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

NCT01382160 | Completed Phase 4 DMC

• 4 other identifiers: PHRI10-DM/AFORA2010-021449-28A100898-302010-R24
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 7

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; adalimumab; pharmacokinetic-pharmacodynamic relationship; immunogenicity; Fc gamma receptors polymorphisms

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• To study the relationship between genetic factors, immunogenicity and response to adalimumab in rheumatoid arthritis

  During the 26 weeks of follow up.

Study Arms (1)

adalimumab

EXPERIMENTAL

40 mg every two weeks, by subcutaneous way

Biological: adalimumab

Interventions

adalimumab BIOLOGICAL

40 mg every two weeks, by subcutaneous way

Also known as: Humira

adalimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (7)

CHRU de Brest

Brest, France

Location

CHR du Mans

Le Mans, France

Location

CHRU de Nantes

Nantes, France

Location

CHR d'Orléans

Orléans, France

Location

CHRU de Poitiers

Poitiers, France

Location

CHRU de Rennes

Rennes, France

Location

CHRU de Tours

Tours, France

Location

Related Publications (1)

• Moulin D, Millard M, Taieb M, Michaudel C, Aucouturier A, Lefevre A, Bermudez-Humaran LG, Langella P, Sereme Y, Wanherdrick K, Gautam P, Mariette X, Dieude P, Gottenberg JE, Jouzeau JY, Skurnik D, Emond P, Mulleman D, Sellam J, Sokol H. Counteracting tryptophan metabolism alterations as a new therapeutic strategy for rheumatoid arthritis. Ann Rheum Dis. 2024 Feb 15;83(3):312-323. doi: 10.1136/ard-2023-224014.

  PMID: 38049981 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Denis MULLEMAN, MD, PhD

  CHRU de Tours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2010
• First Posted: June 27, 2011
• Study Start: January 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

FR (7)