Friday, 3 July 2015

ClinicSpeak: efficacy of fingolimod

Fingolimod works in highly-active MS. #ClinicSpeak #MSResearch #MSBlog

"Post-hoc subgroup analyses are all the vogue and allow one to decide whether or not a particular population of MSers is more or less responsive to a therapy. A particularly important  group are MSers with so called highly-active MS based on disease activity in the last 12 months and baseline features on MRI."

DEFINITION OF HIGHLY ACTIVE MS:  1) ≥ 1 relapse in the previous year and either ≥ 1 gadolinium (Gd)-enhancing T1 lesion or ≥ 9 T2 lesions at baseline  and/or 2) as many or more relapses in the year before baseline as in the previous year.

"The following analysis shows that fingolimod is effective in this highly-active subgroup, but no more than in the overall population. Does this change the way we categorise fingolimod's effectiveness? No, I would still put it below alemtuzumab and natalizumab and above DMF (dimethyl fumarate) in the pecking order of efficacy; i.e. a highly effective DMT, but not a very high efficacy DMT. The average efficacy does not necessarily predict the individual response rate, this is why we have to monitor MSers on treatment to see if they are responders or non-responders and if the latter switch them to another class of drug. We are now firmly ensconced in the era of treat-2-target of NEDA."



BACKGROUND: There is a need to identify effective switch therapies for patients with relapsing-remitting multiple sclerosis (RRMS) who experience high disease activity despite receiving disease-modifying therapy (DMT). 


OBJECTIVE: The objective of this study was to assess the efficacy of fingolimod versus placebo in patients with RRMS who had experienced high disease activity despite previously receiving DMT, using post hoc analyses of two phase 3 trials: FREEDOMS (NCT00289978) and FREEDOMS II (NCT00355134).

RESEARCH DESIGN AND METHODS: Clinical and magnetic resonance imaging outcomes over 24 months were analysed in patients from FREEDOMS and FREEDOMS II who had received treatment in the previous year and had: 1) ≥ 1 relapse in the previous year and either ≥ 1 gadolinium (Gd)-enhancing T1 lesion or ≥ 9 T2 lesions at baseline and/or 2) as many or more relapses in the year before baseline as in the previous year (as per fingolimod's EU label).

MAIN OUTCOME MEASURES: The inclusion criteria were fulfilled by 249 and 257 patients in the fingolimod and placebo groups, respectively. Annualized relapse rates were reduced by 48% for fingolimod versus placebo (p < 0.001). Fingolimod reduced the risk of 3-month and 6-month confirmed disability progression by 34% (p = 0.031) and 45% (p = .016), respectively, versus placebo. Brain volume loss was reduced by 46% for fingolimod versus placebo (p < 0.001). The reduction in Gd-enhancing T1 lesion counts for fingolimod versus placebo was 65% (p < 0.001). Furthermore, fingolimod reduced the number of new or newly enlarged T2 lesions by 69% relative to placebo (p < 0.001).

LIMITATION: The analyses are post hoc, but the population is specified by the European Medicines Agency in the label for fingolimod.

CONCLUSIONS: Fingolimod demonstrated efficacy across all four key RRMS disease measures analysed in patients with high disease activity despite previous DMT.

CoI: multiple

2 comments:

  1. "DEFINITION OF HIGHLY ACTIVE MS: 1) ≥ 1 relapse in the previous year and either ≥ 1 gadolinium (Gd)-enhancing T1 lesion or ≥ 9 T2 lesions at baseline and/or 2) as many or more relapses in the year before baseline as in the previous year."

    I'm confused about this. My neurologist and the MS society say Highly Active MS is two or more relapses in the last 12 months etc. Secondly, is highly active the same as rapidly evolving? In some information it is written as interchangable, others it has different definition.

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    Replies
    1. Re: "I'm confused ..."

      Two disabling attacks in the last 12 months with MRI evidence of disease activity (increase n T2 lesion load and/or Gd-enhancing lesions) refers to rapidly evolving severe MS. The latter is part of the EMA label for natalizumab. In comparison the highly-active label is for fingolimod.

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