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Gross RH, Corboy J. De-escalation and Discontinuation of Disease-Modifying Therapies in Multiple Sclerosis. Curr Neurol Neurosci Rep 2024; 24:341-353. [PMID: 38995483 DOI: 10.1007/s11910-024-01355-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2024] [Indexed: 07/13/2024]
Abstract
PURPOSE OF REVIEW Long-term use of multiple sclerosis (MS) disease-modifying therapies (DMTs) is standard practice to prevent accumulation of disability. Immunosenescence and other age-related changes lead to an altered risk-benefit ratio for older patients on DMTs. This article reviews recent research on the topic of de-escalation and discontinuation of MS DMTs. RECENT FINDINGS Observational and interventional studies have shed light on what happens to patients who de-escalate or discontinue DMTs and the factors, such as age, treatment type, and presence of recent disease activity, that influence outcomes. Though many questions remain, recent findings have been valuable for the development of an evidence-based approach to making de-escalation and discontinuation decisions in MS.
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Affiliation(s)
- Robert H Gross
- Department of Neurology, University of Colorado School of Medicine, 12631 East 17thAvenue, Mail Stop F727, Aurora, CO, 80045, USA.
- Department of Neurology, Rocky Mountain Regional Veterans Administration Medical Center, Aurora, CO, USA.
| | - John Corboy
- Department of Neurology, University of Colorado School of Medicine, 12631 East 17thAvenue, Mail Stop F727, Aurora, CO, 80045, USA
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Hegen H, Berek K, Deisenhammer F, Berger T, Enzinger C, Guger M, Kraus J, Walde J, Di Pauli F. Sex impacts treatment decisions in multiple sclerosis. J Neurol 2024; 271:3256-3267. [PMID: 38441611 PMCID: PMC11136719 DOI: 10.1007/s00415-024-12270-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/24/2024] [Accepted: 02/19/2024] [Indexed: 05/30/2024]
Abstract
BACKGROUND Individual disease-modifying treatment (DMT) decisions might differ between female and male people with MS (pwMS). OBJECTIVE To identify sex-related differences in DMT strategies over the past decades in a real-world setting. METHODS In this cohort study, data from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), a nationwide prospectively collected registry mandatory for reimbursement, were retrospectively analyzed. Of 4840 pwMS, those with relapsing-remitting MS, aged at least 18 years, who started DMT and had at least two clinical visits, were identified. At baseline, demographics, Expanded Disability Status Scale (EDSS) score, annualized relapse rate (ARR) in the prior 12 months and MRI lesion load were assessed. At follow-up, ARR, EDSS scores, and DMT were determined. RESULTS A total of 4224 pwMS were included into the study and had a median of 10 (IQR 5-18) clinical visits over an observation period of 3.5 (IQR 1.5-6.1) years. Multivariable Cox regression analysis revealed that the probability of DMT escalation due to relapse activity was lower in female than male pwMS (HR 4.1 vs. 8.3 per ARR). Probability of discontinuing moderate-effective DMT was higher in female pwMS when they were younger (HR 1.03 per year), and lower in male pwMS at higher age (HR 0.92). Similarly, female pwMS were more likely to stop highly effective DMT than male pwMS (HR 1.7). Among others, the most frequent reason for DMT discontinuation was family planning in female pwMS. All sex-related effects were independent of disease activity, such as MRI lesion load, baseline ARR or EDSS. CONCLUSIONS Real-world treatment decisions are influenced by sex-related aspects. Awareness of these associations should prevent unwarranted differences in MS care.
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Affiliation(s)
- Harald Hegen
- Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria
| | - Klaus Berek
- Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria
| | - Florian Deisenhammer
- Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria
| | - Thomas Berger
- Department of Neurology, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria
| | | | - Michael Guger
- Department of Neurology, Pyhrn-Eisenwurzen Hospital Steyr, Steyr, Austria
- Medical Faculty, Johannes Kepler University Linz, Linz, Austria
| | - Jörg Kraus
- Department of Laboratory Medicine, Paracelsus Medical University and Salzburger Landeskliniken, Salzburg, Austria
- Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Janette Walde
- Department of Statistics, Faculty of Economics and Statistics, University of Innsbruck, Innsbruck, Austria
| | - Franziska Di Pauli
- Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
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Ben-Zacharia AB, Walker B, Ross AP, Tornatore C, Edwards NC, Lipman Y, Phillips AL. Factors Associated With Disease-Modifying Therapy Adherence and Persistence in Multiple Sclerosis: A Scoping Literature Review. Int J MS Care 2023; 25:188-195. [PMID: 37720259 PMCID: PMC10503813 DOI: 10.7224/1537-2073.2021-139] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2023]
Abstract
BACKGROUND Patients with multiple sclerosis (MS) receiving disease-modifying therapies (DMT) show published adherence rates of 27.0% to 93.8% and published persistence rates of 49.7% to 96.5%. Improvements in DMT adherence and persistence are key to optimizing MS care, and enhanced understanding could improve MS disease management and identify research gaps. This scoping literature review aims to examine the nature and findings of the literature evaluating factors associated with DMT adherence and persistence in patients with MS. METHODS Eligible articles included in the literature review were quantitative clinical studies written in English, included adherence or persistence as primary outcomes, and accounted for covariates/confounders. The articles were assessed to identify factors associated with adherence/persistence and analyzed according to DMT type (self-injectable, oral, infusion). RESULTS Fifty-eight studies (103,450 patients) were included. Study distribution by DMT type was self-injectable only (n = 41), oral only (n = 2), infusion only (n = 1), and more than 1 type (n = 14). Older age and previous DMT use were associated with increased adherence and/or persistence. Increased alcohol consumption, DMT adverse events, higher education, and higher body mass index were negatively associated with adherence and/or persistence. Greater number and severity of relapses was associated with increased adherence but decreased persistence. CONCLUSIONS Most studies examined factors associated with adherence and persistence to self-injectable DMTs. These factors should be evaluated further for oral and infusion DMTs. Insights into the modifiable factors associated with adherence and persistence could guide treatment decisions and help improve adherence and clinical outcomes.
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Affiliation(s)
- Aliza Bitton Ben-Zacharia
- From Bellevue School of Nursing, Hunter College, New York, NY, USA (AB-Z)
- Mount Sinai Medical Center, New York, NY, USA (AB-Z)
| | - Bryan Walker
- Duke University School of Medicine, Durham, NC, USA (BW)
| | | | - Carlo Tornatore
- Medstar Georgetown University Hospital, Washington, DC, USA (CT)
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Vural E, Engin E, Sünter G, Yıldırım KA, Günal D. Real-life outcomes for oral disease-modifying treatments of relapsing-remitting multiple sclerosis patients: Adherence and adverse event profiles from Marmara University. Turk J Med Sci 2023; 53:771-779. [PMID: 37476900 PMCID: PMC10388038 DOI: 10.55730/1300-0144.5640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/01/2023] [Indexed: 07/22/2023] Open
Abstract
BACKGROUND Disease-modifying treatments (DMT) are used to prevent future relapses and disability. High long-term adherence to treatment is important to achieve disease control. This study aims to investigate and compare adherence, adverse event (AE) profiles, and frequencies, main reasons for treatment discontinuation under Teriflunomide (TERI), Dimethyl Fumarate (DMF), and Fingolimod (FNG) for relapsing-remitting MS (RRMS) patients. This study is designed to explore patient-reported experiences in real-life settings. METHODS Patients who were older than 18 years with a definite diagnosis of RRMS and no history of stem-cell transplantation were included. Outpatient clinic data files at the Neurology Department of Marmara University from June 2012 to June 2019 were examined retrospectively. RESULTS One hundred and ninety MS patients were enrolled. 118 FNG, 51 DMF, 44 TERI treatment cycles were recorded. Time sincedisease onset, time since diagnosis, and treatment duration were significantly longer for FNG (p = 0.012, p = 0.004, p < 0.001). 72.8% of all the treatment cycles were continued. There was no significant difference in treatment continuity between the 3 DMT groups. The most common reasons for treatment discontinuation in order of frequency were adverse events, the progression of the disease, and the persistence of relapses. No significant difference was found for treatment discontinuation reasons. 32% of the patients reported at least one AE. 28% FNG, 49 % DMF, and 27.3% TERI using patients reported AEs. AEs were much more frequently reported for DMF (p = 0.015). The most common adverse events for each DMT were alopecia (n = 6, 13.6%) for TERI, flushing for DMF (n = 20, 39.2%), and persistent lymphopenia for FNG (n = 9, 7.6%). No severe or life-threatening AE was reported for DMF, one patient experienced pancreatitis under TERI, and 11 (9.3%) patients using FNG had to stop treatment due to serious or life-threatening AEs including cardiac adverse events, opportunistic infections, and dysplasia. DISCUSSION Overall treatment discontinuation because of AEs is as low as 10.3% in this study. However, AEs are still the main reason for treatment drop-out.
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Affiliation(s)
- Ezgi Vural
- Department of Neurology, School of Medicine, Marmara University, İstanbul, Turkey
| | - Esin Engin
- Department of Neurology, School of Medicine, Marmara University, İstanbul, Turkey
| | - Gülin Sünter
- Department of Neurology, School of Medicine, Marmara University, İstanbul, Turkey
| | | | - Dilek Günal
- Department of Neurology, School of Medicine, Marmara University, İstanbul, Turkey
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Moccia M, Affinito G, Berera G, Marrazzo G, Piscitelli R, Carotenuto A, Petracca M, Lanzillo R, Triassi M, Brescia Morra V, Palladino R. Persistence, adherence, healthcare resource utilization and costs for ocrelizumab in the real-world of the Campania Region of Italy. J Neurol 2022; 269:6504-6511. [PMID: 35953597 PMCID: PMC9618479 DOI: 10.1007/s00415-022-11320-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/27/2022] [Accepted: 08/01/2022] [Indexed: 11/15/2022]
Abstract
Aims We aim to provide real-world evidence on the use of ocrelizumab for treating multiple sclerosis (MS), with specific regard to prescription pattern, adherence, persistence, healthcare resource utilization and related costs, also in relation to other disease-modifying treatments (DMTs). Methods We included 2495 people with MS from the Campania Region (South Italy) who received first or switch DMT prescription from Jan 2018 to Dec 2020, and with at least 6-month follow-up. We collected hospital discharge records, drug prescriptions, and related costs, and calculated persistence (time from first prescription to discontinuation or switch to other DMT), adherence (proportion of days covered (PDC)), annualized hospitalization rate (AHR) for MS-related hospital admissions, and DMT costs. Results Ocrelizumab was the most commonly prescribed DMT (n = 399; age = 45.74 ± 10.98 years; females = 224), after dimethyl fumarate (n = 588) and fingolimod (n = 401); 26% patients treated with ocrelizumab were naïve. When compared with ocrelizumab, the risk of discontinuation was higher for other highly active DMTs (HR = 3.78; p = 0.01), and low/medium efficacy DMTs (HR = 7.59; p < 0.01). When compared with ocrelizumab, PDC was similar to other highly active DMTs (Coeff = 0.01; p = 0.31), but higher for low/medium efficacy DMTs (Coeff = 0.09; p < 0.01). When compared with ocrelizumab, AHR was similar to other highly active DMTs (Coeff = 0.01; p = 0.51), and low/medium efficacy DMTs (Coeff = 0.01; p = 0.55). When compared with ocrelizumab, DMT monthly costs were higher for other highly active DMTs (Coeff = 92.30; p < 0.01), but lower for low/medium efficacy DMTs (Coeff = − 1043.61; p < 0.01). Discussion Ocrelizumab was among the most frequently prescribed DMTs, with 26% prescriptions to treatment-naïve patients, suggesting its relevance in addressing unmet clinical needs (e.g., first approved treatment for primary progressive MS). Ocrelizumab was associated with the highest persistence, confirming its favorable benefit-risk profile. Costs for ocrelizumab were lower than those associated to similarly effective DMTs, in absence of changes in healthcare resource utilization.
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Affiliation(s)
- Marcello Moccia
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, via Sergio Pansini 5, 80131, Naples, Italy.
| | - Giuseppina Affinito
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Giulia Berera
- ROCHE Spa, Viale GB Stucchi 110, 20900, Monza, MB, Italy
| | | | | | - Antonio Carotenuto
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, via Sergio Pansini 5, 80131, Naples, Italy
| | - Maria Petracca
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, via Sergio Pansini 5, 80131, Naples, Italy.,Department of Human Neurosciences, Sapienza University, Rome, Italy
| | - Roberta Lanzillo
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, via Sergio Pansini 5, 80131, Naples, Italy
| | - Maria Triassi
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Vincenzo Brescia Morra
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, University of Naples Federico II, via Sergio Pansini 5, 80131, Naples, Italy
| | - Raffaele Palladino
- Department of Public Health, University of Naples Federico II, Naples, Italy.,Department of Primary Care and Public Health, Imperial College, London, UK
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Sabsabi S, Mikhael E, Jalkh G, Macaron G, Rensel M. Clinical Evaluation of Siponimod for the Treatment of Secondary Progressive Multiple Sclerosis: Pathophysiology, Efficacy, Safety, Patient Acceptability and Adherence. Patient Prefer Adherence 2022; 16:1307-1319. [PMID: 35637684 PMCID: PMC9148218 DOI: 10.2147/ppa.s221882] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 05/05/2022] [Indexed: 11/24/2022] Open
Abstract
INTRODUCTION A number of disease-modifying therapies have been approved for use in relapsing-remitting multiple sclerosis (MS) in the past two decades. However, only few treatment options are available for patients with secondary progressive multiple sclerosis (SPMS). Siponimod has recently been approved for use in patients with active forms of SPMS (who experience clinical relapses or new lesions on MRI superimposed on secondary progression independent of relapse activity). OBJECTIVE The aim of this article is to provide a comprehensive review on the mechanism of action, efficacy, safety, cost effectiveness and patient adherence with siponimod. METHODS We performed a PubMed search using the search terms: "siponimod", "secondary progressive multiple sclerosis", "sphingosine 1-phosphate modulators". Titles and abstract were screened and selected for relevance to the key section of this article. FINDINGS Siponimod is an oral sphingosine-1-phosphate receptor (S1PR) modulator with selectivity to S1PR-1 and 5. Modulation of this receptor on lymphocytes causes its internalization and degradation, preventing their egress from lymphoid tissues to the blood. In the pivotal Phase 3 randomized controlled trial EXPAND, siponimod was superior to placebo in reducing the risk of disability progression confirmed at 3 and 6 months, as well as the development of new MRI lesions and the rate of brain volume loss. Secondary analysis also showed a benefit on measures of cognitive functioning. The risk of lymphopenia and first-dose bradycardia appears to be lower with siponimod compared to non-selective S1P1R modulators. Different CYP2C9 genotypes affect the metabolism of siponimod; hence, genetic testing is required to adapt the titration and final dose accordingly. CONCLUSION Long-term extension and real-world studies will allow further evaluation of efficacy and safety in this population. Future research should focus on better defining SPMS, and identifying biomarkers of progression and outcome measures of treatment response in this category of patients.
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Affiliation(s)
- Sajida Sabsabi
- Department of Neurology, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Elio Mikhael
- Department of Internal Medicine, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Georges Jalkh
- Department of Neurology, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
| | - Gabrielle Macaron
- Department of Neurology, Hotel Dieu de France Hospital, Saint Joseph University, Beirut, Lebanon
- Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USA
| | - Mary Rensel
- Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USA
- Correspondence: Mary Rensel, Email
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Moccia M, Affinito G, Capacchione A, Lanzillo R, Carotenuto A, Montella E, Triassi M, Morra VB, Palladino R. Interferon beta for the treatment of multiple sclerosis in the Campania Region of Italy: Merging the real-life to routinely collected healthcare data. PLoS One 2021; 16:e0258017. [PMID: 34587188 PMCID: PMC8480611 DOI: 10.1371/journal.pone.0258017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 09/15/2021] [Indexed: 11/18/2022] Open
Abstract
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.
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Affiliation(s)
- Marcello Moccia
- Department of Neuroscience, Reproductive Science and Odontostomatology, Multiple Sclerosis Clinical Care and Research Centre, Federico II University of Naples, Naples, Italy
- * E-mail: ,
| | - Giuseppina Affinito
- Department of Public Health, Federico II University of Naples, Naples, Italy
| | - Antonio Capacchione
- Merck Serono S.p.A (an affiliate of Merck KGaA, Darmstadt, Germany), Rome, Italy
| | - Roberta Lanzillo
- Department of Neuroscience, Reproductive Science and Odontostomatology, Multiple Sclerosis Clinical Care and Research Centre, Federico II University of Naples, Naples, Italy
| | - Antonio Carotenuto
- Department of Neuroscience, Reproductive Science and Odontostomatology, Multiple Sclerosis Clinical Care and Research Centre, Federico II University of Naples, Naples, Italy
| | - Emma Montella
- Health Management Office, Federico II University Hospital of Naples, Naples, Italy
| | - Maria Triassi
- Department of Public Health, Federico II University of Naples, Naples, Italy
| | - Vincenzo Brescia Morra
- Department of Neuroscience, Reproductive Science and Odontostomatology, Multiple Sclerosis Clinical Care and Research Centre, Federico II University of Naples, Naples, Italy
| | - Raffaele Palladino
- Department of Public Health, Federico II University of Naples, Naples, Italy
- Department of Primary Care and Public Health, Imperial College, London, United Kingdom
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Mardan J, Hussain MA, Allan M, Grech LB. Objective medication adherence and persistence in people with multiple sclerosis: a systematic review, meta-analysis, and meta-regression. J Manag Care Spec Pharm 2021; 27:1273-1295. [PMID: 34464209 PMCID: PMC10391062 DOI: 10.18553/jmcp.2021.27.9.1273] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND: Medication adherence is critical for the realization of pharmacotherapy benefits and reduced healthcare expenditure. Studies have shown up to 60% of people with Multiple sclerosis (MS) experience suboptimal medication adherence, which is associated with poorer health outcomes and subsequent discontinuation. The current systematic review reported on objectively measured adherence and discontinuation rates for self-administered oral and injectable disease-modifying therapies (DMTs). OBJECTIVES: To identify whether, in people with MS, the introduction of oral DMTs has improved medication adherence when compared with injectable DMTs. The secondary aim was to report synthesized objectively measured medication adherence and persistence rates for both oral and injectable DMTs in MS across varying study durations. METHODS: Literature searches were conducted through PubMed, Web of Science, Scopus, and PsycINFO. Inclusion criteria were limited to English, peer-reviewed, objective, self-administered DMT articles, published between July 1993 to December 2019. Publications reporting combined intravenous and self-administered DMT data, or that did not account for DMT switching in discontinuation rates, were excluded. Data were synthesized into observation lengths ranging from less than 8 months to greater than 36 months. Meta-analysis and meta-regression were undertaken on both oral and injectable 12-month adherence and discontinuation data. RESULTS: In total, 61 articles were included; 46 articles examined adherence and 26 examined discontinuation. Twelve-month adherence ranged between 53.0% to 89.2% for oral (N = 7) and 47.0% to 77.4% for injectable DMTs (N = 7). Results from the meta-analysis and meta-regression show significantly higher pooled mean medication possession ratio (MPR) adherence for oral DMTs (91.0%) when compared to injectable DMTs (77.0%) over 12 months (β = -0.146; 95% CI: -0.263 to -0.029). Results indicate major asymmetry across studies (LFK index: -5.18), proposing the presence of significant publication bias. Mean discontinuation over 12 months was between 10.5% to 33.3% for oral (N = 7) and 15.2% to 50.8% for injectable DMTs (N = 10), with meta-analysis results indicating the presence of significant heterogeneity (I2 Injectable: 99.5%; I2 Oral: 93.1%) between studies included in each subgroup. However, no appreciable difference in mean discontinuation rates across groups (Injectable: 27%; 95% Cl: 19.0%-34.0%; Oral: 24%; 95% CI: 17.0%-31.0%) was found. CONCLUSIONS: Medication adherence for oral DMTs suggests a significant improvement compared to adherence for injectable DMTs. No significant difference in discontinuation rates between oral and injectable DMTs was found. Oral DMT adherence and persistence studies are limited, given their relatively recent introduction. Suboptimal medication adherence and discontinuation issues remain present for both oral and injectable DMTs. Future studies would benefit from improved consistency in methodology, such as comparable adherence and persistence definitions. DISCLOSURES: The authors did not receive any funding for this study. Mardan and Hussain have nothing to disclose. Grech reports grants from Merck Pharmaceutical, outside the submitted work. Allan reports grants received from Merck Pharmaceutical outside the submitted work. Allan holds advisory board and consulting positions with Merck and advisory board positions for Bristol Myers Squibb and Novartis, for which Monash Institute of Neurological Diseases receives consulting fees.
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Affiliation(s)
- Joshua Mardan
- School of Health Sciences, Swinburne University of Technology, and Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia
| | - Mohammad Akhtar Hussain
- Public Health Unit, Central Coast Local Health District, New South Wales, Australia, and Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
| | - Michelle Allan
- Department of Neurology, Monash Health, Melbourne, Australia
| | - Lisa B Grech
- School of Health Sciences, Swinburne University of Technology; Department of Medicine, School of Clinical Sciences at Monash Health, Monash University; Department of Cancer Experiences Research, Peter MacCallum Cancer Centre; and Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia
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Bauer B, Brockmeier B, Devonshire V, Charbonne A, Wach D, Hendin B. An international discrete choice experiment assessing patients' preferences for disease-modifying therapy attributes in multiple sclerosis. Neurodegener Dis Manag 2020; 10:369-382. [DOI: 10.2217/nmt-2020-0034] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Aim: This discrete choice experiment aimed to assess patients' preferences for treatment attributes in multiple sclerosis (MS). Patients & methods: Patients with relapsing-remitting MS completed an online survey assessing treatment preferences. Descriptive statistical analysis and discrete choice hierarchical Bayesian modeling were performed. Results: Across the overall sample (n = 485), dosing regimen, efficacy and safety were equally important. Within the whole sample, and among those diagnosed <10 years ago, intravenous infusion ≤3 times/year was the preferred dosing regimen; among patients diagnosed ≥10 years ago it was preferred equally to oral treatments. Patients were more willing to accept frequent but mild over rare but severe side effects. Conclusion: Several factors influence patient preferences for MS treatments and must be considered in patient-centered care.
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Affiliation(s)
- Birgit Bauer
- Patient Advocate for MS – Manufaktur für Antworten UG, 93326 Abensberg, Germany
| | | | - Virginia Devonshire
- Department of Medicine, University of British Columbia, V6T 2B5 Vancouver, BC, Canada
- Djavad Mowafaghian Centre for Brain Health, V6T 1Z3 Vancouver, BC, Canada
| | | | - Daniela Wach
- F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland
| | - Barry Hendin
- University of Arizona Medical School, 85724 Tucson, AZ, USA
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Moccia M, Loperto I, Lanzillo R, Capacchione A, Carotenuto A, Triassi M, Brescia Morra V, Palladino R. Persistence, adherence, healthcare resource utilisation and costs for interferon Beta in multiple sclerosis: a population-based study in the Campania region (southern Italy). BMC Health Serv Res 2020; 20:797. [PMID: 32847587 PMCID: PMC7448448 DOI: 10.1186/s12913-020-05664-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 08/17/2020] [Indexed: 12/19/2022] Open
Abstract
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.
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Affiliation(s)
- Marcello Moccia
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Via Sergio Pansini 5, Building 17, Ground floor, 80131, Naples, Italy.
| | - Ilaria Loperto
- Department of Public Health, Federico II University, Naples, Italy
| | - Roberta Lanzillo
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Via Sergio Pansini 5, Building 17, Ground floor, 80131, Naples, Italy
| | - Antonio Capacchione
- Merck Serono S.p.A (an affiliate of Merck KGaA, Darmstadt, Germany), Rome, Italy
| | - Antonio Carotenuto
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Via Sergio Pansini 5, Building 17, Ground floor, 80131, Naples, Italy
| | - Maria Triassi
- Department of Public Health, Federico II University, Naples, Italy
| | - Vincenzo Brescia Morra
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Via Sergio Pansini 5, Building 17, Ground floor, 80131, Naples, Italy
| | - Raffaele Palladino
- Department of Public Health, Federico II University, Naples, Italy.,Department of Primary Care and Public Health, Imperial College, London, UK
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11
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Gross RH, Corboy JR. Monitoring, Switching, and Stopping Multiple Sclerosis Disease-Modifying Therapies. Continuum (Minneap Minn) 2019; 25:715-735. [PMID: 31162313 DOI: 10.1212/con.0000000000000738] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW This article reviews appropriate monitoring of the various multiple sclerosis (MS) disease-modifying therapies, summarizes the reasons patients switch or stop treatment, and provides a framework for making these management decisions. RECENT FINDINGS With the increasing number of highly effective immunotherapies available for MS, the possibility of better control of the disease has increased, but with it, the potential for side effects has rendered treatment decisions more complicated. Starting treatment early with more effective and better-tolerated disease-modifying therapies reduces the likelihood of switching because of breakthrough disease or lack of compliance. Clinical and radiographic surveillance, and often blood and other paraclinical tests, should be performed periodically, depending on the disease-modifying therapy. Helping patients navigate the uncertainty around switching or stopping treatment, either temporarily or permanently, is one of the most important things we do as providers of MS care. SUMMARY Ongoing monitoring of drug therapy is a crucial component of long-term MS care. Switching treatments may be necessary for a variety of reasons. Permanent discontinuation of treatment may be appropriate for some patients with MS, although more study is needed in this area.
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12
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Nicholas JA, Electricwala B, Lee LK, Johnson KM. Burden of relapsing-remitting multiple sclerosis on workers in the US: a cross-sectional analysis of survey data. BMC Neurol 2019; 19:258. [PMID: 31660897 PMCID: PMC6816180 DOI: 10.1186/s12883-019-1495-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 10/13/2019] [Indexed: 12/31/2022] Open
Abstract
Background Multiple sclerosis (MS) is prevalent among working age individuals (20–60 years), leading to high burden on work productivity. Few data are available about the absenteeism and presenteeism in employed individuals with MS in comparison to non-MS personnel. This study aimed to quantify the burden of illness of employed US adults with relapsing-remitting multiple sclerosis (RRMS) and examine burden by levels of work impairment. Methods A retrospective cross-sectional analysis was conducted using patient-reported responses from the US National Health and Wellness Survey (NHWS). Data from NHWS 2015–2016 were analyzed from 196 employed RRMS respondents who were matched 1:4 to employed respondents without MS based on demographic and general health characteristics. Demographic and general health characteristics for employed RRMS individuals were analyzed by levels of work impairment (none, 1–30%; 31–68%; 69–100%). Work productivity (absenteeism, presenteeism, and work impairment), decrements in health-related quality of life (HRQoL) (short form-36, EQ-5D), and healthcare resource utilization (HCRU) were compared to determine the burden of RRMS. Results After propensity score matching, the levels of absenteeism and presenteeism were 2 and 1.8 times higher in the employed RRMS population than the employed non-MS population, respectively (P < 0.001 for both). HRQoL was significantly lower in employed respondents with RRMS than those without MS (P < 0.001 for all). Employed respondents with RRMS had significantly more HCRU over 6 months compared to those without MS (P < 0.001). Furthermore, among employed RRMS respondents, greater levels of impairment were associated with increasing disease severity, greater healthcare resource use, fatigue, and cognitive impairment and inversely associated with mental and physical HRQoL (P < 0.0001 for all). Conclusions Among employed individuals, respondents with RRMS had lower, work productivity, HRQoL, and higher HCRU as compared with those without MS. Given the large impact RRMS has on work impairment, a need exists to manage individuals on therapies that improve HRQoL, reduce symptoms, and improve their ability to perform in the workforce.
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Affiliation(s)
- Jacqueline A Nicholas
- OhioHealth Multiple Sclerosis Clinic, Riverside Methodist Hospital, Columbus, OH, USA
| | - Batul Electricwala
- Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936, USA
| | | | - Kristen M Johnson
- Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936, USA.
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13
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Saccà F, Lanzillo R, Signori A, Maniscalco GT, Signoriello E, Lo Fermo S, Repice A, Annovazzi P, Baroncini D, Clerico M, Binello E, Cerqua R, Mataluni G, Bonavita S, Lavorgna L, Zarbo IR, Laroni A, Rossi S, Pareja Gutierrez L, La Gioia S, Frigeni B, Barcella V, Frau J, Cocco E, Fenu G, Torri Clerici V, Sartori A, Rasia S, Cordioli C, Di Sapio A, Pontecorvo S, Grasso R, Barrilà C, Russo CV, Esposito S, Ippolito D, Bovis F, Gallo F, Sormani MP. Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study. Mult Scler 2018; 25:1263-1272. [DOI: 10.1177/1352458518790390] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. Objectives: To identify prognostic factors for early switch after first therapy choice. Methods: Newly diagnosed relapsing–remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. Results: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047). Conclusion: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.
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Affiliation(s)
- Francesco Saccà
- Multiple Sclerosis Center, Department of Neuroscience, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy
| | - Roberta Lanzillo
- Multiple Sclerosis Center, Department of Neuroscience, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy
| | - Alessio Signori
- Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, Genova, Italy
| | - Giorgia T Maniscalco
- Neurological Clinic and Multiple Sclerosis Center, “AORN A.Cardarelli,” Naples, Italy
| | - Elisabetta Signoriello
- Multiple Sclerosis Center, II Division of Neurology, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Salvatore Lo Fermo
- Neurological Clinic, A.O.U. Policlinico Vittorio Emanuele, Catania, Italy
| | - Annamaria Repice
- 2nd Neurology Unit and CRRSM (Regional Referral Multiple Sclerosis Center), Careggi University Hospital and University of Florence, Florence, Italy
| | - Pietro Annovazzi
- Multiple Sclerosis Study Center, ASST Valle Olona, PO di Gallarate (VA), Gallarate, Italy
| | - Damiano Baroncini
- Multiple Sclerosis Study Center, ASST Valle Olona, PO di Gallarate (VA), Gallarate, Italy
| | - Marinella Clerico
- Clinical and Biological Sciences Department, Neurology Unit, University of Torino, San Luigi Gonzaga University Hospital, Torino, Italy
| | - Eleonora Binello
- Centro Sclerosi Multipla, Dipartimento di Neuroscienze, AOU Città della Salute e della Scienza di Torino, Torino, Italy
| | - Raffaella Cerqua
- Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy
| | | | - Simona Bonavita
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Luigi Lavorgna
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Ignazio Roberto Zarbo
- Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
| | - Alice Laroni
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research (CEBR) and IRCCS San Martino-IST, University of Genova, Genova, Italy
| | - Silvia Rossi
- Neuro-immunology and Neuromuscolar Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy
| | - Lorena Pareja Gutierrez
- Neuro-immunology and Neuromuscolar Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy
| | - Sara La Gioia
- Centro Sclerosi Multipla, ASST Papa Giovanni XXIII di Bergamo, Bergamo, Italy
| | - Barbara Frigeni
- Centro Sclerosi Multipla, ASST Papa Giovanni XXIII di Bergamo, Bergamo, Italy
| | - Valeria Barcella
- Centro Sclerosi Multipla, ASST Papa Giovanni XXIII di Bergamo, Bergamo, Italy
| | - Jessica Frau
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Eleonora Cocco
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Giuseppe Fenu
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Valentina Torri Clerici
- Neuro-immunology and Neuromuscolar Diseases Unit, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy
| | - Arianna Sartori
- Neurology Clinic, Department of Medical, Surgical, and Health Sciences, University of Trieste, Trieste, Italy
| | - Sarah Rasia
- Multiple Sclerosis Center, ASST Spedali Civili, PO di Montichiari (BS), Montichiari, Italy
| | - Cinzia Cordioli
- Multiple Sclerosis Center, ASST Spedali Civili, PO di Montichiari (BS), Montichiari, Italy
| | - Alessia Di Sapio
- 2nd Neurology Unit and CRRSM (Regional Referral Multiple Sclerosis Center), AOU San Luigi Gonzaga, Torino, Italy; Regina Montis Regalis Hospital, Mondovì, Italy
| | - Simona Pontecorvo
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | | | | | - Cinzia Valeria Russo
- Multiple Sclerosis Center, Department of Neuroscience, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy
| | - Sabrina Esposito
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Domenico Ippolito
- Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Francesca Bovis
- Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, Genova, Italy
| | - Fabio Gallo
- Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, Genova, Italy
| | - Maria Pia Sormani
- Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genova, Genova, Italy
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14
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Lanzillo R, Prosperini L, Gasperini C, Moccia M, Fantozzi R, Tortorella C, Nociti V, Annovazzi P, Cavalla P, Radaelli M, Malucchi S, Clerici VT, Boffa L, Buttari F, Ragonese P, Maniscalco GT, Di Filippo M, Buscarinu MC, Pinardi F, Gallo A, Coghe G, Pesci I, Laroni A, Gajofatto A, Calabrese M, Tomassini V, Cocco E, Solaro C. A multicentRE observational analysiS of PErsistenCe to Treatment in the new multiple sclerosis era: the RESPECT study. J Neurol 2018; 265:1174-1183. [PMID: 29549468 DOI: 10.1007/s00415-018-8831-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 03/11/2018] [Indexed: 11/27/2022]
Abstract
In this independent, multicenter, retrospective study, we investigated the short-term persistence to treatment with first-line self-injectable or oral disease-modifying treatments (DMTs) in patients with relapsing-remitting multiple sclerosis. Data of patients regularly attending 21 Italian MS Centres who started a self-injectable or an oral DMT in 2015 were collected to: (1) estimate the proportion of patients discontinuing the treatment; (3) explore reasons for discontinuation; (3) identify baseline predictors of treatment discontinuation over a follow-up period of 12 months. We analyzed data of 1832 consecutive patients (1289 women, 543 men); 374 (20.4%) of them discontinued the prescribed DMT after a median time of 6 months (range 3 days to 11.5 months) due to poor tolerability (n = 163; 43.6%), disease activity (n = 95; 25.4%), adverse events (n = 64; 17.1%), convenience (i.e. availability of new drug formulations) and pregnancy planning (n = 21; 1.1%). Although the proportion of discontinuers was higher with self-injectable (n = 107; 22.9%) than with oral DMT (n = 215; 16.4%), the Cox regression model revealed no significant between-group difference (p = 0.12). Female sex [hazard ratio (HR) = 1.39, p = 0.01] and previous exposure to ≥ 3 DMTs (HR = 1.71, p = 0.009) were two independent risk factors for treatment discontinuation, regardless of prescribed DMTs. Our study confirms that persistence to treatment represents a clinical challenge, irrespective of the route of administration.
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Affiliation(s)
- Roberta Lanzillo
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
| | - Luca Prosperini
- Department of Neurosciences, S. Camillo-Forlanini Hospital, C.ne Gianicolense 87, 00152, Rome, Italy.
- Department of Neurology and Psychiatry, Sapienza University, Rome, Italy.
| | - Claudio Gasperini
- Department of Neurosciences, S. Camillo-Forlanini Hospital, C.ne Gianicolense 87, 00152, Rome, Italy
| | - Marcello Moccia
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy
| | | | - Carla Tortorella
- Department of Neurosciences, S. Camillo-Forlanini Hospital, C.ne Gianicolense 87, 00152, Rome, Italy
| | - Viviana Nociti
- Department of Geriatrics, Neurosciences and Orthopedics, Institute of Neurology, Catholic University, Rome, Italy
| | - Pietro Annovazzi
- MS Study Center, ASST Valle Olona, Gallarate Hospital, Gallarate, VA, Italy
| | - Paola Cavalla
- MS Center, Neurology 1 Unit, City of Health and Science University Hospital, Turin, Italy
| | - Marta Radaelli
- Division of Neuroscience, Institute of Experimental Neuroscience (INSpe), S. Raffaele Scientific Institute, Milan, Italy
| | - Simona Malucchi
- SCDO Neurologia 2-Regional Multiple Sclerosis Center, University Hospital San Luigi Gonzaga, Orbassano, TO, Italy
| | - Valentina Torri Clerici
- Department of Neuroimmunology and Neuromuscular Diseases, Neurological Institute C. Besta IRCCS Foundation, Milan, Italy
| | - Laura Boffa
- MS Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy
| | - Fabio Buttari
- Department of Neurology, IRCCS NEUROMED, Pozzilli, IS, Italy
- MS Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy
| | - Paolo Ragonese
- Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, Italy
| | | | | | - Maria Chiara Buscarinu
- Department of Neurosciences, Center for Experimental Neurological Therapies, S. Andrea Hospital, Mental Health and Sensory Organs (NESMOS), Sapienza University, Rome, Italy
| | - Federica Pinardi
- MS Centre, Bellaria Hospital, UOSI-SM Rehabilitation, Bellaria, BO, Italy
| | - Antonio Gallo
- I Clinic of Neurology, University of Campania, Naples, Italy
| | - Giancarlo Coghe
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Ilaria Pesci
- MS Centre, Neurology Unit, S. Secondo Hospital, Fidenza, PA, Italy
| | - Alice Laroni
- Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy
| | - Alberto Gajofatto
- Department of Neuroscience, Biomedicine and Movement Sciences, University Hospital of Verona, Verona, Italy
| | - Massimiliano Calabrese
- Department of Neuroscience, Biomedicine and Movement Sciences, University Hospital of Verona, Verona, Italy
| | - Valentina Tomassini
- Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK
| | - Eleonora Cocco
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Claudio Solaro
- Neurology Unit, Centro di Recupero e Rieducazione Funzionale, Moncrivello, VC, Italy
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15
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Moccia M, Palladino R, Carotenuto A, Saccà F, Russo CV, Lanzillo R, Brescia Morra V. A 8-year retrospective cohort study comparing Interferon-β formulations for relapsing-remitting multiple sclerosis. Mult Scler Relat Disord 2017; 19:50-54. [PMID: 29128737 DOI: 10.1016/j.msard.2017.11.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Revised: 10/13/2017] [Accepted: 11/05/2017] [Indexed: 11/28/2022]
Abstract
BACKGROUND Interferon-β has been approved for the treatment of relapsing-remitting (RR) multiple sclerosis (MS), whereas its efficacy in preventing long-term disability and conversion to secondary progressive (SP) MS is still debated. We aim to compare long-term clinical evolution of newly-diagnosed RRMS patients treated with different Interferon-β formulations. METHODS 507 patients were included in the analysis and followed-up for 8.5 ± 3.9 years. 37.6% were treated with subcutaneous Interferon-β1a 44mcg, 33.4% with intramuscular Interferon-β1a 30mcg, and 29.0% with subcutaneous Interferon-β1b 250mcg. Relapse occurrence, 1-point EDSS progression, reaching of EDSS 4.0 and conversion to SP were recorded as outcome measures. To reduce the selection bias, we calculated the propensity score of receiving the specific treatment considering age (32.7 ± 8.3 years), gender (female 63.1%), disease duration (2.7 ± 2.8 years), and baseline EDSS (1.5, range 1.0-3.5). Propensity score and covariates (age, gender, disease duration and EDSS) were included in the statistical models. RESULTS At Cox regression models, the reaching of EDSS 4.0 was not-significantly higher for Interferon-β1b 250mcg (HR = 1.207; p = 0.063) and for Interferon-β1a 30mcg (HR = 1.363; p = 0.095), when compared with Interferon-β1a 44mcg. The rate of SP conversion was higher for Interferon-β1b 250mcg (HR = 2.054; p = 0.042), and not-significantly higher for Interferon-β1a 30mcg (HR = 1.884; p = 0.081), when compared with Interferon-β1a 44mcg. CONCLUSIONS Patients treated with Interferon-β1a 44mcg presented with a marginally reduced risk of disability accrual in the long-term, when compared with Interferon-β1b 250mcg and, at least in part, with Interferon-β1a 30mcg. Formulation, frequency of administration and dose of Interferon-β might affect the long-term clinical evolution of RRMS.
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Affiliation(s)
- Marcello Moccia
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Via Sergio Pansini, 5 - Building 17, Ground floor, Naples, Italy.
| | - Raffaele Palladino
- Department of Primary Care and Public Health, Imperial College, London, United Kingdom; Department of Public Health, Federico II University, Naples, Italy
| | - Antonio Carotenuto
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Via Sergio Pansini, 5 - Building 17, Ground floor, Naples, Italy
| | - Francesco Saccà
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Via Sergio Pansini, 5 - Building 17, Ground floor, Naples, Italy
| | - Cinzia Valeria Russo
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Via Sergio Pansini, 5 - Building 17, Ground floor, Naples, Italy
| | - Roberta Lanzillo
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Via Sergio Pansini, 5 - Building 17, Ground floor, Naples, Italy
| | - Vincenzo Brescia Morra
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Via Sergio Pansini, 5 - Building 17, Ground floor, Naples, Italy
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16
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Moccia M, Lanzillo R, Cerullo G, De Rosa A, Brescia Morra V. The importance of being persistent to multiple sclerosis treatments. J Clin Neurosci 2017; 40:198-199. [PMID: 28246007 DOI: 10.1016/j.jocn.2017.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Accepted: 02/07/2017] [Indexed: 10/20/2022]
Affiliation(s)
- Marcello Moccia
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy.
| | - Roberta Lanzillo
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy
| | - Giovanni Cerullo
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy
| | - Anna De Rosa
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy
| | - Vincenzo Brescia Morra
- Multiple Sclerosis Clinical Care and Research Centre, Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy
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17
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Healthcare Costs for Treating Relapsing Multiple Sclerosis and the Risk of Progression: A Retrospective Italian Cohort Study from 2001 to 2015. PLoS One 2017; 12:e0169489. [PMID: 28056103 PMCID: PMC5215923 DOI: 10.1371/journal.pone.0169489] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Accepted: 12/16/2016] [Indexed: 11/19/2022] Open
Abstract
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.
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Melesse DY, Marrie RA, Blanchard JF, Yu BN, Evans C. Persistence to disease-modifying therapies for multiple sclerosis in a Canadian cohort. Patient Prefer Adherence 2017; 11:1093-1101. [PMID: 28721023 PMCID: PMC5499788 DOI: 10.2147/ppa.s138263] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
PURPOSE To examine the long-term persistence to the first-line injectable disease-modifying therapies (DMTs) for multiple sclerosis (MS) and to identify the factors associated with nonpersistence. PATIENTS AND METHODS We used population-based administrative data from Manitoba, Canada. All adult subjects who were diagnosed with MS and dispensed a first-line injectable DMT (beta-interferon-1b, beta-interferon-1a, and glatiramer acetate) between 1996 and 2011 and had a minimum of 1 year of follow-up were included. The primary outcome was the median time to discontinuation of any DMT. The associations between potential predictors and persistence were estimated using multivariable Cox-proportional hazard models. RESULTS Overall, 721 subjects were followed for a median of 7.8 years (interquartile range 6.1). The median time to discontinuation of all first-line DMTs was 4.2 years (25th and 75th percentile: 1.7, 10.6 years). Of the 451 (62.6%) subjects who discontinued their DMT during the study period, 259 (57.4%) eventually resumed or restarted a DMT. Subjects who were younger when starting a DMT, had prior MS-related hospitalizations, were more recently diagnosed with MS, or had a greater lag time between their MS diagnosis and DMT initiation were more likely to discontinue therapy. CONCLUSION Over half of the individuals receiving a DMT for MS in Manitoba remained on therapy for at least 4 years. DMT discontinuation occurred in 60% of the cohort, but most restarted a DMT within 1 year. While not all of the factors identified with discontinuing DMT are modifiable, they may help practitioners enhance MS care by identifying individuals who may be at particular risk for DMT discontinuation.
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Affiliation(s)
| | - Ruth Ann Marrie
- Department of Community Health Sciences
- Department of Internal Medicine, University of Manitoba
| | | | - Bo Nancy Yu
- Centre for Global Public Health
- Public Health, Manitoba Health Seniors and Active Living, Winnipeg, Manitoba
| | - Charity Evans
- College of Pharmacy & Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
- Correspondence: Charity Evans, College of Pharmacy & Nutrition, University of Saskatchewan, 104 Clinic Place, Saskatoon, SK, S7N 2Z4, Canada, Tel +1 306 966 2836, Fax +1 306 966 6377, Email
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Boyko AN, Gusev EI. Current algorithms of diagnosis and treatment of multiple sclerosis based on the individual assessment of the patient. Zh Nevrol Psikhiatr Im S S Korsakova 2017; 117:92-106. [DOI: 10.17116/jnevro20171172292-106] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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