Healthcare costs for treating relapsing multiple sclerosis and the risk of progression: a retrospective Italian cohort study from 2001 to 2015

Background Disease modifying treatments (DMTs) are the main responsible for direct medical costs in multiple sclerosis (MS). The current investigation aims at evaluating possible associations between healthcare costs for treating relapsing remitting MS (RRMS) and disease evolution. Methods The present cohort study retrospectively included 544 newly diagnosed RRMS patients, prospectively followed up for 10.1±3.3 years. Costs for DMT administration and management were calculated for each year of observation. Following clinical endpoints were recorded: time to first relapse, 1-point EDSS progression, reaching of EDSS 4.0, reaching of EDSS 6.0, and conversion to secondary progressive MS (SP). Covariates for statistical analyses were age, gender, disease duration and EDSS at diagnosis. Results At time varying Cox regression models, 10% increase in annual healthcare costs was associated with 1.1% reduction in 1-point EDSS progression (HR = 0.897; p = 0.018), with 0.7% reduction in reaching EDSS 6.0 (HR = 0.925; p = 0.030), and with 1.0% reduction in SP conversion (HR = 0.902; p = 0.006). Conclusion Higher healthcare costs for treating MS have been associated with a milder disease evolution after 10 years, with possible reduction of long-term non-medical direct and indirect costs

The glycopeptide CSF114(Glc) detects serum antibodies in multiple sclerosis.

Synthetic glycopeptides have the potential to detect antibodies in multiple sclerosis (MS). In the present study, we analyzed the antibodies (IgM class, IgG class and IgG subclasses) to the synthetic glycopeptide CSF114(Glc) in the serum of 186 MS patients, 166 blood donors (BDs), 25 patients affected by meningitis/encephalitis, 41 affected by systemic lupus erythematosus (SLE) and 49 affected by rheumatoid arthritis (RA). The IgM antibody level to CSF114(Glc) was significantly increased in MS patients versus BDs (p<0.001) or versus other autoimmune diseases (SLE or RA, p<0.001). The IgG response was restricted to the subclass IgG2. IgM antibodies to CSF114(Glc) were found in 30% of relapsing/remitting MS patients and, at lower levels, in subjects affected by meningitis/encephalitis. The study of antibodies to CSF114(Glc) is a new, potential immunological marker of MS

Effects of immunomodulatory treatment with subcutaneous interferon beta-1a oncognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis

The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNbeta-1a) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Patients aged 18-50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score <or=4.0) were assigned IFNbeta therapy at the physician's discretion and underwent standardized magnetic resonance imaging, neurological examination and neuropsychological testing at the baseline and regular intervals for up to three years. This analysis included 459 patients who received sc IFNbeta-1a (44 mcg: n = 236; 22 mcg: n = 223; three-year follow up was available for 318 patients). The hazard ratio for cognitive impairment over three years (44 mcg versus 22 mcg) was 0.68 (95% confidence interval [CI]: 0.480-0.972), suggesting a 32% lower risk with the higher dose treatment. At year 3, the proportion of patients who were cognitively impaired increased slightly from 23.5% at the baseline to 24.8% in the IFNbeta-1a 22 mcg treatment group, but remained stable at 15.2% in the IFNbeta-1a 44 mcg treatment group. The proportion of patients with cognitive impairment at year 3 was significantly higher in the 22 mcg group than in the 44 mcg group (P = 0.03), although a trend was also seen at the baseline (P = 0.058). Multivariate logistic regression (corrected for baseline cognitive deficits) indicated that treatment with the higher dose of IFNbeta-1a was predictive of lower cognitive impairment at three years (odds ratio: 0.51, 95% CI: 0.26-0.99) compared with the lower dose of IFNbeta-1a. These findings suggest that sc IFNbeta-1a may have dose-dependent cognitive benefits in mildly disabled patients with RRMS, and may support early initiation of high-dose IFNbeta-1a treatment

Sample size for oxidative stress and inflammation when treating multiple sclerosis with interferon-beta 1a and coenzyme Q10

Studying multiple sclerosis (MS) and its treatments requires the use of biomarkers for underlying pathological mechanisms. We aim to estimate the required sample size for detecting variations of biomarkers of inflammation and oxidative stress. This is a post-hoc analysis on 60 relapsing-remitting MS patients treated with Interferon-β1a and Coenzyme Q10 for 3 months in an open-label crossover design over 6 months. At baseline and at the 3 and 6-month visits, we measured markers of scavenging activity, oxidative damage, and inflammation in the peripheral blood (180 measurements). Variations of laboratory measures (treatment effect) were estimated using mixed-effect linear regression models (including age, gender, disease duration, baseline expanded disability status scale (EDSS), and the duration of Interferon-β1a treatment as covariates; creatinine was also included for uric acid analyses), and were used for sample size calculations. Hypothesizing a clinical trial aiming to detect a 70% effect in 3 months (power = 80% alpha-error = 5%), the sample size per treatment arm would be 1 for interleukin (IL)-3 and IL-5, 4 for IL-7 and IL-2R, 6 for IL-13, 14 for IL-6, 22 for IL-8, 23 for IL-4, 25 for activation-normal T cell expressed and secreted (RANTES), 26 for tumor necrosis factor (TNF)-α, 27 for IL-1β, and 29 for uric acid. Peripheral biomarkers of oxidative stress and inflammation could be used in proof-of-concept studies to quickly screen the mechanisms of action of MS treatments

Persistence, adherence, healthcare resource utilisation and costs for interferon Beta in multiple sclerosis: a population-based study in the Campania region (southern Italy)

Background To differentiate five formulations of Interferon Beta for the treatment of multiple sclerosis (MS) in clinical practice, by analysing persistence, adherence, healthcare resource utilisation and costs at population level. Methods In this population-based study, we included individuals with MS living in the Campania Region of Italy from 2015 to 2017, on treatment with intramuscular Interferon Beta-1a (Avonex® = 618), subcutaneous pegylated Interferon Beta-1a (Plegridy® = 259), subcutaneous Interferon Beta-1a (Rebif® = 1220), and subcutaneous Interferon Beta-1b (Betaferon® = 348; and Extavia® = 69). We recorded healthcare resource utilisation from administrative databases (hospital discharges, drug prescriptions, MS-related outpatients), and derived costs from the Regional formulary. We classified hospital admissions into MS-related and non-MS-related. Persistence (time to switch to other disease modifying treatments (DMTs)), and adherence (medication possession ratio (MPR) = medication supply obtained/medication supply expected during follow-up period) were calculated. Results Patients treated with Rebif® were younger, when compared with other Interferon Beta formulations (p < 0.01). The probability of switching to other DMTs was 60% higher for Betaferon®, 90% higher for Extavia®, and 110% higher for Plegridy®, when compared with Rebif® (p < 0.01). Plegridy® presented with 7% higher adherence (p < 0.01), and Betaferon® with 3% lower adherence (p = 0.03), when compared with Rebif®. The probability of MS-related hospital admissions was 40% higher in Avonex® (p = 0.03), 400% higher in Betaferon® (p < 0.01), and 60% higher in Plegridy® (p = 0.04), resulting into higher non-DMT-related costs, when compared with Rebif®. Discussion Interferon Beta formulations presented with different prescription patterns, persistence, adherence, healthcare resource utilisation and costs, with Rebif® being used in younger patients and with less MS-related hospital admissions

Interferon beta for the treatment of multiple sclerosis in the Campania Region of Italy: Merging the real-life to routinely collected healthcare data

Background We aim to overcome limitations of previous clinical and population-based studies by merging a clinical registry to routinely-collected healthcare data, and to specifically describe differences in clinical outcomes, healthcare resource utilization and costs between interferon beta formulations for multiple sclerosis (MS). Methods We included 850 patients with MS treated with interferon beta formulations, from 2015 to 2019, seen at the MS Clinical Care and Research Centre (Federico II University of Naples, Italy) and with linkage to routinely-collected healthcare data (prescription data, hospital admissions, outpatient services). We extracted and computed clinical outcomes (relapses, 6-month EDSS progression using a roving EDSS as reference), persistence (time spent on a specific interferon beta formulation), adherence (medication possession ratio (MPR)), healthcare resource utilization and costs (annualized hospitalization rate (AHR), costs for hospital admissions and DMTs). To evaluate differences between interferon beta formulations, we used linear regression (adherence), Poisson regression (AHR), mixed-effect regression (costs), and Cox-regression models (time varying variables); covariates were age, sex, treatment duration, baseline EDSS and adherence. Results Looking at clinical outcomes, rates of relapses and EDSS progression were lower than studies run on previous cohorts; there was no differences in relapse risk between interferon beta formulations. Risk of discontinuation was higher for Betaferon®/Extavia® (HR = 3.28; 95%CI = 2.11, 5.12; p<0.01). Adherence was lower for Betaferon®/Extavia® (Coeff = -0.05; 95%CI = -0.10, -0.01; p = 0.02), and Avonex® (Coeff = -0.06; 95%CI = -0.11, -0.02; p<0.01), when compared with Rebif® and Plegridy® (Coeff = 0.08; 95%CI = 0.01, 0.16; p = 0.02). AHR and costs for MS hospital admissions were higher for Betaferon®/Extavia® (IRR = 2.38; 95%CI = 1.01, 5.55; p = 0.04; Coeff = 14.95; 95%CI = 1.39, 28.51; p = 0.03). Conclusions We have showed the feasibility of merging routinely-collected healthcare data to a clinical registry for future MS research, and have confirmed interferon beta formulations play an important role in the management of MS, with positive clinical outcomes. Differences between interferon beta formulations are mostly driven by adherence and healthcare resource utilization

Multiple sclerosis in the campania region (South Italy): algorithm validation and 2015-2017 prevalence

We aim to validate a case-finding algorithm to detect individuals with multiple sclerosis (MS) using routinely collected healthcare data, and to assess the prevalence of MS in the Campania Region (South Italy). To identify individuals with MS living in the Campania Region, we employed an algorithm using different routinely collected healthcare administrative databases (hospital discharges, drug prescriptions, outpatient consultations with payment exemptions), from 1 January 2015 to 31 December 2017. The algorithm was validated towards the clinical registry from the largest regional MS centre (n = 1460). We used the direct method to standardise the prevalence rate and the capture-recapture method to estimate the proportion of undetected cases. The case-finding algorithm including individuals with at least one MS record during the study period captured 5362 MS patients (females = 64.4%; age = 44.6 ± 12.9 years), with 99.0% sensitivity (95% CI = 98.3%, 99.4%). Standardised prevalence rate per 100,000 people was 89.8 (95% CI = 87.4, 92.2) (111.8 for females [95% CI = 108.1, 115.6] and 66.2 for males [95% CI = 63.2, 69.2]). The number of expected MS cases was 2.7% higher than cases we detected. We developed a case-finding algorithm for MS using routinely collected healthcare data from the Campania Region, which was validated towards a clinical dataset, with high sensitivity and low proportion of undetected cases. Our prevalence estimates are in line with those reported by international studies conducted using similar methods. In the future, this cohort could be used for studies with high granularity of clinical, environmental, healthcare resource utilisation, and pharmacoeconomic variables

Subcutaneous interferon β-1a may protect against cognitive impairment in patients with relapsing-remitting multiple sclerosis: 5-year follow-up of the COGIMUS study

OBJECTIVE: To assess the effects of subcutaneous (sc) interferon (IFN) -1a on cognition over 5 years in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Patients aged 18-50 years with RRMS (Expanded Disability Status Scale score ≤4.0) who had completed the 3-year COGIMUS study underwent standardized magnetic resonance imaging, neurological examination, and neuropsychological testing at years 4 and 5. Predictors of cognitive impairment at year 5 were identified using multivariate analysis. RESULTS: Of 331 patients who completed the 3-year COGIMUS study, 265 participated in the 2-year extension study, 201 of whom (75.8%; sc IFN β-1a three times weekly: 44 µg, n = 108; 22 µg, n = 93) completed 5 years' follow-up. The proportion of patients with cognitive impairment in the study population overall remained stable between baseline (18.0%) and year 5 (22.6%). The proportion of patients with cognitive impairment also remained stable in both treatment groups between baseline and year 5, and between year 3 and year 5. However, a significantly higher proportion of men than women had cognitive impairment at year 5 (26.5% vs 14.4%, p = 0.046). Treatment with the 22 versus 44 µg dose was predictive of cognitive impairment at year 5 (hazard ratio 0.68; 95% confidence interval 0.48-0.97). CONCLUSIONS: This study suggests that sc IFN β-1a dose-dependently stabilizes or delays cognitive impairment over a 5-year period in most patients with mild RRMS. Women seem to be more protected against developing cognitive impairment, which may indicate greater response to therapy or the inherently better prognosis associated with female sex in MS