Artikel ; Online: Adjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial.
2023 Band 115, Seite(n) 191–200
Abstract: Background: Clinical trials of anti-inflammatories in schizophrenia do not show clear and replicable benefits, possibly because patients were not recruited based on elevated inflammation status. Interleukin 1-beta (IL-1β) mRNA and protein levels are ... ...
| Abstract | Background: Clinical trials of anti-inflammatories in schizophrenia do not show clear and replicable benefits, possibly because patients were not recruited based on elevated inflammation status. Interleukin 1-beta (IL-1β) mRNA and protein levels are increased in serum, plasma, cerebrospinal fluid, and brain of some chronically ill patients with schizophrenia, first episode psychosis, and clinical high-risk individuals. Canakinumab, an approved anti-IL-1β monoclonal antibody, interferes with the bioactivity of IL-1β and interrupts downstream signaling. However, the extent to which canakinumab reduces peripheral inflammation markers, such as, high sensitivity C-reactive protein (hsCRP) and symptom severity in schizophrenia patients with inflammation is unknown. Trial design: We conducted a randomized, placebo-controlled, double-blind, parallel groups, 8-week trial of canakinumab in chronically ill patients with schizophrenia who had elevated peripheral inflammation. Methods: Twenty-seven patients with schizophrenia or schizoaffective disorder and elevated peripheral inflammation markers (IL-1β, IL-6, hsCRP and/or neutrophil to lymphocyte ratio: NLR) were randomized to a one-time, subcutaneous injection of canakinumab (150 mg) or placebo (normal saline) as an adjunctive antipsychotic treatment. Peripheral blood hsCRP, NLR, IL-1β, IL-6, IL-8 levels were measured at baseline (pre injection) and at 1-, 4- and 8-weeks post injection. Symptom severity was assessed at baseline and 4- and 8-weeks post injection. Results: Canakinumab significantly reduced peripheral hsCRP over time, F(3, 75) = 5.16, p = 0.003. Significant hsCRP reductions relative to baseline were detected only in the canakinumab group at weeks 1, 4 and 8 (p's = 0.0003, 0.000002, and 0.004, respectively). There were no significant hsCRP changes in the placebo group. Positive symptom severity scores were significantly reduced at week 8 (p = 0.02) in the canakinumab group and week 4 (p = 0.02) in the placebo group. The change in CRP between week 8 and baseline (b = 1.9, p = 0.0002) and between week 4 and baseline (b = 6.0, p = 0.001) were highly significant predictors of week 8 change in PANSS Positive Symptom severity scores. There were no significant changes in negative symptoms, general psychopathology or cognition in either group. Canakinumab was well tolerated and only 7 % discontinued. Conclusions: Canakinumab quickly reduces peripheral hsCRP serum levels in patients with schizophrenia and inflammation; after 8 weeks of canakinumab treatment, the reductions in hsCRP are related to reduced positive symptom severity. Future studies should consider increased doses or longer-term treatment to confirm the potential benefits of adjunctive canakinumab in schizophrenia. Australian and New Zealand Clinical Trials Registry number: ACTRN12615000635561. |
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| Mesh-Begriff(e) | Humans ; Schizophrenia/drug therapy ; C-Reactive Protein/analysis ; Antibodies, Monoclonal/therapeutic use ; Interleukin-6 ; Australia ; Inflammation/drug therapy ; Chronic Disease ; Double-Blind Method ; Treatment Outcome |
| Chemische Substanzen | canakinumab (37CQ2C7X93) ; C-Reactive Protein (9007-41-4) ; Antibodies, Monoclonal ; Interleukin-6 |
| Sprache | Englisch |
| Erscheinungsdatum | 2023-10-15 |
| Erscheinungsland | Netherlands |
| Dokumenttyp | Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 639219-2 |
| ISSN | 1090-2139 ; 0889-1591 |
| ISSN (online) | 1090-2139 |
| ISSN | 0889-1591 |
| DOI | 10.1016/j.bbi.2023.10.012 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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