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

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ClinicalTrials.gov Identifier: NCT01382160
Recruitment Status : Completed
First Posted : June 27, 2011
Last Update Posted : October 7, 2013
Sponsor:
Information provided by (Responsible Party):
University Hospital, Tours

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.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Biological: adalimumab Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: Serum Concentration of Adalimumab (Humira) as a Predictive Factor of Clinical Outcomes in Rheumatoid Arthritis (AFORA)
Study Start Date : January 2011
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: adalimumab
40 mg every two weeks, by subcutaneous way
Biological: adalimumab
40 mg every two weeks, by subcutaneous way
Other Name: Humira




Primary Outcome Measures :
  1. To characterize the concentration-effect relationship of adalimumab in rheumatoid arthritis [ Time Frame: During the 26 weeks of follow up. ]
    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.


Secondary Outcome Measures :
  1. To study the relationship between genetic factors, immunogenicity and response to adalimumab in rheumatoid arthritis [ Time Frame: During the 26 weeks of follow up. ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01382160


Locations
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, France
Sponsors and Collaborators
University Hospital, Tours
Investigators
Principal Investigator: Denis MULLEMAN, MD, PhD CHRU de Tours

Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT01382160     History of Changes
Other Study ID Numbers: PHRI10-DM/AFORA
2010-021449-28 ( EudraCT Number )
A100898-30 ( Other Identifier: Afssaps )
2010-R24 ( Other Identifier: CPP )
First Posted: June 27, 2011    Key Record Dates
Last Update Posted: October 7, 2013
Last Verified: October 2013

Keywords provided by University Hospital, Tours:
Rheumatoid arthritis
adalimumab
pharmacokinetic-pharmacodynamic relationship
immunogenicity
Fc gamma receptors polymorphisms

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents