To Investigate Genetic Factors Associated With the Response to Anti-TNF Therapy in Patients With Early AS
Condition: Ankylosing Spondylitis
MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
Study type: Observational

Summary: 
      Ankylosing spondylitits (AS) is a chronic, systemic rheumatic disease primarily affecting
      spine and sacroiliac joints, which belongs to the group of conditions known as
      spondyloarthopathies and causes eventual fusion of the spine. Twin study in AS estimated a
      heritability of over 90%. HLA-B27 is regarded as the earlist and most important gene
      associated with AS heritability, and over 90% of AS patients carry HLA-B27 gene. HLA-B27 was
      highly polymorphic, and more than 89 subtypes of B27 gene have been found. Subtypes of
      HLA-B27 vary between different regions, and so on as the relationship between HLA-B27
      subtypes and disease development among different races. Anti-TNF- agents were regarded as one
      milestone in recent years development on treatment of ankylosing spondylitis, and most
      patients showed significant improvement after anti-TNF- therapy. Yet part of patients still
      showed insufficient response. Our previous study suggested AS patients carrying different
      genotype of SNP in TNF gene had different response to anti-TNF- therapies. But more studies
      should be carried out to identified more gene polymorphisms associated with treatment
      response. In this study we designed a prospective, open-label trial to investigate the
      genetic difference beween AS patients with different response to anti-TNF- therapy. We plan
      to enroll 50-100 early AS patients which fulfill the 2009 ASAS axial spondyloarthritis
      classification criteria and have axial symptom for no more than 2 years. The patients must
      have high disease activity defined as BASDAI 4, and HLA-B27 test must be positive. The
      patients should be able to receive 24 weeks of etanercept treatment. And patients who have
      previous other anti-TNF- therapy and any contraindication of anti-TNF- therapy must be
      excluded. Other medicines should be stable for at least 4 weeks before etanercept treatment
      begins. For the clinic assessment, patients should fill in the AS questionaires and receive
      physical examination at each visit. ASAS20 is thought as the primary endpoint. For the
      genetic polymorphysm detection, we select 10-20 SNP in MHC region associated with AS and 5-10
      HLA-B27 subtypes which have been worked over and have definite association with AS. At the
      first visit 4ml of anticoagulated blood was collected and DNA was extracted. Target SNPs are
      detected by PCR then direct sequencing. HLA-B27 subtypes are identified using PCRSSP methods.
      And the relationship between SNPs/HLA-B27 subtypes and different response to anti TNF-
      therapy is accessed using chi-square statistic process in SPSS software. In this study we
      plan to investigate the relationship between genetic background and the clinical response to
      anti-TNF- therapy in AS patients, which has been seldom reported before. Our group have been
      studying the disease-associated gene of AS for years, and got plenty of data and experience
      about genetic study of AS.
    


Observational model: Case-Crossover
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Chinese patients with early AS