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EDSS and disease duration associate with progression independent of relapse and MRI activity in natalizumab-treated
Marco Puthenparampil1, Margherita Passamonti2, Martina Rozzi2
1University of Padua, Department of Neurosciences, Via Belzoni, 160, Padua, Veneto, 35121 Padova, Italy; Azienda Ospedale Università Padova, Multiple Sclerosis Centre Via Giustiniani 2 Padua, Veneto, 35128 Padova, Italy; Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Immune-Mediated Nervous System Disease Study Group, Corso Stati Uniti 47, 35127 Padova, Italy.
Background:
Clinical, biological and radiological data that may help in predicting and managing the Progression Independent of Relapse and MRI Activity (PIRMA) in multiple sclerosis (MS). We designed a retrospective, longitudinal study to identify prognostic factors of PIRMA in natalizumab (NTZ) treated patients with MS (pwMS).
Methods:
Clinical and radiological data from pwMS starting NTZ in the period July 2007 to February 2017 were retrospectively collected.
Results:
238 patients (age of 29.1 ± 8.5 years) were followed up for 5.5 ± 4.3 years. PIRMA was observed in 70 patients (29.4%). PIRMA was predicted by both EDSS (Cox regression analysis: H.R.= 1.7, p < 0.0001) and disease duration at NTZ first administration (H.R.= 1.0, p = 0.025). Combining disease duration (138 months) and EDSS (4.0) cut-offs, pwMS with lower and disease duration had lower probability of PIRMA compared to patients with 1 risk factor (disease duration ≥138 months or EDSS ≥ 4, H.R. 5.321, 95%IC 2.943 - 9.622, p < 0.0001) or 2 risk factors (H.R. 6.100, 95%IC 2.100 - 17.730, p < 0.0001). To evaluate the effect of age on PIRMA, we focused the analysis on patients that reached at least the age of 45 during the follow-up (age at follow-up end: 51.8 ± 5.7; range: 45-75). Higher baseline EDSS was independently associated with an increased risk of PIRMA (HR 1.65, 95% CI 1.24-2.24, p = 0.0005). Conversely, older age at natalizumab initiation was associated with a lower risk of PIRMA (HR 0.87 per year, 95% CI 0.81-0.95, p = 0.0007).
Conclusions:
PIRMA was identified as the main driver of disability progression in RRMS treated with NTZ and is predicted by disease duration and EDSS at therapy initiation.
Insights
Progression Independent of Relapse and MRI Activity (PIRMA) in multiple sclerosis (MS) is driven by disease duration and Expanded Disability Status Scale (EDSS) scores at treatment initiation. These factors predict PIRMA in patients receiving natalizumab (NTZ).
Area of Science:
- Neurology
- Immunology
- Clinical Research
Background:
- Understanding Progression Independent of Relapse and MRI Activity (PIRMA) is crucial for managing multiple sclerosis (MS).
- Identifying prognostic factors for PIRMA in patients treated with natalizumab (NTZ) is essential for optimizing treatment strategies.
- This study retrospectively analyzed clinical, biological, and radiological data to predict PIRMA in MS patients on NTZ therapy.
Purpose of the Study:
- To identify prognostic factors for Progression Independent of Relapse and MRI Activity (PIRMA) in multiple sclerosis patients treated with natalizumab (NTZ).
- To evaluate the impact of disease duration, Expanded Disability Status Scale (EDSS), and age on PIRMA development.
Main Methods:
- Retrospective, longitudinal study design.
- Collection of clinical and radiological data from MS patients initiating natalizumab (NTZ) between July 2007 and February 2017.
- Cox regression analysis was used to identify predictors of PIRMA.
Main Results:
- PIRMA was observed in 29.4% of 238 MS patients over a mean follow-up of 5.5 years.
- Both higher Expanded Disability Status Scale (EDSS) scores (HR=1.7) and longer disease duration at NTZ initiation (HR=1.0) predicted PIRMA.
- Increased baseline EDSS (HR 1.65) and older age at NTZ initiation (HR 0.87 per year) were independently associated with PIRMA risk.
Conclusions:
- Progression Independent of Relapse and MRI Activity (PIRMA) is a primary driver of disability progression in relapsing-remitting MS (RRMS) patients treated with natalizumab (NTZ).
- Disease duration and EDSS score at therapy initiation are key predictors of PIRMA.
- These findings aid in predicting and managing MS progression in patients on NTZ therapy.
