Publications by authors named "Raymond M M Hupperts"

11 Publications

  • Page 1 of 1

Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients.

Neurology 2016 Nov 12;87(19):1985-1992. Epub 2016 Oct 12.

From Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Medical Faculty, Charles University in Prague, Czech Republic; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; Sanofi Genzyme (D.H.M., S.L.L., M.A.P.), Cambridge, MA; and Evidence Scientific Solutions (S.M.K.), Philadelphia, PA (at the time the work was conducted).

Objective: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy.

Methods: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation.

Results: Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a-treated patients.

Conclusions: In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities.

Classification Of Evidence: This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a.
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November 2016

The effect of postpartum intravenous immunoglobulins on the relapse rate among patients with multiple sclerosis.

Int J Gynaecol Obstet 2016 Aug 18;134(2):194-6. Epub 2016 Apr 18.

Neurology, Zuyderland Medisch Centrum, Sittard-Geleen, Netherlands.

Objective: To evaluate the effect of intravenous immunoglobulins (IVIGs) on the expected increase in postpartum relapse rate (RR) among patients with multiple sclerosis (MS).

Methods: In a retrospective study, data were analyzed from patients with relapsing remitting MS who received postpartum IVIG at the Academic MS Center Limburg, Sittard-Geleen, Netherlands, between April 2005 and January 2015. Patients received 10g IVIG (Nanogam) for 3 consecutive days after childbirth, and then once monthly until 5months after delivery. Data were compared with results from the Pregnancy in Multiple Sclerosis (PRIMS) I and II studies, which followed the natural outcomes of patients with MS with no intervention.

Results: Overall, 42 pregnancies were evaluated. The RR in the first 3months after delivery was 0.48±1.31, as compared with 1.2 in the PRIMS studies. The RR also remained low at 3-6, 6-9, and 9-12months after delivery for patients who received IVIG.

Conclusion: Postpartum administration of IVIG could be beneficial in preventing childbirth-associated relapses among patients with MS. It led to a substantial decrease in RR.
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August 2016

Comparative efficacy of first-line natalizumab vs IFN-β or glatiramer acetate in relapsing MS.

Neurol Clin Pract 2016 Apr;6(2):102-115

Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital (TS, TK, VJ, HB), University of Melbourne, Australia; Biogen Idec Inc. (AZ, FP, SB, RH), Cambridge, MA; Department of Neurology (HW), University of Münster, Germany; Groene Hart Ziekenhuis (FV), Gouda, the Netherlands; MS Center, Department of Neuroscience, Imaging and Clinical Sciences (AL), University "G. d'Annunzio," Chieti, Italy; MS Center, Department of Neurology, First Medical Faculty (EH, DH), Charles University, Prague, Czech Republic; Center de Réadaptation Déficience Physique Chaudière-Appalache (PG), Levis; Hôpital Notre Dame (PD, AP), Montreal, Canada; Ospedali Riuniti di Salerno (G. Iuliano), Salerno, Italy; 19 Mayis University (M. Terzi), Medical Faculty, Turkey; Hospital Universitario Virgen Macarena (G. Izquierdo), Sevilla, Spain; Orbis Medical Centre (RMMH), Sittard-Geleen, the Netherlands; KTU Medical Faculty Farabi Hospital (CB), Trabzon, Turkey; Neurology Unit (EP, GG), ASUR Marche-AV3, Macerata; Nuovo Ospedale Civile S. Agostino (PS), Modena; AORN San Giuseppe Moscati (DLAS), Avellino, Italy; John Hunter Hospital (JL-S), Newcastle, Australia; Neurological Institute IRCCS Mondino (RB), Pavia, Italy; Neuro Rive-Sud (F. Grand'Maison), Hôpital Charles LeMoyne, Quebec, Canada; University of Parma (F. Granella), Italy; Department of Neurology (LK), University Hospital Basel, Switzerland; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; and Department of Neurology (HB), Eastern Health, Monash University, Australia.

Background: We compared efficacy and treatment persistence in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS) initiating natalizumab compared with interferon-β (IFN-β)/glatiramer acetate (GA) therapies, using propensity score-matched cohorts from observational multiple sclerosis registries.

Methods: The study population initiated IFN-β/GA in the MSBase Registry or natalizumab in the Tysabri Observational Program, had ≥3 months of on-treatment follow-up, and had active RRMS, defined as ≥1 gadolinium-enhancing lesion on cerebral MRI at baseline or ≥1 relapse within the 12 months prior to baseline. Baseline demographics and disease characteristics were balanced between propensity-matched groups. Annualized relapse rate (ARR), time to first relapse, treatment persistence, and disability outcomes were compared between matched treatment arms in the total population (n = 366/group) and subgroups with higher baseline disease activity.

Results: First-line natalizumab was associated with a 68% relative reduction in ARR from a mean (SD) of 0.63 (0.92) on IFN-β/GA to 0.20 (0.63) ( [signed-rank] < 0.0001), a 64% reduction in the rate of first relapse (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.28-0.47; < 0.001), and a 27% reduction in the rate of discontinuation (HR 0.73, 95% CI 0.58-0.93; = 0.01), compared with first-line IFN-β/GA therapy. Confirmed disability progression and area under the Expanded Disability Status Scale-time curve analyses were not significant. Similar relapse and treatment persistence results were observed in each of the higher disease activity subgroups.

Conclusions: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse and treatment persistence outcomes compared to first-line IFN-β/GA. This needs to be balanced against the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients.

Classification Of Evidence: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse rates and treatment persistence outcomes compared to first-line IFN-β/GA.
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April 2016

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.

BMC Neurol 2013 Oct 16;13:146. Epub 2013 Oct 16.

Department of Dermatology, Erasmus Medical Center, Burg, s' Jacobsplein 51, 3015 CA, Rotterdam, the Netherlands.

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.
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October 2013

Treatment experience, burden, and unmet needs (TRIBUNE) in Multiple Sclerosis study: the costs and utilities of MS patients in The Netherlands.

J Med Econ 2013 Jul 12;16(7):939-50. Epub 2013 Jun 12.

Institute of Environmental Medicine, Division of Epidemiology, Karolinska Institutet, Stockholm, Sweden.

Background: Multiple sclerosis (MS) is an important, highly disabling neurological disease, common among young adults in The Netherlands. Nevertheless, only a few studies to date have measured the burden imposed by MS on society in The Netherlands.

Objectives: To estimate the cost and quality-of-life associated with MS in The Netherlands, while focusing on the burden of relapses and increasing disease severity.

Methods: MS patients in The Netherlands (n = 263) completed a web-based questionnaire which captured information on demographics, disease characteristics and severity (Expanded Disability Status Scale [EDSS]), co-morbidities, relapses, resource consumption, utilities, fatigue and activities of daily living (ADL).

Results: Most patients included in the study were receiving treatment for MS (76% of the sample). The mean cost per patient per year increased with worsening disability and was estimated at €30,938, €51,056, and €100,469 for patients with mild (EDSS 0-3), moderate (EDSS 4-6.5), and severe (EDSS 7-9) disability, respectively. The excess cost of relapses was estimated at €8195 among relapsing-remitting patients with EDSS score ≤5. The quality-of-life of patients decreased with disease progression and existence of relapses.

Conclusions: The cost of MS in The Netherlands was higher compared to the results of previous studies. The TRIBUNE study provides an important update on the economic burden of MS in The Netherlands in an era of more widespread use of disease-modifying therapies. It explores the cost of MS linked to relapses and disease severity and examines the impact of MS on additional health outcomes beyond utilities such as ADL and fatigue.

Study Limitations: Patients were selected from specialized treatment centers, therefore this sample may not be representative of the entire MS population in The Netherlands, i.e., few patients not receiving MS therapies were included. In addition, only a few patients with severe disability were included in the study sample; therefore, results for this disease severity sub-group should be interpreted with caution.
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July 2013

The contribution of disease severity, depression and negative affectivity to fatigue in multiple sclerosis: a comparison with ulcerative colitis.

J Psychosom Res 2010 Jul 21;69(1):43-9. Epub 2010 Jan 21.

Department of Medical Psychology and Psychiatry, Orbis Medical Centre, Sittard, The Netherlands.

Background: Fatigue is one of the most common and troubling symptoms of multiple sclerosis (MS) and more severe and disabling than fatigue in other somatic populations. Although fatigue seems MS specific, its pathogenesis is still poorly understood.

Objective: To study the disease specificity of fatigue in MS by comparing its level, its physical and psychological correlates to those of patients with ulcerative colitis (UC), a peripheral chronic auto-immune disease. We focused on the relative contribution of disease severity, depression and negative affectivity to fatigue in both patient samples.

Methods: A total of 88 MS and 76 UC patients were included in this cross-sectional study. Fatigue, depression and negative affectivity were assessed respectively with the physical and mental fatigue subscales of the Multidimensional Fatigue Inventory, the depression subscale of the Hospital Anxiety and Depression Scale, and the neuroticism subscale of the Dutch NEO Five-Factor Inventory. The Expanded Disability Status Scale and the Colitis Activity Index were used to measure disease severity in MS and UC patients respectively.

Results: While levels of both physical and mental fatigue were significantly higher in MS patients than in UC patients, there were no group differences in the contribution of disease severity, depression and negative affectivity to both physical and mental fatigue.

Conclusion: Although levels of fatigue are higher for MS patients when compared with UC patients, the correlates of fatigue do not indicate MS specificity. As such our results support a transdiagnostic approach to fatigue in MS.
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July 2010

The impact of fatigue on cognitive functioning in patients with multiple sclerosis.

Clin Rehabil 2010 Sep 24;24(9):854-62. Epub 2010 Jun 24.

Department of Medical Psychology and Psychiatry, Orbis Medical Centre, Sittard, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.

Objective: To study the impact of physical and mental fatigue on cognitive complaints and cognitive performance in patients with multiple sclerosis.

Design: Cross-sectional study.

Setting: An outpatient neurology clinic.

Subjects: Eighty patients diagnosed with clinically definite multiple sclerosis.

Measures: The subscales physical and mental fatigue of the Multidimensional Fatigue Inventory; the Hospital Anxiety and Depression Scale and the Cognitive Failure Questionnaire. Cognitive performance was assessed by an extensive neuropsychological test battery, including several tasks requiring effortful information processing.

Results: Both anxiety and depression and mental fatigue significantly contributed to cognitive complaints, explaining respectively about 9% and 39% of the total variance. The contribution of physical fatigue to cognitive complaints was not significant. Both physical and mental fatigue did not significantly contribute to cognitive performance in terms of mental speed, attention, memory and executive functioning.

Conclusions: To refine interventions for those patients with cognitive complaints, we advise adding measurements of anxiety, depression and fatigue to their neuropsychological assessment. Fatigue permits extensive neuropsychological assessment, which is needed to detect cognitive impairment in multiple sclerosis.
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September 2010

Fatigue and physical disability in patients with multiple sclerosis: a structural equation modeling approach.

J Behav Med 2010 Oct 28;33(5):355-63. Epub 2010 May 28.

Department of Medical Psychology and Psychiatry, Orbis Medical Centre, PO Box 5500, 6130 MB Sittard, The Netherlands.

Although fatigue is one of the most common and disabling symptoms in patients with multiple sclerosis (MS), its pathogenesis is still poorly understood and it is difficult to treat. The aim of the current study was to test the assumptions of a cognitive-behavioral model that explains fatigue and physical disability in MS patients, by comparing this approach with a more traditional biomedical approach. Structural equation modeling was applied to a sample of 262 MS patients. Neither the cognitive-behavioral, nor the biomedical model showed an adequate fit of our data. The modification indices supported an integration of both models, which showed a better fit than those of the separate models. This final model, is notable for at least three features: (1) fatigue is associated with depression and physical disability, (2) physical disability is associated with disease severity and fatigue-related fear and avoidance behavior, and (3) catastrophic interpretations about fatigue, fueled by depression, mediated the relationship between fatigue and fatigue-related fear and avoidance behavior. Our results suggest that an integrated approach, including the modification of catastrophic thoughts about fatigue, would be beneficial in the treatment of fatigue in MS patients.
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October 2010

The psychology of fatigue in patients with multiple sclerosis: a review.

J Psychosom Res 2009 Jan 24;66(1):3-11. Epub 2008 Sep 24.

Department of Psychology, Maastricht University Medical Center, Maastricht, The Netherlands.

Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS), but it is difficult to define and measure. Today, MS-related fatigue is not fully understood, and evidence related to explanatory pathophysiological factors are conflicting. Here, we evaluate the contribution of psychological factors to MS-related fatigue. Insight into the possible underlying psychological mechanisms might help us to develop adequate psychological interventions and to improve the overall management of fatigue. Conceptual issues and the relationships between MS-related fatigue and mood, anxiety, cognition, personality, and cognitive-behavioral factors are discussed, and the implications for clinical practice and research are presented.
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January 2009

The influence of sex hormones on cytokines in multiple sclerosis and experimental autoimmune encephalomyelitis: a review.

Mult Scler 2005 Jun;11(3):349-59

Department of Neurology, University Hospital Maastricht, P Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, The Netherlands.

The female predominance of multiple sclerosis (MS) has suggested that hormonal differences between the sexes must confer some protective effect on males or enhance the susceptibility of females to this disease. There has been evidence that gonadal hormones can modulate the immune response regulated by antigen presenting cells and T cells. These cells control the immune response by the production of interacting pro- and anti-inflammatory cytokines. The first include the acute phase pro-inflammatory cytokines of the innate immune response as well as the T-helper 1 (Th1) cytokines, while the later contain the Th2 cytokines as well as the suppressor cytokines. There is some evidence that MS and experimental autoimmune encephalitis (EAE) are Th1 cell-mediated diseases. For this reason many studies have been done to influence the pro-inflammatory cytokine production of these Th1 cells in favour of an anti-inflammatory immune response as mediated by Th2 cells. However the role of the regulatory T cells in this context is not clearly understood. Here we review the studies concerning the role of sex hormones on the cytokine production in relation to the disease course of MS and EAE and in particular in the light of the recent revival of the regulatory T cells and their suppressive cytokines.
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June 2005