Ankylosing Spondylitis
Conditions
Keywords
Ankylosing spondylitis;predictive factors
Brief summary
The objective of this observational study is to determine the incidence of response in patients with predictive factors of major clinical response in active ankylosing spondylitis (AS) in patients who start anti-tumor necrosis factor (anti-TNF) therapy and correlate these findings in patients who switch from one to another anti-TNF due to inefficacy under usual clinical practice conditions in Spain.
Detailed description
A sample size of 240 patients, 120 of them exposed and 120 not exposed to factors of response. Sample will be obtain from all the consecutive patients attending the rheumatology settings included in the study who fulfill the inclusion criteria
Interventions
OTHERTreatment switching
If the patients do not response to first AntiTNF treatment, Investigator can switch to another anti TNF.Spanish Guidelines will be provided to the investigators, which recommend stopping biologics if there is an inadequate response after 16w of therapy and switch to another biologic. Responsive patients to the first anti-TNF who continue with this first anti-TNF adjusting dose treatment according to the Spanish guidelines or investigator criteria. The doses for each Anti TNF will be done following specific SmPc and under Investiagtor criteria
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed of active AS who will start anti-TNF therapy following standard clinical practice as per summary of product characteristics doses. * \>18 years, both genders, any disease duration * Signature of informed consent
Exclusion criteria
* Previous treatment with biological therapies * Active tuberculosis infection (local guidelines for appropriate screening and treatment of tuberculosis in the setting of anti-TNF therapy must be followed)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Clinical Response | Week 16 | Assessment of clinical response was as per investigator's discretion. Investigators were provided with the final consensus document of the Spanish Society for Rheumatology (SER) for the biological treatment of spondyloarthropathies as a guide for defining active AS, the indication of treatment with biological therapy and the assessment of response to it. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Low Probability of Response and no Response Who Received Second Anti-TNF Treatment | Week 32 | Low probability of response = participants who met no more than 2 of 5 criteria at time of treatment start: CRP \> 15 mg/L; time from onset of disease less than \< 10 years; total spinal pain \> 30 mm, measured as mean score on 100 mm VNS (higher score=more severe pain) for nocturnal and total spinal pain; BASDAI \> 4 cm, measured as mean score on 10 cm VNS (higher score=more severe state) for discomfort, pain and fatigue; BASFI \< 4.5 cm; measured as mean score on 10 cm VNS (higher score=less functionality) evaluating functional capacity. Assessment of response was as per investigator's criteria. |
| Percentage of Participants With Low Probability of Response and a Clinical Response at Week 16 | Week 16 | Low probability of response = participants who met no more than 2 of 5 criteria at time of treatment start: CRP \> 15 mg/L; time from onset of disease less than \< 10 years; total spinal pain \> 30 mm, measured as mean score on 100 mm VNS (higher score=more severe pain) for nocturnal and total spinal pain; BASDAI \> 4 cm, measured as mean score on 10 cm VNS (higher score=more severe state) for discomfort, pain and fatigue; BASFI \< 4.5 cm; measured as mean score on 10 cm VNS (higher score=less functionality) evaluating functional capacity. Assessment of response was as per investigator's criteria. |
| Percentage of Participants With High Probability of Response and no Response Who Received Second Anti-TNF Treatment | Week 32 | High probability of response=participants who met at least 3 of 5 criteria at start of treatment:C-reactive Protein (CRP) \>15 mg/Liter (mg/L);time from onset of disease \<10 years;total spinal pain \>30 millimeter (mm), mean score on 100 mm visual numeric scale (VNS) for nocturnal, total spinal pain;Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) \>4 centimeter (cm), mean score on 10 cm VNS for discomfort, pain, fatigue;Bath Ankylosing Spondylitis Functional index (BASFI) \<4.5 cm, mean score on 10 cm VNS evaluating functional capacity. Assessment of response was per investigator. |
| Percentage of Participants Who Switched to Another Anti-TNF Treatment Due to Lack of Efficacy | Week 16 | — |
| Percentage of Participants With ASAS 40 Response Who Started Second Anti-TNF Treatment and Were Treated for at Least 16 Weeks | Week 32 | ASAS measures symptomatic improvement in ankylosing spondylitis (AS) participants ASAS = 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement from baseline and an absolute change of greater than or equal to (\>=) 2 units on a 0-10 scale (0=no disease activity, 10=high disease activity) for \>= 3 domains, and no worsening in remaining domain. |
| Percentage of Participants With Assessment in Ankylosing Spondylitis (ASAS) 40 Response at Week 16 | Week 16 | ASAS measures symptomatic improvement in ankylosing spondylitis (AS) participants ASAS = 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40 percent (%) improvement from baseline and an absolute change of greater than or equal to (\>=) 2 units on a 0-10 scale (0=no disease activity, 10=high disease activity) for \>= 3 domains, and no worsening in remaining domain. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anti-tumor Necrosis Factor Agents (Evaluable Population) Participants with active ankylosing spondylitis (AS) who were prescribed with an anti-TNF agent, either etanercept 50 milligram (mg) once weekly or 25 mg twice weekly subcutaneously (s.c.) or infliximab infusion 5 mg per kilogram (mg/kg) body weight intravenously (IV) at Week 0, 2, 6, 14 and 22 or adalimumab 40 mg s.c. every other week, in Phase 1 of the study and who were eligible for the analysis. | 121 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Between Phase 1 and Phase 2 | Responded to therapy- ineligible for Ph2 | 110 |
| Phase 1 | Lacked sufficient information | 4 |
| Phase 1 | Missing information at Week 16 | 7 |
| Phase 2 | Lost to Follow-up | 5 |
Baseline characteristics
| Characteristic | Anti-tumor Necrosis Factor Agents (Evaluable Population) |
|---|---|
| Age Continuous | 42.7 years STANDARD_DEVIATION 11.6 |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 132 |
| serious Total, serious adverse events | 1 / 132 |
Outcome results
Primary
Percentage of Participants With a Clinical Response
Assessment of clinical response was as per investigator's discretion. Investigators were provided with the final consensus document of the Spanish Society for Rheumatology (SER) for the biological treatment of spondyloarthropathies as a guide for defining active AS, the indication of treatment with biological therapy and the assessment of response to it.
Time frame: Week 16
Population: Analysis population included all participants enrolled in the study who gave their consent, satisfied all evaluation criteria and had information available at Week 16 after starting the first anti-TNF treatment (Phase 1).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anti-tumor Necrosis Factor Agents (Phase 1) | Percentage of Participants With a Clinical Response | Adequate Response | 90.9 percentage of participants |
| Anti-tumor Necrosis Factor Agents (Phase 1) | Percentage of Participants With a Clinical Response | Inadequate response | 9.1 percentage of participants |
Secondary
Percentage of Participants Who Switched to Another Anti-TNF Treatment Due to Lack of Efficacy
Time frame: Week 16
Population: Analysis population included all participants enrolled in the study who gave their consent, satisfied all evaluation criteria and had information available at Week 16 after starting the first anti-TNF treatment (Phase 1). Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-tumor Necrosis Factor Agents (Phase 1) | Percentage of Participants Who Switched to Another Anti-TNF Treatment Due to Lack of Efficacy | 72.7 percentage of participants |
Secondary
Percentage of Participants With ASAS 40 Response Who Started Second Anti-TNF Treatment and Were Treated for at Least 16 Weeks
ASAS measures symptomatic improvement in ankylosing spondylitis (AS) participants ASAS = 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement from baseline and an absolute change of greater than or equal to (\>=) 2 units on a 0-10 scale (0=no disease activity, 10=high disease activity) for \>= 3 domains, and no worsening in remaining domain.
Time frame: Week 32
Population: Analysis population included all participants with an inadequate response, 16 weeks after starting the first anti-TNF treatment as determined by ASAS 40 and who received second anti-TNF treatment for at least 16 weeks (Phase 2).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-tumor Necrosis Factor Agents (Phase 1) | Percentage of Participants With ASAS 40 Response Who Started Second Anti-TNF Treatment and Were Treated for at Least 16 Weeks | 0 percentage of participants |
Secondary
Percentage of Participants With Assessment in Ankylosing Spondylitis (ASAS) 40 Response at Week 16
ASAS measures symptomatic improvement in ankylosing spondylitis (AS) participants ASAS = 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40 percent (%) improvement from baseline and an absolute change of greater than or equal to (\>=) 2 units on a 0-10 scale (0=no disease activity, 10=high disease activity) for \>= 3 domains, and no worsening in remaining domain.
Time frame: Week 16
Population: Analysis population included all participants enrolled in the study who gave their consent, satisfied all evaluation criteria and had information available at Week 16 after starting the first anti-TNF treatment (Phase 1).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-tumor Necrosis Factor Agents (Phase 1) | Percentage of Participants With Assessment in Ankylosing Spondylitis (ASAS) 40 Response at Week 16 | 33.1 percentage of participants |
Secondary
Percentage of Participants With High Probability of Response and no Response Who Received Second Anti-TNF Treatment
High probability of response=participants who met at least 3 of 5 criteria at start of treatment:C-reactive Protein (CRP) \>15 mg/Liter (mg/L);time from onset of disease \<10 years;total spinal pain \>30 millimeter (mm), mean score on 100 mm visual numeric scale (VNS) for nocturnal, total spinal pain;Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) \>4 centimeter (cm), mean score on 10 cm VNS for discomfort, pain, fatigue;Bath Ankylosing Spondylitis Functional index (BASFI) \<4.5 cm, mean score on 10 cm VNS evaluating functional capacity. Assessment of response was per investigator.
Time frame: Week 32
Population: Analysis population included all participants with an inadequate response, 16 weeks after starting the first anti-TNF treatment as determined by the investigator and who received second anti-TNF treatment for at least 16 weeks (Phase 2).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-tumor Necrosis Factor Agents (Phase 1) | Percentage of Participants With High Probability of Response and no Response Who Received Second Anti-TNF Treatment | 66.7 percentage of participants |
Secondary
Percentage of Participants With Low Probability of Response and a Clinical Response at Week 16
Low probability of response = participants who met no more than 2 of 5 criteria at time of treatment start: CRP \> 15 mg/L; time from onset of disease less than \< 10 years; total spinal pain \> 30 mm, measured as mean score on 100 mm VNS (higher score=more severe pain) for nocturnal and total spinal pain; BASDAI \> 4 cm, measured as mean score on 10 cm VNS (higher score=more severe state) for discomfort, pain and fatigue; BASFI \< 4.5 cm; measured as mean score on 10 cm VNS (higher score=less functionality) evaluating functional capacity. Assessment of response was as per investigator's criteria.
Time frame: Week 16
Population: Analysis population included all participants enrolled in study who gave their consent, satisfied all evaluation criteria and had information available at Week 16 after starting first anti-TNF treatment (Phase 1). N (number of participants analyzed) signifies those participants who had low probability of response and were evaluable for the measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-tumor Necrosis Factor Agents (Phase 1) | Percentage of Participants With Low Probability of Response and a Clinical Response at Week 16 | 96.4 percentage of participants |
Secondary
Percentage of Participants With Low Probability of Response and no Response Who Received Second Anti-TNF Treatment
Low probability of response = participants who met no more than 2 of 5 criteria at time of treatment start: CRP \> 15 mg/L; time from onset of disease less than \< 10 years; total spinal pain \> 30 mm, measured as mean score on 100 mm VNS (higher score=more severe pain) for nocturnal and total spinal pain; BASDAI \> 4 cm, measured as mean score on 10 cm VNS (higher score=more severe state) for discomfort, pain and fatigue; BASFI \< 4.5 cm; measured as mean score on 10 cm VNS (higher score=less functionality) evaluating functional capacity. Assessment of response was as per investigator's criteria.
Time frame: Week 32
Population: Data was not analyzed as no participant met the criteria for low probability of response in phase 2 of the study.