Contributions
Abstract: P1256
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Background: Natalizumab (NTZ) related PML risk is highly variable depending on studied cohorts. By Feb. 2018, the global incidence if of 4.163/1000. However, it is well-known treatment duration and JC index value increase this risk. Recently, we demonstrated in a retrospective study that CD62L could be used as a marker to minimize this risk (< 10% CD62L; HR = 7; sensibility 80% / specificity 85%) (Pignolet et al., 2016). Currently, we do not know if quitting NTZ based on disease duration and JCV index decrease the PML incidence and prospective study have to be perform to validate JCV index as a marker. PML risk also exists with other biologics. By May 2018, the global risk for Fingolimod (FGL) is of 0.082/1000. However, it is likely that in sub-group patients such as those presenting more than 4y of FGL this risk could be increased knowing that mean FGL exposure at PML diagnosis was 50 months (mean range: 18-84 months). Here, the major unmet need is to find prognosis factors in order to prevent FGL-related PML.
Objectives: To determine the observed number vs expected number of PML when applying an algorithm based on JCV index and CD62L to minimize PML risk.
Methods: In 2014, we started a prospective multicentric ancillary study BEST-MS (NTC01981161). The inclusion criteria were the followings NTZ or FGL >18 months, JCV positive, and for NTZ either with JCV index >0.9 or prior immunosuppressor. Treatment was discarded based on physicians decision if JCV index >1.5 or if CD62L < 10 %.
Results: We included 342 patients for NTZ. In BIONAT cohort of NTZ treated patients, the risk with JCV index >0.9 and < 2 years of NTZ was of 3.3%. Thus, 11 PML were expected in BEST-MS study when in NTZ-treated patients. In this NTZ-treated group, only 12% of the patients experienced a low level of CD62L (< 10%). All patients have been switched to another drug. Currently and after a mean follow-up of 23 months, we observed 2 PML when under NTZ. Since we could not calculate the expected number of PML with FGL, this study is exploratory. None of the FGL treated patients experienced a CD62L < 10%. No PML has been observed (mean follow-up 16.4 months (n=52). Influence of delayed infusion on PML risk into the BIONAT and BEST-MS cohorts will be provided.
Conclusion: Combining JCV index and CD62L should decrease the risk of PML and be proposed to physicians for patients who want to go on with NTZ despite a high risk. However, confirmatory studies still need to be performed.
Disclosure: Dr Pignolet, F Bucciarelli, L Scandella, Dr Ciron, Dr Dorcet, Dr Rigal, Dr Robinson, Dr Patry, Dr Montcuquet, Dr Angibaud, Dr Cabrejo, Dr Sablot, Dr Guennoc, Dr Larrieu, Dr Formosa, Dr Elias, Prof Debouverie, Dr Pittion, Dr Rico, : nothing to disclose. OC: consulting and lecture fees, travel grants from biogen, genzyme, novartis, almogran, BB: consultancy fees, speaker fees, research grants (non-personal), or honoraria from Novartis, Biogen-Idec, Merck, Bayer Schering, Roche, Medday, Bayer, Actelion, Teva and Genzyme Sanofi, MC: has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma.,DBi: received speaker honoraria from Teva, Merck, Roche, Biogen, Novartis. NS: has received travel support from Genzyme and Novartis. JP: Consulting fees and travels from Biogen, Sanofi-Genzyme, Novartis, Teva, Merck-Serono, Roche, Medday , CLF: boards for Biogen, Merck, Teva, Medday, Roche, Novartis, DB: received research grant from EU FP7, 305477-2012, EU Marie Curie action 2008 (Co I) ABIRISK (co I), French ministery of health -2008 (PHRC), French MS society 2009, 2012, 2017. Lectures, congress invitation, board participation with Bayer, Biogen, Medday, Merck, Novartis, Roche, Sanofi-Genzyme and Teva..
Abstract: P1256
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Background: Natalizumab (NTZ) related PML risk is highly variable depending on studied cohorts. By Feb. 2018, the global incidence if of 4.163/1000. However, it is well-known treatment duration and JC index value increase this risk. Recently, we demonstrated in a retrospective study that CD62L could be used as a marker to minimize this risk (< 10% CD62L; HR = 7; sensibility 80% / specificity 85%) (Pignolet et al., 2016). Currently, we do not know if quitting NTZ based on disease duration and JCV index decrease the PML incidence and prospective study have to be perform to validate JCV index as a marker. PML risk also exists with other biologics. By May 2018, the global risk for Fingolimod (FGL) is of 0.082/1000. However, it is likely that in sub-group patients such as those presenting more than 4y of FGL this risk could be increased knowing that mean FGL exposure at PML diagnosis was 50 months (mean range: 18-84 months). Here, the major unmet need is to find prognosis factors in order to prevent FGL-related PML.
Objectives: To determine the observed number vs expected number of PML when applying an algorithm based on JCV index and CD62L to minimize PML risk.
Methods: In 2014, we started a prospective multicentric ancillary study BEST-MS (NTC01981161). The inclusion criteria were the followings NTZ or FGL >18 months, JCV positive, and for NTZ either with JCV index >0.9 or prior immunosuppressor. Treatment was discarded based on physicians decision if JCV index >1.5 or if CD62L < 10 %.
Results: We included 342 patients for NTZ. In BIONAT cohort of NTZ treated patients, the risk with JCV index >0.9 and < 2 years of NTZ was of 3.3%. Thus, 11 PML were expected in BEST-MS study when in NTZ-treated patients. In this NTZ-treated group, only 12% of the patients experienced a low level of CD62L (< 10%). All patients have been switched to another drug. Currently and after a mean follow-up of 23 months, we observed 2 PML when under NTZ. Since we could not calculate the expected number of PML with FGL, this study is exploratory. None of the FGL treated patients experienced a CD62L < 10%. No PML has been observed (mean follow-up 16.4 months (n=52). Influence of delayed infusion on PML risk into the BIONAT and BEST-MS cohorts will be provided.
Conclusion: Combining JCV index and CD62L should decrease the risk of PML and be proposed to physicians for patients who want to go on with NTZ despite a high risk. However, confirmatory studies still need to be performed.
Disclosure: Dr Pignolet, F Bucciarelli, L Scandella, Dr Ciron, Dr Dorcet, Dr Rigal, Dr Robinson, Dr Patry, Dr Montcuquet, Dr Angibaud, Dr Cabrejo, Dr Sablot, Dr Guennoc, Dr Larrieu, Dr Formosa, Dr Elias, Prof Debouverie, Dr Pittion, Dr Rico, : nothing to disclose. OC: consulting and lecture fees, travel grants from biogen, genzyme, novartis, almogran, BB: consultancy fees, speaker fees, research grants (non-personal), or honoraria from Novartis, Biogen-Idec, Merck, Bayer Schering, Roche, Medday, Bayer, Actelion, Teva and Genzyme Sanofi, MC: has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma.,DBi: received speaker honoraria from Teva, Merck, Roche, Biogen, Novartis. NS: has received travel support from Genzyme and Novartis. JP: Consulting fees and travels from Biogen, Sanofi-Genzyme, Novartis, Teva, Merck-Serono, Roche, Medday , CLF: boards for Biogen, Merck, Teva, Medday, Roche, Novartis, DB: received research grant from EU FP7, 305477-2012, EU Marie Curie action 2008 (Co I) ABIRISK (co I), French ministery of health -2008 (PHRC), French MS society 2009, 2012, 2017. Lectures, congress invitation, board participation with Bayer, Biogen, Medday, Merck, Novartis, Roche, Sanofi-Genzyme and Teva..