Research: predicting response to 1st-line DMTs

#MSBlog: Are you being treated-2-target? If no ask your neurologist why not!

Epub: Romeo et al. Clinical and MRI predictors of response to interferon-beta and glatiramer acetate in relapsing-remitting multiple sclerosis patients. Eur J Neurol. 2013 Feb 20. doi: 10.1111/ene.12119.

BACKGROUND AND PURPOSE: It is still unclear which MSers benefit more from available disease-modifying treatments (DMTs) in multiple sclerosis (MS). The objective of this study was to identify the baseline clinical and magnetic resonance imaging (MRI) predictors of response to first-line DMTs in a cohort of relapsing-remitting (RR) MSers in a real-world clinical setting.

METHODS: Consecutive naïve RRMSers treated with interferon-beta or glatiramer acetate have been included and followed for 2 years. MSers were grouped into responders (R) in case of absence of clinical and MRI activity, and non-responders (NR) if the on-treatment annualized relapse rate (ARR) reduction was < 50% of the ARR in the 2 years before treatment or in the presence of MRI activity (≥ 2 active lesions at 1-year MRI or ≥ 4 active lesions at 1 + 2-year MRI).

RESULTS: At 2-year follow-up, 272 MSers were R (34.6%) and 322 NR (40.9%), and multivariate analysis revealed that a later age at onset of the disease (P < 0.0001), a lower disability (P < 0.0001) and a lower number of gadolinium-enhancing lesions at baseline MRI (P = 0.002) were predictors of efficacy of DMTs. Moreover, the first year response had a good predictive power on the second year, as 73.7% of 1-year R had no evidence of clinical and MRI activity within the ensuing year.

CONCLUSION: A lower baseline MRI and clinical activity have been identified as predictors of DMT efficacy in MSers with RRMS in routine clinical practice. Evaluation of clinical and MRI activity at 1 year is recommended to monitor MSers over time.

"This study supports other findings that not everyone responds to first-line DMTs and if they don't  they need to be switched or escalated to more effective treatments. This is what I have been referring to as treat-to-target; i.e. the target being NEDA (no evidence of disease activity) (see algorithm below). The problem is that a lot of people in the field fuel therapeutic nihilism by extraoplating the natural history data that suggests clinical relapses and MRI activity are poor predictors of long-term disability. Therefore they claim it makes little difference if you have disease activity or not because the acquisition of disability is a different process. This position is incorrect, misleading and resulting in the mismanagement of many MSers; the studies that these nihilists refer to were done in the pre-DMT era. Relapses and ongoing MRI activity on DMTs is a different story and is associated with a poor prognosis; in other words if you are on a DMT and you have relapses or ongoing MRI activity you are much more times likely to become disabled in the future compared to MSers who are on a DMT and have no relapses and MRI activity.

"What surprised me in our recent poll on NEDA is how few MSers are being treated-2-target. We are planning to hold a meeting in the UK to address this issue; may be we can convince more neurologists to be more aggressive in their approach to treating MSers with active disease."


"This algorithm is still a work in progress and will be updated and embedded in a website to allow MSers to negotiate their way around it. Any further comments would be appreciated."



12 Feb 2013
At present NEDA is defined using a composite of a) no relapses, or b) no EDSS progression, or c) no MRI activity (new or enlarging T2 lesions or no Gd-enhancing lesions) (Havrdova, Galetta et al. 2009; Giovannoni, Cook et ...
08 Jan 2013
Treat-2-Target: NEDA (no evidence of disease activity). "I would appreciate your comments on the following beta version of a treatment or monitoring algorithm for relapsing MSers. The idea is to adopt the strategy of ...

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