Kojiro Sato

Objectives: The effects of HCQ dose based on actual body weight (ABW) on SLE remain unclear. We investigated the effects of HCQ dose based on ABW of patients with SLE. Methods: Patients were classified into ≥5 mg/kg ABW [high dose (HD)] and <5 mg/kg ABW [low dose (LD)] groups. Patient backgrounds were adjusted using inverse probability of treatment weighting method. The discontinuation rate owing to adverse events of overall cohort (group 1) was evaluated. Subgroups with a disease duration ≥1 year (group 2) and without additional immunosuppressive agents and biologics after HCQ initiation (group 3) were compared with evaluated flare rates, prednisolone dose and serological data. Results: Among 182 patients in group 1, 60 (33%) comprised the HD group. Five-year discontinuation rates were 18.9% and 13.6% in the HD and LD groups, respectively (P = 0.314). Three-year flare-free rates in HD group were higher than those in LD group: 75.0% (HD) vs 60.7% (LD) (P = 0.239) in group 2, and 79.2% (HD) vs 57.8% (LD) (P = 0.141) in group 3. In group 3, each 0.2 mg/kg increase in the HCQ dose reduced flares (hazard ratio 0.91; 95% CI 0.84–0.99). Conclusion: No clear differences in efficacy and safety were observed between the HD and LD groups; however, a higher HCQ dose was associated with a reduced flare risk. Our findings suggest that a lower HCQ dose may be associated with a higher flare risk in patients with SLE, highlighting the importance of HCQ dose based on ABW.

Full Papers; Authors: Y. Kamata, H. Kusaka, S. Yamamoto, C. Hayashi, T. Sato, K. Sato

Aim: This study aimed to evaluate the predictive value of serum humoral factors in determining the therapeutic responses to biologic DMARDs (bDMARDs), especially TNF inhibitors (TNFis), in patients with RA.Methods: A cohort of 52 patients with RA who were treated with bDMARDs, including TNFis, abatacept, and tocilizumab, was analyzed. Serum samples were collected at baseline (t1), 5 ± 1 (t2), and 14 ± 2 weeks (t3) after treatment. A bead‐based immunoassay was used to quantify serum cytokines/chemokines. Treatment response was determined 1 year after initiation.Results: Distinct patterns of IL‐6 behaviors were observed among different bDMARDs. Patients exhibiting IL‐6 rebound at 14 weeks were more likely to be non‐responders to TNFi after 1 year, and this rebound appeared to be associated with increases in IFN‐γ and IL‐12 levels. IFN‐β was more detectable than IFN‐α2 in RA. Additionally, patients with measurable IFN‐β at baseline tended to be TNFi responders.Conclusion: Monitoring serum humoral factors may offer valuable insights into the likelihood of therapeutic success of TNFi in patients with RA. IL‐6 rebound at 14 weeks might serve as an early indicator of non‐responsiveness to TNFi. These findings highlight the potential of personalized treatment strategies for RA based on serum humoral factor profiling. Larger prospective studies are needed to validate these results and elucidate the underlying mechanisms.

During osteoclast differentiation, the expression of the transcription factor nuclear factor of activated T cell 1 (Nfatc1) increases in an autoproliferative manner. Nfatc1 isoforms are of three sizes, and only the short isoform increases during osteoclast differentiation. Genetic ablation of the whole Nfatc1 gene demonstrated that it is essential for osteoclastogenesis; however, the specific role of the Nfatc1 short form (Nfatc1/αA) remains unknown. In this study, we engineered Nfatc1 short form-specific knockout mice and found that these mice died in utero by day 13.5. We developed a novel osteoclast culture system in which hematopoietic stem cells were cultured, proliferated, and then differentiated into osteoclasts in vitro. Using this system, we show that the Nfatc1/αA isoform is essential for osteoclastogenesis and is responsible for the expression of various osteoclast markers, the Nfatc1 short form itself, and Nfatc1 regulators.

Full Papers; Authors: A. Kokuzawa, J. Nakamura, Y. Kamata, K. Sato

Full Papers; Authors: Y. Aizaki, H. Yazawa, K. Sato, T. Mimura

Aim The use of an immunosuppressant is recommended as a treatment for remission induction in anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV). However, the immunosuppressant is sometimes discontinued due to an adverse event. We sought to identify the cause and risk factors for immunosuppressant discontinuation in patients with AAV receiving remission induction treatment. Methods We retrospectively analyzed the cases of AAV patients treated in 2005‐2016 with immunosuppressants to induce remission. We defined “discontinuation” as stopping, switching, or delaying immunosuppressant administration due to adverse events. We performed a multivariate analysis to identify risk factors for immunosuppressant discontinuation. Results We identified 50 patients treated with an immunosuppressant for remission induction: cyclophosphamide was used in 45 patients (90%), methotrexate in 4 (8%), and cyclosporine A in 1 patient (2%). Among them, 26 patients (52%) underwent discontinuation of the immunosuppressant. Infection and myelosuppression were the major causes of discontinuation. Multivariate Cox proportional hazards regression analysis revealed that a cumulative dose of prednisolone ≥ 2000 mg (hazard ratio [HR] =2.18, 95% confidence interval [CI] =1.37‐3.70, P < .001), performance status of 3‐4 (HR = 1.80, 95% CI = 1.07‐3.03, P = .027), and oral cyclophosphamide (HR = 1.81, 95% CI = 1.11‐2.97, P = .018) were independent risk factors correlated with immunosuppressant discontinuation. Conclusion Physicians should be aware of risk factors predicting immunosuppressant discontinuation when treating AAV patients with an immunosuppressant.