Clinical trial NCT02765074: Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of Subcutaneous Tocilizumab in Rheumatoid Arthritis
Official title: Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of 12 Months Subcutaneous Tocilizumab in Rheumatoid Arthritis Phase IV Prospective Multicentrique Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: subcutaneous tocilizumab
High Resolution peripheral QCT (HR-pQCT)
bone erosion
bone microarchitecture
rheumatoid arthritis
Lead sponsor: Centre Hospitalier Régional d'Orléans
Sponsor class: OTHER
Collaborators: name: Rennes University Hospital
First posted: 2016-05-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Bone erosion change after 12 months of subcutaneous tocilizumab
timeFrame: baseline and 12 months
measure: Bone erosion change after 12 months of subcutaneous tocilizumab
timeFrame: baseline and 12 months
measure: Bone erosion change after 12 months of subcutaneous tocilizumab
timeFrame: baseline and 12 months
Secondary outcomes:
measure: Associated factors with erosion changes assessed by HRqQCT
timeFrame: baseline, 3 months, 12 months
measure: Effect of 12 months of tocilizumab on bone density in the PR
timeFrame: baseline, 12 months
measure: Effect of Tocilizumab on synovitis/tenosynovitis assessed by US and agreement with disease activity scores
timeFrame: Predictors baseline, 1 and 3 months of clinical remission and / or ultrasound at 6 and 12 months
measure: Effect of 12 months of tocilizumab on bone microarchitecture in the PR
timeFrame: baseline, 12 months
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hopital Edouard HERIOT
city: Orleans
country: France
facility: CHR d'ORLEANS
city: Saint Etienne
country: France
facility: Hopital Nord CHU de SAint ETIENNE
city: Toulouse
country: France
facility: Chu Toulouse
Study officials:
affiliation: CHR ORLEANS
name: SALLIOT Carine, MD
role: STUDY_DIRECTOR
affiliation: CHR ORLEANS
name: LESPESSAILLES Eric, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Toulouse
name: CANTAGREL Alain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospices Civils de Lyon
name: CHAPURLAT Roland, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: HOPITAL NORD SAINT ETIENNE
name: MAROTTE Hubert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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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.
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.