ORLANDO – Alemtuzumab is far more effective than is high-dose interferon beta-1a in treating patients with highly active relapsing-remitting multiple sclerosis despite prior therapy, according to a new subgroup analysis of the CARE-MS II trial.
Twenty-four percent of alemtuzumab-treated patients in the subgroup with highly-active disease at baseline remained entirely free of demonstrable MS disease activity – both clinically and by MRI – throughout the 2-year randomized trial. In contrast, none of the patients on subcutaneous interferon beta-1a (Rebif) achieved that high standard, Dr. Stephen Krieger reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.
"That’s an unusual result to see in any of our trials and in any subgroups: zero percent of patients achieving an efficacy goal with one of our approved and highly efficacious agents. I think this demonstrates the high disease activity of these patients, the efficacy gradient between alemtuzumab and interferon, and it also highlights the unmet need for patients with highly-active disease," said Dr. Krieger of Mount Sinai Medical Center, New York.
The CARE-MS II subanalysis also strongly suggests alemtuzumab may provide an important new treatment option for this group of severely affected patients, he added.
Alemtuzumab is a humanized monoclonal antibody to CD52, a protein present on the surface of mature lymphocytes but not on the stem cells from which they originate. Alemtuzumab is approved as Campath for treatment of B-cell chronic lymphocytic leukemia. Genzyme has applied to the Food and Drug Administration and European regulators for a new indication under the trade name Lemtrada for treatment of MS.
CARE-MS II (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis) was a 2-year, rater-blinded, multicenter, international, phase III clinical trial in which 667 patients with relapsing-remitting MS who had experienced two or more relapses despite treatment during the 2 years immediately prior to enrollment. Participants were randomized 2:1 to alemtuzumab or interferon beta-1a. Alemtuzumab at 12 mg was administered intravenously on 5 consecutive days at the start of the study and again on 3 consecutive days at the 1-year mark, for a total of just 8 doses in 2 years. In contrast, subcutaneous interferon beta-1a at 44 mcg was given three times weekly throughout the study.
The overall results, now published (Lancet 2012;380:1829-39), showed the alemtuzumab group had reductions of 49% in the risk of relapse and 42% in the risk of sustained accumulation of disability, compared with the interferon group.
Dr. Krieger presented a new analysis restricted to the 145 CARE-MS II participants with the most highly active disease as defined by two or more relapses in the year prior to randomization as well as the presence of at least one gadolinium-enhancing lesion on baseline MRI.
"Basically, we’re taking the most active patients from the trial of the more active patients who had already experienced disease activity despite prior therapy," the neurologist explained.
The annualized relapse rate in these patients with highly active disease was 0.33 events with alemtuzumab and .65 events with interferon, for a 51% reduction in favor of the investigational agent. Sixty-four percent of the alemtuzumab group and 36% on interferon remained relapse free during the 2-year study.
Freedom from clinical disease activity was defined as being relapse free as well as free of sustained accumulation of disability, meaning an absence of at least a 1-point increase over baseline on the Expanded Disability Status Scale lasting for at least 6 months. Clinical disease activity–free status for the full 2 years of follow-up was attained by 61% of the alemtuzumab group, compared with 33% of patients on interferon. The adjusted odds ratio was 3.18, meaning patients with highly active disease were more than three times more likely to remain free of clinical disease activity throughout the study if they were on alemtuzumab rather than interferon.
Turning to the serial MRI results, Dr. Krieger noted that 40% of the alemtuzumab group remained free of disease activity by MRI, meaning no new gadolinium-enhancing lesions and no new or enlarging T2 lesions. Only 7.5% of patients with highly active disease assigned to interferon therapy remained free of MRI evidence of disease activity during the 2-year study. Patients on alemtuzumab were an adjusted ninefold more likely to be free of MRI activity than were those on interferon.
The post hoc composite endpoint of freedom from demonstrable MS disease activity required 2 years of freedom from relapse, freedom from MRI activity, and freedom from sustained accumulation of disability. This was the outcome achieved by 24% of patients on alemtuzumab and 0% of those on interferon.