Predictors and prognostic factors influencing outcomes of anti-CD20 monoclonal antibodies in systemic lupus erythematosus: A systematic review update.

BACKGROUND: Anti-C20 monoclonal antibodies (MAb), such as rituximab, are commonly used for the treatment of patients with severe or refractory systemic lupus erythematosus (SLE) but clinical outcomes are highly variable. We aimed to provide an update of a systematic review of predictive and prognostic factors of anti-CD20 MAb treatment in SLE. METHODS: A systematic literature search was undertaken to identify predictive and prognostic factors of clinical response following treatment with anti-CD20 therapies in SLE patients. Studies examining rituximab published prior to 2015 were excluded. Risk of bias was assessed for randomized controlled trials (RCTs) using the Cochrane Collaboration (RoB2) tool for RCTs and the Quality In Prognosis Studies Tool (QUIPS) for cohort studies. A narrative synthesis of the evidence was undertaken and quality of evidence (QoE) was assessed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: From 850 studies identified, 17 studies met the inclusion criteria. A further 8 studies were identified and included through search updates. There were two post-hoc analyses of RCTs of rituximab, one RCT of ocrelizumab and one of obinutuzumab; and 16 cohort studies examining rituximab treatment. The overall QoE was low or very low. There was wide heterogeneity in definitions of clinical disease activity and outcome measures, non-standardized laboratory cut-offs, failure to account for confounders and multiple subgroup analyses of differing outcomes. B cell depletion as well as novel biomarkers, such as S100 proteins, FCGR genotype, anti-vimentin and anti-drug antibodies showed some evidence of prognostic value but QoE was limited due to moderate to high risk of bias, early phase of investigation and imprecision of results. CONCLUSION: There has been no validation of previously identified prognostic factors to guide outcome in anti-CD20 treated lupus patients. Hypothesis-driven studies of several novel markers however, demonstrate prognostic value and require replication and validation to support their use in routine clinical practice. PROSPERO REGISTRATION NUMBER: CRD42020220339.

Human mesenchymal stem cells for the management of systemic sclerosis. Systematic review.

INTRODUCTION: Sistemic Sclerosis (SSc) is a heterogeneous autoimmune disease with a high rate of progression and therapeutic failure, and treatment is a challenge, new therapeutic proposals being needed, being mesenchymal stem cells (MSCs) considered as alternative therapy for SSc for its immunomodulatory capacity. We evaluated the efficacy and safety of human MSC (hMSC) in patients with SSc through a systematic literature review (SLR). METHODS: SLR (PRISMA guideline) on MEDLINE/OVID, LILACS, EMBASE, and Cochrane/OVID bases (until July 2020, without limits). All types of clinical studies were considered: patients ≥18 years old with SSc and treatment with hMSC. EXCLUSION CRITERIA: animal models, autologous/allogenic hematopoietic stem cell transplants, narrative reviews, letters to the editor. MeSH and "Key word" terms were used. The level of evidence and the quality rating were rated [Joanna Briggs Institute (JBI) lists]. Registration in PROSPERO repository (ID CRD42020185245) The Synthesis Without Meta-analysis (SWiM) guideline was followed. RESULTS: We initially identified 508 articles, of which 11 were finally included (8 case series and 3 case reports). The 11 articles included 101 patients (85 female, age range 18-75 years). The level of evidence was mostly 4 (JBI); the quality of evidence was met (≥50% of JBI items). SWiM showed that vascular skin involvement (digital ulcers, necrosis, and gangrene) and associated pain were the predominant outcomes, while improvements were found in almost all cases. One patient died in the first month, and the frequency of complications was low. Expanded hMSCs were used in 24 patients and other cell sources in the remaining patients. CONCLUSION: There is too little reported data to reach definite conclusions about the use of hMSC in SSc. Further studies with better epidemiological designs are needed to evaluate the benefit of hMSCs in SSc patients.

Comparing cytology, colposcopy and human papillomavirus cervical intraepithelial lesion screening methods in women with systemic lupus erythematosus.

OBJECTIVE: To compare the performance of cytology, colposcopy and human papillomavirus in detecting cervical intraepithelial lesions in women with systemic lupus erythematosus. METHODS: Papanicolaou smears (normal, low-grade squamous intraepithelial lesion, high grade squamous intraepithelial lesion), colposcopy findings, human papillomavirus and co-testing (Papanicolaou smear + human papillomavirus) were compared with cervical biopsy findings in women with systemic lupus erythematosus. Sensitivity, specificity, false-positive and false-negative rates, positive and negative predictive values and likelihood ratios of cytologic smears, colposcopy findings, human papillomavirus and co-testing were determined. RESULTS: Cytology and colposcopy were performed in 170 systemic lupus erythematosus women (mean age and disease duration of 43.7±12.1 years and 9.7±5.3 years, respectively) and biopsies were performed in 55 patients (38.2% normal, 60.0% low-grade squamous intraepithelial lesion and 1.8% high grade squamous intraepithelial lesion). The sensitivity, specificity, positive predictive value and negative predictive value of cytology were 14.7% (95% confidence interval 5.5-31.8%), 95.2% (95% confidence interval 74.1-99.7%), 83.3% (95% confidence interval 36.4-99.1%) and 40.8% (95% confidence interval 27.3-55.7%), respectively. The sensitivity, specificity and positive predictive value of colposcopy findings were 100.0% (95% confidence interval 87.3-100.0%), 0.0% (95% confidence interval 0.0-19.2%) and 61.8% (95% confidence interval 47.7-74.2%), respectively. The sensitivity and specificity of co-testing were 8.0% (95% confidence interval 1.3-27.5%) and 100.0% (95% confidence interval 71.6-100.0%). The positive predictive value and negative predictive values were 100.0% (95% confidence interval 19.7-100.0%) and 36.1% (95% confidence interval 33.5-38.8%), respectively. CONCLUSIONS: In systemic lupus erythematosus patients, colposcopy impressions were more sensitive than cytology and co-testing. However, cytology and co-testing were the most specific tests. The results should be interpreted with caution due to the small sample size.

Helicobacter pylori infection and gastroduodenal lesions in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to determine the frequency of Helicobacter pylori in SLE patients and to compare clinical characteristics and gastroduodenal lesions in patients with and without H. pylori infection. METHODS: Adult SLE patients were selected and subjected to endoscopy. Gastroduodenal lesions were examined by endoscopy and biopsy (antrum and corpus). Biopsies were evaluated by hematoxylin and eosin and Giemsa staining. Immunochromatographic membrane-based assay using amplification was used to test for H. pylori antigen (coproantigen) in stool samples in all participants. Clinical characteristics and gastroduodenal lesions were compared between patients with and without H. pylori infection. RESULTS: A total of 118 SLE patients were included (mean age 44.7 ± 11.7 years, mean disease duration 11.6 ± 6.0 years), of whom 101 (85.6%) were receiving non-steroidal anti-inflammatory drugs (NSAIDs). The coproantigen test was positive in 32 (27.1%) patients. H. pylori was present in twenty six patients (22.0%) in the gastric biopsy. The frequency of gastric erosions and gastric ulcers were 55.1% and 0.8%, respectively. Gastric erosions were less frequent in SLE patients with H. pylori infection than those without H. pylori (43.5.7% vs. 62.5%; p = 0.04). The age, disease duration, disease activity, chronic damage, gastroprotective drugs, and immunosuppressive therapy did not differ between the two groups. CONCLUSIONS: We found a high frequency of H. pylori infection in SLE patients. The severity of SLE and reception of gastroprotective therapy do not seem to be related to H. pylori infection. Immunosuppressive therapy may not be protective against H. pylori infection in SLE patients.Key Points• In patients with systemic lupus erythematosus (SLE), the frequency of Helicobacter pylori infection was 39% and gastric erosions were frequent.• Disease activity, chronic damage, gastroprotective drugs, and immunosuppressive therapy may not affect the prevalence of H. pylori infection in SLE patients.

25-Hydroxyvitamin D concentrations and risk of metabolic syndrome in systemic lupus erythematosus women.

OBJECTIVE: A protective function of vitamin D in metabolic syndrome (MetS) has been described. The objective of the present study was to examine the relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations and MetS in non-diabetic systemic lupus erythematosus (SLE) women. METHODS: Cross-sectional analyses of the relationship between concentrations of 25(OH)D, MetS, and its components were made in 160 non-diabetic SLE women. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. Serum 25(OH)D was measured by chemiluminescent immunoassay. Serum 25(OH)D concentrations were categorized into quartiles (<16.6, 16.6-21.1, 21.2-26.3, ≥26.4 ng/mL). RESULTS: A total of 79 (49.3%) SLE women had MetS. Without adjusting for body mass index (BMI) or smoking, the odds of having MetS decreased according to increasing quartiles of 25(OH)D concentrations (P for trend = .03). The odds ratio (OR) of having MetS was 0.4 (95% confidence interval: 0.2-0.9, P = .04) for the highest vs the lowest quartile of 25(OH)D concentrations when adjusted by age. The crude OR of having elevated hypertriglyceridemia decreased according to increasing quartiles of 25(OH)D concentrations (P for trend = .036). However, further adjustments for BMI and smoking removed the inverse association between 25(OH)D concentrations and MetS and its individual components. CONCLUSION: In non-diabetic SLE women with mild activity, 25(OH)D concentrations are not associated with MetS and its components.

Prevalence of cervical HPV infection in women with systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVE: The objectives of this systematic review and meta-regression were: 1) to compare the prevalence of cervical HPV infection between SLE patients and healthy controls and 2) to evaluate the relationship between cervical HPV infection and traditional and SLE-related risk factors for cervical HPV infection in these patients. METHODS: We conducted a systematic literature review (PubMed, Cochrane Library, Embase, Virtual Health Library and SciELO databases) following PRISMA guidelines and using meta-regression to investigate the pooled prevalence of cervical HPV infection in adult women with SLE. The articles included were independently evaluated by two investigators who extracted information on study characteristics, defined outcomes, risk of bias and summarized strength of evidence [Quality of evidence using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence]. Using meta-regression, we further analyzed whether factors such as multiple sexual partners and immunosuppressive therapy were associated with HPV prevalence. We evaluated the quality of evidence included using the Oxford Centre for EBM levels of evidence. Pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated for studies providing data on HPV prevalence in women with SLE and in healthy controls. RESULTS: A total of 687 articles were identified; 9 full-text articles examining the prevalence of cervical HPV infection in SLE women were included, comprising 751 SLE women. Eight studies employed PCR using general primers. The HPV prevalence varied from 3.1% to 80.7%. In the random effects meta-analysis, the pooled prevalence of cervical HPV infection in SLE vs. controls was 34.15% (95% CI: 19.6%-52.5%) vs. 15.3% (95% CI 0.79-27.8%), OR = 2.87 (95% CI: 2.20-3.76) p < .0001, with large between-study heterogeneity (I2 = 95.4%). When only SLE women were evaluated, meta-regression showed no significant differences between patients with and without a background of multiple sexual partners and any immunosuppressive therapy. In addition, the prevalence of cervical HPV infection did not significantly differ between SLE patients on azathioprine or cyclophosphamide. CONCLUSIONS: This meta-analysis suggests that the prevalence of cervical HPV infection is higher in SLE women than in healthy controls. However, multiple sexual partners and any immunosuppressive therapy or specific immunosuppressive treatment (azathioprine and cyclophosphamide) were not associated with the prevalence of cervical HPV infection.

Vitamin D and Sjögren syndrome.

The immunomodulatory effects of vitamin D have been extensively studied in the context of autoimmunity. Multiple studies have demonstrated a high prevalence of vitamin D deficiency in autoimmune diseases. Recently, a possible protective role of vitamin D in autoimmunity has been described; however, this function remains controversial. Few studies have investigated the role of vitamin D in patients with Sjögren syndrome (SS). In this review, we compiled the main features of SS pathogenesis, the vitamin D immunomodulatory effects and the possible interaction between both. Data suggests that vitamin D may play a role in the SS pathogenesis. In addition, vitamin D low levels have been found in SS patients, which are associated with extra-glandular manifestations, such as lymphoma or neuropathy, suggesting a possible benefit effect of vitamin D in SS.