No abstract available.
Azathioprine/*therapeutic use ; Crohn Disease/*drug therapy ; Female ; Humans ; Immunosuppressive Agents/*therapeutic use ; Leukocytes/*cytology ; Male

No abstract available.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antimetabolites/therapeutic use ; Azathioprine/therapeutic use ; Chronic Disease ; Colitis, Ulcerative/diagnosis/*therapy ; Hemoglobins/analysis ; Humans ; Mesalamine/therapeutic use ; Recurrence ; Risk Factors

OBJECTIVETo observe the effects of Shugan Jianpi Gusui Recipe (SJGR) on multiple sclerosis (MS).

METHODSA case cohort study was used. The MS patients were assigned to the test group (14 cases) and the control group (21 cases) according to whether they would combine with Chinese herbs. Corticosteroids or gamma globulin was administered to all patients in the acute phase. SJGR was administered to patients in the test group in the remission phase, while those in the control group were not treated or treated by azathioprine alone. They were followed-up for a long time after their first visits. The observation time ranged 10-131 successive months. The recurrence intervals and the yearly average recurrence times were calculated in the two groups.

RESULTSWhen compared with before treatment, the recurrence interval was obviously prolonged, and the yearly average recurrence times decreased in the test group after treatment with statistical difference (P < 0.05). There was statistical difference in the recurrence interval and the yearly average recurrence times between the test group and the control group (P < 0.05).

CONCLUSIONSSJGR showed better effects in prolonging the recurrence interval and reducing the yearly average recurrence times of MS patients. It is worth further researches.

Adrenal Cortex Hormones ; therapeutic use ; Adult ; Azathioprine ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Middle Aged ; Multiple Sclerosis ; drug therapy ; Recurrence ; gamma-Globulins ; therapeutic use

Adjuvants, Immunologic ; adverse effects ; therapeutic use ; Azathioprine ; adverse effects ; therapeutic use ; Cyclosporine ; adverse effects ; therapeutic use ; Glucocorticoids ; adverse effects ; therapeutic use ; Humans ; Mycophenolic Acid ; adverse effects ; analogs & derivatives ; therapeutic use ; Tacrolimus ; adverse effects ; therapeutic use

Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms.
Anti-Inflammatory Agents/*therapeutic use ; Autoantibodies/*blood ; Azathioprine/therapeutic use ; Biomarkers/blood ; Diagnosis, Differential ; Drug Therapy, Combination ; Hepatitis, Autoimmune/*diagnosis/*drug therapy ; Humans ; Immunosuppressive Agents/*therapeutic use ; Prednisolone/therapeutic use ; Prednisone/therapeutic use

The risk of lymphoproliferative disorders (LPDs) has been reported to be increased in autoimmune diseases and chronic inflammatory diseases. Similar with other chronic inflammatory diseases such as rheumatoid arthritis, there is a concern about the risk of LPDs in patients with inflammatory bowel disease (IBD). Generally, in IBD patients, the risk of LPDs appears to be similar with or very slightly higher, compared to the general population. The association of therapeutic agents with the risk of LPDs is difficult to evaluate due to multiple other potentially involved factors and co-treatment with other agents. To date, data show that thiopurine is associated with a moderately increased risk of LPDs in patients with IBD. Evidence regarding the risk of LPDs in IBD patients using methotrexate is not sufficient, but the risk of LPDs seems low. The responsibility of anti-TNF-alpha agents on the risk of LPDs is difficult to determine, because most of IBD patients receiving anti-TNF-alpha agents are co-treated with thiopurines. Attention should be given to the high risk of hepatosplenic T-cell lymphoma in young male patients treated with anti-TNF-alpha agents together with thiopurines. The risk and benefit of immunosuppressive therapy for IBD should be carefully evaluated and individualized considering the risk of LPDs.
Anti-Inflammatory Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Azathioprine/adverse effects/therapeutic use ; Humans ; Immunosuppressive Agents/adverse effects/therapeutic use ; Inflammatory Bowel Diseases/complications/*drug therapy ; Lymphoproliferative Disorders/chemically induced/*etiology ; Methotrexate/therapeutic use ; Risk Factors

Thiopurine S-methyltransferase (TPMT) methylates purine analogues, showing TPMT activity in inverse relation to concentrations of active metabolites such as 6-thioguanine nucleotide (6-TGN). With conventional dosing of thiopurines, patients with homozygous variant TPMT alleles consistently suffer from severe myelosuppression. Here, we report a patient with TPMT*3C/*3C who managed successfully with monitoring of thiopurine metabolites. The patient was an 18-year-old male diagnosed with Crohn's disease. The standard dose of azathioprine (AZA) (1.8 mg/kg/day) with mesalazine (55.6 mg/kg/day) was prescribed. Two weeks after starting AZA treatment, the patient developed leukopenia. The DNA sequence analysis of TPMT identified a homozygous missense variation (NM_000367.2: c.719A>G; p.Tyr240Cys), TPMT*3C/*3C. He was treated with adjusted doses of azathioprine (0.1-0.2 mg/kg/day) and his metabolites were closely monitored. Leukopenia did not reoccur during the follow-up period of 24 months. To our knowledge, this is the first case of a patient homozygous for TPMT*3C successfully treated with azathioprine in Korea. While a TPMT genotyping test may be helpful to determine a safe starting dose, it may not completely prevent myelosuppression. Monitoring metabolites as well as routine laboratory tests can contribute to assessing drug metabolism and optimizing drug dosing with minimized drug-induced toxicity.
Adolescent ; Azathioprine/adverse effects/*therapeutic use ; Homozygote ; Humans ; Inflammatory Bowel Diseases/*drug therapy/*enzymology/*genetics/metabolism ; Male ; Methyltransferases/*genetics

This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) or tacrolimus (TAC) compared with azathioprine (AZA) as maintenance therapy for active lupus nephritis (ALN). Patients with ALN who responded to 24 weeks of induction treatment were enrolled. Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period, whereas those who received intravenous cyclophosphamide were subjected to AZA treatment. The primary endpoint was the incidence of renal relapse. Secondary endpoints included extrarenal flares and composite endpoints (deaths, end-stage renal disease, or doubling of serum creatinine levels). A total of 123 ALN patients (47 in the MMF group, 37 in the TAC group, and 39 in the AZA group) were enrolled. The median follow-up time was 60 months. Ten MMF-treated patients, ten TAC-treated patients, and eight AZA-treated patients experienced renal relapses (P = 0.844). The cumulative renal relapse rates in the MMF group (P = 0.934) and TAC group (P = 0.673) were similar to the renal relapse rate in the AZA group. No significant difference in the incidence of severe adverse event was observed among the groups. Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.
Humans ; Mycophenolic Acid/adverse effects* ; Azathioprine/adverse effects* ; Tacrolimus/therapeutic use* ; Lupus Nephritis/complications* ; Immunosuppressive Agents ; Treatment Outcome ; Recurrence

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by a relapsing and remitting course. The quality of life can decreases significantly during exacerbations of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies are currently used for the management of UC. However, many challenging issues exist and sometimes these lead to differences in practice between clinicians. Therefore, Inflammatory Bowel Diseases (IBD) Study Group of Korean Association for the Study of Intestinal Diseases (KASID) set out the Korean guidelines for the management of UC. These guidelines are made by the adaptation using several foreign guidelines and encompass treatment of active colitis, maintenance of remission and indication for surgery in UC. The specific recommendations are presented with the quality of evidence. These are the first Korean treatment guidelines for UC and will be revised with new evidences on treatment of UC.
Administration, Oral ; Adrenal Cortex Hormones/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Azathioprine/therapeutic use ; Colitis, Ulcerative/*drug therapy/surgery ; Humans ; Hydrocortisone/therapeutic use ; Injections, Intravenous ; Mesalamine/therapeutic use ; Methylprednisolone/therapeutic use ; Severity of Illness Index ; Sulfasalazine/therapeutic use

BACKGROUNDThe thiopurine drugs are well established in the treatment of inflammatory bowel disease (IBD). However, uncertainty regarding the risk for neutropenia and hepatotoxicity deters its using. Thiopurine methyltransferase (TPMT) is the key enzyme in the metabolism of thiopurine. The aim of this study was to investigate the association of TPMT polymorphisms and activity with azathioprine (AZA)-related adverse events and clinical efficacy in Chinese Han patients with IBD.

METHODSFifty-two Han IBD patients treated with AZA were assessed for TPMT 2, 3A, 3B, and 3C, and for adverse events. Then, using reverse-phase high-performance liquid chromatography, TPMT activity was measured in 13 patients to analyze its correlation with AZA-related toxicity and clinical efficacy.

RESULTSOf the 52 patients, five experienced myelotoxicity and one experienced hepatotoxicity during treatment. No TPMT 2, 3A, 3B or 3C polymorphisms were detected in any of the 52 patients. In the 13 patients with TPMT activity measurement, TPMT activity ranged from 7.2 to 28.8 U/ml packed red blood cells (pRBCs). Among the 5 patients who suffered from myelotoxicity, 3 were affected in the early stage of AZA therapy. In these 3 patients, TPMT levels were significantly lower than those in patients without myelotoxicity, which reached statistical significance ((9.3 ± 2.1) U/ml pRBC vs. (18.0 ± 6.2) U/ml pRBC; P = 0.046). One patient who had higher TPMT activity (28.8 U/ml pRBC) suffered from hepatotoxicity during AZA therapy. Patients who achieved a clinical response had lower TPMT activity than those failed to respond ((13.7 ± 3.5) U/ml pRBC vs. (22.0 ± 5.5) U/ml pRBC; P = 0.009).

CONCLUSIONSTPMT variants do not completely account for the AZA-related myelotoxicity in Chinese Han IBD patients. However, measurement of TPMT activity may be helpful in reducing the risk of toxicity, and predicting the therapeutic efficacy.

Adolescent ; Adult ; Aged ; Antimetabolites ; therapeutic use ; Azathioprine ; adverse effects ; therapeutic use ; Female ; Humans ; Inflammatory Bowel Diseases ; drug therapy ; enzymology ; Male ; Methyltransferases ; genetics ; metabolism ; Middle Aged ; Polymorphism, Genetic