Author Topic: Gilenya may be best in MS patients failing initial treatment  (Read 161 times)

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Offline agate

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Gilenya may be best in MS patients failing initial treatment
« on: February 14, 2015, 02:42:13 pm »
From MedPage Today, February 10, 2015:

Oral Drug May Be Best in MS Patients Failing Initial Tx

by Kristina Fiore
Staff Writer, MedPage Today

Switching multiple sclerosis patients with disease activity despite treatment with a first-line injectable to oral fingolimod (Gilenya) was associated with fewer relapses than switching them to another standard injectable, researchers found.

In a retrospective study of prospectively collected observational data, patients on either interferons or glatiramer acetate (Copaxone) who were switched to fingolimod had a significantly lower mean annualized relapse rate than those who changed to another injectable immunomodulator (0.31 versus 0.42; absolute difference 0.11, 95% CI 0.02-0.19, P=0.009), according to Tomas Kalincik, MD, PhD, of Royal Melbourne Hospital in Australia, and colleagues.

Patients in the study, reported online in JAMA Neurology, were switching medications following clinical relapse or disability progression while on the initial treatment.

In an accompanying editorial, Olaf Stuve, MD, PhD, of the University of Texas, and Diego Centonze, MD, PhD, of To Vergata University and Hospital in Rome, said the study adds to growing evidence that switching to newer agents like natalizumab (Tysabri) or fingolimod may be more effective.
Although it was an observational study, it assessed high-quality data and used appropriate propensity score matching to control for potential confounding factors, they wrote.

They noted, however, that the study's median follow-up of 13.1 months may be "too short to draw definite conclusions on the relapse rate."

Kalincik and colleagues conducted their matched retrospective analysis of data that was collected prospectively from MSBase, which collects data on MS patients in routine clinical care, from July 1996 to April 2014.

Patients with relapsing-remitting MS had been on a beta-interferon drug or glatiramer acetate for at least 6 months before making the change to another injectable (beta-interferon or glatiramer acetate) or to fingolimod because of clinical disease activity. They were then observed on the new medication for at least 3 months. Some of the patients initially taking a beta-interferon drug were switched to a different beta-interferon.
Overall, 379 patients in the injectable group were matched to 148 patients in the fingolimod group. Median follow-up was 13.1 months.

Kalincik and colleagues found that those switched to fingolimod not only had a lower mean annualized relapse rate but also a lower risk of first on-treatment relapse (hazard ratio 0.74, 95% CI 0.56-0.98, P=0.04) than those switched to another injectable immunomodulator.

Those changed to the oral drug also a lower risk of disability progression (HR 0.53, 95% CI 0.31-0.91, P=0.02) and a higher rate of disability regression (HR 2.0, 95% CI 1.2-3.3, P=0.005), they reported.
They also had a lower rate of treatment discontinuation at 2 years (17.5% versus 26.8%, HR 0.55, P=0.04).

The researchers noted that sensitivity analyses replicated in full the relapse and disability outcomes seen in the primary analysis. They did not, however, replicate the finding that switching to fingolimod improved treatment persistence, suggesting that this finding be interpreted with caution.

Kalincik and colleagues concluded that in the absence of randomized clinical trials, use of high-quality observational data like those from MSBase provides an important tool for comparisons of drug effectiveness in a real-world setting.

In their editorial, Stuve and Centonze agreed that the quality of observational data in their study can provide "crucial information to support decision making relevant for MS management in real-world practice."

They said the results provide the first evidence that "switching to fingolimod is superior to switching to a second injectable immunomodulator with respect to disability outcomes, likely owing to the more efficient prevention of relapses associated with an incomplete recovery."

The results are in line with studies such as TRANSFORMS, one of the clinical trials leading up to fingolimod's approval, which found patients with active disease activity despite immunomodulatory therapy "may still have optimal disease control after switching to fingolimod."

In addition to the limitation of a short follow-up time, the study was also limited by lack of data on interferon-neutralizing antibodies, and because patients who were switched from one interferon preparation to another may not have served as true controls: "Most MS experts would not likely recommend this strategy because the agents are biochemically almost identical, and their mechanisms of action identical," they noted. The study, which was funded by fingolimod's manufacturer, also did not examine switches to natalizumab or newer oral agents.

Still, they concluded that evidence has accumulated that "escalating to the more effective medications natalizumab or fingolimod should be an early consideration for most patients with breakthrough disease. Switching to another injectable immunomodulator may still be considered in certain cases only."

The study was supported by Novartis, MSBase Foundation, Multiple Sclerosis Research Australia, National Health and Medical Research Council, and the Center for Research Excellence.

MSBase Foundation receives support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, and Sanofi.

The researchers disclosed financial relationships with Biogen Idec, Novartis, Genzyme, Merck Serono, Teva, Bayer Schering, Sanofi, Lundbeck, Bayer, Biologix, GSK, Roche, and bioCSL.

The editorialists disclosed financial relationships with Teva, Opexa, Merck Serono, Genzyme, Bayer Schering, Biogen Idec, Novartis, Almirall, GW Pharmaceuticals, Roche, and Mitsubishi.

Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
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SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.