Protocol Title : A Randomised, open labelled study in anti ... - EME

Protocol Version 3 14/01/2013
• SF-36
The Short Form (36) Health Survey is a survey of patient health. The SF-36 is a measure of health
status and is commonly used in health economics as a variable in the quality-adjusted life year
calculation to determine the cost-effectiveness of a health treatment. The SF-36 consists of eight
scaled scores, which are the weighted sums of the questions in their section. Each scale is directly
transformed into a 0-100 scale on the assumption that each question carries equal weight.
The eight sections are: vitality, physical functioning, bodily pain, general health perceptions,
physical role functioning, emotional role functioning, social role functioning and mental health.
• FACIT-Fatigue
The FACIT-Fatigue scale is a 13-item, symptom-specific subscale of the FACIT scales.13 Lower
values of the FACIT-Fatigue score denote higher fatigue (score range, 0 to 52). Cella et. al.
validated a brief measure of fatigue in rheumatoid arthritis (RA), the Functional Assessment of
Chronic Illness Therapy (FACIT) Fatigue Scale. The FACIT Fatigue was tested along with
measures previously validated in RA: the Multidimensional Assessment of Fatigue (MAF) and
Medical Outcomes Study Short-Form 36 (SF-36) Vitality. The FACIT Fatigue showed good internal
consistency (alpha = 0.86 to 0.87), strong association with SF-36 Vitality (r = 0.73 to 0.84) and
MAF (r = -0.84 to -0.88), and the ability to differentiate patients according to clinical change using
the American College of Rheumatology (ACR) response criteria (ACR 20/50/70). This suggests
that the FACIT Fatigue is a brief, valid measure for monitoring this important symptom and its
effects on patients with RA.
5.11 Imaging Evaluations
Patients will have plain x-rays and ultrasound assessments of disease activity and joint damage
and will be related to the secondary outcome measures in this study.
• X-rays
Plain radiographs of the hands and feet will be recorded at baseline, 12 months and 24 months
follow up as per routine clinical practise.
A chest x-ray will be acquired as per routine screening for TB prior to biological therapy
• Ultrasound
An Ultrasound assessment will be performed at baseline, 1, 2, 3, 4, 6, 9, 12, 13 and 24 months
follow up. Images will be acquired and scored for Doppler signal and synovial thickness within a
limited joint set
5.12 Laboratory Assessments
Routine laboratory bloods for safety will be taken as per routine clinical care for patients receiving
Rituximab or Tocilizumab.
5.12.1 Peripheral Blood analysis
Lab: Local site laboratory - The following blood tests will be performed at screening and at
each visit: FBC, urea, creatinine, electrolytes, liver function tests, ESR, CRP, immunoglobulins and
serum protein electrophoresis. These investigations will be performed at the local site laboratory.
In addition 50ml of blood will be collected for the study at baseline and every months as per study
procedure chart (section 5.5). The details of sample requirements, handling, transfer and storage
are contained in detail in the R4-RA study Laboratory Manual.
• FACS analysis
Lab: QMUL, Experimental Medicine and Rheumatology - Whole blood FACS analysis will be
carried out at baseline and 2-monthly using a Beckman Coulter CyAn analyser (Beckman Coulter,
3 laser-9 colors) as routinely done in our laboratory. Typical analysis will include B-cells:
CD19/CD27/CD38/IgD/IgM; T-cells: CD3/CD4/CD8/CD25; Monocytes: CD14/CD16/HLA-DR. In
addition B cells will be analysed for expression of chemokine receptors (CXCR5, CXCR4, CCR7)
and FCRLs expression profile. Once B cells start repopulate in peripheral blood and/if relapse
occurs (the former usually precedes the latter) further characterisation studies of B cells will be
performed. FACS B cell sorting.
Study: R4RA EudraCT: 2012-002535-28 27 / 34