Minimal disease activity (MDA) in psoriatic arthritis (PsA) is a composite outcome measure that represents the multifaceted domains of psoriatic disease including the joints, enthesis and skin, as well as patient's reported outcomes (PRO). MDA is currently used as a goal of treatment in the "treat-to-target" (T2T) approach in PsA management. 1
Objectives
To assess the implementation of the T2T concept in PsA patients.
Methods
A retrospective analysis of all the patients included in a PsA registry during 2016- 2017 was performed. Medical charts were reviewed by an independent rheumatologist and the following data were collected: patient demographics, duration of PsA and psoriasis, alcohol and tobacco use, treatment changes, as well as items that constitute the MDA including the tender and swollen joint count, enthesitis, psoriasis area skin score (PASI), physician and patient evaluation of disease activity and pain and the health assessment questionnaire (HAQ) score. Medical records were reviewed to assess whether T2T concept was indeed followed by the treating rheumatologist to determinate whether MDA was achieved and medication changes were made. The associations between T2T concept implementation and categorical and continuous variables were assessed by Chi square test, or t-test as appropriate. The association between the physician's assessment at each visit with each of the MDA parameters (active versus inactive) was assessed by Chi square test.
Results
The records of 117 consecutive patients were evaluated, one patient was excluded due to lack of data. The mean age was 58.4±13 years, of whom 76 (65.5%) were women. The T2T approach was implemented in 76 (65.5%) patients. There was no correlation between the T2T implementation and patient age, gender, alcohol and tobacco use, disease activity parameters at the patient's visit and the various treatment regimens. The physician assessment of disease activity did not correlate with the MDA score in 40 (34.5%) patients. In most cases 30 (75%), this discrepancy occurred because physicians labelled patients as having inactive disease while disregarding the PRO category of the MDA score, including 29 patients who reported a high VAS pain score, 22 patients reporting a high patient global disease activity and 25 patients reporting a high HAQ- score. In the other 10 (25%) of cases, the treating rheumatologists made treatment changes because they considered patients as having active disease based on one tender or swollen joint or enthesis, despite these patients actually meeting MDA criteria.
Conclusions
In our cohort, the T2T concept was implemented in 65.5% of the visits in accordance with other PsA studies. The main obstacle that we encountered in implementation of MDA concept was in physicians' overlooking the PRO components of the score. Efforts are needed to increase the accurate use of the MDA score and treat to target concept in daily practice.
Reference
[1] Gossec L, McGonagle D, Korotaeva T, Lubrano E, de Miguel E, Østergaard M, Behrens F. Minimal Disease Activity as a Treatment Target in Psoriatic Arthritis: A Review of the Literature. J Rheumatol2018Jan;45(1):6–13.
Abstract BackgroundTreatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX).MethodsWe analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls immunized with BNT162b2 mRNA vaccine participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG measured at 2 to 6 weeks after the second vaccine dose. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX patients (n=48) immunized with the BNT162b2 mRNA vaccine.Results AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from non-responders by lower number of RTX courses (median (range) 3 (1-10) vs 5 (1-15), p=0.007; lower cumulative RTX dose 6943.11±5975.74 vs 9780.95±7240.12 mg, p=0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78±576.28 vs. 884.33±302.31 mg/dL, p=0.002, and extended interval between RTX treatment and vaccination, 469.82±570.39 vs 162.08±160.12 days, p=0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046-0.96, p=0.044 and OR 0.189, 95% CI 0.036-0.987, p=0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, 63.3% positive and 88.9% negative predictive values.ConclusionsThe predicting calculator might guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients.
Despite the increasing recognition of cardiac involvement in systemic sarcoidosis, the diagnosis of cardiac sarcoidosis (CS) remains challenging. Our aim is to present a comprehensive, retrospective case series of CS patients, focusing on the current diagnostic guidelines and management of this life-threatening condition. In our case series, patient data were collected retrospectively, including hospital admission records and rheumatology and cardiology clinic visit notes, detailing demographic, clinical, laboratory, pathology, and imaging studies, as well as cardiac devices and prescribed medications. Cases were divided into definite and probable CS based on the 2014 Heart Rhythm Society guidelines as well as presumed CS based on imaging criteria and clinical findings. Overall, 19 CS patients were included, 17 of whom were diagnosed with probable or presumed CS based on cardiac magnetic resonance imaging (CMR) and/or cardiac positron emission tomography using 18F-Fluorodeoxyglucose (PET-FDG) without supporting endomyocardial biopsy (EMB). The majority of CS patients were male (53%), with a mean age of 52.9 ± 11.8, with CS being the initial manifestation of sarcoidosis in 63% of cases. Most patients presented with high-grade AVB (63%), followed by heart failure (42%) and ventricular tachyarrhythmia (VT) (26%). This case series highlights the significance of utilizing updated diagnostic criteria relying on CMR and PET-FDG given that cardiac involvement can be the initial manifestation of systemic sarcoidosis, requiring prompt diagnosis and treatment to prevent morbidity and mortality.
Angiogenesis is critical for rheumatoid arthritis (RA) progression. The effects of tofacitinib, a JAK-STAT inhibitor used for RA treatment, on angiogenesis in RA are unclear. We, therefore, evaluated the levels of angiogenic factors in two systems of a human co-culture of fibroblast (HT1080) and monocytic (U937) cell lines treated with tofacitinib and in serum samples from RA patients before and after six months of tofacitinib treatment. Tofacitinib reduced CD147 levels, matrix metalloproteinase-9 (MMP-9) activity, and angiogenic potential but increased endostatin levels and secreted proteasome 20S activity. In vitro, tofacitinib did not change CD147 mRNA but increased miR-146a-5p expression and reduced STAT3 phosphorylation. We recently showed that CD147 regulates the ability of MMP-9 and secreted proteasome 20S to cleave collagen XVIIIA into endostatin. We show here that tofacitinib-enhanced endostatin levels are mediated by CD147, as CD147-siRNA or an anti-CD147 antibody blocked proteasome 20S activity. The correlation between CD147 and different disease severity scores supported this role. Lastly, tofacitinib reduced endostatin' s degradation by inhibiting cathepsin S activity and recombinant cathepsin S reversed this in both systems. Thus, tofacitinib inhibits angiogenesis by reducing pro-angiogenic factors and enhancing the anti-angiogenic factor endostatin in a dual effect mediated partly through CD147 and partly through cathepsin S.
Background: Persistence in biologic therapy in psoriatic arthritis is critical to optimize symptom remission, functional capacity and health care costs. Objectives: To estimate the persistence to biologic treatment prescribed to PsA patients in a real-life setting as well as factors associated with improved biologic drug survival in these patients. Methods: Patients with PsA from a large health care provider database with at least two consecutive dispensed prescriptions of a biologic agent indicated for PsA from January 1 st , 2002 until December 31 st , 2018 were identified and followed until medication stop date or the end of observation period. Patients were considered non-persistent whenever a new prescription was dispensed and a permissible gap of 6 months was exceeded prior to starting on this biologic agent from the prescription date. Treatment changes were based on physician decisions and patient preferences. Demographic data including age, sex, BMI, ethnicity, smoking history and socioeconomic status as well as Charlson comorbidity index were retrieved. Data regarding use of steroids and non-biologic disease-modifying anti-rheumatic drugs were also extracted. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Persistence estimates were derived using non-parametric survival analysis using Kaplan-Meier functions, with treatment discontinuations as failure events. Cox regression hazard ratio models were conducted to investigate factors associated with drug persistence. Results: 2301 PsA patients with 2958 treatment periods were identified and included in the analyses. The mean age was 50.9±14 years of whom 54% were females, 70.4% of the study population had a BMI>25, and 36% were obese(BMI>30), 40% were current smokers, and 76% had a Charlson comorbidity index higher than 1. The most commonly prescribed drug was etanercept, followed by adalimumab, golimumab, secukinumab, ustekinumab and infliximab at 33%, 29%, 12%, 10%,8% and 8%, respectively. Only about 20% of patients remained on a particular biologic agent after 5 years, whereas about 40% persisted on therapy following 20 months of treatment. A Kaplan-Mayer survival analysis with pairwise comparisons of all treatment choices with respect to lines of therapy was conducted. When analyzing the data for all treatment periods and taking into account all lines of therapy, secukinumab had a higher persistency than adalimumab, infliximab and ustekinumab, with a Log Rank of 0.022, 0.047 and 0.001, respectively, as is shown in figure 1. Female sex and smoking were associated with lower drug persistence (HR=1.25, 95%CI 1.13-1.38 and HR=1.109, 95%CI 1.01-1.21, respectively). When analyzing the data regarding second-line biologic agents, secukinumab was found to be superior to adalimumab, etanercept, infliximab and ustekinumab but not to golimumab with a Log-Rank P value of 0.001, 0.004, 0.025 and 0.002, respectively (figure 2). On analyzing the data using only the first indicated biologic line, no superiority of any single anti-Tumor Necrosis Factor-alpha (anti-TNFα) agent was observed. Conclusion: In this large observational cohort, in the era of biologic therapy, a relatively low persistence was observed, with female sex and smoking having a negative impact on persistency. None of the anti-TNFα agents as first line therapy was found to be more persistent than others, while secukinumab was found to be superior to other biologics when indicated as second line of therapy. References: None Figure 1. Figure 2. Acknowledgments: none Disclosure of Interests: None declared
Calcinosis or dystrophic soft-tissue calcification occurs in damaged/devitalized tissues in the presence of normal calcium/phosphorus metabolism.1 It is a known complication of connective tissues diseases, especially juvenile dermatomyositis and systemic sclerosis (SSc), and may be localized or widespread.2 Previous data from the Scleroderma Clinical Trials Consortium showed calcinosis to be most commonly associated with digital ulceration, osteoporosis, telangiectasias, and acroosteolysis,3 as well as with anticentromere, anti-PM/Scl, and anticardiolipin antibodies.3 …
To evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls.A prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2-6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample.The two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, p<0.0001, and 96.55% versus 74.26%, p<0.0001 at 2-6 weeks and at 6 months, respectively. The third vaccine dose restored the seropositive response in all controls and 80.47% of patients with AIIRD, p=0.0028. All patients treated with methotrexate monotherapy, anticytokine biologics, abatacept and janus kinase (JAK) inhibitors regained the humoral response after the third vaccine, compared with only a third of patients treated with rituximab, entailing a 16.1-fold risk for a negative humoral response, p≤0.0001. Cellular immune response in rituximab-treated patients was preserved before and after the third vaccine and was similar to controls. Breakthrough COVID-19 rate during the Delta surge was similar in patients and controls, 1.83% versus 1.43%, p=1.The two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.
Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease.The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs).Calcium ions (Ca 2+ ) are required for PAD activation, but the intracellular Ca 2+ concentration in normal cells is much lower than the optimal Ca 2+ concentration needed for PAD activation.For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca 2+ enters the cells, with the high Ca 2+ concentration activating PAD.Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that "hypercitrullination," citrullination of multiple intracellular proteins, occurs within synovial fluid (SF) cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination.In order for Romero's hypothesis to hold, it is reasonable to surmise that PMN-Citrullination in RA-A Process Promoted by PMN Lysis?
