Before Initiation of Therapy :
- Have recent (<3months) cerebral MRI
- CBC, liver enzymes, creatinine, bilirubin, glucose,TSH, JCV index, HBsAg, anti-HBc, anti-HBs, hepatitis C. HIV, VZV serology
- CD4+ and CD8+ T cells titers, pregnancy test
- Chest Xray and/or Quantiferon for TB
- Verification of vaccination status and update if necessary
- Give Pneumococcal and Haemophilius influenza type B vaccines
- We do not administer Tysabri in patients whose JCV index >0.4 until their CD4+ >500 and CD8+ > 250 (repeat monthly if necessary)
Monitoring During Therapy :
- Anti natalizumab antibody level after the 6th infusion and upon resuming tysabri after a prolonged absence such as pregnancy or anytime a patient develops serious infusion reactions
- CBC, liver enzymes is done Q1month for the first 6 months then Q4 months
- JCV index if negative or less than 0.9 is repeated Q4months
- JCV index if >1.5 or becomes >1.5 should be repeated only once to confirm the result. There is no need to further repeat it.
- Unenhanced cerebral MRI at 12 months and subsequently every 12 months if JCV index < 0.9 or Q4-6 months if JCV index is > 0.9
- CSF PCR for JCV if there is a new definite T2 MRI lesion and/or new progressive neurological symptoms unexplained by MS relapse or seizure de novo
- An annual discussion with the patient concerning the forward looking PML risk and the decision to continue or not with Tysabri therapy is documented. Patients are not automatically taken off Tysabri after two years of therapy. This is a case by case and year by year decision.
Discontinue Therapy :
- MS baseline disease activity returns in the 3rd or 4th month after stopping Tysabri. Some patients however may experience a very severe relapse (MS rebound). This has been estimated to occur in about 10% of cases
- A switch to a new disease modifying therapy should be instituted prior to the 3rd month after stopping Tysabri
- If this is not possible then monthly Solumedrol 1.0gm IV can be used until the new therapy is instituted
- An unenhanced cerebral MRI at discontinuation to exclude PML or GCN. A follow up cerebral enhanced MRI in the 3rd or 4th month after discontinuation of Tysabri to monitor for MS rebound is to be considered if switching to a less efficacious therapy such as any of the oral agents.
- In patients that are JCV positive a CSF PCR for JCV prior to switching to Alemtuzumab (Lemtrada) or Ocrelizumab (Ocrevus) is recommended.
- Tysabri should be discontinued in patients with persisting neutralizing antibodies.
(Some studies only include abstracts)
Averse Events :
- Infusion related reactions occurred in 23% of study patients but less than 1% were serious. Most can be controlled with premedication such as Benadryl and or prednisone.
- Hepatic injury has been reported in post marketing surveillance and appears to be reversible once Tysabri is stopped.
- Mild thrombocytopenia can occur.
- Serious infections with herpes simplex and varicella zoster virus meningitis, encephalitis or acute retinal necrosis have been reported in post marketing.
- Neutralizing antibody occurs in 6%. These usually occur by week 12 but can occur later and should be suspected in all patients with serious infusion reactions. They tend to be more common in patients who resume Tysabri therapy after a prolonged interruption ie pregnancy.
- Progressive Multifocal Leukoencephalopathy (PML) and cerebellar Granule Cell Neuronopathy (GCN) are the main concerns with Tysabry use. See the section Common Concerns for more details.