Evaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis

In severe refractory sarcoidosis not responding to conventional immunosuppressive treatment, the third-line tumor necrosis factor (TNF)-alpha inhibitor infliximab is an alternative. Treatment duration is not known, although it has been suggested that relapse rates after withdrawal could be high. We hypothesize that a prolonged course of TNF-alpha would be better for maintaining remission in sarcoidosis.The population consists of histologically-proven adults sarcoidosis patients who were treated with infliximab and are in remission for at least 6 months with less than or equal to 10 milligrams of steroids (prednisone).The present study is a phase 3, prospective, randomized, parallel groups, comparative, open-labelled 2 arms study superiority trial comparing a STOP to a REMAIN strategy. Patients will be randomized in the 2 groups in a 1:1 ratio.

Inclusion Criteria:Age superior or equal to 18 yearsClinical and radiological presentation consistent with sarcoidosisPresence of non-caseating granulomas in at least one organExclusion or other causes of granulomasInfliximab treatment for at least 6 monthsSteroid dosage < or equal to 10 mg/day for at least 6 monthsNo activity of the disease (ePOST score 0) for at least 6 monthsNormal ACE (angiotensin converting enzyme) and serum calcemia levelSigned informed consentAffiliated to the National French social security systemAs infliximab is the most used TNF-alpha antagonists, we decided to include only patients treated with infliximab to increase the homogeneity.Exclusion Criteria:Pregnancy or breast-feedingPositive IGRA (Interferon Gamma Release Assays) test without previous antituberculous antibiotherapyActive infectionPatients with moderate to severe heart failure (NYHA class III/ IV)Severe liver function disordersAlcoholismSevere kidney function disordersPre-existing blood dyscrasiasHistory of cancer in the 5 years before enrolment (except for cutaneous non melanoma cancers)Concurrent vaccination with live vaccines during therapyInability to understand information about protocolAdult subject under legal protection or unable ton consentAbsence of effective contraceptive method for men and women for duration of the study and 6 months after the end of participationConcomitant participation to another biomedical research (only Category 1 trial according to the french law)