Multiple sclerosis is a chronic, demyelinating, and degenerative disease of the central nervous system with an immune-based pathologic origin. The present pilot study aimed to assess whether the ...change in the route of treatment administration is associated with a variation in adherence and whether there is a change in quality of life, treatment satisfaction, and fatigue.
Patients with relapsing-remitting multiple sclerosis who were >18 years of age and who used to receive immunomodulatory parenteral treatment and were ready to change administration route were eligible for the study. Data were collected at baseline and 3 months later. Adherence, quality of life, treatment satisfaction, and fatigue were measured via the following questionnaires: Morisky-Green questionnaire on patient-reported medication adherence, Multiple Sclerosis Quality of Life Instrument, Treatment Satisfaction Questionnaire for Medication, and Modified Fatigue Impact Scale.
The study sample included 30 patients (mean age, 43.2 years; age range, 24–71 years; 60% female and 40% male). There was a significant improvement in adherence (p = 0.048). Mean (SD) physical and mental health quality-of-life summary scores varied from 52.50 (24.15) and 54.13 (21.24) to 67.55 (20.92) and 62.30 (21.75) (p < 0.001 and p = 0.001, d = −0.426 and d = −0.643, respectively). In the Treatment Satisfaction Questionnaire for Medication, an improvement of the score was observed in effectiveness of the medication (p = 0.0041, d = −0.563), adverse effects of the medication (p < 0.001, d = −0.976), convenience of the medication (p < 0.001, d = −1.235), and global satisfaction (p = 0.006, d = −0.725). Patients had a higher mean (SD) score (45.13 26.7) on the Modified Fatigue Impact Scale while receiving injectable treatment compared with that obtained with oral treatment (34.86 23.16; p = 0.009, d = 0.41).
When the route of administration changed from injectable to oral, there was an increase in adherence, quality of life, and degree of patient satisfaction with their treatment and a decrease in the degree of fatigue.
Introduction
Spasticity is one of the most disabling and difficult‐to‐treat symptoms shown by patients with multiple sclerosis, who often show a suboptimal and unsatisfactory response to classic ...treatment and new available nonpharmacological alternatives. Due to the progressive nature of this condition, the early management should be essential to improve long‐term outcomes.
Methods
We performed a narrative literature review of the contribution of spasticity to the burden of multiple sclerosis and the potential role of classic disease‐modifying drugs.
Results
Added to the underlying pathophysiology of spasticity, certain external factors and drugs such as interferon may exacerbate the existing condition, hence their awareness is crucial as part of an effective management of spasticity. Furthermore, the evidence for the effectiveness of glatiramer acetate in preventing spasticity in naïve patients and in those switching from interferon should not be ignored.
Conclusions
This literature review proposes the examination of spasticity and the influence of classic disease‐modifying agents on the level of existing condition among the variables to be considered when deciding on therapy for multiple sclerosis in clinical practice.
The management of spasticity in multiple sclerosis is complex and, therefore, constitutes a challenge for neurologists. As part of an effective spasticity management, the awareness or even the elimination of externally exacerbating factors is considered as crucial. The evidence, although limited and well recognized, of worsening spasticity after interferon should be not ignored, nor the effectiveness GA shows in preventing spasticity when deciding on therapy for MS in clinical practice.
Abstract Background: Treatment with interferon-β (IFN-β) has been related to worsening of muscle spasticity in patients with multiple sclerosis (MS). However, there are no specific data on the ...effects of glatiramer acetate (GA) on spasticity. Objective: The aim of the present study was to assess the effects of GA on spasticity in patients with relapsing-remitting MS who had been previously treated with IFN-β or were treatment naive. Methods: Two cohorts of MS patients with spasticity who were about to begin treatment with GA at the approved dosage (20 mg/d) were enrolled in the study: patients who were being switched from IFN-β due to adverse events or lack of efficacy (cohort 1) and patients who were treatment naive (cohort 2). The follow-up periods for cohorts 1 and 2 were 18 and 12 months, respectively. Patients' physical condition was assessed at baseline and at the end of follow-up using the Modified Ashworth Scale (MAS), Penn Spasm Frequency Scale (PSFS), Global Pain Score (GPS), Adductor Tone Rating Scale, Expanded Disability Status Scale (EDSS), and neurophysiologic tests (latency and amplitude of the Hoffmann reflex H reflex in the soleus, and ratio of maximum H reflex to maximum motor response H/M ratio in the lower limb). The frequency and severity of adverse events were recorded throughout follow-up, and investigators rated the causal relationship to GA (unrelated, unlikely, possibly, or probably). Results: Twenty-eight patients were included in the study, 13 in cohort 1 and 15 in cohort 2. All patients were white. Cohort 1 was 76.9% female, with a mean (SD) age of 39.85 (9.25) years; cohort 2 was 66.7% female, with a mean age of 40.73 (11.52) years. Cohort 1 had significant reductions from baseline to the end of follow-up in mean scores on the MAS for the right hemibody (from 1.85 0.61 to 1.18 0.60; P = 0.002) and left hemibody (from 1.86 0.55 to 1.27 0.65; P = 0.045), PSFS (from 2.00 0.91 to 0.36 0.81; P = 0.002), and GPS (from 47.69 13.94 to 24.09 17.15 mm; P = 0.002). The changes from baseline were not significant on the mean Adductor Tone Rating Scale, EDSS, H-reflex latency or amplitude on either side, or lower-limb H/M ratio on either side. Cohort 2 had significant reductions from baseline in H-reflex latency on the left side (from 30.31 2.44 to 28.75 2.01; P = 0.005) and H/M ratio on the right side (from 0.45 0.15 to 0.35 0.19; P = 0.025). There were no significant changes in mean scores on the MAS for either hemibody, PSFS, GPS, Adductor Tone Rating Scale, EDSS, H-reflex latency on the right side, H-reflex amplitude on either side, or lower-limb H/M ratio on the left side. Sixteen patients experienced a total of 28 adverse events. Seven mild adverse events were considered related to GA: local reaction at the injection site (3 patients); headache/migraine, anxiety, and skin reaction (1 patient each); and an unspecified adverse drug reaction (1 patient). Two serious adverse events (pyelonephritis and pyrexia) occurred during the study, neither of them considered related to GA. Conclusions: In this pilot study in patients with relapsing-remitting MS, GA treatment did not increase spasticity. Furthermore, the results suggest that GA may reduce spasticity in patients previously treated with IFN-β. These findings support the conduct of large randomized controlled trials of the effects of GA on spasticity.
Treatment with natalizumab once every 4 weeks is approved for patients with relapsing-remitting multiple sclerosis, but is associated with a risk of progressive multifocal leukoencephalopathy. ...Switching to extended-interval dosing is associated with lower progressive multifocal leukoencephalopathy risk, but the efficacy of this approach is unclear. We aimed to assess the safety and efficacy of natalizumab once every 6 weeks compared with once every 4 weeks in patients with relapsing-remitting multiple sclerosis.
We did a randomised, controlled, open-label, phase 3b trial (NOVA) at 89 multiple sclerosis centres across 11 countries in the Americas, Europe, and Western Pacific. Included participants were aged 18–60 years with relapsing-remitting multiple sclerosis and had been treated with intravenous natalizumab 300 mg once every 4 weeks with no relapses for at least 12 months before randomisation, with no missed doses in the previous 3 months. Participants were randomly assigned (1:1), using a randomisation sequence generated by the study funder and contract personnel with interactive response technology, to switch to natalizumab once every 6 weeks or continue with once every 4 weeks. The centralised MRI reader, independent neurology evaluation committee, site examining neurologists, site backup examining neurologists, and site examining technicians were masked to study group assignments. The primary endpoint was the number of new or newly enlarging T2 hyperintense lesions at week 72, assessed in all participants who received at least one dose of assigned treatment and had at least one postbaseline MRI, relapse, or neurological examination or efficacy assessment. Missing primary endpoint data were handled under prespecified primary and secondary estimands: the primary estimand included all data, regardless of whether participants remained on the assigned treatment; the secondary estimand classed all data obtained after treatment discontinuation or study withdrawal as missing. Safety was assessed in all participants who received at least one dose of study treatment. Study enrolment is closed and an open-label extension study is ongoing. This study is registered with EudraCT, 2018-002145-11, and ClinicalTrials.gov, NCT03689972.
Between Dec 26, 2018, and Aug 30, 2019, 605 patients were assessed for eligibility and 499 were enrolled and assigned to receive natalizumab once every 6 weeks (n=251) or once every 4 weeks (n=248). After prespecified adjustments for missing data, mean numbers of new or newly enlarging T2 hyperintense lesions at week 72 were 0·20 (95% CI 0·07–0·63) in the once every 6 weeks group and 0·05 (0·01–0·22) in the once every 4 weeks group (mean lesion ratio 4·24 95% CI 0·86–20·85; p=0·076) under the primary estimand, and 0·31 (95% CI 0·12–0·82) and 0·06 (0·01–0·31; mean lesion ratio 4·93 95% CI 1·05–23·20; p=0·044) under the secondary estimand. Two participants in the once every 6 weeks group with extreme new or newly enlarging T2 hyperintense lesion numbers (≥25) contributed most of the excess lesions. Adverse events occurred in 194 (78%) of 250 participants in the once every 6 weeks group and 190 (77%) of 247 in the once every 4 weeks group, and serious adverse events occurred in 17 (7%) and 17 (7%), respectively. No deaths were reported. There was one case of asymptomatic progressive multifocal leukoencephalopathy (without clinical signs) in the once every 6 weeks group, and no cases in the once every 4 weeks group; 6 months after diagnosis, the participant was without increased disability and remained classified as asymptomatic.
We found a numerical difference in the mean number of new or newly enlarging T2 hyperintense lesions at week 72 between the once every 6 weeks and once every 4 weeks groups, which reached significance under the secondary estimand, but interpretation of statistical differences (or absence thereof) is limited because disease activity in the once every 4 weeks group was lower than expected. The safety profiles of natalizumab once every 6 weeks and once every 4 weeks were similar. Although this trial was not powered to assess differences in risk of progressive multifocal leukoencephalopathy, the occurrence of the (asymptomatic) case underscores the importance of monitoring and risk factor consideration in all patients receiving natalizumab.
Biogen.
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