The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 Lurbinectedin patient-years. and Participants This observational study used data in the MS registry OFSEP (Observatoire Fran?ais de la Sclrose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n?=?6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018. Exposures Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation. Main Outcomes and Measures Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by Rabbit polyclonal to Caspase 3 period (2007-2013 and 2013-2016). Results In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, Lurbinectedin with a mean (SD [range]) age at MS onset of 28.5?(9.1 [1.1-72.4]) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR,?1.45; 95% CI, 1.15-1.83; ValueValue /th th valign=”top” align=”left” scope=”col” rowspan=”1″ colspan=”1″ IRR (95% CI) /th /thead Overall, 2007-2016Year0.12 (?0.02 to 0.25).091.12 (0.98 to 1 1.29)0.12 (0.01 to 0.24).041.13 (1.00 to 1 1.27)Sex MaleNANANA0.22 (?0.41 to 0.86).491.25 (0.66 to 2.36) FemaleNANANA1 [Reference]1 [Reference]Age group, y 30NANANA?1.19 (?1.95 to ?0.43).0020.30 (0.14 to 0.65) 30-40NANANA1 [Reference]1 [Reference] 40NANANA?0.15 (?0.83 to 0.54).680.86 (0.43 to 1 1.72)Before Risk Stratification, 2007-2012Year0.36 (0.14 to 0.59).0011.44 (1.15 to 1 1.80)0.37 (0.14 to 0.60).0011.45 (1.15 to 1 1.83)Sex MaleNANANA0.10 (?0.77 to 0.98).821.11 (0.46 to 2.65) FemaleNANANA1 [Reference]1 [Reference]Age group, y 30NANANA?1.5927 (?2.7874 to ?0.3981).0090.203 (0.06 to 0.67) 30-40NANANA1 [Reference]1 [Reference] 40NANANA?0.07 (?1.01 to 0.86).880.93 (0.36 to 2.37)After Risk Stratification, 2013-2016Year?0.27 (?0.36 to ?0.18) .0010.76 (0.70 to 0.84)?0.26 (?0.50 to ?0.03).030.77 (0.61 to 0.97)Sex MaleNANANA?0.47 (?0.02 to 0.97).061.60 (0.98 to 2.63) FemaleNANANA1 [Reference]1 [Reference]Age group, y 30NANANA?0.83 (?1.54 to ?0.12).020.44 (0.21 to 0.88) 30-40NANANA1 [Reference]1 [Reference] 40NANANA0.04 (?0.47 to 0.54).891.04 (0.63 to 1 1.71) Open in a separate window Abbreviations: IRR, incidence rate ratio; NA, not applicable. Open in a separate window Figure 3. Poisson Regression Graphical Representation of the Risk of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy (PML) Before and After 2013 By contrast, in the 2013 to 2016 period, the univariate analysis found a statistically significant decrease in the incidence of PML (IRR,?0.76; 95% CI, 0.70-0.84; em P /em ? ?.001), that is, a yearly reduction by 23.6%. This decrease remained statistically significant in the multivariate analysis (IRR,?0.77; 95% CI, 0.61-0.97; em P /em ?=?.03), with a trend toward a more important risk in male patients (IRR,?1.60; 95% CI, 0.98-2.63; em P /em ?=?.06) and a statistically significantly lower risk Lurbinectedin in younger patients (IRR,?0.44; 95% CI, 0.21-0.89; em P /em ?=?.02). Pearson residual analysis and residuals deviance confirmed good quality ( em P /em ?=?.95) and good fit ( em P /em ?=?.79) of the model, with no overdispersion ( em P /em ?=?.99). Conditional Probability of Developing PML by Treatment Duration The probability of developing PML in a time interval, assuming the patient developed no PML before and was still exposed to natalizumab, increased from the second year onward to reach the highest figure in the fourth year of exposure, 6.1 per 1000 patients (95% CI, 3.2-8.99) (Figure 4). The decrease observed thereafter had to be considered with caution, given that CIs were wide, numbers of patients were low, and.