Single Patient Study to Treat Relapsing Polychondritis With Tocilizumab

Study Overview
=================
Brief Summary
-----------------
Relapsing polychondritis (RP) is a rare, immune-mediated disease associated with inflammation in cartilaginous structures and other tissues throughout the body. Prognosis can be poor, especially in cases where there is acute involvement of the laryngotracheal cartilages leading to airway destruction, which are resistant to treatments such as corticosteroids, immunosuppressive or cytotoxic drugs. The pathogenesis remains unclear although it is thought that autoimmune reactions to antigens present in cartilages, such as type II collagen and matrilin may evoke symptoms. There are no known clinical or laboratory measures that predict the expression of specific disease manifestations or the overall disease course. Two recently published case reports have shown an association with elevated serum IL-6 levels and relapsing polychondritis. In these case reports, both patients with refractory relapsing polychondritis were treated with tocilizumab, a humanized monoclonal antibody to the Interleukin 6 receptor, and achieved sustained response to the drug. This single patient trial aims to evaluate the response to Tocilizumab in an eight year old boy with relapsing polychondritis who has been shown to have elevated serum IL-6 levels and who has responded poorly to conventional therapies. The study hypothesis is that Tocilizumab will be able to control the disease in this patient.

Detailed Description
-----------------
In this N = 1 study a single known patient with relapsing polychondritis who has failed methotrexate, various anti TNF medications, anti IL1 medication and prolongued glucocorticosteroids will be recruited to receive Tocilizumab 8 mg /kg q 2 weeks iv. The objective is to assess efficacy of tociliuzmab in combination with stable ongoing therapy. Our patient received tocilizumab 8 mg/kg over 1 hour by intravenous infusion every 2 weeks throughout the course of the study. To assess tocilizumab efficacy, the primary objective is the change in physician global assessment on a 100-mm horizontal visual analogue scale (VAS) of disease activity. The secondary objectives were the change in parent global assessment of disease activity on a 100 mm VAS and the glucocorticoid dose in mg per day. Frequency of adverse events was also measured at baseline and after each biweekly tocilizumab infusion.

Official Title
-----------------
Efficacy of Tocilizumab in a Patient With Relapsing Polychondritis

Conditions
-----------------
Relapsing Polychondritis

Intervention / Treatment
-----------------
* Drug: Tocilizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Refractory relapsing polychondritis Failed glucocorticoid and methotrexate therapy Exclusion Criteria: This is an N=1 clinical trial with a known patient, therefore, exclusion criteria are non-applicable.
Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocilizumab<br>Single arm open label study. In this arm patient will receive 8mg/kg of Tocilizumab q 2 weeks iv. | Drug: Tocilizumab<br>* 8mg/kg every 2 weeks i.v.<br>* Other names: Actemra;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician Global Assessment of Disease Activity | Physician global assessment of disease activity was assessed on a 100 mm Visual Analogue Scale where 0 would be no disease activity and 100 would be the maximum disease activity. Higher values therefore indicate higher disease activity and therefore a worse outcome. Change of this outcome measure over time was documented. | Baseline and then every 2 weeks prior to each infusion for total duration of 30 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prednisone Dose | Prednisone dose administered to patient reduction through treatment course | 30 weeks | 
| Parent/Patient Global Assessment of Overall Well Being | A 100 mm visual analogue scale was used for the assessment of the parent/patient globale well being, maximum value is 100 and minimum value is 0 with lower values being better well being and therefore improved outcome and higher values worse well being and therefore worse outcome. Changes in this score over time are being assessed with this measure. | 30 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Relapsing Polychondritis, Single Patient Study, Tocilizumab