Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of Subcutaneous Tocilizumab in Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— REPAIR  

Official title:

Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of 12 Months Subcutaneous Tocilizumab in Rheumatoid Arthritis Phase IV Prospective Multicentrique Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02765074
• Other study ID #: CHRO 2014-03
• Status: Recruiting
• Phase: Phase 4
• Start date: June 30, 2016
• Est. completion date: June 30, 2025

Study information

• Verified date: June 2023
• Source: Centre Hospitalier Régional d'Orléans
• Contact: SALLIOT Carine, MD
• Phone: 33 2 38 22 99 22
• Email: carine.salliot[@]chr-orleans.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Rheumatoid arthritis (RA) is a chronic inflammatory disease mediated by the production of several cytokines, which leads to the destruction of bone and cartilage tissue in multiple joints and to bone loss. Conventional radiographs (CR) are considered as the gold standard for diagnosis and follow up of joint changes in RA. But this method has low sensitivity to detect early erosive changes and is unable to evaluate periarticular bone loss.

High Resolution peripheral QCT (HRpQCT) enables the detection of erosions less than 0.5 mm in width or depth at metacarpo-phalangeal (MCP) joints. Using 3-D high resolution analysis of cortical bone erosions, this one is also able to evaluate the volumes of erosion and the evolution under treatments IL6 (6- interleukin) plays a major role in inflammatory process and bone damages related to RA. Tocilizumab (TCZ) is a humanized anti-IL-6R monoclonal antibody, developed and investigated in several clinical trials in RA. This biotherapy, in association with methotrexate (MTX) or given in monotherapy, is efficient in RA with inadequate response to MTX or anti-TNF b (tumor necrosis factor). TCZ reduces dramatically systemic inflammation, structural progression and improves clinical symptoms and quality of life.

Tocilizumab may help reducing bone erosions, periarticular osteopenia and systemic bone loss.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Active RA, < 10 years disease duration, diagnosed according to the ACR-EULAR 2010 classification criteria

• DAS 28 superior or equal to 3.2 despite DMARD or biological treatment (other than tocilizumab)

• Superior or equal to one joint erosion at the right or left MCP 2, 3 on X-rays

• Oral corticosteroid = 10 mg/day prednisone or equivalent stable for at least one month

• RA patients eligible to subcutaneous Tocilizumab monotherapy

Exclusion Criteria:

• Treatment with zoledronic acid or denosumab (less than one year)

• Intra-articular injection of corticosteroids at the MCP in the previous three months

• Tocilizumab contra-indications in accordance with SPC (Summary of Product Characteristics) :Hypersensitivity to the active substance or to any of the excipients Active, severe infections including active tuberculosis Diverticulitis Active hepatic disease and hepatic Impairment including viral hepatitis Elevated Alanine Aminotransferase or Aspartate Aminotransferase >5×ULN Absolute neutrophil count < 0.5 × 10 exp 9 /L Platelet count < 50×10 exp 3 /µL,

General:

• Absence of informed consent

• Prior or planned joint surgery of the hands which might impact the interpretation of imaging assessments.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• subcutaneous tocilizumab
162 mg subcutaneous, once a week during 12 months

Locations

Country	Name	City	State
France	Hopital Edouard HERIOT	Lyon
France	CHR d'ORLEANS	Orleans
France	Hopital Nord CHU de SAint ETIENNE	Saint Etienne
France	Chu Toulouse	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Régional d'Orléans	Rennes University Hospital

Country where clinical trial is conducted

France, 

References & Publications (10)

Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2005 Dec;90(12):6508-15. doi: 10.1210/jc.2005-1258. Epub 2005 Sep 27. — View Citation

Dohn UM, Ejbjerg B, Boonen A, Hetland ML, Hansen MS, Knudsen LS, Hansen A, Madsen OR, Hasselquist M, Moller JM, Ostergaard M. No overall progression and occasional repair of erosions despite persistent inflammation in adalimumab-treated rheumatoid arthritis patients: results from a longitudinal comparative MRI, ultrasonography, CT and radiography study. Ann Rheum Dis. 2011 Feb;70(2):252-8. doi: 10.1136/ard.2009.123729. Epub 2010 Oct 26. — View Citation

Dohn UM, Ostergaard M, Bird P, Boonen A, Johansen JS, Moller JM, Hansen MS. Tendency towards erosive regression on magnetic resonance imaging at 12 months in rheumatoid arthritis patients treated with rituximab. Ann Rheum Dis. 2009 Jun;68(6):1072-3. doi: 10.1136/ard.2008.098962. No abstract available. — View Citation

Ellouz R, Chapurlat R, van Rietbergen B, Christen P, Pialat JB, Boutroy S. Challenges in longitudinal measurements with HR-pQCT: evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility. Bone. 2014 Jun;63:147-57. doi: 10.1016/j.bone.2014.03.001. Epub 2014 Mar 12. — View Citation

Finzel S, Rech J, Schmidt S, Engelke K, Englbrecht M, Schett G. Interleukin-6 receptor blockade induces limited repair of bone erosions in rheumatoid arthritis: a micro CT study. Ann Rheum Dis. 2013 Mar;72(3):396-400. doi: 10.1136/annrheumdis-2011-201075. Epub 2012 May 14. — View Citation

Finzel S, Rech J, Schmidt S, Engelke K, Englbrecht M, Stach C, Schett G. Repair of bone erosions in rheumatoid arthritis treated with tumour necrosis factor inhibitors is based on bone apposition at the base of the erosion. Ann Rheum Dis. 2011 Sep;70(9):1587-93. doi: 10.1136/ard.2010.148395. Epub 2011 May 27. — View Citation

Fouque-Aubert A, Boutroy S, Marotte H, Vilayphiou N, Bacchetta J, Miossec P, Delmas PD, Chapurlat RD. Assessment of hand bone loss in rheumatoid arthritis by high-resolution peripheral quantitative CT. Ann Rheum Dis. 2010 Sep;69(9):1671-6. doi: 10.1136/ard.2009.114512. Epub 2010 Jun 4. — View Citation

Garnero P, Thompson E, Woodworth T, Smolen JS. Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum. 2010 Jan;62(1):33-43. doi: 10.1002/art.25053. — View Citation

Moller Dohn U, Boonen A, Hetland ML, Hansen MS, Knudsen LS, Hansen A, Madsen OR, Hasselquist M, Moller JM, Ostergaard M. Erosive progression is minimal, but erosion healing rare, in patients with rheumatoid arthritis treated with adalimumab. A 1 year investigator-initiated follow-up study using high-resolution computed tomography as the primary outcome measure. Ann Rheum Dis. 2009 Oct;68(10):1585-90. doi: 10.1136/ard.2008.097048. Epub 2008 Nov 19. — View Citation

Stach CM, Bauerle M, Englbrecht M, Kronke G, Engelke K, Manger B, Schett G. Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high-resolution computed tomography. Arthritis Rheum. 2010 Feb;62(2):330-9. doi: 10.1002/art.27252. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone erosion change after 12 months of subcutaneous tocilizumab	changes of width measured by HRpQCT.	baseline and 12 months
Primary	Bone erosion change after 12 months of subcutaneous tocilizumab	changes of depth measured by HRpQCT.	baseline and 12 months
Primary	Bone erosion change after 12 months of subcutaneous tocilizumab	changes of volume measured by HRpQCT.	baseline and 12 months
Secondary	Associated factors with erosion changes assessed by HRqQCT	Number of participants with associated factors with erosion changes by HRpQCT (Associated therapeutic, clinical and biological response )ultrasound ...)	baseline, 3 months, 12 months
Secondary	Effect of 12 months of tocilizumab on bone density in the PR	Changes of Bone mineral density by DXA at the lumbar spine and proximal femur	baseline, 12 months
Secondary	Effect of Tocilizumab on synovitis/tenosynovitis assessed by US and agreement with disease activity scores	Correlation Between clinical activity measured by various indices (Disease Activity Score 28, Clinical Disease Activity Iindex , Simplify Disease Activity Index , American College of Rheumatology - European League against Rheumatism: ACR EULAR) and ultrasound data.	Predictors baseline, 1 and 3 months of clinical remission and / or ultrasound at 6 and 12 months
Secondary	Effect of 12 months of tocilizumab on bone microarchitecture in the PR	changes of bone microarchitecture by tibia HRpQCT	baseline, 12 months