Efficacy and Safety of Mizoribine by One Single Dose Administration for Patients with Rheumatoid Arthritis

Abstract

Objective Mizoribine (MZR) is an immunosuppressant that inhibits nucleic acid metabolism and is a relatively safe disease-modifying anti-rheumatic drug (DMARD). We evaluated the efficacy and safety of one single dose per day for patients with rheumatoid arthritis (RA). Patients and MethodsIn this study 32 patients with RA received MZR therapy. We evaluated the average dose of MZR and prednisolone, response to treatment and peak plasma level of MZR. Results The average dose of MZR was 146.1±31.2 (range: 50-200) mg/day. The average dose of prednisolone was 4.63±3.59 (range: 0-14) mg/day. The average plasma level of MZR, measured after 3 hours, was 2.20±0.49 μg/mL in the responder group and 1.59±0.82 μg/mL in the non-responder group (p=0.020). The treatment with MZR for 24 weeks was completed by 71.9% of patients and the proportion of patients who achieved a good and moderate response rate according to the European League Against Rheumatism (EU-LAR) criteria was 56.3% at 24 weeks. The plasma level of MZR which was greater than or equal to 2.12 μg/ mL was significantly correlated with the clinical response (p<0.01). Only one of thirty-two cases discontinued the treatment, because of skin eruption. Conclusion This study included patients that could not be treated with other DMARDs and/or biologic agents because of age, interstitial pneumonia and other complications. We show that MZR may be a useful and relatively safe therapy for patients in this group.

Stimulation of human TRPA1 channels by clinical concentrations of the antirheumatic drug auranofin

“…Using these HEK-TRPA1 cells, we examined the effects of nine DMARDs on TRPA1. According to the literature (7,9,11,16,17,26,34,37,40), DMARDs except AUR and CPP were applied at concentrations of 3 and 30 M. AUR and CPP were also applied at relatively lower concentrations (1 and 10 M). As shown in the representative time series plots (Fig.…”

A case of microscopic polyangiitis in an elderly patient presenting predominantly with cholecystitis successfully treated with mizoribine

“…Previous studies suggested that the peak plasma level of MZR is important for the clinical efficacy of this drug [16,17]. In patients with rheumatoid arthritis, the peak plasma level of MZR correlated with the clinical response-even those of elderly patients [2]. MZR inhibits human mixed-lymphocyte reaction with 50 % inhibition at a concentration of approximately 1 lg/mL [3].…”

“…MZR also has been approved in Japan for the treatment of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and nephrotic syndrome and immunoglobulin A (IgA) nephropathy [2]. MZR inhibits human mixed-lymphocyte reaction with 50 % inhibition at a concentration of approximately 1 lg/mL [3].…”

Chronopharmacology of Mizoribine in Collagen-Induced Arthritis Rats

“…To measure CRP levels, blood was taken at different times (2,6,10,14,18, or 22 h after the light was turned on (HALO) in CIA (n = 6) rats. Blood was collected from the tail vein on day 20 after the first immunization when arthritis showed in all rats.…”

“…In recent years, MZR has been used as a drug against autoimmune diseases such as rheumatoid arthritis (RA) and lupus nephritis because it has immunosuppressive and anti-inflammatory effects (4,5). In clinical studies, MZR shows antirheumatic effects in RA patients (6,7). It was thought that MZR had higher safety than other antirheumatic drugs, whereas its efficacy was inferior.…”