PIRA
Progression Independent of Relapse Activity
PIRA（再発に依存しない障害進行 / くすぶり型進行）
1. Biological & Technical Mechanism
Progression Independent of Relapse Activity (PIRA) refers to confirmed disability accumulation (measured via EDSS, Timed 25-Foot Walk, or 9-Hole Peg Test) that occurs during relapse-free intervals—as opposed to Relapse-Associated Worsening (RAW). Large harmonized registry studies (MSBase, MSDA) and clinical trial re-analyses have demonstrated that PIRA accounts for >50–80% of all disability accumulation even in early Relapsing-Remitting MS (RRMS) patients treated with high-efficacy therapies.
PIRA（Progression Independent of Relapse Activity）は、急性の臨床的再発およびその前後の影響期間（通常は再発前30日〜再発後90日）を除いた無再発期間中に生じる確定障害進行（24週確定EDSS悪化や歩行・上肢機能低下）を指します。従来、進行性病態は二次性進行型（SPMS）への移行後に始まるものと考えられていましたが、大規模リアルワールドデータ（MSBase / MSDA）の解析により、発症早期の再発寛解型（RRMS）であっても障害蓄積の過半数（50〜80%以上）がPIRAに起因することが実証されました。
2. Open Science & Clinical Trial Significance
PIRA is the primary clinical correlate of 'smoldering MS' pathology—linked to Paramagnetic Rim Lesions (PRLs), Slowly Expanding Lesions (SELs), cortical demyelination, and elevated serum GFAP—and is the central therapeutic target for CNS-penetrant BTK inhibitors.
PIRAは、常磁性リム病変（PRL）、緩徐拡大病変（SEL）、皮質脱髄、視床・脊髄萎縮、および血清GFAP上昇と強く相関する「くすぶり型MS（Smoldering MS）」の臨床的指標であり、脳移行性BTK阻害薬や再髄鞘化促進薬の最重要エンドポイントとなっています。
Related Neuroscience Terms & Standards
Standard 0.0–10.0 ordinal clinical rating scale quantifying neurological disability across 8 functional systems and ambulation capacity in Multiple Sclerosis.
Chronic white matter MS lesions bordered by a dense rim of iron-laden, proinflammatory activated microglia/macrophages, visible on T2* phase MRI, SWI, and QSM.
Intermediate filament protein of astrocytes released into CSF and blood during reactive astrogliosis; tracks smoldering PIRA progression in MS and amyloid-induced astrocytic reactivity in Alzheimer's.
Axonal cytoskeletal protein released into CSF and blood upon neuroaxonal injury; a cross-disease biomarker of neurodegeneration rate in ALS, MS, AD, and FTD.
Oral small-molecule therapeutics crossing the blood-brain barrier to simultaneously inhibit B-cell receptor signaling and FcγR-mediated proinflammatory microglial activation in Multiple Sclerosis.
Open-community clinical data standard that transforms heterogeneous hospital EHR and disease registry databases into a unified relational schema and standardized vocabulary for federated analytics.
Open Datasets & Research Publications Related to PIRA
Global Data Sharing Initiative (GDSI): Containerized Federated Analysis Pipeline for MS Registries
International federated research initiative and containerized query framework allowing participating national MS registries to analyze disease-modifying therapy (DMT) safety, anti-CD20 outcomes, and PIRA progression without transferring identifiable patient data.
MSDA Global Registry & Cohort Metadata Discovery Catalogue (BigMS Network)
A centralized metadata discovery catalogue indexing over 30 national and international MS registries (>120,000 patients), detailing variable availability for EDSS, relapse history, MRI, fluid biomarkers, and DUA governance.
Assessing respiratory rates and signs of air hunger using the PneumoRator sensor.
ObjectivesTo investigate whether the PneumoRator wearable sensor could accurately assess Respiratory Rate (RR) and signs of air hunger (SAH) compared with clinician-observed assessment in adults with and without breathing pattern disorder (BrPD). DesignA pilot cross-sectional observational study. ...
MSBase & BigMS Harmonized Cohort: Quantifying Progression Independent of Relapse Activity (PIRA) Under High-Efficacy DMTs
Multi-center longitudinal real-world evidence study evaluating roving-baseline EDSS trajectories, Relapse-Associated Worsening (RAW) versus PIRA rates, and early anti-CD20 / natalizumab intervention across harmonized international MS registries.
Interaction Between Exercise Intensity and Sedentary Behavior on VO2max Change in Patients with De Novo Parkinson Disease: The Study in Parkinson Disease of Exercise (SPARX) Phase 2 Randomized Clinical Trial
BackgroundParkinson disease (PD) is associated with increased sedentary time and reduced cardiorespiratory fitness, making exercise an important component of disease management. Although exercise improves cardiorespiratory fitness, individuals with PD vary substantially in their response to exercise...
ENCALS Consensus Statement: Stratification Biomarkers and Clinical Trial Endpoints in Motor Neuron Disease
European Network to Cure ALS framework for incorporating serum Neurofilament Light Chain (NfL) and digital respiratory monitoring into adaptive clinical trial design.
Disclaimer: This encyclopedia entry is intended for academic neuroscience research and data science reference only, and does not constitute medical advice.