Glucosamine in OA: second positive trial published

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Oct 21, 2002

Glucosamine in OA: second positive trial published

Prague, Czech Republic The second large positive trial with glucosamine

sulfate in knee osteoarthritis (OA), showing significantly greater symptom

relief and less progression of radiological joint space narrowing (JSN) than

with placebo, has been published in the Archives of Internal Medicine [1].

This study was presented at EULAR 2001 and reported at the time by

rheumawire.

The results show that long-term oral administration of glucosamine sulfate

" can delay the natural progression of knee OA, " say the authors, led by Prof

Karel Pavelka (Institute of Rheumatology and University, Prague,

Czech Republic). As the " first pharmacologic intervention that retards

progression of osteoarthritis during long-term treatment, " the compound

merits further attention as a disease-modifying agent for OA, they add.

" These results are of particular relevance in that they independently

confirm and extend the results [of the Reginster study]. "

" These results are of particular relevance, " they continue, " in that they

independently confirm and extend the results " from another similar study

the glucosamine trial by Reginster et al, published last year in the Lancet

and hailed by an accompanying editorial as a " landmark study. " However,

there has also been some skepticism about the OA disease-modifying claim for

glucosamine made on the basis of both these studies, with the main criticism

focusing on the x-ray methodology used to document joint space narrowing in

the knee, as reported in detail previously in rheumawire.

Same study design, same positive results

Reginster et al's results " have been welcomed with enthusiasm by most of the

scientific community, but in some cases with reservations, mainly because

such impressive data need to be appropriately confirmed, " Pavelka et al

comment. It was for this reason that their own study was designed and

conducted in parallel, they explain.

Both studies used the same glucosamine sulfate product, DonaTM, and both

were funded by the manufacturer, Rotta Research (Italy). Oral administration

of 1500 mg of the product once daily was compared with placebo over 3 years

in patients with mild to moderately severe knee OA. The study enrolled 202

patients at a single center, the Prague Institute of Rheumatology, between

1995 and1999.

Symptoms were evaluated at quarterly clinic visits using 2 indices Lequesne

and WOMAC (Western Ontario and McMaster Universities). Pain and function

limitation decreased in all participants during the course of the study, but

the improvements were significantly larger in patients receiving

glucosamine, with score reductions of 20% to 25% compared with baseline.

" The glucosamine group had progressive and constant improvement compared

with the placebo group, especially during the first year and maintained

during the second and third years, " Pavelka et al comment.

" The glucosamine group had progressive and constant improvement compared

with the placebo group, especially during the first year and maintained

during the second and third years. "

Disease progress was assessed by a series of x-rays taken at baseline and at

the end of each year. The primary efficacy outcome was the difference

between the treatment groups in the change in joint space width, ie, in JSN.

On enrollment, patients had an average joint space width of slightly less

than 4 mm. In the placebo group, progressive JSN was -0.19 mm (95%

confidence interval -0.29 mm to -0.09 mm) after 3 years. Conversely, there

was no average change in the glucosamine group (0.04 mm, 95% CI -0.06 mm to

-0.14 mm), and the difference between the 2 groups was significant

(p=0.001).

There were no statistically significant differences between groups in the

proportions or patterns of adverse events. Most frequently reported

complaints related to the gastrointestinal tract. Pavelka et al allowed the

use of acetaminophen 500 mg as rescue medication, and its use was recorded

in a patient daily diary. In contrast, the study by Reginster et al also

allowed selected nonsteroidal anti-inflammatory drugs (NSAIDs). However,

neither study found a difference between treatment groups in the use of

rescue medication.

First drug to modify both symptoms and structure in OA

" Glucosamine sulfate, therefore, is the first agent that meets the current

requirements to be classified as a symptom- and structure-modifying drug in

osteoarthritis, " Pavelka et al conclude.

The rate of JSN seen in the control group was similar to that reported

recently in other long-term randomized controlled trials, the researchers

note, pointing out that glucosamine prevented this naturally occurring slow

JSN.

The researchers performed another analysis on the x-ray data. They

pinpointed patients who experienced severe JSN (according to an arbitrary

cutoff value of >0.5 mm), and found 14 such patients on placebo and 5 in the

glucosamine group (p=0.05) The number of patients needed to be treated with

glucosamine sulfate to prevent such a progression is therefore 11, they

write. " This means 11 patients have to be treated with glucosamine sulfate

to prevent 1 from experiencing clinically substantial joint space loss, "

they elaborate. " This way of presenting joint space narrowing data, besides

being more easily interpretable, has been suggested to be more relevant in

clinical terms. "

" Eleven patients have to be treated with glucosamine sulfate to prevent 1

from experiencing clinically substantial joint space loss. "

Separately, the researchers also used a validated atlas to score secondary

radiological features of OA and found that " substantially more patients

taking placebo vs glucosamine sulfate worsened their osteophyte score. " This

is the first time, to the authors' knowledge, that this has been done in a

large randomized intervention trial, and while the result should be

interpreted with caution as it was not a primary outcome measure, it is

unlikely to be biased by the radiographic technique adopted. This likely

confirms an overall beneficial effect of glucosamine on the progression of

joint structure changes, they conclude.

Zosia Chustecka

Cited source

1. Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine Sulfate Use and

Delay of Progression of Knee Osteoarthritis: A 3-Year, Randomized,

Placebo-Controlled, Double-blind Study. Arch Intern Med 2002 Oct 14;

162(18):2113-23.