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Benefit-harm assessment of Fingolimod: a novel methodology to inform patients with MS, industry, guideline developers and regulatory agencies on the balance of benefits and harms








Benefit-harm assessment of Fingolimod: a novel methodology to inform patients with MS, industry, guideline developers and regulatory agencies on the balance of benefits and harms


Alessandra Spanu


University of Zurich
Institute of Social and Preventive Medicine
Hirschengraben 84
CH-8001 Zurich


University of Zurich


None


02 January 2018


Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system and, with a lifetime risk of one in 400, is considered the leading cause of disability and morbidity in young adults (Compston, 2002).
There is still no cure for MS and until the 1990’s the disorder was untreatable. The introduction of the first Disease Modifying Therapy (DMT) two decades ago represented a dramatic step forward for drug treatment of MS. Since this main discovery, the number of DMTs has been increasing progressively (La Mantia, 2016), making available to MS patients new pharmaceuticals products as oral agents. These have a more acceptable route of administration and a better efficacy in comparison to the older injectable drugs (Oh J, 2013).
One of them, Fingolimod, showed significant reduction of the relapse rate in patients with Relapsing-Remitting Multiple sclerosis (RRMS) as compared with placebo and with Interferon beta-1a (Oh J 2013). Some safety concerns emerged with post-marketing surveillance (AIFA 2015, EMA 2015; Oh J 2013). According to our searches, there is one systematic review that targets specifically the efficacy and safety of Fingolimod (La Mantia L, 2016), but no quantitative benefit-harm assessment has been conducted until now to assess if the benefits of Fingolimod outweigh its harms.
At our institute, we developed a new method to assess the benefits and harms of a treatment based on individual patient data of a trial. In contrast to most other methods for benefit-harm assessment, our approach shows for each patient how his or her health status develops over time depending on whether relapses or side effects occur.
Our aim is to apply this novel method for benefit harm analysis to four trials on Fingolimod, that compared two different doses of Fingolimod to placebo and Interferon-beta 1a, respectively. In a second step, our purpose is to develop a (network) meta-analytic methods to summarize the results across trials.
We will use individual patient data from these four trials and model for each patient how his or her health status develops over time, depending on whether relapses or side effects occur. To estimate the starting point of health status and how much health status changes as a function of relapses or side effects, we will review the literature for appropriate data. For each trial, we will compare the average health status over time of the treatment groups within each trial.
Our research will inform patients with MS, industry, guideline developers and regulatory agencies on the balance of benefits and harms of Fingolimod but it may also become an attractive way for benefit-harm assessment of other drugs.



[{ "PostingID": 4084, "Title": "NOVARTIS-CFTY720D2301", "Description": "A 24-month, Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of Fingolimod 1.25 mg and 0.5 mg Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multiple Sclerosis

Medicine: fingolimod , Condition: Multiple Sclerosis, Phase: 3, Clinical Study ID: CFTY720D2301, Sponsor: Novartis" },{ "PostingID": 4085, "Title": "NOVARTIS-CFTY720D2302", "Description": "A 12-month Double-blind, Randomized, Multicenter, Active-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Interferon ß-1a (Avonex) Administered im Once Weekly in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase

Medicine: fingolimod , Condition: Multiple Sclerosis, Phase: 3, Clinical Study ID: CFTY720D2302, Sponsor: Novartis" },{ "PostingID": 4089, "Title": "NOVARTIS-CFTY720D2309", "Description": "24-month Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase

Medicine: fingolimod, Condition: Multiple Sclerosis, Phase: 3, Clinical Study ID: CFTY720D2309, Sponsor: Novartis" },{ "PostingID": 4594, "Title": "NOVARTIS-CFTY720D2306", "Description": "A Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5mg FTY720 Administered Orally Once Daily Versus Placebo in Patients With Primary Progressive Multiple Sclerosis

Medicine: fingolimod , Condition: Multiple Sclerosis, Phase: 3, Clinical Study ID: CFTY720D2306, Sponsor: Novartis" }]

Statistical Analysis Plan


The publication citation will be added after the research is published.