Friday, 1 March 2013

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 na├»ve 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 ...


  1. Last week I had my 1-year MRI and came out with no new disease activity! I'm thrilled, because I'd managed to convince myself that glaterimer couldn't possibly be good enough to keep anyone disease activity free. I thought sure they'd find all kinds of new lesions. Instead, they found significantly shrunken lesions!

    That said, what do you think it really means that those with later disease onset are better responders? That confuses me as I thought older onsetters were actually just closer to secondary progression and not having relapses much anyway. Are they better off or not?

    1. How do they diagnose if a lesion has shrunk?? First time I hear of it.

    2. By shrunken, I mean lesions that appeared large a year ago now appear much smaller or almost gone on the MRI.

    3. Thanks Cat. You seem to have a good neuro if he is willing to look at your MRI in such a detail. My radiologist just looks for new lesions and would not dream of comparing old ones for shrinkage etc. It would be great to have a software available which could count and compare lesions, I can't believe we have ipods but not such a device.

  2. How likely is it that we'll be offered an MRI under the NHS? I haven't had one since dx (10 years) and I am treated at a centre of excellence!

    1. Depends where you are being seen. We now do annual MRIs on all our MSers in DMTs to make a call on whether or not they are responding. The cost of these drugs is substantial so working out who is a responder or not is important.


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