Combination Methotrexate and Infliximab

The Efficacy of Combination Methotrexate and Infliximab in Patients With Ankylosing Spondylitis:A Clinical and Magnetic Resonance Imaging Correlation

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

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis
• Intervention / Treatment: Drug: Infliximab and MTX

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; placebo with infliximab	Drug: Infliximab and MTX; MTX 15mg weekly Infliximab 5mg/kg given at day 0, wk 2, wk6; Other Names: remicade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of patient exhibited an ASAS 20 response to treatment at week 20.	wk52

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Edmund K Li, MD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): August 1, 2006
• Study Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: February 6, 2007
• First Submitted That Met QC Criteria: February 6, 2007
• First Posted (Estimate): February 7, 2007

Study Record Updates

• Last Update Posted (Estimate): February 13, 2012
• Last Update Submitted That Met QC Criteria: February 10, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Infliximab; Ankylosing Spondylitis; MTX
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: AS-2005-003