While clinicians have seen an increasing number of treatment options emerge for rheumatoid arthritis (RA) in recent years, a new study reveals that etanercept has sustained efficacy and safety for up to nine years in patients with moderate to severe RA.

According to the study, which was presented recently at the American College of Rheumatology (ACR) Scientific Meeting, researchers found sustained improvement with etanercept (Enbrel, Amgen/Wyeth) in both patients with early RA and those with longstanding RA.

In assessing 77 patients with early RA and 280 patients with longstanding RA who completed eight years of treatment with etanercept, researchers found that 75 percent of patients with early RA and 76 percent of those with longstanding RA achieved an ACR 20 score. Sixty percent of those with early RA and 52 percent of patients with longstanding RA achieved an ACR 50 score. The study findings also revealed that 35 percent of those with early RA and 26 percent of patients with longstanding RA had an ACR 70 score.

Additionally, when it came to patients with longstanding RA who received etanercept for nine years, 74 percent achieved an ACR 20, 41 percent had an ACR 50 response and 22 percent had an ACR 70 score.
“Overall, we have had a very good clinical experience with etanercept and recognize that it has resulted in significant improvements for many patients who have RA,” says Mark Genovese, MD, the lead investigator of the study and an Associate Professor of Medicine in the Division of Immunology and Rheumatology at the Stanford University School of Medicine.



Nathan Wei, MD, calls etanercept “an excellent drug,” noting that he probably chooses etanercept more than other anti-TNF medications for RA due to his greater experience with the drug. He believes the majority of clinicians choose etanercept as their first-line anti-TNF drug for treating RA.

“It has been around the longest and the perception is that (etanercept) is the safest,” notes Dr. Wei, the Clinical Director of the Arthritis and Osteoporosis Center in Frederick, Md.

Etanercept’s perceived safety appears to be backed up by the study findings. In addition to the sustained efficacy, researchers found that the rates of serious adverse events and serious infections “remained low over time.”

When it comes to choosing a biologic therapy for patients with moderate to severe RA, Drs. Genovese and Wei say they consider a number of factors including efficacy, patient tolerability, the route of administration and cost. Long-term safety, as demonstrated by the etanercept study, is also a key consideration in making the best choice for the patient.

“Long-term safety is certainly important and will be one of many factors that have weight on the clinician’s choice,” explains Dr. Genovese.

While the rate of lymphoma was reportedly higher among the study patients than the expected rate in the general population, researchers say it was unclear whether this was related to etanercept or an inherently elevated risk of lymphoma among patients with RA.

Overall, however, Dr. Genovese says etanercept as well as other biologics have a “favorable risk-benefit profile for patients with active RA.” Dr. Wei adds that the advent of anti-TNF drugs have raised expectations when it comes to managing RA.

“Before the anti-TNF medications, we would be happy with a good ACR 20 response,” points out Dr. Wei. “We now expect a significant ACR 50 and ACR 70 response.”

Can Adalimumab Have An Impact For JRA?
Juvenile rheumatoid arthritis (JRA) affects an estimated 285,000 people in the United States. Symptoms range from joint stiffness and swelling to reduced activity levels. However, a new study reveals that adalimumab may have an impact in treating this condition.

Researchers of the multicenter, double-blind study, which was presented at the aforementioned ACR conference, found that patients achieved significant response rates with adalimumab at the end of the 48-week evaluation period.

According to the study, 60 percent of patients in the adalimumab group achieved an ACR 30, 59 percent achieved an ACR 50 and 56 percent garnered an ACR 70 response. The ACR 70 response with adalimumab was double the response achieved by the placebo group. Researchers of the study reported that the most common side effects were mild respiratory infections.

Daniel J. Lovell, MD, MPH, one of the study investigators, notes they see more than 800 patients with JRA in the rheumatology clinic at Cincinnati Children’s Hospital Medical Center and adalimumab has been used off-label to help treat the children with JRA. Based upon the study results and his clinical experience with the drug, Dr. Lovell says adalimumab is “effective and well-tolerated” for patients with JRA.

A new study reveals that adalimumab may have an impact in treating juvenile rheumatoid arthritis (JRA).

The study initially evaluated 171 JRA patients, who ranged between 4 and 17 years of age. According to the study, these patients had five or more swollen joints, and three or more joints with limited range of motion. Researchers note that the adalimumab dosing was based upon the child’s size as patients received 24 mg/M2 BSA (a maximum of 40 mg) as a subcutaneous injection every two weeks over an initial 16-week period.

At the end of 16 weeks, researchers identified 142 of the patients as “responders” and these patients were subsequently randomized into a group that continued to receive adalimumab and a placebo group. According to the study, 43 percent of the adalimumab group (not taking methotrexate) had a disease flare whereas 71 percent of the non-methotrexate placebo group flared. In regard to those who were also taking methotrexate, 37 percent of the adalimumab group had a disease flare-up whereas 65 percent of the placebo group experienced a disease flare.

Dr. Lovell says a key benefit of the study is the demonstration of an effective and safe dose for adalimumab for use in children with JRA. He says this simpler dosing should facilitate better compliance. An injection every two weeks (compared to daily, weekly or twice weekly with other products) is a step in the right direction from a kid’s point of view, according to Dr. Lovell, the Chairman of the Pediatric Rheumatology Collaborative Study Group.
— A.L.

FDA Issues Warning About Rituximab For SLE
The FDA recently issued a warning about the off-label use of rituximab (Rituxan, Genentech) for the treatment of systemic lupus erythematosus (SLE).

According to the FDA, two patients who were treated with rituximab for SLE developed progressive multifocal leukoencephalopathy (PML), a fatal viral infection of the central nervous system. The FDA notes that this side effect has been reported in patients as late as a year after their last dose of Rituxan.

SLE is not an approved indication for Rituxan.

The FDA urges clinicians to educate patients who are taking rituximab to report “any major changes in vision, balance or coordination (or confusion)” to their doctor.
— A.L.

FDA Approves Celecoxib For Juvenile Rheumatoid Arthritis
The Food And Drug Administration (FDA) recently announced that celecoxib (Celebrex, Pfizer) has garnered approval for treating the signs and symptoms of juvenile rheumatoid arthritis (JRA) in patients two years of age and older.

The FDA approval was based upon celecoxib’s demonstrated efficacy in a 24-week study involving 242 patients with JRA between the ages of 2 and 17.

Donald Goldsmith, MD, also notes that several pediatric rheumatologists presented additional positive data on celecoxib at recent FDA hearings.

Dr. Goldsmith, a Professor of Pediatrics at the Drexel University College of Medicine in Philadelphia, has previously used celecoxib off-label to treat JRA and believes his experience mirrors that of the pediatric rheumatology community.

“(Celecoxib) is basically as effective as other NSAIDs and offers an alternative preparation for those children who are intolerant to routine NSAIDs,” notes Dr. Goldsmith, the Director of the Section of Rheumatology at St. Christopher’s Hospital For Children in Philadelphia.

“Compared to the adult rheumatic disease community, (pediatric rheumatologists) have fewer drugs that are formally approved,” adds Dr. Goldsmith. “When a large study of pediatric patients shows (that celecoxib has) efficacy and good tolerance, then celecoxib should be an available option for this condition.”
— A.L.

Study Says: Abatacept Offers Sustained Benefits In RA Patients
After two years of receiving treatment with abatacept, patients with RA maintained significant improvements, according to study findings that were presented recently at the aforementioned ACR conference.

The study, an open-label extension of the six-month, phase III ATTAIN trial, evaluated the use of abatacept at the 24-month mark in patients with active RA who previously had an inadequate response to three months or more of anti-TNF therapy.

In the original six-month trial, 59.4 percent of patients in the abatacept (Orencia, Bristol-Myers Squibb) group achieved an ACR 20 score, 23.5 percent had an ACR 50 and 11.5 percent had an ACR 70 score. In regard to the patients on abatacept who completed two years of the study, 56.2 percent had an ACR 20 score, 33.2 percent achieved an ACR 50 and 16.1 percent had an ACR 70 response.

A recent study reveals that patients with RA had sustained improvements after two years of treatment with abatacept.

While Michael Luggen, MD, has primarily used abatacept to treat RA patients who have failed anti-TNF treatment, he says the ACR 20 and ACR 50 scores for abatacept in the study are comparable with the results of other biologic therapies used to treat RA.

“I suspect that I will be using abatacept sooner in some of my patients in the near future,” adds Dr. Luggen, who was one of the study investigators.

If the clinician is using a first-line anti-TNF therapy to treat RA and the patient does not have significant relief of pain and inflammation, Dr. Luggen says he would lean more toward a different biologic agent as opposed to another anti-TNF medication.

“If the patient has no or a minimal response to the first TNF inhibitor, I would be less likely to switch to another anti-TNF agent and more likely to switch to a different biologic,” says Dr. Luggen, who is also a Professor of Immunology at the University of Cincinnati in Cincinnati.

Additionally, Dr. Luggen was surprised to see in the study that patients with RA for 10 to 12 years responded well to abatacept.

“After a certain period of time, it is generally believed that RA is self-sustaining and may no longer be antigen-driven,” points out Dr. Luggen. “Even if this were true, the results of the ATTAIN trial suggest that T cells continue to be important in disease pathogenesis at some level and that abatacept should be considered even in patients with disease of longer duration.”
— A.L.

Could A Protein Marker Predict AS Damage?
Approximately 500,000 people in the United States have ankylosing spondylitis (AS).

Here is a view of moderate ankylosing spondylitis. New research suggests the MMP3 protein marker may help predict joint damage from the disease.

However, new research presented at the aforementioned ACR conference indicates that the protein marker metalloproteinase 3 (MMP3) may be a key predictive factor of joint damage from the disease, and may enable clinicians to tailor treatment regimens accordingly.

In assessing data from an ongoing study of 100 AS patients, researchers reportedly evaluated blood samples for protein markers that are associated with cartilage breakdown and RA-related deformities. The researchers found that metalloproteinase 3 was a “significant independent predictor of radiographic progression in AS.”
Walter P. Maksymowych, MD, one of the investigators of the study, says this is a key finding for clinicians who treat AS.

“If the patient already has a mild degree of X-ray damage at baseline and an elevated MMP3, there is a very high likelihood that the patient will progress to further damage so the patient should be more vigorously treated,” explains Dr. Maksymowych, a Professor of Medicine at the University of Alberta in Canada.

Lori Markowitz, BS, MS, PA-C, says this development is a “breakthrough” in the current treatment approach to AS. She says she will use the MMP3 to identify whether patients have a predisposition to more severe AS.
Markowitz, the President-Elect of the Association of Family Practice PAs, says the MMP3 biomarker could facilitate more proactive treatment “before the patients actually develop more severe damage in the spine.”
— A.L.

Survey Reveals The Impact Of Gout
A recent poll conducted by the newly created Gout and Uric Acid Education Society shows that 65 percent of patients with gout rank their typical gout flares as extremely painful with flares lasting an average of eight days.

Here are characteristic X-ray changes with late stage gout. A new survey notes that 65 percent of patients with gout say a typical gout flare is extremely painful.

Out of 321 gout patients who participated in an online survey, 75 percent said that a painful flare had a significant impact on walking while 70 percent reported that recreational sports and activities were impacted as well. The survey also reveals that 21 percent of respondents have missed work in the last year because of a gout flare with 23 percent of those respondents missing seven days of work or more.

While 57 percent of the survey respondents see a clinician for treatment, only 13 percent of these respondents go to a rheumatology office whereas 80 percent go to a primary care practice for treatment.
“What will surprise clinicians is how much gout — both the acute flare and the chronic condition — goes untreated or under-treated,” notes Joan McTigue, MS, PA-C, who is affiliated with the Division of Rheumatology at the University of Florida College of Medicine. She says the goal of treating hyperuricemia and gout is to get the serum uric acid to under 6.0 mg/dL.

McTigue, who helped developed the survey, also hopes it will raise awareness among clinicians on just how incapacitating gout can be for patients. She encourages clinicians to monitor the impact of treatment upon a patient’s serum uric acid levels and emphasizes the importance of patient education on appropriate lifestyle modifications.
— A.L.

Ongoing Study Shows Potential Of Abatacept For JIA
Preliminary findings from an ongoing study reveal that abatacept may have a favorable impact when it comes to treating juvenile idiopathic arthritis (JIA).

Researchers presented findings from the first two phases of the study at the aforementioned ACR conference. The study is currently in the open-label phase so researchers can assess the long-term safety and efficacy of abatacept (Orencia, Bristol-Myers Squibb) for JIA.

The study initially evaluated the use of abatacept in 190 JIA patients, who had a previously inadequate response to one or more biologic DMARDs. Seventy-four percent of the patients were taking methotrexate prior to the study and continued to take methotrexate (a mean dosage of 13.2 mg/m2 per week) throughout the study.

According to the study, nearly 65 percent of study participants achieved an ACR Pedi 30 response at the end of four months, nearly 50 percent had an ACR Pedi 50 score and 28.4 percent achieved an ACR Pedi 70 response.

Edward H. Giannini, MSc, DrPH, one of the principal investigators of the study, says the ACR Pedi 70 response with abatacept is significant.

“Achieving an ACR Pedi 70, particularly in patients who had tried multiple other agents without dramatic clinical success, is a sign that the drug has a high degree of efficacy,” explains Dr. Giannini, a Professor of Pediatrics in the Division of Rheumatology at the Cincinnati Children’s Hospital Medical Center in Cincinnati.
Researchers subsequently proceeded to the double-blind phase of the study, in which all of the patients (with the exception of one) who had an ACR Pedi 30 response in the first phase of the study were randomized to either continue receiving abatacept or a placebo every 28 days for a six-month period.

According to the study, 53.2 percent of placebo patients experienced disease flares in comparison to 20 percent of the abatacept group.

Some of the common side effects recorded in the study included upper respiratory tract infection, influenza, bacteriuria and nasopharyngitis. However, researchers noted that no patient receiving abatacept during the six-month phase of the study had a serious adverse event.

Dr. Giannini says abatacept is the first in a new class of biologics that mitigates “inappropriate immune response” in people with autoimmune diseases via the mechanism known as co-stimulatory blockade. He says abatacept blocks the secondary signal between antigen-presenting cells and T-cells that is necessary for T-cell activation.

Dr. Giannini says he was surprised by the “rather dramatic beneficial clinical effect” that researchers were able to achieve with abatacept in this study. If and when abatacept garners FDA approval for a JIA indication, Dr. Giannini says it could be an important addition to the armamentarium for this disease.

“It is now well established that not all children with arthritis will respond clinically to anti-TNF agents such as Enbrel or there may be toxic side effects to such therapy,” points out Dr. Giannini. “Clinicians and patients need choices with this disease.”

— A.L.

In Brief

• The FDA recently approved an expanded psoriatic arthritis (PsA) indication for adalimumab (Humira, Abbott).

The expanded indication includes inhibiting structural joint damage and improving physical function in patients with PsA. This was reportedly based upon the results from the ADEPT study, a phase III, randomized study involving more than 300 patients with moderate to severe PsA.

Adalimumab originally gained FDA approval for the treatment of psoriatic arthritis in 2005. It is also indicated for moderate to severe RA and active ankylosing spondylitis.

• As this issue went to press, Genzyme announced that its viscosupplement hylan G-F 20 (Synvisc), which is indicated for OA knee pain, will maintain a separate reimbursement code and rate for 2007 as per the Centers for Medicare and Medicaid Services (CMS). The code is Q4084.

Clarification

In the print version of this issue, a photo showing moderate ankylosing spondylitis inadvertently ran with the article “Ongoing Study Shows Potential Of Abatacept For JIA” on page 11. The photo should have run with the article “Could A Protein Marker Predict AS Damage?” on page 10. We regret the error.