01.07.2014
by Nancy Walsh
Staff Writer, MedPage Today

A supplement containing extracts of avocado and soybeans showed promise as a structure-modifying treatment for hip osteoarthritis (OA), a French randomized trial suggested.

On the study’s primary endpoint of change in joint space width, no significant differences were seen between patients taking 300 mg per day of avocado-soybean unsaponifiables compared with placebo, according to Emmanuel Maheu, MD, of St-Antoine Hospital in Paris, and colleagues.

But on a secondary analysis of that endpoint, there were 10% fewer who were considered progressors after 3 years of treatment with the supplement (40% versus 50%,P=0.040).

This additional endpoint was added to the study protocol before unblinding followingrecommendations from international consensus groups that joint space narrowing not be used as a study primary endpoint in OA, the researchers reported in the February Annals of the Rheumatic Diseases.

“As more scientific information arose during the trial, it became obvious that [joint space narrowing] in OA is not a quantitative linear normally distributed parameter,” they noted.

Osteoarthritis remains the most common joint disorder, with hip OA being reported by one in 10 individuals older than 65.

However, no disease-modifying treatments have been approved, “because no treatment has proven beyond doubt its efficacy in preventing, stopping, or delaying the disease,” Maheu and colleagues wrote.

While certain agents such as glucosamine sulfate have shown some degree of benefit for knee OA, little effect has been seen for hip OA.

The avocado-soybean supplement consists of the unsaponifiable fractions of avocado and soybean oils. Its mechanisms of action include inhibition of interleukin 1, stimulation of the synthesis of articular collagen, and effects on osteoblasts.

Some previous studies have found clinical benefits with use of this supplement, so Maheu’s group conducted a prospective trial that enrolled 399 patients with symptomatic hip OA from 122 centers in France between February 2000 and January 2004.

Participants were randomized to receive placebo or 300 mg of a proprietary formulation (Piascledine 300 capsule) once daily. They were permitted to take analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), but had to keep track of their use.

Three different radiographic views of the hip were obtained at baseline and yearly for each patient.

More than half were women. Mean age was 62, and mean time since symptoms began was 4.4 years.

At the site of maximal narrowing of the joint space, patients receiving the active treatment had a mean change of -0.64 mm at 3 years while those on placebo had a change of -0.67 mm, which represented a difference of only 0.034 mm (P=0.72).

When the protocol was amended to include the binary endpoint before unblinding, progressors were defined as patients whose loss of joint space width was 0.5 mm or more.

After 1 year of treatment, 30% of patients in the avocado-soybean supplement group were classified as progressors as were 28% of those in the placebo group (P=0.696), and at year 2 the numbers were 34% and 41% (P=0.162). By the third year, the difference between the groups was statistically significant, with a relative risk reduction for progression of 20% for the active treatment.

The number needed to treat to have one nonprogressor was 11.

There were no significant differences between the group on various secondary endpoints including pain, disease severity, and use of analgesics or NSAIDs.

More than 85% of patients reported one or more adverse events during the trial, which most often were infections and musculoskeletal or connective tissue complaints. In the active treatment group, 16.9% withdrew because of an adverse event, as did 14.8% of those in the placebo group.

An important strength of this study was its “high level methodology,” particularly the addition of the progressors/nonprogressors endpoint and the “missing at random” approach rather than the “last observation carried forward” to account for absent data.

The researchers noted that the clinical significance of the reduction in number of progressors will require further investigation, and they plan a further analysis using total hip replacement as a primary outcome.

An additional limitation was the lack of difference in clinical effects between the groups.

• Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

LAST UPDATED 01.07.2014