Natalizumab was approved by the FDA in 2008 for adult patients with moderately to severely active CD with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α. The TYSABRI Outreach: Unified Commitment to Health (TOUCH®) Prescribing Program, Crohn's Disease: Investigating Natalizumab through Further Observational Research & Monitoring (CD INFORM), TYSABRI Global Observation Program In Safety (TYGRIS), and TYSABRI® Pregnancy Exposure Registry (TPER) are ongoing risk management activities designed to further evaluate the safety of natalizumab. This report summarizes recent data on natalizumab utilization and safety in patients with Crohn's disease (CD) and relapsing multiple sclerosis (MS). TOUCH® is a mandatory prescribing program for all patients, prescribers, pharmacies and infusion centers in the US using natalizumab. TOUCH® is designed to inform about the risk of progressive multifocal leukoencephalopathy (PML); warn against concurrent use with antineoplastic, immunosuppressant, or immunomodulating agents, and in patients who are immunocompromised; and promote early diagnosis of PML and timely discontinuation of natalizumab in the event of suspected PML. CD INFORM, a post-marketing commitment, collects patient history, efficacy as assessed by the Harvey Bradshaw Index (HBI), Health Related Quality of Life outcomes, and serious adverse events (SAE) in CD patients on natalizumab therapy. TYGRIS, also a post-marketing commitment, is evaluating the long-term safety of natalizumab in MS. Post-marketing surveillance data are also collected. TPER evaluates the outcomes of pregnancy in women with CD and MS exposed to natalizumab. As of 30 June 2012, ˜104,300 patients have been exposed to natalizumab in the post-marketing setting (103,259 MS; 1,041 CD),. As of 01 August 2012, 271 cases of PML have been confirmed (270 MS, 1 CD). Of the 271 natalizumabtreated patients who developed PML, 212 (78%) had survived, exhibiting varying levels of disability and there were 59 (22%) deaths. Presence of anti-JCV antibodies, prior treatment with immunosuppressants and longer treatment duration with natalizumab, especially beyond 2 years, are identified risk factors for potential development of PML. As of 07 August 2012, 163 patients were enrolled in CD INFORM with the number of natalizumab infusions ranging from 1-56, with a mean and median of 14.6 and 10, respectively. The average HBI at time of entry for these patients was 8.2 (range 0 to 28). Of the 99 CD patients with an HBI assessment after receiving 6 months of natalizumab therapy, the average total score was 4.8, a mean decrease of 2.8 points from baseline. Cumulatively, as of 07 August 2012, there were 93 SAEs occurring in 51 patients reported in CD INFORM, 4 patients experienced 8 SAEs that were considered treatment related. As of 23 May 2012, 375 women (7 with CD) were prospectively enrolled in the TPER with372 outcomes reported, including 8 twin pregnancies resulting in 2 outcomes for each pregnancy. Current exposure and safety data from patients receiving natalizumab in both indications will be presented. Cumulative data from both indications suggest a safety profile consistent with natalizumab product labeling.
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Jan 5, 2016
Paul W O’Connor + 1
Open Access
