Examination of Radiographic Progression, Efficacy and Safety of Long-Term Treatment With Infliximab in Patients With Ankylosing Spondylitis

Sponsor

Rheumazentrum Ruhrgebiet (Other)

Overall Status

Unknown status

CT.gov ID

NCT00237419

Collaborator

Centocor BV (Industry), Trial Coordination Center, 9713 GZ Groningen (Other), PPD (Industry)

149

Enrollment

Locations

Duration (Months)

9.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Ankylosing spondylitis (AS) is a chronic inflammatory disease that involves the sacroiliac joints, axial skeleton, entheses and peripheral joints. Current therapy for AS is mainly NSAIDs and physiotherapy which are oft insufficient. Treatment with the TNF-alpha blocking agent infliximab was shown to have definite clinical efficacy in patients with active AS on a short- and a long-term-basis over 2 years. We want to show that treatment with infliximab on a long-term basis over 4 years is safe and efficient and can prevent radiographic progression over a long period of time. Further we want to learn about the outcome after discontinuation of anti-TNF-alpha therapy.

Condition or Disease	Intervention/Treatment	Phase
Ankylosing Spondylitis	Drug: infliximab	N/A

Detailed Description

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown etiology that involves the sacroiliac joints, axial skeleton, entheses and peripheral joints. Chronic inflammation of entheses leads to new bone formation, syndesmophytes and ankylosis of joints, primarily in the axial skeleton. This leads to a dramatic loss of range of motion and to disability. The disease may also have nonskeletal manifestations including uveitis, carditis, pulmonary fibrosis and cardiac conduction abnormalities.

Current therapy for AS is mainly with NSAIDs and physiotherapy which are often insufficient. Clinical outcome with conventional therapies has not been good, with 50-70% of patients progressing to fusion of the spine by 10 to 15 years. Treatment with the TNF-alpha blocking agent infliximab was shown to have definite clinical efficacy in patients with active ankylosing spondylitis on a short- and a long-term basis over 2 years.

There is limited data available on the efficacy and safety of long-term anti-TNF therapy for 3 and more years, the outcome after discontinuation of anti-TNF therapy and the effect of anti-TNF therapy on radiographic progression over a long period of time.

The ASSERT trial was a 2 year international randomized placebo controlled trial to evaluate the efficacy and safety ot treatment with infliximab in patients with active and severe AS. The EASIC trial is initiated to follow the European participants of the ASSERT trial for at least an additional 2 years of treatment combined with systematic data collection.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

149 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label Extension, Investigator Initiated Trial to Examine Radiographic Progression , Efficacy and Safety of Long-Term Treatment With Infliximab in Patients With Ankylosing Spondylitis. EASIC (European Ankylosing Spondylitis Infliximab Cohort)

Study Start Date :

Dec 1, 2005

Anticipated Primary Completion Date :

Nov 1, 2010

Anticipated Study Completion Date :

Apr 1, 2011

Outcome Measures

Primary Outcome Measures

Degree of structural damage (radiographic progression)after 4 and 6 years of infliximab therapy (2 years of ASSERT trial plus 2 years of EASIC trial) [November 2008 and November 2010]

Secondary Outcome Measures

Proportion of patients which have received anti-TNF-alpha therapy as standard care after the end of ASSERT [November 2005]
Description of the various treatment regimens after the end of ASSERT of the participating AS patients in various countries [November 2005]
Degree of spinal inflammation analyzed by MRI after discontinuation of infliximab and 4-8 weeks and 2 and 4 years after re-treatment [November 2010]
Long-term efficacy of infliximab over 4 and 6 years of therapy measured by the ASAS response criteria [November 2010]
Efficacy and safety of a new start of infliximab therapy after discontinuation for several months after 2 and 4 years of continuous treatment [November 2008 and November 2010]
Long-term effects on QoL [November 2010]
Long-term effects on health resource utilisation and productivity in paid and unpaid work [November 2010]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All patients in Europe who have completed visit "week 96" of ASSERT (last infusion of infliximab)
Capacity to understand and sign an informed consent form
Capacity to read and understand subject assessment forms
Using adequate birth control measures for the duration of the study and for 6 months after receiving the last infusion, if the patient is of childbearing potential
Serum creatinine < 1,4 mg/dl
Hemoglobin > 9,0 mg /dl for males and > 8,5 mg/dl for females
Serum transaminase levels within 3 times the upper limit of normal range

Exclusion Criteria:

Have used systemic prednisolone > 20 mg during the 2 weeks prior to screening
Have used cytotoxic drugs after the end of ASSERT including chlorambucil, cyclophosphamide and alkylating agents
Have received any previous treatment with etanercept or any other anti-TNF agent (other than infliximab) after the end of the ASSERT trial
General medical exclusion criteria
Use of any investigational drug within 30 days prio to screening
Concomitant diagnosis or history of congestive heart failure
History of latent or active tuberculosis
Signs or symptoms suggestive of active tuberculosis
Recent close contact with a person with active tuberculosis

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Erasme University Hospital	Brussels	Belgium
2	Limburg University Centre	Diepenbeek	Belgium
3	Universitair Ziekenhuis, Afdeling Rheumatologie	Gent	Belgium	9000
4	University Hospital Leuven	Leuven	Belgium	3000
5	University Central Hospital, Division of Rheumatology	Helsinki	Finland	00029HYKS
6	Groupe Hopitalier Cochin	Paris	France
7	Universitat R. Descartes, Hopital Cochin	Paris	France
8	Charite Mitte	Berlin	Germany	10117
9	Charite Klinikum Steglitz	Berlin	Germany	12200
10	Rheumazentrum Ruhrgebiet	Herne	Germany	44652
11	Ludwigs-Maximilian-Universität	München	Germany	80336
12	Academic Ziekenhuis	Amsterdam	Netherlands	1007MB
13	University Hospital Maastricht	Maastricht	Netherlands	6202 AZ
14	University of Cambridge/ Clin Med	Cambridge	United Kingdom	CB2 QQ
15	University of Leeds	Leeds	United Kingdom	LS2 9N2