SIROC Study
Research type
Research Study
Full title
Secure Anonymised Information Linkage (SAIL) databank analysis of Infection Related Outcomes in people with schizophrenia taking Clozapine (SIROC) Study
IRAS ID
179877
Contact name
Stephen Jolles
Contact email
Sponsor organisation
Cardiff and Vale University Health Board
Duration of Study in the UK
1 years, 11 months, 30 days
Research summary
Research Summary:
SIROC is an observational study with two arms.
Arm 1 is an investigation of the distribution of serum immunoglobulins in people with schizophrenia. The study population consists of two groups of individuals with schizophrenia: those with treatment-resistant schizophrenia (TRS) receiving clozapine therapy (Group A), and those receiving “conventional” (non-clozapine) antipsychotic therapies (Group B). These individuals will be invited to participate in the study whilst attending for regular monitoring visits at NHS community mental health centres across Wales. Pending appropriate permissions, the research team will obtain a blood sample for immunological testing (alongside routine phlebotomy wherever possible) and review their relevant medical records (for instance to document infection and medication history). De-identified data will be passed to the Secure Anonymised Information Linkage (SAIL) Databank for further analysis.
Arm 2 will examine the personal and societal costs associated with infection-susceptibility in adults with schizophrenia (Groups A and B) participating in Arm 1, and compare these relative to individuals with a known diagnosis of immunocompromise/immunodeficiency (Group C) who have provided consent for linkage of details of their immunodeficiency diagnosis and immunological testing to the SAIL Databank. An age- and gender- matched group of healthy individuals without a known diagnosis of schizophrenia or immunocompromise (Group D) will be identified from the SAIL Databank to provide an additional comparator group.
The two arms will be described separately in this protocol but remain one linked study. More detailed information is given in the sections for each arm.Summary of Results:
Results: SIROC recruited two hundred and ninety-two patients taking clozapine or an alternative antipsychotic from across the six Welsh health boards. We confirmed enrichment of hypogammaglobulinemia (IgG < 6g/L) amongst clozapine-treated participants, being 7-times more likely to have an IgG level below the lower limit of normal than clozapine-naïve comparators.
We identified individuals who had participated in both our pilot and present SIROC study, enabling longitudinal monitoring of immunoglobulin levels over almost a decade. This confirmed a longer duration of clozapine therapy was associated with a greater reduction of IgG, with no significant change in those on alternative antipsychotic therapy.
Within the SAIL databank, we identified over 42,000 adults with schizophrenia receiving either clozapine, or an alternative antipsychotic around Wales. The rate of a lower respiratory tract infection diagnoses for individuals prescribed clozapine was 2-fold greater following adjustment for age, smoking status, and socioeconomic deprivation status compared to those receiving an alternative antipsychotic.
We identified over forty individuals with clozapine associated immunodeficiency managed by Immunology Centres across UK. These patients experienced a high rate of recurrent and severe infections, particularly sinopulmonary (in keeping with the pattern of infection expected for antibody deficiency). Specialist intervention with antibiotic prophylaxis and immunoglobulin replacement therapy were commonly observed.Assessment: The SIROC study confirms the existence of clozapine-associated antibody deficiency and provides strong evidence for its contribution to pneumonia risk in this vulnerable patient group. This is part of a wider mix of risk factors including smoking, obesity, and age. Clozapine is associated with cost savings of £3700 annually*, relative to alternate antipsychotic therapies in real-world data from UK psychiatric practice. Immunoglobulin testing costs approximately £19 per patient.
Recommendations:
Clozapine prescription requires regular blood test monitoring (at present 4-weekly within the UK) however antibody deficiency is not included in its listed adverse effects or in drug monitoring schemes despite alerts to the MHRA. We propose the inclusion of antibody testing as part of the routine drug monitoring programme.REC name
South Central - Hampshire A Research Ethics Committee
REC reference
23/SC/0016
Date of REC Opinion
12 Jan 2023
REC opinion
Favourable Opinion