Treatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter, non-randomised, single-arm, open-label, phase II trial.
Name: Anakinra
Description: One daily subcutaneous injection of a fixed dose of 100 mg will be administered at a fixed time during a five day periodType: DrugAnakinra
Description: Improvement is defined as the minimal clinically important improvement of joint pain and is assessed on a 0-100 mm visual analogue scale (VAS)
Measure: Rate of patients with improvement of joint pain Time: Day 15Description: Assessment of the disease activity by Visual analog scale (VAS)
Measure: Assessment of the disease activity Time: Day 0, day 15, day 30, day 60, day 90Description: Assessment of the number of painful joints by a clinical exam
Measure: Assessment of the number of painful joints Time: Day 0, day 15, day 30, day 60, day 90Description: Assessment of the number of swollen joints by a clinical exam
Measure: Assessment of the number of swollen joints Time: Day 0, day 15, day 30, day 60, day 90Description: Assessment of the quality of life by the SF36 questionnaire
Measure: Assessment of the quality of life Time: Day 0, day 15, day 30, day 90Description: Assessment of the quality of life by the HAQ questionnaire
Measure: Assessment of the quality of life Time: Day 0, day 15, day 30, day 90Description: Functional evaluation by WOMAC index for hip and knee
Measure: Functional evaluation Time: Day 0, day 15, day 30, day 90Description: Functional evaluation by Dreiser index for hands
Measure: Functional evaluation Time: Day 0, day 15, day 30, day 90Description: Assessment of joint damage by X-rays and Doppler ultrasound
Measure: Assessment of joint damage Time: Day 0, day 90Description: Puncture if acute joint effusion : cells count
Measure: Synovial fluid analysis Time: 3 monthsDescription: Puncture if acute joint effusion : search for crystals presence
Measure: Synovial fluid analysis Time: 3 monthsDescription: Puncture if acute joint effusion : iron parameters markers
Measure: Synovial fluid analysis Time: 3 monthsDescription: Biological/Vaccine : iron and inflammatory markers
Measure: Biological effects on inflammation and iron metabolism Time: Day 0, day 15, day 30, day 60, day 90Description: Pharmacokinetics study
Measure: Time at which Cmax of anakinra was observed (Tmax) Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Maximum observed concentration (Cmax) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Half-life (T1/2) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Area under the concentration-time curve of time 0 to the last detectable concentration (AUC0−last) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Area under the concentration-time curve of time 0 to infinity (AUC0−∞) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Plasma clearance after administration (CL/F) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseSingle Group Assignment
There is one SNP
Inclusion Criteria: - Patients with age equal to or over 18 years old, - Patients with proved hereditary hemochromatosis with homozygosity for the C282Y mutation of the HFE gene, - Patients with rheumatism related to hemochromatosis, considered by the rheumatologist refractory to usual treatment defined by a persistent painful symptomatology despite a treatment of at least one month with level 2 analgesics (weak opioids) at maximal dose, NSAID, colchicine, steroid injection or a combination of these treatments, - Patients with pain > 40/100mm measured by VAS (pain of the last 48 hours), - Effective contraception to be used during treatment and until 48h after the last administration for women of reproductive age, - Patients who have given written informed consent. --- C282Y ---