Friday, 30 December 2016

Fingol against Nataliziumab...and the Winner is....

A longitudinal real-life comparison study of natalizumab and fingolimod.Lanzillo R, Carotenuto A, Moccia M, SaccĂ  F, Russo CV, Massarelli M, De Rosa A, Brescia Morra V.
Acta Neurol Scand. 2016 Dec 15. doi: 10.1111/ane.12718. [Epub ahead of print]

BACKGROUND:Different retrospective studies compared natalizumab and fingolimod in relapsing-remitting multiple sclerosis (RRMS), with conflicting results. We aimed to explore the prescriptive attitude and the clinical outcome of the two therapies.
METHODS:We retrospectively included all RRMS patients treated with natalizumab (n=101) or fingolimod (n=78) as their first second-line therapy with at least 24-month follow-up. Demographic and clinical features were recorded to calculate the propensity score (PS). Outcomes of interest were annualized relapse rate (ARR), risk of relapse, and change in the EDSS RESULTS: At baseline, natalizumab patients were younger and had a shorter disease duration, a higher number of relapse in 1 year (1yR) and 2 years (2yR) and overall (ARR-PT) pretherapy, compared to fingolimod patients. On therapy, the proportion of relapsing patients and the mean RR were similar in the two groups. However, the change in the ARR was higher in natalizumab than in fingolimod group (P<.002), but, using PS as a covariate, it was comparable (P=.960). Similarly, the change in EDSS was significantly different for the two groups (P<.004), but not after adjusting for the PS (P=.321).
CONCLUSION:We observed a comparable efficacy on ARR reduction and on EDSS progression with natalizumab and fingolimod correcting through PS, suggesting that the efficacy difference observed before correction might derive from the clinical attitude in prescribing natalizumab in more active MS patients in real life.

Tsivgoulis G, Katsanos AH, Mavridis D, Grigoriadis N, Dardiotis E, Heliopoulos I, Papathanasopoulos P, Karapanayiotides T, Kilidireas C, Hadjigeorgiou GM, Voumvourakis K; HELANI (Hellenic Academy of Neuroimmunology). The Efficacy of Natalizumab versus Fingolimod for Patients with Relapsing-Remitting Multiple Sclerosis: A Systematic Review, Indirect Evidence from Randomized Placebo-Controlled Trials and Meta-Analysis of Observational Head-to-Head Trials. PLoS One. 2016; 11(9):e0163296

BACKGROUND:Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT).
METHODS AND FINDINGS: We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95% CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect = 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95% CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95% CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95% CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95% CI: from 1.15 to 4.18; p = z0.020).
CONCLUSIONS: Indirect analyses of RCT data and head-to-head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation.

You have been asking for comparisons of different drugs, but it cant be horses for courses because it is clear that efficacy is not top of the list otherwise we would not be going to the CRAB drugs. However, it is a balancee between efficacy, conveninece, safety etc etc etc. In this study they try and compare fingolimod and come to the conclusion that natalizumab is abit more efficacious. This is not a head to head, and companies are never going to do this exept when it is a no-brainer e.g. they put a new drug against beta interferon, like alemtuzumab and oceliziumab and it is obvious that the latter two are better than the CRAB drugs. However it can backfire, look at laquinimod verses beta interferon...oooops. Academics want to do these studies, but they cost too much  to do. The funders say is this a good use of our limited resource and the answer is usually no. Maybe the regulators should insist that drugs are compared to current best practise, but then we may get no new drugs as to show your new drug is better than a good drug is going to mean the studies are very large...and costly.

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