Correction: The short-term prognosis of very late onset generalized myasthenia gravis: a single-center retrospective cohort study

Le résumé fourni par la source

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by muscular weakness with distinctive fluctuation of symptoms and fatiguability. Considerable phenotypic and biological heterogeneity exists, with researchers and clinicians classifying patients with MG by autoantibody profiles and/or the presence of thymic pathology and/or the isolated involvement of extraocular muscles and/or the age of symptom onset [1]. Epidemiologic studies report a bimodal incidence with two discrete peaks, one in young adults around the age of 30 years (consistent with the typical high frequency of autoimmune disorders in young women) and one in older adults after the age of 50 years [2]. Of note, more recent evidence suggests that the age of MG onset has been significantly altered with an increasingly growing occurrence in individuals older than 65 years [3]. Within this group, incidence rates surge at the first half of the 8 th decade of life and men are predominantly affected, as opposed to the typical female preponderance of early-onset MG (eoMG) [3,4].Based on the age of symptom onset, MG is typically classified as juvenile (onset before 18 years of age) and adult-onset MG [5]. The latter group is further divided into early-onset (eoMG, 18-50) and lateonset MG (loMG, >50 years of age) [6]. Lately, due to the phenotypic and biological differences of MG occurring above the age of 65, a new MG subgroup is widely recognized; very late-onset MG (vloMG, >65 years of age) [7]. In turn, according to the age of onset, adult-onset MG is predominantly categorized as eoMG (18-50 years), loMG (50-65 years) and vloMG (>65 years). Considering their distinctive presentations, the operationalization of these age categories is very important in clinical practice and research. The use of alternative age cut-offs hinders standardized research, conduction of replication studies and data synthesis [8,9].Regarding the phenotypic and biological heterogeneity among and between vloMG, loMG and eoMG, it has been reported that ocular MG and male predominance are more frequent in the vloMG and loMG groups [3,7,10]. The presence of anti-acetylcholine receptor antibodies (AchR Abs) is more common in those with vloMG, whereas thymus hyperplasia and thymoma are less common [3,7,10]. Of course, the biological differences are anticipated to introduce additional heterogeneity in the clinical course and treatment responses of vloMG in relation to eoMG and loMG (eloMG).To date, only a few studies have investigated the short-term prognosis of generalized vloMG. Only one focused on the onset of generalized vloMG and found a more severe, potentially more life-threatening onset [7]. Several reports support that similar or better clinical outcomes compared to eloMG may be achieved at follow-up, often using lower doses or fewer immunosuppressants [7,11,12]. On the other hand, conflicting evidence occasionally suggests that individuals with generalized vloMG show worse clinical courses, poorer therapeutic responses and greater dependency on immunosuppressive agents [3,13]. Apart from these inconsistencies, the literature also presents several important methodological drawbacks that limit the value and generalizability of published evidence. The overwhelming majority of published studies performed cross-sectional, unadjusted analyses, occasionally without including an appropriate eloMG group [3,7,12,[14][15][16]. Cross-sectional studies do not consider the different monitoring periods of the participants and/or the potential clinical fluctuations over the course of the follow-up. In the case of clinically labile conditions such as MG, it is inappropriate to utilize single (often the last) assessments as prognostic outcomes. Unadjusted analyses fail to account for the well-established biological differences between vloMG and eloMG and capture if a fraction of the variability can be explained by known biological differences. Instead, several researchers have partially addressed this issue by performing subgroup analyses based on immunological profiles and/or thymus pathology; again, this approach may provide some evidence about between group differences but cannot confirm with certainty and quantify these differences.As for studies not involving a proper eloMG comparator, they are not fit to explore the prognosis of vloMG and reveal if vloMG has a relatively more benign prognosis than eloMG.Therefore, the aim in undertaking the current study was to shed additional light on the short-term prognosis of the generalized vloMG in comparison with eloMG. For this purpose, we conducted a singlecenter retrospective cohort study. The onset and early 2-year clinical course of generalized vloMG and eloMG were compared. To account for the methodological pitfalls of previous research, our longitudinal investigations took repeated assessments per individual into account. Both unadjusted and adjusted analyses were performed, to determine between group differences and determine if at least part of the variability can be explained by the well-established biological differences between vloMG and eloMG.The present single-center retrospective cohort conforms with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guidelines for observational studies [17]. The study protocol was approved by the Ethics Committee of the University of Patras (4129 /09-02-2023).The current study was based on the medical records of patients with generalized MG who are followed and Data were collected on: age of symptom onset, age of diagnosis, time interval between symptom onset and diagnosis, sex, antibody profile, presence of thymus pathology (thymoma or hyperplasia) and time of surgical removal, predominant symptoms at onset (ocular, bulbar, respiratory, generalized weakness or combination), rescue therapy within 1 month from diagnosis, intubation within 1 month from diagnosis, duration of follow-up, rescue therapies at follow-up (>1 month from diagnosis), QMG scores at baseline and follow-up, MGFA at baseline and follow-up, as well as corticosteroid intake (in equivalent doses of prednisolone, in mg) and rituximab (RTX) or other non-steroidal immunosuppressive therapies (NSITs, azathioprine, mycophenolate mofetil and methotrexate) intake over the follow-up (time of onset and treatment duration).According to MGFA, participants were dichotomized in two groups: moderate/high MGFA status (MGFA ≥IIb, predominant weakness -even mild-in oropharyngeal and/or respiratory muscles; in case of predominant limb and/or axial symptoms, at least moderate weakness) and mild MGFA status (MGFA <IIb, any ocular weakness ±mild weakness predominantly affecting limb and/or axial muscles) [18]. This classification was based on our experience that patients' expectations are generally satisfied/met when achieving an MGFA <IIb. According to the QMG score, relapses at follow-up were defined as an increase of QMG score by ≥3 from 1 or more items and a total QMG score ≥6 [19]. At last (recent) follow-up, the post-intervention status (PIS) achieved was classified as minimal manifestation status or better, improved, unchanged or worse.Eligible individuals with generalized MG diagnosed by or referred immediately to (within 3 months from diagnosis) the Unit of Neuromuscular Disorders and the Neurology Department of the University Hospital of Patras were enrolled. The maximum follow-up period for our study was set at 24 months. Therefore, we capitalized on baseline and follow-up visits within the first 2 years of the MG course. Patients with MG are typically evaluated on approximately 3-month intervals, over the first 24 months, in our specialized Unit.Depending on loss at follow-up, the follow-up period ranged between 3 and 24 months per participant.During the follow-up visits, serial clinical assessments involve the QMG (relapses are defined based on this), MGFA categorization and medication intake (dosage of steroid and o

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.