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Benefits and Harms of Treatments for Chronic Non-Specific Low Back Pain Without Radiculopathy: Systematic Review and Meta-analysis

Published:November 15, 2022DOI:https://doi.org/10.1016/j.spinee.2022.11.003

      ABSTRACT

      Background context

      Currently, there are no published studies that compare non-pharmacological, pharmacological and invasive treatments for chronic low back pain in adults and provide summary statistics for benefits and harms.

      Purpose

      The aim of this review was to compare the benefits and harms of treatments for the management of chronic low back pain without radiculopathy and to report the findings in a format that facilitates direct comparison (Benefit-Harm Scale: level 1 to 7).

      Design

      Systematic review and meta-analysis of randomized controlled trials, including trial registries, from electronic databases up to 23rd May 2022.

      Patient sample

      Adults with non-specific chronic low back pain, excluding radicular pain in any clinical setting.

      Outcome measures

      Comparison of pain at immediate-term (≤2 weeks) and short-term (>2 weeks to ≤12 weeks) and serious adverse events using the Benefit-Harm Scale (level 1 to 7).

      Methods

      This was a registered systematic review and meta-analysis of randomized controlled trials. Interventions included non-pharmacological (acupuncture, spinal manipulation only), pharmacological and invasive treatments compared to placebo. Best evidence criteria was used. Two independent reviewers conducted eligibility assessment, data extraction and quality appraisal.

      Results

      The search retrieved 17,362 records. Three studies provided data on the benefits of interventions, and 30 provided data on harms. Studies included interventions of acupuncture (n = 8); manipulation (n = 2); pharmacological therapies (n = 9), including NSAIDs and opioid analgesics; surgery (n = 8); and epidural corticosteroid injections (n = 3). Acupuncture (standardized mean difference (SMD) -0.51, 95%CI -0.88 to -0.14, n = 1 trial, moderate quality of evidence, benefit rating of 3) and manipulation (SMD -0.39 (96%CI -0.56 to -0.21, n = 2 trials, moderate quality of evidence, benefit rating of 5) were effective in reducing pain intensity compared to sham. The benefit of the other interventions was scored as uncertain due to not being effective, statistical heterogeneity preventing pooling of effect sizes, or the absence of relevant trials. The harms level warnings were at the lowest (e.g. indicating rarer risk of events) for acupuncture, spinal manipulation, NSAIDs, combination ingredient opioids, and steroid injections, while they were higher for single ingredient opioid analgesics (level 4) and surgery (level 6).

      Conclusions

      There is uncertainty about the benefits and harms of all the interventions reviewed due to the lack of trials conducted in patients with chronic non-specific low back pain without radiculopathy. From the limited trials conducted, non-pharmacological interventions of acupuncture and spinal manipulation provide safer benefits than pharmacological or invasive interventions. However, more research is needed. There were high harms ratings for opioids and surgery.

      Registration

      This review was registered on the International Prospective Register of Systematic Reviews.

      Keywords

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      Reference

        • Chen S
        • Chen M
        • Wu X
        • Lin S
        • Tao C
        • Cao H
        • et al.
        Global, regional and national burden of low back pain 1990–2019: A systematic analysis of the Global Burden of Disease study 2019.
        J Orthop Translat. 2022; 32: 49-58
        • Vos T
        • et al.
        Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019.
        The Lancet. 2020; 396: 1204-1222
        • Dieleman JL
        • Cao J
        • Chapin A
        • et al.
        US Health Care Spending by Payer and Health Condition, 1996-2016.
        JAMA. 2020; 323: 863-884
        • Oliveira CB
        • Maher CG
        • Pinto RZ
        • Traeger AC
        • Lin C-WC
        • Chenot J-F
        • et al.
        Clinical practice guidelines for the management of non-specific low back pain in primary care: an updated overview.
        Eur Spine J. 2018; 27: 2791-2803
        • Kreiner DS
        • Matz P
        • Bono CM
        • Cho CH
        • Easa JE
        • Ghiselli G
        • et al.
        Guideline summary review: an evidence-based clinical guideline for the diagnosis and treatment of low back pain.
        Spine J. 2020; 20: 998-1024
        • Qaseem A
        • Wilt TJ
        • McLean RM
        • Forciea M.
        Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians.
        Ann Intern Med. 2017; 147: 478-491
      1. National Institute for Health and Care Excellence (NICE). Low back pain and sciatica in over 16s: assessment and management. National Institute for Health and Care Excellence. 2020. Available at:https://www.nice.org.uk/guidance/ng59/resources/low-back-pain-and-sciatica-in-over-16s-assessment-and-management-pdf-1837521693637.

        • Varga Z
        • Sabzwari SRA
        • Vargova V.
        Cardiovascular risk of nonsteroidal anti-inflammatory drugs: an under-recognized public health issue.
        Cureus. 2017; 9: e1144
        • Degenhardt L
        • Grebely J
        • Stone J
        • Hickman M
        • Vickerman P
        • Marshall BDL
        • et al.
        Global patterns of opioid use and dependence: harms to populations, interventions, and future action.
        The Lancet. 2019; 394: 1560-1579
      2. Fischhoff B, Brewer NT, Downs JS. Communicating Risks and Benefits: An Evidence-Based User's Guide. 2018. Available at http://www.fda.gov/ScienceResearch/SpecialTopics/RiskCommunication/default.htm.

        • Vandenbroucke JP
        • Psaty BM.
        Benefits and risks of drug treatments: how to combine the best evidence on benefits with the best data about adverse effects.
        JAMA. 2008; 300: 2417-2419
        • Schers H
        • Wensing M
        • Huijsmans Z
        • van Tulder M
        • Grol R.
        Implementation barriers for general practice guidelines on low back pain. a qualitative study.
        Spine. 2001; 26: E348-E353
        • Qaseem A
        • McLean RM
        • O'Gurek D
        • et al.
        Nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults: a clinical guideline from the American College of Physicians and American Academy of Family Physicians.
        Ann Intern Med. 2020; 173: 739-748
        • Enthoven WT
        • Roelofs PD
        • Deyo RA
        • van Tulder MW
        • Koes BW.
        Non-steroidal anti-inflammatory drugs for chronic low back pain.
        Cochrane Database Syst. Rev. 2016; 2CD012087
        • Page MJ
        • McKenzie JE
        • Bossuyt PM
        • Boutron I
        • Hoffmann TC
        • Mulrow CD
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ. 2021; 372: n71
      3. Boyd CM, Singh S, Varadhan R, Weiss CO, Sharma R, Bass EB, Puhan MA. Methods for benefit and harm assessment in systematic reviews. methods research report. (Prepared by the Johns Hopkins University Evidence-based Practice Center under contract No. 290-2007-10061-I). AHRQ Publication No. 12(13)-EHC150-EF. Rockville, MD: Agency for Healthcare Research and Quality; November 2012.

      4. Conway J, Federico F, Stewart K, Campbell MJ. Respectful management of serious clinical adverse events (Second Edition). IHI Innovation Series white paper. 2011. Cambridge, Massachusetts: Institute for Healthcare Improvement.

      5. Food and Drug Administration (FDA) What is a Serious Adverse Event? 2018. Available at http://www.fda.gov/safety/medwatch/howtoreport/ucm053087.htm

        • Furlan AD
        • Malmivaara A
        • Chou R
        • Maher CG
        • Deyo RA
        • Schoene M
        • Bronfort G
        • van Tulder MW
        • Editorial Board of the Cochrane Back, Neck Group
        2015 Updated method guidelines for systematic reviews in the Cochrane Back and Neck Group.
        Spine. 2015; 40: 1660-1673
      6. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. Available at www.training.cochrane.org/handbook.

        • Kendall S.
        Evidence-based resources simplified.
        Can Fam Physician. 2008; 54: 241-243
        • Davidson M
        • Iles R.
        Evidence-based practice in therapeutic health care.
        in: Liamputtong P. Research Methods in Health: Foundations for Evidence-Based Practice. 2nd ed. Oxford University Press, South Melbourne2013
        • Cohen J.
        Statistical power analysis for the behavioral sciences.
        Academic Press, New York1977: 1-27
        • Ostelo RW
        • Deyo RA
        • Stratford P
        • Waddell G
        • Croft P
        • Von Korff M
        • et al.
        Interpreting change scores for pain and functional status in low back pain: towards international consensus regarding minimal important change.
        Spine (Phila Pa 1976). 2008; 33: 90-94
      7. European Medicine Agency. European Commission: Enterprise and Industry Direcorate-General. A guideline on summary of product characteristics (Summary of Product Characteristics). Available at: https://healtheceuropaeu/system/files/2016-11/smpc_guideline_rev2_en_0pdf. 2009.

        • Guyatt GH
        • Oxman AD
        • Vist GE
        • Kunz R
        • Falck-Ytter Y
        • Alonso-Coello P
        • et al.
        GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.
        BMJ. 2008; 336: 924-926
        • Groubi S
        • Elleuch H
        • Baklouti S
        • Elleuch MH.
        Les lombalgiques chroniques et manipulations vertébrales. Étude prospective à propos de 64 cas.
        Ann Readapt Med Phys. 2007; 50: 570-576
        • Sung WS
        • Hong Y
        • Jeon SR
        • Yoon J
        • Chung EK
        • Jo HG
        • Kim TH
        • Shin S
        • Lee HJ
        • Kim EJ
        • Seo BK
        • Choi J
        • Nam D
        Efficacy and safety of thread embedding acupuncture combined with acupuncture for chronic low back pain: A randomized, controlled, assessor-blinded, multicenter clinical trial.
        Medicine (Baltimore). 2020; 99: e22526
        • Witt CM
        • Jena S
        • Selim D
        • Brinkhaus B
        • Reinhold T
        • Wruck K
        • et al.
        Pragmatic randomized trial evaluating the clinical and economic effectiveness of acupuncture for chronic low back pain.
        American J Epidemiol. 2006; 164: 487-496
        • Brinkhaus B
        • Witt CM
        • Jena S
        • Linde K
        • Streng A
        • Wagenpfeil S
        • et al.
        Acupuncture in patients with chronic low back pain: a randomized controlled trial.
        Arch Intern Med. 2006; 166: 450-457
        • Cho Y-J
        • Song Y-K
        • Cha Y-Y
        • Shin B-C
        • Shin I-H
        • Park H-J
        • et al.
        Acupuncture for chronic low back pain: a multicenter, randomized, patient-assessor blind, sham-controlled clinical trial.
        Spine. 2013; 38: 549-557
        • Haake M
        • Müller HH
        • Schade-Brittinger C
        • Basler HD
        • Schäfer H
        • Maier C
        • et al.
        German acupuncture trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups.
        Arch Intern Med. 2007; 167: 1892-1898
        • Lee HJ
        • Choi BI
        • Jun S
        • Park MS
        • Oh SJ
        • Lee JH
        • et al.
        Efficacy and safety of thread embedding acupuncture for chronic low back pain: a randomized controlled pilot trial.
        Trials. 2018; 19: 680
        • Leibing E
        • Leonhardt U
        • Koster G
        • Goerlitz A
        • Rosenfeldt JA
        • Hilgers R
        • et al.
        Acupuncture treatment of chronic low-back pain - A randomized, blinded, placebo-controlled trial with 9-month follow-up.
        Pain. 2002; 96: 189-196
        • Pach D
        • Xiaoli Y-S
        • Lüdtke R
        • Roll S
        • Icke K
        • Brinkhaus B
        • et al.
        Standardized versus individualized acupuncture for chronic low back pain: a randomized controlled trial.
        eCAM. 2013; 2013: 1
        • Licciardone JC
        • Minotti DE
        • Gatchel RJ
        • Kearns CM
        • Singh KP.
        Osteopathic manual treatment and ultrasound therapy for chronic low back pain: a randomized controlled trial.
        Ann Fam Med. 2013; 11: 122-129
        • Birbara CA
        • Puopolo AD
        • Munoz DR
        • Sheldon EA
        • Mangione A
        • Bohidar NR
        • et al.
        Treatment of chronic low back pain with etoricoxib, a new cyclo-oxygenase-2 selective inhibitor: improvement in pain and disability - a randomized, placebo-controlled, 3-month trial.
        J Pain. 2003; 4: 307-315
        • Buynak R
        • Shapiro DY
        • Okamoto A
        • Van Hove I
        • Rauschkolb C
        • Steup A
        • et al.
        Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study.
        Expert Opin Pharmacother. 2010; 11: 1787-1804
        • Chu LF
        • D'Arcy N
        • Brady C
        • Zamora AK
        • Young CA
        • Kim JE
        • et al.
        Analgesic tolerance without demonstrable opioid-induced hyperalgesia: a double-blinded, randomized, placebo-controlled trial of sustained-release morphine for treatment of chronic non-radicular low-back pain.
        Pain. 2012; 153: 1583-1592
        • Cloutier C
        • Taliano J
        • O'Mahony W
        • Csanadi M
        • Cohen G
        • Sutton I
        • et al.
        Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: a placebo-controlled, randomized study.
        Pain Res Manag. 2013; 18: 75-82
        • Gordon A
        • Callaghan D
        • Spink D
        • Cloutier C
        • Dzongowski P
        • O'Mahony W
        • et al.
        Buprenorphine transdermal system in adults with chronic low back pain: a randomized, double-blind, placebo-controlled crossover study, followed by an open-label extension phase.
        Clin Ther. 2010; 32: 844-860
        • Uberall MA
        • Mueller-Schwefe GH
        • Terhaag B.
        Efficacy and safety of flupirtine modified release for the management of moderate to severe chronic low back pain: results of SUPREME, a prospective randomized, double-blind, placebo- and active-controlled parallel-group phase IV study.
        Curr Med Res Opin. 2012; 28: 1617-1634
        • Webster LR
        • Butera PG
        • Moran LV
        • Wu N
        • Burns LH
        • Friedmann N.
        Oxytrex minimizes physical dependence while providing effective analgesia: a randomized controlled trial in low back pain.
        J Pain. 2006; 7: 937-946
        • Peloso PM
        • Fortin L
        • Beaulieu A
        • Kamin M
        • Rosenthal N.
        Analgesic efficacy and safety of tramadol/acetaminophen combination tablets (Ultracet) in treatment of chronic low back pain: a multicenter, outpatient, randomized, double blind, placebo controlled trial.
        J Rheumatol. 2004; 31: 2454-2463
        • Ruoff GE
        • Rosenthal N
        • Jordan D
        • Karim R
        • Kamin M
        • Protocol C-SG
        Tramadol/acetaminophen combination tablets for the treatment of chronic lower back pain: A multicenter, randomized, double-blind, placebo-controlled outpatient study.
        Clin Ther. 2003; 25: 1123-1141
        • Brox J
        • Sorense R
        • Friis A
        • Nygaard O
        • Indahl A
        • Keller A
        • et al.
        Randomized clinical trial of lumbar instrumental fusion and cognitive intervention and exercises of patients with chronic low back pain and disc degeneration.
        Ann Rheum Dis. 2003; 62: 88-89
        • Hartwig T
        • Schaser KD
        • Pumberger M
        • Streitparth F
        • Druschel C
        • Jacobs C
        • et al.
        A prospective randomized analysis of spinal fusion and clinical outcome parameters of titanium versus carbon composite rods for single-level transforaminal lumbar interbody fusion: a 12 months follow up.
        Eur Spine J. 2014; 23: 2477-2478
        • Hedlund R
        • Johansson C
        • Hägg O
        • Fritzell P
        • Tullberg T.
        The long-term outcome of lumbar fusion in the Swedish lumbar spine study.
        Spine J. 2016; 16: 579-587
        • Hellum C
        • Johnsen LG
        • Storheim K
        • Nygaard OP
        • Brox JI
        • Rossvoll I
        • et al.
        Surgery with disc prosthesis versus rehabilitation in patients with low back pain and degenerative disc: two year follow-up of randomised study.
        BMJ. 2011; 342: d2786
        • Marsh GDJ
        • Mahir S
        • Leyte A.
        A prospective randomised controlled trial to assess the efficacy of dynamic stabilisation of the lumbar spine with the Wallis ligament.
        Eur Spine J. 2014; 23: 2156-2160
        • Thalgott JS
        • Fogarty ME
        • Giuffre JM
        • Christenson SD
        • Epstein AK
        • Aprill C.
        A prospective, randomized, blinded, single-site study to evaluate the clinical and radiographic differences between frozen and freeze-dried allograft when used as part of a circumferential anterior lumbar interbody fusion procedure.
        Spine. 2009; 34: 1251-1256
        • Van de Kelft E
        • Goethem J
        • Van Goethem J.
        Trabecular metal spacers as standalone or with pedicle screw augmentation, in posterior lumbar interbody fusion: a prospective, randomized controlled trial.
        Eur Spine J. 2015; 24: 2597-2606
        • Zhao HE
        • Gao HR
        • Zhou CP
        • Qian S
        • Yuan YF
        • Xue WG
        • et al.
        A randomized controlled trial with 5 years of follow-up comparing minimally invasive and open transforaminal lumbar interbody fusion in disc herniation at single level.
        Exp Ther Med. 2019; 17: 3614-3620
        • Lakemeier S
        • Lind M
        • Schultz W
        • Fuchs-Winkelmann S
        • Timmesfeld N
        • Foelsch C
        • et al.
        A comparison of intraarticular lumbar facet joint steroid injections and lumbar facet joint radiofrequency denervation in the treatment of low back pain: a randomized, controlled, double-blind trial.
        Anesth Analg. 2013; 117: 228-235
        • Manchikanti L
        • Manchikanti KN
        • Manchukonda R
        • Cash KA
        • Damron KS
        • Pampati V
        • et al.
        Evaluation of lumbar facet joint nerve blocks in the management of chronic low back pain: preliminary report of a randomized, double-blind controlled trial: clinical trial NCT00355914.
        Pain Physician. 2007; 10: 425-440
        • Ribeiro LH
        • Furtado RNV
        • Konai MS
        • Andreo AB
        • Rosenfeld A
        • Natour J.
        Effect of facet joint injection versus systemic steroids in low back pain: a randomized controlled trial.
        Spine. 2013; 38: 1995-2002
        • Xiang Y
        • He JY
        • Tian HH
        • Cao BY
        • Li R.
        Evidence of efficacy of acupuncture in the management of low back pain: a systematic review and meta-analysis of randomised placebo- or sham-controlled trials.
        Acupunct Med. 2020; 38: 15-24
        • Rubinstein SM de Zoete A
        • van Middelkoop M
        • Assendelft WJJ
        • de Boer MR
        • van Tulder MW.
        Benefits and harms of spinal manipulative therapy for the treatment of chronic low back pain: systematic review and meta-analysis of randomised controlled trials.
        BMJ. 2019; 364: 1689
        • Shanthanna H
        • Gilron I
        • Rajarathinam M
        • AlAmri R
        • Kamath S
        • Thabane L
        • et al.
        Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials.
        PLoS Med. 2017; 14e1002369
        • Abdel Shaheed C
        • Maher CG
        • Williams KA
        • Day R
        • McLachlan AJ
        Efficacy, tolerability, and dose-dependent effects of opioid analgesics for low back pain: a systematic review and meta-analysis.
        JAMA Intern Med. 2016; 176: 958-968
        • Anderson DB
        • Ferreira ML
        • Harris IA
        • Davis GA
        • Stanford R
        • Beard D
        • Li Q
        • et al.
        SUcceSS, SUrgery for Spinal Stenosis: protocol of a randomised, placebo-controlled trial.
        BMJ Open. 2019; 9e024944
        • Abdel Shaheed C
        • Ferreira GE
        • Dmitritchenko A
        • McLachlan AJ
        • Day RO
        • Saragiotto B
        • Lin C
        • Langendyk V
        • Stanaway F
        • Latimer J
        • Kamper S
        • McLachlan H
        • Ahedi H
        • Maher CG
        The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews.
        Med J Aust. 2021; 214: 324-331
        • Johansen ME.
        Gabapentinoid use in the United States 2002 through 2015.
        JAMA Intern Med. 2018; 178: 292-294
        • Torrance N
        • Veluchamy A
        • Zhou Y
        • Fletcher EH
        • Moir E
        • et al.
        Trends in gabapentinoid prescribing, co-prescribing of opioids and benzodiazepines, and associated deaths in Scotland.
        Brit J Anaesth. 2020; 125: 159-167
        • Montastruc F
        • Loo SY
        • Renoux C.
        Trends in first gabapentin and pregabalin prescriptions in primary care in the United Kingdom, 1993-2017.
        JAMA. 2018; 320: 2149-2150
        • Mathieson S
        • Valenti L
        • Maher CG
        • Britt H
        • Li Q
        • McLachlan AJ
        • Lin CC.
        Worsening trends in analgesics recommended for spinal pain in primary care.
        Eur Spine J. 2018; 27: 1136-1145
        • Cairns R
        • Schaffer AL
        • Ryan N
        • Pearson SA
        • Buckley NA.
        Rising pregabalin use and misuse in Australia: trends in utilization and intentional poisonings.
        Addiction. 2019; 114: 1026-1034
        • Fonseca F
        • Lenahan W
        • Dart RC
        • et al.
        Non-medical use of prescription gabapentinoids (gabapentin and pregabalin) in five European countries.
        Front Psychiatry. 2021; 12676224
        • Ibiloye EA
        • Barner JC
        • Lawson KA
        • Rascati KL
        • Evoy KE
        • Peckham AM.
        Prevalence of and factors associated with gabapentinoid use and misuse among Texas Medicaid recipients.
        Clin Drug Invest. 2021; 41: 245-253
        • Iacobucci G.
        UK government to reclassify pregabalin and gabapentin after rise in deaths.
        BMJ. 2017; 358: j4441
        • Peckham AM
        • Ananickal MJ
        • Sclar DA.
        Gabapentin use, abuse, and the US opioid epidemic: the case for reclassification as a controlled substance and the need for pharmacovigilance.
        Risk Manag Healthc Policy. 2018; 11: 109-116
        • Hamilton M
        • Mathieson S
        • Blyth F
        • Gnjidic D
        • Jansen J
        • Weir K
        • Abdel Shaheed C
        • Lin CW-C
        Barriers, facilitators and resources to opioid deprescribing in primary care: experiences of general practitioners in Australia.
        PAIN. 2022; 163: e518-e526
        • Hulley SB
        • Cumming SR
        • Browner WS
        • Grady DG
        • Newman TB.
        Designing clinical research.
        Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia2013
        • Chou R
        • Qaseem A
        • Snow V
        • Casey D
        • Cross Jr, JT
        • Shekelle P
        • et al.
        Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society.
        Ann Intern Med. 2007; 147: 478-491