Clinical trial NCT01382160: Serum Concentration of Adalimumab as a Predictive Factor of Clinical Outcomes in Rheumatoid Arthritis (AFORA)
Official title: Serum Concentration of Adalimumab (Humira) as a Predictive Factor of Clinical Outcomes in Rheumatoid Arthritis (AFORA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
adalimumab
pharmacokinetic-pharmacodynamic relationship
immunogenicity
Fc gamma receptors polymorphisms
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2011-06-27
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: Adalimumab is a fully human monoclonal antibody to tumor necrosis factor-alpha (TNF-α) approved in rheumatoid arthritis (RA) refractory to disease modifying anti rheumatic drugs (DMARDs) and for the treatment of severe, active and progressive RA in adults not previously treated with methotrexate.

However, almost one third of patients have no response and approximately 15% develop antibodies towards adalimumab (ATA) after a 6 month course of treatment. There is a relationship between adalimumab concentration and clinical response obtained after 6 month of treatment. Furthermore adalimumab concentration measured 3 months after initiation seems to predict the clinical response at 6 months.

There is an important inter individual pharmacokinetic variability of adalimumab. Side effects may occur at the recommended dose and more than 3 months of treatment are generally required to estimate the clinical response.

A therapeutic drug monitoring could help clinicians to early adjust the dose to optimize the response and to avoid dose related side effects. To date there is no definite adalimumab target concentration predictive of the clinical response to allow such a pharmacologic monitoring.


Eligibility criteria: Inclusion Criteria:

* RA according to the American College of Rheumatology (ACR) 1987 criteria
* Treatment with Adalimumab has been chosen by the physician / patient
* Treatment given in accordance to the SPC
* Stable Disease modifying anti rheumatic drugs (DMARDs) and glucocorticoids 4 weeks before enrollment and during the study period.
* Signed consent

Exclusion Criteria:

* more than one previous treatment with anti TNF-alpha
* Past history of malignancy, AIDS
* Pregnancy
* Change in DMARDS or glucocorticoid dose 4 weeks before entering the study
* Active or latent tuberculosis, other active infections
* Surgery scheduled during the study period

Primary outcomes:
measure: To characterize the concentration-effect relationship of adalimumab in rheumatoid arthritis
timeFrame: During the 26 weeks of follow up.
Secondary outcomes:
measure: To study the relationship between genetic factors, immunogenicity and response to adalimumab in rheumatoid arthritis
timeFrame: During the 26 weeks of follow up.
Other outcomes:
Locations:
city: Brest
country: France
facility: CHRU de Brest
city: Le Mans
country: France
facility: CHR du Mans
city: Nantes
country: France
facility: CHRU de Nantes
city: Orléans
country: France
facility: CHR d'Orléans
city: Poitiers
country: France
facility: CHRU de Poitiers
city: Rennes
country: France
facility: CHRU de Rennes
city: Tours
country: France
facility: CHRU de Tours
Study officials:
affiliation: CHRU de Tours
name: Denis MULLEMAN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: