Tuesday, 29 October 2013

Does having JC virus affect the choice to stay on Tysabri

Lonergan R, Kinsella K, Kelly S, Duggan M, Scott J, O'Rourke K, Lynch T, Hutchinson M, Tubridy N, McGuigan C. Does JCV antibody positivity encourage cessation of Natalizumab therapy in Multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):e2


BACKGROUND: Natalizumab, a monoclonal α-4-integren receptor antibody, is an effective immunomodulator in highly active relapsing remitting Multiple Sclerosis (HARRMS). Natalizumab has been associated with PML (progressive multifocal leucoencephaopathy), due to opportunistic reactivation of JC polyomavirus (JCv). PML risk may influence decisions to continue therapy. Risk relates to 3 identified risk factors: serum anti-JCv antibodies, prior immunosuppression and prolonged natalizumab therapy (>2 years). Recent commercial availability of a serum JCv-antibody screening test (STRATIFY JCV TM) has been incorporated into a risk-stratification algorithm, presented to patients to help guide treatment. Influence of antibody testing on risk perception and decision to proceed with treatment has not been widely established.
AIM: To examine treatment decisions of patients receiving natalizumab based on their JCv-antibody status.
PATIENTS AND METHODS: Serum JCv-antibodies tested annually in patients receiving natalizumab for HARRMS. Clinical data and decisions to stop natalizumab based on JCv status recorded.
RESULTS:JCv antibody status was available in 112 natalizumab patients. Mean natalizumab duration 27.4 months (2-72). Antibodies detected in 55 (49.1%): 2 (3.6%) stopped due to JCv+ve alone, 14 (25.5%) due to prolonged therapy (>2years), 1 (1.8%) due to prolonged therapy and past immuosuppression, 3 (5.5%) disability progression, 1 (1.8%) to conceive. (12.3% of JCv negative patients stopped due to prolonged therapy). No significant difference in mean natalizumab duration or disease-modifying therapy history between JCv Ab+ve and Ab-ve groups (p>0.05). Other PML risks (>2 years, past immunosuppression) did not differ significantly between JCv+ve patients who opted to continue compared to those choosing to stop (p>0.05).
DISCUSSION: JCv antibody status had little influence on this cohort's decision to discontinue or remain on natalizumab therapy. It is important that patients understand therapeutic benefits and potential risks of alternative treatments before discontinuing due to JCv status alone. Further validation of this risk stratification measure is important.

6 comments:

  1. I feel lucky to have a neurologist who allows me to make the choice. Many patients I know have had doctors refuse to sign off on their continuation of Tysabri once they were found to be JC+.

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  2. I was given the choice to go on ASCEND trial despite being JC +ve To me it was a no-brainer. 50% are placebo, all patients are carefully monitored and if Tysabri treatment is good for SPMSers then progress might even stop. Alternative is a guarantee of SPMS progress. At end of trial option to go on Tysabri paid fro by Pharma - must be a win-win

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    1. Also remember being on placebo is usually better than being on nothing as people in trials tend to do better than if they are not in trials.

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  3. Is there any existing evidence that Tysabri helps those with SPMS?

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    1. The ASCEND trial is ongoing. Whilst I am personally doubtful it will stop progression, it may change the slope lets hope so, maybe it will do much better. If you look at the brains of people with SPMS, although it is less inflammatory than earlier in the disease course, immune cells and cuffs are still there these should respond to tysabri.

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    2. Thank you for taking the time to do this blog and respond to our questions. I am extremely grateful for the work done by you and the team!

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