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

Serum Concentration of Adalimumab (Humira) 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 Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: adalimumab

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Brest, France
    • CHRU de Brest
  • Le Mans, France
    • CHR du Mans
  • Nantes, France
    • CHRU de Nantes
  • Orléans, France
    • CHR d'Orléans
  • Poitiers, France
    • CHRU de POITIERS
  • Rennes, France
    • CHRU de Rennes
  • Tours, France
    • CHRU De Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: adalimumab; 40 mg every two weeks, by subcutaneous way	Biological: adalimumab; 40 mg every two weeks, by subcutaneous way; Other Names: Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Principal Investigator: Denis MULLEMAN, MD, PhD, CHRU De Tours

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: December 2, 2010
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Estimate): October 7, 2013
• Last Update Submitted That Met QC Criteria: October 1, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: immunogenicity; adalimumab; Rheumatoid arthritis; pharmacokinetic-pharmacodynamic relationship; Fc gamma receptors polymorphisms
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: PHRI10-DM/AFORA; 2010-021449-28 (EudraCT Number); A100898-30 (Other Identifier: Afssaps); 2010-R24 (Other Identifier: CPP)