September 2015 natalizumab PML update: underestimating the PML risk? #ClinicSpeak #MSBlog #MSResearch
"Apologies about the delay in posting the last natalizumab PML risk data; simply too many tasks and not enough time. The following are the latest risk figures for PML as a result of being treated with natalizumab. Please note that the embedded slideshow is for health professionals only; if you are not a healthcare professional Biogen would like you to ignore this presentation."
"As of the 31st August 2015 there have been 588 cases of natalizumab-associated PML, on a background of over 142,000 MSers exposed to natalizumab and 433,208 treatment years. The number of new PML cases per month is obviously decreasing, which indicates that the PML de-risking programme is working. In other words less MSers at risk of PML are staying on the natalizumab.
"The overall mortality associated with PML is 23% in December; in other words 135 MSers have died as result of PML. Please note that the majority of the PML survivors have a poor functional outcome."
"We are continuing to de-risk our natalizumab-treated population and remain hopeful that we can prevent anyone at our centre from getting PML. Despite this we still have several MSers who are not prepared to stop natalizumab, simply because they are doing so well on the drug."
"The following is the most important headline data slide for MSers regarding risks based on the three identified PML risk factors:
- JCV serostatus
- Duration of treatment
- Previous exposure to immunosuppression
In addition to this the levels of anti-JCV antibodies also play a role in risk (see below) and has been incorporated into our risk model."
"Our simple infographic helps integrates all this information. You can download and print this infographic for your own information."
METHODS: The association between serum or plasma anti-JCV antibody levels and PML risk was examined in anti-JCV antibody-positive multiple sclerosis (MS) patients from natalizumab clinical studies and postmarketing sources. For PML and non-PML patients, the probabilities of having an index below and above a range of anti-JCV antibody index thresholds were calculated using all available data and applied to the PML risk stratification algorithm. Longitudinal stability of anti-JCV antibody index was also evaluated.
RESULTS: Anti-JCV antibody index data were available for serum/plasma samples collected >6 months prior to PML diagnosis from 71 natalizumab-treated PML patients and 2,522 non-PML anti-JCV antibody-positive patients. In patients with no prior immunosuppressant use, anti-JCV antibody index distribution was significantly higher in PML patients than in non-PML patients (p < 0.0001). Among patients who were anti-JCV antibody negative at baseline in the AFFIRM and STRATIFY-1 trials, 97% remained consistently negative or below an index threshold of 1.5 over 18 months. Retrospective analyses of pre-PML samples collected longitudinally from PML patients displayed sustained higher anti-JCV antibody index over time.
INTERPRETATION: Anti-JCV antibody levels in serum/plasma, measured as index, may differentiate PML risk in anti-JCV antibody-positive MS patients with no prior immunosuppressant use. Continued evaluation of anti-JCV antibody index and PML risk is warranted.
"The figures in the bottom table are derived from Table 2 above and present the data in a different way, rather as per thousand an absolute risk. You have to realise that these figures are derived from relatively small numbers, i.e. 51 cases of PML. But the data is what it is and will not be confirmed by anyone else. I assume as more cases emerge the data set will be updated. The implications of this data is that many MSers who are doing well on natalizumab and have low titres, or a low index, may choose to stay on natalizumab rather than switch. In those MSers who are high risk and have elected to stay on natalizumab we have started doing 3 monthly MRI monitoring for early signs of PML. The idea behind the latter strategy is to detect PML very early and wash-out natalizumab. It is clear that if PML is picked up in the asymptomatic phase and managed quickly MSers do much better."
Labels: ClinicSpeak, Natalizumab, PML, PML Risk update