Impact of IL‑17 blockade on nucleus accumbens glutamate in psoriatic disease: a randomised placebo controlled waiting list study using 7T MRS
Depressive symptoms in people with active psoriatic disease and how IL-17 inhibition affects inflammation in brain and immune processes.
Randomised placebo-controlled waiting list experimental medicine study. Participants will be randomised 1:1 to either immediately receive (fast-tracked) IL-17 blockade (secukinumab/ bimekizumab/ Ixekizumab) as per normal dose loading regime or a placebo. The duration of placebo exposure is justified on the basis that it is consistent with current local routine screening and waiting times to start biologics from treatment decision. Active treatment period is 6 weeks, with IL 17 inhibitors administered according to the participants local care prescription: • Secukinumab 150mg or 300mg every week for 5 doses; • Bimekizumab 160mg or 320mg every 4 weeks; • Ixekizumab 160mgs for one dose then 80mgs 2 weekly or 4 weekly. • Placebo (normal saline 0.9%) is administered on the same schedule to mirror the chosen biologic. Participants undergo Baseline assessments (Week 0) and Follow-up assessments at Week 6 (Day 42). After 6 weeks, all participants transition back to local standard care, including initiation or continuation of IL-17 inhibitors. Randomisation is performed centrally using a computer generated randomisation system (Interactive Voice Response System) managed by the Robertson Centre for Biostatistics using randomised permuted blocks of variable size. The randomisation schedule is prepared by the study statistician without involvement of the investigators.
1. Adults aged 18 years to less than 75 years 2. Diagnosis of PsO or PsA made by a dermatologist or rheumatologist 3. Selected to start secukinumab, bimekizumab, or ixekizumab by their usual dermatology team for PsO or rheumatology team for PsA in line with the drug licence and eligible using NICE or SMC criteria 4. No contraindications to MRI, for example metal fragments or implantable devices not compatible with MRI; no additional x‑ray imaging will be obtained and existing images may be used to check for possible contraindications 5. Satisfactory completion of standard pre‑biologic safety screening, including but not limited to exclusion of latent TB infection according to local protocol, chest x‑ray, negative HIV screen, negative hepatitis screen antibody, negative hepatitis B surface antigen, and negative hepatitis B anti‑core antibody 6. Recent use of intramuscular or intra‑articular steroid injections, but not within 4 weeks prior to baseline 7. Women of child‑bearing potential must be willing to use effective contraception for the study duration 8. Willing to participate and give informed consent
1. Inability to provide written informed consent 2. Severe physical impairment (e.g. blindness, deafness, paraplegia) 3. Clinically important active infections e.g. active TB 4. History of inflammatory bowel disease 5. Pregnant or breast feeding 6. Severe claustrophobia precluding MRI 7. Contraindications to 7T MRI 8. Confounding neurological disease including MS, stroke, traumatic brain injury 9. Previous exposure to IL‑17A, IL‑17A/F, IL‑17R inhibitors or IL‑23 (p19/p40) inhibitors in the last 6 months 10. Hypersensitivity to any of the excipients in secukinumab, bimekizumab, or ixekizumab 11. Any clinical, psychological, social or geographical reason which, at the investigator’s discretion, would make them unsuitable to take part in the study