Hydroxychloroquine as a Steroid-sparing Agent in Extrapulmonary Sarcoidosis
Status:
Not yet recruiting
Trial end date:
2028-09-01
Target enrollment:
Participant gender:
Summary
Sarcoidosis is a systemic granulomatous disease of unknown aetiology, mainly affecting the
lungs and lymphatics. It affects people worldwide (incidence, 4.7-64/100000; prevalence,
1-36/100000/year). Although it is most often a benign acute or subacute condition,
sarcoidosis may progress to a disabling chronic disease in 25% of the cases, with severe
complications in about 5%, such as lung fibrosis, cardiac or neurosarcoidosis, defacing lupus
pernio or blindness due to uveitis.
When indicated, corticosteroids (CS) are the mainstay of treatment. Due to the kinetics of
granuloma resolution, the usual and quite 'dogmatic' duration of treatment is said to be one
year, following four classical steps. The long-term use of CS is hindered by cumulative
toxicity and efforts have to be made to taper them, as quickly as possible, to the lowest
effective dose. A recent report mentioned 39% of the CS-treated patients requiring a
steroid-sparing agent. Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-malarial drugs
that have been used since the 1960's as steroidsparing agents on the basis of a landmark
study by Siltzbach reporting their efficacy in 43 patients with skin and intrathoracic
sarcoidosis. Subsequently, two small randomized controlled trials have shown significant and
prolonged improvement on pulmonary symptoms. Only small case series/reports have shown CQ/HCQ
efficacy on extra-pulmonary sarcoidosis with response rates ranging from 67 to 100%.
Nevertheless, CQ/HCQ are daily used for skin, bone, and joint sarcoidosis, as well as
hypercalcemia. Nowadays, HCQ is preferred over CQ because of a lower incidence of
gastrointestinal and ocular adverse reactions, which can be minimized by close attention to
the dosage and regular retinal examination. Its profile of safety is well-known since it has
long been employed to treat systemic lupus erythematous or rheumatoid arthritis. Its action
is thought to rely on its ability to accumulate in lysosomes of phagocytic cells, to affect
antigen presentation and reduce pro-inflammatory cytokines. The investigator hypothesize that
HCQ may be an efficacious add-on therapy for extra-pulmonary sarcoidosis leading to a
significant steroid-sparing effect.