BACKGROUND: As an initial treatment for primary membranous nephropathy (PMN), there remains a significant proportion of patients for whom rituximab is not fully effective. Here, we aimed to assess the effectiveness and safety of obinutuzumab as initial treatment in patients with PMN.
METHODS: In this observational case series, patients diagnosed with PMN and treated with obinutuzumab as initial treatment were included. Treatment response was assessed by 24-h urine total protein (24 h UTP) and serum albumin, and immunologic remission was assessed by phospholipase A2 receptor (PLA2R) antibodies.
RESULTS: Twelve patients with PMN receiving obinutuzumab as initial treatment were included. Over 6 months, a statistically significant reduction in 24 h UTP levels (p = 0.003) and an increase in serum albumin levels were observed (p < 0.001). By the 6-month follow-up, two patients (16.7%) achieved complete remission, eight (66.6%) reached partial remission, and two (16.7%) showed no remission. Immunological remission was observed in 44.4% of evaluable patients (n = 9) after 3 months, increasing to 100% (6/6) at 6 months. Except for cases 1, 2, and 3, the total B cell counts in the remaining patients fell to less than 5 cells/μL before the administration of the second dose of obinutuzumab, including seven patients with counts as low as 0 cells/μL. Mild to moderate treatment-related adverse events (TRAEs) were reported in 58.3% (7/12) of the patients. No serious TRAEs were reported.
CONCLUSIONS: Obinutuzumab demonstrates promising potential as an initial treatment for PMN, with good effectiveness and a manageable safety profile. Further large-scale prospective studies are needed to confirm these findings.

BACKGROUND: Hydroxychloroquine (HCQ) influences both toll-like receptor (TLR) signaling and leukocyte activation, which are speculated to play a role in the pathogenesis of IgA nephropathy (IgAN).
METHODS: This is a single-centered retrospective study involving 426 IgAN patients diagnosed from May 2016 to August 2020. All patients were matched according to a propensity score matching (PSM) to produce three groups: renin-angiotensin-aldosterone system inhibitors (RAASi) group (RAASi only), corticosteroids group (corticosteroids only or combined with RAASi), and HCQ group (HCQ only or combined with RAASi), consisting of 63 patients for each group.
RESULTS: After PSM, the median urine protein/creatinine ratio (UPCR) of overall patients was 0.91 g/g, while their median serum creatinine was 87.00 μmol/L. After the median follow-up period of 11.03 months, the total remission rates of the RAASi group, corticosteroids group, and HCQ groups were 49.21% (n = 31), 74.60% (n = 47), and 52.38% (n = 33), respectively (p = 0.017). Thirteen (6.88%) patients experienced a decline in estimated glomerular filtration rate (eGFR) of more than 25% from baseline, including six (9.52%) patients in the RAASi group, three (4.76%) patients in the corticosteroids group, and four (6.35%) patients in HCQ group (p = 0.677). One (1.59%) patient in the HCQ group had blurred vision and continued to use HCQ after ruling out retinal lesions by ophthalmic examination.
CONCLUSIONS: HCQ is effective in inducing remission and well-tolerated in IgAN patients with mild to moderate proteinuria.

Azathioprine (AZA) interferes with the activation of T and B lymphocytes, which are the main cells involved in the pathogenesis of Graves\' disease (GD). The aim of this study was to investigate the effectiveness of AZA as an adjuvant therapy to antithyroid drugs (ATDs) for moderate and severe GD. In addition, we conducted an incremental cost-effectiveness analysis of AZA to determine its cost-effectiveness.
We conducted a randomized, open-label, and parallel-group clinical trial. We randomized untreated hyperthyroid patients with severe GD into three groups. All patients received 45-mg carbimazole (CM) as the starting dose and propranolol 40-120 mg daily. The first group (AZA1) received an additional 1 mg/kg/day AZA, the second group (AZA2) received an additional 2 mg/kg/day AZA, and the third group (control group) received only CM and propranolol. We measured thyroid-stimulating hormone (TSH) and TSH-receptor antibody (TRAb) levels at baseline and every 3 months, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were measured at the time of diagnosis, 1 month after initiation of therapy, and every 3 months thereafter until 2 years after remission. Thyroid volume (TV) was assessed by ultrasound at baseline and 1 year after remission.
A total of 270 patients were included in this trial. By the end of follow-up, there was higher remission rate in the AZA1 and AZA2 groups compared with controls (87.5% and 87.5% vs. 33.4%, p = 0.002). Throughout the course of follow-up, FT3, FT4, TSH, and TRAb were significantly different between the AZA groups and the control group, but there was no significant difference regarding TV. The decline in the concentrations of FT4, FT3, and TRAb was significantly faster in the AZA2 group than in the AZA1 group. The relapse rate during the 12-month follow-up was insignificantly higher in the control group than in either the AZA1 or AZA2 group (10, 4.4, and 4.4%, p = 0.05, respectively). The median relapse time was 18 months for the control group and 24 months for the AZA1 and AZA2 groups. The incremental cost-effectiveness ratio for the AZA group compared with the conventional group was 27,220.4 Egyptian pounds per remission reduction for patients using AZA as an adjuvant for ATDs.
AZA could be a novel, affordable, cost-effective, and safe drug offering hope for patients with GD to achieve early and long-lasting medical remission.
The trial is registered at the Pan African Clinical Trial Registry (Registration number: PACTR201912487382180).

Rapidly progressive interstitial lung disease (RP-ILD) clearly harms the prognoses of dermatomyositis/polymyositis (DM/PM) patients, however there is a dearth of numerical prevalence and therapy comparison in this field. Therefore, the purpose of this study was to determine the prevalence of RP-ILD in DM/PM patients and compare prognoses, including remission rate and survival data, between treatments. Studies with reports of RP-ILD in DM/PM patients and studies with definite remission and/or survival data of DM/PM-RP-ILD were included in the study. Data sources were Pubmed, Embase, and Cochrane Library without language restrictions. Two authors (WHL and WWQ) extracted independently the data. Estimates of the pooled effects were calculated using the Mantel-Haenszel technique (random effects). The prevalence meta-analysis included 18 papers with 6058 DM/PM patients, and 31 papers were analyzed for treatment effects, including remission rate, 6-month survival rate, 1-year survival rate, and 5-year survival rate. Database search yielded 1816 articles. In the DM/PM population, the combined prevalence of RP-ILD was 8.9% (95% CI, 5.8% to 12.1%). Patients with RP-ILD have a remission rate of 58.4% (95% CI, 47.3% to 69.4%), with biologic treatment with the highest remission rate, followed by triple therapy (defined as adding a third intravenous medication, including cyclophosphamide and immunoglobulin). Biologics therapy had the highest overall survival rate at six months (95% CI, 49.8% to 73.9%), followed by cDMARDs, plasma exchange, and triple therapy. The 1-year survival rate was 77.4% (95% CI, 66.7% to 88.1%), and triple therapy and cDMARDs had the best survival rates. The 5-year survival rate was 40.0% (95% CI, 10.0% to 69.9%). The prevalence of RP-ILD in DM/PM was approximately 8.9%, with a poor long-term prognosis. The use of biological agents appears to provide the best therapeutic outcomes, providing RP-ILD management with a novel evidence-based therapy. The use of strong immunosuppressive treatments may result in life-threatening side effects, thus clinicians must closely monitor the condition.

Background and Objectives: Hypercholesterolemia in patients with nephrotic syndrome (NS) may predispose to cardiovascular events and alter kidney function. We aimed to evaluate statins efficiency in NS patients under immunosuppression using four endpoints: remission rate (RR), end-stage kidney disease (ESKD), major cardiovascular events (MACE), and thrombotic complications (VTE). Materials and Methods: We retrospectively examined the outcome at 24 months after diagnosis of 154 NS patients (age 53 (39-64) years, 64% male, estimated glomerular filtration rate (eGFR) 61.9 (45.2-81.0) mL/min). During the follow-up, the lipid profile was evaluated at 6 months and at 1 and 2 years. Results: The median cholesterol level was 319 mg/dL, and 83% of the patients received statins. Patients without statins (17%) had similar age, body mass index, comorbidities, blood lipids levels, NS severity, and kidney function. The most used statin was simvastatin (41%), followed by rosuvastatin (32%) and atorvastatin (27%). Overall, 79% of the patients reached a form of remission, 5% reached ESKD, 8% suffered MACE, and 11% had VTE. The mean time to VTE was longer in the statin group (22.6 (95%CI 21.7, 23.6) versus 20.0 (95%CI 16.5, 23.5) months, p 0.02). In multivariate analysis, statin therapy was not associated with better RR, kidney survival, or fewer MACE; however, the rate of VTE was lower in patients on statins (HR 2.83 (95%CI 1.02, 7.84)). Conclusions: Statins did not improve the remission rate and did not reduce the risk of MACE or ESKD in non-diabetic nephrotic patients. However, statins seemed to reduce the risk of VTE. Further randomized controlled studies are needed to establish statins\' role in NS management.

UNASSIGNED: Rheumatoid arthritis (RA) is an autoinflammatory disease, its core treatment principle is to achieve remission as soon as possible. There is no good prediction model that can accurately predict the remission rate of patients to choose a good treatment scheme. Here, we aimed to verify the prognostic value of some inflammatory indicators in RA and establish a prediction model to predict the remission rate after treatment.
UNASSIGNED: A total of 223 patients were enrolled at Qilu Hospital from June 2014 to June 2020. Baseline clinical data were collected and plasma was obtained to detect the inflammatory indicators. All patients were treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). All patients were followed up and were recorded the time to reach the disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR) of <2.6. A total of 156 patients were randomly assigned to the development cohort, and 67 patients were assigned to the validation cohort. Inflammatory indicators in plasma were detected by enzyme-linked immunosorbent assay (ELISA). The predictive factors were screeded by using least absolute shrinkage and selection operator (LASSO) and Cox regression. The model was created and verified by using the standard method. A total of 6 independent risk factors were analyzed to construct a nomogram to predict the remission rate in 3, 6 and 12 months.
UNASSIGNED: The remission rates after treatment in 3, 6 and 12 months were 38.76%, 58.91%, and 81.40%, respectively. Patient age, C-reactive protein (CRP), interleukin (IL)-6, galectin-9 (Gal-9), health assessment questionnaire (HAQ), and DAS28-ESR were included in the prognostic model to predict the remission rate. The resulting model had good discrimination ability in both the development cohort (C-index, 0.729) and the validation cohort (C-index, 0.710). Time-dependent receiver operating characteristic (ROC) curve, calibration analysis, and decision curve analysis (DCA) showed that the model has significant discriminant power and clinical practicability in predicting the remission rate.
UNASSIGNED: We established a new predictive model and validated it. The model can predict the remission rate in 3, 6 and 12 months after receiving csDMARDs treatment. By using this model, we can facilitate the identification of high-risk patients early and intervene with them as soon as possible.

BACKGROUND: A large discrepancy between physician-diagnosed and self-reported HS exists. Knowledge regarding incidence and remission rates of self-reported HS is missing, but may help bridge the gap in understanding between these two phenotypes.
OBJECTIVE: To determine the incidence and remission rates of self-reported HS, and to what degree these are affected by sex, smoking and BMI.
METHODS: A prospective cohort of 23,930 Danish blood donors. Information on self-reported HS, symptom-localization, sex, age, BMI and smoking status was collected at baseline and study termination. Self-reported HS fulfilled clinical obligatory diagnostic criteria. Cox proportional hazards regression analyses were conducted for both incidence and remission rates providing a hazard ratio (HR) of risk for each variable in the regression.
RESULTS: incidence rate of self-reported HS was 10.8/1,000 person-years (95% CI: 9.9-11.7), decreasing as a function of numbers of areas affected. Female BMI points above 25 (HR=1.11, 95% CI: 1.09-1.13), male BMI points above 25 (HR=1.07, 95% CI: 1.04-1.11) , active smoking (HR=1.72, 95% CI: 1.15-2.57), male sex (HR=0.55, 95% CI: 0.45-0.67) and years of age above 25 (HR=0.97, 95% CI: 0.96-0.97) were all statistically associated with the development of self-reported HS. Remission rate of self-reported HS was 256.7/1,000 person-years (95% CI: 223.9-292.6), decreasing as a function of numbers of affected areas. Symptoms in ≥3 areas (HR=0.54, 95% CI: 0.34-0.85), active smoking (HR=0.49, 95% CI: 0.32-0.76) and female weight loss (every percentage drop in BMI: HR=1.07, 95%CI: 1.05-1.11) all significantly affected the remission rate.
CONCLUSIONS: Both incidence and remission rates of self-reported HS are high, indicating that many with self-reported HS are unlikely to be diagnosed, as they to a higher degree experience mild transient HS symptoms.

BACKGROUND: The efficacy and safety of rituximab (RTX) for lupus nephritis are still a controversial issue.
METHODS: We systematically searched MEDLINE, EMBASE, and the Cochrane Library databases for all clinical controlled studies.
RESULTS: Six studies with 588 patients were included in our meta-analysis. RTX increased total renal remission rates (TR, odds ratio [OR] 2.16, 95% CI 1.31 to 3.55, P = .003) and complete renal remission rate (CR, OR 2.42, 95% CI 1.18 to 4.94, P = .02) compared with the control group. Subgroup analyses showed that rituximab was more effective at increasing the rate of TR and CR for lupus nephritis patients compared with mycophenolate mofetil (TR, OR 4.6, 95% CI 1.29 to 16.47, P = .02; CR, OR 2.56, 95% CI 1.19 to 5.47, P = .02) and cyclophosphamide (TR, OR 2.89, 95% CI 1.31 to 6.40, P = .009; CR, OR 2.75, 95% CI 1.19 to 6.4, P = .02). Rituximab also had advantage in reducing Systemic Lupus Erythematosus Disease Activity Index score (-2.49, 95% CI -3.77 to -1.22, P = .0001). There were no significant differences between the RTX group and control group on the change of proteinuria (-0.36 g/d, 95% CI -0.71 to -0.00 g/d, P = .05) and serum creatinine (0.13 mg/dL, 95% CI -0.15 to 0.42 mg/dL, P = .36). RTX treatment did not increase the risk of adverse events compared to the control group.
CONCLUSIONS: This study provides clear beneficial effects of RTX in patients with lupus nephritis. In addition, RTX therapy did not increase the risk of adverse events compared to the control group.

BACKGROUND: Chronic spontaneous (previously known as idiopathic) urticaria (CSU) is a chronic skin disease with the potential for natural remission. The objectives of this targeted literature review were to identify evidence on the clinical course of CSU, including remission rates, and to estimate cumulative remission rates for different time points.
METHODS: Electronic databases (MEDLINE, MEDLINE-In Process, Embase, Web of Science, BIOSIS Previews and the Cochrane Library) and relevant conference proceedings were searched to identify studies involving patients with CSU aged ≥ 12 years that provide data on remission rates and disease duration. Observational studies with patient follow-ups of ≥ 1 year or review articles were included. Data extracted from five selected studies were used to run Kaplan-Meier (KM) analyses and best-fit distributions to calculate remission rates per 4-week period and weighted averages.
RESULTS: Ten publications were included in this review. The proportion of patients achieving remission within year 1 ranged from 21 to 47%, while reported remission rate estimates at year 5 were 34% and 45%. Based on calculated 4-weekly remission rates, cumulative remission estimates ranged from 9 to 38% at year 1, from 29 to 71% at year 5 and from 52 to 93% at year 20. Cumulative weighted average estimates for the proportion of patients remitting at years 1, 5 and 20 were 17%, 45% and 73%, respectively.
CONCLUSIONS: Published evidence suggests that CSU is a self-limiting condition with variable disease severity and duration, apparently dependent on multiple factors. However, data sources differed in terms of definitions of disease severity and remission, as well as in conclusions on influencing factors. Further studies and uniform definitions are required.

OBJECTIVE: Globally, evidence from short-term studies is insufficient for the guidelines to uniformly recommend a particular antipsychotic(s) for the maintenance treatment of schizophrenia. Therefore, long-term comprehensive evaluation of antipsychotics is required from a social rehabilitation perspective, especially for drugs that have not yet been studied. The Japan Useful Medication Program for Schizophrenia (JUMPs) is a large-scale, long-term naturalistic study to present pivotal 52-week data on the continuity of second-generation antipsychotics (SGA: aripiprazole, blonanserin, and paliperidone).
METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 52-week study. Enrolled patients had schizophrenia, were ≥20 years old, and required antipsychotic treatment or switched from previous therapy. The primary endpoint was treatment discontinuation rate over 52 weeks. Secondary outcomes included remission rate, social functioning, and quality-of-life scores [Personal and Social Performance Scale (PSP) and EuroQol-5 dimensions], and safety.
RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). The discontinuation rate (P = 0.9771) and remission rates (P > 0.05) over 52 weeks did not differ significantly between the three treatment groups. The discontinuation rates were 68.3%, 68.2%, and 65.5% in the aripiprazole, blonanserin, and paliperidone groups, respectively. Significant improvements (all P < 0.05) from baseline in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favored blonanserin.
CONCLUSIONS: All three SGAs evaluated in this study showed similar treatment discontinuation rates in patients with chronic schizophrenia in Japan.