News Author: Laurie Barclay, MD
CME Author: Hien T. Nghiem, MD

Complete author affiliations and disclosures, and other CME information, are available at the end of this activity.

Release Date: September 14, 2005; Valid for credit through September 14, 2006

Credits Available

Physicians - up to 0.25 AMA PRA Category 1 continuing physician education credits ;
Family Physicians - up to 0.25 AAFP Prescribed continuing physician education credits

All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.
Participants should claim only the number of hours actually spent in completing the educational activity.

Sept. 14, 2005 — Abatacept is beneficial to rheumatoid arthritis patients with inadequate response to tumor necrosis factor (TNF)–alpha inhibitors, according to the results of a randomized, double-blind study published in the Sept. 15 issue of The New England Journal of Medicine.

"A substantial number of patients with rheumatoid arthritis have an inadequate or unsustained response to TNF-α inhibitors," write Mark C. Genovese, MD, from the Stanford University Medical Center in California, and colleagues. "There are currently no clinically proven treatment options for patients with an inadequate response to anti–TNF-α therapy. Abatacept is the first in a new class of agents for the treatment of rheumatoid arthritis that selectively modulate the CD80 or CD86-CD28 costimulatory signal required for full T-cell activation."

In the phase 3 Abatacept Trial in Treatment of Anti-TNF Inadequate Responders (ATTAIN), patients with active rheumatoid arthritis and an inadequate response to anti–TNF-alpha therapy were randomized 2:1 to receive abatacept or placebo on days 1, 15, and 29 and every 28 days thereafter for six months, in addition to at least one disease-modifying antirheumatic drug (DMARD). Before entering the study, patients discontinued anti–TNF-alpha therapy.

After six months, the rates of American College of Rheumatology (ACR) 20 responses, indicating a clinical improvement of 20% or higher, were 50.4% in the abatacept group and 19.5% in the placebo group (P < .001). The abatacept group also fared better than the placebo group in the rates of ACR 50 and ACR 70 responses (20.3% vs 3.8%; P < .001; and 10.2% vs 1.5%, respectively; P = .003).

At six months, clinically meaningful improvement in physical function, reflected by an improvement from baseline of at least 0.3 in the Health Assessment Questionnaire (HAQ) disability index, occurred in 47.3% of patients in the abatacept group and in 23.3% of patients in the placebo group (P < .001). Adverse events and peri-infusional adverse events occurred in 79.5% and 5.0%, respectively, in the abatacept group, and in 71.4% and 3.0%, respectively, in the placebo group. The rate of serious infections was 2.3% in each group.

"Abatacept is clinically efficacious and has an acceptable safety profile in patients with rheumatoid arthritis and an inadequate response to anti–TNF-α therapy," the authors write. "Abatacept may thus represent a potential new treatment for patients with rheumatoid arthritis, including those who have had an inadequate response to anti–TNF-α therapy."

Bristol-Myers Squibb, the maker of abatacept, and the National Center for Research Resources, National Institutes of Health, supported this study. Bristol-Myers Squibb employs five of the study authors and has various financial arrangements with eight other authors, some of whom also report various financial arrangements with Abbott, Amgen, Genentech, Biogen IDEC, Human Genome Services, Wyeth, Merck, and/or Pfizer.

N Engl J Med. 2005;353:1114-1123

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to:

• Describe current therapy options for rheumatoid arthritis.
• Evaluate the efficacy and safety of abatacept in patients with active rheumatoid arthritis refractory to anti–TNF-alpha therapy.

Clinical Context

Rheumatoid arthritis is a chronic inflammatory disease that leads to progressive joint damage; it can be a debilitating disease for those affected. Current therapy relies on DMARDs, such as methotrexate and anti–TNF-alpha therapy. They target the inflammatory effects of the autoimmune activation that is characteristic of rheumatoid arthritis. Despite the efficacy of agents such as TNF-alpha inhibitors, a proportion of patients have no response or unsustained response or form antibodies against the drugs.

Abatacept is a new class of drug for the treatment of rheumatoid arthritis that selectively modulates the CD80 or CD86-CD28 costimulatory signal required for full T-cell activation, inhibiting the autoimmune response. Studies already have demonstrated its efficacy in combination with methotrexate in patients with an inadequate response to methotrexate. The aim of this current study was to evaluate the safety and efficacy of abatacept in patients with active rheumatoid arthritis and an inadequate response to anti–TNF-alpha therapy.

Study Highlights

• From December 2002 to June 2004, patients with active rheumatoid arthritis and an inadequate response to anti–TNF-alpha therapy were enrolled in this muticentered, randomized, double-blinded, phase 3 trial to evaluate abatacept.
• In a 2:1 ratio, 258 received abatacept, and 133 received placebo on days 1, 15, and 29 and every 28 days thereafter for 6 months. In addition, patients were also taking at least one DMARD, including oral corticosteroids.
• Baseline demographic and clinical characteristics were similar in both groups.
• Primary endpoints were assessed with the ACR 20 responses and functional disability, reflected by improvement in scores of the HAQ disability index.
• Secondary endpoints included ACR 50 and ACR 70, Disease Activity Score 28 (DAS28), and health-related quality of life assessed by the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36).
• After six months, the rates of ACR 20 responses were significantly higher in the abatacept group than in the placebo group (50.4% vs 19.5%; P < .001).
• More patients in the abatacept group than in the placebo group had a clinically significant improvement in physical function, reflected in the HAQ disability index (47.3% vs 23.3%; P < .001).
• The rates of ACR 50 and ACR 70 were also significantly higher in the abatacept group than in the placebo group (20.3% vs 3.8%; P < .001; 10.2% vs 1.5%, P = .003).
• Rates of remission (as defined by a DAS 28 of less than 2.6) were significantly higher in the abatacept group than in the placebo (10.0% vs 0.8%; P < .001).
• 17.1% of patients in the abatacept group had a low level of disease activity (defined by a DAS28 of 3.2 or less) as compared with 3.1% of patients in placebo (P < .001)
• Quality of life was assessed with the SF-36 and was significantly improved in the abatacept group.
• The incidence of adverse events, serious infections, and rates of discontinuation were similar in both groups. Infections and acute infusion reactions were more frequent in the abatacept group than in placebo group; however, they were mild to moderate in nature.
• Abatacept did not increase the incidence of autoimmunity.
• Abatacept not only demonstrated significant clinical and functional benefits but also improved quality of life in patients who had an inadequate response to anti–TNF-alpha therapy.

Pearls for Practice

• Current treatment options for rheumatoid arthritis include DMARDs, such as methotrexate and anti–TNF-alpha therapy.
• Abatacept was shown to be clinically efficacious with an acceptable safety profile, making it a potential new treatment for patients with rheumatoid arthritis.

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

FOLLOW THESE STEPS TO EARN CME/CE CREDIT*:

1. Read the target audience, learning objectives, and author disclosures.
2. Study the educational content online or printed out.
3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. Medscape encourages you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 5 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.

Target Audience

This article is intended for primary care physicians, rheumatologists, and other specialists who care for patients with rheumatoid arthritis.

Goal

The goal of this activity is to provide the latest medical news to physicians and other healthcare professionals in order to enhance patient care.

Accreditation Statements

For Physicians

Medscape is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Medscape designates this educational activity for 0.25 Category 1 credit(s) toward the AMA Physician's Recognition Award. Each physician should claim only those credits that reflect the time he/she actually spent in the activity.

Medscape Medical News (MMN) has been reviewed and is acceptable for up to 150 Prescribed credits by the American Academy of Family Physicians. AAFP accreditation begins 09/01/05. Term of approval is for 1 year from this date. This component is approved for 0.25 Prescribed credit. Credit may be claimed for 1 year from the date of this issue.

Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity: mailto:CME@webmd.net For technical assistance, contact CME@webmd.net.

Authors and Disclosures

As an organization accredited by the ACCME, Medscape requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as "financial relationships in any amount, occurring within the past 12 months," that could create a conflict of interest.

Medscape encourages Authors to identify investigational products or off-label uses of products regulated by the U.S. Food and Drug Administration, at first mention and where appropriate in the content.

News Author

Laurie Barclay, MD
is a freelance writer for Medscape.

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Clinical Reviewer

Gary Vogin, MD
Senior Medical Editor, Medscape

Disclosure: Gary Vogin, MD, has disclosed no relevant financial relationships.

CME Author

Hien T. Nghiem, MD
Writer for Medscape Medical News

Disclosure: Hien T. Nghiem, MD, has disclosed no relevant financial relationships.

About News CME

News CME is designed to keep physicians and other healthcare professionals abreast of current research and related clinical developments that are likely to affect practice, as reported by the Medscape Medical News group. Send comments or questions about this program to mailto:%20cmenews@medscape.net.

Medscape Medical News 2005. © 2005 Medscape

Legal Disclaimer

The material presented here does not necessarily reflect the views of Medscape or companies that support educational programming on www.medscape.com. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.

 

Abatacept May Benefit Patients With Rheumatoid Arthritis Refractory to TNF-alpha Inhibitors(Abatacept可能有益于类风湿性关节炎患者抵抗TNFα抑制剂)