A Promising New Dosing Schedule for Natalizumab
A Promising New Dosing Schedule for Natalizumab
While onsite at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015 in Barcelona, Spain, Medscape correspondent Andrew N. Wilner, MD, spoke with John A. Lincoln, MD, PhD, an assistant professor of neurology in the multiple sclerosis research group at the University of Texas in Houston, Texas, about a promising, unique natalizumab dosing schedule.
Dr Wilner: What did you learn today at ECTRIMS that you didn't know before?
Dr Lincoln: There was an interesting presentation by Dr Lana Ryerson on a large cohort of a little over 1000 patients that had used extended dosing of natalizumab. Instead of the typical 28-day cycle, the investigators extended it out to 8 weeks to look at various different things, including efficacy measures. They found that there wasn't a tremendous drop in efficacy even at 8 weeks. For gadolinium-enhancing lesions, the efficacy dropped from 7%, which is what they found for individuals who had taken the every-4-week dose, to 9% of those who had taken the every-8-week dose.
It raises a little bit of a concern, because one would expect that on natalizumab, there would be essentially 0% gadolinium-enhancing lesions—"no evidence of disease activity" is a metric that Biogen, the manufacturer, focuses on. It's a little surprising that they found 7% in this cohort, although admittedly, they didn't check to see whether natalizumab-neutralizing antibodies were present, which can potentially alter efficacy.
Still, it was interesting that even at 8 weeks, the investigators did not see a huge decrease in the number of new lesions; the number of gadolinium-enhancing lesions went from 7% to 9%, which isn't a huge difference. They also didn't see any cases of progressive multifocal leukoencephalopathy (PML) among the 1000-plus patients who were on this extended protocol.
Dr Wilner: Is that the rationale—that maybe by giving natalizumab every 2 months instead of every month, you might decrease the risk for PML?
Dr Lincoln: That's potentially the reason they did it. All of patients were JC-antibody–positive—although the investigators did not report their index, at least at the talk. So the investigators didn't know what the patients' true risk would have been if had they gone with the every-4-week dosing.
Dr Wilner: You mean the quantitative measure?
Dr Lincoln: Right. We know that the risk increases potentially over time, and it also increases to some extent on the basis of JC index level—whether it's greater than or less than 0.9. They didn't report those specific numbers, so we don't know that for sure, but that's the rationale—that you would give natalizumab less frequently, and so therefore reduce the potential risk for PML.
Dr Wilner: What are you going to do in your practice? Do you treat patients with natalizumab?
Dr Lincoln: I do, quite a bit. I still use the every-4-week doses, and I think until we have some better data on what the true risk is of PML by extending the infusions (this study is definitely a great start), I don't think that extending infusions out to every 8 weeks should be largely used in clinical practice.
This is the largest cohort that's been reported thus far. As I said, it's over 1000 patients. Once they can do a subgroup analysis to look at what the true PML risk was in these patients, in this specific cohort—and I'm sure those longitudinal data will come out—at that point, I think for the clinician in practice, extending therapy out might be quite reasonable.
Disclosures: Dr Lincoln is currently a paid speaker for Acorda Pharmaceuticals, Biogen Idec, Sanofi-Gynzyme, Novartis, and Teva. In addition, he has participated in advisory boards for Genzyme-Sanofi, Novartis, and Bayer.
While onsite at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015 in Barcelona, Spain, Medscape correspondent Andrew N. Wilner, MD, spoke with John A. Lincoln, MD, PhD, an assistant professor of neurology in the multiple sclerosis research group at the University of Texas in Houston, Texas, about a promising, unique natalizumab dosing schedule.
Dr Wilner: What did you learn today at ECTRIMS that you didn't know before?
Dr Lincoln: There was an interesting presentation by Dr Lana Ryerson on a large cohort of a little over 1000 patients that had used extended dosing of natalizumab. Instead of the typical 28-day cycle, the investigators extended it out to 8 weeks to look at various different things, including efficacy measures. They found that there wasn't a tremendous drop in efficacy even at 8 weeks. For gadolinium-enhancing lesions, the efficacy dropped from 7%, which is what they found for individuals who had taken the every-4-week dose, to 9% of those who had taken the every-8-week dose.
It raises a little bit of a concern, because one would expect that on natalizumab, there would be essentially 0% gadolinium-enhancing lesions—"no evidence of disease activity" is a metric that Biogen, the manufacturer, focuses on. It's a little surprising that they found 7% in this cohort, although admittedly, they didn't check to see whether natalizumab-neutralizing antibodies were present, which can potentially alter efficacy.
Still, it was interesting that even at 8 weeks, the investigators did not see a huge decrease in the number of new lesions; the number of gadolinium-enhancing lesions went from 7% to 9%, which isn't a huge difference. They also didn't see any cases of progressive multifocal leukoencephalopathy (PML) among the 1000-plus patients who were on this extended protocol.
Dr Wilner: Is that the rationale—that maybe by giving natalizumab every 2 months instead of every month, you might decrease the risk for PML?
Dr Lincoln: That's potentially the reason they did it. All of patients were JC-antibody–positive—although the investigators did not report their index, at least at the talk. So the investigators didn't know what the patients' true risk would have been if had they gone with the every-4-week dosing.
Dr Wilner: You mean the quantitative measure?
Dr Lincoln: Right. We know that the risk increases potentially over time, and it also increases to some extent on the basis of JC index level—whether it's greater than or less than 0.9. They didn't report those specific numbers, so we don't know that for sure, but that's the rationale—that you would give natalizumab less frequently, and so therefore reduce the potential risk for PML.
Dr Wilner: What are you going to do in your practice? Do you treat patients with natalizumab?
Dr Lincoln: I do, quite a bit. I still use the every-4-week doses, and I think until we have some better data on what the true risk is of PML by extending the infusions (this study is definitely a great start), I don't think that extending infusions out to every 8 weeks should be largely used in clinical practice.
This is the largest cohort that's been reported thus far. As I said, it's over 1000 patients. Once they can do a subgroup analysis to look at what the true PML risk was in these patients, in this specific cohort—and I'm sure those longitudinal data will come out—at that point, I think for the clinician in practice, extending therapy out might be quite reasonable.
Disclosures: Dr Lincoln is currently a paid speaker for Acorda Pharmaceuticals, Biogen Idec, Sanofi-Gynzyme, Novartis, and Teva. In addition, he has participated in advisory boards for Genzyme-Sanofi, Novartis, and Bayer.
