Results of a five-year study showed that the majority of patients taking infliximab (Remicade, Centocor) for ankylosing spondylitis safely tolerated the drug and a third of the patients had complete remission without any major side effects.

The study, which was recently presented at the European League Against Rheumatism (EULAR)’s Annual European Congress of Rheumatology, initially enrolled 69 patients with active ankylosing spondylitis. After a three-month, placebo-controlled phase, 65 patients began the open treatment phase and started receiving 5 mg/kg of IV infliximab every six weeks. After three years, researchers discontinued the treatment. However, according to the study, they would re-administer the therapy for those who suffered a clinical relapse.

Out of the original patients enrolled, 54 completed the first year of treatment, 49 completed the second year and 43 completed the third year of therapy. According to the study, which used a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), 68.3 percent of the patients enrolled at the end of the fifth year had a 50 percent regression of the disease activity.

“Anti-TNF therapy has revolutionized our treatment approach to the most common (and most devastating) inflammatory types of arthritis — rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis,” notes Nathan Wei, MD, FACP, FACR, the Clinical Director of the Arthritis and Osteoporosis Center in Frederick, Md.

Jurgen Braun, MD, a physician at the Rheumazentrum Ruhrgebiet and a Professor at the Free University of Berlin in Germany, says the study offers great news for patients with ankylosing spondylitis. A lead investigator on the study, Dr. Braun says patients with this chronic debilitating inflammatory disease typically experience back pain and stiffness, and that some patients in the study had these symptoms for 10 years.

Two recent studies show promising findings in the use of anti-TNF drugs to treat patients with ankylosing spondylitis.

Yet after taking infliximab, these patients had significant improvement after 24 hours, according to Dr. Braun.
However, even though the study shows positive outcomes after five years, Dr. Braun says he is still curious about effects over a longer term. He notes that he wants to see what the results are 10 years out from the beginning of the study.

While it remains unclear as to whether anti-TNF therapy can reduce or repair damage caused by ankylosing spondylitis, Dr. Braun says there is a currently an ongoing study looking into this question.
In a related story, a new phase III, double-blind study shows that adalimumab (Humira, Abbott) can help reduce the symptoms, pain and fatigue in patients with ankylosing spondylitis.

Findings from the Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS (ATLAS) study, which were reported at the aforementioned EULAR conference, found that adalimumab maintains reduced symptoms and signs of ankylosing spondylitis at 12 weeks through a year’s worth of treatment.

According to the study, 315 patients in the United States and Europe were enrolled in the randomized trial and 60 percent of the ankylosing spondylitis patients on adalimumab experienced a 20 percent reduction of symptoms at week 12. After completing the blinded phase of the study, researchers gave all patients the option to enroll in the open label extension phase of the study. Nearly 75 percent of the patients achieved the 20 percent reduction in symptoms at one year.

Study researchers also found that the drug significantly reduces pain and fatigue associated with the disease at two weeks and sustains this improvement for at least six months.

“The studies confirm our clinical impression that anti-TNF therapy is not only useful in ankylosing spondylitis but is also probably a therapy we should be using much sooner than we have been in the past,” says Dr. Wei.
Dr. Wei states that even though the results are positive for treating this disease, it might not change practice patterns for some doctors.

“Rheumatologists who are comfortable using anti-TNF drugs will continue to use them while rheumatologists who are uncomfortable using anti-TNF drugs will continue to feel uncomfortable,” says Dr. Wei, who has experience using both infliximab and adalimumab.

While Charles Moxin, MPAS, PA-C, has used both of the study drugs to treat rheumatoid arthritis, he says he has minimal experience in using the drugs for ankylosing spondylitis. However, Moxin says the studies are promising.

“I believe that these studies will be instrumental in giving rheumatology providers other weapons in the arsenal for the treatment of ankylosing spondylitis,” says Moxin, the President of the Association of Family Practice Physician Assistants. “Though (these medications are) primarily indicated for the treatment of moderate to severe RA, the studies seem to indicate a successful reduction in pain and fatigue (with ankylosing spondylitis).”

The side effects for both medications are typical of anti-TNF agents, according to Dr. Wei and Moxin. They cite possible side effects including infection, tuberculosis, demyelinating disease, infusion reactions from infliximab and injection site reactions from adalimumab.

In regard to ankylosing spondylitis, Moxin says he does prescribe nonsteroidal antiinflammatory drugs (NSAIDS) like indomethacin. He also prescribes physical therapy, exercise and heat and cold thermal applications for his patients.

Abatacept/Methotrexate Combination Shows Promise For RA
N ew data on the potential benefits of abatacept for rheumatoid arthritis (RA) continues to emerge from the phase III trial AIM (Abatacept in Inadequate Responders to Methotrexate).

According to AIM data presented at the EULAR conference, approximately 80 percent of the treatment group, who received a combination of abatacept (Orencia, Bristol Myers Squibb) and methotrexate, achieved an ACR 20 response at the end of the first and second years.

Greater than 50 percent of the treatment group achieved ACR50 responses at the end of the first and second year, and more than 30 percent of the group achieved an ACR70 response at the end of the first and second year.



Eugene Mochan, PhD, DO, says the phase III, double-blind study involving more than 600 patients is interesting and calls abatacept another alternative for patients with RA.

However, he thinks it might be premature to talk about the study at this stage and calls for more long-term outcomes. Dr. Mochan, the Associate Dean for Primary Care/Continuing Education at the Philadelphia College of Osteopathic Medicine, says it is also imperative to gain more information about potential side effects such as malignancies.

Does The Drug Inhibit RA Progress?
Other data reported from the open-label extension of the AIM study examined radiographic changes among patients with RA after two years of receiving the aforementioned combination of abatacept and methotrexate.
Researchers found erosion scores of .62 at year one and .84 at year two among the group who received the combination treatment. They also found a 57 percent reduction in RA disease activity in the combination group at the end of two years.

The study provides evidence of a viable alternative for those who cannot take anti-TNF medications, says Harry Genant, MD, a principal investigator for the study.

“We were pleased to see a substantial beneficial effect in the (affected) joints,” notes Dr. Genant, a Professor Emeritus of Radiology and Medicine at the University of California in San Francisco.

— A.L.

Early Results Show Benefits Of Synvisc For OA Knee Pain
Preliminary findings from a comparative independent study of hylan G-F 20 (Synvisc, Genzyme Corp.) and sodium hyaluronate (Hyalgan, Sanofi-Aventis) reportedly show that hylan G-F 20 offered earlier and longer lasting pain relief for patients with osteoarthritis (OA) of the knee.

According to the controlled prospective study, researchers randomized 348 patients with knee OA and gave them intraarticular injections of either hylan G-F 20 or sodium hyaluronate. The hylan G-F 20 group received three weekly injections of the drug while the sodium hyaluronate group received five weekly injections.

Presenting the early findings from the study at the aforementioned EULAR conference, researchers noted that, in addition to the superior pain relief, hylan G-F 20 also facilitated significantly better improvements in terms of functional outcomes and physical activity. The specific results of the study were not available as this issue went to press.

Michael Rudzinski, PA-C, RPh, says if the information proves to be accurate, he suspects there will be an increased shift in hylan G-F 20 use over sodium hyaluronate. Rudzinski himself uses hylan G-F 20 on his patients.

“I use this therapy as part of a comprehensive holistic approach to managing OA of the knee,” notes Rudzinski, a physician assistant who works in outpatient orthopedics and chronic pain management at the Buffalo Veterans Affairs Medical Center in Buffalo, N.Y. “I have had very good results with my patients and have no hesitation in offering or suggesting and encouraging its use as part of our comprehensive management program.”

Deborah Brown, APRN, BC, MSN, says the study suggests hylan G-F 20 has a “superior magnitude” of pain control and duration, as well as improved functional outcome for those who suffer from OA knee pain. However, she is wary about reading too much into the study given the lack of available data.

Preliminary study results indicate that injections of hylan G-F 20 may be beneficial in treating OA of the knee.

In her experience, however, Brown says viscosupplementation is a beneficial option for managing OA knee pain in patients who are either not ready for surgery or are not surgical candidates.

The lower number of injections needed for hylan G-F 20 is another benefit as it facilitates better patient compliance and follow-up, notes Brown, an Orthopaedic Nurse Practitioner at the Beth Israel Deaconess Medical Center in Boston.

In her experience, Brown says hylan G-F 20 is “very well tolerated” with little side effects. When dealing with viscosupplementation injections, Rudzinski does caution about potential reactions from patients who have allergies to hyaluronan or bird, egg, feather or poultry. He says other possible side effects are headaches, muscle cramps, dizziness and rashes.

— A.L.

In Brief
Infliximab (Remicade, Centocor) recently received an extended approval from the Food and Drug Administration (FDA). According to Centocor, the drug is now indicated for inhibiting the progression of structural damage and improving physical function among patients with psoriatic arthritis in addition to reducing the signs and symptoms of active arthritis in these patients