Ankylosing spondylitis (AS) is an inflammatory condition primarily affecting the spine. The disease may remain symptomatic and progressive life-long. It is part of the family of spondyloarthropathies which also comprises psoriatic arthritis, reactive arthritis and enteropathic arthritis.
Conditions
Interventions
Trade Name: MabThera 500
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
University Hospital of North Staffordshire
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with AS according to the New York modified criteria attending Haywood Hospital, Stoke-on-Trent Age between 18-70 years old Receiving a stable dose of NSAID for at least 1 month Patients willing and able to give informed consent and to comply with the requirements of the protocol. Bath AS disease activity (BASDAI) index > 4 (on a scale of 0-10) Nocturnal and total back pain visual analogue scale (0-100mm) over 40mm Acute inflammatory response (C-reactive protein (CRP) > 10mg/L) Failure to respond to at least one non-steroidal anti inflammatory drugs (NSAID) If the patient is of reproductive potential (males and females), then they must be using a reliable means of contraception (e.g. contraceptive pill, intrauterine device, physical barrier) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: General Contraindications to MRI Bone/joint surgery within 8 weeks prior to screening or joint surgery planned within 36 weeks trial entry Rheumatic autoimmune disease other than AS Psoriasis Inflammatory bowel disease Excluded previous/concomitant therapies Current or previous anti-TNF-a therapy Oral prednisolone dose above 10mg daily Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti CD-3, anti CD-19) Previous treatment within 6 months with iv ?-globulin or Prosorba® Column Intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit or during the trial. General safety History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies Significant cardiac or pulmonary disease Known significant uncontrolled concurrent diseases such as renal, hepatic, nervous system, endocrine or gastrointestinal disorders Known active bacterial, viral, fungal (excluding fungal infections of the nails beds), mycobacterial or other infections, or any major episode of infection requiring hospitalisation within 4 weeks of screening History of significant recurrent infections Primary or secondary immunodeficiency History of cancer. Including solid tumours and haematological malignancies (except basal cell and squamous cell carcinoma of the skin that have been excised and cured) Pregnant or lactating females History of alcohol, drug or chemical abuse within 6 months of screening Lack of peripheral venous access Intolerance or contraindications to oral or iv corticosteroids Laboratory Criteria Serum creatinine > 140umol/L Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) > 2.5 times upper limit of normal Platelet count < 100 109/L Haemoglobin < 8.5 g/dL Neutrophils < 1.5 x 103/µL Levels of IgG and IgM below 5.65 and 0.55 mg/mL respectively
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study is a single centre, 12 month open label proof of concept study, to determine the efficacy of Rituximab (Mabthera), a B cell depleting chimeric monoclonal antibody in Ankylosing Spondylitis (AS). Ten patients with AS according to the New York modified criteria, will be infused with Rituximab. The primary outcome of response to Mabthera treatment will be change in spinal and sacroiliac enthesitis/osteitisbe assessed by MRI scans of the sacroiliac joints and lumbar spine at 0 and 3 months. The Haywood Hospital rheumatology unit already has experience using Rituximab in rheumatology patients both within clinical trials and on a clinical need named patient basis. ;Secondary Objective: Secondary outcomes will include changes before and after treatment in Bath AS Disease Activity Index (BASDAI), Bath AS functional Index (BASFI), Bath AS Metrology Index (BASMI), SF-36, ASQoL and ASQ (AS quality of life), 66 swollen joint count, MASES enthesitis score, CRP/ESR and a broad screen of cytokines linked to AS disease activity including IL-1, IL-6, TNF-a, TGFß1, VEGF, M-CSF, IFN? and MMP-3.;Primary end point(s): To determine the efficacy of Rituximab (Mabthera), a B cell depleting chimeric monoclonal antibody in Ankylosing Spondylitis (AS). The primary outcome of response to Mabthera treatment will be change in spinal and sacroiliac enthesitis/ osteitis and using magnetic resonance imaging (MRI) comparing the score of enthesitis in spine at 0 and 3 months. | — |
Countries
United Kingdom
Outcome results
None listed