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

NCT04175886 | Completed DMC

• 2 other identifiers: 2018_382019-001159-37
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis; tofacitinib; body composition; bone marrow adiposity; bone marrow density

Outcome Measures

Primary Outcomes (1)

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

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

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

Secondary Outcomes (16)

• Measurements of VAT in cm².

  at baseline

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

  at baseline

• Measurements of body fat percentage (%)

  at baseline

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

  at baseline

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

  at baseline

Study Arms (2)

Patients with rheumatoid arthritis

Patients with rheumatoid arthritis with an indication for tofacitinib: 5mgx2 per day

Drug: Tofacitinib

Healthy subjects

Healthy subjects matched to cases (1:1) on age (±5 years), sex, and menopausal status for women and body mass index (BMI, ±3 kg/m²)

Interventions

Tofacitinib DRUG

Patients will be treated with tofacitinib

Patients with rheumatoid arthritis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population is composed of adult patients with moderately to severely active RA for whom tofacitinib is indicated and who are followed in the department of rheumatology at Lille University Hospital

You may qualify if:

• 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.

You may not qualify if:

• 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,

Sponsors & Collaborators

• University Hospital, Lille: lead
• Pfizer: collaborator

Study Sites (1)

Lille University Hospital

Lille, France

Location

Related Publications (10)

• Dodington DW, Desai HR, Woo M. JAK/STAT - Emerging Players in Metabolism. Trends Endocrinol Metab. 2018 Jan;29(1):55-65. doi: 10.1016/j.tem.2017.11.001. Epub 2017 Nov 27.

  PMID: 29191719 BACKGROUND

• Fleischmann RM, Huizinga TW, Kavanaugh AF, Wilkinson B, Kwok K, DeMasi R, van Vollenhoven RF. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis. RMD Open. 2016 Jul 26;2(2):e000262. doi: 10.1136/rmdopen-2016-000262. eCollection 2016.

  PMID: 27493790 BACKGROUND

• Tatsumi Y, Nakao YM, Masuda I, Higashiyama A, Takegami M, Nishimura K, Watanabe M, Ohkubo T, Okamura T, Miyamoto Y. Risk for metabolic diseases in normal weight individuals with visceral fat accumulation: a cross-sectional study in Japan. BMJ Open. 2017 Jan 16;7(1):e013831. doi: 10.1136/bmjopen-2016-013831.

  PMID: 28093438 BACKGROUND

• Letarouilly JG, Paccou J, Badr S, Chauveau C, Broux O, Clabaut A. Stimulatory Effect of Tofacitinib on Bone Marrow Adipocytes Differentiation. Front Endocrinol (Lausanne). 2022 Jul 6;13:881699. doi: 10.3389/fendo.2022.881699. eCollection 2022.

  PMID: 35873000 RESULT

• Book C, Karlsson MK, Akesson K, Jacobsson LT. Early rheumatoid arthritis and body composition. Rheumatology (Oxford). 2009 Sep;48(9):1128-32. doi: 10.1093/rheumatology/kep165. Epub 2009 Jul 13.

  PMID: 19602478 RESULT

• Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum. 2000 Mar;43(3):522-30. doi: 10.1002/1529-0131(200003)43:33.0.CO;2-Y.

  PMID: 10728744 RESULT

• Toussirot E, Mourot L, Dehecq B, Wendling D, Grandclement E, Dumoulin G; CBT-506. TNFalpha blockade for inflammatory rheumatic diseases is associated with a significant gain in android fat mass and has varying effects on adipokines: a 2-year prospective study. Eur J Nutr. 2014 Apr;53(3):951-61. doi: 10.1007/s00394-013-0599-2. Epub 2013 Oct 31.

  PMID: 24173963 RESULT

• Marouen S, Barnetche T, Combe B, Morel J, Daien CI. TNF inhibitors increase fat mass in inflammatory rheumatic disease: a systematic review with meta-analysis. Clin Exp Rheumatol. 2017 Mar-Apr;35(2):337-343. Epub 2016 Dec 13.

  PMID: 27974099 RESULT

• Engvall IL, Tengstrand B, Brismar K, Hafstrom I. Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months. Arthritis Res Ther. 2010;12(5):R197. doi: 10.1186/ar3169. Epub 2010 Oct 21.

  PMID: 20964833 RESULT

• Tournadre A, Pereira B, Dutheil F, Giraud C, Courteix D, Sapin V, Frayssac T, Mathieu S, Malochet-Guinamand S, Soubrier M. Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis. J Cachexia Sarcopenia Muscle. 2017 Aug;8(4):639-646. doi: 10.1002/jcsm.12189. Epub 2017 Mar 18.

  PMID: 28316139 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Whole blood, serum

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Jean-Guillaume Letarouilly, MD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: November 25, 2019
• Study Start: February 25, 2020
• Primary Completion: May 8, 2023
• Study Completion: May 8, 2023
• Last Updated: April 22, 2026

Record last verified: 2023-05

Locations

FR (1)