Contributions
Abstract: EP1529
Type: ePoster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: The short-term safety profile for dimethyl fumarate (DMF) in the phase 3 trials was highly favorable and long-term data from ENDORSE study confirmed a good benefit/risk ratio. However, the most frequent adverse events (AEs) in patients receiving DMF include flushing, gastrointestinal (GI) events, leukopenia and lymphopenia.
Objective: To improve management strategies in clinical setting, we tried to correlate demographic and anthropometric measures to the most common safety and tolerability issues in a cohort of 100 relapsing remitting Multiple Sclerosis (RRMS) patients treated with oral DMF 120 mg BID for 7 days, and then increased to 240 mg BID.
Methods: At the time of the first prescription, anthropometric measures were performed for all patients. Lymphocyte and leukocyte counts at baseline (T0) and after 3 (T3), 6 (T6) and 12 months (T12) of therapy were assessed by flow cytometry method. The observation period was 9.24±5 months. Any AEs were reported immediately upon the occurrence or during the follow-up.
Results: In our cohort, 60% were female. The mean age at DMF beginning was 38 ± 11 years. The mean Body Mass Index (BMI) was 23.54±4.38. Among our patients 46% experienced GI side effects (that in 4 cases lead to the drug discontinuation), and 53 % flushing. The multivariate analysis showed that a lower BMI (p< 0.001) and a younger age at DMF (p=0.049) were related with a higher incidence of GI events, while a higher BMI was related with a higher incidence in flushing (p=0.048). In our setting 40% of patients showed leukopenia and 68% lymphopenia. Compared with the T0 values, we observed statistically significant reduction of 10% in leukocytes (p=0.001 ; 6352.37±3062.78 vs 6010.34±19543) and of 28% in total lymphocytes (p< 0.001; 1932.25±619 vs 1397±613) at T3; this reduction was stable at subsequent follow-ups. Finally, a lower BMI at baseline (p=0.029) appeared a predictive factor for leucopenia, while T0 values of lymphocytes were related to the occurrence of lymphopenia(p=0.047).
Conclusion: Considering the safety profile of DMF, in a tailored therapeutic scenario, clinicians should evaluate also baseline demographic and anthropometric characteristics of MS patients. Further studies in larger cohorts will be necessary to confirm these findings and to evaluate strategies aimed to increase DMF tolerance.
Disclosure: Dr Paolicelli received honoraria for consultancy and/or speaking from Biogen Idec, Merck-Serono, Sanofi- Aventis, TEVA, Novartis and Genzyme. Dr Manni, Iaffaldano, Zoccolella and Di Lecce: nothing to disclose. Dr Tortorella has served on scientific advisory boards for Biogen, Merck Serono, Bayer-Schering and Novartis. She received also funding for travel, consulting and speaker honoraria from Biogen, Merck Serono, Bayer-Schering, Teva, Genzyme, Novartis and Almirall. Dr Iaffaldano has served on scientific advisory boards for Biogen Idec, and has received funding for travel and/or speaker honoraria from Sanofi-Aventis, Biogen Idec, Teva and Novartis. Dr Trojano has received honoraria for consultancy or speaking from Biogen, Sanofi-Aventis, Merck Serono and Bayer-Schering and research grants from Merck Serono, Biogen and Novartis.
Abstract: EP1529
Type: ePoster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: The short-term safety profile for dimethyl fumarate (DMF) in the phase 3 trials was highly favorable and long-term data from ENDORSE study confirmed a good benefit/risk ratio. However, the most frequent adverse events (AEs) in patients receiving DMF include flushing, gastrointestinal (GI) events, leukopenia and lymphopenia.
Objective: To improve management strategies in clinical setting, we tried to correlate demographic and anthropometric measures to the most common safety and tolerability issues in a cohort of 100 relapsing remitting Multiple Sclerosis (RRMS) patients treated with oral DMF 120 mg BID for 7 days, and then increased to 240 mg BID.
Methods: At the time of the first prescription, anthropometric measures were performed for all patients. Lymphocyte and leukocyte counts at baseline (T0) and after 3 (T3), 6 (T6) and 12 months (T12) of therapy were assessed by flow cytometry method. The observation period was 9.24±5 months. Any AEs were reported immediately upon the occurrence or during the follow-up.
Results: In our cohort, 60% were female. The mean age at DMF beginning was 38 ± 11 years. The mean Body Mass Index (BMI) was 23.54±4.38. Among our patients 46% experienced GI side effects (that in 4 cases lead to the drug discontinuation), and 53 % flushing. The multivariate analysis showed that a lower BMI (p< 0.001) and a younger age at DMF (p=0.049) were related with a higher incidence of GI events, while a higher BMI was related with a higher incidence in flushing (p=0.048). In our setting 40% of patients showed leukopenia and 68% lymphopenia. Compared with the T0 values, we observed statistically significant reduction of 10% in leukocytes (p=0.001 ; 6352.37±3062.78 vs 6010.34±19543) and of 28% in total lymphocytes (p< 0.001; 1932.25±619 vs 1397±613) at T3; this reduction was stable at subsequent follow-ups. Finally, a lower BMI at baseline (p=0.029) appeared a predictive factor for leucopenia, while T0 values of lymphocytes were related to the occurrence of lymphopenia(p=0.047).
Conclusion: Considering the safety profile of DMF, in a tailored therapeutic scenario, clinicians should evaluate also baseline demographic and anthropometric characteristics of MS patients. Further studies in larger cohorts will be necessary to confirm these findings and to evaluate strategies aimed to increase DMF tolerance.
Disclosure: Dr Paolicelli received honoraria for consultancy and/or speaking from Biogen Idec, Merck-Serono, Sanofi- Aventis, TEVA, Novartis and Genzyme. Dr Manni, Iaffaldano, Zoccolella and Di Lecce: nothing to disclose. Dr Tortorella has served on scientific advisory boards for Biogen, Merck Serono, Bayer-Schering and Novartis. She received also funding for travel, consulting and speaker honoraria from Biogen, Merck Serono, Bayer-Schering, Teva, Genzyme, Novartis and Almirall. Dr Iaffaldano has served on scientific advisory boards for Biogen Idec, and has received funding for travel and/or speaker honoraria from Sanofi-Aventis, Biogen Idec, Teva and Novartis. Dr Trojano has received honoraria for consultancy or speaking from Biogen, Sanofi-Aventis, Merck Serono and Bayer-Schering and research grants from Merck Serono, Biogen and Novartis.