Detailed Description
Rheumatoid arthritis is the most common form of inflammatory arthritis. It is a condition
where the body's joints become swollen and damaged. Currently, the approach used to manage
rheumatoid arthritis is the so-called 'Treat to Target' approach. The aim of this approach to
treatment is to achieve the absence of signs and symptoms, or best possible state of low
disease activity. It requires the use of frequent routine clinical assessments to help
determine what treatment to use. Ultrasound imaging (using sound waves to take images of the
joints and surrounding tissues) has been shown to be better than standard clinical
measurements in detecting disease activity. Doctors are already using ultrasound imaging as
part of their decisionmaking, in terms of diagnosis and altering treatments, but it is has
not been clearly shown if this is associated with a better control of the disease.
Participants will be randomly put into 1 of 2 treatment groups (standard treatment group or
the imaging group). All patients will also undergo the ultrasound assessment. In the standard
treatment arm, the doctor will not know the ultrasound result and will base treatment on the
routine disease activity score alone. In the imaging group, doctors will use routine clinical
disease activity score plus the ultrasound result to make decisions on which treatment is
given and treatment will be increased if necessary. However, for patients in the imaging
group, even if their rheumatoid arthritis remains stable as judged by the disease activity
score, treatment will be increased based on signs of active disease on the ultrasound.
Participation will last for 2 years. During the study participants will be required to attend
8 clinic visits. Approximately 400 patients from a number of countries in Europe and Japan
are expected to take part in the study.
Study Criteria
Inclusion Criteria:
- Age ≥ 18 years old
- Confirmed Participation by Informed Consent
- Patients fulfilling the ACR/EULAR classification criteria 2010 for rheumatoid
arthritis (RA)
Patients must be:
- Within the first year of starting on methotrexate AND
- Within 5 years of diagnosis AND
- In a stable clinical disease activity state (clinical remission/LDAS /other physician
deemed state) on methotrexate (as monotherapy or combination +/≤ prednisolone 5mg oral
daily) for at least 8 successive weeks (with no change in Disease-Modifying
Anti-Rheumatic Drugs (DMARD) +/steroid therapy - see exclusion criteria)
- Female subjects must be either postmenopausal for at least 1 year, surgically
incapable of childbearing, or effectively practicing an acceptable method of
contraception (oral/parenteral /implantable hormonal contraceptives, intrauterine
device or barrier and spermicide). Subjects must agree to use adequate contraception
during the study and for at least 5 months after study completion (or longer if on
relevant therapy and in line with local regulations).
- Male subjects must agree to ensure they or their female partner(s) use adequate
contraception during the study and for at least 5 months after the end of the study
period.
Exclusion Criteria
- Patients not on a stable dose of methotrexate within 8 weeks of screening, intolerance
or contraindications (as per clinician judgment)
- Intramuscular, intraarticular or change in oral corticosteroid within 8 weeks of
screening visit.
- Oral Prednisolone dose > 5 mg within 8 weeks of screening
- Treatment with any investigational agent within 4 weeks (or 5 halflives of the
investigational drug, whichever is longer) of screening.
- Patients who have previously received any biological therapy for RA.
- History of severe allergic or anaphylactic reactions to human, humanised or murine
monoclonal antibodies
- Evidence of serious +/uncontrolled concomitant disease which in the investigator's
judgment would deem the patient inappropriate for inclusion in the study: including
(but not exclusively)including cardiovascular (NYHA class III/IV heart failure),
nervous system (demyelination), pulmonary (including obstructive pulmonary disease,
pulmonary fibrosis), renal, hepatic, endocrine (include uncontrolled diabetes
mellitus) or gastrointestinal disease (including complicated diverticulitis,
ulcerative colitis, or Crohn's disease.).
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
or other infections (including but not limited to tuberculosis and atypical
mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal
infections of nail beds).
- Any major episode of infection requiring hospitalisation or treatment with IV
antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to
screening. Patients with persistent infections and patients at significant risk of
infection (e.g. leg ulceration, indwelling urinary catheter, septic joint within 1
year (or ever if prosthetic joint still in situ).
- Active TB requiring treatment within the previous 3 years. Patients should be screened
for latent TB (as per local guidelines) and, if positive, treated following local
practice guidelines prior to commencing the study. Patients previously treated for
tuberculosis with no recurrence in 3 years are permitted.
- Primary or secondary immunodeficiency (history of or currently active) unless related
to primary disease under investigation.
12. Evidence of active malignant disease, malignancies diagnosed within the previous
10 years (including haematological malignancies and solid tumours, except basal and
squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has
been excised and cured), or breast cancer diagnosed within the previous 20 years
unless related to primary disease under investigation.
