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- Bejerot, Susanne, 1955-, et al.
(författare)
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Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits)
- 2023
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Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture.METHODS: A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research.DISCUSSION: This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma.TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.
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| 2. |
- Fink, K., et al.
(författare)
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CLADCOMS - CLADribine tablets long-term Control Of MS - a post-marketing investigator driven study
- 2022
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 847-848
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cladribine is a deoxyadenosine analogue prodrug that selectively induces immune reconstitution by targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. CLADCOMS (CLADribine tablets long-term Control Of MS) is a post-marketing investigator driven study. Here we report one year follow-up data on the first 100 patients included in the study in April 2021.Objective: 1) To investigate for how long a full dose treatment with Cladribine 10 mg tablets (3.5 mg/kg over two years) offers freedom of disease activity in relapsing MS patients.2) To collect complete data on safety and effectiveness with the help of the Swedish Neuroregistry to enable future assessment on effectiveness and safety in comparison with other in Sweden commonly used disease modifying treatments.Methods: CLADCOMS includes patients with relapsing MS from the eight academic clinics starting Cladribine treatment after 23rd of March 2018. Data is collected in the Swedish Neuroregistry using highly structured yearly follow-up routines. Descriptive data on relapses, MRI activity, Patient Reported Outcome Measures and Serious Adverse events (SAEs) from the first 100 patient included in the study are obtained from the registry.Results: Up to April 2022 1XX patients were included in the study. In April 2021 the first 100 patient entered the study. 40% of patients included were treatment naïve, 29% switched from natalizumab and 13% from rituximab. By April 2022, 5 patients experienced a relapse during the treatment initiation and showed MRT activity with contrast enhancing (CEL)lesions more than six months after initiation of treatment, of which 2 patients showed CEL more than six months after the second treatment course year two. 20% of the patients showed new lesions on the first MRI performed up to 18 months after treatment initiation. Two patients reported SEAs. Analysis of CD19 and CD27- B-cells counts over time will be performed.Conclusions: Cladribine treatment demonstrates clinical stability in patients treated ⩾ 12 months. However, continued follow-up is needed to assess the effectiveness and safety of treatment with Cladribine over a longer time to investigate time to disease reactivation after the second treatment course year two has been administered.
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| 3. |
- Silfverberg, Thomas, et al.
(författare)
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Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study
- 2023
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA growing evidence base supports the use of autologous haematopoietic stem cell transplantation (aHSCT) for treatment of relapsing-remitting multiple sclerosis (RRMS), but it has not yet been integrated into most national clinical guidelines. The objective of this study was to assess efficacy and safety when aHSCT is implemented in routine healthcare.MethodsWe assessed 231 patients and the final analysis included 174 RRMS patients who were treated with aHSCT in Sweden before 1 January 2020. Efficacy was evaluated by performing a retrospective analysis of prospectively collected data from the Swedish MS registry. Procedure-related safety was assessed by analysing data from electronic patient records covering a period of 100 days following aHSCT.ResultsWith a median follow-up time of 5.5 (IQR: 3.4-7.5) years, the Kaplan-Meier estimate for no evidence of disease activity was 73% (95% CI 66% to 81%) at 5 years and 65% (95% CI 57% to 75%) at 10 years. Out of the 149 patients with baseline disability, 80 (54%) improved, 55 (37%) were stable and 14 (9%) deteriorated. The mean number of adverse events per patient was 1.7 (& PLUSMN;SD: 1.5) for grade 3 events and 0.06 (& PLUSMN;SD: 0.3) for grade 4 events. Febrile neutropenia was the most common adverse event, affecting 68% of patients. There was no treatment-related mortality.ConclusionsTreatment with aHSCT for RRMS is associated with freedom from disease activity in a majority of patients, with acceptable adverse events. This procedure should be considered a standard of care for patients with highly active RRMS.
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