Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics.

BACKGROUND: To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). METHODS: This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. RESULTS: Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. CONCLUSIONS: Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Integrated assessment of the natural purification capacity of tidal flat for persistent toxic substances and heavy metals in contaminated sediments.

Natural purification of pollutants is highly recognized as regulating ecosystem services; however, the purification capacity of tidal flats remains largely unknown and/or unquantified. A 60-day mesocosm transplant experiment was conducted in situ to assess the purification capacity of natural tidal flats. We adopted the advanced sediment quality triad approach, monitoring 10 endpoints, including chemical reduction, toxicity changes, and community recoveries. The results indicated that contaminated sediments rapidly recovered over time, particularly > 50% within a day, then slowly recovered up to âˆ¼ 70% in a given period (60 days). A significant early reduction of parent pollutants was evidenced across all treatments, primarily due to active bacterial decomposition. Notably, the presence of benthic fauna and vegetated halophytes in the treatments significantly enhanced the purification of pollutants in both efficacy and efficiency. A forecast linear modeling further suggested additive effects of biota on the natural purification of tidal flats, reducing a full recovery time from 500 to 300 days. Overall, the triad approach with machine learning practices successfully demonstrated quantitative insight into the integrated assessment of natural purification.

Febuxostat dose requirement according to renal function in patients who achieve target serum urate levels: A retrospective cohort study.

OBJECTIVES: To determine the febuxostat dose requirement according to renal function in patients who achieve target serum urate (SU) levels. METHODS: Of 3153 gout patients who underwent febuxostat treatment, 873 patients with an initial SU level>6mg/dL were included and categorized by the estimated glomerular filtration rate: normal, chronic kidney disease (CKD) stage 3, and stages 4-5. Ninety-five patients with insufficient follow-up were further excluded. The dose of febuxostat in patients who achieved the SU target (< 6mg/dL) was defined as the average daily dosage at the time of SU target achievement. RESULTS: The cohort of 778 gout patients had a median age of 52.0 years (IQR, 41.0-63.0) and comprised 711 (91.4%) men. The mean SU at febuxostat initiation was higher in the CKD 4-5 (9.6 [± 3.1] mg/dL) than in the other groups (CKD 3, 8.7 [± 1.7]; normal, 8.4 [± 1.7]; P<0.001). Patients achieved target SU at a median of 4.0 (1.9-9.6) months and in those who achieved target SU, the dose of febuxostat at the time of SU target achievement was significantly lower in the CKD 4-5 group (50.0 [± 16.5] mg) than in the other groups (vs. CKD stage 3, 60.0 [± 19.5] mg; P<0.01, vs. normal, 60.0 [± 19.8] mg; P<0.01). Furthermore, CKD stage 4-5 had a negative correlation with the febuxostat dose requirement (Beta: -2.334, P<0.05). CONCLUSION: Among patients who achieved SU target, those with severely decreased renal function (CKD 4-5) required a lower febuxostat dose to achieve the target SU level compared to patients with normal or mild renal impairment.

Effect of belimumab in patients with systemic lupus erythematosus treated with low dose or no corticosteroids.

BACKGROUND/AIMS: Systemic lupus erythematosus (SLE) responder index (SRI)-4 response has been achieved with belimumab treatment in patients with moderate disease activity in cornerstone clinical trials and following studies. However, most studies involved patients treated with a mean prednisolone-equivalent dose of approximately 10 mg/d and focused on the steroid-sparing effect of belimumab. We aimed to identify the effect of belimumab in patients with mild-to-moderate SLE who were treated with low-dose or no corticosteroids. METHODS: We retrospectively reviewed the electronic medical records of patients treated with belimumab for at least 6 months between May 2021 and June 2022. The primary endpoint was SRI-4 response at 6 months. RESULTS: Thirty-one patients were included (13 low dose- and 18 steroid non-users). The mean age was 39.2 ± 11.4 years, and 90.3% of patients were female. The baseline Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 6.0 (4.0-9.0). The primary endpoint was achieved in 32.3% (10/31) of patients. Significant improvements in anemia, C4 levels, and SELENA-SLEDAI score were observed during treatment. Univariate analysis showed that the baseline SELENA-SLEDAI and arthritis were significantly associated with SRI-4 response at 6 months, and only the SELENA-SLEDAI remained significant (p = 0.014) in multivariate analysis. CONCLUSION: This cohort study is the first to report the efficacy of belimumab after minimizing the effect of corticosteroids. Belimumab showed efficacy in improving the SELENA-SLEDAI score, anemia, and low C4 in patients who did not receive corticosteroids or received only low doses.

Clinical features of systemic lupus erythematosus patients with splenomegaly: focussed on the cytopenias.

This study aimed to investigate the clinical features of splenomegaly, mainly focussing on cytopenia, in patients with systemic lupus erythematosus (SLE). Cytopenia was commonly observed in 111 SLE patients with splenomegaly (n = 79, 71.2%). During the follow-up period, two patients developed haematologic malignancy after the diagnosis of SLE and splenomegaly, but no patients experienced severe complications (e.g. splenic rupture) related to splenomegaly.

Relapse in patients with antineutrophil cytoplasmic antibody-associated vasculitis undergoing dialysis: a single-centre retrospective study in South Korea.

OBJECTIVES: The disease activity of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) can decrease after dialysis, and relapse after dialysis is not well-studied. We investigated the clinical manifestations and factors associated with relapse in patients with AAV undergoing dialysis. METHODS: This retrospective study included data of patients with AAV undergoing dialysis due to renal involvement from July 2005 to March 2021 in a single tertiary centre in Seoul, Korea. Cox regression analysis was performed to identify relapse-associated factors. RESULTS: The study cohort included 38 patients with a median age of 64.0 years; 28 (73.7%) were female, and 35 (92.1%) patients were diagnosed with microscopic polyangiitis (MPA). At diagnosis, the mean Birmingham vasculitis activity score (BVAS) was 18.3 and 66.3% of the patients exhibited pulmonary manifestations. During follow-up, 12 patients experienced AAV relapse, including nine patients with diffuse alveolar haemorrhage (DAH), two patients with aggravated interstitial lung disease, and one patient with DAH accompanied with neuropathy. Clinical features including age, sex, and baseline BVAS did not significantly differ between the relapse and non-relapse groups. By univariable analysis, lung infiltration, DAH, corticosteroid pulse therapy for induction, and mean corticosteroid dose were significantly associated with relapse. Multivariable analysis revealed that DAH (adjusted hazard ratio 5.509, 95% CI 1.569-19.339; P=0.008) and mean corticosteroid dose (adjusted hazard ratio 1.381, 95% CI 1.161-1.642; P<0.001) were significantly associated with relapse. CONCLUSIONS: In patients with AAV undergoing dialysis, DAH and mean corticosteroid dose were significantly associated with relapse, highlighting the importance of close monitoring.

Clinical effect of progressive pulmonary fibrosis on patients with connective tissue disease-associated interstitial lung disease: a single center retrospective cohort study.

The concept of progressive pulmonary fibrosis (PPF) has been introduced to predict the diverse prognosis of interstitial lung disease (ILD). However, the incidence and effect of PPF on outcomes in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD) need to be elucidated. This study reviewed 197 patients with CTD-ILD. Symptomatic worsening, pulmonary function decline, and radiological deterioration were investigated to assess the fulfillment of PPF diagnostic criteria. Clinical outcomes, including mortality, were compared based on the presence or absence of PPF. The median follow-up duration was 17.4 months. The mean age of the patients was 64.0 years, and 60.9% were female. Among the underlying CTDs, rheumatoid arthritis (42.1%), inflammatory myositis (19.8%), and systemic sclerosis (13.2%) were the most common. Of the 197 patients, 37 (18.8%) met the diagnostic criteria for PPF during the follow-up period. Even after adjusting for other significant risk factors, PPF was independently associated with mortality [hazard ratio (HR) 3.856; 95% confidence interval (CI) 1.387-10.715; P = 0.010] and baseline albumin was marginally significantly associated with mortality (HR 0.549; CI 0.298-1.010; P = 0.054). The median survival was also significantly shorter in the PPF group than in the non-PPF group (72.3 ± 12.9 vs. 126.8 ± 15.5 months, P < 0.001). Baseline KL-6 ≥ 1000 (U/mL) was a significant risk factor for PPF (HR 2.885; CI 1.165-7.144; P = 0.022). In addition to increased mortality, the PPF group had significantly higher rates of respiratory-related hospitalizations, pneumonia, acute exacerbations, and weight loss than the non-PPF group. PPF is a significant prognostic indicator in patients with CTD-ILD. Thus, healthcare professionals should know that patients with CTD-ILD are at risk of PPF.

The Expression of the Alpha7 Nicotinic Acetylcholine Receptor and the Effect of Smoking in Curdlan-Administered SKG Mice.

Nicotine, an abundant molecule in tobacco, has immunomodulatory effects on inflammatory diseases, primarily due to the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR). We aim to evaluate the expression of the α7 nAChR+ cells in joint tissue and the effect of smoking on immune cells and peripheral arthritis in curdlan-administered SKG mice, a murine model of spondyloarthropathy (SpA). The SKG mice were injected with curdlan two times at 2-week intervals and were divided into two groups; one exposed to cigarette smoke and the other not exposed. We found that the α7 nAChR+ cells increased in the joint tissue of curdlan-administered SKG mice compared to in the wild type. Furthermore, the peripheral arthritis scores and histological scores for synovial inflammation were lower in smoke-exposed curdlan-administered SKG mice than in mice not exposed to smoke. Immunofluorescence staining of the α7 nAChR+ and IL-17A+ cells was lower in the synovia of smoke-exposed mice than the control mice. The proportions of α7 nAChR+IL-17A+ and α7 nAChR+IL-17A+FOXP3+ cells also decreased in the synovia of smoke-exposed mice compared with the controls. We observed an increase in the α7 nAChR+ cells within the joint tissue of curdlan-administered SKG mice and that cigarette smoke had an influence on both peripheral arthritis and immune cell population, especially α7 nAChR+ cells. Thus, exposure to cigarette smoke after arthritogenic stimuli may have an anti-arthritogenic effect in curdlan-administered SKG mice.

Self-amplifying mRNA seasonal influenza vaccines elicit mouse neutralizing antibody and cell-mediated immunity and protect ferrets.

Currently licensed influenza vaccines focus immune responses on viral hemagglutinin (HA), while the other major surface glycoprotein neuraminidase (NA) is not tightly controlled in inactivated vaccine formulations despite evidence that anti-NA antibodies reduce clinical disease. We utilized a bicistronic self-amplifying mRNA (sa-mRNA) platform encoding both HA and NA from four seasonal influenza strains, creating a quadrivalent influenza vaccine. sa-mRNA vaccines encoding an NA component induced the production of NA-inhibiting antibodies and CD4+ T-cell responses in both monovalent and quadrivalent formulations. Including NA in the vaccine enabled cross-neutralization against antigenically drifted strains and provided greater protection than HA alone upon A(H3N2) challenge in ferrets. These results demonstrate that next-generation bicistronic sa-mRNA vaccines expressing HA and NA induce potent antibodies against both viral coat proteins, as well as vaccine-specific cell-mediated immunity. When formulated as a quadrivalent seasonal influenza vaccine, the sa-mRNA platform provides an opportunity to increase the breadth of protection through cross-neutralizing anti-NA antibodies.

Recovery and long-term renal outcome of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis who are on dialysis at presentation.

Objective: Renal involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) can lead to severe renal dysfunction requiring dialysis at diagnosis. We aimed to study the clinical and pathologic characteristics of patients with AAV dependent on dialysis at presentation and the long-term renal outcomes of patients who recovered from dialysis. Methods: This retrospective study analyzed data of patients diagnosed with AAV who were on dialysis from July 2005 to May 2021 at a single tertiary center in Korea. Results: Thirty-four patients were included in the study (median age 64.5 years, females 61.8%), of which 13 discontinued and 21 continued dialysis. The proportion of normal glomeruli (p<0.001) and interstitial fibrosis (p=0.024) showed significant differences between both groups. Multivariable analysis showed that the proportion of normal glomeruli was associated with dialysis discontinuation (odds ratio=1.29, 95% confidence interval 0.99~1.68, p=0.063), although without statistical significance. Treatment modalities, including plasmapheresis, did not show significance with dialysis discontinuation. In the follow-up analysis of 13 patients who had discontinued dialysis for a median of 81 months, 12 did not require dialysis, and their glomerular filtration rate values significantly increased at follow-up time compared to when they stopped dialysis (37.5 [28.5~45.5] vs. 24.0 [18.5~30.0] mL/min/1.73 m²; p=0.008). Conclusion: Approximately 38% of AAV patients on dialysis discontinued dialysis, and the recovered patients had improved renal function without dialysis during longer follow-up. Patients with AAV on dialysis should be given the possibility of dialysis discontinuation and renal recovery, especially those with normal glomeruli in kidney pathology.

Urine SERPINC1/ORM1 as biomarkers for early detection of lupus nephritis in MRL-lpr mice.

Background: To evaluate the usefulness of urine SERPINC1 and ORM1 as biomarkers for early detection of lupus nephritis (LN). Methods: Using proteomics, we screened for potential urine biomarkers that differentiate LN from systemic lupus erythematosus (SLE) patients without nephritis. In addition, urine levels of target biomarkers were measured by ELISA in 13- and 23-week-old MRL-lpr (murine model for LN) and MRL/MpJ mice. Histological analysis was also performed on the kidneys of 23-week-old mice. Results: Urine SERPINC1 and ORM1 were elevated in SLE patients with newly diagnosed LN compared with SLE patients without LN (SERPINC1, AUC=.892, P<.001; ORM1, AUC=.886, P<.001). Levels of urine SERPINC1 and ORM1 were also significantly higher in MRL-lpr mice than in MRL/MpJ mice at 13 and 23 weeks (SERPINC1: p<.01 and p<.001 at 13 and 23 weeks, respectively; ORM1: p<.01 at 13 and 23 weeks). In contrast, a significant difference in urine albumin between the two groups was only observed at 23 weeks (p<.001) not at 13 weeks (p=.83). Regarding the kidney pathology of MPL-lpr mice, urine ORM1 and urine albumin, but not urine SERPINC1, were positively correlated with the activity index (ORM1, rho =.879, p<.001; albumin, rho =.807, p=.003) and chronicity index (ORM1, rho =.947, p<.001; albumin, rho =.869, p<.001). Conclusion: We propose that urine SERPINC1 and ORM1 are novel biomarkers for early LN.

When MRI would be useful in patients without evidence of sacroiliitis on radiographs?

We aimed to identify when magnetic resonance imaging (MRI) would be useful to diagnose patients with suspected axial spondyloarthropathy (AxSpA) without evidence of sacroiliitis on radiographs. We retrospectively reviewed electronic medical records of patients who underwent pelvis MRI after radiographs at the rheumatology clinic in a single tertiary center in Korea. Patients underwent imaging from January 2020 to July 2022. We collected data including complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen (HLA)-B27, history of acute anterior uveitis (AAU), peripheral arthritis, dactylitis, inflammatory bowel disease (IBD), enthesopathy, and psoriasis. A total of 105 patients who showed no evidence of sacroiliitis on radiographs were included. The median age of patients was 41.0 years, and 44.8% were male. Of them, 34 showed sacroiliitis on MRI (group 1), and 71 showed no evidence of sacroiliitis even on MRI (group 2). Known AxSpA-related clinical features including AAU, peripheral arthritis, dactylitis, IBD, enthesopathy, and psoriasis were not different between the two groups. HLA-B27 positivity (79.4% vs. 40.0%, p < 0.001), median white blood cell count (7700 vs. 6300, p = 0.007), mean platelet count (307.7 ± 69.7 vs. 265.3 ± 68.9 × 103/µL, p = 0.005), and median CRP level (0.38 vs. 0.10, p = 0.001) showed significant differences between the two groups. In a multivariate analysis, HLA-B27 positivity and platelet count were significantly associated with sacroiliitis on MRI. In our cohort, sacroiliitis was observed on MRI in one-third of patients without radiographic evidence. MRI could be recommended to evaluate sacroiliitis in patients with positive HLA-B27 and a high platelet count.

Long-term renal outcomes of patients with non-proliferative lupus nephritis.

BACKGROUND/AIMS: Although non-proliferative lupus nephritis (LN) (class I, II or V) has been considered as a less severe type of LN, data on long-term renal prognosis are limited. We investigated the long-term outcomes and prognostic factors in non-proliferative LN. METHODS: We retrospectively reviewed patients with systemic lupus erythematosus who were diagnosed with LN class I, II, V, or II + V by kidney biopsy from 1997 to 2021. A poor renal outcome was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. RESULTS: We included 71 patients with non-proliferative LN (class I = 4; class II = 17; class V = 48; class II+V = 2), and the overall rate of poor renal outcomes was 29.6% (21/71). The univariate analysis indicated that older age, low eGFR at 6 or 12 months, failure to reach complete remission at 6 months, and LN chronicity score > 4 or activity score > 6 were significantly associated with poor renal outcomes. The multivariate analysis revealed that low eGFR at 6 months (HR 0.971, 95% CI 0.949-0.991; p = 0.014) was significantly associated with poor renal outcomes. CONCLUSION: Poor renal outcomes occurred in approximately 30% of patients with non-proliferative LN after long-term follow-up. More active management may be needed for non-proliferative LN, especially for patients with eGFR < 60 mL/ min/1.73 m2 at 6 months follow-up after LN diagnosis.

Incidence of and risk factors for myelodysplastic syndromes in patients with rheumatologic diseases.

OBJECTIVE: We investigated the incidence rate and risk factors of myelodysplastic syndromes (MDS) in patients with rheumatologic disease. METHODS: We conducted a retrospective cohort study of patients who were diagnosed with rheumatologic diseases at a tertiary-care hospital between May 2009 and July 2022 and identified the patients who were subsequently diagnosed with MDS. Each patient with MDS was matched with five age- and sex-matched controls chosen from the cohort of patients with each specific rheumatologic disease. RESULTS: During a total follow-up of 55 841 person-years (PY), MDS occurred in 64 patients, yielding an incidence rate of 1.15/1000 PY (median age, 57.0 [IQR, 41.0-69.0]; median duration to MDS diagnosis, 6.5 years [IQR, 3.0-9.0]). In an age-matched analysis, systemic lupus erythematosus (SLE) was a significant risk factor for MDS (adjusted hazard ratio, 2.61 [CI, 1.19-36.06], P= 0.01). Refractory cytopenia with multilineage dysplasia was the most common phenotype of MDS (35.9%), and more than half of the patients had karyotypes with favorable prognoses (54.7%). Compared with matched controls, rheumatoid arthritis, SLE, and ankylosing spondylitis patients with MDS had lower levels of haemoglobin at the time of diagnosis of rheumatologic disease. Furthermore, the MDS patients with SLE and Behcet's disease had higher levels of glucocorticoid use in terms of frequency of use or mean dose than the control patients. CONCLUSION: SLE is a significant risk factor for MDS among patients with rheumatologic diseases. A lower haemoglobin level at the time of diagnosis of rheumatologic disease was associated with the future development of MDS.

Prognostic value of proteinuria monitoring in anti-neutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: To determine the prognostic significance of proteinuria monitoring in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We retrospectively analyzed the data of kidney biopsy-confirmed patients with AAV. Proteinuria was evaluated by a urine dipstick test. Poor renal outcome was defined as stage 4/5 chronic kidney disease (CKD) (estimated glomerular filtration rate < 30 mL/min/1.73 m2). RESULTS: We enrolled 77 patients with a median follow-up duration of 36 months (interquartile range, 18-79) in this study. Excluding 8 patients on dialysis at 6 months, 59/69 (85.5%) achieved remission after induction therapy. Patients were then divided into two groups according to the presence of proteinuria at 6 months after induction therapy (n = 29 with proteinuria, 40 without proteinuria). There was no significant difference in the rate of relapse or death according to the presence of proteinuria (p = 0.304 relapse, 0.401 death). In contrast, patients with proteinuria had significantly lower kidney function than those without proteinuria (41 vs. 53.5 mL/min/1.73 m2, p = 0.003). Multivariate analysis revealed that eGFR values at 6 months (hazard ratio [HR] 0.925; 95% CI 0.875-0.978, p = 0.006) and proteinuria at 6 months (HR 4.613; 95% CI 1.230-17.298, p = 0.023) were significantly associated with stage 4/5 CKD. CONCLUSION: The presence of proteinuria at 6 months after induction therapy and low renal function was significantly associated with a higher risk of stage 4/5 CKD in patients with AAV. Monitoring for proteinuria after induction therapy may help predict poor renal outcomes in patients with AAV.

Anti-S1/RBD-Specific Antibody Formation After SARS-CoV-2 Vaccination in Elderly Rheumatoid Arthritis Patients: Single-Center Prospective Observational Study.

BACKGROUND: The guidelines of coronavirus disease 2019 (COVID-19) vaccination in patients with rheumatoid arthritis (RA) have been continuously updated, with extensive discussion on the effectiveness of the COVID-19 booster vaccines and antibody generation associated with the different types of vaccine. We investigated the effects of the third dose of the mRNA vaccine on antibody titer and the factors associated with antibody production in patients with RA who had previously received two doses of the ChAdOx1-S nCoV-19 vaccine. METHODS: Between October 14, 2021 and June 17, 2022, two patient groups diagnosed with RA were recruited prospectively: one with two doses of ChAdOx1-S nCoV-19 and the second group with the additional third mRNA vaccine. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers were determined through semiquantitative anti-SARS-CoV-2 spike (S) electrochemiluminescence immunoassay. Antibody titers were compared in both groups considering clinical features and medications. Multivariate logistic regression was performed to identify the factors associated with antibody production. Also, we followed up the antibody titers of whom completed the 3rd mRNA vaccination. RESULTS: Among 261 patients, all patients were over 60 years old except for 7 patients and the average age was 65 years; 153 had completed two doses of ChAdOx1-S nCoV-19, while 108 patients had also received the third mRNA vaccine. The positive rates of anti-SARS-CoV-2 anti-S1/receptor binding domain-specific antibody (titer > 0.8 U/mL) were 97% (149/153) and 99% (107/108) respectively. However, positive rates for high antibody titer (> 250 U/mL) were found in only 31% (47/153) of group 1 but 94% (102/108) of group 2. Multivariate analysis revealed that corticosteroid use (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.16-0.75), older age (OR, 0.91; 95% CI, 0.860-0.98), and male sex (OR, 0.23; 95% CI, 0.07-0.74) were associated with a lower rate of high antibody titer acquisition after two doses of ChAdOx1-S nCoV-19. Waning of antibody titers was observed in only two of 46 patients who followed up twice after the third mRNA vaccine inoculation. CONCLUSION: Our findings suggest that the third dose of the mRNA vaccine could be beneficial in RA patients with risk factors including older age, male sex, and corticosteroid use after two doses of ChAdOx1-S nCoV-19.

Serum IgG4 level during initial treatment as a predictor of relapse in IgG4-related disease.

INTRODUCTION: We aimed to investigate the predictors of relapse in immunoglobulin G4-related disease (IgG4-RD), focusing on the serum IgG4 levels during initial treatment. METHODS: We retrospectively recruited 57 patients with IgG4-RD who were treated with immunosuppressants and elevated serum IgG4 levels in a tertiary hospital between January 2011 and December 2020. They were followed up for ≥ 6 months after initiation of immunosuppressive therapy. Clinical and laboratory findings including serum IgG4 levels (reference value: 6-121 mg/dL) were compared between relapsed (n = 13) and non-relapsed (n = 44) groups. Multivariate Cox regression analysis was used to assess the predictors for relapse. We performed a Kaplan-Meier analysis with a log-rank test to evaluate the cumulative relapse rate for two years. RESULTS: Median serum IgG4 levels at baseline were 321 mg/dL in the relapsed group and 299 mg/dL in the non-relapsed group. Serum IgG4 levels were normalized after six months in five (38.5%) relapsed and 28 (63.6%) non-relapsed patients. In multivariate Cox regression analysis, the normalization of serum IgG4 levels at six months was associated with a lower risk of relapse, with a hazard ratio of 0.232 (p = 0.019). Central nervous system involvement was associated with the relapse, with a hazard ratio of 21.130 (p = 0.015). The cumulative relapse rate for two years was lower in the normal serum IgG4 group at six months than in the elevated serum IgG4 group at six months (p = 0.027). CONCLUSION: Our study suggests that normalization of serum IgG4 levels during immunosuppressive treatment for IgG4-RD independently predicts relapse-free outcomes. Thus, monitoring serum IgG4 levels might be used as a marker of prognosis.

Incidence of rheumatic diseases during the COVID-19 pandemic in South Korea.

BACKGROUND/AIMS: The recent coronavirus disease 2019 (COVID-19) pandemic has been associated with changes in the epidemiology of not only infectious diseases but also several non-infectious conditions. This study investigated changes in the recorded incidence of various rheumatic diseases during the COVID-19 pandemic. METHODS: The number of patients for each disease from January 2016 to December 2020 was obtained from the Korean Health Insurance Review and Assessment Service database. We compared the incidence of nine rheumatic diseases (seropositive rheumatoid arthritis, systemic lupus erythematosus [SLE], idiopathic inflammatory myositis [IIM], ankylosing spondylitis [AS], systemic sclerosis, Sjögren's syndrome, Behçet's disease [BD], polymyalgia rheumatica, and gout) and hypertensive diseases to control for changes in healthcare utilisation before and after the COVID-19 outbreak. The disease incidence before and after the COVID-19 outbreak was compared using the autoregressive integrated moving average (ARIMA) and quasi- Poisson analyses. RESULTS: Compared with the predicted incidence in 2020 using the ARIMA model, the monthly incidence of SLE, BD, AS, and gout temporarily significantly decreased, whereas other rheumatic diseases and hypertensive diseases were within the 95% confidence interval (CI) of the predicted values in the first half of 2020. In age- and sex-adjusted quasi-Poisson regression analysis, the annual incidences of IIM (rate ratio [RR], 0.473; 95% CI, 0.307 to 0.697), SLE (RR, 0.845; 95% CI, 0.798 to 0.895), and BD (RR, 0.850; 95% CI, 0.796 to 0.906) were significantly decreased compared with those in the previous 4 years. CONCLUSION: The recorded annual incidence of some rheumatic diseases, including IIM, SLE, and BD, decreased during the COVID-19 pandemic.

Circulating and renal fibrocytes are associated with interstitial fibrosis in lupus nephritis.

OBJECTIVES: Fibrocytes, the extracellular matrix-producing cells derived from bone marrow progenitors, contribute to organ fibrosis. We investigated the presence and characteristics of fibrocytes in the peripheral blood and kidney of patients with lupus nephritis (LN), and the association of the abundance of fibrocytes with renal tubular epithelial cells (RTECs) in LN fibrogenesis. METHODS: Fibrocytes were identified with type I collagen (colI), α-smooth muscle actin (α-SMA), CD34 and CD45 using flow cytometry and confocal imaging. The associations between the levels of fibrocytes and pathological features of patients with LN were analysed. The contribution of RTECs to fibrocyte generation was determined using LN sera-treated HK-2 cells. RESULTS: Spindle-shaped fibrocytes (colI+α-SMA+CD34+CD45+ cells) were present in the peripheral blood and their abundance was especially high in LN patients with interstitial fibrosis compared with healthy control. Renal fibrocytes (colI+α-SMA+CD45+ cells) were found in the tubulointerstitium in patients with LN, and their numbers were significantly associated with the degrees of chronicity indices including interstitial fibrosis and renal dysfunction. Stimulation of peripheral blood mononuclear cells with supernatants from LN serum-treated HK-2 cells led to a significant generation of fibrocytes, which was abrogated by the addition of IL-6 neutralizing antibody. CONCLUSION: Fibrocytes were significantly increased in the blood and kidney tissue of patients with LN, especially those with interstitial fibrosis. Fibrocytes could be differentiated from blood cells, with an active contribution from RTECs. Our results show a possible link between fibrocytes and tubulointerstitial fibrosis, which may serve as a novel therapeutic target for LN fibrogenesis.