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 Ahlbäcks 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 [47]. 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 23 and Ahlbäck grade I (0.76) as well as Kellgren and Lawrence grades 34 and the Ahlbäck grade III (
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