Topical Diclofenac for Knee OA
A metaanalysis of four randomized controlled 4- to 12-week trials totaling 1,412 patients with symptomatic knee OA showed the topical agent's efficacy was equal to oral diclofenac and significantly better than placebo for the end points of stiffness, physical function, and pain on walking, according to Michael Doherty, M.D., professor of rheumatology at the University of Nottingham (England).
The number of patients needed to be treated with topical diclofenac for one patient to achieve greater than 50% pain reduction was six.
The chief advantage of topical as compared with oral diclofenac was that GI side effects were 43% less common with the topical agent and no more frequent than with placebo.
Topical diclofenac is contained in a dimethyl sulfoxide vehicle. The main adverse event associated with the topical therapy was local skin reactions, mainly dry skin and itching, which were 3.6-fold more frequent than with placebo.
The topical diclofenac solution, called Pennsaid, is approved for treatment of knee OA in Canada and seven European countries. A spokesman for Dimethaid Health Care Ltd., of Markham, Canada, told this newspaper the company hopes to gain U.S. marketing approval for Pennsaid in early 2007. The FDA has asked for two additional long-term safety studies, both of which are nearly completed.
Pentosan Polysulfate for OA
A non-commercially funded randomized double-blind placebo-controlled trial involving 114 patients with knee OA demonstrated that 4 weekly 3-mg/kg IM injections of pentosan polysulfate resulted in significantly greater improvements in pain at rest and walking, stiffness, and physical functioning involved in activities of daily living out to 24 weeks follow-up post treatment, reported Peter Ghosh, Ph.D., of the Institute of Bone and Joint Research at Royal North Shore Hospital, Sydney, Australia.
Pentosan polysulfate (approved in the United States only for interstitial cystitis) has been used in Europe for nearly 50 years as a postsurgery thromboprophylaxis agent. It promotes fibrinolysis and has anticoagulant activity. Dr. Ghosh saw its potential as a chondroprotective agent. “We have probably 50 papers of its effect in animals and in vitro. The rationale for its use in arthritis is solid as a rock,” he told this newspaper.
“It mobilizes the clots in subchondral bone, it's anti-inflammatory, it protects the cartilage, and it stimulates the production in synovial fluid of hyaluronic acid. So it has all the markings of a disease-modifying drug for osteoarthritis,” he said.
Pentosan polysulfate is marketed by bene-Arzneimittel GmbH of Munich. It's a small, family-owned company that does not have the financial resources to conduct a multiyear radiographic study with preservation of joint space as the end point, which is what the FDA insists upon if an OA drug is to obtain an indication as disease modifying.
“They're looking for partners in Japan,” he said.
In Europe, Canada, and Australia, pentosan polysulfate has become the leading drug for the prevention of progressive OA in dogs and horses. “In fact, we've been able to move much faster in the veterinary field than we have in humans,” Dr. Ghosh added.
Emu Oil
Daily oral or topical use of oil rendered from the emu, a large flightless bird, resulted in a 2.34-fold greater reduction in pain than a canola oil placebo in a randomized double-blind trial involving 101 patients with OA hand pain. The observed treatment effect was medium to large, and it was apparent from week 4 onward in the 8-week trial, reported Melainie Cameron, Ph.D., of Victoria University, Melbourne, Australia.
As early as 1860, naturalists reported that Australian aborigines and early Anglo settlers used emu oil to treat wounds and relieve musculoskeletal pain, Dr. Cameron added.
Daily application of emu oil reduced hand OA pain significantly better than canola oil or placebo. James Reinaker