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Objective Fatigue is one of the most common complaints and is a potentially modifiable issue in systemic lupus erythematosus (SLE). Studies suggest that alcohol consumption has a protective effect against the development of SLE; however, an association between alcohol consumption and fatigue in patients with SLE has not been studied. Here, we assessed whether alcohol consumption was associated with fatigue using lupus patient-reported outcomes (LupusPRO). Methods This cross-sectional study, conducted between 2018 and 2019, included 534 patients (median age, 45 years; 87.3% female) from 10 institutions in Japan. The main exposure was alcohol consumption, which was defined as the frequency of drinking [Results In total, 326 (61.0%) patients were categorized into the none group, 121 (22.7%) into the moderate group, and 87 (16.3%) into the frequent group. The frequent group was independently associated with less fatigue compared with none group [β = 5.98 (95% CI 0.19–11.76), p = 0.04], and the results did not substantially deviate after MI. Conclusions Frequent drinking was associated with less fatigue, which highlights the need for further longitudinal studies focusing on drinking habits in patients with SLE.

ObjectivePatients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL, among patients with systemic lupus erythematosus (SLE).MethodsThis was a cross-sectional study using baseline data from the Trust Measurement for Physicians and Patients with SLE (TRUMP2-SLE) study, an ongoing multicenter cohort study conducted at 5 academic centers. The 14-item Functional, Communicative, and Critical Health Literacy Scale assessed the 3 dimensions of HL; each item of the scale was scored on a 4-point Likert scale, ranging from 1 to 4. Outcomes were trust in one’s physician and trust in physicians in general using the 5-item Wake Forest Physician Trust Scale, which ranged from 0 to 100 points. General linear models were fit.ResultsA total of 362 patients with SLE were included. Trust in one’s physician increased with higher functional and communicative HL (per 1-point increase: mean difference 3.39, 95% CI 0.39-6.39, and mean difference 5.88, 95% CI 2.04-9.71, respectively). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-point increase: mean difference 7.09, 95% CI 2.34-11.83, and mean difference −6.88, 95% CI −11.72 to −2.04, respectively). Longer internet use was associated with both higher communicative and critical HL.ConclusionThe findings suggest that rheumatologists need to improve their communication to match each patient’s HL, which may foster trust and lead to improved self-management and outcomes in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust.

Supplementary Figure Legend and Tables S1 & S2 from Hyperplasia and Carcinomas in Pten-Deficient Mice and Reduced PTEN Protein in Human Bladder Cancer Patients

Supplementary Figure S1 from Hyperplasia and Carcinomas in Pten-Deficient Mice and Reduced PTEN Protein in Human Bladder Cancer Patients

PTEN is a tumor suppressor gene mutated in many human cancers. We used the Cre-loxP system to generate an urothelium-specific null mutation of Pten in mice [FabpCrePtenflox/flox (FPtenflox/flox) mice]. Histologic examination revealed that all FPtenflox/flox mice exhibited urothelial hyperplasia in which component cells showed enlarged nuclei and increased cell size. With time, 10% of FPtenflox/flox mice spontaneously developed pedicellate papillary transitional cell carcinomas (TCC). This type of tumor also arose in FPtenflox/flox mice treated with the chemical carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine. FPtenflox/flox urothelial cells were hyperproliferative and showed increased activation of the survival signaling molecules Akt and extracellular signal-regulated kinase. In humans, 53% of primary bladder cancer patients exhibited decreased or absent expression of PTEN protein in either the cytoplasm or nucleus of tumor cells. In early bladder cancers, PTEN expression was repressed in 42% of superficial papillary TCC but in only 8% of cases of carcinoma in situ (CIS). In advanced bladder cancers, PTEN protein was significantly reduced (particularly in the nucleus) in 94% of cases, and this decrease in PTEN correlated with disease stage and grade. Thus, PTEN deficiency may contribute to bladder cancer both by initiating superficial papillary TCC and by promoting the progression of CIS to advanced invasive and metastatic forms. (Cancer Res 2006; 66(17): 8389-95)

Objectives To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. Methods We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine–Gray model to assess the association between low IgG (the minimum IgG levels Results Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03–3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. Conclusion Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.

ObjectiveProviding appropriate health information to patients with systemic lupus erythematosus (SLE) is advantageous in the treatment decision-making process. We aimed to investigate how online health information-seeking behavior affects shared decision-making (SDM) in patients with SLE.MethodsThis cross-sectional study included 464 patients with SLE from five institutions. The main exposure was time spent on the Internet per day, which was divided into four categories (none, ResultsCompared with no Internet use, longer internet use was associated with a higher SDM-Q-9 score: ConclusionsThe present study suggests that SDM between physicians and patients is positively (rather than adversely) associated with online information-seeking behavior, with no negative influence associated with accessing the Internet prior to visits to a rheumatologist. Rheumatologists may need to introduce their patients to websites offering high-quality health information to establish a productive physician–patient relationship for SDM.

Background A family member’s negative experiences with medical care have long-term effects on a patient’s attitudes and emotions. However, the impact of family members’ experiences on patients’ trust in their own physicians and in physicians generally is poorly understood. This study aims to quantify these associations. Methods A cross-sectional online survey involving adults with non-communicable diseases (cardiac disease, diabetes, cancer, depression, and rheumatic disease) was conducted in Japan during April 2020. The main exposure variable was dissatisfaction with the medical care that family members had received. The main outcomes were patients’ (N = 661) own trust in their personal physicians and in physicians generally. The study adopted the Japanese version of the Abbreviated Wake Forest Physician Trust Scales. Both 5-item scales (general and individual physician trust) were translated and validated for the study. The total scores were transformed into a scale of 0-100 points. A series of linear mixed-effects models with consideration for clustering effect by prefectures were fit. Results The results showed a lower rating for trust in physicians generally as compared to trust in the respondent’s personal physician (mean 57.0 vs. 66.4 points; p Conclusions We suggest that physicians enquire about past patients’ negative experiences, including dissatisfaction with family members’ medical care, to repair hidden loss of trust, when they sense that patients doubt them or physicians generally.

Background Thoracoscopic esophagectomy, with CO2 insufflation as a prerequisite, is increasingly performed for esophageal cancer. However, there is limited evidence on the influence of CO2 insufflation on the long-term postoperative survival. We aimed to estimate long-term outcomes with or without CO2 insufflation during thoracoscopic esophagectomy. Methods We enrolled 182 patients who underwent thoracoscopic esophagectomy for esophageal cancer between January 2003 and October 2013 and categorized them into two groups: with and without CO2 insufflation. The primary endpoint was the 5-year overall survival (5y-OS). Secondary endpoints included other long-term (i.e., 5-year relapse-free survival [5y-RFS] and 5-year cancer-specific survival [5y-CSS]) and short-term (i.e., surgical and non-surgical complications and 30-day reoperation) outcomes. Results Follow-up until death or the 5-year postoperative period was 98.9% complete (median follow-up duration: 6 years, in survivors). After adjusting for age and sex, the analyses showed no significant differences in 5y-OS (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.50–1.40), 5y-RFS (0.79, 0.49–1.31), and 5y-CSS (0.74, 0.43–1.27). For short-term outcomes, significant intergroup differences in the thoracic operative time (p = 0.02), thoracic blood loss (p p p = 0.004) were observed, and the results of sensitivity analysis were similar to the main results. Conclusions CO2 insufflation in thoracoscopic surgery for esophageal cancer seemingly does not change the long-term prognosis and is possibly safe in other thoracic procedures.

Patients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL among patients with systemic lupus erythematosus (SLE).This was a cross-sectional study using baseline data from the TRUMPA total of 362 SLE patients were included. Trust in one's physician increased with higher functional and communicative HL (per 1-pt increase, 3.21 [95%CI 0.61, 5.81], 5.8 [95%CI 1.96, 9.63]). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-pt increase, 7.01 [95%CI 2.27, 11.76], -6.83 [95%CI -11.67, -1.99]). Longer internet use was associated with both higher communicative and critical HL.The findings suggest that rheumatologists need to improve their communication to match each patient's health literacy, which may foster trust and lead to improved self-management and outcome in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust.

ObjectivePoor medication adherence among patients with SLE is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one’s physician and goal-oriented thinking, hope and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians.MethodsThis cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centres. Patients with SLE who were prescribed oral medications were included. The main exposures were trust in one’s physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. Medication adherence was measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects and concerns regarding lupus medications.ResultsAltogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years; among them, 329 (88.2%) were women. Both trust in one’s physician (per 10-point increase: 0.86, 95% CI 0.49, 1.22) and the Health-related Hope score (per 10-point increase: 0.66, 95% CI 0.35, 0.97) were associated with better medication adherence.ConclusionsThis study demonstrated that patients’ health-related hope and trust in their rheumatologist were both associated with better medication adherence in SLE.

Objectives The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis. Methods PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach. Results For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively. Conclusions This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis.

Objective The EULAR recommends that the disease activity of systemic lupus erythematosus (SLE) be stable before pregnancy because complications and disease flares increase if pregnancy occurs while disease activity is high. However, some patients have ongoing serological activity even after treatment. Herein, we investigated how physicians decide on the acceptability of pregnancy in patients showing only serological activity. Methods A questionnaire was administered from December 2020 to January 2021. It included the characteristics of physicians, facilities, and the allowance for pregnancies of patients using vignette scenarios. Results The questionnaire was distributed to 4,946 physicians, and 9.4% responded. The median age of respondents was 46 years, and 85% were rheumatologists. Pregnancy allowance was significantly affected by duration of the stable period and status of serological activity (duration: proportion difference, 11.8 percentage points [p.p.]; p Conclusions Serological activity had a significant effect on the acceptability of pregnancy. However, some physicians allowed patients with serological activity alone to become pregnant. Further observational studies are required to clarify such prognoses.

BACKGROUND: Previous qualitative research has described that previous misdiagnoses may reduce patient and their families’ trust in healthcare. OBJECTIVE: To quantify the associations between patients or family members’ misdiagnosis experiences and trust in their physician. DESIGN: Cross-sectional study. PARTICIPANTS: Adult Japanese people with non-communicable diseases (cancer, diabetes, depression, heart disease, and connective tissue disease), recruited using a web-based panel survey. MAIN MEASURES: Surveys assessed the patient and the patient’s family’s experience with misdiagnosis. Trust in the respondent’s current physician was measured using the Japanese version of the 11-item Trust in Physician Scale. KEY RESULTS: Among 661 patients (response rate 30.1%), 23.2% had a personal history of misdiagnosis and 20.4% had a family history of misdiagnosis. In a multivariable-adjusted general linear model, patients or a family members’ misdiagnosis experiences were associated with lower confidence in their current physician (mean difference −4.3, 95%CI −8.1 to −0.49 and −3.2, 95%CI −6.3 to −0.05, respectively). The impact of having a personal and a family member’s experience of misdiagnosis on trust was additive, with no evidence of interaction (P for interaction = 0.494). CONCLUSIONS: The patient’s or family members’ misdiagnosis experiences reduced trust in the patient’s current physicians. Interventions specifically targeting misdiagnosed patients are needed to restore trust. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06950-y.

Background Infection is a major cause of mortality in patients with systemic lupus erythematosus (SLE). Therefore, minimizing the risk of infection is an important clinical goal to improve the long-term prognosis of SLE patients. Treatment with ≥7.5 mg prednisolone (PSL) or equivalent has been reported to increase the risk of infections. However, it remains unclear whether Methods This prospective cohort study included patients from the Japanese multicenter registry of patients with SLE (defined as ≥4 American College of Rheumatology 1997 revised criteria) over 20 years of age. The PSL dose was categorized as PSL 0–2.5, 2.6–5.0, 5.1–7.5, and 7.6–15.0 mg. The primary outcome was infection requiring hospitalization. We conducted a multivariable analysis using time-dependent Cox regression analysis to assess the hazard ratio of infection occurrence compared with a dose of 0–2.5 mg PSL or equivalent in the other three PSL dose groups. Based on previous reports and clinical importance, the covariates selected were age, sex, and concurrent use of immunosuppressants with GC. In addition, two sensitivity analyses were conducted. Results The mean age of the 509 SLE patients was 46.7 years; 89.0% were female, and 77.2% used multiple immunosuppressants concomitantly. During the observation period, 52 infections requiring hospitalization occurred. The incidence of infection with a PSL dose of 5.0–7.5 mg was significantly higher than that in the PSL 0–2.5 mg group (adjusted hazard ratio: 6.80, 95% confidence interval: 2.17–21.27). The results of the two sensitivity analyses were similar. Conclusions Our results suggested that the use of 5.0–7.5 mg PSL or equivalent could pose an infection risk in SLE patients. This finding indicates that PSL dose should be reduced to as low as possible in SLE patients to avoid infection.

Objectives Although personality characteristics of patients with SLE affect their disease activity and damage, it is unclear whether those of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait for achieving long-term goals that may influence the decision-making for continuing treatment plans for patients. We aimed to evaluate the relationship between the grit of attending physicians and achievement of treatment goals in patients with SLE. Methods This cross-sectional study was conducted at five referral hospitals. The main exposure was ‘consistency of interest’ and ‘perseverance of effort’ of the attending physicians, measured by the Short Grit Scale. The primary outcome was achievement of a lupus low disease activity state (LLDAS). The association between physicians’ grit score and LLDAS was analysed by generalized estimating equation (GEE) logistic regression with cluster robust variance estimation, with adjustment for confounders. Results The median (interquartile range) total, consistency and perseverance scores of 37 physicians were 3.1 (2.9–3.6), 3.3 (2.8–3.8) and 3.3 (3.0–3.5), respectively. Among the 386 patients, 154 (40%) had achieved LLDAS. Low consistency score (≤2.75) in physicians was related to LLDAS achievement independently using GEE logistic regression. The score of the question ‘I often set a goal but later choose to pursue a different one’ was significantly higher in patients achieving LLDAS. Conclusions Difficulty of attending physicians to change treatment goals might be related to lower LLDAS achievement in patients with SLE.

ObjectivesPoor medication adherence among patients with systemic lupus erythematosus (SLE) is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one’s physician and goal-oriented thinking, hope, and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians.MethodsThis cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centers. Patients with SLE who were prescribed oral medications were included. The main exposure was trust in one’s physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. The outcome was medication adherence measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects, and concerns regarding lupus medications.ResultsAltogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years, and among them, 329 (88.2%) were women. Both trust in one’s physician (per 10-point increase: 0.88, 95% confidence interval [95%CI]: 0.53 to 1.24) and the Health-related Hope score (per 10-point increase: 0.64, 95%CI: 0.33 to 0.95) were associated with better medication adherence.ConclusionsPhysician communication to build trust and coaching on self-management to maintain or achieve what is important in the patient’s life and to enhance hope may lead to better medication adherence.Key messagesWhat is already known on this topicThe possible association of loss of trust in the attending physician with medication adherence in systemic lupus erythematosus has been conflicting in previous research, in which the effect of physician–patient racial mismatch has not been considered. The protective role of hope and goal-oriented thinking for mental symptoms has been suggested among patients with SLE.What this study addsThis study revealed that both trust in one’s physician and health-related hope were associated with better medication adherence in Japanese patients who were ethnically matched to their physicians.How this study may affect research, practice, or policyThe results indicated that physician communication to build trust and coaching on self-management to maintain or achieve what is important in the patient’s life may lead to better medication adherence.

Objective This study aimed to assess the prevalence and actual treatment conditions for hypertension and dyslipidaemia complicated with systemic lupus erythematosus (SLE). Methods This was a cross-sectional study. We established the lupus registry of nationwide institutions (LUNA), a multi-centre cohort of SLE patients in Japan. From February 2016 to July 2018, 597 SLE patients were registered in the LUNA. We evaluated the incidence of hypertension and dyslipidaemia and analysed the risk factors for hypertension and dyslipidaemia by logistic regression analysis. Results Overall, 597 patients were enrolled in the study. The median age was 44 years, and 88.0% of the patients were female. Among all the patients, 92.9% used prednisolone. The prevalence of hypertension and dyslipidaemia was 43.9% and 54.7%, respectively. Among the patients receiving medication for hypertension, 24.7% exhibited insufficient control (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg), and among those receiving medication for hyperlipidaemia, 48.1% showed insufficient control (low-density lipoprotein cholesterol >140 mg/dL or triglyceride >150 mg/dL). The risk factors for hypertension were age, body mass index (BMI), disease duration, past maximum dose of prednisolone, and renal involvement, whereas those for dyslipidaemia were age and BMI. Conclusion About half of the patients had hypertension or dyslipidaemia, and a considerable number of cases were poorly controlled despite medication. Our data suggest that physicians should treat SLE activity as well as its complications, especially the common risk factors for atherosclerosis.

ObjectivesAccessing the Internet has increased the gap in patient health literacy (HL), impacting patient-doctor trust. We examined how trust in physicians is affected by functional HL (the ability to read and write) and by broader concepts of HL, including communicative HL (the ability to extract information from communication to use) and critical HL (the ability to analyze and use information) among patients with systemic lupus erythematosus (SLE).MethodsThis cross-sectional study enrolled 362 SLE patients at five academic centers between June 2020 and August 2021. The 14-item Functional Communicative Critical Health Literacy Scale assessed the three dimensions of HL (range: 1-4 points). Outcomes were trust in one’s physician and physicians generally using the 5-item Wake Forest Physician Trust Scale (range: 0-100 points). General linear models adjusted for age, sex, education, income, disease activity, disease duration, depression, and time using the Internet.ResultsTrust in one’s physician increased with higher functional and communicative HL (per 1-pt increase, 3.21 [95%CI 0.61, 5.81], 5.8 [95%CI 1.96, 9.63]). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-pt increase, 7.01 [95%CI 2.27, 11.76], -6.83 [95%CI -11.67, -1.99]). Longer Internet use was associated with both higher communicative and critical HL.ConclusionsOur findings suggest that rheumatologists can help patients build trust by encouraging dialogue about their health issues with their doctors and family members, rather than trying to improve their ability to discern health information.Key messagesWhat is already known on this topicFactors affecting trust in one’s physician among chronic diseases including SLE are economic status, misdiagnosis experience, and the duration of the physician-patient relationship.In the general population, higher trust in physicians generally was associated with functional HL as patients’ external factors.What this study addsThis is the first study to reveal an association between trust in one’s own physician and HL among patients with SLE. In addition, we were able to expand the correlates of HL by measuring broader concepts of HL dimensions, such as communicative and critical HL.How this study may affect research, practice, or policyThis study suggests the importance of rheumatologists’ encouragement of patients to communicate, share their concerns, and resolve their misunderstandings to develop a trusting relationship. This study recommends that communictive HL (ability to obtain useful health information) should be the focus and not critical HL (ability to discern health information).

Background Although vitamin D concentration is reportedly associated with the pathogenesis and pathology of systemic lupus erythematosus (SLE), benefits of vitamin D supplementation in SLE patients have not been elucidated, to our knowledge. We investigated the clinical impacts of vitamin D supplementation in SLE. Methods A cross-sectional analysis was performed using data from a lupus registry of nationwide institutions. We evaluated vitamin D supplementation status associated with disease-related Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) as a parameter of long-term disease activity control. Results Of the enrolled 870 patients (mean age: 45 years, mean disease duration: 153 months), 426 (49%) received vitamin D supplementation. Patients with vitamin D supplementation were younger (43.2 vs 47.5 years, P < 0.0001), received higher doses of prednisolone (7.6 vs 6.8 mg/day, P = 0.002), and showed higher estimated glomerular filtration rates (79.3 vs 75.3 mL/min/1.73m2, P = 0.02) than those without supplementation. Disease-related SDI (0.73 ± 1.12 vs 0.73 ± 1.10, P = 0.75), total SDI, and SLE Disease Activity Index (SLEDAI) did not significantly differ between patients receiving and not receiving vitamin D supplementation. Even after excluding 136 patients who were highly recommended vitamin D supplementation (with age ≥ 75 years, history of bone fracture or avascular necrosis, denosumab use, and end-stage renal failure), disease-related SDI, total SDI, and SLEDAI did not significantly differ between the two groups. Conclusions Even with a possible Vitamin D deficiency and a high risk of bone fractures in SLE patients, only half of our cohort received its supplementation. The effect of vitamin D supplementation for disease activity control was not observed.

IntroductionLupus nephritis (LN) is more prevalent in patients with SLE of Asian ethnicity than in Caucasian patients. Belimumab became available in Japan in 2017 to treat patients with SLE, including those with LN. In the BLISS-LN trial (NCT01639339), belimumab showed a favourable effect on renal outcomes when combined with standard therapy (ST) starting at the induction treatment phase for active LN, but real-world effectiveness of belimumab in LN has not been extensively studied. Here we describe the protocol for the MOONLIGHT (post-Marketed effectiveness of belimumab cOhOrt and JapaN Lupus NatIonwide ReGistry (LUNA) coHorT) study, which will use data from a Japan postmarketing surveillance study and the Lupus Registry of Nationwide Institutions (LUNA) to evaluate the real-world effectiveness of belimumab plus ST versus ST alone in patients with a history of active LN who are not in the induction phase.Methods and analysisThis multicentre, retrospective, observational study (GSK Study 214710) will enrol adults with SLE and a history of active LN, holding ≥3 years of complete follow-up data from the initiation of belimumab (no continuous treatment required). Data for patients with belimumab plus ST treatment (postmarketing registry data, belimumab cohort) will be compared with those for patients with ST only treatment (LUNA data, comparison cohort). Patients who discontinue/initiate belimumab after the start of the follow-up may be included in the comparison/belimumab cohort, respectively. The primary endpoint will be the occurrence of renal flares, for which belimumab’s effectiveness will be estimated using a marginal structural model to consider time-dependent treatment and confounding factors. Secondary endpoints will include change in corticosteroid dose, renal disease activity, extrarenal disease activity, disease severity/activity biomarkers, LN class changes, end-stage kidney disease events and hospitalisations.Ethics and disseminationThis study will be conducted according to the Declaration of Helsinki and the local ethical guidelines. Findings will be submitted to peer-reviewed journals and presented at scientific meetings.