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

Rheumatoid Arthritis Clinical Trial

— TOFAT  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04175886
• Other study ID #: 2018_38
• Secondary ID: 2019-001159-37
• Status: Terminated
• Start date: February 25, 2020
• Est. completion date: May 8, 2023

Study information

• Verified date: May 2023
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: May 8, 2023
• Est. primary completion date: May 8, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (TNFa). Patients who were receiving anti-TNFa 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-TNFa 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,

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Obesity
• Rheumatoid Arthritis

Intervention

Drug:
• Tofacitinib
Patients will be treated with tofacitinib

Locations

Country	Name	City	State
France	Lille University Hospital	Lille

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	Pfizer

Country where clinical trial is conducted

France, 

References & Publications (9)

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. — View Citation

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. — View Citation

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 T — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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 Mus — View Citation

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 s — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Measurements of VAT in cm².	Measurements of VAT in cm²	at baseline
Secondary	Measurements of total fat mass (TBF) in kg, total lean mass (TLM) in kg, appendicular lean mass (aLM) in kg	Measurements of total fat mass (TBF) in kg, total lean mass (TLM) in kg, appendicular lean mass (aLM) in kg	at baseline
Secondary	Measurements of body fat percentage (%)	Measurements of body fat percentage (%)	at baseline
Secondary	Measurements of fat mass index (FMI) in kg/m² and skeletal muscle mass index (SMI) in kg/m²	Measurements of fat mass index (FMI) in kg/m² and skeletal muscle mass index (SMI) in kg/m²	at baseline
Secondary	Measurements of Bone mineral Density (BMD) in g/cm².	Measurements of Bone mineral Density (BMD) in g/cm².	at baseline
Secondary	Change in body fat percentage (% between measurement	Change in body fat percentage (%) between measurement	Before and after 6 months of tofacitinib treatment (difference before/after).
Secondary	Change in total fat mass (TBF) between measurement	Change in total fat mass (TBF) in kg between measurement	Before and after 6 months of tofacitinib treatment (difference before/after).
Secondary	Change in fat mass index (FMI) in kg/m², between measurement	Change in fat mass index (FMI) in kg/m², between measurement	Before and after 6 months of tofacitinib treatment (difference before/after).
Secondary	Change in total lean mass (TLM, kg) and appendicular lean mass (aLM) in kg between measurement	Change in total lean mass (TLM, kg) and appendicular lean mass (aLM) in kg between measurement	Before and after 6 months of tofacitinib treatment (difference before/after).
Secondary	Change in skeletal muscle mass index (SMI) in kg/m² between measurement	Change in skeletal muscle mass index (SMI) in kg/m² between measurement	Before and after 6 months of tofacitinib treatment (difference before/after).
Secondary	Change in BMD (in g/cm²) at the lumbar spine (L1-L4) and non-dominant total hip between measurement	Change in BMD (in g/cm²) at the lumbar spine (L1-L4) and non-dominant total hip between measurement	Before and after 6 months of tofacitinib treatment (difference before/after).
Secondary	Variation of bone remodelling markers (Cross-laps (CTX) and Type I procollagen N-terminal propeptide (P1NP)) between measurement	Variation of bone remodelling markers (Cross-laps (CTX) and Type I procollagen N-terminal propeptide (P1NP)) between measurement	Before and after 6 months of tofacitinib treatment.
Secondary	Variation in leptin (ng/ml) between measurement.	Variation in leptin (ng/ml) between measurement.	Before and after 6 months of tofacitinib treatment
Secondary	Change in bone marrow adiposity (%) at the lumbar spine between measurement	Change in bone marrow adiposity (%) at the lumbar spine between measurement	Before and after 6 months of tofacitinib treatment.
Secondary	Variation in Short Physical Performance Battery Protocol (SPPB) between measurement	Variation in Short Physical Performance Battery Protocol (SPPB) between measurement	Before and after 6 months of tofacitinib treatment.
Secondary	Changes in the parameters of the primary outcome and the secondary outcomes (n°2 to 8)	Changes in the parameters of the primary outcome and the secondary outcomes (n°2 to 8)	Before and after 12 months of tofacitinib treatment.