Clinical trial NCT05095103: Immune Profiles in Myasthenia Gravis
Official title: Comparison of Lymphocyte Subset, Cytokine and Complement Profiles in Myasthenia Gravis of Different Severity, Disease Time-points, and Treatment History
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Myasthenia Gravis
Lead sponsor: University of Manchester
Sponsor class: OTHER
Collaborators: name: Northern Care Alliance NHS Foundation Trust
name: Walton Centre NHS Foundation Trust
name: Oxford University Hospitals NHS Trust
name: University College London Hospitals
name: University Hospital Birmingham NHS Foundation Trust
name: Imperial College Healthcare NHS Trust
name: Newcastle-upon-Tyne Hospitals NHS Trust
name: King's College Hospital NHS Trust
name: Nottingham University Hospitals NHS Trust
name: University Hospital Southampton NHS Foundation Trust
name: Cardiff University
First posted: 2021-10-27
Enrollment: 163
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Acetylcholine receptor antibody positive myasthenia gravis

Brief summary: The investigators aim to better describe the immune profile in myasthenia gravis (MG), including lymphocyte subset, cytokine and complement profiles; how they differ between patients of different severity, at times of disease exacerbation, and with different immunosuppressive treatments. The investigators hope to build a clearer picture of how different immune measures vary in MG, contributing to the understanding of the patho\[physiology of the disease, and working towards a biomarker that might help clinicians optimise an individual's treatment.

the investigators aim to take into account the heterogeneity of MG by taking into account age of onset of MG (early vs late onset) and focussing on acetylcholine receptor antibody (AChR) positive, non-thymomatous MG aged 18-80.

Detailed description: This study is designed to confirm and refine the knowledge around these changes in the immune profile, including lymphocyte subsets, and complement analysis, between different subgroups of patients with MG of different severity, different levels of immunosuppressive treatment, and at different time points in the disease course, ensuring these are put into the context of the patient's disease subtype (late-onset (LOMG) vs early-onset (EOMG)). This should enable us to understand more about the underlying immune changes in MG, how they relate to disease activity or severity, how this is impacted upon by immunosuppression, and guide us towards a markers for disease severity and effective immunosuppression that could be used in clinical practice, and help guide treatment decisions. One of the challenges in studying patients with MG with the relatively low prevalence of the condition, meaning it can be difficult to recruit large enough numbers of patients; the investigators will work with other tertiary neurology centres throughout England in order to meet recruitment targets.

The research project will consist of three work streams:

1. A one-off observational comparison of the immune profile of patients with different MG severity and in comparison to healthy controls.
2. A prospective observational study examining changes in lymphocyte subset, cytokine and complement profiles associated with clinical exacerbation of myasthenia gravis.
3. A prospective cohort study comparing lymphocyte subset, cytokine and complement profile with disease activity following B cell depletion for refractory myasthenia gravis.

Eligibility criteria: Inclusion Criteria:

* All participants:
* Are able to give valid written consent
* are aged between the ages of 18 and 80

Stable Immunosuppressed

* Have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)
* MGFA Post-intervention Status MM or better with no clinical relapse for 2 years
* On either azathioprine or MMF along with ≤5mg/day of prednisolone
* No prednisolone dose increase or decrease in past 12 months
* No increase in azathioprine or MMF dose for 2 years (allowing for cessation for up to 1 month)

Stable Non-Immunosuppressed

* have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)
* MGFA Post-intervention Status MM or better on only low-dose cholinesterase inhibitors (≤\<120 mg pyridostigmine/day) for over two years and ≤5mg/day of prednisolone for over two years.
* No prednisolone dose increase or decrease in past 12 months

Refractory

* have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)
* have been deemed eligible to be refractory to standard treatment and eligible for rituximab as per the NHS England criteria.

Exclusion Criteria for all participants:

* Are unable to give valid consent
* Co-existing autoimmune condition for which azathioprine or mycophenolate mofetil are treatments (e.g. inflammatory bowel disease, rheumatoid arthritis, neuromyotonia)
* Currently undergoing treatment for solid organ or haematological malignancy, or previous thymoma
* Clinical frailty scale ≥6

Primary outcomes:
measure: Primary outcome work stream 1
timeFrame: Baseline
measure: Primary outcome work stream 2
timeFrame: Relapse within 18 months of recrutiment
measure: Primary outcome work stream 3
timeFrame: 12 months after B cell depletion
Secondary outcomes:
measure: MG Composite Score
timeFrame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups,
measure: MGFA - Post Intervention status
timeFrame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
measure: MG QOL-15r
timeFrame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
measure: Acetylcholine receptor antibody titre
timeFrame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
measure: Lymphocyte Count
timeFrame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
measure: Number of relapses requiring hospital admission or rescue therapy
timeFrame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
measure: Average daily dose of prednisolone over the three months prior to review
timeFrame: Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups
Other outcomes:
Locations:
Study officials:
affiliation: University of Manchester
name: Katherine Dodd, MBChB MRCP
role: PRINCIPAL_INVESTIGATOR
References: