NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of Structural Damage in Ankylosing Spondylitis

The aim of the proposed trial is to evaluate the efficacy of combined treatment with a non-steroidal anti-inflammatory drug (NSAID) added to anti-tumour necrosis factor (TNF) therapy as compared to anti-TNF therapy alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis (AS). The trial consists of two phases. In the phase I (run-in phase), patients with active AS despite treatment with NSAIDs and elevated C-reactive protein will be included and treated with a TNF blocker (golimumab). Patients with good clinical response to golimumab at week 12 will be eligible for the phase II (core phase) of the study and will be randomized 1:1 to 1) golimumab + celecoxib (experimental intervention) for 2 years (weeks 12-108) or 2) golimumab alone (control intervention) also for 2 years. The primary outcome parameter will be the absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) - currently a standard of structural spinal damage progression evaluation in AS - over two years of therapy (weeks 12-108).

Major Inclusion Criteria:

• Definite diagnosis of AS according to the "modified New York criteria".
• History of an inadequate response to ≥2 NSAIDs taken for at least 2 weeks each.
• Active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) value of ≥4 at screening.
• Presence of at least one of the following risk factors for radiographic spinal progression:

• Elevated C reactive protein (CRP; >5mg/l) at screening at the absence of reasons for elevated CRP other than AS;
• Presence of ≥ 1 syndesmophyte on prior X-rays of the spine.
• Subject is a candidate for anti-TNF therapy based on the Investigator's opinion.
• Subject is able and willing to give a written informed consent and comply with the requirements of the study protocol. Only patients who give written informed consent will be included in the trial.
• If female: either unable to bear children (postmenopausal for at least 1 year or surgically sterile) or is willing and able to practice a reliable method of contraception throughout the study and 6 months after

Inclusion Criterion for Phase II (randomized part of the study):

• adequate response to Golimumab during Phase I (referred to as decline in BASDAI)

Major Exclusion Criteria:

• For female subjects: pregnancy or lactating
• subjects with chronic inflammatory articular disease other than spondyloarthritis / AS or systemic autoimmune disease, e.g. systemic lupus erythematosus, Sjögren´s syndrome, rheumatoid arthritis.
• history of inadequate response to anti-TNF-therapy
• intolerability/hypersensitivity to one of the drugs or other components of the study medication
• presence ot total spinal ankylosis
• contraindications to anti-TNF-therapy (current or remitting clinical significant infections, tuberculosis, viral hepatitis, HIV; malignancies; demyelinating disease; vaccination with live vaccine within 3 months before, during and until 6 months after study)
• (relative) contraindications to Celecoxib therapy (uncontrolled arterial hypertension, high cardiovascular risk / history of cardiovascular events; history of gastrointestinal ulcers or relevant bleeding; known M. Crohn or ulcerative colitis)
• diagnosis of fibromyalgia
• significant lab abnormalities