Intended for healthcare professionals


Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study

BMJ 2008; 336 doi: (Published 17 January 2008) Cite this as: BMJ 2008;336:138
  1. Martin Underwood, professor of general practice1,
  2. Deborah Ashby, professor of medical statistics2,
  3. Pamela Cross, study clinician 1,
  4. Enid Hennessy, senior lecturer in medical statistics2,
  5. Louise Letley, senior nurse manager 3,
  6. Jeannett Martin, visiting fellow 4,
  7. Shahrul Mt-Isa, statistician 2,
  8. Suzanne Parsons, research fellow 1,
  9. Madge Vickers, research director 5,
  10. Ken Whyte, study manager1
  11. on behalf of the TOIB study team
  1. 1Centre for Health Sciences, Barts and The London, Queen Mary, University of London, London E1 2AT
  2. 2Wolfson Institute of Preventive Medicine, Barts and The London, Queen Mary, University of London, London EC1M 6BQ
  3. 3MRC General Practice Research Framework, London NW1 2ND
  4. 4Department of Primary and Social Care, London South Bank University, London SE1 6EN
  5. 5Clinical Trials Co-ordinating Centre, University of Hertfordshire, Hatfield, Herts AL10 9LB
  1. Correspondence to: M Underwood m.underwood{at}
  • Accepted 7 November 2007


Objective To determine whether older patients with chronic knee pain should be advised to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs).

Design Randomised controlled trial and patient preference study.

Setting 26 general practices.

Participants People aged ≥50 with knee pain: 282 in randomised trial and 303 in preference study.

Interventions Advice to use topical or oral ibuprofen.

Primary outcome measures WOMAC (Western Ontario and McMaster Universities) osteoarthritis index, major and minor adverse effects.

Results Changes in global WOMAC scores at 12 months were equivalent. In the randomised trial the difference (topical minus oral) was two points (95% confidence interval −2 to 6); in the preference study, it was one point (−4 to 6). There were no differences in major adverse effects in the trial or study. The only significant differences in secondary outcomes were in the randomised trial. The oral group had more respiratory adverse effects (17% v 7%,95% confidence interval for difference −17% to −2%), the change in serum creatinine was 3.7 mmol/l less favourable (0.9 µmol/l to 6.5 µmol/l); and more participants changed treatments because of adverse effects (16% v 1%, −16% to −5%). In the topical group more participants had chronic pain grade III or IV at three months, and more participants changed treatment because of ineffectiveness.

Conclusions Advice to use oral or topical preparations has an equivalent effect on knee pain over one year, and there are more minor side effects with oral NSAIDs. Topical NSAIDs may be a useful alternative to oral NSAIDs.

Trial registration ISRCTN 79353052.


  • We thank all the people who took part in the study and the following hospital laboratories for processing blood tests: Ashford and St Peter’s Trust, Chertsey; Barnet and Chase Farm Hospitals NHS Trust, Barnet; Belfast City Hospital Trust, Belfast; County Durham and Darlington Acute Hospitals NHS Trust, Darlington; Fife Acute Hospitals NHS Trust, Kirkcaldy; James Paget University Hospitals NHS Foundation Trust, Gorleston; Kettering General Hospital NHS Trust, Kettering; Maidstone and Tunbridge Wells NHS Trust, Tunbridge Wells; Mater Hospital Trust, Belfast; North Cumbria Acute Hospitals NHS Trust; Pembrokeshire and Derwent NHS Trust, Haverfordwest; Peterborough and Stamford Hospital NHS Foundation Trust, Peterborough; Poole Hospital NHS Trust, Poole; Sherwood Forest Hospitals NHS Trust, Sutton-in-Ashfield; Shrewsbury and Telford Hospital NHS Trust, Shrewsbury; South Devon Healthcare NHS Trust, Torquay; South Tees Hospitals NHS Trust, Middlesbrough; Taunton and Somerset NHS Trust, Taunton; United Bristol Healthcare NHS Trust, Bristol; United Hospitals Health and Social Services Trust, Antrim; University Hospitals of Morecambe Bay NHS Trust, Kendal; Walsall Hospitals NHS Trust, Walsall; West Suffolk Hospital NHS Trust, Bury St Edmunds; Wirral Hospital NHS Trust, Upton; Worcestershire Acute Hospitals NHS Trust, Redditch; York Hospitals NHS Trust, York.

  • We thank Lynette Edwards for comments on earlier drafts of this paper and Dawn Carnes for assistance in preparing this paper.

  • Other members of the study team were Valerie Brueton, Gene Feder, Bruce Kidd, Hansa Shah, and Helen Tate.

  • General practice research framework

  • Regional nurses: Jane Elwood, Kay Foulger, Sue Fox, Anne Hall, Lesley Hand, Angela Hill, Fiona Leslie, Eileen Marshall, Anna Williams.

  • Lead general practitioners: P G Austin, R Brownlie, V Buntwal, H Byrne, A Darrah, J Durkan, Christopher Hand, D P Houlahan, A Howitt, D Jones, M Leci, S H Rogerson, E Montague, N McGreevy, T McVey, C R Pierce, E Rule, A Sood, W H Smithson, G Stein, Amrit Takhar, P Thrower, S Warlow, C J Watkins, A J S White, SM Williams, Michael Yardley.

  • Research nurses:G Bryant, J Byrne, M Clark, J Copland, M Cotterill, M Couche, J Elwood, S Fox, A Hall, S Hallam, L Hand, D Hanlon, A Hogg, A Houlahan, J Jackson, M Lloyd, J Madden, J McArdle, C McVey, F Morris, A Norton, K O’Brien, S Robinson, M Rogerson, J Simmonds, C Teward, A Thompson, G White, A Williams, G Wilkinson.

  • Randomisation team at MRC Clinical Trials Unit: Omobola Fadahunsi, Rhian Gabe, Ann Gerrard, Farid Miah, Sinead Nally, Angela Poland.

  • Trial steering committee: Marta Buszewicz, John Grimley-Evans (chair), Elaine Hay, Stephen Lemon, Paul Little, Ursula Shine.

  • Data monitoring and ethics committee: Ade Adebajo, Liam Smeeth (chair), Richard Morris.

  • Contributors: MU was the principal investigator, was primarily responsible for the original grant application, and led the trial team. He contributed to analysing and interpreting the data, wrote the first draft, and is guarantor. DA was study statistician and contributed to the analysis plan and analyses. PC was the clinical research fellow and led on developing the study paperwork, assisted with management, and liaised with laboratories and general practices on medical matters. She wrote the MIQUEST searches and worked with the practice research nurses to identify participants. EH produced the analysis plan and statistical analyses and is guarantor for statistical aspects. LL was responsible for all nursing activity, contributed to implementation of design, selecting and recruiting participants, and developing trial documentation, and managed the recruitment of participating practices. JM was one of the original applicants and contributed to development of protocol and procedures and developed fieldwork costings and was responsible for quality control of the fieldwork. SMtI contributed to the statistical analysis plan and carried out statistical analyses. SP was one of the original applicants, was a member of the project board, and contributed to the study design and development of the protocol. MV was one of the original applicants, contributed to the original design and procedures and had overall responsibility for trial fieldwork and management. She was a member of the project board and the trial steering committee. KW was the study manager.

  • Funding: This study was commissioned by the NHS Health Technology Assessment Programme, project reference 01/09/02. Goldshield Pharmaceuticals supplied the starter packs of topical ibuprofen.

  • Competing interests: MU has received speaker fees from Pfizer, the manufacturers of celecoxib.

  • Ethical approval: Northern and Yorkshire multi-centre research ethics committee (MREC 2/3/1). The 28 local research ethics committees also gave approval.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Accepted 7 November 2007
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