Knee osteoarthritis is a public health issue of gigantic proportions1, with the burden likely to increase in the coming decades. Pain and functional disability from knee osteoarthritis are major patient concerns. Given the lack of a disease-modifying agent for knee osteoarthritis (the promise of platelet-rich plasma and stem cells as disease-modifying or symptomatic-relief agents has little standing in the current literature), therapies that can reduce pain and improve function are our best alternatives. In addition to analgesics and strengthening exercises, intra-articular corticosteroids are the mainstay of treatment in clinical practice. There is debate about the efficacy of intra-articular corticosteroids, their longevity in providing symptom relief, and potential adverse effects on cartilage thickness2-4. Thus, the alternative of an extended-release corticosteroid formulation is quite attractive.
Conaghan and colleagues performed a well-designed and robust multicenter clinical trial. They report the efficacy of FX006, a microsphere-based extended-release formulation of triamcinolone acetonide, as compared with placebo (saline solution). The results convincingly demonstrate the superiority of FX006 over placebo for pain relief and functional outcomes at 12 weeks (as assessed by change in weekly mean average daily pain [ADP] intensity, the primary outcome measure, and the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] and Knee Injury and Osteoarthritis Outcome Score [KOOS]). The results were not as impressive for the comparison of FX006 and standard triamcinolone acetonide crystalline suspension (TAcs). The authors did not identify a significant difference between FX006 and TAcs for the primary outcome. However, some of the exploratory end points, changes in the WOMAC and KOOS, were suggestive of a significant difference.
What are the clinical implications of this study? At this point, the study provides evidence of the efficacy of FX006 compared with saline-solution placebo. Hence, implications are likely limited to clinicians who have concerns that TAcs is not effective in knee osteoarthritis. The likely increased cost of FX006 over TAcs may not sufficiently justify its use in clinical practice. The big question is whether FX006 is superior to TAcs, which is arguably the standard of care for intra-articular corticosteroid therapy. A follow-up trial with a primary head-to-head comparison of FX006 and TAcs could potentially make a major impact on clinical practice. Given the infrastructure available to the authors, they are encouraged to perform this trial.
In the era of limited federal funding of research, this clinical trial is an example of an industry and academic partnership that can produce high-quality patient-oriented research. Certainly, industry has an interest in evaluating its products, and academic physicians are in a strong position to deliver on such projects. With safeguards in place to avoid compromising research ethics, such partnerships may lead to important scientific advancements.
1. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008 Jan;58(1):26-35.
2. McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M, Ward RJ. Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial. JAMA. 2017 May 16;317(19):1967-75.
3. Raynauld JP, Buckland-Wright C, Ward R, Choquette D, Haraoui B, Martel-Pelletier J, Uthman I, Khy V, Tremblay JL, Bertrand C, Pelletier JP. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2003 Feb;48(2):370-7.
4. Jüni P, Hari R, Rutjes AW, Fischer R, Silletta MG, Reichenbach S, da Costa BR. Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev. 2015 Oct 22;(10):CD005328.