Multiple Sclerosis (MS) is a chronic, progressive and debilitating disease that places a high burden on young patients and on society. Being disability the main contributor to the burden of MS, the reduction of its progressive accumulation is a major running objective in MS care.
Nowadays, several clinical tests have high sensitivity to evaluate disability in progressive MS (PMS). Expanded Disability Status Scale (EDSS) is the most well know clinical measure, though with some limitations. Other measures, such as Multiple Sclerosis Functional Composite (MSFC) or Brief International Cognitive Assessment for MS (BICAMS), are usually combined with EDSS and contribute to increase the informativeness of PMS evaluation.
In 2011 an original efficacy outcome, Clinical Disability Improvement (CDI - defined as at least 1-point EDSS score decrease sustained for 6 months, in patients with baseline score ¿ 2.0) was used in several studies as a measure to evaluate the efficacy of recent therapies to improve pre-existing disability.
The aim of our study is to evaluate if Siponimod, a selective sphingosine-1-phosphate receptor modulator, recently approved for Secondary Progressive MS (SPMS), can reach CDI. This outcome measure will be integrated by the other motor and cognitive scales (MSFC, BICAMS) to evaluate its effects against disability accumulation, and by some Patient Reported Outcomes (PROs), to evaluate also patient perceptions. To this aim, we will carry out a real-world study, controlled-group, on SPMS patients consecutively referred to our MS Clinic with approved indications for Siponimod treatment. Over a 2 years-period of follow-up we will apply the above scales at two time points, 0 and 12 months. This study may contribute to both extend and refine the clinical evaluation of PMS patients, and to explore new outcome measures dealing with disability changes.
The current trend of increased attention to PMS, and to therapeutic approaches capable of acting as DMT also in this phase of the disease, urges new outcome measures to be easily applicable in clinical practice. This exploratory study based on a multi-test approach will be useful to understand whether and how the metrics already used in RRMS may be used in PMS patients.
On the other hand, the demonstration of improvement at the disability status scales implies an action of the drug under scrutiny on the neurodegenerative component of the pathogenetic loop. This may be very useful to provide hints on both the drug¿s mechanism of action and new, not-yet-known, pathogenetic processes that lead to tissue damage and disability.
Last, but not least, the use of PROs will contribute to the implementation of these outcome measures in the clinical trials and in the clinical practice for the management of PMS.
-Jones JL, Anderson JM, Phuah CL, Fox EJ, Selmaj K, Margolin D, Lake SL, Palmer J, Thompson SJ, Wilkins A, Webber DJ, Compston DA, Coles AJ. Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity. Brain. 2010 Aug;133(Pt 8):2232-47. doi: 10.1093/brain/awq176. Epub 2010 Jul 21.