New Clinical End-points in Patients With Primary Sjögren's Syndrome

Exclusion Criteria

• •For both cohorts:
• •Age \< 18 years
• •Pregnant or breastfeeding women or women wanted to conceive either during or within two years after the end of the treatment period
• •Women of childbearing potential not using highly effective methods of contraception (as defined in section 6.3)
• •Participation in another interventional trial
• •Contra-indication to HCQ: pre-existing retinopathy, hypersensitivity to HCQ or to any of the excipients of the specialty used
• •Contra-indication to MMF: hypersensitivity to mycophenolate mofetil, acid mycophenolic, mycophenolate sodium or to any of the excipients of the specialty used
• •Contra-indication tor LEF: hypersensitivity to the active substance, the main active metabolite teriflunomide or to any excipients of the specialty used.
• •Concomitant treatment with corticosteroids more than 10 mg/day of prednisone equivalent at screening or inclusion (randomisation)
• •Concomitant treatment with other immunomodulators including methotrexate, azathioprine, cyclophosphamide, cyclosporine and tacrolimus
• •Previous treatment with HCQ, LEF, MMF in the last 3 months
• •Previous treatment with rituximab, other B-cell targeted biologic therapy or cyclophosphamide in the last 6 months
• •Previous treatment with anti-TNF, abatacept, tocilizumab or belimumab or any other biologic in the setting of a past clinical trial in the last 3 months
• •Impairment of other severe immunodeficiency states
• •Patients with active malignancy or history of malignancy within the last 5 years except non-melanoma skin cancer
• •Patients with history of gastrointestinal tract ulceration, hemorrhage and perforation
• •Patients with history of cardiomyopathy
• •Patients with known hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome
• •Serious infection in the past month
• •Evidence of active tuberculosis infection
• •Active HCV (positive PCR)
• •Active HBV infection (positivity for HBS antigen, or positivity for anti-HBC antibody without any HBS antigen)
• •HIV infection (positive serology)
• •Positive SARS-Cov2 PCR (if vaccinated for COVID-19, no PCR is required; if history of COVID-19 infection, positive serology is sufficient)
• •Cytopenia defined as neutrophils \< 1.0 G/L, lymphocytes \< 0.5 G/L, Hb \< 10 g/dl or platelets \< 100 G/L
• •Moderate to severe renal insufficiency (GFR \< 30 ml/min)
• •Severe hypogammaglobulinemia defined as gamma globulins or IgG \< 5 g/l Reduced hepatic function: AST or ALT \> 2x ULN (re-testing is allowed, see section 5.10)
• •Prolonged ECG's corrected QT interval (\>500 ms)
• •Known history of maculopathy
• •Patients will be informed of the risk of alcohol consumption and will be recommended to avoid alcohol during the entire study
• •Not affiliated to a social security regime (specific for France)