ACR: No Clear Benefit for Painful Knees in Big Glucosamine-Chondroitin Study

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ACR: No Clear Benefit for Painful Knees in Big Glucosamine-

Chondroitin Study

By Lynne , MedPage Today Staff Writer

Reviewed by Jasmer, MD; Assistant Professor of Medicine,

University of California, San Francisco

MedPage Today Action Points

Be aware that an NIH-sponsored trial of glucosamine/chondroitin for

patients with osteoarthritis demonstrated no clear benefit.

Explain that a European study reported here used a prescription

glucosamine formulation that is not available in the U.S.

These studies were was published as abstracts and presented at a

conference either as an oral or poster presentation. These data and

conclusions should be considered to be preliminary as they have not

yet been reviewed and published in a peer-reviewed publication.

Review

SAN DIEGO, Nov. 21 - The value of glucosamine and chondroitin

supplements in osteoarthritic knee pain remains unclear even after

results of a large study was released here.

On first glance, the results of the Glucosamine/Chondroitin Arthritis

Intervention Trial (GAIT), funded by the NIH, were straightforward.

Neither supplement alone, nor in combination, was effective in the

primary endpoint of a 20% improvement from baseline in WOMAC (Western

Ontario and McMaster Universities Osteoarthritis Index) pain at week 24.

The response rate for all patients was 60.1% in a placebo group, 64%

in a glucosamine hydrocholoride arm (500 mg TID); 65.4% in a

chondroitin alone arm (400 mg TID); and 66.6% in a glucosamine-plus-

chondroitin arm (500 mg/400mg TID) (p=0.09), according to a study

results reported at the American College of Rheumatology meeting in

San Diego.

But the situation was muddied by results from a pre-specified

subgroup analysis that found a statistically significant benefit for

the combination of glucosamine and chondroitin in osteoarthritis

patients with moderate-to-severe knee pain, defined as WOMAC Pain

301-400 mm, (P=0.002).

As a result, some rheumatologists viewed the study results as putting

the last nail in the glucosamine-chondroitin coffin, while others

pointed to some patients being clearly helped by the supplement combo.

The 1,538-patient GAIT trial compared the effectiveness and safety of

these supplements taken alone and in combination in patients with

painful knee osteoarthritis (WOMAC Pain 125-400 mm) treated at 16

academic medical centers in the U.S.

All patients were allowed up to use Tylenol (acetaminophen) as rescue

analgesia, except within 24 hours of study visits.

" It is tempting to believe the ingestion of glucosamine-chondroitin

should be beneficial to cartilage, " said Clegg, M.D., of the

University of Utah, the GAIT principal investigator. This temptation

was made even more appealing when an " expert panel at NIH reviewed

the current status of glucosamine-chondroitin and concluded there was

a real and urgent need to study these agents in a rigorous way, " he

added.

This randomized, double-blind, parallel-group trial was conducted

under an Investigational New Drug (IND) application, and the

glucosamine and chondroitin used were required to meet FDA

pharmaceutical standards. Dr. Clegg said no commercial products met

the FDA standards, so NIH had tablets specially formulated for the

trial.

To confuse matters even more, an industry-funded study from Spain

found that Rota Research Laboratories' glucosamine sulfate (which

differs from the glucosamine hydrochloride used in the GAIT study)

was more effective in controlling pain from knee osteoarthritis than

acetaminophen. In contrast to the U.S., where glucosamine is a

dietary supplement, in many European countries it is a prescription

medication.

The multicenter European study was a randomized, double-blind,

parallel group trial of 318 osteoarthritis patients, comparing

glucosamine with acetaminophen and placebo. All patents were allowed

to use ibuprofen as needed, and more patients on placebo used

ibuprofen than either of the study's drug arms. Researchers reported

that glucosamine sulfate significantly reduced pain (P=0.032), but

acetaminophen did not. There were no differences among groups in safety.

" According to our results, the prescription of oral glucosamine

sulfate at a dose of 1.5 grams per day should be the preferred

medication for osteoarthritis patients, " said Herrero-

Beaumont, M.D., of the Jiménez Díaz Foundation -- CAPIO in Madrid,

principal investigator of the European study.

He said, however, that acetaminophen is better for acute pain,

although after two to three months " glucosamine has an analgesic

effect. "

Asked to explain the different findings in U.S. and European studies,

Dr. Herrero-Beaumont suggested it was the different glucosamine

formulation that was used (sulfate) and the different dosing (QD vs.

TID). Dr. Clegg disagreed, saying he thought the difference could be

due to higher baseline pain levels in the patients in the European

study.

" It doesn't seem physiologic to me to suggest that the amount of

sulfate would make a physiological difference, " he said. Noting that

patients with more severe baseline pain are likely to report more

significant improvements with any treatment, he said, " I think (the

European study) patients had more pain. "

Not surprisingly given the results of both trials, there was

disagreement about what physicians should tell their patients about

these supplements.

Dr. Clegg said, " Patients should wait for peer-reviewed publication

(of the GAIT results) before considering use (of the combination). "

He added, however, that " there are patients who respond, and we need

to see what is different about those patients and design a trial and

see why they respond. I don't think we have the answer as to whether

patients should take (glucosamine-chondroitin). " He predicted that

the peer-review process may provide recommendations that will be

helpful.

Arthur Kavanaugh, M.D., of the University of California at San Diego,

said, " I'll tell my patients that there are some patients in whom

glucosamine-chondroitin sulfate works. "

Matteson, M.D., of the Mayo Clinic, disagreed, saying, " These

studies showed very clearly that there is no clinical role for

glucosamine-chondroitin in the management of osteoarthritis. The

studies failed to show a compelling benefit. They were null studies. "

Primary source: American College of Rheumatology