J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2012-303884
  • Cochrane Neurological Field Corner

Secondary progressive multiple sclerosis: a shared therapeutic decision

  1. Peter A G Sandercock3
  1. 1Cochrane Neurological Field, c/o Direzione salute, coesione sociale e società della conoscenza, Regione Umbria Perugia, Italy
  2. 2Department of Neurology, Royal Perth Hospital, Perth, Australia
  3. 3Department of Clinical Neurosciences, Western General Hospital, Edinburgh Neuroscience, Edinburgh, UK
  1. Correspondence to Dr Teresa Anna Cantisani, Cochrane Neurological Field, Perugia, Italy; cochrane.neuronet{at}
  • Received 18 September 2012
  • Accepted 24 September 2012
  • Published Online First 6 December 2012

Over a 15 year period, half of patients with relapsing remitting multiple sclerosis (RR-MS) will develop secondary progressive-multiple sclerosis (SP-MS). Recombinant beta interferons (IFN-β) are well established for relapsing remitting-multiple sclerosis (RR-MS) but often they continue to be used as the first line treatment in the secondary progressive phase of the disease (SP- MS), without good evidence that they reverse or retard the progression of the disease.

There are several reasons why IFN-beta (IFN-β) are used in SP-MS: perception of clinical efficacy of IFN-β in SP-MS, difficulty informing the patient about the worsening of the condition in the progressive phase of the disease, the ‘force of habit’ of the clinician and the patient, and the current absence of therapeutic agents able to significantly change the course of the disease.

The Cochrane Library

Information coming from the literature has until now been in short supply due to the fact that results from the largest trials are conflicting.1 ,2 This leaves the medical community (and patients) confused about the different choices available in a delicate disease like multiple sclerosis (MS). Prognosis is often unpredictable and diagnosis of the progression in the secondary progressive (SP) phase is not an easy task, requiring from 6 months to 1 year of observation.

A support tool for clinicians is provided by the paper ‘Interferon beta for secondary progressive Multiple Sclerosis: a systematic review’,3 an updated and abridged version of a systematic review published in Issue 1, 2012 of the Cochrane Library. The Cochrane Collaboration focuses on the processes involved in the synthesis of qualitative evidence. Applying the Cochrane Collaboration methodology, the review authors searched for randomised controlled trials of interferon β in SP-MS patients. A total of 129 records were identified, of which five studies were considered qualitatively adequate and included in the review. The validity of each study was assessed to emphasise the risk of bias in results, offering readers more complete clinical and methodological tools, while underlining their strengths and weaknesses (the GRADE-approach).4

Meta-analysis of the five trials shows that among 3122 participants who were randomly allocated IFN-β (n=1829) or placebo (n=1293), there was no significant difference in the primary outcome; the number of patients who had 6 months' sustained progression of disability (increase in EDSS>1 point) assessed at 3 years was 1177 (64%) in the interferon group and 849 (69%) controls (risk ratio 0.98, 95% CI: 0.82 to 1.16], p=0.79). There was a significant difference in a secondary outcome; the number of patients who experienced at least one relapse at 3 years was 742 (47%) in the interferon group and 556 (53%) controls (risk ratio: 0.91, 95% CI: 0.84 to 0.97).

The implications of this updated synthesis of the best available evidence for the treatment of SP-MS are four-fold.

The patient with SP-MS needs to be empowered and made aware of the scarce treatment efficacy at this difficult phase of the disease to be able to decide whether to discontinue interferon β and treat any eventual relapse with steroids.

The physician assisting the patient needs to feel confident that the patient could participate in clinical trials for alternative treatment options; offer their expertise and new ideas on how to improve MS care; enhance effective communication time with the patient; and reinforce non-pharmacological evidence-based treatments.5–8

The researcher needs to set up adequate trials with a follow-up phase that is long enough (MS is a chronic disease!) to measure sensible key outcomes like ‘real’ disability, made up of physical deficits and cognitive and psychological ones.

The policy maker could apply a ‘disinvestment process’, withdrawing health care resources from practices that deliver ineffective health care.9


  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.


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