Sirukumab: A Potential Treatment for Mood Disorders?

Abstract

Convergent evidence indicates that abnormalities in the innate immune system may be pertinent to the pathogenesis, phenomenology, and possible treatment of several mental disorders. In keeping with this view, the targeting of interleukin-6 with the human monoclonal antibody sirukumab may represent a possible treatment and disease modification approach, for adults with brain-based disorders (e.g., major depressive disorder). A PubMed/Medline database search was performed using the following search terms: sirukumab; anti-IL-6; IL-6; major depressive disorder; inflammation. A systematic review was conducted of both preclinical and clinical trials reporting on the pharmacology of sirukumab or investigating the efficacy of targeting IL-6 signaling. Overall, sirukumab has been reported to be a safe and well-tolerated agent, capable of modulating the immune response in healthy populations as well as in subjects with inflammatory disorders (e.g., rheumatoid arthritis). Sirukumab’s effects on cytokine networks as part of the innate immune system provide a coherent rationale for possible application in neuropsychiatric disorders with possible benefits across several domains of the biobehavioral Research Domain Criteria matrix (e.g., general cognitive processes, positive valence systems). Amongst individuals with complex brain-based disorders (e.g., mood disorders), the dimensions/domains most likely to benefit with sirukumab are negative valence disturbances (e.g., anxiety, depression, rumination), positive valence disturbances (e.g., anhedonia) as well as general cognitive processes. We suggest that sirukumab represents a prototype and possibly a proof-of-concept that agents that engage IL-6 targets have salutary effects in psychiatry.

Rheumatoid Arthritis: The Impact of Mental Health on Disease: A Narrative Review

“…Sarilumab, by targeting IL-6, improves depression in RA patients [ 60 ]. It is also evident that sirukumab targeting IL-6 and reducing the CRP level improved major depressive symptoms [ 89 ]. An observational study showed a positive correlation between the FACIT-F score and depression (BDI scale) (linear regression β = 0.714 and β = 0.777) ( p < 0.001).…”

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets

“…IL-6 has also been considered a new relevant pharmacological target in TRD (Zhou et al, 2017). Sirukumab (Janssen Biotech; Horsham, Pennsylvania) is a monoclonal antibody endowed with anti-inflammatory properties against IL-6 that has shown preliminary antidepressant efficacy in patients with rheumatoid arthritis (Sun et al, 2017).…”

“…Sirukumab is a safe and well-tolerated drug, and improvement in depressive symptoms in patients with rheumatoid arthritis positively correlates with baseline soluble IL-6 receptor levels (Sun et al, 2017). According to the Biobehavioral Research Domain Criteria Matrix, it has been hypothesized that the symptoms of MDD most sensitive to sirukumab may be anhedonia and cognitive deterioration (Zhou et al, 2017). A phase II clinical trial is currently ongoing to evaluate the antidepressant efficacy of adjunctive subcutaneous sirukumab compared with placebo in patients with depression (NCT02473289).…”

Interleukin 6 as a pathogenic factor mediating clinical manifestations and a therapeutic target for rheumatic diseases and depressive disorders

“…[82], посвященный изучению влияния известных синтетических БПВП и ГИБП, использующихся для лечения РА, на психическое здоровье, продемонстрировал, что ГИБП более существенно улучшают психическое здоровье, чем БПВП, причем ингибиторы ИЛ6 (клазакизумаб, сарилумаб, сирукумаб и ТЦЗ) с 90% вероятностью способны позитивно влиять на показатели, характеризующие психическое здоровье пациентов. Некоторые авторы считают, что ингибиторы ИЛ6 могут быть эффективны в отношении биполярного аффективного расстройства [83], БДР [84] и шизофрении [85]. В настоящее время инициированы рандомизированные контролирумые двойные слепые клинические исследования II фазы, посвященные изучению эффективности и переносимости сирукумаба (NCT02473289), а также ТЦЗ (NCT02660528) как дополнительного к антидепрессантам препарата для лечения БДР у взрослых [83], силтуксимаба (NCT02796859) и ТЦЗ (NCT02034474 и NCT02874573) для лечения шизофрении [86].…”