Refractory Hemochromatosis Rheumatism Clinical Trial
Official title:
Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study
Treatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter, non-randomised, single-arm, open-label, phase II trial.
Hereditary hemochromatosis (HH) is a genetic disease characterized by tissue iron overload.
The most common genotype is homozygosity for the p.Cys282Tyr mutation of the HFE gene (MIM
235200). It is a serious disease which can lead to life threatening complications such as
cirrhosis, liver carcinoma, heart failure or diabetes mellitus. Currently, these
complications can be prevented by phlebotomies. Two-thirds of patients complain of joint
symptoms which represent a major cause of impaired quality of life. Phlebotomies are
ineffective on HH rheumatism and patients' quality of life is very often altered while life
threatening complications are prevented. Furthermore, there is a significant higher risk for
joint replacement surgery in these patients compared to controls (X 9). There is currently no
approved treatment for hemochromatosis rheumatism. As it looks like severe osteoarthritis,
calcium pyrophosphate deposition disease (CPDD) or chondrocalcinosis, symptomatic treatments
are employed such as analgesics (type I or II), non-steroidal anti-inflammatory drugs or
colchicine in case of acute joint flare, corticosteroids intra-articular injections or
occasionally oral glucocorticoids. However in some cases these treatments remain ineffective
leading to a true disability.
Frequently, there are local inflammatory symptoms. Interleukin 1ß (IL1ß) plays a key role in
the pathogenesis of crystal arthropathies (CPDD or gout).
Anakinra (IL-1Ra), a drug approved in France for rheumatoid arthritis, has been tested in
short series or case controls in refractory gout, CPDD and only in two patients with HH
rheumatism. The aim of this phase II study is to test the efficacy of anakinra in patients
with hemochromatosis and refractory joint pain. It is also to evaluate the opportunity to
perform a phase III trial. In the absence of available data on the evolution of this
rheumatism treated by anakinra in this population of patients resistant to standard therapy,
the investigators consider that a phase III trial would not be justifiable if the rate of
success is insufficient.
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