Efficacy and safety of iguratimod compared with placebo and salazosulfapyridine in active rheumatoid arthritis: a controlled, multicenter, double-blind, parallel-group study.

We conducted a 28-week, randomized, double-blind, parallel-group study of iguratimod in 376 Japanese patients with active rheumatoid arthritis to compare the efficacy and safety of the drug with those of placebo and salazosulfapyridine. In the American College of Rheumatology (ACR) 20 response rate, iguratimod was superior to placebo (53.8% versus 17.2%; Fisher's exact test, P < 0.001) and was not inferior to salazosulfapyridine (63.1% versus 57.7%, 95% confidence interval for the rate difference, -7.9% to 18.7%). Iguratimod began exhibiting its therapeutic effect within 8 weeks after the initiation of treatment and was effective even in patients who had a poor response to previous treatment with disease-modifying antirheumatic drugs. No statistically significant difference was noted in the incidence of adverse reactions between iguratimod and salazosulfapyridine. The study results suggest that iguratimod could become a new option for the treatment of rheumatoid arthritis.

Long-term safety study of iguratimod in patients with rheumatoid arthritis.

We conducted a 52-week clinical study of iguratimod in 394 Japanese patients with rheumatoid arthritis to evaluate the long-term safety of the drug. Iguratimod was administered orally at a daily dose of 25 mg for the first 4 weeks and 50 mg for the subsequent 48 weeks. Some of the patients continued the treatment for 100 weeks for their benefit. The cumulative incidence of adverse events for 100 weeks was 97.6%. The cumulative incidence of adverse reactions was 65.3%; unfavorable symptoms and signs (excluding abnormal laboratory data changes) accounted for 33.2% of the reactions, and abnormal laboratory data changes accounted for 50.4%. The continued treatment rate was 66.8% at week 28 and 53.6% at week 52. For reference, the American College of Rheumatology (ACR) 20 response rate was calculated for the patients who had assessable disease activity, who did not violate the study protocol, and who continued the study treatment at weeks 28 and 52. The rate was 46.9% at week 28 and 41.0% at week 52. To use iguratimod safely for a long time, patients should be observed closely for adverse reactions such as increased hepatic enzymes.

Efficacy and safety of tacrolimus (FK506) in treatment of rheumatoid arthritis: a randomized, double blind, placebo controlled dose-finding study.

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus (FK506) in patients with active rheumatoid arthritis (RA) exhibiting resistance to disease modifying antirheumatic drug (DMARD) therapy, and to determine the optimal dosage. METHODS: A total of 212 patients with DMARD-resistant RA were enrolled in this double blind, multicenter, randomized, placebo controlled study and allocated to 3 groups. Patients were administered tacrolimus at a dosage of 1.5 mg/day (68 patients) or 3 mg/day (70 patients), or placebo (74 patients), for 16 weeks. They were allowed to continue taking prednisolone (< or = 5 mg/day) and/or one nonsteroidal antiinflammatory drug (NSAID) during the study. Clinical assessment was based on the American College of Rheumatology (ACR) 20% criteria. RESULTS: ACR 20% response rates were higher in both tacrolimus groups (3 mg: 48.3%; 1.5 mg: 24.6%) than in the placebo group (14.1%), with the rate in the 3 mg group significantly higher. There were no significant differences between the tacrolimus groups and placebo group in the incidence of adverse events. The main adverse events in the tacrolimus groups, especially in the 3 mg group, were renal function abnormalities and gastrointestinal symptoms. However, no significant differences were observed among the 3 groups in the incidence of any adverse event except decrease in serum Mg level. CONCLUSION: Our findings demonstrate excellent dose-dependent efficacy of tacrolimus in patients with DMARD-resistant RA and strongly suggest the usefulness of tacrolimus for treatment of RA. The optimal dosage appears to be 3 mg/day in terms of efficacy and safety.

[The current status of infectious enteritis in Japan--reports of the "Research Group for Infectious Enteric Diseases, Japan" in the last 5 years (1996-2000)].

The patients or carriers with infectious enteritis admitted to the Hospitals for infectious diseases in the last 5 years (1996-2000) were studied. The total number of cases admitted in each year were 969, 1,113, 981, 637 and 573 respectively. A total of 1,527 Shigella spp. strains including 1,078 strains from overseas travelers' cases were isolated. The isolates of Salmonella spp. excluding S. Typhi and S. Paratyphi A were 562 in number. A total of 61 Vibrio cholerae O1 strains including 44 strains from overseas travelers was isolated. These V. cholerae O1 strains were all of El Tor type. Entamoeba histolytica, Giardia lamblia, Cryptosporidium parvum and Isospora belli were detected in 225, 46, 3 and 3 cases respectively. Abdominal pain, nausea and vomiting were frequently observed in the cases caused by Vibrio parahaemolyticus. The highest body temperature and the highest frequency of bowel movements were revealed in the cases caused by Salmonella spp. Bloody stool was observed in 55.3% of the cases due to Escherichia coli, in 40.5% of the cases due to Campylobacter spp. and in 24.1% of cases due to Shigella spp. As for shigellosis and salmonellosis, the clinical symptoms were more serious in the domestic cases than those in travelers. OFLX-resistant strains accounted for 1.7% of Shigella spp. isolates. No strains of Salmonella spp. were resistant to OFLX. The incidence of drug-resistant isolates of Campylobacter jejuni were 26.0% for OFLX and 2.5% for EM.