Assessment of the Response to Etoricoxib in Patients With Ankylosing Spondylitis (AS) and Inadequate Response to ≥2 NSAIDs
Recruitment status was Recruiting
The spondylarthropathies (SpA) are a group of rheumatic inflammatory inter-related diseases that share common etiopathogenesis, clinical, genetic and radiological features, in which ankylosing spondylitis (AS) is the prototype of the family. Ankylosing spondylitis is a chronic rheumatic disease with a prevalence of around 0.1-0.3% in Spain (1). The disease is characterized by a localized inflammatory process especially at the axial skeleton including pelvis and spine, but also it can be associated with peripheral arthritis. Ankylosing spondylitis is a rheumatic disease less prevalent than rheumatoid arthritis (2), but its chronic course leads to a degree of long term disability similar to that observed in rheumatoid arthritis (3, 4). The standard therapy for AS, especially in case of axial involvement, mainly comprises non-steroidal anti-inflammatory drugs (NSAIDs) and physiotherapy. Additionally, disease-modifying antirheumatic drugs (DMARD) did not demonstrate any therapeutic benefit.
In the last years, anti-TNF therapy has shown great efficacy in the treatment of patients with ankylosing spondylitis (5, 6, 7) however, biological therapy requires a high financial cost and entails many potential risks. In this sense, consensus document developed by the Spanish Society of Rheumatology (SER) recommend that the indication of biological therapy should be preceded by the evidence of therapeutic ineffectiveness (BASDAI≥ 4) of ≥2 conventional NSAIDs properly administered (consecutively and at full or maximum tolerated dose and for a minimum of 3 months) (8). Preliminary data from the database REGISPONSER show that 40-50% of patients with AS visited regularly in the Rheumatology Services in Spain are under-treated (9). This situation is similar to the observed in other countries with the same group of patients (10).
The use of a COX-2 inhibitor for the symptomatic relief in the treatment of AS is recommended by guidelines (8, 11).
Etoricoxib is a selective inhibitor of COX-2 and it has shown greater efficacy compared to naproxen in the symptomatic treatment of patients with axial forms of AS (12).
Likewise, etoricoxib 90 mg/day has shown efficacy in a six-week open study in which 22 patients with established AS, not responded adequately to therapy with ≥ 2 NSAID for at least three months and potential candidates to initiate anti-TNF therapy, had been recruited. The result of the primary endpoint was that eight out 20 completers (40%) treated with etoricoxib responded positively to therapy, fulfilling the ASASBIO criteria and a 56% fulfilled the ASAS20 criteria (13).
In spite of the clearly limited size of this cohort, this study shows that treatment with etoricoxib could provide clinical improvement in the two most commonly used criteria for the estimation of effectiveness and of the response (ASAS20 and ASASBIO, respectively) (11) in this specific population.
Thus, etoricoxib could be a good therapeutic option for those patients with AS who do not respond adequately to treatment with conventional NSAIDs and they are eligible to receive biological therapy.
The aim of this study is to confirm the result of a previous study in a wider similar population. Basing on previous results (13), 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.
We also will assess the response to etoricoxib at week 2 in order to explore if the responses at week 2 could be predictor of the future response at week 4.
Furthermore, in those patients who respond positively to a 4-week treatment with etoricoxib 90 mg and, in investigator opinion, should continue the therapy, the maintenance of the response at week 12 and 24 will be studied.
Ankylosing Spondylitis (AS) and Inadequate Response to ≥2 NSAIDs.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Assessment of the Response to Etoricoxib in Patients With Ankylosing Spondylitis (AS) and Inadequate Response to ≥2 NSAIDs.|
- To evaluate the percentage of patients fulfilling the ASAS response criteria [ Time Frame: To evaluate the percentage of patients fulfilling the ASAS response criteria for biologic therapies (ASASBIO) after a 4-week treatment with etoricoxib 90 mg/day ] [ Designated as safety issue: No ]To evaluate the percentage of patients fulfilling the ASAS response criteria for biologic therapies (ASASBIO) after a 4-week treatment with etoricoxib 90 mg/day
- To assess the percentage of patients fulfilling the ASAS response criteria for biologic therapies (ASASBIO) at week 2 and to evaluate if a positive response is predictor of the future response at week 4. [ Time Frame: The response rate to therapy at week 2 will be similar to the response at week 4, and the response at week 2 should be predictor of the response at week 4. ] [ Designated as safety issue: No ]In those patients with a positive response to therapy at week 4 and that, in investigator opinion, are suitable to continue the treatment, to evaluate the maintenance of the response to therapy with etoricoxib 90 mg at week 12 and 24. A clinically significant percentage of patients, who responded positively to therapy at week 4, will maintain the response in the follow-up at week 12 and 24.
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||April 2012|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
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 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.
Design: A multicenter, open-label 4-week study. Those patients that, under the investigator criteria, have achieved a sufficient clinical response will be followed to asses the maintenance of the effects of the therapy at 12 and 24 weeks.
1. To evaluate the percentage of patients fulfilling the ASAS response criteria for biologic therapies (ASASBIO) after a 4-week treatment with etoricoxib 90 mg/day.
- To assess the percentage of patients fulfilling the ASAS response criteria for biologic therapies (ASASBIO) at week 2 and to evaluate if a positive response is predictor of the future response at week 4.
- In those patients with a positive response to therapy at week 4 and that, in investigator opinion, are suitable to continue the treatment, to evaluate the maintenance of the response to therapy with etoricoxib 90 mg at week 12 and 24.
|Contact: Esther Martin Blas, Foundation Reumatology Coord.||+ 34 91 576 77 99 ext email@example.com|
|H. Central de Asturias||Recruiting|
|Oviedo, Asturias, Spain, 33006|
|Contact: Ruben Queiro, MD +34 985108000 firstname.lastname@example.org|
|Hospital Parc Tauli||Recruiting|
|Sabadell, Barcelona, Spain|
|Contact: Jordi Gratacos, MD email@example.com|
|Principal Investigator: Jordi Gratacos|
|Barcelona, Spain, 08907|
|Contact: Xavier Juanola, MD +34 932 60 77 12 firstname.lastname@example.org|
|H. Clinic I Provincial||Active, not recruiting|
|Barcelona, Spain, 08036|
|H. Sant Rafael||Recruiting|
|Barcelona, Spain, 08035|
|Contact: Estefania Moreno, MD email@example.com|
|H.U. Reina Sofia||Recruiting|
|Cordoba, Spain, 14004|
|Contact: Eduardo Collantes, MD +34 957 01 16 31 firstname.lastname@example.org|
|Contact: Pilar Font, MD +34 957 01 16 31|
|H. Puerta de Hierro||Recruiting|
|Madrid, Spain, 28222|
|Contact: Juan Mulero, MD +34 911917292 email@example.com|
|Contact: Jesus Sanz, MD +34 911917292 firstname.lastname@example.org|
|H. Ramon Y Cajal||Recruiting|
|Madrid, Spain, 28034|
|Contact: Elia Brito, MD +34 913368000 ext 7802 email@example.com|
|H. General de Mostoles||Recruiting|
|Madrid, Spain, 28935|
|Contact: Mª Cruz Fernandez-Espartero, MD firstname.lastname@example.org|
|H. Doce de Octubre||Active, not recruiting|
|Madrid, Spain, 28041|
|H. Virgen de la Arrixaca||Recruiting|
|Murcia, Spain, 30120|
|Contact: Luis Francisco Linares, MD +34 968369534 email@example.com|
|H. Clinico de Salamanca||Recruiting|
|Salamanca, Spain, 37007|
|Contact: Carlos Alberto Montilla, MD firstname.lastname@example.org|
|Principal Investigator:||Jordi Gratacos, PhD/ MD||Hospital Parc Tauli. Barcelona. Spain|
|Principal Investigator:||Eduardo Collantes Estevez, PhD/ MD||H.U. Reina Sofia|
|Principal Investigator:||Xavier Juanola Roura, PhD/MD||H. Bellvitge|
|Principal Investigator:||Raimon Sanmartí Sala, PhD/MD||H. Clinic I Provincial|
|Principal Investigator:||Juan Mulero Mendoza, PhD/MD||H. Puerta de Hierro|
|Principal Investigator:||Estefania Moreno Ruzafa, PhD/MD||H. San Rafael|
|Principal Investigator:||Luis Francisco Linares Ferrando, PhD/MD||H. Virgen de la Arrixaca|
|Principal Investigator:||Rubén Queiro Silva, PhD/MD||H. de Asturias|
|Principal Investigator:||Elia Brito Brito, PhD/MD||H. Ramon y Cajal|
|Principal Investigator:||Carlos Alberto Montilla Morales, PhD/MD||H. Clinico de Salamanca|
|Principal Investigator:||Mª Cruz Fernández Espartero, PhD/MD||H. General de Mostoles|
|Principal Investigator:||Mª Pilar Fernández Dapica, PhD/MD||H. 12 de Octubre|