Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04200833 |
| Other study ID # |
31-301ex18/19 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2010 |
| Est. completion date |
August 1, 2021 |
Study information
| Verified date |
April 2022 |
| Source |
Medical University of Graz |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
To asses the use of golimumab, a fully humanized anti-TNF Alpha monoclonal antibody, in
juvenile idiopathic Arthritis-associated uveitis refractory to adalimumab.
Description:
Background:
Uveitis is a potentially blinding complication of juvenile idiopathic arthritis (JIA).
Treatment remains a substantial challenge, even though the use of tumor necrosis factor
(TNF)-α-antagonists has improved visual outcomes substantially. Among these agents,
adalimumab has been recently approved for the treatment of non-infectious uveitis and is thus
the first biologic disease-modifying anti-rheumatic drug (bDMARD) approved for JIA-associated
uveitis. However, some patients do not respond sufficiently or lose response over time. In
these cases switching to another biologic DMARD is recommended. Recently golimumab, a fully
humanized anti-TNF-α monoclonal antibody, demonstrated efficacy in a small case series,
leading to uveitis inactivity in 4 of 7 patients Golimumab is approved for the treatment of
polyarticular JIA.
Hypothesis:
Patients with JIA-associated uveitis failing treatment with adalimumab benefit from the
treatment with golimumab.
Methods:
Study design and patient recruitment (retrospectively)
Retrospective single-center study in patients with JIA-associated active uveitis at the
Medical University of Graz/Austria, in whom golimumab was started after failure of standard
conventional immunosuppressive drugs and adalimumab. All patients that have started golimumab
from March 2010 are included in the study. Uveitis is defined and anatomically classified
according to the recommendations of the Standardization of Uveitis Nomenclature (SUN) Working
Group. Primary failure to adalimumab was diagnosed in patients without change in the SUN
score and an entry grade of 3 or higher or with worsening activity, defined as either a
two-grade increase in inflammation or an increase to grade 4. With bilateral disease, the eye
with the higher grade of uveitis was analysed. Relapse of uveitis was defined as active
inflammation after an inactivity for at least 3 months. Loss of response was defined as
failure to improve under continued treatment with adalimumab despite intermitting
intensifying concomitant therapy, such as local or systemic steroids.
Golimumab treatment was administered in the standard dose of 50 mg sc every 4 weeks in
patients with a weight of at least 40 kg. Previous therapy with a conventional DMARD such as
methotrexate (MTX) was continued, if tolerated.
The outcome measures of uveitis include the reduction in grade of intraocular inflammation,
the best-corrected visual acuity, eye soreness, redness of eyes, light sensitivity and the
steroid sparing potential. Response to treatment is classified as complete, partial or no
response. Complete response constitute achieving inactive uveitis, defined as <0.5 cell per
field in the anterior chamber or posterior segment (grade 0) and absence of vitreous haze and
macular edema. Partial response is diagnosed in patients with improved uveitis, defined as
decrease of one grade in the level of inflammation, without a decrease to grade 0 in the
anterior chamber (AC) and posterior segment. Primary failure, relapse and loss of response to
golimumab is defined in the same way as for adalimumab.
Patients receiving Golimumab were evaluated clinically and immunologically at regular
intervals. At each visit the laboratory analysis included complete blood cell counts, levels
of creatinine, hepatobiliary-injury biomarkers, and C-reactive protein. Side effects were
assessed by patient's reported history.
Statistical analysis Continuous variables will be analyzed by Student's t-test or
Mann-Whitney U test. Correlations will be analyzed by Spearman's rank correlation test.
Binary variables were analyzed using Fisher's exact test. Statistical significance was
defined as p<0.05. All statistical analyses were performed using GraphPad Prism V.6.0
(GraphPad, San Diego, CA).
