Effect of the Interleukin-6 Receptor Antagonist Tocilizumab in Patients With Hand Osteoarthritis

Study Overview
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Brief Summary
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Hand osteoarthritis (HOA) which affects the interphalangeal joints and the metacarpophalangeal of the thumb is a common disease, the prevalence of which being about 30 % of the population over than 70. Some forms of HOA are refractory to usual treatments (analgesics, NSAIDs, local injections) and can lead to a high disability. In vitro and in vivo studies showed that IL-6 is involved in the OA process. The aim of the present study is to assess the efficacy of an Interleukin-6-Receptor Inhibitor (tocilizumab) on pain and function in patients with refractory hand OA.

Detailed Description
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Patient is randomized to receive investigational product or placebo at week 0 and week 4 (1:1) arm 1: 2 infusions four weeks apart of tocilizumab 8mg/kg arm 2: 2 infusions four weeks apart of saline solution Follow-up visits are organized at week 6, and then week 8 and week 12. Primary outcome is the pain as assessed with the VAS at week 6. Secondary outcomes include morning stiffness duration, patient and practitioner global assessments, functional indexes for hand OA, number of painful joints, number of swollen joints. 110 patients is expected to be randomized in 36 months. Each patient sign an informed consent before the beginning of the study.

Official Title
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Double-blind, Randomized, Placebo-controlled Trial Evaluating the Effect of Two Infusions Four Weeks Apart of Interleukin-6-Receptor Inhibitor (Tocilizumab) on Pain Relief in Patients With Severe Osteoarthritis of the Hand Refractory to Usual Treatment

Conditions
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Hand Osteoarthritis

Intervention / Treatment
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* Drug: tocilizumab
* Drug: saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 40-85 Hand OA according to the ACR criteria (with recent X-rays of the hands - less than 6 months ) Symptomatic hand OA lasting more than 3 months (DIP or PIP) despite analgesics and NSAIDs OA affecting more than three finger joints (DIP or PIP) (Kellgren and Lawrence equal or more than 2) Pain intensity superior to 40 (VAS 0-100 mm) in the last 24 hours Not breastfeeding throughout the study and for 150 days after the last infusion Negative pregnancy test or effective contraception for women of childbearing age throughout the study and for 150 days after the last infusion or postmenopausal or surgically sterile Written informed consent Affiliated to health system Exclusion Criteria: Patients having already been treated with an anti-TNF alpha within 6 months Patients having already been treated with an Interleukin-6-Receptor Inhibitor Hand OA secondary to inflammatory rheumatism Existence of painful syndrome of upper limbs likely to interfere with the monitoring of pain (cervicobrachial neuralgia, incapacitating carpal tunnel syndrome, joint disorders of the elbow or shoulder) Inflammatory rheumatism Psoriasis Contraindications to Interleukin-6-Receptor Inhibitor Contraindications to acetaminophen Anticoagulant (oral) or treatment with heparin at a curative dose Surgery scheduled within 6 months following recruitment Local injection of a corticosteroid in a symptomatic finger joint during the previous month Local injection of hyaluronic acid in a symptomatic finger joint during the prior 6 months Treatment with a slow-acting anti-osteoarthritis agent initiated within the previous 3 months Treatment with methotrexate, hydrochloroquine, sulfasalazine, colchicine within the last month History of symptomatics sigmoiditis or intestinal ulceration Oral corticosteroid within 3 days for hydrocortisone or cortisone, within 8 days for prednisone, prednisolone, methylprednisolone or triamcinolone, and within 12 days for betamethasone or dexamethasone Psychiatric illness Antidepressants initiated or modified within previous month Non-controlled diabetes mellitus Known viral hepatitis B or C, HIV infection Current infectious (active or latent tuberculosis) Excessive drinking Participation in another search Lidocain plasters on digital joint within two months

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tocilizumab<br>2 infusions four weeks apart | Drug: tocilizumab<br>* Le tocilizumab is administered by intravenous infusion at a dose of 8 mg / kg.<br>* Other names: ROACTEMRA®;|
| Placebo Comparator: saline solution<br>2 infusions four weeks apart | Drug: saline solution<br>* La saline solution is administered by intravenous infusion.<br>* Other names: NaCl 0,9 %;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of pain | Change of pain between the first infusion (week 0) and 2 weeks after the second infusion (week 6) as assessed on the VAS (0 -100 mm) | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of pain | Change of pain between the first infusion (week 0) and 4, 8,12 weeks after the first infusion as assessed on the VAS (0 -100 mm) | weeks 4, 8, 12 | 
| Number of painful joints |  | weeks 4, 6, 8, 12 | 
| Number of swollen joints |  | weeks 4, 6, 8, 12 | 
| Overall assessment of disability | Patient and practitioner global assessments | weeks 4, 6, 8, 12 | 
| Morning stiffness duration |  | weeks 4, 6, 8, 12 | 
| Evaluation of the function | Dreiser's algofunctional index + Functional Cochin hand index | weeks 4, 6, 8, 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hand OA, Tocilizumab, Osteoarthritis, Interleukin-6