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

NCT02765074 | Completed Phase 4

• 1 other identifier: CHRO 2014-03
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Rheumatoid Arthritis

Keywords

subcutaneous tocilizumab; High Resolution peripheral QCT (HR-pQCT); bone erosion; bone microarchitecture; rheumatoid arthritis

Outcome Measures

Primary Outcomes (3)

• Bone erosion change after 12 months of subcutaneous tocilizumab

  changes of width measured by HRpQCT.

  baseline and 12 months

• Bone erosion change after 12 months of subcutaneous tocilizumab

  changes of depth measured by HRpQCT.

  baseline and 12 months

• Bone erosion change after 12 months of subcutaneous tocilizumab

  changes of volume measured by HRpQCT.

  baseline and 12 months

Secondary Outcomes (4)

• Associated factors with erosion changes assessed by HRqQCT

  baseline, 3 months, 12 months

• Effect of 12 months of tocilizumab on bone density in the PR

  baseline, 12 months

• Effect of Tocilizumab on synovitis/tenosynovitis assessed by US and agreement with disease activity scores

  Predictors baseline, 1 and 3 months of clinical remission and / or ultrasound at 6 and 12 months

• Effect of 12 months of tocilizumab on bone microarchitecture in the PR

  baseline, 12 months

Study Arms (1)

Roactemra

EXPERIMENTAL

subcutaneous tocilizumab

Drug: subcutaneous tocilizumab

Interventions

subcutaneous tocilizumab DRUG

162 mg subcutaneous, once a week during 12 months

Also known as: Roactemra

Roactemra

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Régional d'Orléans: lead
• Rennes University Hospital: collaborator

Study Sites (4)

Hopital Edouard HERIOT

Lyon, 69437, France

Location

CHR d'ORLEANS

Orléans, 45067, France

Location

Hopital Nord CHU de SAint ETIENNE

Saint-Etienne, France

Location

Chu Toulouse

Toulouse, France

Location

Related 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.

  PMID: 16189253 BACKGROUND

• 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.

  PMID: 20112404 BACKGROUND

• 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.

  PMID: 20525847 BACKGROUND

• 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.

  PMID: 24614646 BACKGROUND

• 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.

  PMID: 19019887 BACKGROUND

• 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.

  PMID: 21622765 BACKGROUND

• 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.

  PMID: 19435723 BACKGROUND

• 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.

  PMID: 20980282 BACKGROUND

• 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.

  PMID: 22586162 BACKGROUND

• 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.

  PMID: 20039425 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab

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

• SALLIOT Carine, MD

  CHR ORLEANS

  STUDY DIRECTOR

• LESPESSAILLES Eric, MD, PhD

  CHR ORLEANS

  PRINCIPAL INVESTIGATOR

• CANTAGREL Alain, MD, PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

• CHAPURLAT Roland, MD, PhD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

• MAROTTE Hubert, MD, PhD

  HOPITAL NORD SAINT ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 19, 2016
• First Posted: May 6, 2016
• Study Start: June 30, 2016
• Primary Completion: April 3, 2025
• Study Completion: April 3, 2025
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)