Peginterferon β-1a Efficacy in MS Sustained Long-term

Megan Brooks

April 22, 2016

VANCOUVER — At the US Food and Drug Administration (FDA)–approved every-2-weeks dosing schedule, peginterferon β-1a (Plegridy, Biogen Idec) maintains efficacy for up to 6 years in adults with relapsing-remitting multiple sclerosis (RRMS), new long-term data suggest.

The FDA approved peginterferon β-1a for RRMS in August 2014 on the basis of results of the phase 3 Efficacy and Safety Study of BIIB017 (PEGylated Interferon Beta-1a) in Participants With Relapsing Multiple Sclerosis (ADVANCE) trial, a multicenter, randomized, double-blind, placebo-controlled study involving 1516 patients.

As reported previously by Medscape Medical News, the ADVANCE trial showed that peginterferon β-1a, dosed subcutaneously once every 2 weeks, significantly reduced annualized relapse rate (ARR) at 1 year by 36% compared with placebo (P = .0007).

The drug also reduced the risk for 12-week confirmed disability progression, as measured by the Expanded Disability Status Scale, by 38% (P = .0383) compared with placebo.

With peginterferon β-1a, there was also a significant 86% reduction in the number of new gadolinium-enhancing lesions (P < .0001) and a 67% reduction in new or newly enlarging T2-hyperintense lesions (P < .0001) compared with placebo.

Results of the ADVANCE extension study, called ATTAIN, suggest that the drug is safe and effective for up to 6 years, Damian Fiore, from of Biogen, Cambridge, Massachusetts, reported at an Emerging Science session here at the at the American Academy of Neurology (AAN) 2016 Annual Meeting.

Efficacy Sustained in ATTAIN

With more than 1500 patients with RRMS, the ADVANCE trial was the "largest trial that has been done with an interferon," and most of those patients have been moved over to the ATTAIN study, Fiore said.

In ADVANCE, patients were randomly assigned to 125 μg of peginterferon β-1a every 2 weeks or every 4 weeks or placebo for 1 year. After the first year, patients in the placebo group were randomly reassigned to 1 of the 2 dose regimens for the remaining year of the study.

Patients who completed ADVANCE were eligible for enrollment in ATTAIN and were maintained on the peginterferon β-1a dosing regimen they were assigned to in year 2 of ADVANCE.

The ATTAIN intention-to-treat (ITT) population included 730 patients who started active treatment in year 1 of ADVANCE, including 376 receiving peginterferon β-1a every 2 weeks and 354 receiving peginterferon β-1a every 4 weeks.

Over 6 years, the adjusted ARR was significantly improved with peginterferon β-1a every 2 weeks compared with the every-4-weeks regimen (0.188 vs 0.263; rate ratio, 0.714; 95% confidence interval, 0.563 - 0.904; P = .0052). Year-over-year adjusted ARRs were generally reduced in the every-2-weeks group.

Table. Adjusted ARR (Objective Relapses) by Study Year

Time Point ARR
Year 0 - 1 0.241 (vs 0.418 with placebo)
Year 1 - 2 0.179
Year 2 - 3 0.203
Year 3 - 4 0.129
Year 4 - 5 0.055

 

"Equally, on the imaging side, we see similar results," Fiore reported. "From the perspective of the T2 lesion count there was a 67% reduction from placebo in year 1 sustained over 4 years and an 86% reduction in (gadolinium-enhancing) lesions in year 1 sustained over 4 years."

Asked for comment, Raghav Govindarajan, MD, from the University of Missouri, Columbia, told Medscape Medical News, the ATTAIN study "reinforces what was clinically known about the efficacy of 2-weekly peginterferon β-1a."

"With more than 10 FDA-approved DMTs [disease-modifying therapies], patients and MS specialists have lots of options in choosing therapy," he added. "While oral DMTs are in vogue, injectables still have their place in MS therapy. There is long-term experience and a better understanding of the side effect profile with these medications on MS patients as compared to oral medications. Further, there is ease of use with 2-weekly peginterferon β-1a, as compared to a 'daily' pill."

Dr Govindarajan said he would be "very interested to know how many patients in this study discontinued the medication, how long before they discontinued and what were the common reasons. In my experience the most common reason for discontinuing peginterferon β-1a was injection site reaction, which sometimes was painful and persisted despite changing sites."

"The future of choosing DMTs depends on discussing the efficacy/side effect profile of various DMTs and partnering with the patients in helping them make an informed decision," Dr Govindarajan concluded.

The ADVANCE and ATTAIN studies were supported by Biogen. All of the authors are employees of or have declared financial relationships with the company. Dr Govindarajan has disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 2016 Annual Meeting. Emerging Science Abstract P4.010. Presented April 19, 2016.

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