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Why should we expect a structure-modifying osteoarthritis drug to relieve osteoarthritis pain?
  1. Kenneth D Brandt
  1. Correspondence to Kenneth D Brandt, Clinical Professor of Medicine, University of Kansas Medical Center, Kansas City, 5755 Windsor Drive, Fairway, Kansas USA 66205; kenbrandt{at}

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In patients with knee osteoarthritis (OA) the real problem, for the clinician and the patient, is not radiographic OA but painful OA. As noted by Liang, ‘x-rays don't weep'.1 Patients weep.

In this issue of the Annals, Snijders et al2 report results of a randomised controlled (RCT), placebo-controlled trial of doxycycline (doxy) in patients with symptomatic knee OA. Their primary end point was the difference in the proportion of subjects in the two treatment groups who achieved a clinical response at 24 weeks, as judged by OMERACT-OARSI responder criteria. Secondary outcomes included joint pain, stiffness, function, quality of life, OA-related medication use and side effects of treatment. The results showed no difference between doxy and placebo with respect to symptomatic benefit; about one-third of each treatment group met the responder criteria. The authors conclude that doxy is ineffective in reducing symptoms of knee OA over 24 weeks.

The study was prompted by our 2005 report that doxy slowed the rate of joint space narrowing (JSN) over 30 months in patients with knee OA; significant differences from placebo were seen as early as 16 months.3 In contrast to the study by Snijders et al,2 our primary outcome measure was the effect of doxy on radiographic progression of OA, not on symptoms. Specifically, our intent was to ascertain whether a fluoroscopically assisted semiflexed radiographic view of the knee4 was suitable for use in a multicentre clinical trial of a putative structure-modifying OA drug (SMOAD). Subjects enrolled in the study, which was implemented in 1997, were recruited chiefly from the community, rather than from clinics for patients with joint pain. Our inclusion criteria did not contain a threshold for severity of joint pain and levels of knee pain at entry were low. Post hoc comparison showed …

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