Glatiramer acetate and Interferons the 15-year follow-ups

Ford C, Goodman AD, Johnson K, Kachuck N, Lindsey JW, Lisak R, Luzzio C, Myers L, Panitch H, Preiningerova J, Pruitt A, Rose J, Rus H, Wolinsky J. Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate. Mult Scler. 2010;16:342-50.

The US Glatiramer Acetate (GA) Trial is the longest evaluation of continuous immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to evaluate up to 15 years of GA as a sole disease-modifying therapy. Two hundred and thirty-two patients received at least one GA dose since study initiation in 1991 (mITT cohort), and 100 (43%, Ongoing cohort) continued as of February 2008.  
Patients were evaluated every 6 months using the Expanded Disability Status Scale (EDSS). Mean GA exposures were 8.6 +/- 5.2, 4.81 +/- 3.69, and 13.6 +/- 1.3 years and mean disease durations were 17, 13, and 22 years for mITT, Withdrawn and Ongoing cohorts, respectively. For Ongoing patients, annual relapse rates (ARRs) maintained a decline from 1.12 +/- 0.82 at baseline to 0.25 +/- 0.34 per year; 57% had stable/improved EDSS scores (change < or = 0.5 points); 65% had not transitioned to secondary progressive multiple sclerosis (SPMS); 38%, 18%, and 3% reached EDSS 4, 6, and 8. For all patients on GA therapy (the mITT cohort), ARRs declined from 1.18 +/- 0.82 to 0.43 +/- 0.58 per year; 54% had stable/improved EDSS scores; 75% had not transitioned to SPMS; 39%, 23%, and 5% reached EDSS 4, 6, and 8. In conclusion, multiple sclerosis patients with mean disease duration of 22 years administering GA for up to 15 years had reduced relapse rates, and decreased disability progression and transition to SPMS. There were no long-term safety issues.

I am stood accused of being blinkered when it comes to Glaterimer acetate and I have ignored the 15 year data. So let's take a look.

This study looked at the long term effect of glaterimer acetate over a number of years and in that time,  57% have dropped off drug. One suspects the reasons will be for reasons of poor tolerability or insufficient efficacy as the time on drug of those people was about 5 years compared to 14 years who had continued to take glaterimer acetate. In this group of  they were relapsing once every 4 years on average and only 35% had become secondary progressive. 

If we looked at the beta interferon (rebif), 15 year data
Kappos L, Kuhle J, Multanen J, Kremenchutzky M, Verdun di Cantogno E, Cornelisse P, Lehr L, Casset-Semanaz F, Issard D, Uitdehaag BM. Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15. J Neurol Neurosurg Psychiatry. 2015; 86:1202-7.

About 56% of those followed up had dropped off beta interferon and only 12% had been continuously on the same drug and dose.
The relapse rate dropped to about one every 3 years on average and between 21%-52% converting to secondary progression. So not that dissimilar from the copaxone data. Therefore being on DMT is a good thing as about 80% of MSers may have converted if they took nothing.

However, what will happen in the era of "highly efffective" DMT these can reduce the relapse rate to one every 5 to ten years. One would expect these figures to better. In the 10 year follow up of Alemtuzumab the conversion rate was about 4%, but to get the best comparision we would need to see the natalizumab data as this has been around the longest. However people are switching not because of lack of eficacy, but because of the risk of PML.

So moral of the story get on a DMT as early as possible and make sure you are NEDA, whatever treatment you decide to take.

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