Assessment of the Response to Etoricoxib in Patients With Ankylosing Spondylitis (AS) and Inadequate Response to ≥2 NSAIDs

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Spanish Foundation of Rheumatology
ClinicalTrials.gov Identifier:
NCT01091675
First received: March 22, 2010
Last updated: March 10, 2014
Last verified: October 2010
  Purpose

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.


Condition Intervention Phase
Ankylosing Spondylitis (AS) and Inadequate Response to ≥2 NSAIDs.
Drug: Etoricoxib
Phase 3

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Spanish Foundation of Rheumatology:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 59
Study Start Date: September 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.

Detailed Description:

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.

Primary Objective:

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.

Secondary objectives:

  1. 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.
  2. 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients ≥ 18 years.
  2. Patients with diagnosis of AS (according to the modified New York criteria 1984) 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 with AS with inadequate clinical response demonstrated by with a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 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 molulate 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 (eg, uveitis, endocarditis).
  16. Patients with fibromyalgia or other rheumatic disorders (e.g., systemic lupus erythematosus, gout, Paget's disease of bone, inflammatory bowel disease active, ochronosis, polymyalgia rheumatica, psoriatic arthritis) that could confound the evaluation of efficacy
  17. Patients with AS who received anti-TNF therapy. Note: The use of approved nonstudy antirheumatic therapy at a stable dose(methotrexate, sulfasalazina) 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 (GI) 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 COX-2 (cyclooxygenase-2) inhibitors
  26. Patients with hypertension whose blood pressure is persistently elevated above 140/90mmHg and has not been adequately controlled

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  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01091675

Locations
Spain
H. Central de Asturias
Oviedo, Asturias, Spain, 33006
Hospital Parc Tauli
Sabadell, Barcelona, Spain
H. Bellvitge
Barcelona, Spain, 08907
H. Clinic I Provincial
Barcelona, Spain, 08036
H. Sant Rafael
Barcelona, Spain, 08035
H.U. Reina Sofia
Cordoba, Spain, 14004
H. Puerta de Hierro
Madrid, Spain, 28222
H. Ramon Y Cajal
Madrid, Spain, 28034
H. General de Mostoles
Madrid, Spain, 28935
H. Doce de Octubre
Madrid, Spain, 28041
H. Virgen de la Arrixaca
Murcia, Spain, 30120
H. Clinico de Salamanca
Salamanca, Spain, 37007
Sponsors and Collaborators
Spanish Foundation of Rheumatology
Investigators
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
  More Information

No publications provided

Responsible Party: Spanish Foundation of Rheumatology
ClinicalTrials.gov Identifier: NCT01091675     History of Changes
Other Study ID Numbers: GRE-2009-01
Study First Received: March 22, 2010
Last Updated: March 10, 2014
Health Authority: Spain: AEMPS (Spanish Drug Agency)
Spain: Comité Ético de Investigación Clínica (Clinical Research Ethics Committee)

Keywords provided by Spanish Foundation of Rheumatology:
ankylosing spondylitis
biologic therapies
ASAS
ASASBIO
etoricoxib
NSAIDs

Additional relevant MeSH terms:
Spondylitis
Spondylitis, Ankylosing
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis
Joint Diseases
Arthritis
Anti-Inflammatory Agents, Non-Steroidal
Etoricoxib
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014