Clinical and Radiological Manifestations of Coxitis in Patients With Ankylosing Spondylitis Treated With Golimumab (GO-COX)

A Prospective Observational Study to Evaluate Clinical and Radiological Manifestations of Coxitis in Patients With Ankylosing Spondylitis Treated With Simponi® (Golimumab)

Rationale. Coxitis in AS is inflammation of hip(s) affecting significant number of patients. It is associated with worse function and more expressed axial disease requiring hip replacement at end-stage. Number of studies dedicated to coxitis treated with TNF alpha inhibitors is very limited.

Primary objective. To evaluate change of functional impairment in AS patients with coxitis from baseline to 12 months of therapy with golimumab by BASFI in daily clinical practice

Study design. This study is a non-interventional prospective observational cohort study conducted in multiple centers across Russia.

Study population. Patients with ankylosing spondylitis (according to the modified New York criteria) with coxitis newly prescribed golimumab during the course of usual clinical care will be enrolled and followed prospectively for 24 months with data collection at the approximate time points: baseline (pre-treatment) and consequent every 6 months. Patients will receive golimumab as prescribed in regular clinical practice.

Statistical Methods. Quantitative variables will be tested for normal distribution using the Shapiro-Wilk test. The hypothesis of equality of variances will be tested using Levene's test. Quantitative variables matching a normal distribution will be described in terms of the mean ± standard deviation, and values outside of the normal distribution as medians, 25% and 75% quartiles. Qualitative variables will be presented in the form of percentages of the absolute value N.

Sample Size and Power Calculations. Sample size calculation is based on data from GO-RAISE registration study in which golimumab was evaluated in patients with AS. The baseline BASFI was 5.0 which changed by mean (± SD, standard deviation) -2.5 (± 2.12) at week 52 (approximately 12 months). The analysis of the data shows that the minimum necessary sample size should be 18 patients to show a statistically significant change of BASFI from baseline to 12 months. On this basis and considering that the dropout rate over the two years is expected to be 30%, we decided that the necessary number of patients to be included into protocol should be 39 individuals. It is expected that around 27 patients will be included in the patient set completing the study. Power of the study is 90% with formula evaluation P = 1-β where P is power and β is type 2 error = 10%.

Study Overview

• Status: Unknown
• Conditions: Ankylosing Spondylitis; Coxitis
• Intervention / Treatment: Drug: Golimumab Injection

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• Russian Federation
  • Khanty-Mansiysk, Russian Federation
    • KhMAO Regional Clinical Hospital
  • Moscow, Russian Federation
    • Moscow Clinical Scientific Center
  • Moscow, Russian Federation
    • Pirogov National Medical Surgical Center
  • Moscow, Russian Federation
    • Rheumatology Research Institute
  • Rostov-on-Don, Russian Federation
    • Regional Clinical Hospital #2
  • Yakutsk, Russian Federation
    • City Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with ankylosing spondylitis and coxitis followed in normal practice, in whom golimumab has been newly prescribed.

Description

Inclusion Criteria:

1. Adult patients (>18 years of age) with definite AS (as per modified New York criteria)
2. Coxitis with BASRI-hip score 0-2
3. Newly prescribed golimumab according to usual clinical practice
4. Naïve to anti-TNFs or other biologic agents prior to initiation of golimumab as indicated by the patient's medical records
5. Patient is enrolled after the investigator's decision to treat with golimumab, but before initiation of treatment with golimumab
6. Patient was informed of the benefits and risks of golimumab as per normal practice using the product leaflet
7. Signed informed consent form

Exclusion Criteria:

1. Any contraindication to golimumab in accordance to the label of Simponi®
2. BASRI-hip score 3-4
3. Any contraindication to MRI, e.g. previous hip joint replacement, heart pace maker.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Golimumab injection; Patients with ankylosing spondylitis and coxitis being treated with Simponi (golimumab) according to local clinical practice and label.	Drug: Golimumab Injection; Simponi (golimumab) in fixed dose of 50 mg sc per month according to local label and local clinical practice.; Other Names: Based on decision of investigators.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of BASFI (Bath Ankylosing Spodylitis Functionality Index)	The BASFI is a self-assessment instrument for defining and monitoring functional ability (physical functioning) in patients with AS. Contains 10 items: 8 items concerning activities referring to the functional anatomy of the patients (bending, reaching, changing position, standing, turning, and climbing steps) and 2 items assessing the patients' ability to cope with everyday life.	From baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of BASFI (Bath Ankylosing Spodylitis Functionality Index)	The BASFI is a self-assessment instrument for defining and monitoring functional ability (physical functioning) in patients with AS. Contains 10 items: 8 items concerning activities referring to the functional anatomy of the patients (bending, reaching, changing position, standing, turning, and climbing steps) and 2 items assessing the patients' ability to cope with everyday life.	From baseline to 24 months
Change of BASMI (Bath Ankylosing Spodylitis Mobility Index)	The BASMI is an instrument that is typically used to assess mobility of spine and hip joints. The BASMI consists of 5 items which are clinical measures of cervical rotation, tragus to wall distance, lumbar flexion, lumbar side flexion, and intermalleolar distance. Each item is scored from 0 to 10 based on individually defined cut points.	From baseline to 12 and 24 months
Change of ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score)	ASDAS is an instrument to measure disease activity in AS based on a composite score. The score includes patient-reported assessments of back pain, duration of morning stiffness, peripheral joint pain and/or swelling, general well-being, and a serologic marker of inflammation (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]).	From baseline to 12 and 24 months
BASRI-hip (Bath Ankylosing Spondylitis Radiology Index)	In BASRI-hip hips radiographs are graded on a scale of 0-4 (0 - no change; 1 - suspicious: focal joint space narrowing; 2 - mild: circumferential joint space narrowing >2mm; 3 - moderate: circumferential joint space narrowing ≤ 2mm or bone-on-bone apposition of <2 cm; and 4 - severe: bone deformity or bone-on-bone apposition of ≥2 cm)	From baseline to 12 and 24 months
BASDAI (Bath AS Disease Activity Index)	BASDAI is an instrument to measure disease activity in AS based on a omposite score. The index includes patient-reported levels of back pain, fatigue, peripheral joint pain and swelling, localized tenderness, and the duration and severity of morning stiffness.	From baseline to 12 and 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of MRI signs of coxitis	At the moment, there is no standardized MRI scores available for hips. Information on hip(s) MRI (STIR (short tau inversion recovery) sequence and fat-saturated contrast-enhanced T1-weighted sequence) will be collected for patients based on availability. The following parameters of active inflammation will be determined: No lesions suggesting inflammation; Subchondral bone marrow edema (expressed as Yes or No); Joint effusion (expressed as Yes or No); Enthesitis at sites where ligaments and tendons are attached to bone in structures adjacent to the hip joint (expressed as Yes or No); Fatty degeneration (expressed as Yes or No); Change of a parameter from previous examination (Positive change or No change or Negative change).	From baseline to 6 and 12 months
Change of Ultrasound (US) signs of coxitis	At the moment, there is no standardized US scores available for hips. Information on hip(s) US will be collected for patients based on availability in the patient charts. The following parameters of active inflammation will be determined: Joint effusion (expressed as Yes or No); Distance between lower margin of femoral neck and lower part of joint capsule expressed in millimeters; Enthesitis at sites where ligaments and tendons are attached to bone in structures adjacent to the hip joint (expressed as Yes or No); Change of enthesitis from previous examination (Positive change or No change or Negative change).	From baseline to 6 and 12 months
Change of occupational status of AS patients with coxitis	Occupational status is to be registered at baseline and followed-up. It is to be desribed as one of the following: employed, self-employed, studying, pensionner, unemployed, disabled.	From baseline to 12 and 24 months

Collaborators and Investigators

• Sponsor: MSD Pharmaceuticals LLC
• Investigators: Study Director: Ekaterina Lukyanova, MD, MSD Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: June 5, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): June 21, 2018
• Last Update Submitted That Met QC Criteria: June 19, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Golimumab
• Other Study ID Numbers: MK-8259-021

Drug and device information, study documents

• 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.: Yes