The study below shows treating-2-target finaling getting traction in the real-world. Interestingly when you treat to target NEDA rates increase substantially. Why? One of the criticisms is that NEDA is very difficult to attain and several data sets have shown that NEDA rates are low. The reason why NEDA rates were low is because all these data were collected in an era when we weren’t treating to a target; in other words people failing on a DMT, or with a suboptimal response, were left on their DMT. However, by treating to a target you are enriching for responders on a DMT and if someone is not responding you switch/escalate them to another DMT. By doing this you keep increasing the proportion of pwMS who are NEDA on a particular drug.
The next development that has to enter the field is rebaselining. Not all people understand the need for rebaselining. This means that you exclude the period of time when the drug is not fully effective; with most DMTs this is first 3-6 months; the exceptions being glatiramer acetate (9 months) and PIRTS (pulsed immune reconstitution therapies) when you rebaseline after the treatment period, for example with alemtuzumab and cladribine this will be at 24 months.
Surprise, surprise in the study below natalizumab and fingolimod or more effective at rendering pwMS NEDA than the injectables (interferon-beta and glatiramer acetate) and natalizumab has the edge over fingolimod. These hierarchy of efficacy is what you would expect from pivotal clinical trial results.
Prosperini et al. Real-world effectiveness of natalizumab and fingolimod compared with self-injectable drugs in non-responders and in treatment-naïve patients with multiple sclerosis.
J Neurol. 2016 Nov 22. [Epub ahead of print]
Background: In this independent, multicentre post-marketing study we directly compared the effectiveness of natalizumab (NTZ), fingolimod (FNG) and self-injectable drugs (INJ), in non-responders to first immunomodulating treatment and in highly active treatment-naïve patients with multiple sclerosis.
Methods: As main outcome measure we considered the proportions of patients with no evidence of disease activity (NEDA-3), defined as absence of relapses, disability worsening and radiological activity. A total of 567 non-responders to interferon beta (IFNB) or glatiramer acetate (GA) [dataset A] and 216 highly active treatment-naïves [dataset B] were followed up to 24 months from the beginning of NTZ, FNG or INJ, i.e. switching from IFNB to GA or viceversa (in the case of non-responders) or starting high-dose IFNB (in the case of highly active treatment-naïves). Propensity score matching in a 1:1:1 ratio was used to select only patients with similar baseline characteristics, retaining 330 and 120 patients in dataset A and B, respectively.
Results: In dataset A, the 24-month proportion with NEDA-3 was greater in both NTZ group (67%) and FNG group (42%) than in INJ group (35%) (p ≤ 0.016); however, NTZ was superior to FNG in promoting the attainment of NEDA-3 status (p = 0.034). In dataset B, the 24-month proportion with NEDA-3 was greater in NTZ group (75%) and FNG group (67%) than in INJ group (40%), but the small cohort sizes most likely prevented the detection of any statistically significant difference.
Conclusion: Our study provides real-world evidence that NTZ was more effective than both FNG and INJ in non-responders, while it could seem that, in highly active treatment-naïves, NTZ was as effective as FNG and both were superior to INJ.