Patients with gout may have a new ally when it comes to reducing hyperuricemia. Two emerging studies show a significantly higher percentage of patients achieved reduced serum uric acid levels with febuxostat than those who took allopurinol.

One study, which was presented at the American College of Rheumatology (ACR) Annual Scientific Meeting in November, assessed more than 1,000 patients over a 28-week period. Three treatment groups were given doses of febuxostat at 80 mg/day, 120 mg/day and 240 mg/day respectively. Another treatment group received 100 or 300 mg of allopurinol while another group received a placebo treatment, according to the study.

Here one can see characteristic X-ray changes with late stage gout. Two recent studies show that febuxostat may be a viable treatment option for patients with gout.

The study showed a reduction of the uric acid level to less than 6 mg/dL at the last three monthly visits in 48 percent of patients who received 80 mg/day of febuxostat; 65 percent of patients who received 120 mg/day of febuxostat; and 69 percent of patients who took 240 mg/day of febuxostat. In comparison, only 22 percent of patients taking allopurinol achieved the primary endpoint target reduction and none of the patients in the placebo group achieved the reduction.

Another study comparing febuxostat and allopurinol was recently published in The New England Journal of Medicine (NEJM). This randomized, 52-week study evaluated over 700 patients with gout and serum uric acid levels of at least 8 mg/dL. More than 50 percent of patients taking 80 mg/day of febuxostat achieved a serum uric acid level of less than 6 mg/dL at the last three monthly measurements, according to the study. This was in comparison to 62 percent of patients who reached this primary endpont with 120 mg/day of febuxostat and 21 percent of patients who achieved this target with 300 mg/day of allopurinol.

Joan McTigue, MS, PA-C, says these findings are significant in presenting a viable treatment alternative for patients with gout.

“A good number of people with gout are either allergic to allopurinol, take medications that interact negatively with allopurinol or have a poor tolerance to it (especially gastrointestinal intolerance),” explains McTigue, who is affiliated with the Division of Rheumatology at the University of Florida College of Medicine.

McTigue says febuxostat is a more selective agent than allopurinol and does not have to be renally dosed.
“(Febuxostat) will be a boon to a good segment of gout sufferers with renal impairment,” points out McTigue.

Michael A. Becker, MD, the lead author of the NEJM study, concurs with McTigue. He cites the “remarkable difference” between febuxostat and allopurinol in reducing serum uric acid levels at the doses used in the study.

“(Febuxostat) is an alternative for long-term management that did not exist before and may be particularly useful in the nearly 20 percent of people who react adversely to allopurinol and to those with kidney impairment that may preclude adequate allopurinol dosing,” notes Dr. Becker, a Professor of Medicine at the University of Chicago Pritzker School of Medicine.

In regard to the ACR study, McTigue says febuxostat helped patients get to 6mg/dL faster than allopurinol and patients were able to retain that level longer as well.

However, Dr. Becker states there is no evidence of a faster response to febuxostat than allopurinol. He says all groups reached the level of urate-lowering maintained by week 2 of the study. Dr. Becker agrees that the degree of urate lowering was sustained over the course of both studies.

Discussing the NEJM study, Dr. Becker took note of the “very high rate of gout flares in the period immediately after withdrawal of prophylaxis (with colchicine or naproxen), which was provided to all patients during the first eight weeks of the study.”

He notes the incidence of gout flares subsequently diminished in all study groups with continued treatment.

Studies Look At Combination Therapy For RA

Two recent studies on combination therapy show improved results for patients with rheumatoid arthritis (RA).
The first study, which was presented at the aforementioned ACR conference, compared the combination of 40 mg/eow adalimumab (Humira, Abbott) and methotrexate versus monotherapy treatment arms of adalimumab and methotrexate in treating RA.

Researchers of the double-blind, phase III study found that combination therapy resulted in significantly greater improvements than the methotrexate monotherapy in physical function and health-related quality of life after 12 weeks of treatment. Authors of the study, which involved nearly 800 patients with RA, also emphasize these improvements were sustained at the conclusion of two years of therapy.

Results from a three-year study found the combination of etanercept and methotrexate for RA led to a 56 percent improvement for patients in performing the activities of daily living.

Another study presented at the ACR conference evaluated the combination of 25 mg/wk of etanercept (Enbrel, Wyeth) and weekly methotrexate to treat RA. The researchers compared the combination arm versus etanercept monotherapy and methotrexate monotherapy. The three-year, randomized study of more than 600 patients found that over 75 percent of patients with combination therapy had no progression of joint damage at three years.

There was also a 56 percent mean improvement from the baseline among the combination therapy patients in being able to perform activities of daily living. The authors of the study note this percentage was over 20 percent higher than those patients treated with methotrexate monotherapy.

While Roger Green, ND, FNP, FAANP, cites the promise of both studies, he says the combination of etanercept and methotrexate is particularly exciting for patients with RA.

“The key point is that patients experienced no progression of joint damage while on the combination of (etanercept) and methotrexate, and the results demonstrated a more significant response with dual therapy versus monotherapy,” notes Dr. Green, the President of the American College of Clinicians.

However, he cautions that insurance companies might decline coverage of these types of combination therapies.

Antonio Giannelli, MsA, PA-C, says the combination of methotrexate and Enbrel is “readily accepted by a majority of our patients” and challenges the standard of care for RA.

“With the advent of biologics such as etanercept, we can improve outcomes and potentially reduce the number and dose of medications required, thereby reducing side effects and, at times, the overall out-of-pocket expense to the patient,” offers Giannelli, who is in practice at Associated IM Specialists, Rheumatology in Battle Creek, Mich.
– A.L.

FDA Approves Abatacept For RA

The U.S. Food and Drug Administration (FDA) recently approved abatacept (Orencia, Bristol-Myers Squibb) for the treatment of RA. In three double-blind, randomized phase III trials, researchers have shown that abatacept reduces the signs and symptoms of the autoimmune disease.

Clinicians say the FDA approval of abatacept is good news for many RA sufferers who have not had success with disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor antagonists.

As the first selective modulator of a co-stimulatory signal required for full T-cell activation, abatacept can help curtail the initiation and progression of RA, according to Mark C. Genovese, MD, an Associate Professor of Medicine in the Division of Rheumatology at the Stanford University School of Medicine.

The aforementioned Phase III trials evaluated more than 2,600 patients and researchers of the AIM and ATTAIN studies found that abatacept achieved significant and sustained improvement of the signs and symptoms of RA. Additionally, authors of the AIM study found that 14 percent of patients taking the combination of abatacept and methotrexate maintained an ACR 70 score for six months.

In addition to the proven efficacy, Dr. Genovese says the infusion therapy facilitates patient compliance and has few reported side effects. The lead author of the ATTAIN study, Dr. Genovese says there was little in the way of adverse reactions for abatacept as the most prevalent side effect was headache while some patients had other adverse events including upper respiratory tract infection, nasopharyngitis and nausea.

The manufacturer of the drug says clinicians should exercise caution in using abatacept in patients with chronic obstructive pulmonary disease and only use it in pregnant patients if the drug is clearly indicated.
– A.L.

Can Sodium Hyaluronate Reduce Chronic Shoulder Pain?

A recent study shows that patients with chronic shoulder pain have significant improvement after receiving injections of sodium hyaluronate over a six-month period.

The double-blind, randomized study, which was recently presented at the aforementioned ACR conference, assessed over 600 patients between the ages of 35 and 63, who suffered from moderate to severe shoulder pain due to osteoarthritis, rotator cuff tear and/or adhesive capsulitis.

Researchers of the study showed that patients receiving either three to five weekly injections of sodium hyaluronate (Hyalgan, Sanofi-Aventis) over a six-month period experienced a considerable amount of pain reduction compared to the control group.

A new study cites the benefits of sodium hyaluronate injections for reducing chronic shoulder pain.

Nathan Wei, MD, says he has also found success in using viscosupplements for this condition.

“I use viscosupplements for chronic shoulder pain, which has not responded to intraarticular steroid injections. Viscosupplements appear to work best for people who have an osteoarthritis component to their shoulder problem,” notes Dr. Wei, who is in private practice at the Arthritis and Osteoporosis Center of Maryland in Frederick, Md.

He adds that viscosupplements are “less effective” for pure rotator cuff problems in his experience.
As this issue went to press, sodium hyaluronate is being reviewed by the FDA for a chronic shoulder pain indication. The medication is currently indicated for osteoarthritis of the knee in patients who have failed to respond adequately to conservative, nonpharmacologic therapy and simple analgesics.
– A.L.

Early Study Cites Benefits Of Twice-A-Year Injection For Osteoporosis

There is good news for postmenopausal women who suffer with osteoporosis. Preliminary results from the first two years of an ongoing study found that an emerging injectable medication helped increase bone mineral density (BMD) in the lumbar spine, total hip and total body compared to a placebo. These results were presented at the aforementioned ACR conference.

The phase II trial compared twice-a-year injections of denosumab (60 mg) versus 70 mg/wk of alendronate (Fosamax) and a placebo treatment. Researchers found that the twice-a-year injection of denosumab increased total hip BMD by 5.1 percent at the two-year mark whereas the weekly dose of alendronate resulted in a 3.4 percent increase over the same time period.

Michael Lewiecki, MD, one of the researchers involved with the study, says denosumab increases bone density and bone turnover. One of the reported goals behind the therapy is to counteract a protein called RANK Ligand, which acts as a signal to start bone removal in the body.

“The antibody gets to the root cause of bone resporption,”explains Dr. Lewiecki, a Clinical Assistant Professor of Medicine at the University of New Mexico School of Medicine in Albuquerque, New Mexico.

While denosumab has been explored in many trials, Ethel Siris, MD, the Director of the Toni Stabile Osteoporosis Center at Columbia University Medical Center, says these latest findings are significant for those who treat osteoporosis.

With the phase II trial showing positive results, such as increased BMD of the lumbar spine by 7.4 percent, for denosumab, the phase III trial is underway.

“There is a lot of potential at this point but it will be a few years before the complete data is available,” notes Dr. Lewiecki.
– A.L.