tacrolimus and bucillamine

Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) other than methotrexate (MTX: anchor csDMARDs) are effective for single use, reinforcement of MTX, biologics and induction and maintenance of biologics-free condition. Newly developed iguratimod (IGU) does not suppress immunological reaction, therefore, it is useful for single use or combination with other csDMARDs in patients with complications. IGU can be used as a first csDMARDs before MTX use during the screening for MTX. IGU might be effective for reinforcement of MTX, biologics and induction and maintenance of biologics-free condition just like other csDMARDs. IGU can be used in wide variety of situation of the treatment of rheumatoid arthritis and it is desired that after the all-case surveillance condition for approval, IGU become a standard csDMARDs all over the world which was made in Japan.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Chromones; Cysteine; Drug Discovery; Drug Interactions; Drug Substitution; Drug Therapy, Combination; Drugs, Generic; Female; Humans; Male; Ribonucleosides; Sulfasalazine; Sulfonamides; Tacrolimus

Disease-modifying antirheumatic drugs (DMARDs) have largely contributed to recent paradigm shift of rheumatoid arthritis (RA) treatment strategy. DMARDs can be indicated for all RA patients and early use of DMARDs after diagnosis of RA is recommended. Individual DMARDs have common characteristics. Understanding these characteristics is very important in treating RA. As for safety, the pattern of adverse reactions (ADRs) associated with DMARDs has been generally understood. It is necessary to select DMARDs and follow up patients with recognition of the pattern of ADRs. Regular monitoring is also essential to ensure the safety of DMARDs. This chapter deals with some major DMARDs in Japan, including methotrexate, which is indispensable in current RA treatment; salazosulfapyridine and bucillamine; tacrolimus, which is recently increasing in use; and iguratimod, which became available in 2012.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Cysteine; Humans; Japan; Methotrexate; Sulfasalazine; Tacrolimus

The primary goal in the treatment of rheumatoid arthritis (RA) is to maintain good quality of life by preventing joint destruction and avoiding disability. For this purpose, all patients with the diagnosis of RA should be treated by disease-modifying antirheumatic drugs (DMARDs) including biologic DMARDs and non-biologic DMARDs. All DMARDs are expected to prevent the progression of bone and cartilage destruction of RA patients from the results of in vitro research, and prevention of joint destruction is confirmed in vivo in all biologic DMARDs, but not in all non-biologic DMARDs. In this chapter, we would like to review the results of basic researches and clinical studies to demonstrate the prevention of joint destruction by non-biologic DMARDs that have been frequently used I daily practice.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Bone and Bones; Cartilage; Clinical Trials as Topic; Cysteine; Humans; Isoxazoles; Joints; Leflunomide; Methotrexate; Sulfasalazine; Tacrolimus

Because of a paradigm shift in the therapeutic strategy of RA by biologics, the goal of RA therapy became not only the clinical remission, but also the imaging remission. From the results of randomized controlled clinical trials of disease modifying anti-rheumatic drugs (DMARDs), decreased radiographic progression has been documented. In particular, methotrexate (MTX) is described as "anchor drug" of RA therapy because inhibitory effects of MTX on radiographic progression are proved by many clinical trials. Although DMARDs can slow down the radiographic progression with the achievement of clinical remission in RA, some patients still have subclinical synovitis detected by imaging technique. Such subclinical inflammation may explain the observed discrepancy between disease activity and radiographic progression in RA during DMARD therapy.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Cyclosporine; Cysteine; Disease Progression; Drug Therapy, Combination; Gold Sodium Thiomalate; Humans; Isoxazoles; Leflunomide; Methotrexate; Penicillamine; Radiography; Randomized Controlled Trials as Topic; Sulfasalazine; Tacrolimus

In this trial, we investigated the safety and efficacy of tacrolimus used in addition to standard antirheumatic drugs in patients with rheumatoid arthritis. Tacrolimus 3 mg or placebo was orally administered once daily for 52 weeks in a double-blind manner to patients with early active rheumatoid arthritis receiving other disease-modifying antirheumatic drugs (DMARDs). A total of 123 patients were randomized to the tacrolimus group (61 patients) and to the placebo group (62 patients). In the tacrolimus group, 70.5% achieved a clinical response according to American College of Rheumatology (ACR) 20 criteria, whereas 45.2% in the placebo group did so (P = 0.005). The tacrolimus group also showed significant improvement in terms of the European League Against Rheumatism (EULAR) response criteria of "good or moderate" versus the placebo group (86.9 vs. 56.5%, respectively). Likewise, significantly more patients in the tacrolimus group versus the placebo group achieved remission of the Disease Activity Score in 28 joints (DAS28) (45 vs. 21%). The mean changes in the Total Sharp Score and erosion score were lower in the tacrolimus group, but the differences between the two groups were not significant. There was no significant difference between the two groups in the incidence of adverse events. Based on these results, we can conclude that the additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to other DMARD treatments is useful, and this could become one of the treatment options for these rheumatoid arthritis patients.

Topics: Adult; Antirheumatic Agents; Arthritis, Rheumatoid; Cysteine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Joints; Male; Methotrexate; Middle Aged; Severity of Illness Index; Sulfasalazine; Tacrolimus; Treatment Outcome

To retrospectively evaluate the efficacy and safety of combination therapy with tacrolimus (TAC) and other disease-modifying antirheumatic drugs (DMARDs). One hundred fifteen rheumatoid arthritis (RA) patients treated with tacrolimus were enrolled in this retrospective analysis. We collected clinical information, including patient background, treatment efficacy (evaluated using the DAS score), and adverse events observed. Multiple logistic regression analysis was conducted to analyze factors contributing to clinical response and adverse effects. The disease activity score of 28 joints (DAS28) improved significantly at 24 weeks, and continuation rate at 1 year was 57.9%. There was no difference in continuation rate between different DMARD combinations, and not only methotrexate (MTX) but also bucillamine (BUC) and salazosulfapyridine (SSZ) were effective combination partners with TAC. No serious adverse events were observed, and no different inefficacy or safety was observed between non-elderly (<65 years old) and elderly (≥65 years old) RA patients. By conducting multiple logistic regression analysis, combination therapy with MTX and TAC, the number of baseline DMARDs (specifically, ≥3), and old age were identified as risk factors for adverse events. Our findings indicate that TAC is a valuable DMARD for second-line combination therapy in RA.

Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Cysteine; Disease Progression; Drug Therapy, Combination; Female; Humans; Male; Methotrexate; Middle Aged; Retrospective Studies; Risk Factors; Severity of Illness Index; Sulfasalazine; Tacrolimus; Treatment Outcome

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Cysteine; Female; Humans; Methotrexate; Sulfasalazine; Tacrolimus