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The effects of doxycycline on reducing symptoms in knee osteoarthritis: results from a triple-blinded randomised controlled trial
  1. Gijs F Snijders1,
  2. Cornelia HM van den Ende1,
  3. Piet LCM van Riel2,
  4. Frank HJ van den Hoogen1,
  5. Alfons A den Broeder1 on behalf of NOAC study group
  1. 1Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands
  2. 2Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  1. Correspondence to Gijs F Snijders, Sint Maartenskliniek, Department of Rheumatology, PO Box 9011, 6500 GM, Nijmegen, The Netherlands; gijssnijders{at}


Objectives Evidence suggests that doxycycline might have disease-modifying properties in osteoarthritis. However, the clinically relevant question as to whether doxycycline also modifies symptoms in knee osteoarthritis is unanswered. The objective of this study was to investigate the effectiveness of doxycycline on pain and daily functioning in symptomatic knee osteoarthritis.

Methods A 24-week, randomised, triple-blind, placebo controlled trial on the symptomatic effectiveness of doxycycline twice a day 100 mg in knee osteoarthritis patients according to the clinical and radiological American College of Rheumatology classification criteria. The primary endpoint was the difference in the proportion of participants in both study groups achieving a clinical response defined by the OMERACT–OARSI set of responder criteria. Secondary endpoints included pain, stiffness, daily functioning, patient global assessment, quality of life, osteoarthritis-related medication and side effects.

Results 232 patients were randomly assigned. At study end, 31% of participants met the primary endpoint in both groups. Except for more adverse events in the doxycycline group, no differences were also found on the secondary endpoints.

Conclusions Doxycycline is not effective in reducing symptoms in knee osteoarthritis patients over a 24-week study period, but is associated with an increased risk of adverse events. Although a possible structure-modifying effect of doxycycline was previously suggested, this is not accompanied by symptom relief in the short and medium term.

Dutch Trial Register no NTR1111.

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  • See Editorial, pg 1175

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the local Medical Research Ethics Committee, region Arnhem/Nijmegen, The Netherlands, and the national Central Committee on Research involving Human Subjects (CCMO).

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

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