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Improved treatment satisfaction after switching therapy to rituximab in relapsing-remitting MS
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neurology, Östersund Hospital, Östersund, Sweden.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
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2017 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, no 9, p. 1249-1257Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: New disease-modifying treatment strategies in multiple sclerosis offer possibilities for individualised treatment. In this study, we evaluated patient-reported outcome measures before and after a switch in therapy from first-line injectable treatments to rituximab.

METHOD: A total of 75 patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) receiving ongoing first-line injectable treatment at three Swedish centres had their treatment switched to rituximab in this open-label phase II multicentre study. Assessment of treatment satisfaction, patient-perceived impact of the disease on daily life, fatigue, cognitive symptoms and disease progression was performed 3 months before and at the time of the treatment shift and then for a subsequent 2-year period.

RESULTS: The overall treatment satisfaction rating improved significantly from a mean of 4.8 (scale range: 1-7), while on injectable therapies, to a mean of 6.3 after 1 year of rituximab treatment ( p < 0.001). This improvement was sustained after 2 years. There was no significant change in scores for patient-perceived impact of disease, fatigue or disease progression.

CONCLUSION: A shift in therapy from first-line injectables to rituximab in a cohort of clinically stable RRMS patients was followed by improved treatment satisfaction. This is clinically relevant as it may influence long-term adherence to immunomodulating therapy.

Place, publisher, year, edition, pages
2017. Vol. 23, no 9, p. 1249-1257
Keywords [en]
B-cell depletion therapy, Multiple sclerosis, clinical trial, patient-reported outcome measures, rituximab, treatment satisfaction
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-134988DOI: 10.1177/1352458516676643ISI: 000406386600013PubMedID: 27780912OAI: oai:DiVA.org:umu-134988DiVA, id: diva2:1095654
Available from: 2017-05-15 Created: 2017-05-15 Last updated: 2018-06-09Bibliographically approved
In thesis
1. Treatment with the monoclonal antibody rituximab in Multiple Sclerosis: a study based on an academic clinical trial
Open this publication in new window or tab >>Treatment with the monoclonal antibody rituximab in Multiple Sclerosis: a study based on an academic clinical trial
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Multiple sclerosis (MS) is a chronic, inflammatory disease, affecting the central nervous system. A growing number of disease modifying treatment alternatives entails a need for an individualised risk-benefit- convenience analysis in the counselling of patients and methods to monitor the treatment effect, including markers for subclinical inflammation. Today, MRI and the biomarker neurofilament light chain (NFL) in cerebrospinal fluid (CSF- NFL) are commonly used. The development of new techniques for analysing NFL in very low concentrations in serum or plasma provides a promising opportunity for a less invasive method. Rituximab is a chimeric monoclonal antibody with B- cell depleting properties vastly used in rheumatological disease and certain haematological malignancies. Phase II studies have shown a beneficial effect on inflammation also in MS, the detailed mechanisms of action yet to be explained.

Aims: The aims of this thesis were to evaluate rituximab as a treatment alternative in relapsing remitting MS (RRMS) by describing the clinical effect and patient related outcome measures after a switch of therapy from first-line injectables to rituximab and to explore possible immunological mechanisms of B cell depletion as well as to evaluate the use of neurofilament in plasma (p-NFL) as an end-point in a clinical trial setting.

Methods: The thesis is based on the open-label phase II multicentre clinical trial Switch-To-RItuXimab in MS (STRIX-MS; EudraCT 2010-023021-38), in which 75 patients completed a therapy switch from first-line injectables to rituximab, and, to some part, the extended follow-up study, STRIX-MS extension (EudraCT 2013-002378-26). The disease modifying effect was evaluated by regular clinical evaluations, MRI and analyses of CSF-NFL. The clinical outcome was evaluated by the EDSS and SDMT scales. The questionnaires MSIS-29, FSMC and TSQM were used for the evaluation of patient related outcome measures. Immunological mechanisms of the B cell depletion were explored by the analysis of a broad panel of cyto- and chemokines in CSF by an electrochemiluminiscens method before and after therapy switch, and in comparison to healthy controls. The concentration of p-NFL was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit and explored for the use as a clinical trial end-point.

Results: During the follow-up, signs of inflammatory activity decreased. Both the mean number of Gd enhancing lesions (0.03 vs 0.36, p=0.029) and the number of new or enlarged T2 lesions were reduced (0.01 vs 0.28, p=0.01). The mean concentration of CSF-NFL was reduced during the first year (491 vs 387, p=0.01). The corresponding reduction in plasma did not reach the level of statistical significance. The rating of overall treatment satisfaction improved significantly (6.3 vs 4.8, scale range 1-7, p<0.001). In the explorative immunological study, the immunological profile was altered after therapy switch with the most prominent reduction observed in the concentrations of IP-10 and IL-12/23p40.

Conclusions: The results indicate a disease modifying effect of rituximab in line with other studies and provide support for a superior treatment satisfaction with rituximab as compared with injectable therapies. However, the lack of control group hampers the possibility to draw definite conclusions on the therapy effect. The immunological effects of B cell depletion need to be further explored.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2018. p. 50
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1951
Keywords
Multiple sclerosis, Rituximab, Cytokines, Immunological profile, Neurofilament light, Treatment satisfaction
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-145875 (URN)978-91-7601-854-5 (ISBN)
Public defence
2018-04-27, Hörsalen Snäckan, Östersunds sjukhus, Östersund, 09:00 (Swedish)
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Supervisors
Available from: 2018-04-06 Created: 2018-03-26 Last updated: 2018-06-09Bibliographically approved

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de Flon, PierreLaurell, KatarinaSvenningsson, Anders

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