Extending natalizumab dosing intervals reduces the risk of PML
Quoting a Friday, March 9, 2018 post at:
multiple-sclerosis-research.blogspot.com/
“Natalizumab extended interval dosing (EID) is associated with a significant reduction in PML risk compared with standard interval dosing (SID) in the TOUCH® Prescribing Program
Natalizumab, a highly efficacious medication approved for relapsing forms of MS, is used to prevent relapses, slow worsening disability, and may improve the quality of life for some patients. The medication is indicated to be prescribed as 300-milligram infusion dosed every four weeks.
However, taking the medication longer than two years may increase risk of PML, which is caused by JCV. There have been 756 PML cases reported worldwide as of December 2017, with a global incidence rate of 4.19 per 1,000 PML cases in people treated with natalizumab. Patients who test JCV antibody-positive and therefore are presumed to have been infected with the virus, which comprises roughly half of the world population, are typically either told to not to start natalizumab, or have had treatment stopped after two years, when risk is deemed to be too high.
Our new study… adds an important caveat to known PML risk in natalizumab users. According to the comprehensive analysis of TOUCH database, which includes all natalizumab users in the Unites States, the risk of PML is very significantly lower in JCV Antibody positive patients whose natalizumab infusions have been extended from 4 weeks to 5-12 weeks.
The results showed clinically meaningful and statistically significant risk reductions… – there were no PML cases among 815 patients who met the inclusion criteria as compared to 96 cases noted in standard interval group (comprised of 23,168 patients). The average dosing interval extension ranged from 35 to 42 days. It is important to note that patients with dosing gaps over 12 weeks were excluded since numerous studies have demonstrated loss of drug efficacy after 3 months period.
The TOUCH database does not capture efficacy data. Key outstanding question at this point is whether the efficacy of monthly natalizumab could be maintained with less frequent dosing (e.g. q 6 weeks). Our prior retrospective work found that extending the dose up to 8 weeks did not negatively affect the medication’s efficacy in a retrospective review of 2,000 patients in 6 MS Centers across the US.
In the meantime, our recent findings could influence how neurologists prescribe the medication. Neurologists have been looking for safer ways to administer natalizumab infusions to their patients, but there hasn’t been clear data on whether decreasing dosing frequency improves safety. The large risk reduction seen with extending natalizumab infusions by just 2 weeks is potentially practice-changing since it could give neurologists an opportunity to prescribe a highly efficacious medication in a safer way.
Our research team includes I. Kister, J.D. Goldberg, X. Li from New York University Langone Medical Center, J. Foley and R. Metzger from Rocky Mountain Multiple Sclerosis Clinic, G Cutter from University of Alabama at Birmingham School of Medicine, and I. Chang, B. Yu, Z. Ren, C. Hotermans, P.R. Ho, and N. Campbell from Biogen.
Post by Lana Zhovtis”
Quoting a Friday, March 9, 2018 post at:
multiple-sclerosis-research.blogspot.com/
“Natalizumab extended interval dosing (EID) is associated with a significant reduction in PML risk compared with standard interval dosing (SID) in the TOUCH® Prescribing Program
Natalizumab, a highly efficacious medication approved for relapsing forms of MS, is used to prevent relapses, slow worsening disability, and may improve the quality of life for some patients. The medication is indicated to be prescribed as 300-milligram infusion dosed every four weeks.
However, taking the medication longer than two years may increase risk of PML, which is caused by JCV. There have been 756 PML cases reported worldwide as of December 2017, with a global incidence rate of 4.19 per 1,000 PML cases in people treated with natalizumab. Patients who test JCV antibody-positive and therefore are presumed to have been infected with the virus, which comprises roughly half of the world population, are typically either told to not to start natalizumab, or have had treatment stopped after two years, when risk is deemed to be too high.
Our new study… adds an important caveat to known PML risk in natalizumab users. According to the comprehensive analysis of TOUCH database, which includes all natalizumab users in the Unites States, the risk of PML is very significantly lower in JCV Antibody positive patients whose natalizumab infusions have been extended from 4 weeks to 5-12 weeks.
The results showed clinically meaningful and statistically significant risk reductions… – there were no PML cases among 815 patients who met the inclusion criteria as compared to 96 cases noted in standard interval group (comprised of 23,168 patients). The average dosing interval extension ranged from 35 to 42 days. It is important to note that patients with dosing gaps over 12 weeks were excluded since numerous studies have demonstrated loss of drug efficacy after 3 months period.
The TOUCH database does not capture efficacy data. Key outstanding question at this point is whether the efficacy of monthly natalizumab could be maintained with less frequent dosing (e.g. q 6 weeks). Our prior retrospective work found that extending the dose up to 8 weeks did not negatively affect the medication’s efficacy in a retrospective review of 2,000 patients in 6 MS Centers across the US.
In the meantime, our recent findings could influence how neurologists prescribe the medication. Neurologists have been looking for safer ways to administer natalizumab infusions to their patients, but there hasn’t been clear data on whether decreasing dosing frequency improves safety. The large risk reduction seen with extending natalizumab infusions by just 2 weeks is potentially practice-changing since it could give neurologists an opportunity to prescribe a highly efficacious medication in a safer way.
Our research team includes I. Kister, J.D. Goldberg, X. Li from New York University Langone Medical Center, J. Foley and R. Metzger from Rocky Mountain Multiple Sclerosis Clinic, G Cutter from University of Alabama at Birmingham School of Medicine, and I. Chang, B. Yu, Z. Ren, C. Hotermans, P.R. Ho, and N. Campbell from Biogen.
Post by Lana Zhovtis”
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