Relapsing Polychondritis
Conditions
Keywords
Relapsing Polychondritis, Single Patient Study, Tocilizumab
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.
Interventions
DRUGTocilizumab
8mg/kg every 2 weeks i.v.
Sponsors
Children's Hospital of Eastern Ontario
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Refractory relapsing polychondritis * Failed glucocorticoid and methotrexate therapy
Exclusion criteria
* This is an N=1 clinical trial with a known patient, therefore,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physician Global Assessment of Disease Activity | Baseline and then every 2 weeks prior to each infusion for total duration of 30 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prednisone Dose | 30 weeks | Prednisone dose administered to patient reduction through treatment course |
| Parent/Patient Global Assessment of Overall Well Being | 30 weeks | 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. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tocilizumab Tocilizumab: 8mg/kg every 2 weeks i.v. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Tocilizumab | — |
|---|---|---|
| Age, Categorical <=18 years | 1 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Age, Continuous | 10 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Canada | 1 participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 1 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
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.
Time frame: Baseline and then every 2 weeks prior to each infusion for total duration of 30 weeks
Population: a known patient for whom this trial was designed was recruited into this open label single arm study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Physician Global Assessment of Disease Activity | Baseline | 21 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 2 weeks | 14 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 4 weeks | 12 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 6 weeks | 43 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 8 weeks | 14 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 10 weeks | 12 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 12 weeks | 8 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 14 weeks | 6 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 16 weeks | 5 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 18 weeks | 8 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 20 weeks | 0 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 22 weeks | 2 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 24 weeks | 0 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 26 weeks | 37 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 28 weeks | 19 mm |
| Tocilizumab | Physician Global Assessment of Disease Activity | 30 weeks | 0 mm |
Secondary
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.
Time frame: 30 weeks
Population: Patient receiving Tocilizumab
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 14 weeks | 1 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | Baseline | 53 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 2 weeks | 0 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 4 weeks | 0 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 6 weeks | 33 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 8 weeks | 12 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 10 weeks | 2 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 12 weeks | 0 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 16 weeks | 1 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 18 weeks | 2 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 20 weeks | 0 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 22 weeks | 1 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 24 weeks | 0 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 26 weeks | 30 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 28 weeks | 15 mm |
| Tocilizumab | Parent/Patient Global Assessment of Overall Well Being | 30 weeks | 0 mm |
Secondary
Prednisone Dose
Prednisone dose administered to patient reduction through treatment course
Time frame: 30 weeks
Population: single arm open label study for 1 patient with relapsing polychondritis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tocilizumab | Prednisone Dose | Baseline | 25 mg |
| Tocilizumab | Prednisone Dose | 2 weeks | 25 mg |
| Tocilizumab | Prednisone Dose | 4 weeks | 25 mg |
| Tocilizumab | Prednisone Dose | 6 weeks | 25 mg |
| Tocilizumab | Prednisone Dose | 8 weeks | 25 mg |
| Tocilizumab | Prednisone Dose | 10 weeks | 30 mg |
| Tocilizumab | Prednisone Dose | 12 weeks | 30 mg |
| Tocilizumab | Prednisone Dose | 14 weeks | 30 mg |
| Tocilizumab | Prednisone Dose | 16 weeks | 30 mg |
| Tocilizumab | Prednisone Dose | 18 weeks | 30 mg |
| Tocilizumab | Prednisone Dose | 20 weeks | 25 mg |
| Tocilizumab | Prednisone Dose | 22 weeks | 25 mg |
| Tocilizumab | Prednisone Dose | 24 weeks | 25 mg |
| Tocilizumab | Prednisone Dose | 26 weeks | 20 mg |
| Tocilizumab | Prednisone Dose | 28 weeks | 20 mg |
| Tocilizumab | Prednisone Dose | 30 weeks | 20 mg |