Multiple Sclerosis is not a single pathological entity but rather two abnormal processes that advance in parallel yet inter-connected tracks and varying degrees of severity, which results in different clinical presentations. In the beginning the infiltrative inflammation predominates in the brain and spinal cord with the clinical imprimatur of relapses and remissions. Patients, who are usually young, have the illusion that once the inflammation process subsides, they would be disease-free for a long time.
However, a more sinister and crippling process has already started: degeneration. The clinical picture consists of progression with limiting sequelae like chronic pain and spasticity of upper and lower limbs. The available drugs targeted the first process but failed to address the second one. Until a new drug was studied: siponimod. Like fingolimod, it is a modulator of sphingoside-1-phosphate (SIP) receptors but it only selectively modulates types 1 and 5 receptors of the lymphoid tissue; the first one promotes the disposal of lymphocytes while the second one is stored in the CNS.
Kapos et al. collected more than 1600 patients from almost 300 clinical centers in the USA and Europe to study the administration of 2 mg of sipominod per day to half the cohort to compare it to the other half that only received a placebo for a median period of eighteen months. The principal studied index was “time to three-month confirmed disease progression” (CPD), which was defined as a 1.0 point increase in expanded Disability Status Scale (EDSS) score for the participants with moderate disability or 0.5 point increase for those with severe disability initially.
Only 26% of participants receiving siponimod had grave, prolonged disability compared to 32% of those receiving only the placebo; the drug had a hazard ration of 0.79 and a relative reduction of 21% of the risk to develop crippling symptoms. Once the study was finished all the participants were offered the chance to take it. Imaging studies showed a reduction from baseline in T2 lesion volume and the gadolinium-enhancing lesions. Moreover, those participants taking the drug had less decline in the brain volume between the 12th and 14th months compared to placebo.
Investigators are moderately optimistic about these results, but they point out that, in order to prevent the serious disabilities this disease provokes in young people, they must strive to intervene earlier in progressive forms of MS. Much, much earlier.
What do you think? Please tell us.
Don’t leave me alone.