Siponimod for active secondary progressive multiple sclerosis

Long-term neurological conditions rarely lend themselves to being easily categorised into different syndromes or stages of a particular disease. Multiple sclerosis (MS) is case in point. The standard classification primary progressive (PPMS), relapsing remitting (RRMS) secondary (SPMS) may give the impression that each category well defined and could be confidently diagnosed.1 However, reality MS spectrum with overlapping components two main pathological processes: inflammation degeneration. Many patients present contradictory clinical, radiological and/or biochemical data making it impossible certain under which they should included. From clinical management standpoint, time when RRMS evolves SPMS probably most contentious. As several disease modifying therapies (DMTs) are available for treatment, diagnosing limits DMT options single agent, interferon beta-1b. A recent NICE recommendation siponimod (Mayzent, Novartis) welcome step address difference between pharmacological agents both SPMS.2 Sphingosine 1-phosphate (S1P) one studied lysophospholipids as plays an important role many physiological pathophysiological processes. It exerts its signalling effect through five G protein-coupled receptor (GPCR) subtypes, S1PR1 S1PR5. Fingolimod, ozanimod modulate S1P all three were evaluated DMTs MS.3 Fingolimod acts on S1PR1,3,4,5 receptors; therefore, impact rapid strong leading depletion T lymphocytes resulting reduction their migration CNS subsequent inhibition immunological process underpinning relapses. Siponimod other hand act only S1PR1,5. Such increased selectivity receptors reduces risks adverse side-effects. was licensed US 2019. obtained Europe-wide licence March 2020 recommended by November 2020. active relied results trial, known EXPAND trial.4 In common trials evaluating DMTs, trial outcomes difficult interpret.5 Patients recruited from 31 countries trial. definitions subtypes can differ country other, had examine equivalence trial's subjects establish if conclusions recommendations apply UK practice. specific point method activity established. presented confidential considered commercially sensitive. satisfied evidence efficacy. also added observational extending six years use drug showing usually sustained. Having said that, these did not include control arm part study open label. first oral medication UK. precautions required initiating monitoring drug.6 recommends prescribed neurologist experience including DMT. Before initiation must genotyped CYP2C9 determine metaboliser status. CYP2C9*3*3 genotype, used. CYP2C9*2*3 *1*3 maintenance dosage 1mg taken once daily. genotype 2mg. full course vaccination varicella vaccine antibody-negative prior commencing treatment siponimod, following which, postponed month allow occur. blood count (FBC) (ie within last months after discontinuation therapy) available. Assessments FBC periodically during treatment. Initiation transient decrease heart rate. stringent applied fingolimod needed routinely siponimod. Macular oedema without visual symptoms more frequently reported (1.8%) than placebo (0.2%) phase 3 study. An ophthalmology assessment before Treatment has started titration pack lasts 5 days. starts 0.25mg daily days 1 2, followed once-daily doses 0.5mg day 3, 0.75mg 4, 1.25mg 5, reach patient's dose starting 6. expecting widespread will disappointed. overwhelming majority unlikely fulfil criteria hallmark superimposed relapses diagnosed clinically radiologically (active MRI lesions).7 Most have scanning so extremely activities would established radiologically. therapy hardly transformative, national programme take place pick up lesions such large population. everyday practice, likely scenario meeting indication patient, already DMT, whose seems start evolve SPMS. recommendation, neurologists often faced dilemma treating suspected moving Making diagnosis automatically mean current beta-1b alternative agent. rational continue avoid destabilising relapse putting at risk rebound deterioration. Now, availability feel comfortable another suitable agent treat patients.8 Measuring outcome relatively easy frequency severity reliable drug's impact. Clinical tests measuring progression disability 10 metre walk When using SPMS, tools play prominent Traditional medical practice requires high bar medications used aim slowing down progress long-term conditions. met according NICE. Only tell how enthusiastically embraced community routine No conflicts interest declared.