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Combination Methotrexate and Infliximab

Phase 4
Completed
Conditions
Ankylosing Spondylitis
Interventions
Registration Number
NCT00432432
Lead Sponsor
Chinese University of Hong Kong
Brief Summary

Combination Methotrexate and Infliximab:Influence of immunogenicity on the efficacy of infliximab in patients with Ankylosing Spondylitis.

Detailed Description

Forty consecutive patients will be recruited from the rheumatology clinic of the Prince of Wales Hospital with AS meeting the modified New York criteria with active disease as defined (see below). They will be randomized to receive MTX 7.5 mg/week initially with a weekly 2.5mg increment until 15mg/week dosage is reached,( i.e by week 6) or a placebo together with folic acid 5mg daily for a period of 16 week. After 16 weeks, all patients will receive infliximab at 5 mg/kg per dose, at weeks 16, 18, and 22 (3 doses), and will continue with MTX 15 mg/week or placebo. Thereafter, they will be followed up at week 30, 38 weeks. MRI changes in the sacroiliac joints (SI) before and after infliximab treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
38
Inclusion Criteria
  • Fulfilled the AS:meeting the modified New York criteria
  • Active disease despite NSAID treatment defined as:
  • Spinal inflammation ≧ 30 and a score of 30 on at least two of the other three domains
  • Back pain
  • Patient global assessment of disease activity
  • Physical function
  • Informed consent
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Exclusion Criteria
  • Complete ankylosis of the spine
  • On sulphasalazine
  • Previous use of TNF inhibitors
  • Multiple use of NSAIDS
  • Prednisolone > 10mg/day
  • Changes of NSAIDS or dose of prednisolone within 2 weeks of baseline
  • Little or no ability for self-care
  • Received intra-articular,intramuscular, or intravenous corticosteroids in the 4 weeks before screening
  • Infected joint prosthesis during the previous 5 years
  • Serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous 3 months
  • Any chronic infectious disease such as renal infection, chest infection with bronchiectasis or sinusitis
  • Active tuberculosis requiring treatment within the previous 3 years
  • Opportunistic infections such as herpes zoster within the previous 2 months
  • Any evidence of active cytomegalovirus; active Pneumocystis carinii; or drug-resistant atypical mycobacterial infection
  • Known hypersensitivity to murine proteins
  • Current signs or symptoms of severe,progressive,or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease
  • A history of lymphoproliferative disease including lymphoma or signs suggestive of disease, such as lymphadenopathy of unusual size or location (ie,lymph nodes in the posterior triangle or the neck, infraclavicular epitrochlear, or periaortic areas); splenomegaly;
  • Any known malignant disease except basal cell carcinoma currently or in the past 5 years.
  • A hemoglobin level < 8.5 gm/dl, a white blood cell count < 3.5 × 10^9/liter, a platelet count < 100 × 10^9/liter, a serum creatinine level > 150 µmol/l, serum transaminase levels 1.25 times the upper limit of normal, or alkaline phosphatase levels > 2 times the upper limit of normal.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2Infliximab and MTXplacebo with infliximab
Primary Outcome Measures
NameTimeMethod
The number of patient exhibited an ASAS 20 response to treatment at week 20.wk52
Secondary Outcome Measures
NameTimeMethod
Proportion of patients with 50% and 70% improvement in disease activity.Patient global assessment of disease activity and pain;BASFI;early morning stiffness;physician global assessment of disease activity.Changes in the pre and post infusion MRI.wk52
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