Evaluating the Role of IL-17 as an Orchestrator of Peripheral-central Cross Talk in Depressive Symptoms

Summary

The investigators seek clinically actionable understanding of the mechanisms that underlie depression in the context of immune mediated inflammatory diseases (IMIDs), delivered by a focused immune intervention study examining brain circuitry using state of the art imaging in the context of exquisitely specific therapeutic immune interception in human immune disease. Glutamate concentration in the NAcc will be positively correlated with the magnitude of the inflammatory response and will be attenuated by IL-17A inhibition. Ultimately, this will be associated with an improvement in depressive symptoms. The strength of coupling between early and late systems will be attenuated in the context of IL-17A-driven inflammation and will be correlated with less frequent switching behaviour following negative outcomes and ultimately depressive symptoms. This coupling will be re-established following IL-17 antagonism. Patients whose depressive symptoms benefit most from IL-17A antagonism will exhibit greatest resting-state and task-specific functional connectivity between Th-NAcc.

Eligibility

Inclusion Criteria:

* Adults ≥18 years \< 75years
* Diagnosis of PsO or PsA, made by a dermatologist or rheumatologist.
* Selected to start secukinumab/ bimekizumab/ Ixekizumab as part of their standard clinical care by their usual dermatology team for PsO or rheumatology clinical team for PsA in line with the license for secukinumab/ bimekizumab/ Ixekizumab and NICE/SMC criteria.
* No contraindications to MRI (for example metal fragments or implantable devices not compatible with MRI. (no extra x-ray images will be obtained to check placement of metal fragments or clips insitu. Existing images may be used to check for possible contraindications)
* 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 \[Hep B sAg\] and negative Hepatitis B anti-core antibody \[Hep B cAb\])
* Recent (but not within 4 weeks prior baseline) use of intra-muscular or intra-articular steroid injections
* Women of Child-Bearing Potential (WoCBP) must be willing to use effective contraception for study duration. Further information is provided in appendix 1.
* Willing to participate and give informed consent

Exclusion Criteria:

* Inability to provide written informed consent
* Severe physical impairment (e.g., blindness, deafness, paraplegia).
* Clinically important, active infections e.g. active TB
* History of inflammatory bowel disease
* Pregnant or breast feeding
* Severe claustrophobia precluding MRI
* Contraindications to 7T MRI (metal implants in the ears, head or neck, microbladed/ tattooed eyebrows, metal fragments in the eyes)
* Confounding neurological disease including MS, Stroke, Traumatic Brain Injury
* Previous exposure to IL-17A, IL-17A/F, IL-17R inhibitors or IL-23 p19/p40 inhibitors in the last 6 months
* Hypersensitivity to any of the excipients in secukinumab/ bimekizumab/ ixekizumab.
* Any reason which, at the investigator's discretion, would make them unsuitable to take part in the study.

Conditions4

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