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PubMed2026

Big data in multiple sclerosis.

PURPOSE OF REVIEW: This review summarizes recent key advancements in multiple sclerosis (MS) achieved through the utilization of big data from diverse sources and advanced analytical techniques. RECENT FINDINGS: Real-world evidence (RWE) derived from MS big data has significantly enhanced treatment strategies, redefined the concept of disease progression, refined prognostic models, and facilitated personalized medicine. RWE has highlighted the long-term benefits of early intensive treatment compared to escalation strategies, the unfavorable risk profile associated with treatment de-escalation and the importance of managing treatments during pregnancy. Additionally, it has revealed similarities and differences in the effectiveness and safety of specific high-efficacy therapies, as well as key predictors for switching treatments. RWE has also emphasized the central role of progression independent of relapse activity as a significant driver of disability and predictor of unfavorable long-term outcomes in both adult and pediatric onset MS. A data-driven approach utilizing artificial intelligence and big data has established a comprehensive framework for understanding the disease's evolution. Multimodal big data frameworks - encompassing clinical data, MRI, genomics, biomarkers, and app-based metrics - have demonstrated their ability to enhance diagnostic performance and risk stratification in MS. SUMMARY: Big data approaches are transforming MS research and clinical practice by providing stronger RWE to guide therapeutic decision-making, refining models of disease progression, and developing more precise prognostic tools.

Humans↗

PubMed2026

Sutimlimab for cold agglutinin disease: an updated perspective from approval to real-world clinical treatment.

INTRODUCTION: Sutimlimab, a classical complement pathway (CP) inhibitor, was approved in 2022 in the US, EU, and Japan for the treatment of cold agglutinin disease (CAD), a rare form of autoimmune hemolytic anemia (AIHA) characterized by CP‑mediated extravascular hemolysis and circulatory symptoms related to IgM‑mediated red blood cell (RBC) agglutination. This review reexamines the clinical trial data and compares those findings with published real‑world experience (RWE), providing clinicians with efficacy and safety data that extend beyond the clinical trial experience in this rare AIHA. AREAS COVERED: The first-in-human trials, the two seminal clinical trials (CARDINAL and CADENZA), and the published post‑marketing RWE are presented. Literature searches for CAD and sutimlimab were conducted in PubMed and in abstracts from ASH and EHA from 2016 to present. All articles and abstracts regarding sutimlimab and CAD were included. EXPERT OPINION: Long-term data from clinical trials and published RWE support the safety and efficacy of sutimlimab. Targeting the CP as primary therapy for CAD offers a unique, targeted management strategy that minimizes exposure to immunosuppressive regimens. The rapid onset of sutimlimab's activity provides a potentially lifesaving treatment option in situations where immediate control of hemolysis is critical. Opportunities remain to increase our understanding of the role of complement inhibition combined with immunosuppressive therapy in CAD. The impact of complement inhibition on morbidity and mortality in CAD remains to be determined.

Humans↗

PubMed2026

GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. OBJECTIVE: This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid® platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). RESULTS: From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I2 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. CONCLUSIONS: This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings.

Journal Article↗

PubMed2026

Pegcetacoplan Delivers Real-World Therapeutic Benefits and Reduces Disease Burden for Patients With Paroxysmal Nocturnal Haemoglobinuria: A Systematic Literature Review of Pegcetacoplan Real-World Clinical and Patient-Reported Outcomes.

AIMS: Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, acquired, non-malignant haematological disorder that, if left untreated, can lead to significant morbidity. This systematic literature review (SLR) summarized real-world evidence (RWE) for pegcetacoplan, a complement 3/3b inhibitor (C3i) available since 2021. METHODS: The SLR (PROSPERO-CRD420251043506) followed 2020 PRISMA guidelines and included RW studies of pegcetacoplan (n > 1 pts.; English; to April 2025) in adults (age ≥ 18 years) with PNH. RESULTS: Of 409 identified records, 39 qualified, representing 12 distinct studies. Six studies (n = 4-39) reported median haemoglobin (Hb) with baseline 8.1-9.6 g/dL. Ending median Hb and maximum pegcetacoplan durations were: 12.0 g/dL at 12 months, 11.1-12.1 g/dL at 6 months (3 studies), and 11.1 g/dL at 3 months (1 study). In 4 other studies (n = 48-70), ending mean Hb (maximum pegcetacoplan duration) was: 11.3 g/dL (7.2 months), 11.5 g/dL (6.6 months), 11.5 g/dL (5.9 months), and 11.58 g/dL (3 months). Six studies reported reduced absolute reticulocyte count (ARC; n = 4-39) from baseline median 155-301 × 109/L to median 56-106 × 109/L from 14 days of pegcetacoplan, maintained to maximum pegcetacoplan of 1-12 months. Three studies reported lactate dehydrogenase (LDH; n = 4-62); all showed reductions from baseline median 543.0 to 161.7 U/L after 3 months, and baseline median 299.5-316.0 U/L to 193.5-187.0 U/L after 6 months of pegcetacoplan. In complement 5 inhibitor-naïve, LDH reduced from 977.8 to 358.9 U/L after 8.4 months, and 503.6 to 292.5 U/L in C5i-experienced after 7.2 months. Three studies (n = 4-63) reported reduced LDH from above the upper limit of normal levels. Six studies (n = 23-70) reported reduced red blood cell transfusions (RBCt) after maximum pegcetacoplan durations of up to 12 months, and median durations of 3.0 and 10.2 months. Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale scores in 1 study increased from baseline (mean 28.4) to 38.6 at 3 months, 36.3 at 6 months, and 34.9 at 9 months of pegcetacoplan treatment. Two studies reported FACIT-Fatigue scores of 34.6-40.1 with pegcetacoplan for ≥ 1 month. EQ-5D mean utility scores (0.85-0.94) in 2 studies were comparable to population normative values. On the Short-Form 36 Health Survey, mental and physical component scores were slightly lower than US normative values. CONCLUSIONS: RWE indicates pegcetacoplan is associated with improved haematological outcomes, reduced RBCt dependence and fatigue, and enhanced HRQoL. These findings from real-world studies with diverse cohorts support generalizability and are broadly comparable with clinical trial evidence.

Humans↗

PubMed2026

Enhancing Evidence Generation by Linking Randomized Clinical Trials to Real-World Data: The INVESTED-Medicare Linkage Study.

Real-world evidence (RWE) derived from real-world data (RWD) can complement randomized controlled trials (RCTs), yet the validity of RWD relative to RCT data remains insufficiently characterized. We obtained post hoc consent and linked individual participant data from the US-based INVESTED trial (2016-2019) with Medicare fee-for-service claims (2012-2020) to validate demographic factors, baseline characteristics (using 183-, 365-, and 730-day lookback periods) and outcomes, and to assess post-trial events. Among 5260 trial participants, 126 were enrolled and eligible for linkage. Among 115 participants with demographic information available from Medicare enrollment files, agreement between RCT- and RWD-based demographic factors was high: only one major age discrepancy, 100% agreement for sex, and an overall agreement of 0.89 for race. Participants with Medicare claims data (n = 65) were older and more likely to be White compared with the overall RCT population. For the 365-day lookback period, baseline comorbidities showed high sensitivity (median 0.80) and specificity (0.89), as did medication use (sensitivity 1.00, specificity 0.88). Lengthening the lookback period to 730 days increased sensitivity but decreased specificity, whereas shortening to 183 days decreased sensitivity but increased specificity. Clinical outcomes showed high specificity (0.88-0.94) but low sensitivity (0.18-0.50). Among those with Medicare coverage beyond the trial end date (n = 45), 22% experienced cardiopulmonary, 18% cardiovascular, and 7% heart failure (HF) hospitalizations, highlighting the value of RWD for extending RCT evidence. Proactive planning of future RCT-RWD linkage initiatives can improve the efficiency of linkage studies, leading to more actionable results.

Journal Article↗

PubMed2024

Mass Spectrometry-Based Proteomics for Assessing Epitranscriptomic Regulations.

Epitranscriptomics is a rapidly evolving field that explores chemical modifications in RNA and how they contribute to dynamic and reversible regulations of gene expression. These modifications, for example, N6-methyladenosine (m6A), are crucial in various RNA metabolic processes, including splicing, stability, subcellular localization, and translation efficiency of mRNAs. Mass spectrometry-based proteomics has become an indispensable tool in unraveling the complexities of epitranscriptomics, offering high-throughput, precise protein identification, and accurate quantification of differential protein expression. Over the past two decades, advances in mass spectrometry, including the improvement of high-resolution mass spectrometers and innovative sample preparation methods, have allowed researchers to perform in-depth analyses of epitranscriptomic regulations. This review focuses on the applications of bottom-up proteomics in the field of epitranscriptomics, particularly in identifying and quantifying epitranscriptomic reader, writer, and eraser (RWE) proteins and in characterizing their functions, posttranslational modifications, and interactions with other proteins. Together, by leveraging modern proteomics, researchers can gain deep insights into the intricate regulatory networks of RNA modifications, advancing fundamental biology, and fostering potential therapeutic applications.

Proteomics↗

PubMed2025

Real-world frontline treatments in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions and adjusted comparisons versus amivantamab plus chemotherapy from the PAPILLON study.

INTRODUCTION: In PAPILLON, frontline amivantamab + carboplatin + pemetrexed (ACP) demonstrated superior efficacy over carboplatin + pemetrexed in patients with advanced or metastatic non-small-cell lung cancer (aNSCLC) harboring mutations in epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins). Real-world (RW) treatment patterns and comparative effectiveness of ACP versus RW treatments are unknown. MATERIALS AND METHODS: The present study (NECTAR) retrospectively analyzed frontline treatments prescribed 2012-2023 for patients with aNSCLC and confirmed EGFR exon20ins from English (ENG-NCRD), French (FR-ESME), and US (US-COTA and US-ConcertAI) datasets. Overall survival (OS), time to next treatment (TTNT), and progression-free survival (PFS) were assessed in RW pooled and individual treatment classes and in indirect treatment comparisons (ITC) between ACP from PAPILLON and RW treatments using Cox proportional hazards model adjusted for prognostic factors. RESULTS: NECTAR assessed 208 RW patients: ENG-NCRD, n = 23; FR-ESME, n = 91; US-COTA, n = 39, and US-ConcertAI, n = 55. Common frontline treatment classes were platinum-based chemotherapy (33.7 %), platinum + immunotherapy (23.1 %), EGFR tyrosine kinase inhibitors (TKIs) alone (15.4 %), platinum + VEGF inhibitors (VEGFi) (11.1 %), and immunotherapy alone (7.7 %). Compared with platinum-based chemotherapy, none of the evaluated treatment classes demonstrated improved OS, TTNT, and PFS. Exceptions were platinum + VEGFi in TTNT and PFS and platinum + immunotherapy in TTNT. In ITCs, ACP significantly improved OS over pooled RW treatments (HR = 0.48 [95 % CI, 0.32-0.71]; P < 0.001), platinum-based chemotherapy (HR = 0.48 [0.30-0.77]; P = 0.003), platinum + immunotherapy (HR = 0.41 [0.23-0.73]; P = 0.003), and EGFR TKI alone (HR = 0.48 [0.23-1.02]; P = 0.055). TTNT and PFS results were similar to OS. CONCLUSIONS: In patients with EGFR exon20ins aNSCLC, frontline ACP was superior to common RW treatments, highlighting the need for practice change.

Humans↗