Contributions
Abstract: P1151
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: The efficacy of Natalizumab (NTZ) and Fingolimod (FGD) in patients with relapsing remitting multiple sclerosis (RRMS) has never been directly compared in randomized clinical trials (RCT). We sought to evaluate the comparative efficacy of NTZ to FGD using data from both eligible placebo-controlled RCTs (indirect meta-analysis) and observational studies (pairwise meta-analysis).
Methods: We calculated odds ratios (ORs) in each study protocol to evaluate the comparison of the reported dichotomous outcomes, while we expressed the unadjusted mean differences of reported continuous outcomes between subgroups as standardized mean differences (SMDs). The mixed-effects model was used to calculate the pooled point estimates in each subgroup and the overall estimates in all occasions. We also compared the baseline characteristics of RRMS patients treated with NTZ or FGD in the corresponding RCTs, and estimated the indirect effect sizes with their corresponding 95%CI.
Results: We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). Baseline characteristic analyses in the included studies suggest that NTZ treated patients had a more aggressive disease profile at baseline (more active lesions on brain MRI) compared to those treated with FGD. In the indirect meta-analysis NTZ was found to be associated with a greater (p=0.005) reduction in the 2-year annualized relapse rate (ARR) compared to FGD (SMDindirect=-0.24; 95%CI:-0.44--0.04), while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect=1.20; 95%CI:0.84-1.71) and those with disability progression (ORindirect= 0.76; 95%CI:0.48-1.21) at 2 years. In the subgroup analysis of observational data no significant differences between NTZ and FGD were found in the 2-year ARR (SMD=-0.05; 95%CI:-0.26-0.16), and disability progression at 1 (OR: 1.37; 95%CI:0.95-1.98) and 2 years (OR: 1.08; 95%CI:0.77-1.52). However, NTZ-treated patients had a higher (p=0.020) probability of remaining relapse-free at 2-years compared to those treated with FGD (OR: 2.19; 95%CI:1.15-4.18). They tended (p=0.09) also to have a higher likelihood to be relapse-free at 1 year (OR:1.61; 95%CI:0.94-2.78).
Conclusion: Randomized and observational data suggest that NTZ is probably more effective than FGD in terms of relapse reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation.
Disclosure:
Dr. Tsivgoulis reports no disclosures
Dr. Katsanos reports no disclosures
Dr Mavridis reports no disclosures
Dr. Grigoriadis reports no disclosures
Dr. Dardiotis reports no disclosures
Dr. Heliopoulos reports no disclosures
Dr Papathanasopoulos reports no disclosures
Dr. Kilidireas reports no disclosures
Dr. Hadjigeorgiou reports no disclosures
Dr. Voumvourakis reports no disclosures
Abstract: P1151
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: The efficacy of Natalizumab (NTZ) and Fingolimod (FGD) in patients with relapsing remitting multiple sclerosis (RRMS) has never been directly compared in randomized clinical trials (RCT). We sought to evaluate the comparative efficacy of NTZ to FGD using data from both eligible placebo-controlled RCTs (indirect meta-analysis) and observational studies (pairwise meta-analysis).
Methods: We calculated odds ratios (ORs) in each study protocol to evaluate the comparison of the reported dichotomous outcomes, while we expressed the unadjusted mean differences of reported continuous outcomes between subgroups as standardized mean differences (SMDs). The mixed-effects model was used to calculate the pooled point estimates in each subgroup and the overall estimates in all occasions. We also compared the baseline characteristics of RRMS patients treated with NTZ or FGD in the corresponding RCTs, and estimated the indirect effect sizes with their corresponding 95%CI.
Results: We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). Baseline characteristic analyses in the included studies suggest that NTZ treated patients had a more aggressive disease profile at baseline (more active lesions on brain MRI) compared to those treated with FGD. In the indirect meta-analysis NTZ was found to be associated with a greater (p=0.005) reduction in the 2-year annualized relapse rate (ARR) compared to FGD (SMDindirect=-0.24; 95%CI:-0.44--0.04), while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect=1.20; 95%CI:0.84-1.71) and those with disability progression (ORindirect= 0.76; 95%CI:0.48-1.21) at 2 years. In the subgroup analysis of observational data no significant differences between NTZ and FGD were found in the 2-year ARR (SMD=-0.05; 95%CI:-0.26-0.16), and disability progression at 1 (OR: 1.37; 95%CI:0.95-1.98) and 2 years (OR: 1.08; 95%CI:0.77-1.52). However, NTZ-treated patients had a higher (p=0.020) probability of remaining relapse-free at 2-years compared to those treated with FGD (OR: 2.19; 95%CI:1.15-4.18). They tended (p=0.09) also to have a higher likelihood to be relapse-free at 1 year (OR:1.61; 95%CI:0.94-2.78).
Conclusion: Randomized and observational data suggest that NTZ is probably more effective than FGD in terms of relapse reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation.
Disclosure:
Dr. Tsivgoulis reports no disclosures
Dr. Katsanos reports no disclosures
Dr Mavridis reports no disclosures
Dr. Grigoriadis reports no disclosures
Dr. Dardiotis reports no disclosures
Dr. Heliopoulos reports no disclosures
Dr Papathanasopoulos reports no disclosures
Dr. Kilidireas reports no disclosures
Dr. Hadjigeorgiou reports no disclosures
Dr. Voumvourakis reports no disclosures