Probability is the likelihood that an event will or will not occur.


MS - is a serious disease
, where the probability of disease progression is significant. As disease-modifying treatments of MS reduces the probability of progression, they also come with probability of treatment related adverse events. So, as always, when you decide about a treatment regime you must make a fair and rational assessment where you balance the benefits against the probabilities or risks of adverse events of the treatment.

 

Tysabri™ (natalizumab)

Tysabri, natalizumab, is a treatment for adult patients with highly active relapsing remitting MS. It is given every four weeks and has been approved for over a decade.(1)

 

Tysabri treatment comes with benefits shown in both clinical trials and clinical practice to reduce the number of relapses and inflammation in the brain. However, as any other therapy, it also comes with the probability of developing adverse events. One rare but serious adverse event is PML. The probability of PML looks different for different patients and estimated probability can be estimated by using the algorithm that has been developed from a large number of available patient data.(2)

 

Factors that impact the probability of PML are (2)

-       presence of anti-JCV-antibodies, and their concentration in the blood, JCV-index

-       treatment duration

-       and prior use of immunosuppressants before starting Tysabri for JCV positive patients.







45 % of MS-patients are JCV negative and 55 % are JCV positive.(2)

It is important to know the patient’s JCV index value to be able to stratify for the probability of PML. It’s also important to note that each treatment start is independent of each other.(1)

 

The estimated probability of PML in the first 2 years of Tysabri treatment is low, however, patients who were treated with immunosuppressants in the past have somewhat higher probability of PML.(2) For JCV negative patients, the PML estimates are based on post-marketing data from 125,000 Tysabri exposed patients.(2)

 

JCV negative patients

The estimated probability for PML for JCV negative patients is 1 in 10,000.(2) Or that the probability of not getting PML is 9999 in 10,000 patients.

 

This does not mean that there is no risk, the JCV value may change over time due to a new JCV infection or fluctuating antibody status or a false negative test result. This is a reason for re-testing all patients on a regular basis when treated with Tysabri. Also be advised to make tests until 6 months after completed treatment.(2)

 

 

JCV positive patients

Estimates for JCV positive patients are based on pooled cohort of 21,696 patients from four clinical trials.(2) The probability of PML for JCV positive patient depends on the JCV index. 

 

Patients with an index level below or equal to 0,9 has low estimated probability of PML. It varies from 1 to 6 in 10,000 patients during a treatment period from 1 to 6 years.(2) It also shows that the probability of not getting PML is between 9994 and 9999 in 10,000 patients. 

 

 

How, does it look for patients with an index above 1.5?

As for all patients, in the first 2 years of treatment the estimated probability is low.(2) It increases over time and after 5 to 6 years of treatment the probability is 100 in 10,000 patients.(2) Or that the probability is that 9900 out of 10,000 patients will not get PML.

 

 

Probability is the likelihood that an event will or will not occur.

So, when assessing Tysabri treatment, look at both the probability for PML and the probability of not getting PML to be able to create a fair objective picture of the situation.

 

When treating patients with Tysabri.

-       Test all patients for JCV on a regular basis

-       and use the stratification algorithm to monitor the estimated probability of PML(2)

 

 

Text: Biogen
Bild: Biogen

Biogen-35702 augusti 2023
Senast uppdaterad: 2023-09-12

 

 

Referenser:

1. Tysabri™ (natalizumab) Summary of product characteristics, visit fass.se

2. Physician* Information and Management Guidelines for Multiple Sclerosis patients on TYSABRI therapy (Version 19) (*Tysabri therapy is to be initiated and supervised by specialized physicians experienced in the diagnosis and treatment of neurological conditions in centres with timely access to MRI)

 


Tysabri™ (natalizumab) Rx ATC kod: L04AA23
Koncentrat till infusionsvätska 300 mg EF, ej förmån. Förfylld spruta 150 mg F, inom förmån.
Baserad på SPC Tysabri IV SPC 12/2023 & SPC Tysabri SC 05/2022

Indikation: I monoterapi hos vuxna med mycket aktiv skovvis förlöpande multipel skleros (MS), för följande patientgrupper: Patienter med mycket aktiv sjukdom trots fullständig och adekvat behandling med minst en sjukdomsmodifierande behandling; eller patienter med snabb utveckling av svår RRMS, definierat som två eller flera funktionsnedsättande skov under ett år och en eller flera Gd+ lesioner vid MRT eller en avsevärd ökning av T2-lesioner jämfört med nyligen utförd MRT. Kontraindikation: PML. Patienter med förhöjd risk för opportunistiska infektioner, inklusive patienter med nedsatt immunförsvar. Kombination med andra sjukdomsmodifierande behandlingar. Aktiva maligniteter undantaget basalcellscancer i huden. Varning och försiktighet: Behandling med TYSABRI har förknippats med en förhöjd risk för PML (progressiv multifokal leukoencefalopati) som orsakas av JC-virus. Riskfaktorer för PML är behandlingens varaktighet, användning av immunosuppressiva läkemedel före behandling med TYSABRI och förekomst av anti-JCV antikroppar. Patienten bör upplysas om tidiga tecken och symtom på PML. Graviditet: Vid graviditet bör utsättning av TYSABRI övervägas. Risk-nyttabedömning av behandling med TYSABRI under graviditet ska göras utifrån patientens kliniska status och risken för återkommande sjukdomsaktivitet vid utsättning av läkemedlet. Amning: Amning ska avbrytas under behandling. 
Förfylld spruta ska administreras av sjukvårdspersonal.

För ytterligare information om dosering, kontraindikationer, varningar och försiktighet, biverkningar, förpackningar och pris vänligen se www.fass.se. Biogen-31823 januari 2024

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John Cunningham virus (JCV)

John Cunningham Virus (JCV) and Progressive Multifocal Leukoencephalopathy (PML)

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