The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), which was recently published in The New England Journal Of Medicine, has sparked controversy within the arthritis community. Some have called the National Institutes of Health-funded study a success while others call it a failure.

The randomized, multicenter study, which involved nearly 1,600 patients with symptomatic osteoarthritis (OA) of the knee, found no significant difference in efficacy between glucosamine, chondroitin, a combination of the two supplements and the placebo. However, in regard to the subgroup of study patients who had moderate to severe pain, the researchers noted that the combination of glucosamine and chondroitin had significantly better results at six months than the placebo.

“This is a somewhat complicated finding,” notes Daniel O. Clegg, MD, the lead author of the study.
While the patients in the study were stratified on the basis of pain, Dr. Clegg says the subgroup of patients with moderate to severe OA pain (22 percent) was “relatively small.” That said, 79.2 percent of those with moderate to severe pain in the supplement combination group had a 20 percent reduction in their OA knee pain whereas only 54.3 percent of those patients in the placebo group achieved the 20 percent reduction in pain.

Nearly 80 percent of patients with moderate to severe OA pain in a supplement combination treatment group had a 20 percent reduction in pain, according to the GAIT study.

While these results were interesting, further studies are necessary before making any definitive statements about the use of the supplement combination for this specific patient population, according to Dr. Clegg, the Chief of Rheumatology at the University of Utah School of Medicine.

However, Jason Theodosakis, MD, MS, MPH, emphasizes that the findings for this subgroup of patients were particularly noteworthy.

“People with moderate to severe pain are the ones who end up taking medications, using physical therapy services and getting surgery,” points out Dr. Theodosakis, an Assistant Professor of Medicine at the University of Arizona College of Medicine. “In this subgroup, Celebrex was not different than placebo and the supplement combination was highly and statistically significant.”

According to the study, patients were randomized into five different groups. Over a six-month period, the patients received either 1500 mg of glucosamine three times a day, 1200 mg of chondroitin three times a day, a combination of the two aforementioned supplements at the previously mentioned doses, a placebo or a daily dose of celecoxib (Celebrex, Pfizer) at 200 mg.

Patients were also allowed to take up to 4000 mg daily of acetaminophen (except within 24 hours of the time of each of the GAIT pain evaluations), notes Dr. Clegg, who is a consultant for McNeil Consumer and Specialty Pharmaceuticals. However, he says the average daily intake of acetaminophen was less than 1,000 mg a day and this intake rate was similar among the different groups in the study.

In regard to the study’s main finding that neither of the aforementioned supplements, alone or in combination, demonstrated effective pain reduction in the overall group of patients, Dr. Theodosakis cautions clinicians about reading too much into the study.

A member of the GAIT study’s Steering Oversight Committee, Dr. Theodosakis notes that the positive comparator drug, celecoxib, “failed to beat the placebo in 48 of the 52 separate outcome measures” in the GAIT study.

“This indicates that the effect of all treatments was likely understated (given the) high placebo response,” notes Dr. Theodosakis, who is a consultant for supplement and pharmaceutical companies. “Even so, chondroitin was highly significant in reducing joint swelling and edema, which is arguably the most specific indicator of antiinflammatory effect.”

FDA Approves Rituximab For Moderate To Severe RA
Clinicians now have a new medication at their disposal for treating rheumatoid arthritis (RA). The Food and Drug Administration (FDA) recently announced that it has approved the use of rituximab (Rituxan, Genentech) in combination with methotrexate to treat symptoms of moderate to severe RA.

“(Rituximab) is an important addition to the RA armamentarium because 30 percent of RA patients do not have an adequate or persistent improvement with anti-TNF therapy,” notes Stephen Paget, MD, the Physician-in-Chief of the Department of Medicine, Division of Rheumatology at the Hospital for Special Surgery in New York.

The FDA approval was based upon the results from three randomized, double blind, placebo-controlled studies involving patients with active RA. In particular, the REFLEX trial revealed that 51 percent of patients who received two infusions of rituximab and a dose of methotrexate achieved an ACR 20 response in comparison to 18 percent of the placebo group. In the same study, 27 percent of patients receiving the rituximab/methotrexate combination achieved an ACR 50 response in comparison to 5 percent of patients in the placebo group.

Dr. Paget says rituximab targets B-cells, which play a role in the development of rheumatoid arthritis.

Prior to participating in the REFLEX study, the enrolled patients previously had an inadequate response or could not tolerate prior treatment with anti-TNF therapy and methotrexate.

While previous biologic treatments for RA have focused on T-cell lymphocytes and the cytokine products of immunologically active cells, Dr. Paget says rituximab is innovative in that it targets B-cells, which reportedly play a significant role in the development of RA.

In addition to using rituximab to help treat RA in patients who have not had an adequate response to anti-TNF therapy, Dr. Paget says he has also used the medication in refractory cases of systemic lupus erythematosus and other refractory immune disorders.
— A.L.

Improved Access To Prescription Histories: Safety Boon Or HIPAA Nightmare?
SureScripts, a large provider of electronic prescribing services, is teaming up with a number of chain and independent pharmacies throughout the United States to facilitate improved access to medication histories for patients, clinicians and pharmacies.

Will the benefits of such a system outweigh potential privacy issues? SureScripts says the sharing of information such as prescription history, allergies and medication distribution dates can greatly aid clinicians in prescribing safer and more effective treatment regimens for their patients.

Mike Rudzinski, PA-C, concurs, calling the initiative a bold step toward the electronic information age that is “valuable and necessary” in facilitating an accurate medication history.



“If the patient, for whatever reason, is unable to give the accurate medication history, it is great that this information will be available for the practitioner via electronic means through SureScripts,” says Rudzinski, who is affiliated with the Buffalo Veterans Affairs Medical Center in Buffalo.

For example, Rudzinski says he may see an elderly patient who has high blood pressure and a history of mild renal impairment. The patient reveals that he recently saw an orthopedist for osteoarthritis and was prescribed a medication but is not sure of the drug’s name.

Now with the availability of the electronic medication history system, Rudzinski says he would be able to find out the name of the medication and whether that medicine will have any adverse reactions with a type of medication he has in mind for the patient.

Given the advent of HIPAA, people may raise concerns about potential privacy issues. Organizers behind the initiative say privacy and security will be heavily emphasized.

“I have concerns but I think the benefits as noted above outweigh security issues,” notes Rudzinski. “I also think the security will be significant although the specifics are not spelled out.”
— A.L.

Injections For OA Knee Pain: What A New Study Reveals
For clinicians who perform joint injections to help relieve knee pain from osteoarthritis, a new study comparing two agents reveals intriguing results.

The 12-week trial compared a weekly three-injection regimen of highly purified sodium hyaluronate (Euflexxa, Ferring Pharmaceuticals) to a weekly three-injection regimen of avian-derived hyaluronan (Synvisc, Genzyme). The multicenter, randomized study, which was recently published in Osteoarthritis and Cartilage, was comprised of over 300 patients with OA knee pain.



At the end of the study, 63 percent of the patients treated with Euflexxa were symptom-free compared to 52 percent of those treated with Synvisc.

“All of these findings indicate that (Euflexxa) can offer clinicians an alterative to hyaluronic acid use for patients with poultry allergies, says Deborah Brown, APRN, BC, an Orthopaedic Nurse Practitioner at the Beth Israel Deaconess Medical Center in Boston. “Also, patients in the Euflexxa group seemed to have improved outcomes and there was less post-injection analgesic use in comparison to the Synvisc group.”

In other news, revised labeling for Euflexxa was recently approved by the FDA. Clinicians can now store the product at room temperature or refrigerate the product.
— A.L.

Study Says New Drug Is Promising For Fibromyalgia
Preliminary results from a phase II trial show that sodium oxybate may be beneficial in treating symptoms associated with fibromyalgia.

The phase II, double-blind, randomized study involving approximately 150 patients consisted of three treatment groups with some patients receiving 4.5 g per day of sodium oxybate, another group receiving 6 g per day of sodium oxybate and another group receiving a placebo. Researchers measured the primary outcome as a composite of patient self-assessments of pain and fatigue via a visual analog score, a fibromyalgia impact questionnaire and a patient global impression of change.

Study researchers note that patients in the 4.5 g sodium oxybate group had a 34.5 percent response rate and patients in the 6 g sodium oxybate group had a 27.3 percent response rate whereas the placebo group had a 12.5 percent response rate.

Kim Dupree Jones, PhD, RN, FNP, who was one of the researchers involved in the multicenter study, says Xyrem is the only sleep agent known to increase the amount of time patients spend in stages III and IV of sleep. She notes that 70 to 80 percent of growth hormone (GH) is made during these sleep stages. Given these findings, Xyrem may have benefit for other symptoms associated with fibromyalgia, according to Dr. Jones.

“We have done several studies that have demonstrated that one-third of fibromyalgia patients have low IGF-1 (a long-term marker of growth hormone),” explains Dr. Jones, an Assistant Professor within the School of Nursing at Oregon Health And Science University. “More recently, we have shown that 90 percent of these patients fail an exercise-induced growth hormone test regardless of IGF-1. Xyrem has the potential to not only help sleep but help restore GH and IGF-1, which should help in reducing muscle soreness, pain and fatigue.”

Additionally, Dr. Jones, a principal investigator on multiple fibromyalgia research grants, theorizes that combining pyridostigmine bromide and sodium oxybate might maximize the GH release and grant fibromyalgia patients even more relief. However, she notes there are no currently published studies on this combination.

Xyrem is FDA-approved for cataplexy and excessive daytime sleepiness associated with narcolepsy. However, it is not currently FDA-approved for the treatment of fibromyalgia.

Still, Dr. Jones says the preliminary results from the sodium oxybate study are encouraging for fibromyalgia patients and the clinicians who treat them.

“MDs, NPs and PAs need to help patients understand that we will keep working with them until they get some symptom relief,” emphasizes Dr. Jones.
— A.L.

In Brief

The FDA has approved revised labeling for Supartz Joint Fluid Therapy (Smith and Nephew). While the modality is still indicated for five weekly injections for OA knee pain, clinicians can now use just three weekly injections if they think patients will benefit from this amount.