Comparison of anti-IL-6 receptor and JAK inhibitors in patients with rheumatoid arthritis from the real-world practice FIRST study.

OBJECTIVES: A molecular-targeted drug that is suitable as the second choice for patients with rheumatoid arthritis (RA) who show an inadequate response to the first biological disease-modifying antirheumatic drug (bDMARD) is unknown. This study aimed to analyze the efficacy and safety of interleukin-6 receptor (IL-6Ri) and Janus kinase inhibitors (JAKis), often selected as molecular-targeted drugs for second or subsequent treatments. METHODS: The efficacy and safety of JAKis and IL-6Ri were compared using propensity score-based inverse probability of treatment weighting (PS-IPTW) using propensity scores after 26 weeks of therapy in patients with RA. RESULTS: The remission rate at week 26, determined by the clinical disease activity index (CDAI), and the incidence of infection were higher in the JAKis than in the IL-6Ri group. The CDAI trajectories were divided into four according to the growth mixture modeling. IL-6Ri demonstrated greater efficacy in RA patients with ineffective to single bDMARD therapy compared with those with multiple ineffective bDMARDs. In patients who failed to respond to one bDMARD, there was no significant difference in the CDAI remission rate at week 26 between the JAKis (29.1%) and IL-6Ri (21.8%) groups (p= 0.21). However, for patients who did not respond to at least two bDMARDs, the CDAI remission rate at week 26 was higher in the JAKis than in the IL-6Ri group. CONCLUSIONS: IL-6Ri offers a superior balance of efficacy and safety compared with JAKis for RA patients unresponsive to one bDMARD. However, JAKis may suit patients who do not respond to multiple bDMARDs.

Biological/targeted synthetic DMARDs do not arrest bone loss in patients with rheumatoid arthritis: a multicenter prospective observational study.

OBJECTIVE: To elucidate the differential effects of biological/target synthesized DMARDs (b/tsDMARDs) on bone metabolism in patients with rheumatoid arthritis (RA) in a real-world cohort. METHODS: This was a multicentre prospective observational study of RA patients enrolled at the time of 1st b/tsDMARDs administration. Bone mineral density (BMD) and bone turnover markers (BTMs) were measured during the 52-week observation. The study was designed to enrol all eligible RA patients. The end-points were differences in changes in BMD according to b/tsDMARD type, and the correlation between BMD and BTMs. RESULTS: A total of 1,164 patients were enrolled in this study. b/tsDMARDs improved RA disease activity from mean CDAI 25.5 at baseline to 4.5 at week 26. Patients not receiving anti-osteoporotic agents (anti-OP) at baseline with no history of fracture experienced a significant decrease in both femoral neck (F: mean 0.666-0.655 g/cm3) and radial (R: 0.518-0.514) BMD at week 26. Despite maintaining low CDAI levels during weeks 26-52 (5.3-4.4), there was a continued decline in BMD (F: 0.653, R: 0.509. Weeks 52). None of b/tsDMARDs type preserved BMD. Conversely, patients receiving anti-OP at baseline maintained stable BMD throughout the study (Weeks 0/26/52. F: 0.551/0.551/0.555, R: 0.415/0.416/0.415). Although BTMs were changed by b/tsDMARDs, the changes were unrelated to those in BMD. CONCLUSION: Our study suggested the progression of osteoporosis in RA patients during b/tsDMARDs treatment without anti-OP. BTMs may not reflect BMD change. Regular monitoring of BMD in RA should be considered for early management of osteoporosis.

Safety and efficacy of anifrolumab therapy in systemic lupus erythematosus in real-world clinical practice: LOOPS registry.

OBJECTIVES: To determine the safety and efficacy of anifrolumab in patients with systemic lupus erythematosus (SLE) classified based on the Lupus Low Disease Activity State (LLDAS) in real-world clinical practice. METHODS: This retrospective observational study involved SLE patients who started anifrolumab therapy. The primary end point was the retention rate over 26 weeks after initiating anifrolumab therapy; 45 patients followed up for 12 weeks or longer were analyzed in the following groups to determine the safety and efficacy up to week 12 after treatment initiation: 1) non-LLDAS achievement group and 2) minor flare group. Safety and efficacy were compared between the minor flare group and the standard of care (SoC) group (treated by adding glucocorticoids (GCs) or immunosuppressants) after adjustment with inverse probability of treatment weighting using propensity score (PS-IPTW). RESULTS: The retention rate of anifrolumab was 89.7% at week 26.The LLDAS achievement rates at week 12 were 42.9% and 66.7% in the non-LLDAS achievement and minor flare groups, respectively. In both groups, GC doses and SELENA-SLEDAI score significantly decreased. When the anifrolumab group with minor flare was compared with the SoC group or the GC dose increase group, the GC dose and SLEDAI score were significantly lower in the anifrolumab group than in both groups; there was no significant difference in LLDAS achievement. CONCLUSIONS: At week 26 after initiating anifrolumab therapy, ∼90% patients remained on therapy. Anifrolumab might lower disease activity without initiating GCs and reduce GC doses, especially in patients who experience minor flares after LLDAS achievement.

Generation-Dependent Retention Rates and Reasons for Discontinuation of Molecular Targeted Therapies in Patients with Rheumatoid Arthritis: From FIRST Registry.

INTRODUCTION: The study aimed to optimize medical care for elderly patients with rheumatoid arthritis (RA) by examining the 3-year continuation rate of different molecular targeted therapies across age groups in Japan, which has a significant elderly population. METHODS: The study included patients with RA who started molecular targeted therapies between 2013 and 2019 and divided them into three age groups. The primary outcome was to assess the 3-year continuation rate of each drug and analyze reasons for treatment discontinuation using inverse probability of treatment weighting. RESULTS: Among 2292 patients analyzed, tumor necrosis factor (TNF) inhibitors were most commonly used in those younger than 65 years of age (43.5%), while Janus kinase (JAK) inhibitors were also utilized (17.1%). In contrast, JAK inhibitors were less frequently used in patients aged 75 years and older (7.8%), with cytotoxic T lymphocyte antigen 4 immunoglobulin fusion proteins (CTLA4-Ig) being the most common (39.2%). JAK inhibitors and anti-interleukin-6 receptor (IL-6R) antibodies had higher continuation rates than other drugs in patients under 65 years (p < 0.001). For those aged 65-74 years, JAK inhibitors and CTLA4-Ig had higher continuation rates (p < 0.001), while among those aged 75 years and older, CTLA4-Ig and IL-6R antibodies had higher continuation rates (p < 0.001). Inadequate efficacy was the main reason for discontinuation in all age groups, while infection leading to discontinuation increased with age. CONCLUSIONS: The study highlights the need to consider different age groups separately in elderly RA care. Among patients aged 75 years and older, abatacept and anti-IL-6R antibodies showed the highest continuation rates, suggesting their potential suitability and efficacy for this specific age cohort.

Efficacy and safety of guselkumab and adalimumab for pustulotic arthro-osteitis and their impact on peripheral blood immunophenotypes.

OBJECTIVES: We compared the treatment effectiveness between guselkumab and adalimumab in patients with pustulotic arthro-osteitis (PAO). In addition, we performed peripheral blood immunophenotyping to elucidate the immunological background and analyzed the impact of therapeutic drugs to verify the validity of immunological phenotypes as therapeutic targets. METHODS: Patients were treated with guselkumab 100 mg (guselkumab group; n = 12) and adalimumab 40 mg (adalimumab group; n = 13). Arthritis disease activity, skin lesion activity, and patient-reported outcomes (PROs) were evaluated and compared between the two groups. The retention rate and adverse events were evaluated. Comprehensive phenotyping of peripheral immune cells was performed in both groups, and phenotypes were compared before and after treatment. RESULTS: At 6 months, both groups showed significant improvement in arthritis disease activity and PROs. In the guselkumab group, skin symptoms significantly improved. The 6-month continuation rates were 91.7% (11/12) and 69.2% (9/13) in the guselkumab and adalimumab groups, respectively. Adverse events occurred in 2/12 and 5/13 patients in the guselkumab (16.7%) and adalimumab (38.5%) groups, respectively. Peripheral blood immunophenotyping showed that the proportion of activated T helper (Th) 1 cells was significantly lower in patients with PAO than in healthy controls and that the proportion of activated Th17 cells was significantly higher in patients with PAO, which significantly decreased after treatment with guselkumab. CONCLUSION: Although guselkumab and adalimumab have comparable efficacy for PAO, their impact on immunophenotypes varies.

Safety and effectiveness of mepolizumab therapy in remission induction therapy for eosinophilic granulomatosis with polyangiitis: a retrospective study.

OBJECTIVES: To investigate the safety and effectiveness of mepolizumab (MPZ), an anti-interleukin-5 antibody, as remission induction therapy for severe eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: The clinical courses of patients with severe EGPA over 6 months were retrospectively investigated and compared between patients treated with high-dose corticosteroid (CS) plus MPZ therapy (MPZ group, n = 7) and those treated with high-dose CS plus intravenous cyclophosphamide (IVCY) pulse therapy (IVCY group, n = 13). The primary endpoints were the MPZ retention rate and the IVCY completion rate. The secondary endpoints were adverse events and changes in the Birmingham Vasculitis Activity Score (BVAS), Vascular Damage Index (VDI), eosinophil counts, and concomitant CS doses, and the extent and rates of these changes were compared between the MPZ and IVCY groups. RESULTS: Regarding the primary endpoints, the MPZ retention rate was 100%, and the IVCY completion rate was 61.5%. Regarding the secondary endpoints, adverse events were detected in 2/7 patients (28.6%) in the MPZ group and 7/13 patients (53.8%) in the IVCY group. BVAS and eosinophil counts significantly decreased in both groups at and after month 1, but there was no significant difference in the magnitude of changes between the two groups. VDI scores did not significantly increase in either group, and the degree of changes did not significantly differ between the two groups. Although concomitant CS doses significantly decreased at and after month 1 in both groups, the rates of decrease in CS doses at and after month 3 were significantly higher in the MPZ group. CONCLUSIONS: This study suggested that the use of MPZ as remission induction therapy for severe EGPA might be safe and effective for controlling disease activity and reducing CS doses.

Eosinophilic granulomatosis with polyangiitis exhibits T cell activation and IgG4 immune response in the tissue; comparison with IgG4-related disease.

OBJECTIVE: To study the pathophysiological differences of EGPA and IgG4-related disease (RD) by clarifying their clinical, pathological and immunological features. METHODS: Clinical and pathological findings were compared in patients with EGPA and IgG4-RD. Peripheral blood mononuclear cells were used for comprehensive flow cytometric analysis. RESULTS: An elevation of the IgG4 level was found in all EGPA cases, with the accompanying pathological findings of lymphocytic infiltration and fibrosis observed in 30.8% patients, and the elevation of IgG4/IgG ratio in 61.5% patients. However, actual IgG4 levels, as well as the degree of the infiltration of IgG4-positive plasma cells, were still higher in patients with IgG4-RD than patients with EGPA. Examination by ACR/EULAR classification criteria showed only 13.6% of the EGPA patients met entry criteria, while all of them met the exclusion criteria. In regard to the immunophenotyping, EGPA patients had increases in activated CD4 and CD8 T cells compared with the healthy controls. However, no such similar changes occurred in IgG4-RD patients. On the other hand, both the EGPA and IgG4-RD patient groups had correlated increased plasmablasts and Tfh. These results indicate the presence of two axes: namely, the activation of T cells and that of B cells. Both axes are present in EGPA, but the T cell activation axis was not observed in IgG4-RD. CONCLUSIONS: The elevation of serum IgG4 as well as pathological IgG4 infiltration are not specific. Meanwhile, EGPA and IgG4-RD differ in immunological phenotypes, indicating the possible importance of the predominant activation of T cells in the development of vasculitis.

Nailfold microvascular abnormalities are associated with a higher prevalence of pulmonary arterial hypertension in patients with MCTD.

OBJECTIVE: MCTD manifests with microvasculopathy and overlapping clinical features of SLE, SSc and idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the clinical significance of microvasculopathy in patients with MCTD using nailfold videocapillaroscopy (NVC). METHODS: Fifty patients with newly diagnosed and untreated MCTD were enrolled in this multicentre, prospective and observational study. Clinical features and NVC findings were assessed at baseline and after 1 year post-intervention, along with disease controls [SLE (n = 40), SSc (n = 70) and IIM (n = 50)]. RESULTS: All MCTD patients presented Raynaud's phenomenon and were positive for anti-U1 RNP antibodies, and 22.0% (11/50) had pulmonary arterial hypertension (PAH). The prevalence of NVC scleroderma patterns in MCTD was 38.0%, which was lower than SSc (88.6%) but higher than SLE (10.0%). In addition, when we divided MCTD patients into two groups by presence or absence of NVC scleroderma patterns, we found a higher prevalence of PAH in patients with NVC scleroderma patterns. Namely, NVC scleroderma patterns were observed in all MCTD patients with PAH, and in 21.0% of those without PAH. After intensive immunosuppressive therapy, NVC scleroderma patterns disappeared in half of the MCTD patients but were not changed in SSc patients. CONCLUSIONS: MCTD differed from SLE, SSc and IIM in terms of the prevalence and responsiveness of NVC scleroderma patterns to immunosuppressive therapy. Detection of nailfold microvascular abnormalities in MCTD could contribute to predicting PAH and help us to understand further aspects of the pathogenesis of MCTD.

Efficacy and safety of belimumab during maintenance therapy in patients with systemic lupus erythematosus.

OBJECTIVES: The efficacy of belimumab (BEL) during maintenance therapy in patients with 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 <10. Participants comprised patients with SLE on HCQ or MMF [standard-of-care (SoC) group: n = 103] and those on BEL plus SoC (BEL+SoC group: n = 100). Selection bias was minimized using propensity score-based inverse probability of treatment weighting (IPTW). GC dose trajectories were modelled using growth mixture modelling (GMM). The primary end point 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.

Efficacy and safety of high-dose of mycophenolate mofetil compared with cyclophosphamide pulse therapy as induction therapy in Japanese patients with proliferative lupus nephritis.

OBJECTIVES: To clarify the effectiveness and safety of induction therapy with mycophenolate mofetil (MMF) in patients with lupus nephritis (LN). METHODS: Patients with LN administered MMF (n = 35) or intravenous cyclophosphamide pulse therapy (IVCY) (n = 25) plus high-dose corticosteroids between July 2015 and June 2020 were included. MMF was increased from 2 to 3 g/day, with no adverse events (AEs). The primary endpoint was the 6 month renal remission rate. Secondary endpoints were retention rate and AEs. RESULTS: There were no significant differences in age, sex, disease duration, renal histological type, SLE disease activity index, and urine protein creatinine ratio between the two groups. Twenty-six patients (74%) continued with MMF therapy, whereas 12 (48%) completed six IVCY courses. The retention rate was significantly higher in the MMF than in the IVCY group (p = 0.048). Twenty-four and 14 patients in MMF and IVCY groups, respectively, achieved renal remission with insignificant differences. Grade 3 or higher AEs were observed in 8 and 14 patients in the MMF and IVCY groups, respectively (p = 0.014). CONCLUSIONS: The efficacy of high-dose MMF was comparable to that of IVCY in Japanese patients with proliferative LN, with fewer AEs and a higher retention rate than IVCY, suggesting the high tolerability of MMF.

Serum TNFα levels at 24 h after certolizumab pegol predict effectiveness at week 12 in patients with rheumatoid arthritis from TSUBAME study.

OBJECTIVE: To estimate the relationship between serum TNFα, IL-6, and serum CZP levels and the clinical response to CZP in RA patients in the TSUBAME study. METHODS: One hundred patients with RA who received CZP were enrolled and multiple clinical parameters, serum TNFα, IL-6, and CZP levels, were assessed at 0, 24, and 48 h and 12 weeks after first administration of CZP. RESULTS: The CZP therapy significantly improved the DAS28(ESR) at 12 weeks. Serum TNFα and IL-6 levels significantly decreased from baseline at 24 h after the first administration of CZP. Serum TNFα levels at baseline were not related to clinical parameters at baseline and improvement in DAS28(ESR) at week 12 of the CZP therapy. However, serum levels of CZP at 24 h were strongly and negatively correlated with TNFα levels at 24 h, which were negatively correlated with improved rate in DAS28(ESR) at week 12. Only serum levels of TNFα, but not IL-6, at 24 h had a negative correlation with achievement of DAS28(ESR)<2.6 at week 12 by the multivariate analysis (odds ratio 0.01, 95% confidence interval 0.04e-2-0.22, p < 0.01). A receiver operating characteristic analysis was conducted to estimate the achievement of DAS28(ESR)<2.6 at week 12 after the CZP therapy and cut-off value of 0.76 pg/ml for serum levels of TNFα at 24 h was yielded (area under the curve=0.75). DAS28(ESR)<2.6 was achieved at week 12 significantly more patients with lower serum TNF levels (≦0.76 pg/ml) at 24 h than those with higher TNF levels. CONCLUSIONS: CZP was highly effective in RA patients who had low serum TNFα levels at 24 h after the initial administration of CZP. Therefore, we propose that serum TNFα levels at 24 h could serve as a biomarker predicting effectiveness to CZP at week 12 in patients with RA. TRIAL REGISTRATION: Clinical trial registration number: UMIN ID:000022831.

Effectiveness and safety of mepolizumab in combination with corticosteroids in patients with eosinophilic granulomatosis with polyangiitis.

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.

Clinical aspects in patients with rheumatoid arthritis complicated with lymphoproliferative disorders without regression after methotrexate withdrawal and treatment for arthritis after regression of lymphoproliferative disorders.

OBJECTIVES: To identify predictive factors for lymphoproliferative disorders (LPDs) that persist after methotrexate (MTX) withdrawal (Persistent-LPD) and the optimal treatment for rheumatoid arthritis (RA) after LPD regression. METHODS: Among 3666 patients with RA treated with MTX in our department from 2006 to 2017, 26 cases of LPD that regressed after MTX withdrawal (Regressive-LPD) and 25 cases of Persistent-LPD were compared. Multivariate logistic analysis was performed to identify predictive factors for Persistent-LPD. Retention rates of biological disease-modifying antirheumatic drugs (bDMARDs) were calculated using the Kaplan-Meier Method. RESULTS: In Persistent-LPD, the incidence of diffuse large B-cell lymphoma was higher (76%). The overall 2-year survival rate was 83.9%: 95.8% for Regressive-LPD and 71.0% for Persistent-LPD. The International Prognostic Index (IPI) risk classification was useful for predicting Persistent-LPD. bDMARDs were introduced in 38 RA patients after LPD regression. Unadjusted retention rate of bDMARDs in the 51 LPD patients was significantly lower than that in the 1668 non-LPD RA patients in our bDMARD cohort (controls) (p = 0.029). The 1-year retention rates for bDMARDs were 69% and 64% for tocilizumab and abatacept, respectively vs. 46% for TNF-inhibitor (TNFi). CONCLUSION: Risk assessment using IPI predicted Persistent-LPD. After LPD regression, non-TNFi tended to have higher retention rates.

A case of eosinophilic granulomatosis with polyangiitis as a mimicker of IgG4-related disease.

A 62-year-old woman was admitted to our hospital because of fever, renal dysfunction, eosinophilia, and the presence of MPO-ANCA. Based on the renal pathological examination which showed granuloma lesion with eosinophils and crescentic glomerulonephritis, eosinophilic granulomatosis with polyangiitis (EGPA) was diagnosed. On the other hand, laboratory examination showed elevated serum IgG4 levels and renal pathological examination showed marked lymphoplasmacytic infiltration and fibrosis surrounding nest "Bird's eye pattern," which were characteristic of IgG4-related kidney disease (IgG4-RKD). Because there are cases when EGPA has clinical features of IgG4-RKD, we should be careful about diagnoses of IgG4-RKD in patients with EGPA.

The additive effects of hydroxychloroquine to maintenance therapy with standard of care in patients with systemic lupus erythematosus.

AIM: In this retrospective study, the effect of hydroxychloroquine (HCQ) added to maintenance therapy according to the standard of care (SoC) was evaluated for 1 year in 101 patients with systemic lupus erythematosus (SLE). METHODS: The primary endpoint was the SLE Disease Activity Index (SLEDAI). The secondary endpoints were the British Isles Lupus Assessment Group index, serum complement activity (CH50) levels, anti-double-stranded DNA (dsDNA) antibody titer, concomitant corticosteroid (CS) dose, and Systemic Lupus International Collaborating Clinics (SLICC) damage index. These variables were compared between the SoC + HCQ (n = 42) and SoC (n = 59) groups. RESULTS: The SLEDAI improved from 2 (0, 6) to 0 (0, 4) in the SoC + HCQ group (P = .038) but significantly deteriorated from 1 (0, 4) to 2 (0, 8) in the SoC group (P = .033). CH50, anti-dsDNA antibody titer, concomitant CS dose, and SLICC damage index did not significantly change. The increase in the SLEDAI and concomitant CS dose after 1 year were all significantly greater in the SoC group, and the proportion of patients with SLEDAI flare was significantly lower in the SoC + HCQ group (SoC + HCQ: 4.76% vs SoC: 25.4%, P = .006). Univariate logistic regression analyses identified HCQ as a predictive factor for no SLEDAI flare (P = .003, odds ratio 6.81, 95% confidence interval 1.77-45.00). CONCLUSIONS: The use of HCQ effectively improved SLEDAI scores and was a predictive factor for the prevention of SLEDAI flare. Therefore, HCQ may be considered a potential mainstay of maintenance therapy.

5-year remission rate after the discontinuation of adalimumab in patients with rheumatoid arthritis: Long-term follow-up results of the HONOR study.

Objectives: To determine the rate and factors associated with remission (disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) of <2.6) during a 5-year follow-up after the discontinuation of adalimumab (ADA) in patients with rheumatoid arthritis (RA).Methods: 75 patients who had been treated with ADA + methotrexate (MTX) and maintained DAS28-ESR <2.6 for at least 6 months were enrolled. Among them, 52 patients discontinued ADA, and 46 patients completed a 5-year follow-up.Results: During the 5 years, 11 patients had DAS28-ESR <2.6. In 15 patients with DAS28-ESR <3.2, no significant changes were found in the health assessment questionnaire disability index (HAQ-DI) and modified total Sharp score (mTSS). When comparing patients with DAS28-ESR ≤1.61 versus 1.61 2 years). Among 31 patients who experienced flare, ADA was restarted in 24 patients, and 17 patients of these achieved DAS28-ESR <3.2 within 1-year.Conclusion: During the 5-year ADA-free period, remission rate was persistent in 21% of the patients. ADA-free remission was possible especially in patients with deeper remission (DAS28-ESR ≤1.61) and shorter disease duration (≤2 years).

Comparative study of corticosteroid monotherapy, and TNF inhibitors with or without corticosteroid in patients with refractory entero-Behcet's disease.

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.

Effectiveness and safety of hydroxychloroquine therapy with or without corticosteroid in patients with systemic lupus erythematosus.

AIM: The effectiveness and safety of hydroxychloroquine (HCQ) have not been fully validated in Japanese patients with systemic lupus erythematosus (SLE) in the clinical setting. This study evaluated the short-term effectiveness and continuation rate of HCQ therapy in Japanese patients with SLE in the clinical setting for 12 months. METHODS: The primary endpoint was defined as the continuation rate up to 12 months after the introduction of HCQ in 122 patients with SLE. The secondary endpoints included changes in the SLE Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) index, and the effect on concomitant corticosteroid (CS) dose reduction. RESULTS: The primary endpoint, continuation rate up to 12 months after the introduction of HCQ, was 79.5%. Of 25 patients who discontinued HCQ, 23 patients terminated the therapy within 2 months. The secondary endpoints (SLEDAI, BILAG index, and concomitant CS dose [mg/day, prednisolone equivalent]) all showed a significant decrease. SLEDAI and BILAG index scores indicated significant improvement during the remission induction phase, maintenance phase, and HCQ monotherapy phase. CONCLUSIONS: The results of this study suggested that, with attention paid to possible adverse events immediately after initiation, HCQ may be initiated as a mainstay of SLE therapy in Japanese patients, either as a concomitant medication in the remission induction phase, as a maintenance therapy, or as a monotherapy.

Relevance of interferon-gamma in pathogenesis of life-threatening rapidly progressive interstitial lung disease in patients with dermatomyositis.

BACKGROUND: Dermatomyositis (DM) with rapidly progressive interstitial lung disease (DM RP-ILD) is a life-threatening condition. Serum cytokine levels are potentially suitable biomarkers for DM RP-ILD. However, the relationships among cytokine levels, lung imaging findings, and lung pathology have not been investigated. The aim of the present retrospective study was to determine the association between hypercytokinemia and lung inflammation in patients with DM RP-ILD. METHODS: The study subjects were nine patients with life-threatening DM RP-ILD and severe hypoxemia (partial arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio ≤ 200) before receiving intensive care management, who were admitted to our hospital between 2006 and 2015. The controls included 10 patients with DM without RP-ILD and 19 healthy subjects. We assessed the association between serum cytokine levels and computed tomography (CT) scores of the lung (ground glass opacity-score, G-score; fibrosis-score, F-score). Lung, hilar lymph nodes, and spleen from two autopsies were examined by hematoxylin-eosin (H&E) staining and immunostaining. RESULTS: Serum interferon (IFN)-γ, interleukin (IL)-1ß and IL-12 levels were significantly higher in patients with DM RP-ILD than in the other two groups, whereas serum IL-6 levels were elevated in the two patient groups but not in the healthy subjects. Serum levels of IL-2, IL-4, IL-8, IL-10, IFN-α, and TNF (tumor necrosis factor)-α were not characteristically elevated in the DM RP-ILD group. Serum IFN-γ levels correlated with G-scores in patients with DM RP-ILD, while IL-1ß was negatively correlation with F-scores. Immunohistochemical staining showed infiltration of numerous IFN-γ-positive histiocytes in the lung and hilar lymph nodes; but not in the spleen. Serum IL-6 levels did not correlate with the CT scores. Numerous IL-6-positive plasma cells were found in hilar lymph nodes, but not in the lungs or spleen. CONCLUSIONS: Our results suggest strong IFN-γ-related immune reaction in the lungs and hilar lymph nodes of patients with life-threatening DM RP-ILD, and potential IFN-γ involvement in the pathogenesis of DM, specifically in the pulmonary lesions of RP-ILD.