Sažetak | Cilj istraživanja: Cilj je bio prikupiti i analizirati epidemiološke i podatke o kliničkom tijeku bolesti pacijenata liječenih u Klinici za neurologiju KBC Split na prijelazu u sekundarno progresivni oblik multiple skleroze i usporedba tih podataka s otprije poznatim rezultatima kliničkim istraživanjima kliničkog tijeka bolesti i liječenja te utvrđenim prediktivnim čimbenicima vezanim uz sekundarnu progresiju.
Materijal i metode: Izvršeno je retrospektivno presječno istraživanje. Izdvojeni su pacijenti (n = 69) hospitalizirani u razdoblju 2007.-2013. s utvrđenom dijagnozom relapsno-remitentne multiple skleroze kojma je tijekom hospitalizacije ili naknadnim praćenjem utvrđen prijelaz u sekundarno progresivnu multiplu sklerozu. Obrađeni su podaci iz povijesti bolesti o spolu, vrsti i trajanju imunomodulacijskog liječenja, starosti na početku bolesti, trajanju bolesti do prijelaza u sekundarnu progresiju, starosti na prijelazu te EDSS rezultatu. Posebna pažnja pridana je skupini pacijenata koji nisu primali nikakav oblik imunomodulacijske terapije zbog bolje reprezentativnosti u razmatranju prirodnog kliničkog tijeka bolesti.
Rezultati: Najčešće primjenjivani imunomodulacijski lijekovi bili su interferon-β (96.6%) i glatiramer acetat (17.2%). Ostali korišteni lijekovi su fingolimod, alemtuzumab, mitoksantron i azatioprin. Medijan trajanja liječenja bio je 3 godine. Prosjek starosti na početku bolesti bio je 34.7 (SD 11.9) godina. Medijan trajanja bolesti do sekundarne progresije u ukupnom uzorku bolesnika u SPMS bio je 11 (25% - 6, 75% - 15) godina, a među pacijentima bez imunomodulacijskog liječenja 11.5 (25% - 6, 75% - 18) godina. Najdulje trajanje bolesti do progresije imali su pacijenti s početkom bolesti unutar prva 3 desetljeća života (medijan 20 i 18 godina), a nakon 50. godine je medijan trajanja do SPMS pao na 7,5 godina i nakon 60. godine na 5 godina. Trajanje bolesti do progresije bilo je statistički značajno kraće, za 8 godina, kod muškaraca u odnosu na žene u skupini neliječenih pacijenata. Između pacijenata koji su primali imunomodulacijsku terapiju i onih koji nisu nije pronađena značajna razlika u vremenu trajanja bolesti do progresije. Prosječna starost na prijelazu u ukupnom uzorku bila je 46.5 (SD 10.6), a 51 (SD 9.5) kod pacijenata bez imunomodulacijske terapije. Nije pronađena značajna razlika u starosti na prijelazu među spolovima, dok su neliječeni pacijenti prosječno u starijoj dobi, za 10.6 godina, prelazili u SPMS. Medijan EDSS na prijelazu u progresiju bio je 4,5, a 65.2% pacijenata je imalo raspon EDSS 4-5. Nije uočena značajna razlika u EDSS među spolovima, skupinama po liječenju ni početku trajanja bolesti.
Zaključak: Trajanje bolesti do sekundarne progresije među izdvojenim pacijentima bilo je za medijan od 2.5 godina dulje od onog u usporedivim studijama kliničkog tijeka bolesti. Značajna razlika u trajanju bolesti pronađena je među spolovima, s kraćim trajanjem kod muškaraca, te u skupinama prema starosti na nastupu bolesti, pogotovo u skupinama iznad 40. godine. Starost na prijelazu bila je prosječno 51g kod neliječenih pacijenata i u gornjim granicama prijašnjih usporedivih rezultata. Najčešće korišteni lijekovi u terapiji bili su interferon-β i glatiramer acetat, a medijan trajanja liječenja 3 godine. Značajna razlika među liječenim i neliječenim pacijentima primijećena je na starosti nastupa i progresije što je vjerojatno odraz kriterija za primjenu terapije koji isključuju najstarije pacijente. EDSS rezultat bio je u 2/3 slučajeva u rasponu 4-5 s medijanom od 4,5. Nije bilo značajnih razlika u EDSS među uspoređivanim skupinama. Rezultati su indikativni za moguće čimbenike rizika u kliničkom tijeku bolesti i mogu služiti kao osnova za buduća, veća, istraživanja kliničkog tijeka bolesti na razini Klinike i države. |
Sažetak (engleski) | Objectives: The objective was to gather and analyse epidemiological data and data on clinical course of patients treated on Clinic of neurology of KBC Split on the onset of secondary progression of multiple sclerosis and comparison with previously known resulsts and data from clinical studies of natural history and treatment of multiple sclerosis and the established prediction factors of secondary progression.
Patients and Methods: A retrospective cross-section study was conducted. Patients (n=69) were included from the medical documentation of Clinic of neurology. The criteria of inclusion were hospitalization during 2007.-2013., previous diagnosis of relapsing remitting multiple sclerosis and secondary progression established during the course of hospital stay or on their follow-up. Data on gender, type and duration of immunomodulatory treatment, age at desease onset, duration of the disease before progression, age at onset of progression and EDSS score. Special consideration was given to the subgroup of patients who recieved no immunomodulatory treatment as they are more representive of natural course of the disease.
Results: The most frequently used immunomodulatory drugs were interferon-β (96.6%) and glatiramer acetate (17.2%). Other used drugs were fingolamid, alemtuzumab, mitoksantron and azatioprin. The median of duration of immunomodulatory treatment was 3 years before progression onset. The average age of onset was 34.7 (SD 11.9) years. The median age of duration of the diease before progression was 11 (25% - 6, 75% - 15) years in the entire sample and 11.5 (25% - 6, 75% - 18) years among patients with no immunomodulatory treatment. The duration before progression was among patients with age at onset in first 3 decades (median 20 and 18 years) and after 60. year the median fell to 7,5 years from 50-60 and 5 years after 60 years. Disease duration before progression among untreated patients was singnificantly, by median of 8 years, shorter in males than females. No significant difference was fount in disease duration between patients treated and untreated with imunomodulatory drugs. Average age at progression onset was 46.5 (SD 10.6) years in the entire sample and 51 (SD 9.5) years among untreated patients. No significant difference was found in age at onset of progression between genders, and a significant lower age at progression onset by an average of 10.6 years among patients treated with immunomodulatory drugs. Median of EDSS score at onset of progression was 4,5 and 65.2% of patients had a score in the range of 4-5. No significant difference in EDSS score was noticed between genders, groups by treatment or by age at onset.
Conclusion: Disease duration before secondary progression among selected patients was for a median of 2,5 years longer than the one in comparable data in previous natural history studies. There was a significatly shorter duration of the disease among males and in group of pages with a later age at disease onset, especially after 40 years of life. The average age at progression onset was 51 years among patients untreated with immunomodulators which is near the upper limit of the range in comparable data form previous studies. Immunomodulators mostly used were interferon-β and glatiramer acetate and the medain time of treatment was 3 years. There was a significant difference in age at disease and progression onset between treated and untreated patient which is probably due to inclusion criteria in immunomodulatory treatment that excludes the patient among oldest at onset. EDSS score in 2/3 of cases was in the range of 4-5 with a median of 4,5. There was no significant difference in EDSS score between compared subgroups. These results are indicative of possible prediction factors in the clinical course of multiple sclerosis and my be used as a baseline for further, larger, multiple sclerosis natural history and treatment studies nationwide. |