Arthroplasty Rates and Risk in Familial Mediterranean Fever Patients: A large Population-Based Study.

BACKGROUND: Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and inflammation in various organs, including the joints. Traditionally, the arthritis of FMF has been considered relatively harmless. However, anecdotal evidence has suggested that it may contribute to long-term joint damage, which may necessitate surgical joint replacement. This study aimed to investigate the rates of arthroplasty among FMF patients and compare it to the general population. METHODS: The study used the electronic database of the largest healthcare organization in Israel to identify 9,769 FMF patients diagnosed between 2000 and 2016. A similar number of age-, gender-, and residency-matched controls were also identified. The rates of arthroplasty were compared between the two groups. A logistic regression model predicting the need for arthroplasty within the FMF group was formed to identify potential risk factors. RESULTS: Of the 9,769 FMF patients, 114 (1.2%) underwent arthroplasty, compared with 64 (0.7%) of the control group [unadjusted odds ratio (OR)=1.79, 95% confidence interval (CI) 1.32-2.43; partially adjusted OR = 1.97, 95% CI 1.40-2.77; fully adjusted OR = 1.92, 95% CI 1.35-2.72]. Within the FMF cohort, those of North African origin had a significantly higher risk of arthroplasty (OR = 6.89, 95% CI 5.09-9.33; p< 0.001). CONCLUSION: FMF patients can experience long-term joint damage that may require arthroplasty. Although this complication is relatively uncommon in FMF patients, it occurs almost twice as frequently as compared with the general population. FMF patients of North African origin are at an even higher risk.

Exploring the Link Between Ankylosing Spondylitis and Inflammatory Bowel Disease: A Retrospective Cohort Study.

BACKGROUND: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link. OBJECTIVES: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship. METHODS: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors. RESULTS: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls. CONCLUSIONS: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Increased risk for stroke in patients with familial Mediterranean fever: results from a large population-based study.

OBJECTIVE: The association between chronic inflammatory conditions and cardiovascular disease is well established. Considering FMF, few studies exist investigating the risk of ischaemic heart disease, and none address the risk of stroke. We aimed to evaluate the incidence and risk for stroke in FMF patients compared with the general population. METHODS: A retrospective cohort study using the electronic database of Clalit Health Services (CHS), the largest health organization in Israel. All FMF patients diagnosed between 2000 and 2016 were included and matched with control according to age, gender and place of residence. Follow-up continued until the first diagnosis of stroke or death. The incidence of stroke was compared between the groups using univariate and multivariate models adjusting for cardiovascular risk-factors. RESULTS: A total of 9769 FMF patients and a similar number of controls were followed up for a median period of 12.5 years. The mean age at the beginning of the follow-up was 25.7 years. In total, 208 FMF patients were diagnosed with stroke compared with 148 controls, resulting in an incidence rate (per 10 000 persons-years) of 19.8 (95% CI 17.2, 22.7) and 13.9 (95% CI 11.8, 16.4), respectively, and a crude HR of 1.42 (95% CI 1.15-1.76; P < 0.001). In a multivariate analysis, FMF patients who developed amyloidosis with related or non-related renal failure demonstrated significant stroke risk (HR = 2.16; 95% CI 1.38, 3.38; P < 0.001), as well as for those who did not develop these complications (HR = 1.32; 95% CI 1.04, 1.67; P < 0.05). CONCLUSION: FMF patients are at increased risk for stroke regardless of known complications.

Association of fibromyalgia with cancerous and non-cancerous gastrointestinal comorbidities: a cross-sectional study.

OBJECTIVES: Several studies have shown a higher prevalence of irritable bowel syndrome (IBS) among patients with fibromyalgia yet, data regarding association between fibromyalgia and other gastrointestinal disorders have been relatively overlooked. Our aim was to investigate the association between fibromyalgia and gastrointestinal disorders including both benign and malignant conditions. METHODS: We conducted a retrospective cross-sectional study based on the comprehensive electronic database of the largest health maintenance organisation in Israel. All subjects with a diagnosis of fibromyalgia in their medical records and age- and sex-matched controls were included in the study. We investigated the association of fibromyalgia with benign gastrointestinal disorders including IBS, gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), celiac disease, Crohn's disease, ulcerative colitis, and with gastrointestinal malignancies including colorectal, pancreatic, stomach, liver, and bile duct cancers. RESULTS: The study enrolled 18,598 patients with fibromyalgia and 36,985 controls. The mean age was 56.5 years (standard deviation=14) with a female predominance (91%). Fibromyalgia was significantly associated with IBS (OR 4.61, 95% CI 4.09-5.2, p<0.001), GERD (OR 2.62, 95% CI 2.5-2.75, p<0.001), PUD (OR 2.13, 95% CI 1.98-2.3, p<0.001), celiac disease (OR 2.08, 95% CI 1.63-2.65, p<0.001), Crohn's disease (OR 1.85, 95% CI 1.408-2.32, p<0.001) and ulcerative colitis (OR 1.81, 95%CI 1.4-2.33, p<0.001). Nonetheless, no significant differences were found regarding the prevalence of gastrointestinal malignancies between the fibromyalgia patients and controls. CONCLUSIONS: Our findings suggest that FM is positively associated with various benign but not malignant GI disorders.

Secukinumab real world drug retention compared to TNF-alpha inhibitors in psoriatic arthritis.

OBJECTIVES: To prospectively study real-world efficacy and safety of secukinumab in psoriatic arthritis (PsA) patients from the Israeli registry of inflammatory diseases. METHODS: PsA patients fulfilling the CASPAR criteria were included in the analysis from 2010 to 2019. The primary endpoint was secukinumab drug retention compared to other TNF-α inhibitors (TNFi). Bivariate and multivariate analyses were made by Cox regression analysis. Drug retention according to treatment line was examined with Kaplan-Meier curves. RESULTS: Included were 404 PsA patients who had 709 treatment courses during the study period. Ninety patients had been treated with secukinumab (22%). The secukinumab-treated patients were significantly older and their disease duration was longer. Secukinumab was less likely to be the first line of treatment compared to TNFi. Secukinumab had a drug retention comparable to TNFi, and a better drug retention than TNFi among biologic-experienced patients. Neither methotrexate combination nor body mass index affected the inefficacy event rate. Secukinumab had a similar rate of adverse events as TNFi. CONCLUSIONS: This multicentre real-world study demonstrated that secukinumab had a drug retention comparable to TNFi. Secukinumab had a better drug retention than TNFi among biologic-experienced patients. IL-17 inhibition is an effective mechanism of action to treat PsA in real life.

Increased risk of venous thromboembolism among patients with familial Mediterranean fever.

INTRODUCTION: Familial Mediterranean Fever (FMF) is an auto inflammatory disease characterized by acute febrile attacks, serositis, arthritis and skin rash. Previous studies have identified an association between venous thromboembolism (VTE) and various inflammatory and autoimmune disorders, driven in large part by inflammatory processes. Despite these established associations, there remains a paucity of data linking FMF to VTE. The purpose of this study is to evaluate the association between VTE in patients with FMF compared to matched controls. METHOD: A population based cross-sectional study was performed utilizing the electronic medical database of Israel's largest healthcare provider, Clalit Health Services. Using this database, we looked at the prevalence of VTE in a cohort of FMF patients compared to matched controls. Univariate logistic regression was used to evaluate the association between FMF and VTE. Multivariate analysis was conducted to adjust for age, sex, socioeconomic status and comorbidities associated with VTE. RESULTS: A total of 6534 FMF patients were identified and matched with an equal number of controls. In univariate analysis the cumulative percent of VTE was higher in FMF patient compared to matched controls (FMF 3%, Control 2%). In a multivariate logistic regression analysis FMF was found to be independently associated with VTE (HR 1.96, P < 0.001). CONCLUSION: FMF is associated with increased risk of VTE. This association is likely the result of a chronic and persisting inflammatory state. Physicians should be aware of this sequela and care must be undertaken to control unbalanced disease.

The frequency of sacroiliitis on MRI in subjects over 55 years of age.

OBJECTIVE: To evaluate the frequency of sacroiliitis in older subjects. MATERIALS AND METHODS: Consecutive MRI examinations of the sacroiliac joints (SIJs) performed for suspected sacroiliitis (2005-2019) in patients ≥ 18 years were retrospectively evaluated for the presence of active/structural lesions and were categorized for the presence/absence of sacroiliitis. Clinical and imaging parameters were compared between subjects with sacroiliitis according to age groups < 40 years, 40-55, and > 55 years. Clinical parameters including inflammatory back pain (IBP) and other spondyloarthritis (SpA) features were retrieved from the medical records. RESULTS: A total of 431 patients with SIJs MRI were evaluated: median age, 44 [IQR 35-54]; female:male 267(62%):164(38%). Sacroiliitis was diagnosed in 89 (20.6%) subjects-median age, 41 years [IQR 32-54], 52% females- and was equally prevalent among the different age groups: > 40 years old, 23.6%; 40-55, 20%; and > 55 years old, 17%, p = 0.43, with active/structural lesions equally dispersed. Older patients (> 55) started suffering from back pain at an older age and had a longer delay in diagnosis. Gender distribution, the presence of IBP, and other SpA features were no different in patients < 45 and > 55 years of age. CONCLUSIONS: The frequency of sacroiliitis on SIJs-MRI in subjects > 55 years is similar to its frequency in younger subjects and is associated with the same type and magnitude of active and structural MRI lesions. Clinical parameters such as IBP and additional SpA features are similarly prevalent in older and younger subjects suggesting they suffer from the same disease and differing only in age of presentation.

Association Between Behçet's Disease and Depression.

BACKGROUND: Behçet's disease (BD) is a chronic vasculitic multi-systemic disease of unknown etiology. BD is characterized by recurrent attacks of oral aphthae, genital ulcers, and uveitis. BD is a multisystemic disorder and as such it may provoke various psychiatric manifestations, including depression. OBJECTIVES: To evaluate the association between BD and depression, adjusting for established risk factors for depression. METHODS: We executed a cross-sectional study based on the Clalit Health Services database, the largest healthcare organization in Israel, serving over 4.4 million members. For this study 873 BD patients were detected and matched with 4369 controls by age and sex. RESULTS: The rate of depression was higher among the BD patients compared with the control group (9.39% vs 5.49%, respectively, odds ratio [OR] 1.79, 95% confidence interval [95%CI] 1.37-2.31, P < 0.001). An association between BD and depression was also observed on multivariable analysis (OR 1.83, 95%CI 1.39-2.39, P < 0.001). When stratifying the data, according to established risk factors, the association between BD and depression was prominent in the youngest age group (18-39 years of age), low and high socioeconomical status, and non-smokers. CONCLUSIONS: Establishing the association between BD and depression should influence the attitude and the treatment of BD patients, as this relationship requires a more holistic approach and a multidisciplinary treatment regimen for all patient needs.

Familial Mediterranean fever and asthma.

OBJECTIVE: To assess the association between FMF and asthma. METHODS: This study was designed as a cross-sectional study. All patients diagnosed with FMF between 1 January 2000 and 31 December 2016 who were prescribed colchicine were included in the study. Controls were matched by sex, date of birth, residential socioeconomic status and country of birth. Logistic regression models were used to determine the odds ratio for asthma in FMF patients and controls. RESULTS: A total of 7098 FMF patients who were prescribed colchicine were identified. Of them, 3547 (50%) were females, 3632 (51%) were of low residential socioeconomic status and 6160 (87%) were born in Israel. Their median age at the end of follow-up was 37 years (23-54). In an unadjusted logistic regression, FMF was associated with asthma [odds ratio (OR)=1.33, 95% CI: 1.17, 1.51; P <0.001]. The association persisted after adjusting for sex, socioeconomic status and country of birth (OR=1.33, 95% CI: 1.18, 1.52; P <0.001). CONCLUSION: FMF is positively associated with asthma. Further research is required to validate our results and explore possible explanations of this association. These findings cast doubt on previous studies implying FMF to be a protective factor from asthma.

Utilisation of healthcare services and drug consumption in fibromyalgia: A cross-sectional analysis of the Clalit Health Service database.

AIM: To investigate the health care utilisation and drug consumption of patients with fibromyalgia (FM). MATERIALS AND METHODS: This is a cross-sectional study using the Clalit Health Care database. Clalit is the largest HMO in Israel, serving more than 4.4 million enrollees. We identified FM patients and age and sex-matched controls. Indicators of healthcare utilisation and drug consumption were extracted and analysed for both groups. RESULTS: The study included 14 296 FM patients and 71 324 controls. The mean age was 56 years, with a women predominance of 92%. The mean number of visits across of all healthcare services (hospitalisations, emergency department visit, general practitioner clinic visits, rheumatology clinic visits, and pain clinic visits) and the mean difference (MD) were significantly higher for FM patients compared with controls (MD 0.66, P < .001; MD 0.23, P < .001; MD 7.49, P < .001; MD 0.31, P < .001; MD 0.13, P < .001), respectively. Drug use was significantly and consistently higher among FM patients compared with controls; NSAIDs (non-steroidal anti-inflammatory drugs) OR 2.56, P < .001; Opioids OR 4.23, P < .001; TCA (tricyclic antidepressants) OR 8.21, P < .001; Gabapentinoids OR 6.31, P < .001; SSRI (selective serotonin reuptake inhibitors) OR 2.07, P < .001; SNRI (serotonin-norepinephrine reuptake inhibitor) OR 7.43, P < .001. CONCLUSION: Healthcare utilisation and drug use are substantially higher among patients with FM compared with controls.

Autonomic Nervous System Indices in Patients with Systemic Sclerosis without Overt Cardiac Disease.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease that may affect the heart and the autonomic nervous system (ANS). There is little knowledge regarding the degree of ANS involvement in SSc patients with unknown cardiac disease. OBJECTIVES: To evaluate cardiac and pupillary autonomic functions in patients before cardiac involvement has emerged. METHODS: The study comprised 19 patients with SSc and 29 healthy controls. Heart rate variability (HRV) analysis for time and frequency domains, as well as deep breathing test and Ewing maneuvers, were performed in all patients. Automated pupillometry for the evaluation of pupillary diameter and pupillary light reflex was completed in 8 SSc patients and 21 controls. RESULTS: Both groups had similar characteristics, except for medications that were more commonly or solely prescribed for SSc patients. Compared with control subjects, the SSc patients had significantly lower HRV parameters of NN50 (15.8 ± 24.4 vs. 33.9 ± 33.1, P = 0.03), pNN50 (4.9 ± 7.4% vs.10.8 ± 10.8%, P = 0.03), and triangular index (11.7 ± 3.4 vs. 15.7 ± 5.8, P = 0.02). Abnormal adaptive responses in heart rate changes were recorded during deep breathing tests and Ewing maneuvers. There was no significant difference in any of the pupillometric indices or other HRV parameters within groups. CONCLUSIONS: SSc patients may manifest cardiac autonomic dysfunction, while their autonomic pupillary function is seemingly spared. The role of certain medications, the significance of differential organ involvement, as well as the prognostic value of our findings should be evaluated in future studies.

Tumor-like Lesions in Patients with Granulomatosis with Polyangiitis: A Case Series.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis. It usually involves the respiratory tract and kidney. Rarely, tumor-resembling inflammatory changes ensue. OBJECTIVES: To report three unique cases of GPA presenting with tumor-like lesions in various organs. METHODS: We presented three cases of GPA. Case 1 presented with typical upper respiratory symptoms of GPA and a mediastinal mass. Case 2 presented with low back pain, a large retroperitoneal mass, and nodular skin lesions. Case 3 presented with epigastric pain and a paravertebral inflammatory mass. RESULTS: The patients were treated successfully with rituximab. CONCLUSIONS: Clinicians should be aware of this presentation of granulomatosis with polyangiitis, which is known as Tumefaction Wegener's granulomatosis.

Familial Mediterranean fever is associated with increased risk for ischaemic heart disease and mortality-Perspective derived from a large database.

AIMS OF THE STUDY: Familial Mediterranean fever (FMF) is a hereditary, auto-inflammatory disease, characterised by recurrent, self-limiting attacks of fever with inflammation of the serosal membranes, joints, and skin. Chronic inflammation was previously associated with increased risk for ischaemic heart disease (IHD). However, the association between FMF and IHD remains unclear. The objective of this study is to determine whether this association exists. METHODS: Utilising the database of the largest health-care provider in Israel, a cross-sectional study was performed. The incidence of IHD was compared between patients diagnosed with FMF and age and sex-matched controls. Chi-square and t-test were used for categorial and continuous variables, and cox logistics regression model was used for multivariate analysis. Survival analysis was made using Kaplan-Meier plots and log-rank test. RESULTS: The study included 7670 patients diagnosed with FMF and an equal number of controls without FMF. In a univariate analysis FMF was found to be associated with higher prevalence of IHD (OR 1.33) and increased mortality (OR 1.29). In a multivariate analysis FMF was found to be independently associated with increased risk for IHD (OR 1.44). CONCLUSION: The study shows that FMF is associated with both increased risk for IHD and higher mortality rates. An early diagnosis and treatment of this disease can potentially improve patients' life expectancy and decrease cardiac comorbidities.

The long-term prognostic significance of sarcoidosis-associated pulmonary hypertension - A cohort study.

BACKGROUND: Sarcoidosis is a multisystem, chronic, progressive, granulomatous disease. Sarcoidosis-associated pulmonary hypertension is a well described, but not common, complication of sarcoidosis. In small scale studies, it has been previously described as manifestation of advanced disease and was found to be associated increased morbidity and mortality. This study sought to assess the long-term prognostic significance of sarcoidosis-associated pulmonary hypertension (SAPH) by using data obtained from a large population-based registry which contains longitudinal follow-up data. METHODS: Utilizing the records of the largest healthcare provider in Israel, we extracted a cohort consisting of sarcoidosis patients and age-and-sex matched controls. Dates of sarcoidosis registration, pulmonary hypertension and death, as well as anthropometric information and medical comorbidities, were extracted from the database. A multivariate logistic regression model was used to find variables associated with pulmonary hypertension. Cox proportional hazards method and log-rank test were used for survival analysis. RESULTS: The cohort included 3993 sarcoidosis patients and 19,856 controls. Pulmonary hypertension was observed among 269 sarcoidosis patients (6.74%) vs. 400 controls (2.01%). Sarcoidosis was found as independently associated with pulmonary hypertension (OR 3.17). After a mean follow-up of 7.49 years (median 7.24, maximum 17.88 years), 710 (17.8%) of the sarcoidosis patients and 2121 (10.7%) of the controls had died. Both sarcoidosis and pulmonary hypertension were found to be significantly associated with an increased risk of all-cause mortality (HR 1.82 and HR 2.31, respectively). CONCLUSIONS: SAPH is associated with a poor prognosis. Proper screening methods may assess whether early identification and treatment improve life expectancy.

Characterization of adherence and persistence profile in a real-life population of patients treated with adalimumab.

AIMS: Published data on long-term adherence and persistence with adalimumab (Humira® ) in clinical practice are scarce and often limited to selected patient populations. This study assessed adherence with adalimumab across different indications and identified correlates and outcomes of poor adherence. METHODS: We analysed data originating from the electronic database of Maccabi Healthcare Services (MHS) that includes 2.1 million enrolees. We randomly selected patients with at least one dispense of adalimumab since it was included in the local health basket in Israel in 2008 until the end of 2013. Patients with the following indications (n = 1339) were included: Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriatic arthritis (PSA), ankylosing spondylitis (AS) and psoriasis. Adherence with therapy was assessed by the medication possession ratio (MPR) during the follow-up period. RESULTS: Good adherence (MPR ≥ 80%) was observed among 80% of study patients and was associated with lower risk for ≥1 hospitalization per year of follow-up (adjusted-OR = 1.94, 95% CI:1.15-3.28). Patients with AS and CD persisted on adalimumab therapy the most, reaching median use of 27.0 and 26.7 months, respectively. Half (52.4%) of the patients discontinued treatment during a mean (SD) follow-up of 3.07 (1.71) years. High socioeconomic status was associated with lower risk for discontinuation (adjusted-HR = 0.74; 0.60-0.91). UC and concomitant prednisolone use were associated with increased risk for treatment discontinuation (HR = 1.31; 1.00-1.72, and HR = 1.40; 1.17-1.68, respectively). CONCLUSION: Our results indicate encouraging persistence and adherence with adalimumab of patients with inflammatory conditions.

High proportions of dementia among SLE patients: A big data analysis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a wide range of systems including the peripheral and central nervous system. Cognitive impairment leading to dementia is one of the harmful central nervous system afflictions of SLE. The aim of this study was to investigate the association of SLE with dementia. METHODS: A cross-sectional study was conducted using Clalit Health Care database, the largest health maintenance organization in Israel with more than 4.4 million enrollees. Systemic lupus erythematosus patients were compared in a 1:5 ratio to age- and sex-matched controls. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. RESULTS: The study included 4886 SLE patients and 24 430 age-frequency- and sex-frequency-matched controls without SLE. The proportion of dementia was higher among SLE patients compared to controls (1.56% and 0.51%, respectively; P < .001). This finding was consistent across all age groups by univariate analysis. In a multivariate logistic regression analysis, SLE was significantly associated with dementia (odds ratio = 1.51, 95% confidence interval, 1.11-2.04). CONCLUSION: Systemic lupus erythematosus is significantly associated with dementia. This finding should give rise to search for SLE in patients with an ambiguous cause for dementia, especially those with an early onset cognitive decline.

Stroke among Rheumatoid Arthritis Patients: Does Age Matter? A Real-Life Study.

BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disease that affects the joints and it is known to be associated with cardiovascular morbidity. However, the association between RA and stroke among different age groups has not been explored. The objective of our study was to evaluate the association between RA and stroke in different age strata. METHODS: Cross-sectional study, utilizing the database of Israel's largest healthcare provider. The proportion of stroke was compared between patients diagnosed with RA and age- and gender-matched controls. The study sample was divided into 2 age groups: young (≤65 years) and elderly (>65 years). Multivariable analysis was performed using logistic regression. RESULTS: The study included 11,782 RA patients and 57,973 age- and gender-matched controls. RA patients, primarily young, had more cardiovascular risk factors than controls. Stroke rates were significantly elevated among young RA patients in comparison with controls (3.74 vs. 2.20%, respectively, p < 0.001). In multivariate analysis, RA was found to be independently associated with stroke (OR 1.18, 95% CI 1.09-1.28). CONCLUSION: RA is independently associated with stroke, especially among RA patients under 65 years, for whom cardiovascular risk factors were more prominent. Physicians should advise RA patients to manage their risk factors strictly.

Successful modulation of murine lupus nephritis with tuftsin-phosphorylcholine.

In areas where helminths infections are common, autoimmune diseases are rare. Treatment with helminths and ova from helminths, improved clinical findings of inflammatory bowel disease, multiple-sclerosis and rheumatoid-arthritis. The immunomodulatory functions of some helminths were attributed to the phosphorylcholine (PC) moiety. We aimed to decipher the tolerogenic potential of Tuftsin-PC (TPC) compound in mice genetically prone to develop lupus. Lupus prone NZBXW/F1 mice received subcutaneously TPC (5 µg/1 ml), 3 times a week starting at 14 weeks age. Autoantibodies were tested by ELISA, T-regulatory-cells by FACS, cytokines profile by RT-PCR and cytokines protein levels by DuoSet ELISA. Glomerulonephritis was addressed by detection of proteinuria, and immunoglobulin complex deposition in the mesangium of the kidneys of the mice by immunofluorescence. Our results show that TPC attenuated the development of glomerulonephritis in lupus prone mice, in particular, it ameliorated proteinuria (p < 0.02), and reduced immunoglobulin deposition in the kidney mesangium. TPC also enhanced the expression of TGFß and IL-10 (p < 0.001), and inhibited the production of IFNγ and IL-17 (p < 0.03). TPC Significantly enhanced the expansion of CD4+CD25+FOXP3+ T-regulatory cells (Tregs) phenotype in the treated mice. These data indicate that TPC hampered lupus development in genetically lupus prone mice which was exemplified by moderate glomerulonephritis, attenuation of pro-inflammatory cytokines and enhancement of anti-inflammatory cytokines expression, as well as Tregs expansion. Our results propose harnessing novel natural therapy for lupus patients.

Rituximab-induced remission in a woman with coexisting rheumatoid arthritis and nephrotic syndrome.

We describe a patient with rheumatoid arthritis who presented with nephrotic syndrome which was not related neither to drug therapy nor to amyloidosis. Renal biopsy revealed membranous glomerulonephritis. The patient was treated with three cycles of rituximab with complete resolution of the clinical and laboratory evidence of nephrosis. The following report discusses this unusual presentation and clinical response.

Real-World Drug Survival of Biologics and Targeted Synthetic Disease-Modifying Anti-rheumatic Drugs Among Patients with Psoriatic Arthritis.

BACKGROUND: While the variety of biologics (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) available for patients with psoriatic arthritis (PsA) has proved to be efficacious in randomized clinical trials, there is a growing importance to understand the benefits and potential drawbacks of these different therapies in real-world settings, which includes bio-experienced and older patients as well. OBJECTIVE: To evaluate the real-world adherence, drug survival, and discontinuation risk of bDMARDs and tsDMARDs among patients with PsA, comprising both younger and older patients. METHODS: A retrospective study using a computerized database. Treatment-naïve and treatment-experiencedpatients with PsA, younger and older than 60 years, who initiated treatment with bDMARDs [TNF-α inhibitors (TNF-αis), IL-17 inhibitors (IL-17is), IL-12/23 inhibitors (IL-12/23i)] or tsDMARDs (the PDE-4 inhibitor apremilast) during 2015-2018 were included. Adherence was assessed using the proportion of days covered (PDC) method. Time to discontinuation was analyzed using Kaplan-Meier estimates. Risk of discontinuation was estimated by Cox proportional hazard model. RESULTS: We identified 427 eligible patients (22.2 % were older than 60 years), utilizing 673 treatment lines. The proportion of adherent patients (PDC ≥ 0.8) was similar (62.1-66.5%) across all lines of therapy and across different biologics (70.0-72.0%), while apremilast showed the lowest, in both treatment-naïve and experienced settings (43.6% and 25.5%, respectively). The Kaplan-Meier analysis showed that in the treatment-naïve TNF-αis had higher drug survival compared with apremilast (P = 0.032). Apremilast also had the lowest drug survival in the treatment-experienced group (P < 0.0001). Kaplan-Meier analysis by age groups showed similar drug survival rates in older (≥ 60 years) and younger (age < 60 years) patients, regardless of treatment-experience status. The multivariable model showed that apremilast had increased risk for discontinuation compared with TNF-αis. CONCLUSION: Adherence, drug survival and risk for discontinuation were similar for all included bDMARDs, regardless of treatment experience status, while apremilast showed lower rates and increased risk. Adherence and discontinuation rate were similar in older and younger patients. With the variety of drug modes of action available for patients with PsA, these findings may assist caregivers in selecting the appropriate treatment.