Background: Few data exist concerning conversion to secondary progressive MS in patients treated with disease-modifying therapies. Objective: Determine the proportion of alemtuzumab-treated patients converting from relapsing-remitting to secondary progressive MS during the CARE-MS core and extension studies. Methods: Patients (N = 811) were analyzed post hoc for secondary progressive MS conversion. Optimal conversion definition: Expanded Disability Status Scale (EDSS) score ≥4, pyramidal functional system score ≥2, and confirmed progression over ≥3 months including confirmation within the functional system leading to progression, independent of relapse. Results: Over 6.2 years median follow-up, 20 alemtuzumab-treated patients converted (Kaplan-Meier estimate, 2.7%; 95% confidence interval, 1.8%-4.2%). Sensitivity analysis accounting for dropouts showed similar results (3%), as did analyses using alternative definitions with different EDSS thresholds and/or confirmation periods, and analysis of core study subcutaneous interferon beta-1a-treated patients who received alemtuzumab in the extension. Patients converting to secondary progressive MS were older, and had higher EDSS scores and greater brain lesion volumes at baseline, but did not need additional alemtuzumab or other therapies. Conclusions: The 6-year conversion rate to secondary progressive MS was low for alemtuzumab-treated patients, supporting further study of the role alemtuzumab may play in reducing risk of secondary progression.ClinicalTrials.gov identifiers: NCT00530348, NCT00548405, NCT00930553.

• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348). METHODS: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs). RESULTS: Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0-5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2-4, remaining low in year 5 (years 1-5: -0.59%, -0.25%, -0.19%, -0.15%, and -0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined. CONCLUSIONS: Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses. CLINICALTRIALSGOV IDENTIFIER: NCT00530348; NCT00930553. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.

• MeSH
• časové faktory MeSH
• humanizované monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• imunologické faktory škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• mozek diagnostické zobrazování   účinky léků   MeSH
• následné studie MeSH
• posuzování pracovní neschopnosti MeSH
• relabující-remitující roztroušená skleróza diagnostické zobrazování   farmakoterapie   MeSH
• velikost orgánu MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Reduced MS disease activity with alemtuzumab versus subcutaneous interferon beta-1a (SC IFNB-1a) in core phase 2/3 studies was accompanied by increased incidence of infections that were mainly nonserious and responsive to treatment. Alemtuzumab efficacy was durable over 6 years. OBJECTIVE: To evaluate infections over 6 years in alemtuzumab-treated patients. METHODS: Three randomized trials (CAMMS223, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I, and CARE-MS II) compared two courses of alemtuzumab 12 mg with SC IFNB-1a 44 μg in patients with active relapsing-remitting MS. An extension study (CAMMS03409) provided further evaluation and as-needed alemtuzumab retreatment. RESULTS: Infections occurred more frequently with alemtuzumab 12 mg than SC IFNB-1a during Years 1 (58.7% vs 41.3%) and 2 (52.6% vs 37.7%), but declined for alemtuzumab-treated patients in Years 3 (46.6%), 4 (42.8%), 5 (40.9%), and 6 (38.1%). Serious infections were uncommon (1.0%-1.9% per year). Infections were predominantly (>95%) mild to moderate and included upper respiratory tract infections, urinary tract infections, and mucocutaneous herpetic infections. Prophylactic acyclovir reduced herpetic infections. Lymphocyte counts after alemtuzumab therapy did not predict infection risk. CONCLUSION: Infections with alemtuzumab were mostly mild to moderate and decreased over time, consistent with preservation of components of protective immunity.

• MeSH
• alemtuzumab škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• dospělí MeSH
• humanizované monoklonální protilátky škodlivé účinky   MeSH
• infekce MeSH
• interferon beta 1a aplikace a dávkování   MeSH
• lidé MeSH
• náchylnost k nemoci MeSH
• recidiva MeSH
• rizikové faktory MeSH
• roztroušená skleróza farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

U žádné těhotné ženy s pozitivními anti-b-2-GPI nebyly kromě ACA nalezeny pozitivníprotilátky proti ostatním fosfolipidům. Nebyla prokázána statisticky významná korelace meziACA a anti-b-2-GPI ve třídě IgG ani ve třídě IgM. Z 39 vzorků bylo 66 % ACA IgG pozitivních, alezároveň negativních na anti-b-2-GPI, pouze 8 % bylo pozitivních na ACA i na anti b-2-GPI IgG. Veskupině ACA-IgG negativních vzorků pouze jeden (3 %) vykazoval zvýšený titr anti-b-2-GPI-IgG.Ve třídě IgM byla prokázána pouze u jedné ACA negativní ženy pozitivita na anti-b-2-GPI. Naopakani jedna z 5 pacientek, u nichž byly přítomné ACA IgM protilátky, nevykazovala zvýšený titranti-b-2-GPI. Ve 2. trimestru byl zaznamenán ve srovnání s 1. trimestrem statisticky významnýpokles hladin ACA ve třídě IgG (p = 0,0141). Rozdíl hladin ACA IgM a anti-b-2-GPI IgG a IgM ve 2.trimestru nebyl statisticky významný. Hladiny fetoplacentárních antigenů u těhotných s pozitiv-ními anti-b-2-GPI byly v normě.Závěr: Ve studii nebyla prokázána korelace mezi ACA a anti-b-2-GPI. Výsledky naznačují, že sezřejmě jedná o dvě subpopulace autoprotilátek.

Objective: It is accepted now that most antiphospoholipid antibodies (APA) are not directedagainst phospholipids alone but complexes of phospholipid-binding proteins and phospholipids.One of the phospholipid-binding proteins is b2 -glycoprotein I (b2 -GPI), a normal plasma glycopro-tein, which under physiological conditions binds with negative charged phospholipids. Measure-ment of anti-b2 -GPI antibodies requires specific tests, since ELISA for determination ofanticardiolipin antibodies (ACA) may detect both antibodies directly binding cardiolipin andantibodies against cardiolipin-binding proteins. In this study a comparison of APAs against cardi-olipin (CL), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylethanolamine (PE)v.s. anti-b2 -GPI were compared.Setting: First Institute of Medical Chemistry and Biochemistry, First Medical Faculty, CharlesUniversity and Institute for Care of Mother and Child.Design: Retrospective clinical study using stored sera for determination of APA.Methods: One hundred twenty four women in the first and the second trimester, who undergobiochemical prenatal screening for chromosomal disorders by maternal serum alpha-fetoprotein(MS AFP), human chorionic gonadotrophin (MS HCG) and trophoblast-specific b1 -glycoprotein(MS SP1) were studied. In serum samples antibodies against CL, PS, PE, PI (isotype IgG and IgM)were examined by solid ELISA. 19 women who were positive at least for one type of APAs wereselected and in the serum samples the levels of anti-b2 -GPI were measured.Results: No pregnant woman with anti-b2 -GPI had positive antibodies against other phospholipidsexcept CL. There was no significant correlation between levels of ACA IgG and IgM v.s. anti-b 2 -GPI IgG and IgM. Eight percent of serum samples were positive for both anti-b2 -GPI IgG and ACAIgG. In the second trimester a statistically significant decrease of ACA IgG was found (p = 0.014).The difference of ACA IgM and anti-b 2 -GPI IgG and IgM was not statistically significant. Levels offoetoplacental antigens in anti-b2 -GPI positive pregnant women were normal.Conclusion: A correlation between anti-b2 -GPI antibodies and ACA was not found in our study.Anti-b2 -GPI antibodies and ACA may be two different subpopulations of APA.

• MeSH
• antifosfolipidové protilátky analýza   krev   MeSH
• dospělí MeSH
• glykoproteiny analýza   imunologie   krev   MeSH
• lidé MeSH
• prenatální diagnóza MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

BACKGROUND: Alemtuzumab is an effective therapy for relapsing multiple sclerosis. Autoimmune thyroid events are a common adverse event. OBJECTIVE: Describe endocrine and multiple sclerosis outcomes over 6 years for alemtuzumab-treated relapsing multiple sclerosis patients in the phase 3 CARE-MS I, II, and extension studies who experienced adverse thyroid events. METHODS: Endocrine and multiple sclerosis outcomes were evaluated over 6 years. Thyroid event cases, excluding those pre-existing or occurring after Year 6, were adjudicated retrospectively by expert endocrinologists independently of the sponsor and investigators. RESULTS: Thyroid events were reported for 378/811 (46.6%) alemtuzumab-treated patients. Following adjudication, endocrinologists reached consensus on 286 cases (75.7%). Of these, 39.5% were adjudicated to Graves' disease, 2.5% Hashimoto's disease switching to hyperthyroidism, 15.4% Hashimoto's disease, 4.9% Graves' disease switching to hypothyroidism, 10.1% transient thyroiditis, and 27.6% with uncertain diagnosis; inclusion of anti-thyroid antibody status reduced the number of uncertain diagnoses. Multiple sclerosis outcomes of those with and without thyroid events were similar. CONCLUSION: Adjudicated thyroid events occurring over 6 years for alemtuzumab-treated relapsing multiple sclerosis patients were primarily autoimmune. Thyroid events were considered manageable and did not affect disease course. Thyroid autoimmunity is a common but manageable adverse event in alemtuzumab-treated relapsing multiple sclerosis patients.ClinicalTrials.gov Registration Numbers: CARE-MS I (NCT00530348); CARE-MS II (NCT00548405); CARE-MS Extension (NCT00930553).

• Publikační typ
• časopisecké články MeSH

Background: In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline. Methods: Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2. SC IFNB-1a patients who entered the extension discontinued SC IFNB-1a and received 2 alemtuzumab 12 mg courses (IFN-alemtuzumab), followed by additional, as-needed, alemtuzumab. Results: Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy, with lasting suppression of disease activity, improved disability, and slowing of brain volume loss (BVL). In CARE-MS I patients (treatment-naive; less disability; shorter disease duration), disease activity and BVL were significantly reduced in IFN-alemtuzumab patients, similar to alemtuzumab-only patients at year 6. Among CARE-MS II patients (inadequate response to prior treatment; more disability; longer disease duration), alemtuzumab significantly improved clinical and magnetic resonance imaging outcomes, including BVL, in IFN-alemtuzumab patients; however, disability outcomes were less favorable versus alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups. Conclusion: This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups. ClinicalTrialsgov identifiers: NCT00530348; NCT00548405; NCT00930553.

• Publikační typ
• časopisecké články MeSH

Cíl studie:Zjistit, zda kombinace preemptivního podání ketaminu a morfinu je účinnější, než když je jedna látka podána preemptivně a druhá látka až po chirurgické stimulaci. Typ studie:Prospektivní zaslepená randomizovaná klinická studie. Název a sídlo pracoviště: Univerzita Karlova v Praze, 3. lékařská fakulta, Klinika anesteziologie a resuscitace. Materiál a metody: Celkem 63 pacientek indikovaných k abdominální hysterektomii bylo náhodně rozděleno na 3 shodné soubory: s preemptivním podáním ketaminu (K), preemptivním podáním morfinu (M) a preemptivně podanou kombinací obou látek (MK). V premedikaci byl všem skupinám podán pouze atropin a diazepam. Skupině K byl před úvodem do celkové anestezie (CA) aplikován i. v. ketamin 0,6 mg . kg-1 t. h. + fyziologický roztok (FR) a 10 minut po provedení laparotomie morfin 0,1 mg . kg-1 t. h. Skupině M byl aplikován i. v. morfin 0,1 mg . kg-1 + FR před úvodem a 10 minut po provedení laparotomie ketamin 0,6 mg . kg-1 t. h. a skupině MK byl aplikován před úvodem do celkové anestezie ketamin 0,6 mg . kg-1 t. h. + morfin 0,1 mg . kg-1 i. v. a 10 minut po provedení laparotomie fyziologický roztok. Vlastní průběh celkové anestezie i per- a pooperační monitorování byly stejné a standardní u všech skupin. Sledovanými parametry byla pooperační spotřeba morfinu aplikovaného samoobslužným způsobem (PCA). Výsledky:Pacientky ve skupině M měly v průměru vyšší hmotnost a pacientky ve skupině MK byly starší (obě p < 0,05), ale tento rozdíl nebyl pro výsledky podstatný. Pooperační spotřeba morfinu byla v prvních 24 hodinách ve skupině MK významně nižší než ve skupině M, resp. K (22,6 ± 7 mg vs 30,2 ± 12,1; p < 0,05, resp. 34,1 ± 12,1; p < 0,001) i během dalších 24 hodin po operaci. Nižší spotřeba byla i během dalších 24 hodin ve skupině MK vs M, resp. K (13,3 ± 5,4 mg vs 20,1 ± 9 mg, resp. 22,0 ± 10 mg, obě p < 0,01). Ani v jednom sledovaném intervalu nebyl statisticky významný rozdíl ve spotřebě morfinu mezi skupinami K a M. V žádném případě nedošlo k nedostatečné analgezii (hodnoceno verbálně i monitorováním pokusů o aplikaci morfinu v intervalu kratším než nastaveném). Závěr: Preemptivně podaná kombinace ketaminu a morfinu vede k významně nižší spotřebě morfinu pooperačně, než pokud jsou obě látky podány preemptivně každá zvlášť.

Objective:To assess if a pre-emptive combination of morphine and ketamine is more effective than if one drug is administered before surgery and the second one after a surgical stimulation. Design: Prospective single-blinded randomized clinical study. Setting:Charles University, Prague, 3rd Medical Faculty, Dept. of Anaesthesiology and Intensive Care. Material and Method:A total of 63 women scheduled for abdominal hysterectomy were randomly divided in three equal groups. Only atropine and diazepam were used for premedication. The group K was administered ketamine 0.6 mg . kg-1 + normal saline (NS) i. v. before induction to general anaesthesia (GA) and morphine 0.1 mg . kg-1 10 minutes after laparotomy, the group M was administered morphine 0.1 mg.kg-1 + NS before induction to GA and ketamine 0.6 mg . kg-110 minutes after laparotomy and the group MK was administered ketamine 0.6 mg . kg-1 + morphine 0.1 mg . kg-1 i. v. before induction to GA and normal saline 10 minutes after laparotomy. GA and monitoring were performed in a standard way. Post surgery morphine consumption during first and second 24 hours was measured using patient controlled analgesia. Results: The morphine consumption during the first 24 hours post surgery was in MK significantly lower then in M, resp. K (22.6 ± 7 mg vs. 30.2 ± 12.1; P < 0.05, resp. 34.1 ± 12.1; P < 0.001). The morphine consumption was lower also during the second 24 hours post surgery in MK vs. M resp. K (13.3 ± 5.4 mg vs. 20.1 ± 9 mg, resp. 22.0 ± 10 mg, both P < 0.01). There were no significant differences in morphine consumption between M and K in any measured interval. There was no case of an insufficient analgesia in any group.Conclusion: The combination of the pre-emptive ketamine and morphine administration causes better post-operative analgesia (measured by the morphine consumption after surgery), then when one drug is used before surgery and the other one after surgical stimulus.

• MeSH
• analgezie metody   MeSH
• dospělí MeSH
• finanční podpora výzkumu jako téma MeSH
• hysterektomie metody   MeSH
• ketamin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• morfin aplikace a dávkování   farmakokinetika   škodlivé účinky   MeSH
• pooperační bolest farmakoterapie   MeSH
• předoperační péče metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

• MeSH
• autoprotilátky krev   imunologie   MeSH
• COVID-19 imunologie   mortalita   MeSH
• dítě MeSH
• dospělí MeSH
• imunoglobulin G krev   imunologie   MeSH
• interferon alfa imunologie   MeSH
• interferon typ I imunologie   MeSH
• kojenec MeSH
• kritický stav MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neutralizující protilátky krev   imunologie   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

BACKGROUND: A high-quality research identifying the best physiotherapeutic approach for the improvement of balance in people with multiple sclerosis is missing. This study compared aspects of balance improvement such as therapy specificity to balance, therapy method and category, country, intensity and medical conditions. METHODS: A multicentric randomised rater-blinded controlled trial comprised three different physiotherapy programs (Czech and Italian outpatient or inpatient programs). All patients received 20 therapy sessions. Experimental group underwent balance specific physiotherapy (it was Motor Program Activating Therapy in the Czech cohort and Sensory-motor Integration Training in the Italian cohort), control group underwent non-balance specific physiotherapy (it was Vojta reflex locomotion in the Czech cohort and conventional dynamic strengthening exercises in the Italian cohort, respectively). Static balance was evaluated by Berg Balance Scale and dynamic balance was assessed by Timed Up-and-Go Test. RESULTS: A total of 149 patients entered the study. Physiotherapy significantly improved static balance (p < 0.0001, increase by mean 2.6 points (95% confidence interval 2.0-3.5) in BBS score). Balance specific approach had a higher effect than non-specific balance approach (increase in BBS by 1.9 points, 95% confidence interval 0.9-3.7 points). The intensity of the physiotherapy significantly influenced static balance (BBS by 2.7 points higher in the inpatient setting, p= 0.007). Dynamic balance was also improved (TUG decrease by -0.8 s (95% CI -1.4 - -0.1s, p = 0.011)); the balance specificity had no impact. The level of disability played the most important role (p= 0.022). CONCLUSION: Although the overall changes in static and dynamic balance were statistically significant, they were quite small in a clinical sense. A small statistically significant difference between balance specific and non-specific treatment was found. It seems that a high intensity of the therapy is critical to maximize the effectiveness.

• MeSH
• dospělí MeSH
• jednoduchá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• posturální rovnováha fyziologie   MeSH
• prospektivní studie MeSH
• roztroušená skleróza rehabilitace   MeSH
• senioři MeSH
• terapie cvičením metody   MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4-6 years after disease onset. METHODS: In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0-2 years (early) or 4-6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0-10, with higher scores indicating increased disability), at 6-10 years after disease onset, assessed with a linear mixed-effects model. FINDINGS: We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7-8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p<0·0001). This difference persisted throughout each year of follow-up until the tenth year after disease onset (mean EDSS score 2·3 [SD 1·8] vs 3·5 [SD 2·1]; p<0·0001), with a difference between groups of -0·98 (95% CI -1·51 to -0·45; p<0·0001, adjusted for proportion of time on any disease-modifying therapy) across the 6-10 year follow-up period. INTERPRETATION: High-efficacy therapy commenced within 2 years of disease onset is associated with less disability after 6-10 years than when commenced later in the disease course. This finding can inform decisions regarding optimal sequence and timing of multiple sclerosis therapy. FUNDING: National Health and Medical Research Council Australia and MS Society UK.

• MeSH
• čas zasáhnout při rozvinutí nemoci MeSH
• databáze faktografické MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• posuzování pracovní neschopnosti MeSH
• registrace MeSH
• retrospektivní studie MeSH
• roztroušená skleróza terapie   MeSH
• tendenční skóre MeSH
• věk při počátku nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Švédsko MeSH