Injectable Disease-modifying Therapy Research Articles

Correlation between MRI utilization and therapy switches in disease-modifying treatments for multiple sclerosis.

Studies measuring the role of magnetic resonance imaging (MRI) in therapeutic decision-making are rare in people with multiple sclerosis (pwMS). This study aimed to measure the association between MRI utilization and disease-modifying therapy (DMT) switches in pwMS. This retrospective cohort study identified pwMS in 2018 from a de-identified national claims database. PwMS who received MRI in 2018 were compared to pwMS not receiving MRI in 2018. PwMS were observed for six months to assess the incidence of DMT switches. The study sample consisted of 11,972 pwMS. 3,931 (32.8%) pwMS received at least one MRI in 2018. Overall, MRI utilization increased the odds of switching DMT (OR = 1.49, 1.79, and 3.01 for 1, 2, and ≥ 3 CNS locations imaged). For those on injectable or platform DMT, any MRI utilization increased the odds of switching DMT (OR = 1.54, 2.00, and 3.48 for 1, 2, and ≥ 3 locations imaged). For those on oral DMT, only receiving MRI of 2 or ≥ 3 locations increased the odds of a DMT switch (OR = 1.36, 1.89, and 2.40 for 1, 2, and ≥ 3 locations). Finally, for pwMS on infusible therapies, there was little evidence that MRI changed the odds of a DMT switch. Among pwMS on injectable or oral DMT, imaging more CNS locations increased the odds of switching DMT after adjusting for age and relapse incidence. For pwMS on high-efficacy infusible DMTs, MRI did not change the odds of switching DMT but remains essential for safety monitoring.

Relapse-Associated and Relapse-Independent Contribution to Overall Expanded Disability Status Scale Progression in Multiple Sclerosis Patients Diagnosed in Different Eras.

The introduction of disease-modifying therapies for multiple sclerosis (MS) has led to a deceleration of disease course over the years. Although decreased relapse rate constitutes a factor, the role of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) in MS course deceleration is still unclear. We retrospectively examined long-term Expanded Disability Status Scale (EDSS) progression in patients referred to the MS Center of Montichiari (Italy) and diagnosed with relapsing-remitting MS from 1980 to 2022. To isolate PIRA, we deducted all EDSS changes associated with relapses from overall EDSS change. We compared the relative contribution of PIRA and RAW to EDSS progression in patients diagnosed in different periods using mixed-effects models. A total of 1,405 patients were included in the study, of whom 231 were diagnosed in 1980-1996 (pre-treatment era), 577 in 1997-2008 (injectable disease-modifying therapy era), and 597 after 2008 (oral drugs, monoclonal antibodies, and anti-CD20 era). Across ages, both PIRA and RAW were reduced in patients diagnosed in more recent periods as compared with earlier periods. The average contribution of PIRA to overall EDSS progression was already predominant in patients diagnosed in 1980-1996 (78%) and in 1997-2008 (76%), but it was significantly increased (p = 0.0009) in patients diagnosed in later years (87%). The deceleration of MS course observed throughout the years is determined not only by fewer RAW events, but also by a reduction in PIRA. However, the shift toward a mostly relapse-independent progression highlights the importance of evaluating new therapies based on their effect on PIRA. ANN NEUROL 2024.

The first study of real-world efficacy and safety of Natalizumab (Tysabri®) in Iran

Objectives: Natalizumab is an injectable DMT (disease-modifying therapy) which used for RRMS (relapsing-remitting multiple sclerosis) since 2006. The drug has been available in Iran since 2014. Introduction: This study was aimed to evaluate the real-world effectiveness of Natalizumab in a referral center in Tehran, Iran. This study is the first real world analysis of efficacy and safety of Natalizumab in our country. Methods: In this retrospective study, patients with RRMS were investigated in a high-volume center in Tehran from 2019 to 2021. MS (Multiple Sclerosis) patients under treatment with Natalizumab who have received at least 3 infusions of the drug and had completed follow-up data, have been evaluated for safety and efficacy of Natalizumab. Results: 100 patients were included in the final analysis. The mean follow-up time was 20 months (6–33 months). The median EDSS (Expanded Disability Status Scale) score of patients reached to 2 from 2.5 after the treatment course (P < 0.0001). The annualized relapse rate (ARR) decreased from 0.81 (95% CI: 0.73–0.87) to 0.023 (95% CI 0.009–0.061). The median JCV (John Cunningham virus) index remained unchanged before treatment 0.85 (IQR: 0.21–2.41) compare to after the treatment 0.85 (IQR: 0.21–2.31). The number of patients with active brain and cervical MRI (Magnetic Resonance Imaging) lesions decreased significantly (P = 0.001). NEDA-3 (No evidence of disease activity) was improved from 9% to 87% after the treatment with Natalizumab. No serious adverse events except than one progressive multifocal encephalopathy (PML) case have been found. The main reasons of switching from Natalizumab to the other DMDs (Disease Modifying Drugs) were positive JC index, starting phase, noncompliance, pregnancy, MRI activity and seroconversion after starting the drug. Conclusion: Natalizumab is a safe and effective choice in RRMS patients for reducing relapse rate, disability score, active MRI lesion, and improving the NEDA (No evidence of disease activity).

Medication persistence among people with multiple sclerosis in Slovenia treated with dimethyl fumarate

Objective Multiple sclerosis is a chronic, demyelinating inflammatory disease of the central nervous system. Medication persistence is defined as an interval between the initiation and last dose of the applied medication and presents a useful surrogate marker of a stable disease course. This observational study aimed to evaluate medication persistence and discontinuation reasons in Slovenian people with multiple sclerosis treated with dimethyl fumarate. Methods Our retrospective cohort study evaluated people with relapsing-remitting multiple sclerosis treated with dimethyl fumarate as an initial monotherapy or switched from injectable disease-modifying therapy medication between 2014 and 2021. Medication dispenses were extracted from the Slovenian National Institute of Public Health Outpatient Medication Database. The medication persistence criterion was based on the treatment gap. Patients exceeding a 60-day gap were considered nonpersistent. The median time to discontinuation was assessed using survival analyses. Considering discontinuation reasons, patients were further divided into safety and inefficacy groups. Due to the high probability of adverse effects, patients exceeding a 60-day gap were included in the safety group, but definite discontinuation reason remains unknown. The impact of covariates was evaluated by Cox regression. Results A total of 269 patients were included (183 women, mean age 37 years). During the 7-year follow-up period, 123 (45.7%) patients discontinued treatment. The median time to discontinuation was 5.6 years. After 1, 2, and 5 years of treatment, 84%, 77%, and 57% of patients were found to be persistent, respectively. All patients older than 30 years (p = 0.0013) and among them, those in the inefficacy group (p = 0.037) were more likely to be persistent. Conclusions The results of our study proved a high persistence rate among our patients. The most frequent discontinuation reason was gastrointestinal adverse effects. Medication persistence requires interventions in younger patients with an unstable disease course.

A cross-sectional analysis of persistence to disease-modifying therapies in treatment naïve and experienced patients with relapsing multiple sclerosis at a health-system specialty pharmacy

BackgroundPatients with relapsing multiple sclerosis (RMS) are maintained on disease-modifying therapy (DMT) to prevent disease progression. Reported persistence rates to DMTs are varied and concerningly low. Limited data exists on long-term persistence rates and reasons for DMT discontinuation in patients with RMS. This study evaluated long-term DMT persistence, rates and reasons for DMT discontinuation or switch, specialty pharmacist involvement in DMT treatment transitions, and predictors associated with non-persistence in treatment naïve and experienced patients. MethodsWe performed a single-center retrospective, cross-sectional review of patients with RMS and ≥3 fills of DMT from a health-system specialty pharmacy (May-October 2017). Patients were followed for 3 years to determine DMT persistence, defined as the time a patient remained on index DMT. Descriptive statistics were used to summarize sample characteristics and outcomes. The Kaplan-Meier estimation method was used to estimate the probability of remaining persistent and we used the Cox proportional hazards regression model to analyze the primary outcome. Rates and reasons for DMT discontinuation were identified via pharmacy claims and confirmed via chart review of the electronic health record. ResultsThe study included 540 patients, of which 41 (7.6%) were treatment naïve. Over 3 years, 193 (36%) patients remained on index DMT. The probability of remaining persistent for 3 years was 0.51 (95% confidence interval [CI] 0.47–0.56) and median time on index DMT was 642 days (interquartile range 317–1096). For the 347 patients that did not continue index DMT: 91 (26%) discontinued, 136 (39%) switched to a new DMT, 92 (27%) transferred care to a new specialty pharmacy or provider, 21 (6%) were lost to follow-up, and 7 (2%) died. Common reasons for DMT discontinuation or switch were insurance formulary change, side effects, clinical decline, and stable disease. Specialty pharmacists initiated 6 (7%) DMT discontinuations and 49 (36%) DMT switches. A strong non-linear relationship existed between age and risk of non-persistence (p = 0.003). Patients on an injectable index DMT were 1.5 times more likely to be non-persistent than those on an oral DMT (95% CI 1.1–2.1, p = 0.012) and patients with non-commercial insurance were 1.4 times more likely to be non-persistent (95% CI 1.02–2.0, p = 0.040). ConclusionsLong-term persistence to DMTs is low, with many patients switching or discontinuing DMT treatment. Specialty pharmacists identify the need for DMT discontinuation or switch and are uniquely positioned to assist during therapy transitions.

Quantifying the risk of disease reactivation after interferon and glatiramer acetate discontinuation in multiple sclerosis: The VIAADISC score.

Background and purposeThere is a lack of evidence guiding discontinuation of disease‐modifying therapy (DMT) in relapsing multiple sclerosis (RMS). Thus, the objective of this study was to generate and validate a risk score for disease reactivation after DMT discontinuation in RMS.MethodsWe drew a generation and validation dataset from two separate prospectively collected observational databases including RMS patients who received interferon‐β or glatiramer acetate for ≥12 months, then discontinued DMT for ≥6 months and had ≥2 years of follow‐up available. In the generation sample (n = 168), regression analysis was performed to identify clinical or magnetic resonance imaging (MRI) variables independently predicting disease reactivation after DMT discontinuation. A predictive score was calculated using the variables included in the multivariable model and applied to the validation sample (n = 98).ResultsThe variables included in the final model as independent predictors of disease reactivation were age at discontinuation, MRI activity at discontinuation, and duration of clinical stability (all p < 0.001). The resulting score was able to robustly identify patients at high (83%–85%), moderate (36%–38%), and low risk (7%) of disease reactivation within 5 years after DMT discontinuation in both cohorts.ConclusionsThe composite VIAADISC score is a valuable tool to inform and support patients and neurologists in the process of decision making to discontinue injectable DMTs.

Evaluating Treatment Patterns, Relapses, Healthcare Resource Utilization, and Costs Associated with Disease-Modifying Treatments for Multiple Sclerosis in DMT-Naïve Patients.

PurposeEarly diagnosis and treatment of multiple sclerosis (MS) with disease-modifying therapy (DMT) can reduce relapse number and severity, which has cost implications. We describe treatment patterns, healthcare utilization, and cost among MS patients newly initiating DMTs (index).Patients and MethodsDMT-naïve adults with 12 months’ continuous enrollment pre- and post-index and ≥2 MS claims (2009‒2018) were identified from the Optum Clinformatics Data Mart database. Treatment adherence and persistence were measured as time on index DMT. Relapses were identified using a validated claims-based algorithm. All-cause and MS-related healthcare expenditures and utilization were captured pre- and post-index. Outcomes were stratified by route of administration. Multivariate analyses assessed differences in outcomes and costs.ResultsThe analysis included 5906 MS patients (mean age, 46.6 years). The majority initiated injectable (63.5%) followed by oral (28.8%) and infusion (7.7%) DMTs. Post-index, 45.3% of patients were nonadherent and 39.4% were nonpersistent. Relapse rates decreased from pre- to post-index (oral: 24.3%‒16.1%; injectable: 25.0%‒17.1%; infusion: 29.3%‒15.5%). Post-index mean (SD) all-cause total costs were lowest with oral ($70,970 [$36,681]) vs injectable ($82,521 [$58,569]) and infusion ($80,871 [$49,627]) DMTs. MS-related total costs were lowest with oral ($65,149 [$65,133]) vs injectable ($76,197 [$60,204]) and infusion ($72,703 [$47,287]) DMTs. Multivariate analysis showed no differences between oral and injectable DMTs in adherence, persistence, or relapse rate; however, oral DMTs had significantly lower all-cause and MS-related costs.ConclusionWith similar outcomes across DMT administration routes, initiating the least costly DMT may be warranted for many patients. In newly treated MS patients, the need exists to improve adherence and persistence.

Quality of life among injectable and oral disease-modifying therapy users in the Pacific Northwest Multiple Sclerosis Registry

BackgroundNine oral disease-modifying therapies (DMTs) have been approved for the treatment of multiple sclerosis (MS) in the United States. Few studies have examined self-reported quality of life (QoL) and functional status outcomes among patients who switch to oral medications from injectable MS therapies. This study compares self-reported QoL and disability status between participants switching from injectable to oral DMTs, to those who stay on injectable DMTs continuously for the same time period.MethodsLongitudinal data were assessed from relapsing MS participants in the Pacific Northwest MS Registry completing a minimum of two surveys between 2012 and 2018 with a maximum of 36 months between surveys. Stayers were defined as those who remained on injectable DMTs continuously from Time 1 to Time 2; switchers were those who switched from injectable to either fingolimod, teriflunomide or dimethyl fumarate during the same time interval. Outcomes of interest were physical and psychological QoL, measured by the Multiple Sclerosis Impact Scale (MSIS-29), and disability, measured by the Patient Determined Disease Steps (PDDS). To analyze the effect of switching to oral DMT on outcomes at Time 2, a one-to-two propensity score matching (PSM) was used to match switchers to stayers. Outcomes at Time 2 were analyzed using paired t-test for QoL scores, and Stuart Maxwell test for PDDS as a categorical variable.ResultsAmong 2385 participants who returned consecutive yearly surveys, 413 met the inclusion criteria for stayers and 66 for switchers. After one-to-two PSM, 124 stayers were matched to 62 switchers. Paired t-test showed no differences between switchers and stayers for physical (mean difference: − 0.41; [95% confidence interval CI: − 3.3-2.4]; p = 0.78) or psychological (mean difference: − 0.23; [95% CI, − 1.6- 1.1]; p = 0.74) QoL. Additionally, no differences were seen between switchers and stayers in self-reported disability status.ConclusionsMS registry participants who switched to an oral DMT from injectable showed no significant differences in QoL or self-reported disability status compared to those remaining on injectable DMT continuously in the same time period.

Comparison of first-line and second-line use of fingolimod in relapsing MS: The open-label EARLIMS study.

BackgroundTreatment of MS often begins with low-efficacy injectable disease-modifying therapy (iDMT).ObjectivesTo compare the effect of fingolimod 0.5 mg/day on clinical, MRI, patient-reported, and safety outcomes, in treatment-naïve and previously treated (≥1 iDMT) patients with early MS.MethodsEARLIMS was a multicentre, open-label, non-randomized, parallel-group phase 3 b/4 study in Australia and Spain. Patients with relapsing–remitting MS, Expanded Disability Status Scale (EDSS) score <4.0, and ≥1–5 years since diagnosis, received daily fingolimod for 48 weeks. The primary endpoint was annualized relapse rate (ARR).ResultsOf 347 patients enrolled at 51 sites (treatment-naïve, 200 [57.6%]; previously treated, 147 [42.4%]), 320 completed the study (treatment-naïve, 184 [92.0%]; previously treated, 136 [92.5%]), but the study remained underpowered (planned enrolment, n = 432). Fingolimod reduced ARR to similar levels in both treatment-naïve (mean ARR [95% confidence interval], 0.21 [0.14, 0.29]) and previously treated groups (0.30 [0.20, 0.41]; p = 0.1668). There were no new safety signals.ConclusionsFingolimod appeared equally effective as first- or second-line therapy in relapsing MS. There was a trend for better outcomes with fingolimod in treatment-naïve patients than in those previously treated with >1 iDMT.

Early predictors of injectable disease modifying drugs suboptimal response based on clinical and radiological data assessment in Polish Multiple Sclerosis patients.

Prospective database studies can provide useful information regarding 'real-world' outcomes and drug efficacy. To determine the early predictors of suboptimal treatment responses at two and three years under injectable Disease Modifying Therapy (DMT). This was a multi-centre prospective database study. Adult patients who started injectable DMTs between January 2008 and June 2013 were included. The follow-up continued until July 2014. Suboptimal treatment responses were defined as: the presence of clinical relapse and/or Expanded Disability Status Score (EDSS) progression and/or newly emerging T2 lesions or/and gadolinium enhancing lesions on magnetic resonance imaging (MRI). The parameters were assessed up to 24 months prior to, and every 12 months during, the treatment. Analysis included 297 MS (multiple sclerosis) patients followed for a mean time of 2.3 ± 1.3 years (range 1-5). Within the three years of observation, the persistence and efficacy with injectable DMTs was high. With increased disability, defined by EDSS ≥ 3, the risk of treatment failure increased up to seven times, OR 7.33 in the second year radiological analysis (CI 95% : 1.69-29.2) p < 0.01, similar to over two times in the second year clinical analysis, with the baseline symptomatic hemiparesis OR 2.75 (CI 95% : 1.06-7.06) p 0.034. A high relapse rate one year prior to treatment adversely influenced the treatment success at three years, OR 3.04 (CI 95% : 1.49-8.43) p < 0.01. Injectable DMTs should not be chosen for treatment initiation in motoric disabled patients (EDSS ≥ 3) with a high grade of clinical activity. These drugs are effective in less active relapsing-remitting (RR) MS patients.

A retrospective claims analysis: Compliance and discontinuation rates among Canadian patients with multiple sclerosis treated with disease-modifying therapies.

BackgroundCompliance to disease modifying therapy (DMT) is associated with a reduced risk of relapse, lower healthcare resource utilization, and improved health-related quality of life in patients with multiple sclerosis (MS). Our objective was to assess the compliance and discontinuation rates of fingolimod relative to other oral, injectable, and infusible DMTs available on the market at the time of the study in Canada in patients with relapsing—remitting MS (RRMS).Methods and findingsWe conducted a retrospective claims analysis. Patients with RRMS with ≥ 1 prescription for each DMT were included. Compliance (medication possession ratio of ≥ 80%) and discontinuation (gap > 30 days from the end of the index prescription) were calculated at the 6-, 12- and 24-month time points. Compliance with fingolimod at the 6-, 12- and 24-month time points was 75%, 75% and 70%, respectively; compared with DMF [70% (P < 0.001), 68% (P < 0.001), and 56% (P < 0.001), respectively], and BRACE [53% (P < 0.001), 47% (P < 0.001), and 35% (P < 0.001), respectively]. Compliance with fingolimod was comparable to teriflunomide at each time point, but was higher compared to natalizumab [70% versus 57% (P < 0.001)] at the 24-month time point. At the 6-, 12- and 24-month time points, patients on fingolimod had the lowest discontinuation rate (26%, 24%, and 29%, respectively) compared to BRACE [49% (P < 0.001), 44% (P < 0.001), and 57% (P < 0.001)], respectively], and natalizumab [33% (P < 0.001), 29% (P < 0.001), and 45% (P < 0.001), respectively], and was similar to teriflunomide (26%, 25%, and 31%, respectively).ConclusionsThe compliance rate in fingolimod treated patients at the 24 month time point was higher than that observed in natalizumab treated patients. The discontinuation rate was lower with fingolimod compared to other DMTs at all time points but was similar to teriflunomide.

Population-based study of “no evident disease activity” in MS

ObjectiveTo determine the persistence of no evident disease activity (NEDA) in a population-based relapsing-remitting MS (RRMS) cohort.MethodsAll incident cases of RRMS in Olmsted County between 2000 and 2011 were identified using a medical records linkage system. Persistence of NEDA after RRMS diagnosis was determined by retrospective chart review. MRI activity, relapse, or Expanded Disability Status Scale (EDSS) worsening resulted in failure of NEDA.ResultsWe identified 93 incident cases of RRMS including 82 individuals with sufficient follow-up to determine the persistence of NEDA. There were 44 individuals not on disease-modifying therapy (DMT), whereas 37 individuals were prescribed an injectable DMT and 1 received mitoxantrone during the interval over which NEDA was maintained. NEDA was maintained by 63% at 1 year, 38% at 2 years, 19% at 5 years, and 12% at 10 years according to routine care assessment. At 10 years, there was no difference in EDSS disability among patients who maintained NEDA vs those who failed NEDA at 1 year (p = 0.3).ConclusionsNEDA infrequently persists beyond 2 years in a population-based cohort of newly diagnosed patients with RRMS.

GP.02 A population-based study of “no evident disease activity” (NEDA) in multiple sclerosis

Background: NEDA is a composite measure that may ultimately influence clinical decisions concerning switches of disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS) patients. Cohort studies from MS clinics suggest NEDA is not sustained over time in most patients despite DMT but may be limited by referral bias. We investigated NEDA in a population-based RRMS cohort. Methods: We identified all incident cases of RRMS in Olmsted County from 01/01/2000-12/31/2011. Retrospective chart review was conducted to determine persistence of NEDA -following RRMS diagnosis. NEDA failure was defined as new MRI activity, relapse, or expanded disability status scale (EDSS) -worsening. Results: There were 93 incident cases of RRMS with 82 individuals having sufficient follow-up to determine persistence of NEDA. Prior to NEDA failure 44 were not on DMT, 37 were on first-tier, injectable DMT, and 1 received mitoxantrone. NEDA was maintained by 63% at 1 year, 38% at 2 years, 19% at 5 years, and 12% at 10 years. Disability measured by EDSS was no different at 10 years in patients maintaining NEDA versus those that failed NEDA at one year (p=0.3). Conclusions: Maintenance of NEDA beyond 2 years is infrequent among a population-based cohort of newly diagnosed RRMS patients and similar to prior clinic-based cohorts.

Associations Between Treatment Satisfaction, Medication Beliefs, and Adherence to Disease-Modifying Therapies in Patients with Multiple Sclerosis.

Adherence to disease-modifying therapy (DMT) remains problematic for many patients with multiple sclerosis (MS). An improved understanding of factors affecting DMT adherence may inform effective interventions. This study examined associations between treatment satisfaction, medication beliefs, and DMT adherence. A survey was mailed in 2016 to 600 adult patients with relapsing-remitting MS taking an injectable or oral DMT. Patients were sampled from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. The survey measured self-reported DMT adherence (doses taken divided by doses prescribed during previous 2-week period-adherence ≥0.80), DMT satisfaction using the Treatment Satisfaction Questionnaire for Medication version II, medication beliefs using the Beliefs About Medicines Questionnaire, and demographic and clinical covariates. Relationships between variables were examined using multivariate logistic regression. Final analyses included 489 usable surveys. Mean ± SD participant age was 60.5 ± 8.3 years. Most respondents were white (93.8%), female (86.6%), taking an injectable DMT (66.9%), and adherent to DMT (92.8%). Significant predictors of DMT adherence were age (odds ratio [OR], 1.086; 95% CI, 1.020-1.158; P = .011), type of DMT (oral vs. injectable; OR, 23.350; 95% CI, 2.254-241.892; P = .008), and DMT experience (naive vs. experienced; OR, 2.831; 95% CI, 1.018-7.878; P = .046). In patients with MS sampled from a patient registry, treatment satisfaction and medication beliefs were not significantly associated with DMT adherence. Based on significant predictors, younger patients, patients taking injectable DMTs, and patients with previous experience with another DMT(s) are at higher risk for nonadherence. Future research is warranted to assess relationships between variables in more diverse MS populations.

Assessment of treatment patterns associated with injectable disease-modifying therapy among relapsing-remitting multiple sclerosis patients.

BackgroundAvailability of oral disease-modifying therapy (DMT) for relapsing–remitting multiple sclerosis (RRMS) may affect injectable DMT (iDMT) treatment patterns.ObjectiveThe objective of this paper is to evaluate iDMT persistency, reasons for persistency lapses, and outcomes among newly diagnosed RRMS patients.MethodsMedical records of 300 RRMS patients initiated on iDMT between 2008 and 2013 were abstracted from 18 US-based neurology clinics. Eligible patients had ≥3 visits: pre-iDMT initiation, iDMT initiation (index), and ≥1 visit within 24 months post-index. MS-related symptoms, relapses, iDMT treatment patterns (i.e. persistency, discontinuation, switching, and restart), and reasons for non-persistency were tracked for 24 months.ResultsAt 24 months, iDMT persistency was 61.0%; 28.0% of patients switched to another DMT, 8.0% discontinued, and 3.0% stopped and restarted the same iDMT. The most commonly identified reasons for non-persistency were perceived lack of efficacy (22.2%), adverse events (18.8%), and fear of needles/self-injecting (9.4%). At 24 months, 38.0% of patients had experienced a relapse and 11.0% had changes in MRI lesion counts. Patients without MS-related symptoms at index reported increases in the incidence of these symptoms at 24 months.ConclusionsNon-persistency with iDMT remains an issue in the oral DMT age. Many patients still experienced relapses and disease progression, and should consider switching to more effective therapies.

Oral contraceptives and MS disease activity in a contemporary real-world cohort

Background: There is uncertainty regarding the effect of oral hormonal contraceptives (OC) on multiple sclerosis (MS) course. Objective: To evaluate the hypothesis that OC use is associated with decreased risk of relapses in an observational study of women of childbearing age with new-onset MS starting a first-line injectable disease-modifying therapy (DMT). Methods: From our CLIMB longitudinal observational study, we identified 162 women with MS or CIS with known OC use who initiated injectable DMT within two years of symptom onset, and categorized OC use at DMT onset as past, ever or never. Our primary analysis was comparison of annualized relapse rate from baseline DMT start across the three OC use categories using a negative binomial regression model. Results: In this cohort of 162 women, 81 were treated with interferon therapy and 81 with glatiramer acetate. Mean ages for current-, past-, and never-OC users were 31.4 (n = 46), 40.3 (n = 66), and 37.9 (n = 50) years, respectively (p < 0.05); mean disease duration (1.0 years) and median baseline EDSS (1.0) did not differ between groups. Prior OC users had significantly lower relapse rates than never-users (p = 0.031); the lower annualized relapse rate in current-users relative to never-users was not significant (p = 0.91). Annualized relapse rate was not significantly different across the OC groups (p = 0.057, three-group comparison). Results: These observations provide reassurance for women newly diagnosed that OC use, past or current, does not appear to be associated with greater risk of relapses.

Changes in first-line injectable disease-modifying therapy for multiple sclerosis: predictors of non-adherence, switching, discontinuation, and interruption of drugs.

This study was aimed to describe changes of Disease-Modifying Treatments (DMT) in an Italian cohort of patients with multiple sclerosis (MS) and to identify predictors of therapeutic modifications. Patients with MS and treated with the first-line injectable DMT (interferons-IFNs or glatiramer) between 1/7/2009 and 31/10/2012 were selected from administrative databases of the MS Center of Cagliari (Sardinia, Italy). Socio-demographic, therapeutic, and clinical information was collected in the 6months preceding the index date. All patients were followed for 36months to evaluate therapeutic changes in terms of non-adherence, switch, temporary discontinuation, and permanent interruption. Predictors of changes were estimated by multivariable regression models. Data on 1698 patients were collected: glatiramer was prescribed in 27% of cases, IFNβ-1b in 22%, IFNβ-1a-im in 20%, IFNβ-1a-sc-44mcg in 19%, and IFNβ-1a-sc-22mcg in 12%. Non-adherence was observed in 25% of cases, therapeutic switch in 30%, discontinuation in 37%, and permanent interruption in 28%. The risk of non-adherence was higher for IFNβ-1b, compared with IFNβ-1a-im (adjOR=1.73). Therapeutic switch occurred especially in patients recently diagnosed (each year from diagnosis causes a decrease of this risk adjHR=0.97); the risk of discontinuation was higher with EDSS=4-6 and 7-9 (adjHR=1.52 and 4.42, respectively). The risk of permanent interruption increased with the augmentation of disability (adjHR=1.67 and 5.43 for EDSS 4-6 and 7-9). This study mirrored a detailed framework of DMT prescription and identified factors related to changes in the MS therapy. These findings could support healthcare providers in the evaluation and maximization of benefits associated with a long-term DMT.

Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study

BackgroundDiscontinuation of injectable disease-modifying therapy (DMT) for multiple sclerosis (MS) after a long period of relapse freedom is frequently considered, but data on post-cessation disease course are lacking.Objectives(1) To compare...

Impact of a switch to fingolimod on depressive symptoms in patients with relapsing multiple sclerosis: An analysis from the EPOC (Evaluate Patient OutComes) trial

BackgroundDepression is common in patients with multiple sclerosis (MS), may confound evaluation of therapeutic effectiveness and may be impacted by MS-specific treatments. ObjectiveFirst, to assess the impact on depressive symptoms of a switch to fingolimod versus remaining on an injectable disease-modifying therapy (iDMT) in a post-hoc analysis of prospectively collected data from the EPOC study. Secondly, to investigate the underlying Beck Depression Inventory-II (BDI-II) factor structure in patients with MS, and estimate treatment differences using the resulting subscales. MethodsEPOC was a 6-month, open-label study assessing patient-reported outcomes after switch from iDMT to oral fingolimod 0.5mg versus remaining on iDMT in 1053 patients with relapsing–remitting MS. ResultsAt end of study (EOS), a greater proportion of patients on fingolimod versus iDMT no longer had BDI-II scores indicating depression (p<0.001). Fewer mildly and moderately symptomatic patients developed severe depressive symptoms, and fewer severely symptomatic patients continued to have scores indicating severe depression at EOS on fingolimod versus iDMT (p=0.027, p=0.038, p=0.030, respectively). Two BDI-II subscales were identified and labelled Somatic and Affective; fingolimod demonstrated more reduction on both subscales at EOS versus iDMTs (p<0.0001 and p=0.0001, respectively). ConclusionA switch to fingolimod versus remaining on/switching to another iDMT was associated with an improvement in depressive symptoms in patients with relapsing–remitting MS.

Efficacy of fingolimod is superior to injectable disease modifying therapies in second-line therapy of relapsing remitting multiple sclerosis.

Although fingolimod is registered in Europe for treatment of relapsing-remitting multiple sclerosis (RRMS) if earlier disease modifying therapy (DMT) has failed, no data regarding its efficacy in this patient group are available. This observational cohort study of the NeuroTransData network includes German RRMS outpatients with failure of earlier therapy with injectable DMT (iDMT), therefore switching to either another iDMT (n = 133) or to fingolimod (n = 300). Statistical comparison of clinical baseline characteristics showed more severely affected patients in the fingolimod group. A propensity-score matched group comparison was performed (n = 99 in each group) covering more than 2-year observation time. Fingolimod showed statistically significant superior efficacy in comparison to iDMT regarding annualized relapse rate (0.21 versus 0.33 per year), time-to-relapse and likelihood of relapse (iDMT hazard ratio 1.7), proportion and likelihood of patients with EDSS progression (15.10 versus 31.00 %; iDMT hazard ratio 1.7), persistence on medication and likelihood of discontinuation (iDMT hazard ratio 3.0). Significantly more patients were free of relapse and EDSS progression with fingolimod than with their second iDMT (64.4 versus 46.5 %, p < 0.03). This real-life evidence in German RRMS outpatients support data from controlled clinical studies and can quantitatively support clinical decision finding processes if iDMT therapy fails in RRMS.