Serum Concentration of Adalimumab as a Predictive Factor of Clinical Outcomes in Rheumatoid Arthritis (AFORA)

Rheumatoid Arthritis Clinical Trial

— AFORA  

Official title:

Serum Concentration of Adalimumab (Humira) as a Predictive Factor of Clinical Outcomes in Rheumatoid Arthritis (AFORA)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01382160
• Other study ID #: PHRI10-DM/AFORA
• Secondary ID: 2010-021449-28A1
• Status: Completed
• Phase: Phase 4
• First received: December 2, 2010
• Last updated: October 1, 2013
• Start date: January 2011
• Est. completion date: July 2013

Study information

• Verified date: October 2013
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• adalimumab
40 mg every two weeks, by subcutaneous way

Locations

Country	Name	City	State
France	CHRU de Brest	Brest
France	CHR du Mans	Le Mans
France	CHRU de Nantes	Nantes
France	CHR d'Orléans	Orléans
France	CHRU de Poitiers	Poitiers
France	CHRU de Rennes	Rennes
France	CHRU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To characterize the concentration-effect relationship of adalimumab in rheumatoid arthritis	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.	During the 26 weeks of follow up.	No
Secondary	To study the relationship between genetic factors, immunogenicity and response to adalimumab in rheumatoid arthritis	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.	During the 26 weeks of follow up.	No