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Migrena je kompleksna nevrološka motnja, za katero je značilen napad v trajanju od 4 do 72 ur, ki ga spremlja zmeren do hud glavobol. Bolezen se najpogosteje pojavlja pri delovno aktivnem prebivalstvu in povzroča veliko breme tako posamezniku kot tudi celotni družbi. Prepoznana vloga peptida, povezanega z genom za kalcitonin (CGRP), kot ključnega mediatorja vpletenega v patofiziologijo migrene, je omogočila sistematično raziskovanje novih možnosti zdravljenja z ugodnimi profili učinkovitosti, varnosti in tolerance. V zadnjih letih so odobritev s strani FDA in EMA dobila štiri monoklonska protitelesa, ki so usmerjena bodisi proti ligandu CGRP (eptinezumab, fremanezumab in galkanezumab) bodisi proti receptorju CGRP (erenumab). Imajo številne ugodne lastnosti, med katere spadajo visoka specifičnost za tarčo, majhna možnost za medsebojno delovanje z drugimi zdravilnimi učinkovinami, dolga razpolovna doba ter dejstvo, da na račun velikosti ne prehajajo krvno-možganske pregrade. V magistrski nalogi smo naredili sistematični pregled raziskav, ki so vrednotile učinkovitost in varnost omenjenih monoklonskih protiteles. Literaturo, ki se je nanašala na postavljeno raziskovalno vprašanje, smo iskali v prosto dostopnih podatkovnih bazah PubMed, ClinicalTrials.gov ter EU Clinical Trials Register. Identificirali smo 22 multicentričnih, randomiziranih, s placebom kontroliranih študij, ki so učinkovitost in varnost vrednotile na polnoletnih bolnikih z bodisi epizodično bodisi kronično migreno. Predstavili smo njihove lastnosti, ocenili tveganje za pristranost in izpisali podatke o učinkovitosti in varnosti. Vsa obravnavana monoklonska protitelesa pri bolnikih z epizodično in kronično migreno statistično značilno zmanjšajo število mesečnih migrenskih dni (MMD) in izzovejo ⡥50 % zmanjšanje MMD glede na izhodiščno vrednost pri signifikantno večjem deležu bolnikov v primerjavi s kontrolno skupino. Dodatno so se erenumab, fremanezumab in galkanezumab izkazala učinkovita pri posameznikih, ki niso imeli odziva na 2-4 predhodna preventivna zdravila. V okviru kliničnih študij so izkazala ugoden varnostni profil v splošnem je bila pojavnost neželenih učinkov med zdravljenimi in kontrolnimi skupinami uravnotežena, najpogosteje pa je šlo za reakcije na mestu injiciranja (za monoklonska protitelesa, ki se dajejo s subkutano injekcijo), okužbe zgornjih dihal, slabost, nazofaringitis in utrujenost. Protitelesa proti učinkovini so se pojavila pri majhnem deležu preiskovancev in niso imela vpliva na učinkovitost in varnost. Migraine is a complex neurological disorder characterized by an attack lasting between 4 and 72 hours that is accompanied by a moderate to severe headache. Migraine is the most common in the working population and causes a lot of burden to an individual as well as to society. The role of a calcitonin gene-related peptide (CGRP) recognized as a key neuromodulator that is involved in the pathophysiology of migraine has enabled systematic research of novel treatment options with good efficacy, safety, and tolerability profiles. Four monoclonal antibodies targeting either CGRP (eptinezumab, fremanezumab, and galcanezumab) or its receptor (erenumab) have been approved by EMA and FDA in recent years. They have numerous favorable characteristics, including high target-specificity, a small possibility for interactions with other medicines, a long half-life, and the fact that they do not cross the blood-brain barrier due to their size. In this master thesis, we have performed a systematic review of the studies, evaluating the efficacy and safety of the mentioned monoclonal antibodies. We have performed a literature search, referring to the research question, in three publicly available databases: PubMed, ClinicalTrials.gov, and EU Clinical Trials Register. We have identified 22 multicentric, randomized, placebo-controlled studies, that have evaluated efficacy and safety in adults, aged ⡥18 years, with a diagnosis of either episodic or chronic migraine. We have summarized included studies’ characteristics, assessed the risk of bias, and written out results on efficacy and safety. All discussed monoclonal antibodies significantly reduce monthly migraine days (MMD) and provoke a ⡥50 % reduction of MMD in a significantly higher proportion of patients compared to a control group. Additionally, erenumab, fremanezumab, and galcanezumab have proven to be efficient in patients in whom two to four previous migraine preventive treatments were unsuccessful. A favorable safety profile has been demonstrated within clinical studies in general, the incidence of adverse events was similar between treated and control groups with the most common adverse events being injection side reactions (for monoclonal antibodies given by subcutaneous injection), upper respiratory tract infections, nausea, nasopharyngitis, and fatigue. The incidence of anti-drug antibodies was small and had no impact on efficacy and safety. |
