SAN ANTONIO, Texas – Nearly half of rheumatoid arthritis patients receiving monthly injections of the T-cell inactivator abatacept achieved at least a 50% reduction in their symptoms, researchers reported Tuesday at the 2004 annual meeting of the American College of Rheumatology.
Phase III results from the Abatacept in Inadequate Responders to Methotrexate (AIM) Trial indicated that 48.3% of patients on the investigative biologic agent achieved an ACR50 after 1 year of therapy, compared to 18.2% of patients who were given placebo injections. "Abatacept therapy seems to pick up steam the longer patients are on it," Joel Kremer, MD, Clinician and Investigator with the Center for Rheumatology, Albany, New York, said at his poster presentation.
"Having a 50/50 result — half the patients reaching an ACR50 — is pretty dramatic in rheumatology," said Hayes Wilson, MD, As sistant Professor of Medicine at Morehouse School of Medicine, Atlanta, Georgia, and Chief of Rheumatology at Piedmont Hospital in Atlanta. "These are pretty good numbers."
The trial enrolled 433 patients in the abatacept arm and 219 in the placebo arm. The abatacept patients were given 10 mg/kg of abatacept plus methotrexate. Baseline patient characteristics were similar; mean disease duration was about 8.6 years.
At 6 months, the phase III study found that the percentage of patients taking abatacept who achieved ACR20, ACR50, and ACR70 scores was 67.9%, 39.9%, and 19.8%, respectively, versus 39.7%, 16.8%, and 6.5% among those on placebo. After 1 year, the percentages of patients on abatacept who achieved ACR20, ACR50, and ACR70 scores was 73.1% 48.3%, and 28.8%, respectively, versus 39.7%, 18.2%, and 6.1% with the controls (P <0.001).
This new therapeutic agent takes a novel approach to activated T-cells in modulating disease. Abatacept is the first drug in rheumatoid arthritis that selectively modulates the costimulatory signal required for full T-cell activation.
Side effect profiles showed an increased rate of headache, nasopharyngitis, hypertension, and back pain in the abatacept arm when compared with the placebo arm, and serious infections were 3.9% for abatacept compared with 2.3% with placebo, the New York researchers found. Unlike TNF- α inhibitors, there was little suggestion of infusion reactions.
Overall, 65 patients on abatacept (15%) suffered a serious adverse event compared to 26 patients (11.9%) on placebo, but only 10 patients discontinued abatacept due to serious adverse events, compared with 3 on placebo.
"One thing everyone is concerned with are the long-term safety aspects of these new drugs and exploring if there is a potential downside." said Dr. Wilson, Medical Adviser to the Atlanta-based Arthritis Foundation. He said the short-term look at the biologic agents indicate that the drug can dramatically and positively impact the lives of patients. Compared to placebo, radiographic change showed a reduction in the progression of erosions, joint space narrowing, and total score.
Dr. Kremer said that anti-TNF-α agents appear to have a better profile in preventing structural changes, but noted that scientifically such comparisons are not considered proper. "Scientifically we are not allowed to do this," he said, "but of course we do do it." He said that because patients appear to improve the longer they are on abatacept, the differences between the anti-TNF-α molecules and abatacept might also narrow in the second, third, and later years.
In addition to the radiographic and ACR scores, patient satisfaction was apparent, with 88.9% of the abatacept arm patients completing the 1-year trial compared with 74% in the placebo arm.
Bristol-Myers Squibb is planning to submit abatacept for FDA approval by the end of the year. "By the time the company files [for approval], it will have followed the safety of some patients for up to 4 years," said company spokesman Brian Henry.
Reference:
- Kremer J, Westhovens R, Moreland L, et al. Efficacy and safety of the selective co-stimulation modulator abatacept with methotrexate for treating rheumatoid arthritis: 1-year clinical and radiographic results from the Phase III AIM (Abatacept in Inadequate Responders to Methotrexate) trial. Presented at: Annual Meeting of the American College of Rheumatology; October 19, 2004; San Antonio, Texas. Abstract L2.