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4/30/12 As
of April 5, 2012, there were 232 confirmed cases of PML since the reintroduction of Tysabri, out of about 95,000
treated patients. Biogen is currently issuing updates monthly, and there are a number of new cases each month
since many people are now entering the higher risk periods. There are about 52,000 people on Tysabri in the US. The risk for PML varies with duration of treatment. The number
of cases per 1000 patients reported in January, 2011 was 0.40 for people treated 13-24 infusions, 1.49 for 25-36 infusions,
and 0.92 for 37-48 infusions. In the April, 2012 update, the risks were 0.58, 1.94, and 2.17 for the same time
periods and 1.37 for 49-60 infusions. The risk during the first 12 infusions is very low. The estimated rates increased
a little bit in 2011 as more people enter the higher risk periods. I don't expect much change in the future. For
now the estimated risk is staying near the predicted range, and the risk appears to peak in the third year of treatment and
then remain high. I expect the number of cases to continue to increase, since more people are entering the higher risk
periods. There are now enough people on treatment that I don't expect the numbers will change much in the
future, and I am no longer following this on a monthly basis. I should point out that these estimates of risk are for
all people on Tysabri, and the risk will vary considerably depending on JC antibody status and previous chemotherapy treatments.
People who are JC antibody negative will have a very low risk at any time. People who were on mitoxantrone, cytoxan,
or other chemotherapy treatments have a higher risk. The outcome of the PML cases has been varied. About a third are
reported to have done well, with a mild disability score. But about 20% of the cases were fatal, and all survivors had
additional disability, often severe. PML is a serious disease, even with quick recognition and appropriate treatment.
Past updates for historical interest: 10/16/09 A patient treated with Tysabri for 21 months
developed lymphoma in the brain. There was no sign of the Epstein-Barr virus infection which causes some cases of lymphoma.
This is a serious disease, but this is the first case reported in association with Tysabri. 9/22/09 Two additional cases have
been reported. There weren't any details about how long the 2 new cases had been on treatment. There was one additional
case in Europe and one in the US. 8/20/09 There
have now been a total of 11 cases of PML since reintroduction of Tysabri. Three new cases were reported in June and
one in July. All cases have been in MS patients, and 8 of the 11 are in Europe with 3 in the US. There are currently 30,600 patients on treatment for 12 months or more, 18,400 on treatment for 18 months,
and 10,000 on treatment for 2 years. The timeline is as follows: Date reported Months on treatment 7/30/08 17 7/31/08
14 10/29/08
14 12/10/08
26 2/5/09
12 4/15/09
31 5/18/09
24 6/10/09
35 6/19/09
34 6/23/09
30 7/24/09
29 One obvious concern is that the risk of PML may go up with longer treatment.
If this is true, then there should be an increasing number of cases over time, although it is reassuring that only one addition
case occurred in July. I will continue to monitor this situation very closely. At present I have about 15
patients on Tysabri, and all of them have pretty severe MS which makes the risk more acceptable. 2/10/09 An additional case of PML
from Europe, occurring after 12 months of treatment, was reported 2/5/09. This brings the total number of confirmed
cases to 5, with about 20,200 patients on Tysabri for over a year. 1/6/09 An additional case
of PML from Europe was reported on 12/11/08. The patient had received 26 months of Tysabri,and the diagnosis of PML was
confirmed by PCR and MRI. He presented with cognitive changes. He had previously failed treatment with interferon
and was responding well to Tysabri. His last dose was on 10/29. He was treated with immunoadsorption. His
current status is not reported. 10/30/08
An additional case of PML was reported on 10/29/08. This patient had MS since 2001, and had been on Tysabri for
14 months. Following her last dose in late September she had some worsening of her previous MS symptoms, and then developed
troubles with language in late October. Brain MRI was suggestive of PML, and JC virus DNA was detected in the spinal
fluid. The patient was treated with plasma exchange, and is back at home. She was not receiving any other
immunosuppressive medicines while on Tysabri, but she has been treated with methotrexate in the past (not for MS). There are currently 18,000 patients that have been on Tysabri more than 12 months and 9500
that have been on treatment more than 18 months. The
two previous cases of PML, both in Germany, (see report below), have improved, but they continue to have deficits related
to the PML. We will continue to monitor the number of
PML cases. For now, the number of cases is small compared to the number of people on treatment. The risk
of PML seems to be acceptable for people with severe MS, and I am continuing to recommend Tysabri to carefully selected
patients. If you have any concerns, please call the office.
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