Prevalence of cutaneous adverse events associated with long-term disease-modifying therapy and their impact on health-related quality of life in patients with multiple sclerosis: A cross-sectional study

Background: Glatiramer acetate (GA) and interferon-beta (IFN-β) are disease-modifying therapies (DMTs) for multiple sclerosis that are administered through subcutaneous (SC) or intramuscular (IM) injections. Skin reactions associated with DMTs are common and may influence patient's health-related quality of life (QoL). We aimed to determine the prevalence of cutaneous adverse events associated with long-term DMT use, and to assess the impact of cutaneous adverse events on QoL. Methods: A cross-sectional study among patients with multiple sclerosis who had been treated with their first DMT for at least 2 years. Cutaneous events were assessed from photographs of injection-sites by dermatologists blinded for DMT. Generic and dermatology-specific health-related QoL were assessed using validated patient-reported questionnaires. Results: A total of 229 patients were enrolled, of whom 156 (68%) had at least one skin reaction. The prevalence of cutaneous adverse events was higher for SC DMTs (75-82%) compared to IM DMT (41%) (P < 0.001). Erythema and lipoatrophy were the most common skin reactions, observed in 156 (68%) and 45 (20%) patients, respectively. Dermatology-specific, but not generic, QoL was significantly lower among patients with skin reactions compared to those without. Conclusions: The prevalence of cutaneous adverse events was high in long-term DMT-treatment. Patients with cutaneous adverse events had a lower perceived dermatology-specific QoL

Fluoxetine in Progressive Multiple Sclerosis (FLUOX-PMS) : study protocol for a randomized controlled trial

Background: Currently available disease-modifying treatments acting by modifying the immune response are ineffective in progressive multiple sclerosis (MS), which is caused by a widespread axonal degeneration. Mechanisms suspected to be involved in this widespread axonal degeneration are reduced axonal energy metabolism, axonal glutamate toxicity, and reduced cerebral blood flow. Fluoxetine might theoretically reduce axonal degeneration in MS because it stimulates energy metabolism through enhancing glycogenolysis, stimulates the production of brain-derived neurotrophic factor, and dilates cerebral arterioles. The current document presents the protocol of a clinical trial to test the hypothesis that fluoxetine slows down the progressive phase of MS. Methods/Design: The FLUOX-PMS trial is a multi-center, randomized, controlled and double-blind clinical study. A total of 120 patients with the diagnosis of either secondary or primary progressive MS will be treated either by fluoxetine (40 mg daily) or placebo for a total period of 108 weeks. The primary endpoint is the time to confirmed disease progression defined as either at least a 20% increase in the timed 25-Foot Walk or at least a 20% increase in the 9-Hole Peg Test. Secondary endpoints include the Hauser ambulation index, cognitive changes, fatigue, magnetic resonance imaging of the brain, and in a small subgroup optical coherence tomography. Discussion: The FLUOX-PMS trial will gives us information as to whether fluoxetine has neuroprotective effects in patients with progressive MS

Self-reported work productivity in people with multiple sclerosis and its association with mental and physical health

PURPOSE: This study aimed to identify mental health, physical health, demographic and disease characteristics relating to work productivity in people with multiple sclerosis (MS). METHODS: In this cross-sectional study, 236 employed people with MS (median age = 42 years, 78.8% female) underwent neurological and neuropsychological assessments. Additionally, they completed questionnaires inquiring about work productivity (presenteeism: reduced productivity while working, and absenteeism: loss of productivity due to absence from work), mental and physical health, demographic and disease characteristics. Multiple linear and logistic regression analyses were performed with presenteeism and absenteeism as dependent variables, respectively. RESULTS: A model with mental and physical health factors significantly predicted presenteeism F(11,202) = 11.33, p < 0.001, R2 = 0.38; a higher cognitive (p < 0.001) and physical impact (p = 0.042) of fatigue were associated with more presenteeism. A model with only mental health factors significantly predicted absenteeism; χ2(11)=37.72, p < 0.001, with R2 = 0.27 (Nagelkerke) and R2 = 0.16 (Cox and Snell). Specifically, we observed that more symptoms of depression (p = 0.041) and a higher cognitive impact of fatigue (p = 0.011) were significantly associated with more absenteeism. CONCLUSIONS: In people with MS, both cognitive and physical impact of fatigue are positively related to presenteeism, while symptoms of depression and cognitive impact of fatigue are positively related to absenteeism.Implications for rehabilitationMultiple sclerosis (MS) affects people of working age, significantly interfering with work productivity.Higher cognitive and physical impact of fatigue were associated with more presenteeism in workers with MS.A higher cognitive impact of fatigue and more depressive symptoms were associated with absenteeism in workers with MS.Occupational and healthcare professionals should be aware of the impact of both physical and mental health on work productivity in workers with MS

Drug adherence and multidisciplinary care in patients with multiple sclerosis: Protocol of a prospective, web-based, patient-centred, nation-wide, Dutch cohort study in glatiramer acetate treated patients (CAIR study)

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, for which no definitive treatment is available. Most patients start with a relapsing-remitting course (RRMS). Disease-modifying drugs (DMDs) reduce relapses and disability progression. First line DMDs include glatiramer acetate (GA), interferon-beta (INFb)-1a and INFb-1b, which are all administered via injections. Effectiveness of DMD treatment depends on adequate adherence, meaning year-long continuation of injections with a minimum of missed doses. In real-life practice DMD-treated patients miss 30% of doses. The 6-month discontinuation rate is up to 27% and most patients who discontinue do so in the first 12 months.Treatment adherence is influenced by the socio-economic situation, health care and caregivers, disease, treatment and patient characteristics. Only a few studies have dealt with adherence-related factors in DMD-treated patients. Self-efficacy expectations were found to be related to GA adherence. Patient education and optimal support improve adherence in general. Knowledge of the aspects of care that significantly relate to adherence could lead to adherence-improving measures. Moreover, identification of patients at risk of inadequate adherence could lead to more efficient care.In the near future new drugs will become available for RRMS. Detailed knowledge on factors prognostic of adherence and on care aspects that are associated with adequate adherence will improve the chances of these drugs becoming effective treatments. We investigate in RRMS patients the relationship between drug adherence and multidisciplinary care, as well as factors associated with adherence. Given the differences in the frequency of administration and in the side effects between the DMDs we decided to study patients treated with the same DMD, GA.Methods/design: The Correlative analyses of Adherence In Relapsing remitting MS (CAIR) study is an investigator-initiated, prospective, web-based, patient-centred, nation-wide cohort study in the Netherlands.The primary objective is to investigate whether GA adherence is associated with specific disciplines of care or quantities of specific care. The secondary objective is to investigate whether GA adherence is associated with specific aspects of the socio-economic situation, health care and caregivers, disease, treatment or patient characteristics.All data are acquired on-line via a study website. All RRMS patients in the Netherlands starting GA treatment are eligible. Patients are informed by neurologists, nurses, and websites from national MS patient organisations. All data, except on disability, are obtained by patient self-reports on pre-defined and random time points. The number of missed doses and the number of patients having discontinued GA treatment at 6 and 12 months are measures of adherence. Per care discipline the number of sessions and the total duration of care are measures of received care. The full spectrum of non-experimental care that is available in the Netherlands is assessed. Care includes 'physical' contacts, contacts by telephone or internet, health-promoting activities and community care activities. Care received over the preceding 14 days is assessed by patients at baseline and every other week thereafter up to month 12. Every 3 months neurologists and nurses record care disciplines to which patients have been referred.The Dutch Adherence Questionnaire-90 (DAQ-90) is a 90-item questionnaire based on the World Health Organisation (WHO) 2003 report on adherence and comprehensively assesses five domains of evidence-based determinants of adherence: socio-economic, health care and caregivers, disease, treatment, and patient-related factors. In addition, self-efficacy is assessed by the MS Self-Efficacy Scale (MSSES), and mood and health-related quality of life (HRQoL) by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Relapses and adverse events probably or definitively related to GA are also reported.Discussion: In this study data is mainly acquired by patients' self-reporting via the internet. On-line data acquisition by patients does not require study visits to the hospital and can easily be integrated into daily life. The web-based nature of the study is believed to prevent missing data and study drop-outs. Moreover, the automated process of filling in questionnaires ensures completeness and consistency, thus improving data quality. The combination of patient-reported outcomes, fully web-based data capture and nation-wide information to all eligible patients are distinguishing features of the study and contribute to its scientific potential.Trial registration: Netherlands Trial Register (NTR): NTR2432