Effects of Tofacitinib on Body Composition, Bone Mineral Density and Bone Marrow Adiposity in Patients With Rheumatoid Arthritis: the TOFAT Project

University Hospital, Lille10 enrolled

Overview

Inflammatory rheumatic diseases (IRD), such as rheumatoid arthritis, are characterized by adverse changes in body composition. Lean mass and bone mineral density are usually reduced while adiposity (total fat mass, visceral adiposity…) is increased in comparison with healthy controls. Many factors may influence the body composition of those patients such as aging, Disease Modifying Anti-Rheumatic Drugs (DMARDs), nutrition and physical activity. However, data on body composition and adverse changes under DMARDs in patients with rheumatoid arthritis (RA) are actually scarce. This is the case with tofacitinib (targeted synthetic DMARD or tsDMARD) while preliminary data let us think that this treatment may influence body composition and bone mineral density. This study is going to be the first to focus on changes in body composition (fat mass and lean mass), bone mineral density and bone marrow adiposity under tofacitinib.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Rheumatoid Arthritis

Interventions

TofacitinibDRUG

Patients will be treated with tofacitinib

Medical Language ↔ Plain English

Inclusion Criteria: * Adult patient's ≥18 years old with moderately to severely active Rheumatoid Arthritis (RA) (ACR/EULAR criteria ) * Previously untreated with Janus Kinase (JAK) inhibitors * With an indication for tofacitinib will be eligible. * All patients will have to be treated with tofacitinib either alone or with methotrexate. -Healthy volunteers should be ≥18 years old. Exclusion Criteria: * • treatment with more than three anti-Tumor Necrosis Factor alpha (TNFα). Patients who were receiving anti-TNFα will be required a washout period lasting at least five-half-lives before to start tofacitinib, * previously exposed to JAK inhibitors, * patients who were receiving non-anti-TNFα biologics (abatacept, tocilizumab, sarilumab or rituximab) will be required a washout period lasting at least five-half-lives before to start tofacitinib * Concomitant methotrexate (MTX) will be permitted if started ≥3 months prior to study start and at a stable dose (≤25 mg/week) for ≥4 weeks. * history or discovery of an osteoporotic fracture AND/OR T-score≤-3 if ≥50 years AND/OR Z-score ≤-3 if \<50 years during the screening phase, * current treatment with oral corticosteroids higher than 10 mg prednisone/day, * pathologies or treatments that could affect the bone metabolism (breast cancer with aromatase inhibitors, gastrointestinal malabsorption, stomach cancer, primary hyperparathyroidism, uncontrolled hyperthyroidism…), * weight\> 160 kg, * patients on restrictive diets or considering such a diet during the study period, * patients with an intense exercise program or planning to benefit from it during the study period,

Outcomes

Primary Outcomes

Variation in visceral adiposity (VAT or Visceral Adipose Tissue) in cm²

Time frame: Between the measurement before and after 6 months of tofacitinib treatment (difference before/after).

Secondary Outcomes

Measurements of VAT in cm².

Measurements of VAT in cm²

Time frame: at baseline

Measurements of total fat mass (TBF) in kg, total lean mass (TLM) in kg, appendicular lean mass (aLM) in kg

Time frame: at baseline

Measurements of body fat percentage (%)

Time frame: at baseline

Measurements of fat mass index (FMI) in kg/m² and skeletal muscle mass index (SMI) in kg/m²

Time frame: at baseline

Measurements of Bone mineral Density (BMD) in g/cm².

Time frame: at baseline

Change in body fat percentage (% between measurement

Change in body fat percentage (%) between measurement