麻豆传媒

NATIONAL HARBOR, Md. -- Ocrelizumab (Ocrevus) was effective in patients with primary progressive multiple sclerosis (MS), irrespective of the presence of gadolinium-enhancing lesions, researchers reported here.

"This group of patients is a group for which there is a very high unmet need," lead author , of the University of Texas Health Science Center in Houston, said at the Consortium of Multiple Sclerosis Centers annual meeting. "Ocrelizumab met primary and key secondary clinical and MRI endpoints [and] the proportion experiencing adverse events and serious adverse events was similar to placebo."

About 10% of MS patients have the primary progressive form of the disease, and unlike other forms of MS, the primary progressive form affects men and women about equally, Wolinsky noted, adding that there are currently no approved treatments for it.

In the phase III ORATORIO trial, the researchers randomized 732 patients to receive either two 300-mg intravenous infusions of ocrelizumab 14 days apart, or to placebo. The treatment was administered at 24-week intervals for at least 120 weeks, until a prespecified number of 12-week confirmed disability progression (CDP) events occurred.

Study participants were ages 18-55 and had a diagnosis of primary progressive MS with an Expanded Disability Status Scale (EDSS) score of 3.0-6.5. The average age in both the treatment and placebo groups was about 44, and roughly half in each group were female. The mean EDSS score in both groups was 4.7, and the average time since MS symptom onset was 6.7 years in the treatment group and 6.1 years in the placebo group.

The study's primary endpoint was the time to onset of 12-week CDP. Secondary endpoints included time to onset of 24-week CPS and a change in total T2 lesion volume from baseline to 120 weeks. The researchers also analyzed outcomes in patients with and without T1 gadolinium-enhancing lesions at baseline.

Overall, ocrelizumab reduced the risk of CDP by 24% compared with placebo (hazard ratio 0.76, P=0.0321), the investigators found. It also reduced the risk of 24-week CDP by 25% (HR 0.75, P=0.0365) and reduced T2 lesion volume (-3.4% with ocrelizumab versus +7.4% with placebo, P<0.0001).

Patients with T1 gadolinium-enhancing lesions at baseline comprised 27.5% of intervention patients and 24.7% of those on placebo. The researchers found that in patients with and without gadolinium-enhancing lesions, ocrelizumab reduced the risk of 12-week CDP by 35% and 16%, respectively, and cut the risk of 24-week CDP by 33% and 19%, respectively. Total T2 lesion volume also was reduced in both groups.

In terms of adverse events, infections and infestations were reported by 69.8% of the intervention group and 67.8% of the placebo group. The most common infection was nasopharyngitis (reported by 22.6% of the ocrelizumab group and 27.2% of the placebo group), followed by urinary tract infections (19.8% versus 22.6%), influenza, upper respiratory tract infections, and bronchitis. Other adverse events included injury/poisoning/procedural complications (54.1% versus 43.5%), musculoskeletal and connective tissue disorders (37.2% versus 41.0%), and nervous system disorders (35.8% versus 33.1%).

A higher proportion of patients in the ocrelizumab group reported infusion-related reactions, which is to be expected with a treatment involving an IV monoclonal antibody, Wolinsky noted, adding that most of those reactions were mild to moderate.

, of Central Texas Neurology Consultants in Round Rock, who has been an investigator for ocrelizumab but was not involved in this particular trial, said the fact that the drug worked on patients with and without gadolinium-enhancing lesions was good news.

"We presumed that the patients who had gadolinium-enhancing lesions -- which would [mean] more active inflammation -- might be the ones that would drive results entirely for [this] trial," he said. "If they had found it only worked for patients with gadolinium-enhancing lesions, then even when the drug became available to us, we might feel we have to chose [those] lesions in order for us to want to give this medication to somebody with primary progressive MS. But that's not what they found."

This is especially good because "gadolinium-enhancing lesions come and go," Fox continued. "You may be lucky and get an MRI that shows a gadolinium-enhancing lesions, or there may have been one a month ago and you just got the MRI at a time when they didn't have [that] lesion. So I can't say I'm surprised by this data, but I'm relieved ... I'd rather it have a background where I don't feel like I have to subselect the patients."

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