Ankylosing Spondylitis
Conditions
Keywords
ankylosing spondylitis, biologic therapies, ASAS, ASASBIO, etoricoxib, NSAIDs, COX-2 Inhibitor, ARCOXIA 90 mg, BASDAI Bath Ankylosing Spondylitis Disease Activity Index
Brief summary
The goal of this research is to assess the percentage of non-responders to ≥ 2 NSAIDs candidates a biological therapy that could adequately respond to treatment with etoricoxib This study confirm the result of a previous study in a wider similar population. Basing on previous results, the response rate will be assessed by ASASBIO criteria. The efficacy of the treatment with etoricoxib 90 mg will be assessed at week 4 in a population of patients with AS who didn't respond adequately to a previous therapy with ≥ 2 NSAIDs. Those patients that, based on the ASABIO criteria, achieved a sufficient clinical response will be followed until week 24 to asses the maintenance of the study drug effects.
Detailed description
Etoricoxib is an oral, selective cyclooxygenase 2 inhibitor approved for the symptomatic treatment of ankylosing spondylitis (AS) in Spain. Etoricoxib is a marketed product indicated for the relief of symptomatic osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, pain and signs of inflammation associated with acute gouty arthritis. In ankylosing spondylitis,the recommended dose is 90 mg once daily. Clinical pharmacology studies demonstrate that Etoricoxib induce dose-dependent inhibition of COX-2 without inhibit COX-1, up to 150 mg daily dose. Etoricoxib did not inhibit the gastric synthesis of prostaglandin and had no effect on platelet function. Cyclooxygenase is responsible for the prostaglandin synthesis. Were identified two different isoforms of cyclooxygenase, COX-1 and COX-2. It has been shown that COX-2 is the major enzyme responsible for the synthesis of prostanoid mediators involved in pain, inflammation and fever.
Interventions
DRUGEtoricoxib
Etoricoxib 90 mg/day/PO during 4 weeks Positive response to the therapy (in investigator opinion): Ongoing treatment with 90 mg/day/PO until 24 weeks.
Sponsors
Spanish Foundation of Rheumatology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients ≥ 18 years. 2. Patients with diagnosis of AS (based on New York criteria) made ≥ 6 months prior to study start. 3. Patient with axial involvement. 4. Patients who have been treated with ≥ 2 documented NSAID with proven anti-inflammatory potency during at least 3 months at maximal recommended or tolerated doses prior the visit 1. 5. Patients who demonstrate a Bath Ankylosing Spondylitis Disease Activity Index score of ≥ 4 (range 0-10).
Exclusion criteria
1. Patient that according to the investigator opinion is legally unable (i.e. mentally incapable person), with psychiatric disorder precedent, active psychosis or emotional problems at the moment to be enrolled in the study. 2. Patient who is participating in a clinical study with a drug or experimental device or it was done within 4 weeks prior to the inform consent signature. 3. Patient with a recent history (since last 5 years) of abuse or dependence to opiates, tranquilizer or drugs at the inform consent signature moment. Patient with a recent history (since last 5 years) of alcoholism or drug addiction. 4. Patient with a history of neoplastic disease or malignant neoplasia ≤ 5 years prior to the inform consent signature, except basal cell or squamous cell cancer skin adequately treated or uterine cancer insitu without recurrence prior to study entry according to the investigator opinion. Patients with history of leukemia, lymphoma, malignant melanoma or myeloproliferative disease cannot participate at the study. 5. Pregnancy, lactation or waiting to conceive a child 6. Patient with history of disorders, treatments or laboratory abnormality that can interfere with the study results and study participation. 7. Patient cannot comply with the study procedures, study calendar. Patient with plan of moving. 8. Patients awaiting the legal assessment of the degree of disability or the permanent work disability 9. Patients unable to respond to questionnaires (difficulty understanding and / or reading of questionnaires) 10. Any other warning that, in the investigator opinion, could discourage the inclusion of the patient in the study. 11. Patient to be treated with other drug which can modulate the pain perception 12. Patients with AS associated disease (inflammatory bowel disease, psoriasis). 13. Patients with active peripheral articular involvement defined by presence of peripheral arthritis. 14. Patient with predominant enthesitis or an enthesis that, according to investigator's opinion, can confound the correct evaluation. 15. Presence of extra-articular manifestations. 16. Patients with fibromyalgia or other rheumatic disorders that could confound the evaluation of efficacy 17. Patients with AS who received biologic therapy. Note: The use of approved nonstudy antirheumatic therapy at a stable dose(methotrexate, sulfasalazine) for 3 months prior to the study start will be allowed. 18. Patients with AS who received active treatment with etoricoxib 19. Hypersensitivity to the active substance or to any of the excipients 20. Active peptic ulceration or active gastro-intestinal bleeding 21. Patients with severe renal failure (creatinine clearance rate \< 30 ml/min) 22. Congestive heart failure (NYHA II-IV) 23. Established ischaemic heart disease or cerebrovascular disease 24. Patients with severe hepatic dysfunction (serum albumin \<25 g/l or Child-Pugh score ≥10). 25. Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions after taking acetylsalicylic acid or NSAIDs including cyclooxygenase-2 inhibitors 26. Patients with hypertension whose blood pressure is persistently elevated above 140/90mmHg and has not been adequately controlled \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the Percentage of Patients Fulfilling the Assessment Study (ASAS) Response Criteria Were Determined | the ASAS response were evaluated at week 2 and 4 and after 6 months treatment | BASDAI Bath Ankylosing Spondylitis Disease Activity Index, is the gold standard for measuring and evaluating disease activity in Ankylosing Spondylitis consists of a one through 10 scale which is used to answer 6 questions pertaining to the 5 major symptoms of AS. BASDAI has been used to assess the efficacy of the treatment. Possible Patients were considerate respond to ASABIO criteria when presented a change of 2 in the BASDAI score range. |
Countries
Spain
Participant flow
Recruitment details
The study enrolled 58 patients in total, with ankylosing spondylitis, and Inadequate response to ≥2 NSAIDs. Patients who met The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of 4 or higher and all study criteria participate in the study and were randomized at 14 study sites. The last patient completed in May 2013.
Pre-assignment details
From a total of 58 patients recruited 1 did not met the exclusion criteria, so 57 patients start the first phase. 4 patients abandoned the study due to hypertension. 53 patients completed the first phase. 27 did not proceed to phase 2 due to lack of efficacy and 3 patients were withdraw due to hypertension. 23 patients complete the study period.
Participants by arm
| Arm | Count |
|---|---|
| Etoricoxib All the patients who fulfil the eligibility criteria will start a 4-week open label treatment period to evaluate the response to treatment with etoricoxib 90 mg.
Etoricoxib: Etoricoxib 90 mg/day/PO during 4 weeks Positive response to the therapy (in investigator opinion): Ongoing treatment with 90 mg/day/PO until 24 weeks. | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Lack of Efficacy | 27 |
Baseline characteristics
| Characteristic | Etoricoxib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants |
| Age, Continuous | 44 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 55 Participants |
| Region of Enrollment Spain | 58 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 57 |
| serious Total, serious adverse events | 1 / 57 |
Outcome results
Primary
the Percentage of Patients Fulfilling the Assessment Study (ASAS) Response Criteria Were Determined
BASDAI Bath Ankylosing Spondylitis Disease Activity Index, is the gold standard for measuring and evaluating disease activity in Ankylosing Spondylitis consists of a one through 10 scale which is used to answer 6 questions pertaining to the 5 major symptoms of AS. BASDAI has been used to assess the efficacy of the treatment. Possible Patients were considerate respond to ASABIO criteria when presented a change of 2 in the BASDAI score range.
Time frame: the ASAS response were evaluated at week 2 and 4 and after 6 months treatment
Population: Patients with physician-diagnosed Ankylosing Spondylitis at 6 months before study start
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etoricoxib | the Percentage of Patients Fulfilling the Assessment Study (ASAS) Response Criteria Were Determined | 19 percentage of participants |