October 2005 • www.rheumatologynews.com Arthritis 29 Several Unusual Therapies Take Root in Europe

Many treatments may not reach the U.S. because treated to baseline levels, while the MBST years as a postsurgery thromboprophy- group showed further significant im- laxis agent. It promotes fibrinolysis and small companies can’t afford the FDA approval process. provement. has anticoagulant activity. Dr. Ghosh saw Similar results were seen on the Os- its potential as a chondroprotective agent. BY BRUCE JANCIN common than the abdominal pain re- westry Disability Questionnaire. Partic- “We have probably 50 papers of its effect Denver Bureau ported by piroxicam users. ularly striking was the finding that after in animals and in vitro. The rationale for 3 months 74% of MBST-treated patients its use in arthritis is solid as a rock,” he V IENNA — Americans attending the an- Nuclear Magnetic Resonance rated their ability to provide personal told this newspaper. nual European Congress of Rheumatol- Therapy for Low Back Pain care as improved, and none indicated it “It mobilizes the clots in subchondral ogy are often impressed by the discussion That’s right—MRI not for imaging pur- had deteriorated, compared with base- bone, it’s anti-inflammatory, it protects of unfamiliar, even exotic therapies not poses, but as treatment. Therapeutic MRI, line. the cartilage, and it stimulates the pro- available in the United States. called MultiBioSignal Nuclear Resonance In contrast, only 37% of controls rat- duction in synovial fluid of hyaluronic The most intriguing of these are sup- Therapy (MBST) was developed by a Ger- ed their personal care capability as im- acid. So it has all the markings of a dis- ported by encouraging clinical trials data. man company, Medtec Medizintechnik proved, while 11% said it had deterio- ease-modifying drug for osteoarthritis,” Yet many of the therapies may never GmbH, after physicians serendipitously rated. Walking, sitting, standing, and he said. reach the U.S. market because they are noted that patients with disabling chron- lifting were areas where both groups Pentosan polysulfate is marketed by the property of small com- ic low back pain who had to showed significant improvement at 3 bene-Arzneimittel GmbH of Munich. It’s panies that find the Food ‘We have undergo repeated conven- months, with greater gains recorded in a small, family-owned company that does and Drug Administration probably 50 tional MRIs because of tech- the MBST group, said Dr. Kullich of the not have the financial resources to conduct approval process too fiscal- nical imaging problems re- Ludwig Boltzmann Institute for Reha- a multiyear radiographic study with ly daunting. papers of ported feeling much better bilitation of Internal Diseases in preservation of joint space as the end Here is a sample of nov- [pentosan afterward. Saalfelden, Austria. point, which is what the FDA insists upon el therapies, currently un- Physicians and physicists if an OA drug is to obtain an indication as available in the United polysulfate’s] came up with a basic science Topical Diclofenac for Knee OA disease modifying. States, that were the subject effect in animals rationale to explain the ef- A metaanalysis of four randomized con- “They’re looking for partners in Japan,” of research presentations at fect, then modified conven- trolled 4- to 12-week trials totaling 1,412 he said. the meeting, sponsored by and in vitro. The tional MRI equipment to patients with symptomatic knee OA In Europe, Canada, and Australia, pen- the European League rationale for its enhance it. They created a showed the topical agent’s efficacy was tosan polysulfate has become the leading Against Rheumatism. device that generates a stat- equal to oral diclofenac and significantly drug for the prevention of progressive use in arthritis is ic magnetic field and a better than placebo for the end points of OA in dogs and horses. “In fact, we’ve Diacerein solid as a rock.’ three-dimensional alternat- stiffness, physical function, and pain on been able to move much faster in the vet- This plant-derived an- ing radiofrequency field de- walking, according to Michael Doherty, erinary field than we have in humans,” thraquinone derivative blocks the down- signed to induce resonant vibration of hy- M.D., professor of rheumatology at the Dr. Ghosh added. stream proinflammatory effects associated drogen atoms within cartilage and bone in University of Nottingham (England). with stimulation of the interleukin-1 re- order to stimulate cell proliferation. In- The number of patients needed to be Emu Oil ceptors located on chondrocytes and in- vestigators at the University of Munich treated with topical diclofenac for one pa- Daily oral or topical use of oil rendered flammatory cells. It doesn’t affect prosta- have previously demonstrated that MBST tient to achieve greater than 50% pain re- from the emu, a large flightless bird, re- glandin synthesis. increases cartilage thickness in patients duction was six. sulted in a 2.34-fold greater reduction in EULAR guidelines categorize diacerein with knee osteoarthritis. The chief advantage of topical as com- pain than a canola oil placebo in a ran- as a symptomatic slow-acting drug for Sound flaky? Medical officials at one of pared with oral diclofenac was that GI side domized double-blind trial involving 101 both knee and hip osteoarthritis (OA). It Austria’s largest workers’ compensation effects were 43% less common with the patients with OA hand pain. The observed is widely used for this purpose in much of insurer–funded inpatient rehabilitation topical agent and no more frequent than treatment effect was medium to large, Europe, where it has been the subject of centers don’t think so, Werner C. Kullich, with placebo. and it was apparent from week 4 onward more than a dozen randomized controlled Ph.D., told this newspaper. Topical diclofenac is contained in a di- in the 8-week trial, reported Melainie trials. Dr. Kullich explained that the prevail- methyl sulfoxide vehicle. The main ad- Cameron, Ph.D., of Victoria University, At the EULAR meeting, Worowit ing workers’-comp philosophy in Ger- verse event associated with the topical Melbourne, Australia. Louthrenoo, M.D., presented the first ran- man-speaking Europe is that rehabilita- therapy was local skin reactions, mainly As early as 1860, naturalists reported domized double-blind controlled trial of tion of patients with chronic disabling dry skin and itching, which were 3.6-fold that Australian aborigines and early An- diacerein in an Asian population. low back pain is best accomplished more frequent than with placebo. glo settlers used emu oil to treat wounds The Thai study involved 161 OA pa- through a 3- to 4-week inpatient stay at The topical diclofenac solution, called and relieve musculoskeletal pain, Dr. tients randomized to 50 mg b.i.d. of di- specialized centers that provide multi- Pennsaid, is approved for treatment of Cameron added. ■ acerein or 10 mg b.i.d. of piroxicam for modal therapy, including extensive edu- knee OA in Canada and seven European 16 weeks, with an additional 8 weeks of cation, exercises, massage, hydrotherapy, countries. A spokesman for Dimethaid follow-up post discontinuation, Dr. and electrical stimulation. The results, Health Care Ltd., of Markham, Canada, Louthrenoo said. though shown to be superior to the out- told this newspaper the company hopes to The primary end point in the TRB patient therapies that are the norm in gain U.S. marketing approval for Pennsaid Chemedica–sponsored trial was pain relief much of the rest of the world, leave in early 2007. The FDA has asked for two as reflected in WOMAC scores. much to be desired—thus the insurance additional long-term safety studies, both of At week 16 of the investigation, the di- industry’s interest in MBST and other which are nearly completed. acerein group showed a mean 70% im- novel approaches. provement in WOMAC scores, compared Dr. Kullich presented an insurer-spon- Pentosan Polysulfate for OA with baseline—not significantly different sored, double-blind, placebo-controlled A non–commercially funded randomized from the 74% improvement in the piroxi- trial of MBST versus sham therapy in 62 double-blind placebo-controlled trial in- cam group. rehab-clinic patients with chronic low back volving 114 patients with knee OA demon- However, at week 20—which was 4 pain. strated that 4 weekly 3-mg/kg IM injec- weeks following discontinuation—the In addition to the standardized intensive tions of pentosan polysulfate resulted in mean improvement in the diacerein group 3-week inpatient rehab program, study significantly greater improvements in pain remained at 67%, compared with 47% for participants received hour-long MBST or at rest and walking, stiffness, and physical piroxicam. sham therapy sessions on 5 consecutive functioning involved in activities of daily And at week 24, the diacerein group days. The study end points were changes living out to 24 weeks follow-up post treat- maintained a 70% improvement in WOM- in pain and function at 1 and 12 weeks post ment, reported Peter Ghosh, Ph.D., of

AC scores, versus a 27% improvement in MBST. the Institute of Bone and Joint Research at EINAKER R the piroxicam group, said Dr. Louthrenoo, Both groups showed significant im- Royal North Shore Hospital, Sydney, Aus- AMES professor of medicine at Chiang Mai provements in low back pain as assessed by tralia. J (Thailand) University. the Roland-Morris Questionnaire at 1 Pentosan polysulfate (approved in the Daily application of emu oil reduced The most frequent adverse event in the week; by 3 months, however, scores in the United States only for interstitial cystitis) hand OA pain significantly better than diacerein group was diarrhea; it was less rehabilitation-plus-placebo group had re- has been used in Europe for nearly 50 canola oil or placebo.