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

Assistance Publique - Hôpitaux de Paris

Status and phase: Enrolling; Phase 3

Conditions: Sarcoidosis

Treatments: Drug: STOP arm

Study type: Interventional

Funder types: Other

Identifiers

NCT05689879

P160922

Details and patient eligibility

About

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.

Full 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).

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

REMAIN arm

No Intervention group

Description:

Infliximab 3 to 5 mg/kg every 4-8 weeks, methotrexate 7.5-10 mg/week (or azathioprine 1 mg/Kg/day), steroids \< or = 10 mg/day

STOP arm

Other group

Description:

Methotrexate 0.3 mg/kg/week (or azathioprine 2 mg/kg/day (or 1 mg/kg/day if intermediary metabolism TMPT) (the dose of methotrexate will not exceed 25mg/kg/week wathever the weight of the patient), steroids \< or = 10 mg/d

Treatment:

Drug: STOP arm