To assess the percentage of patients with at least one subtherapeutic infliximab trough serum concentration, being < 1 mg/l.To assess the percentage of patients positive for AIAs at a minimum of one timepoint.To assess the percentage of patients…
ID
Source
Brief title
Condition
- Ocular infections, irritations and inflammations
- Respiratory tract infections
- Skin and subcutaneous tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Infliximab trough serum concentrations and the number of patients with at least
one subtherapeutic concentration, being < 1 mg/l.
AIAs and the number of patients who are positive for AIAs at a minimum of one
timepoint.
The number of patients that have both a subtherapeutic serum concentrations of
infliximab and are positive for AIAs at a minimum of one timepoint.
Baseline, trough and peak TNF-α, TACE, and TNF-α receptors concentrations.
Symptoms, ACE-, CRP-, IL-2R-concentrations at baseline and during infliximab
treatment (at 3 months and after 6 months) and concentration changes from
baseline.
FVC and DLCO at baseline and after 6 months of treatment and parameter changes
from baseline.
Response i.e. presence/absence of disease progression and/or changed/unchanged
abnormalities, assessed by X-thorax, HRCT and PET scanning at baseline and
after 6 months of treatment.
The number of patients clinically classified as a responder to infliximab
treatment after 6 months of treatment.
Secondary outcome
Expression of TNF-α, TACE, and TNF-α receptors at mRNA and protein levels at
basline, 3 and 6 months.
Background summary
Sarcoidosis is a systemic granulomatous disease that primarily affects the lung
and lymphatic systems of the body. The cytokine tumor necrosis factor (TNF)-α
is critical to the development of the granulomatous inflammation.
Corticosteroids and methotrexat are considered to be the standard treatment for
sarcoidosis. Due to the non-specificity, long-term toxicity and unproven
efficacy of these therapies (5, 6), there is a clinical need in some cases for
more effective and safer therapies such as infliximab. This is a TNF-α
inhibitor that binds to TNF-α and neutralizes its biological activities.
Infliximab is not registered as a treatment for sarcoidosis yet. However, CVZ
has classified sarcoidosis as an orphan indication for which the drug is
considered to be rational pharmacotherapy. Although most of RA and CD patients
are achieving at least partial clinical response to infliximab, 30-40% of them
are not responding (10, 11). This is also recognized in the treatment of
sarcoidosis in daily clinical practice. Those patients are classified as
responders and nonresponders, due to the interindividual variation in response
to infliximab
So far, the relationship between infliximab concentrations and response in
sarcoidosis patients has not been studied and the optimal dosing regimen is
still unknown. Infliximab serum trough level of < 1 mg/l has been considered as
a sub-therapeutic level, higher trough levels are associated with improved
response in RA (15) and lower level of anti-infliximab antibody development
(16). Researchers have shown that the response to infliximab in RA patients
follows the trough levels of infliximab and the formation of anti-infliximab
antibodies (17). Recently, more data became available regarding the association
between low infliximab serum concentrations and the failure of infliximab in RA
(18,19).
The hypothesis to be tested in this study is that serum infliximab
concentrations, anti-infliximab antibodies, TNF-α levels, and the genetic
background of the patients are responsible to the interindividual variation in
response to infliximab.
Study objective
To assess the percentage of patients with at least one subtherapeutic
infliximab trough serum concentration, being < 1 mg/l.
To assess the percentage of patients positive for AIAs at a minimum of one
timepoint.
To assess the percentage of patients with both a subtherapeutic infliximab
trough serum concentration and positive for AIAs at a minimum of one timepoint.
To assess the percentage of patients classified as responder after 6 months of
infliximab treatment.
To assess the correlation between TNF-α, TNF-α receptors versus TACE
concentrations.
To study the pharmacokinetics of infliximab.
To study the TNF-α concentrations in course of the infliximab treatment and to
compare concentrations with baseline values.
Study design
This is a prospective observational study in patients who are diagnosed with
sarcoidosis and routinely treated with infliximab.
Study burden and risks
Blood will be drawn from the patients prior to each infusion and one hour after
their completion at each visit. The risks of drawing blood from a vein are
minimal. Patients are requested to visit the hospital at two additional
timepoints.
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Listed location countries
Age
Inclusion criteria
- patients diagnosed with sarcoidosis.
- patients treated with infliximab
- capability of giving informed consent
Exclusion criteria
· vaccination with live viral or bacterial vaccines within the previous 3 months, or within the next 3 months of the last doses.
· cases of active or untreated latent tuberculosis (by mantoux-Elispot/TBC-IGRA)
· serious infections within the past 2 months
· serious right-sided heart failure or cor polmunale
· known malignancy
· Hepatitis B
· paitients with allergic reactions to the monocolonal antibodies or their fragments
· oppotunistic infections last 6 months
· HIV
· transplantation
· pregnancy or bearstfeeding
Design
Recruitment
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 |
|---|---|
| Other | 99 |
| CCMO | NL31842.100.10 |