Expansion of P-gpCXCR4 B cells seems to be associated with drug resistance, disease activity and progressive destructive arthritis with extra-articular involvement in RA.

Background Mepolizumab (MPZ), an anti-interleukin-5 antibody, is effective for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). However, its effectiveness has not been adequately evaluated in real-world clinical practice. In this study, we assessed the effectiveness and safety of MPZ (300 mg) for relapsing/refractory EGPA resistant to corticosteroids (CS) for 1 year in real-world settings. Methods We administered MPZ (300 mg) to 16 patients with relapsing/refractory EGPA resistant to CS (Post-MPZ). We also retrospectively collected data from the same patients for the 12 months before the administration of MPZ (Pre-MPZ). The primary endpoint was the 12-month remission rate after MPZ administration and the secondary endpoints were the Birmingham vasculitis activity score (BVAS), vasculitis damage index (VDI), eosinophil counts, changes in concomitant CS doses/concomitant immunosuppressant use, MPZ retention rate, and incidence of adverse events. The clinical course was compared between Pre-MPZ and Post-MPZ. Results The 12-month remission rate after the initiation of MPZ was 75%. No change was observed in BVAS, eosinophil count, or concomitant CS dose over time in the Pre-MPZ group, whereas all these parameters were significantly decreased over time in the Post-MPZ group. The number of patients using concomitant immunosuppressant also decreased over time in the Post-MPZ group. VDI did not increase in either group. The MPZ retention rate was 100% and only three patients (18.8%) had infections. Changes in BVAS, eosinophil count, and cumulative concomitant CS dose were significantly lower in the Post-MPZ group than in the Pre-MPZ group. There was no significant difference in the changes in VDI between the groups. Conclusion This study demonstrated that MPZ is effective and safe for EGPA. Furthermore, MPZ decreases disease activity, increases remission rate, and has a CS-sparing effect.

Background Tumor necrosis factor (TNF) inhibitors (TNF-i) are effective in the treatment of entero-Behcet’s disease (BD). However, there is no objective tool for assessment of disease activity in entero-BD; therefore, it is not easy to evaluate treatment effectiveness in the clinical setting. In addition, because corticosteroid (CS) is considered for standard therapy, the effectiveness of TNF-i without CS has not been well examined. In this retrospective study, the effectiveness of CS without TNF-i and the effectiveness of TNF-i with or without CS therapy were investigated and compared. Methods This study included 71 patients with entero-BD who were followed up for 1 year (CS without TNF-i group: n = 22; TNF-i group: n = 49 [with CS: n = 20, without CS: n = 29]). All patients had active ulcerative lesions. The primary endpoint was the ulcer cure rate evaluated by lower gastrointestinal endoscopy. Secondary endpoints were ulcer improvement rate, disease activity improvement based on the quantitative disease activity index for intestinal Behcet’s disease (DAIBD), and CS-sparing effect. Results Ulcer cure rates were 13.6% in the CS without TNF-i group, 60.0% in the TNF-i with CS group, and 44.8% in the TNF-i without CS group. Ulcer improvement rates were 27.2% in the CS without TNF-i group, 60.0% in the TNF-i with CS group, and 51.7% in the TNF-i without CS group. The multivariate analysis revealed that TNF-i was an independent predictive factor for cure of the ulcerative lesions. The DAIBD and concomitant CS dose were significantly decreased in both the CS without TNF-i group (DAIBD 85.2 → 40.5, CS 32.3 → 18.7 mg/day) and the TNF-i group (DAIBD 64.7 → 21.1. CS 18.7 → 3.88 mg/day). The ulcer cure and improvement rates were significantly higher in the TNF-i group. In addition, the proportion of concomitant CS dose less than 7.5 mg was significantly higher in the TNF-i group (CS without TNF-i group 18.2% vs. TNF-i group 85%, P < 0.01). There were no statistically significant differences between the TNF-i with CS group and the TNF-i without CS group in any of the endpoints. Conclusions This study demonstrated that compared to CS alone, TNF-i improve disease activity and possess a higher ulcer healing effect and CS tapering effect with or without concomitant CS.

Background: The effectiveness and safety of biological disease-modifying antirheumatic drugs (bDMARDs) by age group (< 65, 65-74, and ≥ 75 years) are uncertain. We examined retention rates reflecting the effectiveness and safety of bDMARDs in actual clinical practice for clarifying optimal therapeutic strategies for rheumatoid arthritis (RA) by age groups. Methods: Data of patients who were treated with tumor necrosis factor inhibitors (TNFi), abatacept (ABA), and tocilizumab (TCZ) between February 2011 and April 2017 were collected from a prospective observational registry of RA patients. A total of 1362 patients were enrolled, of which 695 were aged < 65 years, 402 were aged 65-74 years, and 265 were aged ≥ 75 years. Primary outcome was the drug retention rate in adjusted data using inverse probability of treatment weighting based on generalized propensity scores. Results: In patients aged < 65 years, 3-year retention rates of TNFi, ABA, and TCZ were 43%, 47%, and 69%, respectively (ABA versus TCZ, p = 0.017; TNFi versus TCZ, p = 0.002). In patients aged 65-74 years, 3-year retention rates of TNFi, ABA, and TCZ were 44%, 53%, and 60%, respectively (TCZ versus TNFi, p = 0.034). In patients aged ≥ 75 years, 3-year retention rates for TNFi, ABA, and TCZ were 38%, 63%, and 58%, respectively (ABA versus TNFi, p = 0.017). Conclusions: We found that the effectiveness and safety of TCZ were maximal in patients aged < 75 years and that patients aged ≥ 75 years might be suitable candidates for TCZ and ABA therapy. The use of therapeutic strategies appropriate to each age group might improve the outcomes of bDMARD therapy for RA.

Objectives The efficacy of belimumab (BEL) during maintenance therapy in patients with systemic lupus erythematosus (SLE) remains unclear in the real-life clinical setting. This study investigated the efficacy and safety of BEL in patients with SLE during maintenance therapy. Methods In this retrospective observational study, maintenance therapy was defined as low-dose glucocorticoid (GC) therapy (prednisolone equivalent dose of ≤ 0.2 mg/kg/day) in patients with a Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score &lt;10. Participants comprised patients with SLE on hydroxychloroquine or mycophenolate mofetil (standard-of-care [SoC] group: n = 103) and those on BEL plus SoC (BEL+SoC group: n = 100). Selection bias was minimised using propensity score-based inverse probability of treatment weighting (IPTW). GC dose trajectories were modelled using growth mixture modelling (GMM). The primary endpoint was GC dose at 52 weeks. Results No significant difference was observed in patient characteristics between the two groups after IPTW adjustment. The BEL+SoC group exhibited a significant decrease in GC dose. GC dose at 52 weeks and relapse rate were significantly lower in the BEL+SoC group than in the SoC group. The proportion of patients in one of four groups defined by GMM for which GC dose was tapered to 0 mg within 52 weeks (GC tapering-discontinuation group) was significantly higher in the BEL+SoC group than in the SoC group. In the BEL+SoC group, low SELENA-SLEDAI score and low GC dose at baseline were associated with being GC dose-tapering discontinuation. Conclusion The present study suggests that BEL is suitable for patients with SLE during maintenance therapy.