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Rheumatology 2003; 42: 1262
© 2003 British Society for Rheumatology
Letter to the Editor |
Re: Karlsson et al. Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study
Genzyme Corporation, Clinical Research, Cambridge, MA 1Wyeth Pharmaceuticals, Clinical Affairs, St Davids, PA, USA
Correspondence to:
D. Magilavy, Department of Clinical Research, Genzyme, Inc., 55 Cambridge PKWY, Cambridge, MA 0214Z, USA. E-mail: dan.magilavy{at}genzyme.com
SIR, Karlsson et al. [1] are to be congratulated for their well-controlled trial in which the efficacy and safety of intra-articular injections of a hyaluronan (Artzal®) and a cross-linked hylan (Synvisc®) were compared with those in a phosphate-buffered saline placebo control group. They report statistically significant clinical improvement from baseline at 26 weeks after intra-articular injection in all three treatment groups. A longer duration of benefit of the active treatments compared with placebo was noted only when data for the hyaluronan and hylan groups were pooled.
These results would suggest minimal clinical benefit in knee osteoarthritis (OA) from either a hyaluronan or a hylan. However, 40, 39 and 42% of the patients randomized to the Artzal, Synvisc and placebo groups, respectively, had complete loss of joint space, the criterion for Ahlbäck’s grade II classification [2]. These results differ from those of an earlier randomized controlled trial in knee OA reported by Lohmander et al. [3], in which superior clinical benefit from Artzal compared with placebo was found. In that trial, only 17% of the patients who received Artzal had grade II Ahlbäck changes. Moreover, the most severe knee for OA radiological grade entry criterion in the majority of published controlled, prospective studies on the safety and efficacy of Synvisc was Kellgren and Lawrence grade 3 [4–7]. Although the Kellgren and Lawrence grading scale focuses primarily upon osteophytes [8], the grade 3 classification includes definite narrowing but not complete loss of joint space. Indeed, Petersson et al. [9] found agreement between Kellgren and Lawrence grades 2–3 and Ahlbäck grade I (
0.76) as well as Kellgren and Lawrence grades 3–4 and the Ahlbäck grade I–II (0.78).
Hylans and hyaluronans appear to be most efficacious in patients with earlier OA who have maintained some radiographic evidence of joint space [10]. The inclusion of a high proportion of OA patients with more advanced disease that may have been refractory to intra-articular hyaluronan therapy would leave their study underpowered to show differences in efficacy between placebo and either Artzal or Synvisc.
The authors have declared no conflicts of interest.
References
- Karlsson J, Sjogren LS, Lohmander LS. Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study. Rheumatology 2002;41:1240–8
[Abstract/Free Full Text] - Ahlbäck S. Osteoarthritis of the knee: a radiographic investigation. Acta Radiol (Stockholm) 1968;277(Suppl.):7–72
- Lohmander LS, Dalen N, Englund G et al. Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Ann Rheum Dis 1996;55:424–31
[Abstract/Free Full Text] - Wobig M, Dickhut A, Maier R et al. Viscosupplementation with Hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee. Clin Ther 1998;20:410–23[CrossRef][Web of Science][Medline]
- Adams ME, Atkinson MA, Lussier A et al. The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee. Osteoarthritis Cartilage 1995;3:213–26[CrossRef][Web of Science][Medline]
- Raynauld JP, Torrance GW, Band PA et al. A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results. Osteoarthritis Cartilage 2002;10:506–17[CrossRef][Web of Science][Medline]
- Adams ME, Lussier AJ, Peyron JG. A risk–benefit assessment of injections of hyaluronan and its derivatives in the treatment of osteoarthritis of the knee. Drug Safety 2000;23:115–30[CrossRef][Medline]
- Kellgren JH, Lawrence JS. Osteoarthritis and disk degeneration in an urban population. Ann Rheum Dis 1958;17:388–97
[Free Full Text] - Petersson IF, Boegard T, Saxne T et al. Radiographic osteoarthritis of the knee classified by the Ahlbäck and Kellgren & Lawrence systems for the tibiofemoral joint in people aged 35–54 years with chronic knee pain. Ann Rheum Dis 1997;56:493–6
[Abstract/Free Full Text] - Lussier A, Cividino AA, McFarlane CA et al. Viscosupplementation with hylan for the treatment of osteoarthritis: findings from clinical practice in Canada. J Rheumatol 1996;23:1579–85[Web of Science][Medline]
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