Clinical trial NCT05689879: Evaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis
Official title: Evaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis : a Prospective, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Sarcoidosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-01-19
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Infliximab stop Methotrexate (without exceed 25mg/kg/week) or azathioprine
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The screening visit takes place between 60 days and until the baseline visit. The investigator will first check that the patient meets the inclusion criteria and does not present exclusion criteria. Before enrolment and randomization, all patients will receive comprehensive information and provide written consent.

Visit schedule:

* Baseline visit
* Follow-up Visits In the REMAIN arm: visits will be performed each 4-8 weeks depending on the infliximab interval. In the STOP arm, visits will be performed every 8 weeks, and in case of relapse (until M12+/- 2 weeks).

Eligibility criteria: Inclusion Criteria:

* Age superior or equal to 18 years
* Clinical and radiological presentation consistent with sarcoidosis
* Presence of non-caseating granulomas in at least one organ
* Exclusion or other causes of granulomas
* Infliximab treatment for at least 6 months
* Steroid dosage \< or equal to 10 mg/day for at least 6 months
* No activity of the disease (ePOST score 0) for at least 6 months
* Normal ACE (angiotensin converting enzyme) and serum calcemia level
* Signed informed consent
* Affiliated to the National French social security system
* As 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-feeding
* Positive IGRA (Interferon Gamma Release Assays) test without previous antituberculous antibiotherapy
* Active infection
* Patients with moderate to severe heart failure (NYHA class III/ IV)
* Severe liver function disorders
* Alcoholism
* Severe kidney function disorders
* Pre-existing blood dyscrasias
* History of cancer in the 5 years before enrolment (except for cutaneous non melanoma cancers)
* Concurrent vaccination with live vaccines during therapy
* Inability to understand information about protocol
* Adult subject under legal protection or unable ton consent
* Absence of effective contraceptive method for men and women for duration of the study and 6 months after the end of participation
* Concomitant participation to another biomedical research (only Category 1 trial according to the french law)

Primary outcomes:
measure: To compare 2 strategies of remission maintenance in patients who are in remission after infliximab administration
timeFrame: 12 months
Secondary outcomes:
measure: To compare the percentage of patients with minor relapses in the 2 groups
timeFrame: 12 months
measure: To compare the rates of adverse events
timeFrame: 12 months
measure: To determine which are the predictors of relapses
timeFrame: 12 months
measure: To determine which are the predictives of relapses
timeFrame: 12 months
measure: To determine which are the relapsing predictors
timeFrame: 12 months
measure: To determine which are the prediction of relapses
timeFrame: 12 months
measure: To compare results of Short Form (36) Health Survey in the 2 groups
timeFrame: 12 mois
measure: Compare results of Nottingham scale of each groups
timeFrame: 12 mois
measure: To compare results of Fatigue Assessment Scale in the 2 groups
timeFrame: 12 mois
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital de la Pitié-Salpêtrière
Study officials:
affiliation: Internal Medicine Department 2 - Hôpital Pitié-Salpêtrière
name: Fleur COHEN AUBART, PHD
role: STUDY_DIRECTOR
References: