Abbott Laboratories Presents New HUMIRA(TM) (adalimumab) Data Showing Effectiveness in Adult Rheumatoid Arthritis Patients With Early And Established Disease and Sustained Response Up to Four Years
ABBOTT PARK, Ill., June 19 /PRNewswire-FirstCall/ -- Abbott Laboratories (NYSE: ABT - News) is presenting new data this week from pivotal Phase III and ongoing clinical trials of HUMIRA(TM) (adalimumab) at the European League Against Rheumatism (EULAR) annual scientific meeting. Data from these trials in adult rheumatoid arthritis (RA) patients indicate:
-- HUMIRA is effective in patients with both early stage (less than two
years) and established disease (greater than two years), showing a
trend toward higher efficacy in patients with early stage disease;
-- among early disease patients taking HUMIRA in one study, 41 percent
achieved the American College of Rheumatology (ACR) 70 response;
-- there were statistically significant reductions versus placebo in
progression of both joint space narrowing and erosions after 52 weeks
of therapy;
-- a statistically significant reduction in fatigue associated with RA
compared to patients receiving placebo at week 24 and at week 52;
-- sixty-three percent of the 38 patients at four years achieved an ACR 20
response, 50 percent of patients achieved an ACR 50 response, and
nearly one in four patients (24 percent) achieved an ACR 70 response.
All results were from patients taking the recommended dose of HUMIRA 40 mg every other week.
Early Onset versus Established RA
The purpose of a new analysis of a pivotal Phase III trial was to evaluate the effectiveness of HUMIRA in reducing signs and symptoms and inhibiting radiographic progression in patients with moderately to severely active early- stage RA after disease modifying anti-rheumatic drug (DMARD) failure, compared to those with established disease.
The data showed a trend toward greater improvement at six months in signs and symptoms for patients taking HUMIRA with early disease compared to patients with established disease. This trend was seen consistently at all three response levels of the ACR scoring system (ACR 20: 70 percent vs. 62 percent; ACR 50: 59 percent vs. 36 percent; ACR 70: 41 percent vs. 18 percent) [see Table A]. ACR scores represent a percent improvement in tender and swollen joint count and other relevant clinical measures (20 percent, 50 percent, and 70 percent, respectively).
Results also were measured using the modified Sharp X-ray score, which assesses changes in bone on X-rays. After one year, these data showed that in the early RA group, patients taking HUMIRA 40 mg every other week plus methotrexate experienced a significant change in total Sharp score of 0.4 versus 4.7 for patients taking placebo plus methotrexate. Patients with established RA taking HUMIRA 40 mg every other week plus methotrexate experienced a significant change in total Sharp score of 0.1 versus 2.6 for patients taking placebo plus methotrexate [see Table A].
TABLE A
Early RA (less than or Established RA
equal to 2 years) ( > 2 years)
Adalimumab Placebo Adalimumab Placebo
40 mg eow plus plus MTX 40 mg eow plus plus MTX
MTX (n=27) (n=19) MTX (n=180) (n=181)
ACR 20(a) 70% 37% 62% 29%
ACR 50(a) 59% 5% 36% 10%
ACR 70(a) 41% 5% 18% 2%
Improvement in HAQ(a) 0.79 0.43 0.57 0.30
Change in Total Sharp
score(b) 0.4 4.7 0.1 2.6
Erosion 0.2 2.6 0.0 1.6
Joint space narrowing 0.2 2.2 0.1 1.0
a = Change from baseline at 6 months
b = Change from baseline at 1 year
"New analysis of the data shows that HUMIRA can help patients with established disease and also benefit RA patients who have had RA less than two years," said Michael Schiff, M.D., Director of Clinical Research, Denver Arthritis Clinic and Clinical Professor of Medicine at the University of Colorado, Denver, Colorado, United States.
Clinical Results Show Durability Up to Four Years
An open-label extension study was designed to evaluate sustained efficacy and safety of HUMIRA in patients with active RA over a four-year period. Seventy-two percent of the 53 patients who entered this open-label study remained on HUMIRA over the course of this time. Sixty-three percent of patients receiving HUMIRA 40 mg every other week at four years achieved an ACR 20 response, 50 percent achieved an ACR 50 response and nearly one in four (24 percent) achieved an ACR 70 response.
All efficacy measures were maintained, and ACR 50 responses continued to show improvement for three years and were sustained through four years. The rate of adverse events was stable during the long-term follow-up period. Data indicates treatment with HUMIRA over four years provided a sustained benefit and was well-tolerated for patients when combined with methotrexate.
"Because RA is a progressive, life-long disease, patients need an option with sustained effectiveness in treating signs and symptoms and slowing disease progression," said Ferdinand Breedveld, M.D., Professor, Department of Rheumatology, University of Leiden, Leiden, Netherlands, and lead investigator on the study.
Phase III Radiographic Outcomes
This pivotal Phase III trial was designed to evaluate radiographic outcomes, efficacy and safety over a 52-week period in patients with active RA who had inadequate response to methotrexate. The data are from 619 patients randomized to receive HUMIRA 40 mg every other week, 20 mg weekly or placebo. All patients received stable doses of methotrexate. Patients enrolled in the study had an average disease duration of 11 years.
Results were measured using the modified Sharp X-ray score. The mean change for patients receiving HUMIRA 40 mg every other week plus methotrexate was 0.1 compared to 2.7 for patients receiving placebo plus methotrexate.
In addition to comparisons in the Sharp scores, 62 percent of patients receiving HUMIRA 40 mg every other week experienced no new bone erosions compared to 46 percent of those patients receiving placebo. There also were statistically significant differences in mean bone erosion scores and joint space narrowing scores for the patients receiving HUMIRA 40 mg every other week versus those receiving placebo.
The ability of HUMIRA to reduce the signs and symptoms of RA was also studied using the ACR 20, 50 and 70 criteria. Response rates in the trial show differences at 52 weeks between patients receiving HUMIRA 40 mg every other week and placebo (ACR 20: 58.9 percent vs. 24.0 percent; ACR 50: 41.5 percent vs. 9.5 percent; ACR 70: 23.2 percent vs. 4.5 percent).
Measurement of Fatigue
In addition to effectiveness and safety data for HUMIRA, patient fatigue associated with RA was examined by compiling data from two clinical trials involving a total of 890 patients. Fatigue is a major symptom of RA, yet rarely measured separately in clinical trials. Patient fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, a widely used measure of fatigue in chronic illnesses that was recently validated for RA. FACIT-F scores range from 0 to 52, with higher scores representing less fatigue. Score changes of four points or more are considered clinically meaningful.
In one trial, after 24 weeks patients taking HUMIRA 40 mg every other week gained an average of 8.1 points versus a 2.5 point gain for patients on placebo (p < 0.01). In another trial, HUMIRA patients dosed at 40 mg every other week gained an average of 7.1 points after 52 weeks, while patients on placebo gained 3.3 points on average over the same period (p < 0.001).... |
