Clinical trial NCT02492217: Biomarkers Identification of Anti-tumor Necrosis Factor (TNF) α Agent's Efficacy in Ankylosing Spondylitis Patients
Official title: Biomarkers Identification of Anti-TNF α Agent's Efficacy in Ankylosing Spondylitis Patients Using a Transcriptome Analysis and Mass Spectrometry
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ankylosing Spondylitis
Keywords: Ankylosing Spondylitis
adalimumab
TNF-alpha agents
spondyloarthritis
biologic therapies
AS
biomarkers
efficacy prediction
Lead sponsor: Universidade Nova de Lisboa
Sponsor class: OTHER
First posted: 2015-07-08
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To identify new candidate genes and proteins that are differentially expressed in responders' vs non-responders to anti-TNF alpha therapy at the several time points the investigators will use the transcriptomic and proteomic analyses. Demonstrate a link between gene expression and protein markers regarding prediction to anti-TNF alpha therapy efficacy.


Eligibility criteria: Inclusion Criteria:

* AS according to Portuguese Society of Rheumatology (SPR) guidelines (1984 modified New York Criteria, but allowing the use of MRI as imagiological criteria)
* Patient enrolment followed national guidelines for TNF antagonist use for the treatment of AS
* Adults between 18 to 75 years
* Ability to provide informed consent
* Corticosteroid therapy allowed (equivalent to ≤ 10 mg prednisone) and / or NSAID(nonsteroidal antiinflammatory drug), stable dose in 4 weeks before study initiation
* Adequate contraception (barrier or hormonal) in men and women of childbearing age (patients and their partners
* Adequate renal and hepatic function (2 times ULN)

Exclusion Criteria:

* Current pregnancy or breastfeeding
* Previous treatment with biologic DMARD's (disease-modifying antirheumatic drug)
* Intraarticular injections or infiltrations of extraaxial joints and tendons within 28 days before or at screening, or intraarticular injections of sacroiliac joints ≤ 28 days before screening
* History of rheumatic disorder other than AS
* Other forms of spondylarthritis than AS
* Any uncontrolled medical condition (e.g., uncontrolled diabetes mellitus, unstable ischemic heart disease)
* History or signs of demyelinating disease
* Malignancy (except for completely treated squamous or basal cell carcinoma)
* Moderate to severe heart failure (NYHA class III/IV) Positive serology for hepatitis B, hepatitis C, or human immunodeficiency virus
* Active or latent tuberculosis (TB) or histoplasmosis or other severe infections such as sepsis, and opportunistic infections
* Infections requiring hospitalization or intravenous treatment with antibiotics within 30 days or oral treatment with antibiotics within 14 days before enrollment
* Ankylosis of the spine (syndesmophytes presence at all levels from D12 to S1 in X-ray (XR) lateral view)
* Hypersensitivity to the active substance or to any of the excipients

Primary outcomes:
measure: Clinical response biomarkers (Assessment of Spondyloarthritis International Society (ASAS) 20 and Ankylosing Spondylitis Disease Activity Score (ASDAS)
timeFrame: 14 weeks
Secondary outcomes:
measure: QoL evaluation
timeFrame: 14 weeks
measure: MRI progression
timeFrame: 14 weeks
Other outcomes:
Locations:
city: Lisbon
country: Portugal
facility: Faculdade de Ciências Médicas da Universidade Nova de Lisboa
Study officials:
affiliation: NOVA Medical School/Faculdade de Ciências Médicas
name: Fernando M. Pimentel-Santos, MD, PhD
role: STUDY_CHAIR
affiliation: NOVA Medical School/Faculdade de Ciências Médicas
name: Jaime C. Branco, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: