Serum Concentration of Adalimumab as a Predictive Factor of Clinical Outcomes in Rheumatoid Arthritis (AFORA)
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.
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||Serum Concentration of Adalimumab (Humira) as a Predictive Factor of Clinical Outcomes in Rheumatoid Arthritis (AFORA)|
- To characterize the concentration-effect relationship of adalimumab in rheumatoid arthritis [ Time Frame: During the 26 weeks of follow up. ] [ Designated as safety issue: No ]The primary objective is to characterize the concentration-effect relationship of adalimumab in rheumatoid arthritis (RA). To this aim, adalimumab concentration on the one hand and clinical and biological markers of disease activity on the other hand will be measured at baseline, week 4, week 8, week 12 and at week 26. Pharmacodynamic (PD) parameters will be estimated using PK(pharmacokinetic)-PD models in which Emax (maximum effect) and EC50 (concentration at which the effect is 50% of the maximum) will describe adalimumab effect on each markers of response.
- To study the relationship between genetic factors, immunogenicity and response to adalimumab in rheumatoid arthritis [ Time Frame: During the 26 weeks of follow up. ] [ Designated as safety issue: No ]The secondary endpoints consist on the association study between FCGR3A polymorphisms, transcriptomic analysis (at baseline), presence of antibodies toward adalimumab (ATA) on the one hand and estimited individuals pharmacodynamic parameters on the other hand. Measurements will be carried out at baseline, week 4, week 8, week 12 and at week 26.
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||July 2013|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
|Contact: Denis MULLEMAN, MD, PhD||+33 2 47 59 email@example.com|
|Contact: Yoann DESVIGNES||+33 2 47 47 46 firstname.lastname@example.org|
|CHRU de Brest||Recruiting|
|Contact: Valérie DEVAUCHELLE, MD, PhD|
|Principal Investigator: Valérie DEVAUCHELLE, MD, PhD|
|CHR du Mans||Not yet recruiting|
|Le Mans, France|
|Contact: Emmanuelle DERNIS, MD|
|Principal Investigator: Emmanuelle DERNIS, MD|
|CHRU de Nantes||Active, not recruiting|
|CHR d'Orléans||Active, not recruiting|
|CHRU de Poitiers||Recruiting|
|Contact: Elisabeth SOLAU, MD|
|Principal Investigator: Elisabeth SOLAU, MD|
|CHRU de Rennes||Recruiting|
|Contact: Aleth PERDRIGER, MD, PhD|
|Principal Investigator: Aleth PERDRIGER, MD, PhD|
|CHRU de Tours||Recruiting|
|Contact: Denis MULLEMAN, MD, PhD|
|Principal Investigator: Denis MULLEMAN, MD, PhD|
|Principal Investigator:||Denis MULLEMAN, MD, PhD||CHRU de Tours|