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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| REMAIN arm | No Intervention | 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 | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| STOP arm | Drug | TNF-alpha antagonists withdrawal |
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| Measure | Description | Time Frame |
|---|---|---|
| To compare 2 strategies of remission maintenance in patients who are in remission after infliximab administration | Percentage of patients with major relapse (reappearance or worsening of the disease with a ePOST score >0 and involvement of at least one major organ, a life-threatening situation, or both or relapse non responsive to mild treatment intensification) between enrolment and month 12. Major organs are nervous system, heart, kidneys, muscles and lungs. Mild treatment intensification is defined by increasing the dosage of steroids at more than 20 milligrams/day. The primary criterion will be assessed at each visit, in case of relapse and at the end of follow-up (M12). | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| To compare the percentage of patients with minor relapses in the 2 groups | Percentage of patients with minor relapse (reappearance or worsening of the disease with a ePOST score > 0 not corresponding to the definition of major relapse) at months 12. | 12 months |
| To compare the rates of adverse events |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fleur COHEN AUBART, PHD | Internal Medicine Department 2 - Hôpital Pitié-Salpêtrière | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital de la Pitié-Salpêtrière | Paris | 75013 | France |
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| ID | Term |
|---|---|
| D012507 | Sarcoidosis |
| ID | Term |
|---|---|
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006968 | Hypersensitivity, Delayed |
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Infliximab stop Methotrexate (without exceed 25mg/kg/week) or azathioprine
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No masking
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All adverse events occurred between enrolment and Month 12, will be noted with special attention to infection, haematological toxicities and cancers. |
| 12 months |
| To determine which are the predictors of relapses | Percentage of patients with a previous heart involvement at inclusion | 12 months |
| To determine which are the predictives of relapses | Percentage of patients with nervous system involvement at inclusion | 12 months |
| To determine which are the relapsing predictors | Percentage of patients with hypermetabolism elsewhere consistent with sarcoidosis localization in positron emission tomography scan (PET scan) at inclusion | 12 months |
| To determine which are the prediction of relapses | Serum ACE (angiotensin converting enzyme) level at inclusion | 12 months |
| To compare results of Short Form (36) Health Survey in the 2 groups | Quality of life will be assessed by SF-36 (Short Form (36) Health Survey) at inclusion, Month 6 and Month 12 (score from 0 to 100, the higher score is the better). | 12 mois |
| Compare results of Nottingham scale of each groups | Quality of life will be assessed by Nottingham scale at inclusion, Month 6 and Month 12 (score from 0 to 38, the higher score is the worse) . | 12 mois |
| To compare results of Fatigue Assessment Scale in the 2 groups | Quality of life will be assessed by Fatigue Assessment Scale (FAS, Patel 2000) at inclusion, Month 6 and Month 12 (score from 10 to 50, the higher score is the worse) . | 12 mois |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |