Clinical Editor
Dr Sheila Strover is the Founder and previous Clinical Editor of the KNEEguru website.Her medical studies were completed at the University of the Witwatersrand in South Africa - BSc(Hons) (1968) and MBBCh (1974). She emigrated to the United Kingdom in 1983 and worked as an anaesthetist (anaesthesio…
Interpretation by the Editor of a peer-reviewed article in the published medical literature.
Hangody L, et al. Cartilage. 2017 May 1:1947603517703732. doi: 10.1177/1947603517703732. [Epub ahead of print].
This multi-author study was designed to compare in patients with knee osteoarthritis (OA) a product called Cingal - a mix of a hyaluronic acid (HA) derivative and a steroid - with the same company's other product (Monovisc) which did not have the steroid in it and then it was also compared with injections of saline containing neither of the trial substances. Well-known scoring systems were used to evaluate any improvement or otherwise in pain and other indices of function.
The ageing population and the expected associated increase in osteoarthritis has led to projections of significant rising costs associated with knee replacement in this population. Both of the test substances are well documented to provide some symptom relief in OA - the steroid having a shorter effect of up to three weeks and the HA having an effect from about 4 weeks to 6 months, so the idea was to see if a combination provided a better overall relief of pain and improvement of function than the Monovisc alone.
The hypothesis was "that Cingal’s pain reduction would be superior to saline through 12 and 26 weeks, and also be superior to Monovisc for short-term pain relief."
The steroid - triamcinolone hexacetonide - is commonly used in the knee for its anti-inflammatory properties. The hyaluronic acid offers visco-supplementation, increasing the viscosity of fluid inside the knee and improving lubrication.
The study was well-designed but there were some limitations in that it only involved 360 subjects and was discontinued at 26 weeks when it might have been helpful to have followed the patients for even longer. The study was funded by the manufacturer, but it was multicentric and fully double-blinded, which means that no-one at all knew which of the patients received which of the medications all the way through the study.
Twelve people were lost to the study, approximately the same proportion in each of the three groups, and none of these was due to a bad reaction. A further number of patients were withdrawn from the analysis because protocol had been violated, so in the end it was only 335 patients who fully participated and were fully analysed.
The patients were well assessed before and monitored during the study.
With each treatment, the existing joint fluid was fully aspirated (and sent to the laboratory) and then the test injection was given into the knee.
Just aspirating the joint fluid and injecting with saline had some positive effect, but this is something that is well known to occur and is the basis for the procedure known as joint lavage. So it is relevant that the subjects were tested against saline.
The improvement shown by Cingal was significantly greater than saline through 12 weeks ( P = 0.0099) and 26 weeks ( P = 0.0072) which were the two key points of reference. [The low 'P' or probability scores indicate that these findings were statistically significant.]
WOMAC Pain was reduced by 70% at 12 weeks and by 72% at 26 weeks with Cingal. Significant improvements were found in most secondary endpoints for pain and function at most time points through 26 weeks. The advantage of Cingal over Monovisc was clearly related to the inclusion of the steroid, because at 1 and 3 weeks Cingal was significantly better than Monovisc for most endpoints but the two products were similar from 6 weeks through 26 weeks.
A low incidence of related adverse events was reported and these were much the same irrespective of the study group.