Golimumab in Juvenile Idiopathic Arthritis-associated Uveitis Failing Adalimumab

NCT ID: NCT04200833

Last Updated: 2022-05-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 10 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-03-01
• Study Completion Date: 2021-08-01

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).

Conditions

JIA Associated Uveitis

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Study Groups

group 1

All JIA patients that were switched from adalimumab to golimumab because of Treatment failure of their JIA associated uveitis at the Medical University of Graz Austria from 2010 to 2019

Golimumab

Intervention Type: DRUG

subcutaneous injection

Interventions

Golimumab

subcutaneous injection

Intervention Type: DRUG

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Graz

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

31-301ex18/19

Identifier Type: -

Identifier Source: org_study_id