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The risk of disease reactivation rises in adults with multiple sclerosis who discontinue natalizumab treatment after 24 doses, according to findings from the prospective, multicenter, observational TY-STOP Study.
In an intent-to-treat analysis, disease activity was significantly lower among 43 patients who continued natalizumab treatment, compared with 81 who had interrupted treatment (odds ratios, 0.33 for clinical activity and 0.35 for radiologic activity). In an as-treated analysis, clinical disease activity was more than three times higher in 16 patients who switched treatments (OR, 3.28), and more than four times higher in natalizumab quitters (OR, 4.40), compared with 35 patients who continued on natalizumab. Dr. Marinella Clerico of the University of Turin, San Luigi Gonzaga University Hospital, Orbassano, Italy, and her colleagues reported the findings online June 30 in JAMA Neurology.
One patient who discontinued treatment developed progressive multifocal leukoencephalopathy (PML) during the observation period, but recovered completely (JAMA Neurol. 2014 [doi:10.1001/jamaneurol.2014.1200]).
Continuing natalizumab seems to be the most efficacious therapeutic strategy in those who have already received 24 doses and who must – according to a "meticulous risk management plan" implemented by the European Medicines Agency in the wake of increased incidence of PML among natalizumab users – renew consent to continue treatment after 24 doses. However, given the risk of PML, the decision to continue treatment should take into account the risk of disease reactivation associated with discontinuation as well as the risk of PML with continuation, and treatment should be continued, along with meticulous monitoring for PML, in all patients in whom risk is not considered too high, they concluded.
Dr. Clerico reported receiving travel grants from Merck Serono and Biogen Idec. Other authors also made financial disclosures, the details of which are available with the full text of the article at jamaneurology.com.
The findings by Dr. Clerico and her colleagues confirm that natalizumab effectively suppresses disease activity, and that disease activity may return upon treatment withdrawal, but the authors, like others before them, failed to identify a safe exit strategy that minimizes the return of disease activity and lowers the risk of PML, according to Dr. Olaf Stüve and Gary R. Cutter, Ph.D.
"To make a rational decision [about continuing natalizumab] on the recommendation by the authors, the following important information is unavailable to patients and their neurologists: Are the reduction in disease activity and therapeutic benefits gained during natalizumab therapy maintained in the long term and, most important, after treatment cessation?" they wrote in an editorial. (JAMA Neurol. 2014 [doi:10.1001/jamaneurol.2014.1201]).
Natalizumab has had positive effects on many patients, and these effects are relevant even if they are time limited and reversed upon treatment withdrawal, but long-term data are needed to characterize potential long-term benefits and to "calculate discounts to these benefits if there is an accelerated decline after treatment cessation," they said, concluding that answers are needed regarding whom and how long to treat, how to most effectively initiate sequential therapies, and whether disease reactivation after natalizumab withdrawal is a risk factor for increased long-term disability.
Dr. Stüve is with the Veterans Affairs North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, and with Klinikum Rechts der Isar, Technische Universität München, Munich. He also is associate editor for JAMA Neurology. Dr. Cutter is a professor of biostatistics with the University of Alabama at Birmingham. Dr. Stüve reported serving on editorial boards for Multiple Sclerosis Journal, Clinical and Experimental Immunology, and Therapeutic Advances in Neurological Disorders, and participating in data and safety monitoring committees for Pfizer and Sanofi-Aventis. He received grant support from Teva. Dr. Cutter is president of Pythagoras Inc., a private consulting firm and has received numerous National Institutes of Health and Department of Defense grants. Additional disclosures details are available with the editorial at jamaneurology.com.
The findings by Dr. Clerico and her colleagues confirm that natalizumab effectively suppresses disease activity, and that disease activity may return upon treatment withdrawal, but the authors, like others before them, failed to identify a safe exit strategy that minimizes the return of disease activity and lowers the risk of PML, according to Dr. Olaf Stüve and Gary R. Cutter, Ph.D.
"To make a rational decision [about continuing natalizumab] on the recommendation by the authors, the following important information is unavailable to patients and their neurologists: Are the reduction in disease activity and therapeutic benefits gained during natalizumab therapy maintained in the long term and, most important, after treatment cessation?" they wrote in an editorial. (JAMA Neurol. 2014 [doi:10.1001/jamaneurol.2014.1201]).
Natalizumab has had positive effects on many patients, and these effects are relevant even if they are time limited and reversed upon treatment withdrawal, but long-term data are needed to characterize potential long-term benefits and to "calculate discounts to these benefits if there is an accelerated decline after treatment cessation," they said, concluding that answers are needed regarding whom and how long to treat, how to most effectively initiate sequential therapies, and whether disease reactivation after natalizumab withdrawal is a risk factor for increased long-term disability.
Dr. Stüve is with the Veterans Affairs North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, and with Klinikum Rechts der Isar, Technische Universität München, Munich. He also is associate editor for JAMA Neurology. Dr. Cutter is a professor of biostatistics with the University of Alabama at Birmingham. Dr. Stüve reported serving on editorial boards for Multiple Sclerosis Journal, Clinical and Experimental Immunology, and Therapeutic Advances in Neurological Disorders, and participating in data and safety monitoring committees for Pfizer and Sanofi-Aventis. He received grant support from Teva. Dr. Cutter is president of Pythagoras Inc., a private consulting firm and has received numerous National Institutes of Health and Department of Defense grants. Additional disclosures details are available with the editorial at jamaneurology.com.
The findings by Dr. Clerico and her colleagues confirm that natalizumab effectively suppresses disease activity, and that disease activity may return upon treatment withdrawal, but the authors, like others before them, failed to identify a safe exit strategy that minimizes the return of disease activity and lowers the risk of PML, according to Dr. Olaf Stüve and Gary R. Cutter, Ph.D.
"To make a rational decision [about continuing natalizumab] on the recommendation by the authors, the following important information is unavailable to patients and their neurologists: Are the reduction in disease activity and therapeutic benefits gained during natalizumab therapy maintained in the long term and, most important, after treatment cessation?" they wrote in an editorial. (JAMA Neurol. 2014 [doi:10.1001/jamaneurol.2014.1201]).
Natalizumab has had positive effects on many patients, and these effects are relevant even if they are time limited and reversed upon treatment withdrawal, but long-term data are needed to characterize potential long-term benefits and to "calculate discounts to these benefits if there is an accelerated decline after treatment cessation," they said, concluding that answers are needed regarding whom and how long to treat, how to most effectively initiate sequential therapies, and whether disease reactivation after natalizumab withdrawal is a risk factor for increased long-term disability.
Dr. Stüve is with the Veterans Affairs North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, and with Klinikum Rechts der Isar, Technische Universität München, Munich. He also is associate editor for JAMA Neurology. Dr. Cutter is a professor of biostatistics with the University of Alabama at Birmingham. Dr. Stüve reported serving on editorial boards for Multiple Sclerosis Journal, Clinical and Experimental Immunology, and Therapeutic Advances in Neurological Disorders, and participating in data and safety monitoring committees for Pfizer and Sanofi-Aventis. He received grant support from Teva. Dr. Cutter is president of Pythagoras Inc., a private consulting firm and has received numerous National Institutes of Health and Department of Defense grants. Additional disclosures details are available with the editorial at jamaneurology.com.
The risk of disease reactivation rises in adults with multiple sclerosis who discontinue natalizumab treatment after 24 doses, according to findings from the prospective, multicenter, observational TY-STOP Study.
In an intent-to-treat analysis, disease activity was significantly lower among 43 patients who continued natalizumab treatment, compared with 81 who had interrupted treatment (odds ratios, 0.33 for clinical activity and 0.35 for radiologic activity). In an as-treated analysis, clinical disease activity was more than three times higher in 16 patients who switched treatments (OR, 3.28), and more than four times higher in natalizumab quitters (OR, 4.40), compared with 35 patients who continued on natalizumab. Dr. Marinella Clerico of the University of Turin, San Luigi Gonzaga University Hospital, Orbassano, Italy, and her colleagues reported the findings online June 30 in JAMA Neurology.
One patient who discontinued treatment developed progressive multifocal leukoencephalopathy (PML) during the observation period, but recovered completely (JAMA Neurol. 2014 [doi:10.1001/jamaneurol.2014.1200]).
Continuing natalizumab seems to be the most efficacious therapeutic strategy in those who have already received 24 doses and who must – according to a "meticulous risk management plan" implemented by the European Medicines Agency in the wake of increased incidence of PML among natalizumab users – renew consent to continue treatment after 24 doses. However, given the risk of PML, the decision to continue treatment should take into account the risk of disease reactivation associated with discontinuation as well as the risk of PML with continuation, and treatment should be continued, along with meticulous monitoring for PML, in all patients in whom risk is not considered too high, they concluded.
Dr. Clerico reported receiving travel grants from Merck Serono and Biogen Idec. Other authors also made financial disclosures, the details of which are available with the full text of the article at jamaneurology.com.
The risk of disease reactivation rises in adults with multiple sclerosis who discontinue natalizumab treatment after 24 doses, according to findings from the prospective, multicenter, observational TY-STOP Study.
In an intent-to-treat analysis, disease activity was significantly lower among 43 patients who continued natalizumab treatment, compared with 81 who had interrupted treatment (odds ratios, 0.33 for clinical activity and 0.35 for radiologic activity). In an as-treated analysis, clinical disease activity was more than three times higher in 16 patients who switched treatments (OR, 3.28), and more than four times higher in natalizumab quitters (OR, 4.40), compared with 35 patients who continued on natalizumab. Dr. Marinella Clerico of the University of Turin, San Luigi Gonzaga University Hospital, Orbassano, Italy, and her colleagues reported the findings online June 30 in JAMA Neurology.
One patient who discontinued treatment developed progressive multifocal leukoencephalopathy (PML) during the observation period, but recovered completely (JAMA Neurol. 2014 [doi:10.1001/jamaneurol.2014.1200]).
Continuing natalizumab seems to be the most efficacious therapeutic strategy in those who have already received 24 doses and who must – according to a "meticulous risk management plan" implemented by the European Medicines Agency in the wake of increased incidence of PML among natalizumab users – renew consent to continue treatment after 24 doses. However, given the risk of PML, the decision to continue treatment should take into account the risk of disease reactivation associated with discontinuation as well as the risk of PML with continuation, and treatment should be continued, along with meticulous monitoring for PML, in all patients in whom risk is not considered too high, they concluded.
Dr. Clerico reported receiving travel grants from Merck Serono and Biogen Idec. Other authors also made financial disclosures, the details of which are available with the full text of the article at jamaneurology.com.
FROM JAMA NEUROLOGY
Key clinical point: Discontinuing natalizumab in patients who respond should only be considered if the risk of multifocal leukoencephalopathy is high enough to outweigh the benefits of the drug.
Major finding: Clinical disease activity was higher in patients who switched treatment (OR, 3.28), and who quit natalizumab (OR, 4.40), compared with those who continued natalizumab.
Data source: A prospective observational study involving 124 patients.
Disclosures: Dr. Clerico reported receiving travel grants from Merck Serono and Biogen Idec. Other authors also made financial disclosures, the details of which are available with the full text of the article at jamaneurology.com.