Disclosures

March 22, 2013

San Diego, California — One-year results from the phase 3 ADVANCE study suggests that peginterferon-β1a (Plegridy, Biogen Idec) has the potential to offer the efficacy and safety of currently available interferon agents for the treatment of relapsing multiple sclerosis (MS), with the added benefit of reduced frequency of administration, researchers say.

Presenting the data here at the American Academy of Neurology (AAN) 65th Annual Meeting, lead investigator Peter Calabresi, MD, from Johns Hopkins Multiple Sclerosis Center, Baltimore, Maryland noted that both the once-every-2-weeks and once-every-4-weeks injections of peginterferon-β-1a reduced the annualized relapse rate and the number of new or newly enlarging T2 lesions compared with placebo.

The results with the 2-weekly regimen looked better than those with the 4-weekly regimen, with the 2-weekly dose also reducing the number of gadolinium-enhancing lesions.

"Administration every 2 weeks consistently provided statistically significant differences versus placebo for all clinical and radiological outcome measures," Dr. Calabresi said. "Rates of activity neutralizing antibody formation were low for both dosing regimens, and safety was similar across both dosing regimens and reflects that of established interferon-β1a therapies for relapsing MS," he added.

Topline results of the trial were released January 24, 2013, and reported by Medscape Medical News at that time.

Results Well Received

Co-chair of the AAN session at which the results were presented, Tony Reder, MD, from the University of Chicago, commented to Medscape Medical News that, "The once-every-2-weeks injection looks good. I personally found the data on that regimen very compelling. A 35% reduction in annualized relapse rate is a bit better than the existing drugs. But they were studied in sicker patients so probably wouldn't reduce relapse rate so much. A longer-acting formulation should help compliance."

Edward Fox, MD, director of Multiple Sclerosis Clinic of Central Texas, Round Rock, agreed. "I was very impressed by it," he told Medscape Medical News. "The dropout rate was low; the vast majority of people who entered the trial finished the trial, which is always a good sign. The safety and efficacy data is what we would expect. If I had it available, I would give it every 2 weeks rather than every 4 weeks as the 2-weekly regimen looked a bit better."

Dr. Fox added that he thought an injection once every 2 weeks would be attractive to patients compared with the currently available-β-interferons, which have to be dosed by injection every other day.

"It will be an appealing option for patients who are on injectable drugs, who don't want to take on the burdens of safety concerns with some of the newer drugs. I think most patients on the current short acting-β-interferons will switch. I can't think of a reason why they wouldn't. But I can't see a patient doing well on one of the oral drugs switching to an injection, even if it is just once every 2 weeks," he added.

He pointed out that an injection once every 2 weeks would mean that patients who don't like self-injecting could have their medication administered by a healthcare professional. "They could go to the doctor's office to get their shots if they wanted, and they would never have to do it themselves."

ADVANCE Data

The ADVANCE trial randomly assigned 1516 patients with relapsing-remitting MS to 1 of 2 dose regimens of peginterferon-β-1a, 125 μg, administered by subcutaneous injection every 2 weeks or every 4 weeks, or to placebo. The analysis for all primary and secondary efficacy endpoints occurs at 1 year. After the first year, patients on placebo are re-randomly assigned to 1 of the peginterferon groups for the duration of the second year of the study.

One-year results showed that both regimens of peginterferon significantly reduced the annualized relapse rate, with the 2-weekly schedule showing the best outcome.

Table 1. Annualized Relapse Rate at 1 Year

Endpoint Placebo (n = 500) Peginterferon Every 4 Weeks (n = 500) Peginterferon Every 2 Weeks (n = 512)
Annualized relapse rate 0.397 0.288 0.256
Reduction versus placebo (%) - 27.5 5.6
P value - .0114 .0007

 

Both regimens also reduced the number of new or newly enlarging T2 lesions, with the 2-weekly regimen again looking better than the 4-weekly schedule.

Table 2. Number of New/Newly Enlarging T2 Lesions at 1 Year

Endpoint Placebo (n = 476) Peginterferon Every 4 Weeks (n = 462) Peginterferon Every 2 Weeks (n = 457)
New lesions 10.9 7.3 3.6
Reduction versus placebo (%) - 28 67
P value - .0008 <.0001

 

Adverse events looked similar across the 3 treatment groups.

Table 3. Adverse Events at 1 Year

Endpoint Placebo (n = 500), n (%) Peginterferon Every 4 Weeks (n = 500), n (%) Peginterferon Every 2 Weeks (n = 512), (%)
Any adverse event 417 (83) 472 (94) 481 (94)
Severe adverse event 53 (11) 82 (16) 90 (18)
Serious adverse event 76 (15) 71 (14) 55 (11)
Infections 196 (39) 183 (37) 171 (33)
Serious infections 7 (1) 5 (1) 3 (<1)
Discontinuation due to adverse event 7 (1) 24 (5) 25 (5)

 

American Academy of Neurology (AAN) 65th Annual Meeting. Abstract S31.006. Presented March 20, 2013.

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