Clinical trial NCT04200833: Golimumab in Juvenile Idiopathic Arthritis-associated Uveitis Failing Adalimumab
Official title: Golimumab in Juvenile Idiopathic Arthritis-associated Uveitis Failing Adalimumab
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: JIA Associated Uveitis
Keywords: Biological
Uveitis
adalimumab
golimumab
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2019-12-16
Enrollment: 10
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: JIA patients at a tertiary referal Center in Graz /Austria. University setting.

Brief summary: To asses the use of golimumab, a fully humanized anti-TNF Alpha monoclonal antibody, in juvenile idiopathic Arthritis-associated uveitis refractory to adalimumab.

Detailed 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).

Eligibility criteria: Inclusion Criteria:

* JIA associated Uveitis
* Treatment failure with adalimumab

Exclusion Criteria:

* Uveitis due to other causes
* Adalimumab Initiation because of non ocular reasons

Primary outcomes:
measure: Number of Participants Reported as Complete Responders to Golimumab
timeFrame: last follow up, up to 5 years
Secondary outcomes:
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: up to 5 years
measure: Number of Patients With Ocular Discomfort
timeFrame: up to 5 years
measure: Steroid Sparing Potential
timeFrame: Baseline, 12 Months Follow-Up
Other outcomes:
Locations:
Study officials:
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