Botox Adds New Wrinkle to Debated Hyaluronic Acid Treatments for Knee OA


EULAR 2013: More fuel for the debate about hyaluronic acid injections for knee osteoarthritis. A small randomized trial finds that supplementing them with a jab of botulinum toxin (Botox) may significantly increase their effectiveness.

Using the anti-wrinkle drug botulinum toxin (Botox) in combination with hyaluronic acid (HA) may improve pain and function for patients with knee osteoarthritis (OA) significantly more than giving hyaluronic acid alone, according to a poster presentation at the 2013 The European League Against Rheumatism (EULAR) conference in Madrid, Spain.

The double-blind study randomly assigned 45 patients (27 women and 18 men) with Grade 2-3 unilateral knee OA to two injections within seven days of either 2.8  cc of intra-articular hyaluronic acid (HA) alone, the same dose of HA plus 100 units of Botox, or 2.8 cc of saline (as placebo). Assessments took place at baseline and one, three, and six months later.

After one month, the Botox intervention group showed a significant decrease in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain scores from 7.1 to 3.2,  and WOMAC physical function scores improved 8.9 to 3.8 after one month. Scores for the placebo group did not improve significantly.

In the Botox group, walking pain visual analog pain scores (VAS) decreased significantly after one month, from 7.1 to 3.2, with similar improvements at three months that sustained through six months

According to Petrella, Botox inhibits the release of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP), decreasing nociceptor function and resulting in decreased pain and neurogenic inflammation.

Patients who receive both products "have more immediate pain resolution, so they are mobilizing more quickly," says lead investigator Robert Petrella MD. "This is important, as people should not be limited by pain in their activities” Petrella is professor of medicine and research chair in the School of Kinesiology at Western University in London, Ontario. 

“We use a single needle puncture, so we can give both one right after the other, switching vials during treatment,” he explains. “We are now trying to figure out how best to deliver it, since there are no compartmentalized syringes for this treatment" as there are for different forms of HA. 

No serious adverse events according to WHOI criteria were reported. Six placebo patients withdrew after one month due to lack of efficacy, according to the poster abstract. Two patients experienced local pain at the injection site in the HA/Botox group and one patient in the HA/saline group had pain at the injection site.

Botox does have the potential to escape from the joint, but the research team did not observe any evidence of muscle weakness that would result from such an occurrence.

Petrella believes that the HA/Botox treatment may be most appropriate for OA flares and for patients who may have coexisting health problems such as diabetes, and may be taking multiple medications.
“The clinical utility will be in the ability to improve symptom control with less need of ongoing therapy," he adds. "We are looking for ways to have patients get safer, less frequent, treatments,  trying to find a balance between good pain control and long-term functional mobility. We feel this study supports the safety and efficacy of the combined treatment.”

Petrella and coauthors also presented posters at the EULAR meeting on the combined use of Botox and HA for Achilles and patellar tendinopathy.

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