Axial Spondyloarthritis
Conditions
Brief summary
The hypothesis of the study is that the presence of (subclinical) gut inflammation at baseline in patients with early active axial spondyloarthritis predisposes to a more severe disease defined as more need to use anti-tumor necrosis factor α therapy and a shorter time to relapse after stopping anti-tumor necrosis factor α therapy after obtaining sustained clinical remission. Overall, the investigators hypothesize that subclinical gut inflammation is an important predictor in therapy response and outcome. These data could provide better insights into the complex interactions between gut and joint inflammation and guide the physicians in the therapeutic approach.
Interventions
DRUGGolimumab
Axial spondyloarthritis patients who don't have a good treatment response on 2 NSAIDs, will be treated with golimumab. After remission, the therapy will be stopped. All patients will undergo a ileocoloscopy at baseline and, if positive, at time of remission.
Sponsors
Merck Sharp & Dohme LLC
the Flanders Institute for Biotechnology
University Ghent
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 46 Years
Healthy volunteers
No
Inclusion criteria
* Subject must have a diagnosis of axSpA and classified according to ASAS criteria. * Subject has at least 3 months and maximum 1 year (almost) daily chronic back pain. * Subject has an active disease defined as a positive MRI (according to ASAS definition) or elevated CRP (in patients who are HLA-B27+) and an ASDAS score \> 2.1 (at least high disease activity).
Exclusion criteria
* Full anti-inflammatory dose of NSAIDs for more than 4 weeks for the duration of the axSpA symptoms. * Prior exposure to any biologic therapy with a potential therapeutic impact on SpA, including anti-TNF therapy. * Exposure to disease-modifying drugs (DMARDSs; i.e. methotrexate and sulfasalazine) in the last 3 months before the ileocolonoscopy. * Exposure to systemic corticosteroid treatment in the last 14 days before the ileocolonoscopy. * Infection(s) requiring treatment with intravenous antibiotics/antivirals/antifungals within 30 days prior to the baseline visit or oral antibiotics/antivirals/antifungals within 14 days prior to the baseline visit. * Have a known hypersensitivity to human immunoglobulin proteins or other components of golimumab. * History of central nervous system (CNS) demyelinating disease or neurologic symptoms suggestive of CNS demyelinating disease. * History of listeriosis, histoplasmosis, chronic of active hepatitis B infection, hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis. * Have a history of, or concurrent, chronic heart failure, including medically controlled, asymptomatic congestive heart failure. * Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix. * Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months prior to the first administration of study agent, during the trial, or within 6 months after the last administration of study agent. * Positive pregnancy test at screening. * Female subjects who are breast-feeding or considering becoming pregnant during the study. * Female subjects who do not use contraceptives. * History of clinically significant drug or alcohol abuse in the last 12 months. * Clinically significant abnormal screening laboratory results as evaluated by the investigator. * Positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibody at screening if the titers are crossing 3 times the upper limit of the normal. * Subject with diagnosis and current symptoms of fibromyalgia. * Any medical or psychological condition that, in the opinion of the investigator, could jeopardize or compromise the subject's ability to participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving Sustained Clinical Remission | Upon end of trial for individual patient, between 28 and 52 weeks. | The proportion of patients who completed the trial and achieved Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) \< 1.3 recorded on 2 consecutive visits with at least 12 weeks interval. ASDAS-CRP was measured at every study visit, i.e. baseline, week 2, week 4, week 16, week 28, week 40 and week 52. The study endpoint could earliest be achieved at visit week 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Patients With Healed Lesions of the Intestinal Mucosa | At reaching primary outcome (between week 24 and week 52) | According to the protocol, every patient underwent ileocolonoscopy at baseline to screen for macroscopic and microscopic (histopathologic analysis of endoscopic biopsies) signs of inflammation. If baseline ileocolonoscopy was protocolled as positive, the patient would undergo a second ileocolonoscopic assessment at the timepoint of reaching sustained clinical remission (study endpoint). The outcome measure is the proportion of patients with a negative second ileocolonoscopy. |
Countries
Belgium
Participant flow
Recruitment details
Recruitment period: November 2017 - December 2022 across 3 centres: * Gent University Hospital * Imelda Hospital in Bonheiden * Jessa Hospital in Hasselt
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: NSAIDs With Possible Step-up to Golimumab NSAIDs: All patients fulfilling the inclusion criteria will be treated according to the current recommendations for the management of axial spondyloarthritis, i.e. with 2 courses of NSAIDs. If sufficient response is acheived, the patients will continue receiving NSAIDs and after sustained remission, the therapy will be stopped. If therapy with NSAIDs provides insufficient control of disease activity, switch to therapy with Golimumab will be made.
Golimumab: Patients who did not have a good treatment response to 2 NSAIDs, will be treated with golimumab sc 50mg/4 weeks. After sustained remission, the therapy will be stopped.
All patients will undergo a ileocoloscopy at baseline and, if positive, at time of remission. | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Screen failure | 6 |
Baseline characteristics
| Characteristic | Arm 1: NSAIDs With Possible Step-up to Golimumab |
|---|---|
| Age, Continuous | 28.2 years STANDARD_DEVIATION 6.3 |
| Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP | 3.0 units on a scale STANDARD_DEVIATION 0.9 |
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Arthritis | 5 Participants |
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Dactylitis | 0 Participants |
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Good response to NSAIDs | 44 Participants |
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Heel enthesitis | 3 Participants |
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Inflammatory Back Pain | 51 Participants |
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Inflammatory bowel disease | 1 Participants |
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Psoriasis | 0 Participants |
| Assessment of SpondyloArthritis international Society (ASAS) criteria: Uveitis | 0 Participants |
| Assessment of SpondyloArthritis international Society criteria: Elevated C-reactive protein | 24 Participants |
| Assessment of SpondyloArthritis international Society criteria: Family history of spondyloarthritis | 22 Participants |
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | 4.5 units on a scale STANDARD_DEVIATION 1.5 |
| Bath Ankylosing Spondylitis Functional index (BASFI) | 3.0 units on a scale STANDARD_DEVIATION 2.2 |
| Body mass index (BMI) | 23.3 kg/m^2 STANDARD_DEVIATION 4.7 |
| CRP (mg/mL) | 7.6 mg/mL STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Positive for HLA-B27 (%) | 50 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 34 Participants |
| Time from diagnosis | 37 days STANDARD_DEVIATION 18 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 58 |
| other Total, other adverse events | 19 / 58 |
| serious Total, serious adverse events | 0 / 58 |
Outcome results
Primary
Proportion of Patients Achieving Sustained Clinical Remission
The proportion of patients who completed the trial and achieved Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) \< 1.3 recorded on 2 consecutive visits with at least 12 weeks interval. ASDAS-CRP was measured at every study visit, i.e. baseline, week 2, week 4, week 16, week 28, week 40 and week 52. The study endpoint could earliest be achieved at visit week 28.
Time frame: Upon end of trial for individual patient, between 28 and 52 weeks.
Population: Patients who completed the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: NSAIDs With Possible Step-up to Golimumab | Proportion of Patients Achieving Sustained Clinical Remission | 34 Participants |
Secondary
The Proportion of Patients With Healed Lesions of the Intestinal Mucosa
According to the protocol, every patient underwent ileocolonoscopy at baseline to screen for macroscopic and microscopic (histopathologic analysis of endoscopic biopsies) signs of inflammation. If baseline ileocolonoscopy was protocolled as positive, the patient would undergo a second ileocolonoscopic assessment at the timepoint of reaching sustained clinical remission (study endpoint). The outcome measure is the proportion of patients with a negative second ileocolonoscopy.
Time frame: At reaching primary outcome (between week 24 and week 52)
Population: At baseline ileocolonoscopy, macroscopic lesions justifying a repeated ileocolonoscopy at a later timepoint were found in only 1 patient. For this patient, pathologic findings present at baseline assessment were also found during the second assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: NSAIDs With Possible Step-up to Golimumab | The Proportion of Patients With Healed Lesions of the Intestinal Mucosa | 0 Participants |