In the Journals

Rheumatoid arthritis drugs may benefit patients with schizophrenia

Treatment with antirheumatic medications — such as NSAIDs and anticytokine monoclonal antibodies — may benefit patients with schizophrenia, according to data published in Psychiatric Annals.

“Research on the microbiome in schizophrenia is still in its infancy, although there is some evidence for alterations in the gut and oropharyngeal microbiome in patients with schizophrenia compared to controls,” Peter F. Buckley, MD, dean, School of Medicine, Virginia Commonwealth University, and Brian J. Miller, MD, PhD, MPH, associate professor, department of psychiatry and health behavior, Augusta University, Georgia, wrote.

Prior research has shown that immune abnormalities exist in schizophrenia and first-episode psychosis, according to Buckley and Miller. Common medications for rheumatoid arthritis, such as NSAIDs, aim to change the immune response. Using immunotherapies as adjuncts to antipsychotic treatments for patients with schizophrenia presents a new, rapidly evolving area of therapeutic research, the authors wrote.

Research also exists on using NSAIDs — especially aspirin and celecoxib — as add-on treatments for psychosis, but because NSAIDs have nonimmune effects, they are limited. In contrast, monoclonal antibodies do not have off-target effects and offer an opportunity to directly examine whether “inflammation plays a causal role in psychopathology,” Buckley and Miller explained.

Alongside research on using monoclonal antibody inhibitors as anti-inflammatory drugs for rheumatoid arthritis, new studies in psychosis are testing these agents, including monoclonal antibodies against cell adhesion molecules, such as Tysabri (natalizumab, Biogen) which prevents alpha-4 integrin; Actemra (tocilizumab, Genentech) and Sylvant (siltuximab, Janssen), which targets the cytokine IL-6; and Ilaris (canakinumab, Novartis), which targets IL-1, according to the authors.

IV tocilizumab administered twice over an 8-week period showed feasibility and was well-tolerated in six patients with schizophrenia enrolled in a previous open-label study.

Based on these results, Buckley and Miller are currently conducting another trial of tocilizumab, instead only recruiting patients with elevated blood C-reactive protein (CRP). They explained that this area of study is important because neuroinflammation is likely not the only cause of schizophrenia, and immunomodulatory agents are likely only relevant to the subset of patients with schizophrenia who show features of neuroinflammation, like elevated CRP levels.

“Of course, if it were as simple and/or compelling as that, one could easily imagine measuring the CRP level of a patient with schizophrenia in the clinic and, if elevated, then prescribing aspirin as an anti-inflammatory add-on treatment,” they wrote. “The available data do not justify this approach, and certainly the use of monoclonal antibodies by [IV] infusion is itself a drastic approach that requires rigorous scientific inquiry.”

Buckley and Miller are also conducting a trial of siltuximab in patients with schizophrenia who have active inflammation, but results of similar clinical trials by other researchers will not be available for at least 3 years.

“With all that being said, monoclonal antibody therapies are not without risks and drawbacks, such as risk of infections, risk of vascular trauma from repeated infusion, extreme expense, need for adequate space and observation during infusion,” the authors concluded. “Time will tell if and how these innovative strategies will advance the therapeutics of schizophrenia.” – by Savannah Demko

Disclosures: Buckley reports funding from the Stanley Medical Research Institute and the Brain and Behavior Research Foundation. Miller reports grants from Augusta University, the Brain & Behavior Research Foundation, the National Institute of Mental Health and the Stanley Medical Research Institute; consulting for Psychiatric Times; and contracted research for Alkermes and Sunovion.

Treatment with antirheumatic medications — such as NSAIDs and anticytokine monoclonal antibodies — may benefit patients with schizophrenia, according to data published in Psychiatric Annals.

“Research on the microbiome in schizophrenia is still in its infancy, although there is some evidence for alterations in the gut and oropharyngeal microbiome in patients with schizophrenia compared to controls,” Peter F. Buckley, MD, dean, School of Medicine, Virginia Commonwealth University, and Brian J. Miller, MD, PhD, MPH, associate professor, department of psychiatry and health behavior, Augusta University, Georgia, wrote.

Prior research has shown that immune abnormalities exist in schizophrenia and first-episode psychosis, according to Buckley and Miller. Common medications for rheumatoid arthritis, such as NSAIDs, aim to change the immune response. Using immunotherapies as adjuncts to antipsychotic treatments for patients with schizophrenia presents a new, rapidly evolving area of therapeutic research, the authors wrote.

Research also exists on using NSAIDs — especially aspirin and celecoxib — as add-on treatments for psychosis, but because NSAIDs have nonimmune effects, they are limited. In contrast, monoclonal antibodies do not have off-target effects and offer an opportunity to directly examine whether “inflammation plays a causal role in psychopathology,” Buckley and Miller explained.

Alongside research on using monoclonal antibody inhibitors as anti-inflammatory drugs for rheumatoid arthritis, new studies in psychosis are testing these agents, including monoclonal antibodies against cell adhesion molecules, such as Tysabri (natalizumab, Biogen) which prevents alpha-4 integrin; Actemra (tocilizumab, Genentech) and Sylvant (siltuximab, Janssen), which targets the cytokine IL-6; and Ilaris (canakinumab, Novartis), which targets IL-1, according to the authors.

IV tocilizumab administered twice over an 8-week period showed feasibility and was well-tolerated in six patients with schizophrenia enrolled in a previous open-label study.

Based on these results, Buckley and Miller are currently conducting another trial of tocilizumab, instead only recruiting patients with elevated blood C-reactive protein (CRP). They explained that this area of study is important because neuroinflammation is likely not the only cause of schizophrenia, and immunomodulatory agents are likely only relevant to the subset of patients with schizophrenia who show features of neuroinflammation, like elevated CRP levels.

“Of course, if it were as simple and/or compelling as that, one could easily imagine measuring the CRP level of a patient with schizophrenia in the clinic and, if elevated, then prescribing aspirin as an anti-inflammatory add-on treatment,” they wrote. “The available data do not justify this approach, and certainly the use of monoclonal antibodies by [IV] infusion is itself a drastic approach that requires rigorous scientific inquiry.”

Buckley and Miller are also conducting a trial of siltuximab in patients with schizophrenia who have active inflammation, but results of similar clinical trials by other researchers will not be available for at least 3 years.

“With all that being said, monoclonal antibody therapies are not without risks and drawbacks, such as risk of infections, risk of vascular trauma from repeated infusion, extreme expense, need for adequate space and observation during infusion,” the authors concluded. “Time will tell if and how these innovative strategies will advance the therapeutics of schizophrenia.” – by Savannah Demko

Disclosures: Buckley reports funding from the Stanley Medical Research Institute and the Brain and Behavior Research Foundation. Miller reports grants from Augusta University, the Brain & Behavior Research Foundation, the National Institute of Mental Health and the Stanley Medical Research Institute; consulting for Psychiatric Times; and contracted research for Alkermes and Sunovion.