Welcome Address and ECTRIMS LectureThursday, October 03, 2013, 09:20 - 10:05
ECTRIMS lectureG. Comi (Milan, IT)
Early treatment of multiple sclerosis
The importance of early treatment in multiple sclerosis (MS) is definitely accepted as the key factor in the relapsing MS. Many studies have revealed that the amount of inflammatory activity in the early phase of MS predict the time to reach disease milestones, such as onset of the progressive phase, EDSS 3/4 and brain atrophy. On the contrary the clinical and MRI signs of inflammatory activity have much less predictive value if observed in established MS and during the progressive phase of the disease. This is probably the major reason why treatments targeting inflammation (all treatments available today!) have a decreased efficacy during the advanced relapsing phase and during the progressive phase of MS.
From a pathological angle, one can argue that axonal damage starts very early in the course of the disease. Likewise, inflammatory activity in relapsing-remitting MS is not restricted to episodes of clinical impairment, but typically starts before an initial clinical relapse which has led to the concept of "clinically absent syndrome" and generally continuous during remission. Moreover, the immune-mediated processes that underline MS becomes more compartmentalised in the CNS, driven by pathogenetic mechanisms which are quite different from those dominating the relapsing phase of the disease.
Patients with a first event suggestive of MS (also called: clinically isolated syndrome (CIS)) and an abnormal MRI scan have a high risk of developing MS. The risk is particularly elevated in the first six months following the first attack and is modulated by many factors revealed by epidemiological studies and 7 phase III clinical trials performed in CIS patients. Results of these clinical trials will be reviewed and predictive factors will be analysed. The 2010 revision of the McDonald criteria allow for a quicker diagnosis in many of CIS patients and have implications on the decision to start treatment. Since many alternatives now exist for treatment of CIS patients the various algorithms will be discussed and the benefit to risk profile of individual treatments will be presented.
Extension studies of CIS clinical trials have confirmed the long term benefit of early treatment in preventing the conversion to clinically definite MS and some data emerged also in the prevention of disability accumulation. From studies in relapsing-remitting MS, we already have evidence that late treatment initiation or low-dose regimens do not seem to match the benefit of early, high-dose therapy, at least over an observation period of four years (PRISMS Study, 2001). However, now it has been shown that this concept is already applicable at the stage when patients display the first signs of MS, which underline the urgent need to treat patients rather early than wait for further MS signs to develop.
More recently the problem of the so called radiologically isolated syndromes (RIS), a very bad and confusing definition, has emerged, opening the possibility to consider a disease modifying therapy even before the first clinical attack. If treat or not, at least some RIS cases are now the new frontier of early treatment.
In the past two years, I have received honorarium for speaking and consultancy activities from Novartis, Teva, Sanofi, Genzyme, Merck Serono, Biogen, Bayer, Actelion, Almirall and Serono Symposia International Foundation.