Leukocytapheresis (LCAP) is already being used in a clinical setting for the treatment of autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis, and it has been reported to be effective. However, it is totally or partially ineffective in some patients, which has forced clinicians to rethink therapeutic strategies and concurrent treatment. With the aim of enhancing the therapeutic effect, we carried out large volume leukocytapheresis, with a throughput of 5000 mL instead of the 3000-mL throughput of conventional leukocytapheresis in nine patients with rheumatoid arthritis resistant to methotrexate treatment. Using Cellsorba, the column filled with the unwoven fabric made of the polyethylene phthalate, a leukocyte removal filter, large volume leukocytapheresis was carried out once a week for a total of five sessions. The observation period was the 12-week period following completion of treatment. The American College of Rheumatology (ACR) core set was used for assessment of efficacy. Eight weeks after completion of treatment, a 20% improvement in ACR was observed in 77.8% (7/9) of subjects, a 50% improvement in ACR was seen in 55.6% (5/9) of subjects, and a 70% improvement in ACR was observed in 22.2% (2/9) of subjects. C-reactive protein decreased gradually as treatment progressed, and a significant decrease was observed 4 weeks after completion of treatment. The fact that some subjects had an ACR70 response, few reports of which are observed in the case of conventional leukocytapheresis, and the fact that the effect continued up to 12 weeks after completion of treatment suggests that the degree and duration of the effect of large volume leukocytapheresis might be longer than those of conventional leukocytapheresis.

Based on sporadic reports indicating that the effectiveness of leukocytapheresis (LCAP) is proportional to the number of leukocytes removed, it is anticipated that increasing the volume of blood treated, and thus the number of leukocytes removed, will improve the effectiveness of therapy. In advance of its clinical application, the possible clinical usefulness of large volumes of LCAP (pulse LCAP), which treats 5000 mL of blood rather than the usual volume of 3000 mL, was investigated in healthy subjects. As compared with conventional LCAP, pulse LCAP provided comparable safety and enabled the removal of approximately 4.7 times more neutrophils, 1.2 times more lymphocytes, and 1.6 times more monocytes. It also resulted in a more pronounced overshoot phenomenon, as well as lymphocyte and monocyte overshoot, which are not seen with conventional LCAP. The neutrophil overshoot resulted from the recruitment of leukocytes from the bone marrow neutrophil pool as well as from the circulating neutrophil pool and marginal neutrophil pool. Recruitment from the bone marrow pool involved not only recruitment of mature neutrophils but also recruitment from all stages of differentiation and proliferation, including the pluripotent stem cell (CFU-GEMM) fraction; granulocyte-monocyte precursor cell (CFU-GM) fraction; and the fraction of juvenile granulocyte precursors cells capable of cell division, from myeloblasts to myelocytes. Based on the lymphocyte and monocyte overshoot, it was inferred that cells were recruited from mucosal lymphatic tissue, in addition to the lymph nodes, spleen, thymus, and bone marrow. These phenomena might play an important role in the mechanism that underlies the effectiveness of LCAP and the increased effectiveness of pulse LCAP, and it will be necessary to work to elucidate them. Moreover, it appears that investigating the clinical efficacy of pulse LCAP in patients who do not respond to conventional LCAP would be of major significance.

Our results suggest that autofeedback from US assessment provides quick improvement in palpation skills for identifying joint swelling in patients with RA.

Elderly patients with RA receive less aggressive treatment than nonelderly patients with RA, despite laboratory evidence for poorly controlled disease status among the elderly. The use of a less aggressive regimen could be attributed to the higher prevalence of complications and problems. Therefore, the elderly with RA should be considered a different patient population from the viewpoint of treatment and be administered specialized medical care.

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.