Until recently there were only few therapeutic options to treat AS. Efficacy is proven for several tumor necrosis factor (TNF)-blocking agents, including golimumab. 2-8 However, up to now, the efficacy of golimumab treatment on EAMs, like anterior…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Study Objective: Determine the difference in the incidence rate of
uveitis in subjects with Ankylosing Spondylitis (AS), before and after
treatment with golimumab.
Efficacy Analysis: The Primary Efficacy Endpoint for the study is the
difference in the overall incidence rate of uveitis attacks during the 12
months before treatment and after the start of golimumab.
Secondary outcome
Key Secondary Study Objectives:
- Determine the difference in the incidence rate of new onsets or flares of IBD
and psoriasis in AS patients before treatment and after the start of golimumab
- Determine the effectiveness of golimumab on AS disease activity, as assessed
by BASDAI 50% and ASDAS in routine daily practice.
Exploratory study objectives:
- Determine the effectiveness of golimumab on AS disease parameters (including
ASAS20, BASFI, BASMI, MASES, ASQOL) in daily clinical practice
- Investigate the effect of golimumab on the left ventricular heart function
(assessed with transthoracal echocardiography) , the cardiac conduction system
(determined on routine ECG*s) and carotid intima media thickness (cIMT)
(assessed with B-mode echo), as assessed in the participating centers in
Amsterdam
- Identify prevalence of CV risk factors and the occurrence of CV events (new
diagnosis of hypertension, TIA, CVA, MI, unstable angina pectoris, urgent
revascularization) during golimumab treatment.
- Determine the safety of long-term treatment with golimumab in routine daily
practice.
Key Secondary Efficacy Endpoints
- The difference in the overall incidence rate of new onsets or flares of IBD
and psoriasis during the 12 months before treatment and after the start of
golimumab
- Responders with a ASDAS score
- BASDAI 50 response
Exploratory Endpoints, prospectively assessed during entire study:
- The effectiveness of golimumab on AS specific disease parameters in daily
practice
- Risk factors for CV disease and the occurrence of CV events as assessed
during follow-up
Safety Analysis: The following data will be summarized:
Incidence of serious adverse events (SAEs), with special attention to:
- Percentage of subjects admitted to the hospital and the reason(s) why.
- Percentage of subjects suffering from a severe infection that makes
hospitalization necessary and the type of infection.
- Incidence of other infections during the study period treated with
antibiotics by the general practitioner or the rheumatologist.
- Occurrence of malignancies.
Background summary
The TNF-blocking agents which are commonly used now in AS, like infliximab,
adalimumab and etanercept, do not all have the same efficacy on EAMs.The
prevalence of acute anterior uveitis attacks is very high: up to 40% in a
life-time of an AS patient and these attacks can result in severe chronic
visual impairment if not treated properly. The prevalence of colitis is much
lower, approximately 5%, but some TNF-blocking agents seem to be very effective
in preventing colitis, whereas others are not. Until now, data concerning the
efficacy of golimumab in preventing colitis are lacking. Psoriasis also occurs
rather frequently in AS, estimated at 5% of the AS patients, but can also
develop in a small number of AS patients during anti-TNF treatment (e.g.
pustulosis palmoplantaris). Limited data are available so far concerning the
effect of golimumab on psoriasis.
Another important topic nowadays is cardiovascular (CV) disease in inflammatory
arthritis patients. Recently, a survey was completed, that indicates that the
myocardial infarction (MI) risk in AS patients is increased two-fold in
comparison to the general population. Presently, there is accumulating indirect
evidence that TNF-blocking agents have favorable effects on the CV risk in
inflammatory arthritis patients. This may in part be due to beneficial effects
on the lipid profile. Therefore, in the present study, it will be investigated
whether treatment with golimumab results in changes in the lipid profile and in
the risk of CV events.
According to the definition of disease activity and improvement criteria, a lot
of effort has been made to find some other parameters than BASDAI 50 and
Assessment of SpondyloArthritis international Society (ASAS) 20% response,
which are based on patient questionnaires. Recently, the ASDAS was developed
which seems to be a valuable new tool because it also incorporates the acute
phase reactants and joint pain.
Study objective
Until recently there were only few therapeutic options to treat AS. Efficacy is
proven for several tumor necrosis factor (TNF)-blocking agents, including
golimumab. 2-8 However, up to now, the efficacy of golimumab treatment on EAMs,
like anterior uveitis, inflammatory bowel disease (IBD; Crohn's disease or
ulcerative colitis), psoriasis and enthesitis, is lacking. In addition, there
are limited data on the treatment with golimumab in patients with AS in routine
daily practice, since these patients, although eligible for treatment with a
TNF-blocking agent, do not necessarily fulfill all criteria of randomised
controlled clinical trials. Moreover, data on the efficacy and safety of
golimumab during long-term treatment are not yet available. Therefore, a long
term prospective follow-up study is necessary to provide this additional
information.
Study design
This is an open-label, history-controlled, multi-site study of golimumab in
subjects with AS. For evaluation of the primary study end-point, subjects will
serve as their own control. The period before start of treatment with an
anti-TNF agent will serve as historical control for the incidence of EAMs, with
a review of the medical records done for the previous 1 year period.
Efficacy and safety will be assessed by means of well-established
questionnaires, radiographs, physical examination, recording of the occurrence
of CV events as well as serious adverse events (SAEs).
Study burden and risks
Golimumab treatment is efficient in treating AS patients. The risk will not be
higher than those mentioned on the package leaflet of Simponi.
Waarderweg 39
Haarlem 2031 BN
NL
Waarderweg 39
Haarlem 2031 BN
NL
Listed location countries
Age
Inclusion criteria
1. Each subject should not have received golimumab before the study.
2. Each subject is prescribed golimumab according to routine daily practice.
3.Each subject must be able to provide retrospective data concerning EAM episodes with a recall period of at least 12 months prior to anti-TNF use.;4. Each subject must be willing and able to provide written informed consent for the study. The legal representative (e.g. parent or guardian) for a subject unable to provide independent consent may provide written informed consent for the subject.;5. Each subject must be >= 18 years of age. A subject may be of either sex, any race/ethnicity.;6. Each subject must have definite AS according to the modified New York criteria in the Netherlands.;7. Each subject must be candidate for treatment with anti-TNF according to the ASAS consensus.;8. Each subject must be able to adhere to dose and visit schedules.
Exclusion criteria
1. Any exclusion criterion as stated in the SPC for golimumab;2. The subject has used any investigational biological or chemical agents within 30 days or 2 half-lives (whichever is longest) of screening.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002458-21-NL |
| CCMO | NL40935.048.12 |