Dataset Information

?4-integrin receptor desaturation and disease activity return after natalizumab cessation.

ABSTRACT: To describe the time course of ?4-integrin receptor desaturation and disease activity return in patients with relapsing-remitting MS who discontinued natalizumab and to investigate baseline and on-study predictors for the recurrence of disease activity.In the course of TOFINGO, a 32-week, patient- and rater-blinded multicenter, parallel-group study, we performed MRI, counted relapses, and measured ?4-integrin receptor occupancy (RO) at baseline and 8, 12, 16, 20, and 24 weeks. The relationship between RO and total number of new T1 gadolinium-enhancing (Gd+) lesions was modeled using Poisson linear regression.Patients (N = 142) were randomized (1:1:1) to 8-, 12-, or 16-week washout (WO) groups. At randomization, the median RO in the 8-, 12-, and 16-week WO groups was 94.5%, 92.4%, and 90.9%, which declined to 79.8%, 30.7%, and 8.7% after 8, 12, and 16 weeks of WO, respectively. The percentage of patients with new T1 Gd+ lesions increased with longer WO period before commencing fingolimod: 2.1% (8 weeks), 9.1% (12 weeks), and 50.0% (16 weeks). Overall, 71% of patients with first relapse between weeks 6 and 18 had RO values below the time-matched population median. Higher T2 lesion volume (LV) at baseline predicted a higher number of new T1 Gd+ lesions.A faster decline in natalizumab RO, longer WO period, and higher T2 LV at baseline were associated with an increased risk for return of inflammatory disease activity. These results provide a mechanistic rationale and, together with the main outcomes of the TOFINGO study, support initiation of fingolimod within 8 weeks of natalizumab discontinuation.NCT01499667.

SUBMITTER: Derfuss T

PROVIDER: S-EPMC5572051 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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α4-integrin receptor desaturation and disease activity return after natalizumab cessation.

Derfuss Tobias T Kovarik John M JM Kappos Ludwig L Savelieva Marina M Chhabra Richa R Thakur Avinash A Zhang Ying Y Wiendl Heinz H Tomic Davorka D

Neurology(R) neuroimmunology & neuroinflammation 20170825 5

<h4>Objective</h4>To describe the time course of α4-integrin receptor desaturation and disease activity return in patients with relapsing-remitting MS who discontinued natalizumab and to investigate baseline and on-study predictors for the recurrence of disease activity.<h4>Methods</h4>In the course of TOFINGO, a 32-week, patient- and rater-blinded multicenter, parallel-group study, we performed MRI, counted relapses, and measured α4-integrin receptor occupancy (RO) at baseline and 8, 12, 16, 20 ...[more]

PMID: 28856176

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Project description:Background and aimsModelling return on investment (ROI) from smoking cessation interventions requires estimates of their costs and benefits. This paper describes a standardized method developed to source both economic costs of tobacco smoking and costs of implementing cessation interventions for a Europe-wide ROI model [European study on Quantifying Utility of Investment in Protection from Tobacco model (EQUIPTMOD)].DesignFocused search of administrative and published data. A standardized checklist was developed in order to ensure consistency in methods of data collection.Setting and participantsAdult population (15+ years) in Hungary, Netherlands, Germany, Spain and England. For passive smoking-related costs, child population (0-15 years) was also included.MeasurementsCosts of treating smoking-attributable diseases; productivity losses due to smoking-attributable absenteeism; and costs of implementing smoking cessation interventions.FindingsAnnual costs (per case) of treating smoking attributable lung cancer were between €5074 (Hungary) and €52 106 (Germany); coronary heart disease between €1521 (Spain) and €3955 (Netherlands); chronic obstructive pulmonary disease between €1280 (England) and €4199 (Spain); stroke between €1829 (Hungary) and €14 880 (Netherlands). Costs (per recipient) of smoking cessation medications were estimated to be: for standard duration of varenicline between €225 (England) and €465 (Hungary); for bupropion between €25 (Hungary) and €220 (Germany). Costs (per recipient) of providing behavioural support were also wide-ranging: one-to-one behavioural support between €34 (Hungary) and €474 (Netherlands); and group-based behavioural support between €12 (Hungary) and €257 (Germany). The costs (per recipient) of delivering brief physician advice were: €24 (England); €9 (Germany); €4 (Hungary); €33 (Netherlands); and €27 (Spain).ConclusionsCosts of treating smoking-attributable diseases as well as the costs of implementing smoking cessation interventions vary substantially across Hungary, Netherlands, Germany, Spain and England. Estimates for the costs of these diseases and interventions can contribute to return on investment estimates in support of national or regional policy decisions.

Dataset Information

?4-integrin receptor desaturation and disease activity return after natalizumab cessation.

Publications

α4-integrin receptor desaturation and disease activity return after natalizumab cessation.

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