Golimumab in Juvenile Idiopathic Arthritis-associated Uveitis Failing Adalimumab

• Sponsor: Medical University of Graz (Other)
• Overall Status: Completed
• CT.gov ID: NCT04200833
• Collaborator: (none)
• Enrollment: 10
• Actual Duration (Months): 137

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
JIA Associated Uveitis	Drug: Golimumab

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).

Study Design

• Study Type: Observational
• Actual Enrollment: 10 participants
• Observational Model: Case-Only
• Time Perspective: Retrospective
• Official Title: Golimumab in Juvenile Idiopathic Arthritis-associated Uveitis Failing Adalimumab
• Actual Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jul 1, 2021
• Actual Study Completion Date: Aug 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
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	Drug: Golimumab; subcutaneous injection

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reported as Complete Responders to Golimumab [last follow up, up to 5 years]

   Response was classified as complete, partial, or none ("non-response", NR) at each timepoint separately." Complete response (CR) constituted achieving inactive uveitis, defined as 0+ cells in the AC (grade 0). Partial response (PR) was diagnosed in patients with improved uveitis, defined as a decrease in the level of inflammation, without achieving AC grade 0 status. Primary-NR was diagnosed in patients without change in SUN score and an entry grade of 3 or higher or in patients with worsening activity, defined as either a two-grade increase in inflammation or an increase in inflammation to grade 4. Relapse of uveitis was defined as active inflammation after at least 3 months of inactivity,

Secondary Outcome Measures

1. Best Corrected Visual Acuity (BCVA) [up to 5 years]

   best corrected visual acuity

2. Number of Patients With Ocular Discomfort [up to 5 years]

   eye soreness, photophobia

3. Steroid Sparing Potential [Baseline, 12 Months Follow-Up]

   Reduction in systemic steroid dose at the 12 month follow-up compared to baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• JIA associated Uveitis

• Treatment failure with adalimumab

Exclusion Criteria:

• Uveitis due to other causes

• Adalimumab Initiation because of non ocular reasons

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Medical University of Graz

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 14, 2021

More Information

Publications

None provided.

• Responsible Party: Medical University of Graz
• ClinicalTrials.gov Identifier: NCT04200833
• Other Study ID Numbers: 31-301ex18/19
• First Posted: Dec 16, 2019
• Last Update Posted: May 5, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Medical University of Graz: Biological; Uveitis; adalimumab; golimumab
• Additional relevant MeSH terms: Arthritis, Juvenile; Uveitis; Golimumab

Study Results

Participant Flow

Arm/Group Title	Group 1
Arm/Group Description	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: subcutaneous injection
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Group 1
Arm/Group Description	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: subcutaneous injection
Overall Participants	10
Age (Count of Participants)
<=18 years	9 90%
Between 18 and 65 years	1 10%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.0 (6.4)
Sex: Female, Male (Count of Participants)
Female	10 100%
Male	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Austria	10 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reported as Complete Responders to Golimumab
Description	Response was classified as complete, partial, or none ("non-response", NR) at each timepoint separately." Complete response (CR) constituted achieving inactive uveitis, defined as 0+ cells in the AC (grade 0). Partial response (PR) was diagnosed in patients with improved uveitis, defined as a decrease in the level of inflammation, without achieving AC grade 0 status. Primary-NR was diagnosed in patients without change in SUN score and an entry grade of 3 or higher or in patients with worsening activity, defined as either a two-grade increase in inflammation or an increase in inflammation to grade 4. Relapse of uveitis was defined as active inflammation after at least 3 months of inactivity,
Time Frame	last follow up, up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1
Arm/Group Description	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: subcutaneous injection
Measure Participants	10
Count of Participants [Participants]	8 80%

2. Secondary Outcome

Title	Best Corrected Visual Acuity (BCVA)
Description	best corrected visual acuity
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1
Arm/Group Description	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: subcutaneous injection
Measure Participants	10
Mean (Standard Deviation) [LogMAR]	0.27 (0.33)

3. Secondary Outcome

Title	Number of Patients With Ocular Discomfort
Description	eye soreness, photophobia
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1
Arm/Group Description	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: subcutaneous injection
Measure Participants	10
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Steroid Sparing Potential
Description	Reduction in systemic steroid dose at the 12 month follow-up compared to baseline
Time Frame	Baseline, 12 Months Follow-Up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1
Arm/Group Description	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: subcutaneous injection
Measure Participants	10
Mean (Full Range) [mg/kg per day]	0.19

Adverse Events

Time Frame	Up to 66 months
Arm/Group Title	Group 1
Arm/Group Description	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: subcutaneous injection
All Cause Mortality
	Group 1
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Group 1
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Group 1
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.