Induction and Maintenance Treatment of Lupus Nephritis: A Comprehensive Review of Meta-Analyses

Background: Lupus nephritis (LN) is present in over 50% of patients with systemic lupus erythematosus (SLE) which is managed with immunosuppressive and immunomodulatory therapies. However, several novel therapeutic approaches for LN are under investigation due to the adverse effects spectrum of conventional therapy; Methods: We performed a comprehensive review of meta-analyses aggregating the comparative efficacies of various pharmacotherapies for LN. We conducted a literature search and retrieved a total of 23 meta-analyses and network meta-analyses for summarization. Pharmacotherapies were evaluated across six major outcomes: remission, relapse, mortality, end stage kidney disease (ESKD) progression, infection, and malignancy. Result: Calcineurin inhibitors (CNI), particularly tacrolimus (TAC), in combination with glucocorticoids (GC) outperformed cyclophosphamide (CPA) with GC in the rate of remission, either complete or partial remission, and in terms of infectious complications. In maintenance therapy, MMF was superior to azathioprine (AZA) as the MMF-treated patients had lower relapse rate. Interpretation: This review aggregates evidence of therapy for clinicians and sheds light on comparative efficacies of alternative LN treatments. As more promising agents are entering the market, such as voclosporin, belimumab, and obinutuzumab, LN management might undergo significant changes during the next years.

Nationwide cross-sectional survey of patients with relapsing polychondritis in 2019 demonstrates reduction of airway involvement compared with that in 2009

We conducted retrospective cohort studies of patients with relapsing polychondritis (RP) twice in 2009 and 2019, using a physician questionnaire. We compared the patients’ clinical statuses between the years. Age and gender were comparable between the two surveys. Mean disease duration was longer in 2019 survey (8.3 years) than that in 2009 survey (4.8 years, P < 0.001). The mortality rate declined in 2019 survey compared with those in 2009 survey (from 9.2 to 1.6%, P < 0.001). Incidence of airway involvement decreased in 2019 survey compared with that in 2009 survey (from 49 to 37%, P = 0.012). In 2019 survey, we found more frequent use of biological agents and immunosuppressants in patients with airway involvement. When we focused on RP patients with airway involvement, physicians in 2019 chose methotrexate and calcineurin inhibitors preferentially, compared with azathioprine and cyclophosphamide. Of note is that increased use of infliximab was observed in RP patients with airway involvement, but not in those without. Reduction of airway involvement and mortality in patients with RP was observed in 2019 survey. The reduction may associate with the frequent use of biologics including infliximab in RP patients with airway involvement.

Influence of calcineurin inhibitors and genetic polymorphism of transporters on enterohepatic circulation and exposure of mycophenolic acid in Chinese adult renal allograft recipients

Aim: Study the influence of calcineurin inhibitors (CNI) and genetic polymorphisms of transporters on enterohepatic circulation (EHC) of mycophenolic acid (MPA) in Chinese adult renal allograft recipients and estimate the effect of various covariates on prediction performance of MPA AUC0-12h. Method: MPA concentrations of 125 Chinese patients were collected 0-12 hours after administration. Genotypes of transporters were determined in 64 patients. The influence of type of CNI and genetic polymorphisms on MPA exposure was studied. Shapley additive explanations method was used to study the impact of sampling times and covariates related to EHC on AUC0-12h. Extreme gradient boosting (XGboost) machine learning-based model was established to predict AUC0-12h. Results: Dn-AUC6-12h was significantly lower in patients co-administered with CsA (P<0.05). When co-administered with TAC, for SLCO1B1 T521C or ABCC C-24T, patients with wild-type genotype had significantly higher dn-AUC6-12h (P <0.05). Patients with SLCO1B3 334T/699G alleles had significantly lower dn-AUC6-12h than homozygotes (P=0.004). No significant difference was found in CsA subgroup. For estimating AUC0-12h, C0h, C2h, C8h, type of CNI, transporters genotypes and the difference between C0h and C2h were retained in the final model, which had good prediction performance (r2=0.9739). Conclusion: Patients co-administered with CsA had lower MPA EHC than those who received TAC. MPA EHC is affected by ABCC2 C-24T, SLCO1B3 T334G/G699A, and SLCO1B1 T521C genotypes in patients treated with TAC. Type of CNI and genetic polymorphisms of transporters can improve prediction performance of MPA AUC0-12h estimating model, developed using XGboost machine learning method.

Antibody Response to mRNA Vaccines against SARS-CoV-2 with Chronic Kidney Disease, Hemodialysis, and after Kidney Transplantation

Most trials on mRNA vaccines against SARS-CoV-2 did not include patients with chronic kidney disease (CKD), hemodialysis (HD) patients, or kidney transplant recipients (KTR). However, those patients have a higher risk for a severe course of COVID-19 disease and mortality. Available literature has demonstrated a reduced efficacy of mRNA vaccines in HD patients and KTR, while data on CKD patients is scarce. Additionally, factors associated with non-response are poorly understood and not well characterized. We assessed antibody (AB) response (n = 582, 160 CKD patients, 206 patients on HD, 216 KTR) after the administration of two doses of a mRNA-vaccine with either BNT162b2 or mRNA-1273. AB measurements were carried out after a median of 91 days after first vaccinations, demonstrating non-response in 12.5% of CKD patients, 12.1% of HD patients, and 50% of KTR. AB titers were significantly higher in CKD patients than in HD patients or KTR. Factors associated with non-response were treated with rituximab in CKD patients, the use of calcineurin inhibitors in HD patients and older age, and the use of BNT162b2, mycophenolic acid, or glucocorticoids and lower hemoglobin levels in KTR. This study contributes to the understanding of the extent and conditions that predispose for non-response in patients with impaired kidney function.

Epidemiology, Comorbidities, and Prescription Patterns of Korean Prurigo Nodularis Patients: A Multi-Institution Study

Prurigo nodularis (PN) is a chronic dermatosis typified by extraordinarily itchy nodules. However, little is known of the nature and extent of PN in Asian people. This study aimed to describe the epidemiology, comorbidities, and prescription pattern of PN in Koreans based on a large dermatology outpatient cohort. Patients with PN were identified from the Catholic Medical Center (CMC) clinical data warehouse. Anonymized data on age, sex, diagnostic codes, prescriptions, visitation dates, and other relevant parameters were collected. Pearson correlation analysis was used to calculate the correlation between PN prevalence and patient age. Conditional logistic regression modeling was adopted to measure the comorbidity risk of PN. A total of 3591 patients with PN were identified at the Catholic Medical Center Health System dermatology outpatient clinic in the period 2007–2020. A comparison of the study patients with age- and sex-matched controls (dermatology outpatients without PN) indicated that PN was associated with various comorbidities including chronic kidney disease (adjusted odds ratio (aOR), 1.48; 95% confidence interval (CI), 1.29–1.70), dyslipidemia (aOR, 1.88; 95% CI, 1.56–2.27), type 2 diabetes mellitus (aOR, 1.37; 95% CI, 1.22–1.54), arterial hypertension (aOR, 1.50; 95% CI, 1.30–1.73), autoimmune thyroiditis (aOR, 2.43; 95% CI, 1.42–4.16), non-Hodgkin’s lymphoma (aOR, 1.95; 95% CI, 1.23–3.07), and atopic dermatitis (aOR, 2.16, 95% CI, 1.91–2.45). Regarding prescription patterns, topical steroids were most favored, followed by topical calcineurin inhibitors; oral antihistamines were the most preferred systemic agent for PN. PN is a relatively rare but significant disease among Korean dermatology outpatients with a high comorbidity burden compared to dermatology outpatients without PN. There is great need for breakthroughs in PN treatment.

Review on Assessment and Evaluation of Vitiligo in Primary Care

Vitiligo is an acquired skin disorder characterised by the disappearance of melanocytes, resulting in well-defined white patches that are frequently symmetrically distributed. The lack of melanin pigment makes the lesional skin more sensitive to sunburn. Vitiligo can be cosmetically disfiguring, and it is a stigmatising condition that can lead to serious psychologic problems in daily life. Vitiligo is treated with a variety of topical and systemic medications, phototherapy, laser therapy, and surgical therapy. Corticosteroids, calcineurin inhibitors, and vitamin-D analogues are examples of topical treatment modalities. Phototherapy is a highly effective treatment method. It causes repigmentation in the majority of patients with early and localised disease. Because vitiligo is associated with other autoimmune disorders, a multidisciplinary approach is required. Collaboration and communication between primary care physicians and dermatologists are critical. This review aims to assess role of primary care physicians in assessment and management of vitiligo in primary care settings.

Calcium Signaling, Calcineurin and NFAT3 Molecular Pathway in Reprogramming of Fetal Gene (BNP) Expression in Cardiac Hypertrophy and Inhibitors of Cardiac Hypertrophy-Review

G-Protein Coupled Receptor (GPCR) plays a major role in cardiac hypertrophy. Isoproterenol is an agonist which binds to GPCR. This results in the activation of GS subunit. Activated Gs subunit stimulates cAMP mediated pathway. This activates the calcium signaling and elevates the calcium level. Increased calcium activates the phosphatase activity of calcineurin. Activated calcineurin dephosphorylates NFAT in cytoplasm. Dephosphorylated NFAT translocates to nucleus and binds to target region in DNA and activates re-expression of fetal genes in synergy with GATA-4 trascription factor. Reprogramming of fetal genes by NFAT- 3 and GATA-4 results in cardiac hypertrophy. Calcineurin inhibitors and rephosphorylation of NFAT can prevent cardiac hypertrophy.

Different Approaches to Atopic Dermatitis by Allergists, Dermatologists, and Pediatricians

Objectives. Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease, with a vast drug arsenal and guidelines available for its management and diagnosis and different medical specialties engaged in providing care. This study aimed to outline the therapeutic and diagnostic approaches to the AD of allergists, dermatologists, and pediatricians and verify whether they are compliant with the guidelines. Methods. A cross-sectional study using an electronic questionnaire administered through the SurveyMonkey® platform was disclosed by participating medical societies to their medical associates. Results. Of the 1,473 participating physicians, the use of moisturizers as part of AD treatment was observed among pediatricians (91.9%), dermatologists (97.5%), and allergists (100%; p = 0.07 ). The preference for the use of new emollients was lower among pediatricians (57%) than dermatologists (75.9%) and allergists (71.4%; p < 0.001 ). The prevalence of wet-wrap therapy was lower among dermatologists (16.3%) than allergists (51%; p < 0.001 ). The recommendation of proactive treatment with topical corticosteroids was more frequently reported by allergists (65.3%) than pediatricians (43.3%) and dermatologists (40.8%; p < 0.001 ), and the same trend was observed in relation to proactive treatment using calcineurin inhibitors. The use of oral anti-histamines to control pruritus was mainly considered by pediatricians (69.2%) and dermatologists (59.2% p < 0.001 ). Clinical experience with systemic immunomodulating agents was greater among allergists (77.5%) and dermatologists (60.8%; p < 0.001 ), with cyclosporine being the most cited systemic immunomodulating agent. Environmental control of aeroallergens was recommended by pediatricians (89.8%), dermatologists (86.9%), and allergists (100%; p = 0.01 ). Conclusion. There were differences in the therapeutic and diagnostic approaches to AD used by allergists, dermatologists, and pediatricians and those recommended by the guidelines, especially regarding the use of wet-wrap therapy, proactive treatment with topical corticosteroids or calcineurin inhibitors, prescription of anti-histamines, recommendation of phototherapy, and control of aeroallergens.

Antirheumatic Drugs against COVID-19 from the Perspective of Rheumatologists

Coronavirus disease 2019 (COVID-19) remains a global threat to humanity. Its pathogenesis and different phases of disease progression are being elucidated under the pandemic. Active viral replication activates various immune cells and produces large amounts of inflammatory cytokines, which leads to the cytokine storm, a major cause of patient death. Therefore, viral inhibition is expected to be the most effective early in the course of the disease, while immunosuppressive treatment may be useful in the later stages to prevent disease progression. Based on the pathophysiology of rheumatic diseases, various immunomodulatory and immunosuppressive drugs are used for the diseases. Due to their mechanism of action, the antirheumatic drugs, including hydroxychloroquine, chloroquine, colchicine, calcineurin inhibitors (e.g., cyclosporine A and tacrolimus), glucocorticoids, cytokines inhibitors, such as anti-tumor necrosis factor-α (e.g., infliximab), anti-interleukin (IL)-6 (e.g., tocilizumab, sarilumab, and siltuximab), anti-IL-1 (e.g., anakinra and canakinumab) and Janus kinase inhibitors (e.g., baricitinib and tofacitinib), cytotoxic T lymphocyte-associated antigen 4 blockade agents (e.g., abatacept), and phosphodiesterase 4 inhibitors (e.g., apremilast), have been tried as a treatment for COVID-19. In this review, we discuss the mechanisms of action and clinical impact of these agents in the management of COVID-19.