leflunomide for maintenance of remission in igg4 related disease

Conditions: Immunoglobulin G4 Related Sclerosing Disease

Summary: the study has been designed as a 12-month, open-label, randomized, controlled study comparing the use of prednisone mono-therapy and prednisone and leflunomide combination therapy in treating patients with igg4-related disease.

the aim of this clinical trial is to determine the safety and efficacy of leflunomide in treating patients with igg4-related disease by comparing the outcomes of prednisone and leflunomide combination therapy with prednisone mono-therapy. the follow-up period will be 12 months. during the follow-up period, results of laboratory tests and image examinations, igg4-rd ri and other parameters which can reflect treatment response as well as adverse effect events will be recorded.

Eligibility criteria:
inclusion criteria: 1. age between 18 and 80 years. 2. diagnosis of igg4-rd according to either consensus statement on the pathology of igg4-related disease (for those who have undergone biopsies) or 2011 comprehensive diagnostic criteria for igg4-related disease. both of the two criteria for diagnosis are specified below. (1)consensus statement on the pathology of igg4-related disease 1. histopathologic features consisting of dense lymphoplasmacytic infiltrate, fibrosis(usually storiform in character)and/or obliterative phlebitis within involved organs. 2. either an elevated igg4+/igg+cell ratio of \>40% within the affected organs or elevated igg4-bearing plasma cells per high-power field is necessary. the cut-off number of igg4-bearing plasma cells per high-power field is different depending upon the types of affected organs and specimens(through surgery or needle puncture biopsy). (2)2011 comprehensive diagnostic criteria for igg4-related disease 1. clinical examination showing characteristic diffuse/localized swelling or masses in single or multiple organs. 2. hematological examination shows elevated serum igg4 concentrations(135 mg/dl). 3. histopathologic examination shows marked lymphocyte and plasmacyte infiltration and fibrosis or infiltration of igg4+ plasma cells(ratio of igg4+/igg+ cells \> 40% and \>10 igg4+ plasma cells/hpf). definite: a + b + c,probable: a + c,possible: a + b 4. excluded from malignant tumors of each organ (e.g. cancer, lymphoma) and similar diseases (e.g. sjögren's syndrome, primary sclerosing cholangitis, castleman's disease, secondary retroperitoneal fibrosis, wegener's granulomatosis, sarcoidosis, churg-strauss syndrome) by additional histopathological examination. 5. even when patients cannot be diagnosed using the comprehensive diagnostic criteria, they may be diagnosed using organ-specific diagnostic criteria for igg4-rd, such as diagnostic criteria for igg4-mikulicz's disease. exclusion criteria: 1. subjects having received steroids or immunosuppressants in recent 3 months will be excluded. 2. subjects who were hypersensitive to leflunomide will be excluded. 3. alt and/or ast is more than two folds of the upper limit of relevant reference value at baseline. 4. wbc is less than 3×10\*9/l at baseline. 5. female patients who are pregnant or breastfeeding. 6. known significant concurrent medical disease.

Keywords: igg4-related disease igg4-related sclerosing cholangitis mikulicz disease pancreatitis retroperitoneal fibrosis lymphadenopathy