scholarly journals New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

2020 ◽  
Vol 11 ◽  
Author(s):  
Inmaculada Toboso ◽  
Amalia Tejeda-Velarde ◽  
Roberto Alvarez-Lafuente ◽  
Rafael Arroyo ◽  
Harald Hegen ◽  
...  

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression.Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case.Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.

1984 ◽  
Vol 231 (1) ◽  
pp. 26-33 ◽  
Author(s):  
U. Patzold ◽  
U. Wurster ◽  
K. Mardt ◽  
M. Schiemann

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732095981
Author(s):  
Carrie M Hersh ◽  
Haleigh Harris ◽  
Malissa Ayers ◽  
Devon Conway

Background Tobacco exposure is a modifiable risk factor for multiple sclerosis (MS). Studies evaluating the relationship between tobacco, disease activity, and disease modifying therapy (DMT) persistence yielded conflicting results. We sought to address this issue with data from clinical practice. Objective To compare 24-month disease outcomes in tobacco versus non-tobacco users treated with dimethyl fumarate (DMF) or fingolimod (FTY) in clinical practice. Methods We retrospectively identified 659 MS patients treated with DMF or FTY, stratified by patient-reported tobacco use. DMT discontinuation and measures of disease activity at 24 months were assessed using propensity score (PS) weighting. Outcome estimates were calculated as tobacco vs non-tobacco use. Results 164 tobacco users (DMF n = 101; FTY n = 63) and 495 non-tobacco users (DMF n = 294; FTY n = 201) were identified. Tobacco (39.4%) and non-tobacco (34.4%) users were equally likely to discontinue DMT (OR = 1.17, 95% CI 0.79, 1.75), but tobacco users discontinued therapy earlier (HR = 1.53, 95% CI 1.06, 2.43). There were no differences in ARR (rate ratio = 1.39, 95% CI 0.97, 1.96). However, tobacco users had decreased odds of NEDA-2 (OR = 0.61, 95% CI 0.44, 0.83). Conclusion Our findings suggest that tobacco is a negative risk factor for inflammatory disease activity and earlier DMF and FTY discontinuation.


Author(s):  
Nayyereh Ayati ◽  
Lora Fleifel ◽  
Mohammad Ali Sahraian ◽  
Shekoufeh Nikfar

Background: Cladribine tablets are the foremost oral immune-reconstitution therapy for high disease activity relapsing multiple sclerosis (HDA-RMS). We aimed to assess the cost-effectiveness of cladribine tablets compared to natalizumab in patients with HDA-RMS in Iran. Methods: A 5-year cohort-based Markov model was developed with 11 expanded disability status score (EDSS) health states, including patients with HDA-RMS as on and off-treatment. All costs were identified from the literature and expert opinion and were measured in Iranian Rial rates, changed to the 2020 USD rate and were discounted by 7.2%. Quality adjusted life years (QALY), discounted by 3.5%, and life years gained (LYG) were adopted to measure efficacy. The final results were presented as incremental cost-effectiveness ratio that was compared to a national willingness to pay (WTP) threshold of 1 to 3 gross domestic product (GDP) per capita. Deterministic and probabilistic sensitivity analyses (D/PSA) were employed to evaluate uncertainty. Results: Cladribine tablets dominated natalizumab and yielded 6,607 USD cost-saving and 0.003 additional QALYs per patient. LYG was comparable. The main cost component was drug acquisition cost in both arms. DSA indicated the sensitivity of the results to the cost discount rates and also the patients’ body weight; while they were less sensitive to the main clinical variables. PSA indicated that cladribine tablets were cost-effective in Iran, with a probability of 57.5% and 58.6% at lower and higher limits of threshold, respectively. Conclusion: Cladribine tablets yielded higher QALYs and lower costs compared to natalizumab, in patients with HDA-RMS in Iran.


2018 ◽  
Vol 265 (10) ◽  
pp. 2342-2345 ◽  
Author(s):  
Ursela Baber ◽  
Andrew Bouley ◽  
Emily Egnor ◽  
Jacob A. Sloane

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Azza AbdelNaser AbdelAziz ◽  
Prof Dr. Rasha Mamdouh Saleh ◽  
Mahmoud Saad Swelam ◽  
Janet Masoud Ayad

Abstract Background Studies have suggested that vitamin D and lipid profile have been linked to the etiology of multiple sclerosis and have an impact on the activity and progression of the disease. Objectives The aim of the present study was to determine correlation between vitamin D level and lipid profile in multiple sclerosis (MS) patients and their effect on disease activity and progression for better management and control of risk factors. Patients and Methods It is a cross-sectional hospital based study carried on clinically definite 111 Relapsing Remitting MS (RRMS) patients according to McDonald criteria 2010 recruited from Multiple sclerosis unit at Ain Shams University Hospitals, both genders included and aged from 18 to 50 years old. All subjects were assessed regarding their basic demographic data, serum vitamin D level and lipid profile and correlated these data with their state of disease activity and degree of disability. Results The mean level of serum vitamin D was 18.93 ± 9.85 ng/mL. Serum vitamin D level was insufficient (< 30 ng/mL) in 81.08% of patients and sufficient (≥ 30 ng/mL) in 18.92% of patients. The mean level of total cholesterol (TC) was 204.9 ± 50.9 mg/dL, of tri-glycerides (TG) was 105.4 ± 44.6 mg/dL, of low density lipoprotein (LDL) was 122.2 ± 38.8 mg/dL and of high density lipoprotein (HDL) level was 56.2 ± 16.6 mg/dL. High relapse frequency was found to be significantly related to low serum vitamin D level with P-value 0.005. Near all lipid related variables were positively correlated to disease duration. TC and TG were positively related to EDSS while HDL was negatively related with it. Number of brain T2 lesions was significantly correlated with TC and TG levels with P-value 0.001 and 0.002 respectively. Fingolimod was found to be associated with dyslipidemia. We found that each 1 ng/mL increase in vitamin D was associated with decrease in TC of 1.48 mg/dL (95% CI: -2.42 to -0.54, P-value 0.002) and increase in HDL of 0.35 mg/dL (95% CI: 0.04 to -0.66, P-value 0.028). Conclusion Vitamin D deficiency is predominant among Egyptian MS patients. Patients with insufficient vitamin D were found to have higher annualized relapse rate (ARR). Patients with dyslipidemia found to have longer duration, more disability and higher brain T2 lesion load. Vitamin D was correlated positively with HDL and negatively with TC.


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