Timed Release Tablet Prednisone in Polymyalgia Rheumatica

The volunteers will stay overnight in the Rheumatology Centre; 24-hour Research Facility on two occasions (Night A and Night B) 12-16 days apart. This slight flexibility will allow some leeway in arranging residency nights. In general the investigators will aim for 14 days. After Night A, each volunteer will be randomized (in pre-prepared sealed envelopes) to take one tablet morning or evening. Half the patients will take active standard release prednisolone in the morning. The other half will receive active TRT Prednisone 7mg to be taken each evening at 22:00 until the day after Night B. All study medication will then be discontinued and standard therapy (prednisolone 15mg each morning) commenced. Patients will be reviewed after 2 weeks to ensure expected clinical response and to measure IL-6 and other cytokines in the blood sample that is also needed to check the acute phase response.

On Night A and Night B, volunteers will attend the Rheumatology Centre at 15:00.

First, standard assessment tools will be used by the research doctor to assess the state of the patient's condition.

These assessments will be:

• Morning stiffness (minutes)
• Pain (visual analogue scale)
• Patient's opinion of condition
• Clinician's opinion of condition
• Health Assessment Questionnaire
• BRAF-MDQ fatigue scale and the Hospital Anxiety and Depression Scale.

An intravenous (IV) cannula will be inserted into the elbow area. At least one hour after the IV cannula is placed, but usually at 16:30, a blood sample (2ml) will be taken through the IV cannula and the cannula flushed. At 22:30 the main lights will be switched off and the volunteer encouraged to sleep. In total, 20 samples will be taken from the cannula over 24 hours.

The investigators will calculate mean and standard deviation (or non-parametric analysis if the data are not normally distributed) for blood cytokines for each time point. These mean and standard deviations will be compared for pre- and post-TRT prednisone samples.

Inclusion criteria

• Diagnosis of PMR by standard criteria. The Bird criteria will be used. 3 or more features are required to make the diagnosis.

• Bilateral shoulder pain/stiffness
• Duration of symptoms <2/52
• Initial ESR >40 mm/h
• Stiffness >1 h
• Age >65 years
• Depression and/or weight loss
• Bilateral upper arm tenderness
• Are over 50 but less than 85 years old.
• No or stable NSAID or analgesic therapy for at least 7 days.
• Currently active disease defined by a CRP at least 10mg/L, ESR at least 29mm in one hour or PV >1.72

Exclusion criteria

• Currently on oral glucocorticoid treatment or taken within 2 months
• Parenteral glucocorticoid treatment with the last 2 months
• Pregnancy and lactation
• Inflammatory diseases such as inflammatory bowel disease, colitis, asthma
• Co-existent giant cell arteritis
• Other auto-immune diseases
• Cancer
• Infections, treatment with antibiotics within the past 6 weeks
• Significant renal disease (creatinine >150 μmol/L)
• Significant hepatic impairment
• Participation in a clinical trial within the past 30 days
• Working shift employee
• Jet lag