COPENHAGEN — Treatment with etanercept produced significant clinical improvement in heel enthesitis associated with spondyloarthritis, according to Dr. Maxime Dougados.
“This study demonstrates the efficacy of etanercept in [enthesopathy] related to spondyloarthritis, whatever the underlying disease” including ankylosing spondylitis or psoriatic arthritis, said Prof. Dougados, director of the research center in the department of rheumatology at Hôpital Cochin, Paris.
This 12-week, controlled study with 24 patients is the first prospective, placebo-controlled trial of a treatment for enthesopathy related to spondyloarthritis, added Prof. Dougados, who presented the findings at the annual European Congress of Rheumatology.
The benefit on symptoms from 12 weeks of etanercept treatment vs. placebo was clinically as well as statistically significant.
Patients on etanercept experienced substantial improvements from baseline on a variety of measures, including their global assessment (the primary outcome), heel pain, and WOMAC (Western Ontario and McMaster Universities) osteoarthritis index functional subscale score.
“Despite the small sample size [a total of 24 patients], the results seen not only in the primary variable but also in all the secondary variables are strongly in favor” of etanercept's efficacy for heel enthesitis, Prof. Dougados said in an interview with RHEUMATOLOGY NEWS. “I hope the trial will be replicated by evaluating the other TNF [tumor necrosis factor] blockers.”
Heel enthesitis is common in patients with spondyloarthritis regardless of the underlying cause, occurring in 40%–50% of these patients, and can be disabling, according to Dr. Dougados.
Although etanercept and other TNF-blocking drugs have proved to be effective for reducing many of the main clinical manifestations of spondyloarthritis (such as peripheral arthritis, axial symptoms, and psoriatic skin lesions), the impact of these treatments on heel enthesitis was not known prior to this investigation.
The study, which was done at six hospitals in France, Germany, and the Netherlands, enrolled patients older than 18 years who had spondyloarthritis and related heel enthesitis that was refractory to standard treatment with NSAIDs and local injections of corticosteroids.
The AS patients' heel enthesitis was documented by their inferior and/or posterior heel pain and by an MRI scan showing bone marrow edema in the calcaneus adjacent to the insertion of either the Achilles tendon or plantar fascia. The average age of enrolled patients was 37 years.
In all, 12 patients began a 12-week course of standard etanercept treatment, and the other 12 received placebo.
During the study, five patients stopped treatment (four in the placebo group because of lack of efficacy, and one in the etanercept group because of a severe infection in the form of foot cellulitis that required hospitalization).
At the end of the treatment period, the average change in patients' global score on a visual analog scale of 0-100 was a reduction of 29 points from a baseline average of 70 in the etanercept-treated patients, compared with a reduction of 11 points in the placebo-treated patients.
After 2 weeks, the patients receiving etanercept began to show improvement in global score and other measurements.
By the end of 8 weeks, those differences between active treatment and placebo reached a statistically significant difference, compared with placebo, reported Prof. Dougados, who is also professor of rheumatology at René Descartes University in Paris.
During the study, five patients on etanercept and three on placebo had infections, primarily upper respiratory. All resolved once treatment was complete.
The well-documented risk for infection from treatment with etanercept or other TNF blockers must be balanced against the risk from conventional treatments for enthesopathy, as well as the risk that enthesitis poses for causing disability in young patients, Dr. Dougados noted.
The study was sponsored by Wyeth Pharmaceuticals, the company that markets the drug etanercept.
Prof. Dougados has been a consultant to Wyeth and to several other drug companies.
The infection risk seen with all anti-TNF agents is outweighed by the benefit of preventing disability. DR. DOUGADOS
On STIR MR images (above), note the areas of high signal in the inferior calcaneus that correspond to bone marrow edema.
Sagittal T1 MR images of the same heels show thickening with heterogeneous high signal of the plantar fascia in a patient with heel pain due to AS-related enthesitis. Images courtesy Prof. Maxime Dougados
