Efficacy of Tocilizumab in Primary Sjögren's Syndrome. (ETAP)

Inclusion Criteria:

• Patient with primary Sjögren's syndrome according to the European - American consensus group criteria
• Presence of anti SSA (Ro) or of anti-SSA and anti-SSB(La) antibodies
• ESSPR (EULAR consensus patient related index) I ≥ 35/100

AND

- either systemic complications

or - association of the 3 following conditions :

1. SJp diagnosed in the last 5 years
2. Salivary flow ≥ 0,15 ml/mn

3. Presence of at least one of the following biological abnormalities:

   • increase (≥ 25% of higher limit of normal value) of one marker of B-cell activation among beta2-microglobulin, IgG, free light chains of immunoglobulins
   • cryoglobulinemia or presence of a monoclonal component
   • decrease of C4 (≤ 25% of lower limit of normal value)

AND In women in childbearing age, effective contraception during treatment and 3 months following treatment discontinuation

Exclusion Criteria:

• Patient with previous history of therapy with tocilizumab
• Prednisone treatment introduced two weeks before inclusion or a change in this drug dose within two weeks before inclusion.
• A prednisone dose ≥ 15 mg per day.
• Hydroxychloroquine, chloroquine, quinacrine, non-steroidal anti-inflammatory drugs, pilocarpine hydrochloride, cyclosporine, cimeviline if introduced within two weeks before inclusion
• Therapy with methotrexate, leflunomide, psychoactive drug if introduced within 4 weeks before inclusion or a dose change within 4 weeks before inclusion.
• Treatment with azathioprine or mycophenolate mofetil within 4 weeks before inclusion.
• Live and live attenuated vaccines given within 4 weeks before inclusion.
• Biological treatment introduced within 8 weeks before inclusion
• Treatment with cyclophosphamide, intravenous immunoglobulin therapy or plasmapharese therapy in the last 6 months before inclusion.
• Auto-immune disease
• Patient with previous history of diverticular perforations, complications of diverticulitis, peritonite or inflammatory bowel disease.
• Patient with history of severe infection within 4 weeks before inclusion.
• Patient with history of infection within 2 weeks before inclusion.
• Patient with chronic infection or infection returns (e.g. tuberculose, VHB, VHC…)
• Positive serology tests for HIV, HBV, HCV
• Severe uncontrolled dyslipidemia
• Hepatocellular insufficiency
• Unstable cardiovascular disease
• Severe or chronic kidney disease, severe or chronic lung disease, severe or chronic endocrine disorder, severe or chronic neurological disease ( not related to the SJP)
• Patient with history of solid organ transplantation or haematopoietic stem cell transplantation
• Patient with history of lymphoma, neoplasia diagnosed 5 years before inclusion except squamous and basal cell cancers and carcinoma in situ of the uterine cervix.
• Severe complications of SJp at the inclusion: vasculitis with renal neurologic, digestive or cardiac involvement, interstitial lung disease, symptomatic cryoglobulinemia with severe neurologic involvement, renal function impairment, severe myositis, corticotherapy ≥ 1 mg/kg in the last 30 days before inclusion.
• Neutropenia < 1000*106
• Thrombocytopenia < 100 000/µl
• ALT or AST > 1.5 x ULN
• alcohol and drug addiction : withdrawal at least one year before inclusion
• A major surgical procedure in the 8 weeks before inclusion or a scheduled major surgery
• Pregnant woman, breast feeding woman
• Adults under supervision or guardianship
• Patient taking part in another clinical trial