trial showed a better overall improvement
in pain from baseline, favoring celecoxib vs tramadol (508 of 798 pa-
tients [64%] vs 412 of 785 patients [52%] improved by ⱖ30%, re-
spectively; RR, 1.20 [95% CI, 1.11 to 1.32]). One trial compared NSAIDs
with home-based exercise (n = 201) and disability improved more in
participants who exercised, but the pain scores were not different.

Evidence Profile
No. of randomized clinical trials: 13
Study years: 1981-2011 (conducted); 1982-2013 (published)
Last search date: June 24, 2015
No. of patients: 4807
Men: 2067 (43%) Women: 2740 (57%)
Race/ethnicity: Not reported
Age, mean: 49.7 years
Clinical settings: General practice and outpatient
Countries: Australia, Belgium, Brazil, Canada, Costa Rica, Czech
Republic, Denmark, Ecuador, Finland, France, Germany, Hong
Kong, Hungary, Italy, Japan, New Zealand, Norway, Peru, Portugal,
Russian Federation, Singapore, Sweden, Taiwan, Thailand, United
Arab Emirates, United Kingdom, United States, Venezuela
Comparison: NSAIDs vs placebo, paracetamol/acetaminophen, other
types of NSAIDs, pregabalin, tramadol, and home-based exercise
Primary outcome measures: Pain intensity, global measure
(eg, overall improvement), back pain–specific functional
status (eg, Roland Disability Questionnaire), adverse events
Discussion
TheresultsshowedthatNSAIDswereassociatedwithgreaterimprove-
ment in pain intensity and disability compared with placebo. However,
the magnitude of the association was small, the quality of the evidence
was low, and the statistical heterogeneity was high. There were no as-
sociations between type of NSAID and pain scores, although the num-
ber of trials was small. Two trials used an enriched enrollment design,
in which only participants who responded well to NSAIDs before ran-
domization were enrolled. These trials may overestimate the associa-
tion of NSAIDs with benefit and reduce the external validity.
Almost all RCTs mentioned adverse events. However, trials
lacked statistical power and follow-up periods were too short to in-
vestigate serious adverse events. Therefore, conclusions regard-
ing the association of NSAIDs with adverse events cannot be made.
The literature search was updated on September 16, 2016. One
study was identified that compared celecoxib with paracetamol
(acetaminophen) in 50 participants.8 In this trial,8 celecoxib improved
pain and disability compared with paracetamol. No other trials in the
Cochrane review compared celecoxib with paracetamol. One trial in-
cluded in the Cochrane review reported no difference in outcomes
between the NSAID diflunisal compared with paracetamol.

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 Clinical Review & Education JAMA Clinical Evidence Synopsis

Figure. Associations of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) With Pain and Disability for Chronic Low Back Pain vs Placebo

A Mean change in pain intensity from baseline on 100-mm visual analog scalea

NSAID Placebo
Total No. of Total No. of Mean Difference Favors Favors
Source Participants Mean (SD) Participants Mean (SD) (95% CI)b NSAID Placebo Weight, %
Allegrini, 2009 60 –28 (31.7) 59 –16.5 (31.7) –11.50 (–22.89 to –0.11) 8.4
Berry, 1982 37 –11.5 (34) 37 9.4 (34) –20.90 (–36.39 to –5.41) 5.1
Birbara, 2003 107 –7.5 (23.3) 109 0 (23.3) –7.50 (–13.71 to –1.29) 18.2
Coats, 2004 148 –41.9 (27.7) 143 –31.1 (27.7) –10.80 (–17.17 to –4.43) 17.7
Katz, 2011 88 –2.4 (11.6) 41 0 (11.6) –2.40 (–6.70 to 1.90) 24.5
Kivitz, 2013 295 –4.1 (22.3) 230 0 (22.3) –4.10 (–7.94 to –0.26) 26.1
Total 735 619 –6.97 (–10.74 to –3.19) 100.0

–40 –30 –20 –10 0 10 20

Mean Difference (95% CI)

B Mean change in disability from baseline on 24-item Rowland-Morris Disability Questionnairec

NSAID Placebo
Total No. of Total No. of Mean Difference Favors Favors
Source Participants Mean (SD) Participants Mean (SD) (95% CI)d NSAID Placebo Weight, %
Birbara, 2003 107 –2.1 (5.3) 109 0 (5.3) –2.10 (–3.51 to –0.69) 10.1
Coats, 2004 148 –1.1 (3.1) 143 0 (3.1) –1.10 (–1.81 to –0.39) 39.7
Katz, 2011 88 –0.6 (3.1) 41 0 (3.1) –0.60 (–1.75 to 0.55) 15.3
Kivitz, 2013 295 –0.32 (4.4) 230 0 (4.4) –0.32 (–1.08 to 0.44) 35.0
Total 638 523 –0.85 (–1.30 to –0.40) 100.0

–4 –3 –2 –1 0 1 2
Mean Difference (95% CI)

c
The error bars indicate the 95% CIs. The size of the data markers corresponds Score range is 0 to 24; a higher number indicates more disability.
with the weight of the study. Follow-up was 16 weeks or shorter. d
A fixed-effects model was used for the analyses.
a
Score range is 0 to 100 mm; a higher number indicates more pain.
b
A random-effects model was used for the analyses.

Limitations American Pain Society guidelines on chronic back pain recommend

Strict inclusion criteria were used regarding the duration of back pain,
meaning that only trials reporting the results for patients with chronic
low back pain were included.
Comparison of Findings With Current Practice Guidelines
Because of possible adverse effects, the European Guidelines of the
Management of Chronic Low Back Pain recommend using NSAIDs
for up to 3 months, and the American College of Physicians and the
the shortest duration possible.3,4 In the Cochrane review,5 there was
low-quality evidence that NSAIDs are associated with improve-
ment in pain and disability compared with placebo; however, the
strength of the association is small and clinically not meaningful.
Areas in Need of Future Study
Future research is needed to identify patients who are most likely
to respond well to NSAIDs.

ARTICLE INFORMATION
Author Affiliations: Department of General
Practice, Erasmus Medical Center, Rotterdam, the
Netherlands (Enthoven, Koes); Research Centre
Innovations in Care, Rotterdam University of
Applied Sciences, Rotterdam, the Netherlands
(Roelofs).
Corresponding Author: Wendy T. M. Enthoven,
MD, PhD, Erasmus Medical Center, PO Box 2040,
3000 CA Rotterdam, the Netherlands
(w.enthoven@erasmusmc.nl).
Section Editor: Mary McGrae McDermott, MD,
Senior Editor.
Conflict of Interest Disclosures: The authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
none were reported.
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