| Abstract | Cilj istraživanja: Cilj ovog rada je pregledom dostupne i relevantne literature istražiti koje su
to imunorekonstitucijske terapije te njihove mehanizme djelovanja u liječenju multiple
skleroze, istražiti pozicioniranje ove terapije u algoritmu liječenja multiple skleroze te prednosti
i nedostatke u odnosu na druge postojeće terapije za određeni profil bolesnika.
Materijali i metode: Pri izradi ovog preglednog rada napravljen je sustavni pregled relevantne
znanstvene i stručne literature s naglaskom na znanstvene članke s podacima iz svakodnevne
kliničke prakse i službene smjernice hrvatskih i svjetskih stručnih društava. Tijekom
istraživanja korištene su ključne riječi i pojmovi MS treatment algorithm, immune
reconstitution therapy in MS, induction therapy, escalation therapy, mechanism of action for
immune reconstitution therapy (IRT) in MS, disease – modifying therapies (DMTs), smjernice
za liječenja multiple skleroze.
Rezultati: Imunorekonstitucijska terapija je jedna od mogućnosti liječenja multiple skleroze,
čiji se mehanizam djelovanja temelji na redukciji, repopulaciji i rekonstituciji imunološkog
sustava, aplicira se u kratkom vremenskom intervalu, a učinci koje postiže u liječenju MS su
dugoročni. Dio je eskalacijskog i indukcijskog pristupa liječenju te se može sekvencijalno
aplicirati. Uz visoku učinkovitost IRT karakteriziraju nuspojave kao što su odgođena
sekundarna autoimunost, limfopenije i herpes zoster. Prema preporukama spomenutim u ovom
radu, najviše koristi od primjene IRT u liječenju MS imat će bolesnice koje planiraju trudnoću,
bolesnici koji imaju agresivan početak bolesti te sami žele jednu od ovih terapija jer tako
zahtjeva njihov životni stil.
Zaključak: Iako imaju različite mehanizme djelovanja, IRT dovode do kvalitativnih i
kvantitativnih promjena u stanicama imunološkog sustava te time djeluju na smanjenje
aktivnosti MS. U algoritmu liječenja RRMS IRT se primjenjuje nakon progresije bolesti unatoč
liječenju nekom od DMT umjerene učinkovitosti (eskalacijski pristup) ili odmah po
postavljanju dijagnoze visoko aktivne bolesti s lošim prognostičkim faktorima (indukcijski
pristup). IRT su vrijedna visokoučinkovita terapijska opcija liječenja MS, mogu se sekvencijski
aplicirati, potrebno je dugoročno pratiti pacijente kako bi se smanjio rizik od nastanka
nuspojava. Ne postoje usporedne studije učinkovitosti isigurnosti ovih terapija,stoga su podatci
iz svakodnevne kliničke prakse iznimno vrijedni te su potrebne dodatne retrospektivne studije
kako bi se bolje odredile sličnosti i razlike ovih terapija. |
| Abstract (english) | Objectives: The aim of this review paper is to investigate definition of immune reconstitution
therapies and their mechanisms of action in the of multiple sclerosis treatment, to investigate
the positioning of this therapy in the multiple sclerosis treatment algorithm and the advantages
and disadvantages versus other existing therapies for a specific patient profile, by reviewing the
available and relevant literature.
Materials and methods: During the preparation of this review paper, a systematic and
retrospective review of the relevant scientific and professional literature was made,
emphasizing scientific articles with real world evidence and official guidelines of Croatian and
international professional societies. During the research, key words and terms were used: MS
treatment algorithm, immune reconstitution therapy in MS, induction therapy, escalation
therapy, mechanism of action for immune reconstitution therapy (IRT) in MS, disease –
modifying therapies (DMTs), guidelines for the treatment of multiple sclerosis.
Results: Immune reconstitution therapy is one of the treatment options for multiple sclerosis,
which mechanism of action is based on the reduction, repopulation, and reconstitution of the
immune system, it is applied in a short time interval but achieves long-term efficacy. It is part
of the escalation and induction treatment approach and can be administered sequentially. In
addition to high efficacy, IRT is characterized by side effects such as delayed secondary
autoimmunity, lymphopenia, and herpes zoster. According to the recommendations mentioned
in this paper, the most benefit from the use of IRT in the treatment of MS will have patients
who plan to become pregnant, patients who have an aggressive onset of the disease and want
one of these therapies because their lifestyle demands it.
Conclusion: Despite different mechanisms of action, IRT leads to qualitative and quantitative
changes in the cells of the immune system. In the RRMS treatment algorithm, IRT is applied
after disease progression despite treatment with one of the moderately effective DMTs
(escalation approach) or immediately after the diagnosis of highly active disease with poor
prognostic factors (induction approach). IRTs are a valuable highly effective therapeutic option
for the MS treatment, they can be applied sequentially, it requires long term patient monitoring
to reduce the risk of side effects. There are no efficacy and safety comparative studies, therefore
data from daily clinical practice are extremely valuable and additional retrospective studies are
needed to determine the similarities and differences between these therapies. |
