The Incidence of Extra-Articular Manifestations in Participants With Ankylosing Spondylitis Treated With Golimumab (MK-8259-012)

Study Overview
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Brief Summary
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The objective of this study is to determine the difference in the annual incidence rate of uveitis attacks in participants with ankylosing spondylitis (AS) before start initial anti-TNF therapy and after treatment with golimumab (GLM).

Detailed Description
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This is an open-label, history-controlled, multi-site study of GLM in participants with AS. For evaluation of the primary study outcome measure, participants will serve as their own control. The period before start of treatment with an anti-tumor necrosis factor (TNF) agent will serve as historical control for the incidence of extra-articular manifestations, with a review of the medical records done for the previous 1-year period. Each participant will participate in the study for approximately 12 months from the time the participant signs the Informed Consent Form through the final contact. After screening, two to four weeks before study start, each participant will be receiving study treatment for approximately 12 months, depending on the response to GLM after 3 months. All participants will be followed for a minimum of 12 months, irrespective of the duration of GLM treatment.

Official Title
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Open-Label, Phase 4 Study, Investigating the Incidence of Extra-Articular Manifestations in Subjects With Ankylosing Spondylitis Treated With Golimumab; Protocol No. MK-8259-012

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Biological: Golimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: May not have been treated with GLM prior to study enrollment Must be able to provide retrospective data concerning extra-articular manifestations and episodes with a recall period of at least 12 months prior to anti-TNF use Must have definite AS according to the modified New York criteria in the Netherlands Must be candidate for treatment with anti-TNF agent according to the Assessment of SpondyloArthritis International Society (ASAS) consensus Must be able to adhere to dose and visit schedules Exclusion Criteria: Any exclusion criteria stated in the Summary of Product Characteristics for golimumab Use of any investigational biological or chemical agents within 30 days or 2 half-lives (whichever is longest) of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLM 50 mg<br>GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months | Biological: Golimumab<br>* GLM 50 mg subcutaneously once monthly.<br>* Other names: Simponi®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence Rate of Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment | Uveitis is an extra-articular manifestation of ankylosing spondylitis (AS) involving inflammation of the eye. The occurrence rate (assessed as present/absent) of uveitis attacks was determined over two 1-year long periods regardless of whether the event started during the assessed year: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose. | Twelve Months Prior to Enrollment to Study Month 12 | 
| Annual Incidence Rate of New Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment | Uveitis is an extra-articular manifestation of AS involving inflammation of the eye. The annual incidence rate of new uveitis attacks was determined over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose. All participants were counted as contributing a full year of GLM exposure even if discontinuing early. Due to ongoing uveitis cases at time of period entry, participants did not have the same risk of new events during the one year periods. Participants with ongoing uveitis at start of GLM who had the adverse event for the entire treatment period were counted as having the 'new attack' before and no new attack after GLM treatment start. | Twelve Months Prior to Enrollment to Study Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Incidence Rate of New-Onset or Flares of Inflammatory Bowel Disease (IBD) and Psoriasis in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment | IBD (Crohn's disease or ulcerative colitis) and psoriaris are extra-articular manifestations of AS involving the intestinal tract and skin, respectively. The annual incidence rates of new-onset or flares of IBD and psoriasis were to be determined separately (i.e., for each condition) over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose. | Twelve Months Prior to Enrollment to Study Month 12 | 
| Percentage of Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) Responders Following Treatment With GLM | The percentage of participants with a BASDAI 50 response (defined as a 50% improvement or as an absolute improvement of 2 points in their BASDAI physical function score) at three months was determined. The BASDAI consists of total of six visual analog scales (VAS): five VAS (0 to 10 cm; increasing severity) measuring severity of fatigue, spinal pain, peripheral joint pain or swelling, localized tenderness, and severity of morning stiffness and one VAS (0 to 10 cm; increasing duration up to 2 hours) measuring duration of morning stiffness. The morning stiffness scores are averaged and summed with the scores for the remaining four items resulting in a composite score (0-50); the final BASDAI score (0-10) is derived by dividing by 5. | Baseline (BL), Study Month 3 | 
| Percentage of Ankylosing Spondylitis Disease Activity Score (ASDAS) Responders Following Treatment With GLM | The percentage of participants with ASDAS clinically important improvement (ASDAS-CII; ≥ 1.1 units) and major improvement (ASDAS-MI; ≥ 2.0 units) at 3 months were determined. The ASDAS incorporates three items from the BASDAI (spinal pain, duration of morning stiffness, and peripheral joint pain or swelling) each assessed on a VAS (0 to 10 cm; increasing severity) as well as patient global assessment of disease activity (VAS; 0 to 10 cm; increasing severity) and a laboratory measure of inflammation (CRP level [mg/L] or ESR [mm/hr]). ASDAS was calculated using the formula: 0.12*Spinal Pain + 0.06*Duration of Morning Stiffness + 0.11*Patient Global + 0.07*Peripheral Pain/Swelling + 0.58*ln(CRP (mg/L) +1). A decrease in ASDAS at 3 months relative to BL signifies an improvement in physical function; ASDAS-MI (≥ 2.0 units decrease from BL) signifies a comparatively greater improvement in physical function than ASDAS-CII (≥ 1.1 units decrease from BL). | BL, Study Month 3 |