SAN DIEGO – A majority of patients with active relapsing-remitting multiple sclerosis and inadequate response to previous therapy achieved a durable response after treatment with alemtuzumab in the TOPAZ trial, a 5-year extension to the CARE-MS II study.
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Almost half of the 317 participants in TOPAZ received no further therapy beyond their initial two courses of alemtuzumab infusion therapy that they received as part of the CARE-MS II study.
“If you follow patients over time ... you’re seeing a significant group of patients who have improvement. It’s very unexpected, especially when you look at the patients who entered the clinical trial who had a fair amount of active disease,” said Barry A. Singer, MD, director of The MS Center for Innovations in Care at Missouri Baptist Medical Center in St. Louis.
At the 7-year evaluation of patients in TOPAZ, the annualized relapse rate was 0.14. In addition, 87% of patients remained relapse-free in year 7. Dr. Singer and his colleagues also reported that 73% of TOPAZ participants were stable or improved based on their Expanded Disability Status Scale (EDSS) scores.
“As we follow the data out and follow these patients out, we’re seeing how the clinical course for these patients is dramatically improving for the majority of patients,” Dr. Singer said in a video interview at ACTRIMS Forum 2018, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
The TOPAZ study also revealed that 69% of patients were free of clinical disease worsening and 44% experienced clinical disease improvement in the 6 months before year 7. The majority also had no evidence of disease activity, Dr. Singer reported.
“One of the attributes that makes alemtuzumab so attractive as a clinician and for patients is you can go through a couple of series of medication [treatments] ... and really alter your disease course – that is the exciting thing,” he said.
The Food and Drug Administration approved alemtuzumab (Lemtrada) in November 2014 for the treatment of patients with relapsing forms of multiple sclerosis. Use of alemtuzumab is generally reserved for patients who have had an inadequate response to two or more previous drugs indicated for the treatment of multiple sclerosis.
In CARE-MS II, participants received two annual courses of alemtuzumab: intravenous infusion of 12 mg/day for 5 days at baseline and again for 3 days at 12 months. Additional treatment in TOPAZ for relapse or MRI evidence of disease was at the discretion of the investigator and could include alemtuzumab retreatment 12 mg/day on 3 consecutive days 12 months or more after a previous course, or another disease-modifying therapy at any time. Annual follow-up exams included an MRI scan.
A durable treatment effect was achieved by a majority of patients, even though 47% received no further treatment with alemtuzumab or another disease-modifying therapy after the initial two alemtuzumab courses.
The incidence of most adverse events, including infusion-associated reactions and infections, decreased over the course of the TOPAZ study and were lower than the incidence reported in the 2-year CARE-MS II trial. Of note, the incidence of thyroid-related adverse events peaked in the third year of the follow-up and continued to decline out to 7 years, Dr. Singer said. “We’re not seeing any new safety issues.”
Dr. Singer and his coinvestigators plan to continue the research, monitoring and scoring patients over time.
The TOPAZ trial was funded by Sanofi Genzyme, which markets alemtuzumab. Dr. Singer disclosed that he receives clinical research support and is a speaker for Sanofi Genzyme.
SOURCE: Singer B et al. ACTRIMS Forum 2018, abstract P026.