Clinical trial NCT00237419: Examination of Radiographic Progression, Efficacy and Safety of Long-Term Treatment With Infliximab in Patients With Ankylosing Spondylitis
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ankylosing Spondylitis
Keywords: Ankylosing spondylitis
Long-term therapy with infliximab
Radiographic progression
Lead sponsor: Rheumazentrum Ruhrgebiet
Sponsor class: OTHER
Collaborators: name: Centocor BV
name: Trial Coordination Center, 9713 GZ Groningen
name: PPD Development, LP
First posted: 2005-10-12
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: November 2008 and November 2010
Secondary outcomes:
measure: Proportion of patients which have received anti-TNF-alpha therapy as standard care after the end of ASSERT
timeFrame: November 2005
measure: Description of the various treatment regimens after the end of ASSERT of the participating AS patients in various countries
timeFrame: November 2005
measure: Degree of spinal inflammation analyzed by MRI after discontinuation of infliximab and 4-8 weeks and 2 and 4 years after re-treatment
timeFrame: November 2010
measure: Long-term efficacy of infliximab over 4 and 6 years of therapy measured by the ASAS response criteria
timeFrame: November 2010
measure: Efficacy and safety of a new start of infliximab therapy after discontinuation for several months after 2 and 4 years of continuous treatment
timeFrame: November 2008 and November 2010
measure: Long-term effects on QoL
timeFrame: November 2010
measure: Long-term effects on health resource utilisation and productivity in paid and unpaid work
timeFrame: November 2010
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Erasme University Hospital
city: Diepenbeek
country: Belgium
facility: Limburg University Centre
city: Gent
country: Belgium
facility: Universitair Ziekenhuis, Afdeling Rheumatologie
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Helsinki
country: Finland
facility: University Central Hospital, Division of Rheumatology
city: Paris
country: France
facility: Groupe Hopitalier Cochin
city: Paris
country: France
facility: Universitat R. Descartes, Hopital Cochin
city: Berlin
country: Germany
facility: Charite Mitte
city: Berlin
country: Germany
facility: Charite Klinikum Steglitz
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: München
country: Germany
facility: Ludwigs-Maximilian-Universität
city: Amsterdam
country: Netherlands
facility: Academic Ziekenhuis
city: Maastricht
country: Netherlands
facility: University Hospital Maastricht
city: Cambridge
country: United Kingdom
facility: University of Cambridge/ Clin Med
city: Leeds
country: United Kingdom
facility: University of Leeds
Study officials:
affiliation: Rheumazentrum Ruhrgebiet
name: Jürgen Braun, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Webers C, Essers I, van Tubergen A, Braun J, Heldmann F, Baraliakos X, Boonen A. Valuing Treatment With Infliximab for Ankylosing Spondylitis Using a Willingness-to-Pay Approach. Arthritis Care Res (Hoboken). 2018 Apr;70(4):608-616. doi: 10.1002/acr.23299. Epub 2018 Feb 18.