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OBJECTIVES: This study contributes to the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)s effort to define difficult-to-treat PsA (D2T-PsA), leveraging insights of healthcare professionals who are GRAPPA members. The primary objective is to inform GRAPPAs D2T PsA project, ensuring the consensus definition reflects clinical experience and expertise. METHODS: An online survey was conducted among GRAPPAs healthcare professionals managing PsA patients. The survey covered demographic details, structured questions, and open-ended queries to gather comprehensive insights into the experts viewpoints. RESULTS: About 223 physicians completed the survey, comprising 179 (80.2%) rheumatologists and 40 (17.9%) dermatologists. The majority, 184 (82.5%), favoured establishing distinct definitions for D2T-PsA and complex-to-manage PsA (C2M-PsA). Furthermore, 202 (90.5%) supported a definition that includes objective inflammation signs (clinical, laboratory, imaging, among others). However, opinions varied on the criteria for prior treatment failures, with most (93, 41.7%) favouring a definition that includes at least one conventional synthetic disease-modifying anti-rheumatic drug and two or more biological- or targeted-synthetic-DMARDs with different mechanisms of action. CONCLUSION: The survey reveals a majority opinion among GRAPPA experts favouring the differentiation between D2T-PsA and C2M-PsA, and the inclusion of objective inflammatory markers in these definitions. However, there is less than 50% agreement on the specific treatment failure criteria, particularly regarding the number of therapies needed to classify PsA as D2T. These findings suggest a need for continued discussion to reach a more unified approach in defining D2T-PsA, reflecting the complexity of the condition.

Background: The efficacy and safety of bimekizumab (BKZ), an inhibitor of interleukin (IL)-17F in addition to IL-17A, has been established in axial spondyloarthritis (axSpA). Early assessment of new bone formation is possible using 18F-fluoride positron emission tomography-computerised tomography (PET-CT) imaging to quantitatively monitor osteoblastic activity. Objectives: This exploratory study, initiated before phase IIb/III studies, assessed the efficacy and safety of BKZ in patients with radiographic (r-)axSpA and its effect on new bone formation. Design: Patients were randomised 2:1 to BKZ 160 mg every 2 weeks (Q2W; Weeks 0–10) then 320 mg Q4W (Weeks 12–44), or the reference drug: certolizumab pegol (CZP) 400 mg Q2W (Weeks 0–4), then 200 mg Q2W (Weeks 6–10), 400 mg Q4W (Weeks 12–44). Methods: Primary (Axial Spondyloarthritis Disease Activity Score (ASDAS) change from baseline (CfB)) and secondary endpoints (ASDAS-ID, ASDAS-MI) were assessed at Week 12. PET-positive axSpA lesion counts and osteoblastic activity quantification (mean SUVauc) were performed at baseline and Weeks 12 and 48 in the sacroiliac joints and spine (PET-CT substudy; not powered to evaluate differences). Results: In total, 76 patients were randomised; 26/76 entered the PET-CT substudy. At Week 12, the mean ASDAS CfB with BKZ was −2.1 (CZP: −1.8); ASDAS-ID and ASDAS-MI were achieved by 23.9% (11/46) (CZP: 20.8% (5/24)) and 60.9% (28/46) (CZP: 45.8% (11/24)) patients. Across treatments, clinical efficacy was maintained or increased further at Week 48. In the PET-CT substudy, the total number of PET-positive axSpA lesions and mean SUVauc were substantially reduced from baseline at Week 12 with BKZ and CZP, with reductions maintained or further reduced at Week 48. Treatments were well tolerated with no new safety signals. Conclusion: Dual inhibition of IL-17A and IL-17F with BKZ resulted in improved clinical outcomes and reduced osteoblastic activity in patients with r-axSpA, suggesting the potential of BKZ to reduce disease activity and new bone formation within 12 weeks of treatment. CZP findings were consistent with previous data. No new safety signals were identified. Trial registration: ClinicalTrials.gov, NCT03215277 (https://clinicaltrials.gov/study/NCT03215277). [ABSTRACT FROM AUTHOR]

ObjectivesThis pilot study aimed to identify early predictors of drug retention in patients with clinically active peripheral psoriatic arthritis who initiated or switched to therapy with biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs).MethodsClinical and ultrasound assessments were conducted at baseline (t0) and subsequently at 1 (t1), 3 (t3), and 6 (t6) months. Ultrasound evaluations targeted joints/entheses according to PsASon-Score13 and the most clinically involved joint/enthesis/tendon or the two most clinically involved joints/entheses/tendons (MIJET and 2MIJET). After 6 months of follow-up, patients were divided into two groups based on drug retention, determined by the clinician's assessment of treatment efficacy (cResponder vs. non-cResponder). Main endpoints were ultrasound changes in MIJET, 2MIJET, and GUIS (Global US Inflammation Subscore) derived from PsASon-13.ResultsTwenty-nine patients were enrolled, 22 cResponders and 7 non-cResponders at t6. In the comparison between cResponders and non-cResponders, GUIS variation significantly differed in Δt6-t0, while MIJET and 2MIJET variations were significant as early as Δt3-t0 and confirmed in Δt6-t0. The ultrasound response of MIJET and 2MIJET was faster in cResponders treated with JAKi vs. those treated with TNFi and IL-17/12-23i, significant in Δt1-t0.ConclusionsUltrasound imaging of clinically involved joint sites may be a valuable early predictor of therapy response for predicting drug retention at 6 months in patients with psoriatic arthritis.

Abstract Introduction A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab. Methods Individual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI). Results At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure. Conclusions Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered.

Objective Caution has been advocated recently when using Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) patients with an unfavourable cardiovascular risk profile. We aimed to compare the incidences in cardiovascular events between JAKi and biologic DMARDs (bDMARDs) in a large population of RA patients. Methods RA patients starting a new bDMARD or JAKi between 1 August 2018 and 31 January 2022 have been selected from IQVIA's Dutch Real-World Data Longitudinal Prescription database, covering about 63% of outpatient prescriptions in the Netherlands. Study outcome was a cardiovascular event, defined as the start of platelet aggregation inhibitors during the study period. The incidence densities of cardiovascular events were compared between JAKi and bDMARDs using multilevel Poisson regression, adjusted for exposure time and confounders. Results The number of unique patients included was 15 191, with 28 481 patient-years on treatment with either JAKi (2373) or bDMARDs (26 108). Most patients were female (72%) and median age was 62 years. We found 36 cardiovascular events (1.52 events/100 patient-years) during therapy with JAKi and 383 events (1.47 events/100 patient-years) during therapy with bDMARDs, resulting in an adjusted incidence rate ratio (IRR) of 0.99 for JAKi compared with bDMARDs (95% CI: 0.70, 1.41). Sub-analyses in patients >65 years, by sex, or separately for tofacitinib and baricitinib, yielded similar results. Conclusion In a large Dutch general RA population, the risk of cardiovascular events seems not to be different between JAKi users and those using bDMARDs, although a small increase in higher risk patients cannot be excluded. [ABSTRACT FROM AUTHOR]

Introduction: A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab. Methods: Individual patient data from BE MOBILE 2 (bimekizumab 160 mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150 mg), MEASURE 3 (secukinumab 300 mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI). Results: At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150 mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300 mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80 mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure. Conclusions: Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150 mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80 mg were mostly non-significant, depending on the populations considered. [ABSTRACT FROM AUTHOR]

BackgroundRheumatoid arthritis (RA) is a common condition treated with biological disease-modifying anti-rheumatic medicines (bDMARDs). However, many patients exhibit resistance, necessitating the use of machine learning models to predict remissions in patients treated with bDMARDs, thereby reducing healthcare costs and minimizing negative effects.ObjectiveThe study aims to develop machine learning models using data from the Kuwait Registry for Rheumatic Diseases (KRRD) to identify clinical characteristics predictive of remission in RA patients treated with biologics.MethodsThe study collected follow-up data from 1,968 patients treated with bDMARDs from four public hospitals in Kuwait from 2013 to 2022. Machine learning techniques like lasso, ridge, support vector machine, random forest, XGBoost, and Shapley additive explanation were used to predict remission at a 1-year follow-up.ResultsThe study used the Shapley plot in explainable Artificial Intelligence (XAI) to analyze the effects of predictors on remission prognosis across different types of bDMARDs. Top clinical features were identified for patients treated with bDMARDs, each associated with specific mean SHAP values. The findings highlight the importance of clinical assessments and specific treatments in shaping treatment outcomes.ConclusionThe proposed machine learning model system effectively identifies clinical features predicting remission in bDMARDs, potentially improving treatment efficacy in rheumatoid arthritis patients.

Introduction: This study aims to evaluate the persistence, treatment adherence and drug cost associated with biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the management of psoriatic arthritis (PsA) in Italy, with a focus on biosimilar drugs. Methods: This was a retrospective observational study involving eight hospital pharmacies, between January 2017 and December 2020, on naïve patients with at least one b/tsDMARD dispensation indicated for PsA. Patients were followed up for 12 months and persistence and adherence were evaluated by proportion of days covered (PDC). The originator and biosimilar for adalimumab and etanercept were compared. Furthermore, the real annual cost per patient based on adherence to therapy was calculated. Results: Patients initiating b/tsDMARDs for PsA had a mean persistence of 263 days and 48.6% remained persistent for 1 year. Adherent patients (PDC ≥ 0.8) were 47.6% for the overall population. Similar persistence and adherence were observed between patients treated with the adalimumab originator and its biosimilar, while patients treated with the etanercept originator showed lower persistence and adherence compared to those treated with its biosimilar (mean persistence: 222 vs. 267 days, patient persistent at 1 year: 29.4% vs. 51.5%, mean PDC: 0.53 vs. 0.70, adherent patients: 23.5% vs. 51.5%). The average annual drug cost ranged from €8,724 (etanercept) to €14,783 (ustekinumab), with an annual saving of more than €2,500 by using biosimilars. Conclusion: Poor adherence to medications contributes to suboptimal clinical outcomes. The comparison between biosimilar and originator offers further evidence in support of the biosimilar to optimizing resources in healthcare.

Purpose of Review: Limited data is available for tapering or discontinuation of biologic therapy in patients with axSpA who are in disease remission. The current review concentrates on published studies regarding dose tapering or withdrawal of biologics in axSpA. Recent Findings: Recent evidence in light of randomized controlled trials suggests that tapering of b-DMARDs is a feasible strategy to maintain remission or low disease activity in axSpA patients. TNF inhibitors were the studied biologics in most of these trials. The disease flare rates were comparable to those maintained on standard dose in most of these studies, although with variable tapering strategies and follow-up. Additionally, the duration of disease in remission prior to tapering, studied primary outcome, and flare definitions were heterogeneous. Female sex, HLA-B*27 negativity, high physician global score, and high CRP were negative predictors of successful tapering, but not consistently reported in all the trials. Although designed to address efficacy, there were no safety concerns with b-DMARD tapering. Withdrawal or complete discontinuation of biologics met with increased risk of flares compared to standard dosing. Summary: Tapering of TNF inhibitors may be feasible in certain axSpA patients with an acceptable disease state; however, discontinuation is not currently recommended owing to increased risk of flare. Future studies with axSpA patients with longer remission duration prior to taper and different doses and types of b-DMARDs may provide more guidance. [ABSTRACT FROM AUTHOR]

Objective The rate of pleuroparenchymal involvement in patients with SpA varies widely, from 0% to 85%. The most common form is apical fibrobullous disease (AFLD). The aim of this study was to determine the incidence of AFLD and associated factors in SpA patients under and/or planned to start biologic DMARDs (bDMARDs) therapy. Methods The records of 3021 SPA patients registered with HUR-BIO who had indication of bDMARDs between 2010 and 2021 were scanned. The study included 2489 patients with at least one chest radiograph (X-ray). Patient demographics, comorbidities, laboratory data, bDMARDs used, baseline DASs, and purified protein derivative and/or QuantiFERON test results before initiation of bDMARDs were recorded. Results Of the 2489 patients, 36 (1.4%) were found to have AFLD by X-ray and/or CT. The mean disease duration was 11.7 (7.1) years. Patients with AFLD were more likely to be male [28 (77.8%) vs 1321 (53.9%), P  = 0.004], older [56.3 (10.5) years vs 44.8 (11.4) years, P  < 0.001], heavy smokers [27 (79.4%) vs 1468 (60.9%), P  = 0.028] and have had longer disease duration [17. 7 (9.7) years vs 11.6 (7) years, P  = 0.001]. QuantiFERON positivity was higher in the AFLD group [9 (36%) vs 309 (16.1%), P  = 0.013]. While treatment with adalimumab was less preferred in those with AFLD, treatment with etanercept was more frequently preferred. Conclusion As the radiological findings of AFLD can be confused with those of tuberculosis, special attention should be paid to differentiating between tuberculosis and the disease in males and in patients who have had long disease duration. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Psoriasis and psoriatic arthritis (PsA) are closely linked to cancer, as supported by the literature. Systemic treatments for psoriasis and PsA, namely non-biological disease-modifying anti-rheumatic drugs (DMARDs), have been associated with increased cancer risk in both conditions. New, more effective biological DMARDs (bDMARDs) do not seem to be associated with higher overall cancer risk compared to those not receiving bDMARDs, opening up possibilities for treating patients with previous or ongoing oncological disease alongside psoriasis and PsA. However, limited literature exists on treating PsA patients with cancer with bDMARDs. This study aims to assess the safety of secukinumab, a bDMARD, in patients with PsA and concurrent cancer. Here, we describe a case series of four patients with PsA treated with bDMARD secukinumab and review the literature on the subject. CASE SERIES: We assessed the laboratory parameters and clinical characteristics of 4 patients with PsA treated with the bDMARD secukinumab and followed up until 30 months. Three patients had oncological disease in remission, while one had active neoplasia. No cancer progression was observed during the treatment of these patients with secukinumab. CONCLUSIONS: In conclusion, our case series, consisting of four PsA patients with concurrent neoplasia treated with secukinumab, showed no evidence of cancer progression and represents the first case of PsA described in the literature treated during active oncological disease, lending support to the safety of secukinumab for the treatment of patients with PsA and concomitant neoplasia. [ABSTRACT FROM AUTHOR]

This study aimed to examine the changes in biomarker levels in responders and non-responders to tumor necrosis factor alpha inhibitor (TNFi) and interleukin-17A inhibitor (IL-17Ai) in psoriatic arthritis (PsA) patients over a 4-month period after treatment initiation. A total of 68 PsA patients initiating either TNFi, IL-17Ai, or methotrexate treatment were included. Blood plasma and clinical outcome measures were collected adjacent to treatment initiation and after four months. A commercially available multiplex immunoassay was included to evaluate 54 biomarkers. Mean changes were used to evaluate change over time. A statistically significant decrease in pro-inflammatory cytokines IL-6 (log-transformed mean change −0.97, 95%CI −4.30; 2.37, [p = 0.032]) and an increase in anti-inflammatory IL-10 (0.38, 95%CI 1.74; 2.50 [p = 0.010]) were seen in TNFi responders. Meanwhile, a statistically significant increase in the target cytokine IL-17A was seen in both IL-17Ai responders (2.49, 95%CI −1.84; 6.85 [p = 0.031]) and non-responders (2.48, 95%CI −1.46; 6.41 [p = 0.001]). This study demonstrated differing changes in cytokine levels when comparing treatment responders and non-responders, highlighting the need to improve the understanding of the different immune response mechanisms explaining different responses to medical treatment in PsA patients. [ABSTRACT FROM AUTHOR]

Total elbow arthroplasty (TEA), categorized into linked and unlinked types, is a commonly reported treatment for rheumatoid arthritis of the elbow. Although unlinked TEA preserves bone, it may result in instability. This study aimed to assess the outcomes of unlinked TEA in rheumatoid arthritis of the elbow beyond 2 years and to identify factors correlating with postoperative valgus instability of unlinked TEA. This study included patients who underwent TEA for rheumatoid arthritis of the elbow at our department between August 2009 and January 2017, with a follow-up period exceeding 2 years. Elbow joint range of motion (ROM) and clinical scores were evaluated preoperatively and at the final follow-up. Factors contributing to valgus instability, such as the Larsen grade, sex, age, side, preoperative ROM, postoperative ROM, implant placement, preoperative carrying angle, and the use of biological disease-modifying antirheumatic drugs (bDMARDs), were also assessed. This study encompassed 26 elbows from 23 patients, with a mean patient age at surgery of 64.8 years and a mean follow-up duration of 92.4 months. Significant improvements were observed in the ROM (extension: from −31° preoperatively to −21° postoperatively [ P =.02], flexion: from 116° to137° [ P <.001]), Japanese Orthopaedic Association-Japan Elbow Society Elbow Function Score (from 45.9 to 86.3 points [ P <.001]), and Mayo Elbow Performance Score (from 43.6 to 91.7 points [ P <.001]). At the last follow-up, 2 elbows exhibited radiolucent lines around the humeral stem, whereas 7 had valgus instability. Factors correlated with valgus instability included total arc at the final follow-up, preoperative carrying angle, and the use of bDMARDs. Unlinked TEA demonstrated favorable midterm outcomes for rheumatoid arthritis of the elbow, albeit with occasional valgus instability. Surgeons should consider preoperative carrying angle and bDMARD use, and exercise caution regarding intraoperative extensions. [ABSTRACT FROM AUTHOR]

Abstract Background Juvenile idiopathic arthritis (JIA) treatment is aimed at inducing remission to prevent joint destruction and disability. However, it is unclear what is the long-term impact on health-related outcomes of the timing of biological disease-modifying antirheumatic drug (bDMARD) initiation in JIA. Our aim was to evaluate the long-term impact of the time between JIA onset and the initiation of a bDMARD in achieving clinical remission, on physical disability and health-related quality of life (HRQoL). Methods Adult JIA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) and ever treated with bDMARD were included. Data regarding socio-demographic, JIA-related characteristics, disease activity, physical disability (HAQ-DI), HRQoL (SF-36), and treatments were collected at the last visit. Patients were divided into 3 groups (≤ 2 years, 2–5 years, or > 5 years), according to the time from disease onset to bDMARD initiation. Regression models were obtained considering remission on/off medication, HAQ-DI, SF-36, and joint surgeries as outcomes and time from disease onset to bDMARD start as an independent variable. Results Three hundred sixty-one adult JIA patients were evaluated, with a median disease duration of 20.3 years (IQR 12.1; 30.2). 40.4% had active disease, 35.1% were in remission on medication, and 24.4% were in drug-free remission; 71% reported some degree of physical disability. Starting a bDMARD > 5 years after disease onset decreased the chance of achieving remission off medication (OR 0.24; 95% CI 0.06, 0.92; p = 0.038). Patients who started a bDMARD after 5 years of disease onset had a higher HAQ and worse scores in the physical component, vitality, and social function domains of SF-36, and more joint surgeries when compared to an earlier start. Conclusion Later initiation of bDMARDs in JIA is associated with a greater physical disability, worse HRQoL, and lower chance of drug-free remission in adulthood.

Background: Rheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population. Methods: From January 2004 through December 2020, 1068 RA patients undergoing b/tsDMARDs therapy and 416 patients with HBsAg--/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed. Results: During 2845 person-years of follow-up, 27 of 416 (6.5%,9.5 per 1000 personyears) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5 years, 6.1% at 10 years and 24.2% at 17 years. The median interval from beginning b/tsDMARDs to HBV reactivation was 85 months (range: 9--186 months). The risk of HBV reactivation varied by type of b/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person-years), followed by abatacept (incidence rate: 24.0 per 1000 person-years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12--60.32, p = .001), abatacept (aHR: 9.30, 1.83--47.19, p = .007), adalimumab (aHR: 3.86, 1.05--14.26, p = .04) and negative baseline HBV surface antibody (anti-HBs, <10 mIU/mL) (aHR: 3.89, 1.70--8.92, p < .001) were independent risk factors for HBV reactivation. Conclusion: HBsAg--/HBcAb+ RA patients are susceptible to HBV reactivation during b/tsDMARD therapy. Those with negative baseline anti-HBs and those on certain b/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti-HBs titre and type of therapy. [ABSTRACT FROM AUTHOR]

Objectives To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. Methods In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan–Meier analysis for time to resolution, and as-observed data for other outcomes. Results Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52. Conclusion Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition. Trial registration ClinicalTrials.gov , NCT02745080 [ABSTRACT FROM AUTHOR]

Background: Spondyloarthritis (SpA) is a group of related but phenotypically distinct inflammatory disorders that include axial SpA (axSpA) and psoriatic arthritis (PsA). Information on the characteristics and management of these patients in the real world remains scarce. Objectives: To explore the characteristics and management [disease activity assessment and treatment with secukinumab (SEC) or other biologic disease-modifying antirheumatic drugs (bDMARDs)] of axSpA and PsA patients using natural language processing (NLP) in Electronic Health Records (EHRs). Design: National, multicenter, observational, and retrospective study. Methods: We analyzed free-text and structured clinical information from EHR at three hospitals. All adult patients with axSpA, PsA or non-classified SpA from 2018 to 2021 with minimum follow-up of three months were included when starting SEC or other bDMARDs. Clinical variables were extracted using EHRead ® technology based on Systemized Nomenclature of Medicine-Clinical Terms (SNOMED CT) terminology. Results: Out of 887,735 patients, 758 were included, of which 328 had axSpA [58.5% male; mean (SD) age of 50.7 (12.7) years], 365 PsA [54.8% female, 53.9 (12.4) years], and 65 non-classified SpA. Mean (SD) time since diagnosis was 36.8 (61.0) and 24.1 (35.2) months for axSpA and PsA, respectively. Only 116 axSpA patients (35.3%) had available Ankylosing Spondylitis Disease Activity Score (ASDAS) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at bDMARD onset, of which 61 presented active disease. Disease Activity in PSoriatic Arthritis (DAPSA) or Disease Assessment Score - 28 joints (DAS-28) values at bDMARD onset were available for only 61 PsA (16.7%) patients, with 23 of them having active disease. The number of patients with available tender joint count or swollen joint count assessment was 68 (20.7%) and 59 (18%) for axSpA, and 115 (31.5%) and 119 (32.6%) for PsA, respectively. SEC was used in 63 (19.2%) axSpA patients and in 63 (17.3%) PsA patients. Conclusion: Using NLP, the study showed that around one-third of axSpA and one-sixth of PsA patients have disease activity assessments with ASDAS/BASDAI or DAPSA/DAS-28, respectively, highlighting an area of improvement in these patients' management. Plain language summary: Investigating axial spondyloarthritis and psoriatic arthritis patients using natural language processing We conducted a study in Spain to better understand patients with specific rheumatic conditions known as axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). To analyze their characteristics, we used a computer technology called EHRead, which uses Natural Language Processing (NLP) to analyze free text from electronic health records. Out of a large group of patients, we focused on 758 individuals who had axSpA or PsA. Most of the axSpA patients were men, and they were around 51 years old on average. For the PsA patients, most were women, and their average age was about 54 years. We analyzed outcomes and treatments of these patients. Our findings showed that we can describe and assess a cohort of patients from real world using NLP. Besides, only about one-third of axSpA patients and one-sixth of PsA patients had their respective outcomes completely assessed, which indicates that there is potential room for improvement in the management of axSpA and PsA. The most promising feature in our study is the use of NLP, an artificial intelligence technology that helps us understand information in medical records written in free text. This can help us explore the characteristics of patients and their management in the real world, bringing an opportunity to enhance the care of patients with axSpA and PsA. [ABSTRACT FROM AUTHOR]

To describe the efficacy and safety of subcutaneous tocilizumab (SC-TCZ) in a cohort of juvenile idiopathic arthritis (JIA) patients with refractory uveitis. Retrospective observational monocentric study including patients with JIA-associated uveitis treated with SC-TCZ. Thirteen patients were enrolled. The rate of uveitis flare/year per each patient was 1.6 ± 2.0 on the last bDMARDs before SC-TCZ, while it decreased to 0.4 ± 0.7 on SC-TCZ. Nine out of thirteen patients (69%) required the introduction of SC-TCZ only for active uveitis at baseline. Among these patients, five (56%) achieved complete treatment response. No uveitis relapses were observed in patients (4/13, 31%) requiring the introduction of SC-TCZ for active arthritis during follow-up (30.48 ± 21.6 months). Overall, SC-TCZ was safe, and no side effects were observed during the treatment. SC-TCZ can be effective and safe in patients with JIA and uveitis recalcitrant to several bDMARDs. [ABSTRACT FROM AUTHOR]

The objective was to assess the adherence, persistence, and costs of bDMARDs through a multicentre study of nine Italian hospital pharmacies. The drugs analysed were Abatacept, Adalimumab, Certolizumab, Etanercept, Golimumab and Tocilizumab. Adult subjects with Rheumatoid Arthritis were considered in the analysis. In this study, we calculated the following metrics: Adherence to treatment was evaluated as dose-intensity, which is the ratio between the amount of medication received and probably taken by the patient at home (Received Daily Dose, RDD) and the amount prescribed by the clinician (Prescribed Daily Dose, PDD). Persistence was calculated as the number of days between the first and last dispensing of the same drug. Lastly, costs were assessed based on persistence to treatment and normalized for adherence. Adherence to treatment was found to be above 0.8 for all drugs studied. The median persistence for a 5-year treatment period was 1.4 years for Abatacept, 1.7 years for Adalimumab, 1.8 years for Certolizumab, 1.4 years for Etanercept, 1.3 years for Golimumab, and 1.6 years for Tocilizumab. This multicentre retrospective observational study of bDMARDs used in the treatment of RA showed that, for all the drugs studied, there was no problem with adherence to treatment but rather a difficulty in maintaining treatment with the same drug over time. [ABSTRACT FROM AUTHOR]

During the three years that have passed since the beginning of the COVID-19 pandemic, many new fundamental and medical problems have been discovered regarding the relationship between the viral infection and many common chronic non- infectious diseases. Among the latter, an important position is occupied by immuno-inflammatory rheumatic diseases (IIRD), which include rheumatoid arthritis (RA). To date, there is no doubt that patients with RA are at risk for SARS-CoV-2 infection, a severe course of infection that necessitates hospitalization and death. The article presents current data on the course and outcomes of COVID-19 in patients with RA. The literature and own data on postcovid syndrome in this group of patients are presented. The necessity of vaccination against SARS-CoV-2 in patients with IIRD, including those with RA, was substantiated. The prospects for further study of the features of COVID-19 in patients with RA are outlined.

Summary: Background: Older studies uncovered an increased risk of cancer in patients with rheumatoid arthritis between 10% and 30% compared to the general population, with a lack of data concerning infrequent cancers. In recent year, major therapeutic breakthroughs might have affected this risk of cancer by mitigating disease activity or on the contrary by impairing antitumoral immune response. The objectives of this study are to compare cancer risk in patients with treated rheumatoid arthritis to the general population, in all treated patients and according to treatment exposure. Methods: This is a nationwide population-based study within the French national claims database “Système National des Données de Santé” (SNDS) between January 1st 2010 and December 31st 2020, to estimate the age and sex-standardized incidence ratios of cancer (all sites and site specific) of treated rheumatoid arthritis patients, with the French population as reference (by use of the French Network of Population-Based Cancer Registries [FRANCIM]). Findings: During the study period, 257,074 treated patients with rheumatoid arthritis contributed to a total of 2,098,238 person-years for the main analysis. The all-cancer risk was increased in rheumatoid arthritis patients, with a SIR (Standardized Incidence Ratio) of 1.20 (95% CI [1.17–1.23]). This risk was increased particularly for lung (SIR 1.41, 95% CI [1.36–1.46], bladder (SIR 2.38 95% CI [2.25–2.51]), cervix (SIR 1.80, 95% CI [1.62–2.01]), prostate (SIR 1.08, 95% CI [1.04, 1.13]) cancers, melanoma (SIR 1.37, 95% CI [1.29–1.46]), diffuse large B cell lymphoma (SIR 1.79, 95% CI [1.63–1.96], multiple myeloma (SIR 1.42, 95% CI [1.27–1.60]) and Hodgkin's lymphoma (SIR 2.73, 95% CI [2.31–3.23]). Some cancers were less frequent than in the general population such as pancreatic (SIR 0.90, 95% CI [0.83–0.97]) as well as breast and endometrial cancers (SIR 0.91, 95% CI [0.88–0.94] and SIR 0.77, 95% CI [0.71–0.84] respectively). Although we observed a modest but significant relative increase of all-cancer risk over-time in rheumatoid arthritis patients, there was a trend towards a decrease in risk of non-Hodgkin's lymphoma. Patients treated with rituximab were the patients displaying the highest risk of cancer. Interpretation: Compared to the general population, treated rheumatoid arthritis patients were at greater risk of all-cancer and some site specific cancers, except for breast, pancreatic and endometrial cancers which were less frequent than in the general population. Funding: This work was supported by unrestricted grants from the InCA (national institute against cancer) and AP-HP (Assistance Publique des Hôpitaux de Paris).

Objectives: We compared the incidences of four opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with molecular-targeted drugs from big claims data. Materials and Methods: We identified 205,906 patients with RA who were prescribed molecular-targeted drugs in 2010-17 from the National Database of Japan and calculated the incidence of four OIs (Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster). Results: The total number of Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster patients with biological disease-modifying antirheumatic drugs or tofacitinib treatment history in RA was 765, 1158, 834, and 18,336, respectively. The incidence rates of each OI for all biological disease-modifying antirheumatic drugs were 0.14, 0.14, 0.09, and 2.40 per 100 person-years, respectively, while for tofacitinib they were 0.22, 0.22, 0.07, and 7.00 per 100 person-years. No big difference was observed among biological disease-modifying antirheumatic drugs. All OIs showed higher incidence in those >65 years, but Pneumocystis pneumonia, nontuberculous mycobacterial infection, and herpes zoster showed no difference between those 65-74 years old and those >75 years old. The median of occurrence was the third, seventh, ninth, and thirteenth month after treatment, respectively. Conclusions: We counted real incidence rates of OIs for the whole nation from big claims data. [ABSTRACT FROM AUTHOR]

• The ASAS classification criteria cover the entire spectrum of SpA. • MRI of the SIJ plays a crucial role in the diagnosis of axSpA. • Entheses, along with TNFα, IL-17, and IL-12/23, play a central role in disease pathogenesis. • Anti-cytokine therapy, JAK inhibitors, and shared-decision making between patients and physicians are essential for SpA management. Spondyloarthritis (SpA) is a chronic inflammatory disease that affects the axial skeleton (axSpA) and/or the peripheral joints (p-SpA) and entheses. The natural history of SpA in the decades of the 80 and 90 s involved a progressive disease with pain, spinal stiffness, ankylosis of the axial skeleton, structural damage of peripheral joints, and a poor prognosis. In the last 20 years, enormous advances in understanding and managing SpA have occurred. With the introduction of the ASAS classification criteria and MRI, early disease recognition is now possible. The ASAS criteria widened the spectrum of SpA to include all the disease phenotypes, such as radiographic (r-axSpA), non-radiographic (nr-axSpA), and p-SpA and extraskeletal manifestations. Nowadays, the treatment of SpA is based on a shared decision between patients and rheumatologists and includes non-pharmacological and pharmacological therapies. Moreover, the discovery of TNFα, IL-17, which play a pivotal role in disease pathophysiology, has revolutionized disease management. Thus, new targeted therapies and many biological agents are now available and used in SpA patients. TNFα inhibitors (TNFi), IL-17, and JAK inhibitors were proven to be efficacious, with an acceptable toxicity profile. Overall, their efficacy and safety are comparable with some differences. Sustained clinical disease remission, low disease activity, improvement of patient's quality of life, and prevention of progression of structural damage, are the results of the above interventions. The concept of SpA has changed in the last 20 years. The disease burden can be ameliorated by early and accurate diagnosis and targeting therapies. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) affects 24.5 million people worldwide and has been associated with increased cancer risks. However, the extent to which the observed risks are related to the pathophysiology of rheumatoid arthritis or its treatments is unknown. Leveraging nationwide health insurance claims data with 85.97 million enrollees across 8 years, we identified 92 864 patients without cancers at the time of rheumatoid arthritis diagnoses. We matched 68 415 of these patients with participants without rheumatoid arthritis by sex, race, age and inferred health and economic status and compared their risks of developing all cancer types. By 12 months after the diagnosis of rheumatoid arthritis, rheumatoid arthritis patients were 1.21 (95% confidence interval [CI] [1.14, 1.29]) times more likely to develop any cancer compared with matched enrollees without rheumatoid arthritis. In particular, the risk of developing lymphoma is 2.08 (95% CI [1.67, 2.58]) times higher in the rheumatoid arthritis group, and the risk of developing lung cancer is 1.69 (95% CI [1.32, 2.13]) times higher. We further identified the five most commonly used drugs in treating rheumatoid arthritis, and the log‐rank test showed none of them is implicated with a significantly increased cancer risk compared with rheumatoid arthritis patients without that specific drug. Our study suggested that the pathophysiology of rheumatoid arthritis, rather than its treatments, is implicated in the development of subsequent cancers. Our method is extensible to investigating the connections among drugs, diseases and comorbidities at scale. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the cardiovascular safety of interleukin‐6 inhibitors (IL‐6i) and Janus Kinase inhibitors (JAKi) to tumour necrosis factor inhibitors (TNFi). Methods: We conducted a retrospective cohort study using population‐based electronic databases from Hong Kong, Taiwan and Korea. We identified newly diagnosed patients with rheumatoid arthritis (RA) who received b/tsDMARDs first time. We followed patients from b/tsDMARD initiation to the earliest outcome (acute coronary heart disease, stroke, heart failure, venous thromboembolism and systemic embolism) or censoring events (death, transformation of b/tsDMARDs on different targets, discontinuation and study end). Using TNFi as reference, we applied generalized linear regression for the incidence rate ratio estimation adjusted by age, sex, disease duration and comorbidities. Random effects meta‐analysis was used for pooled analysis. Results: We identified 8689 participants for this study. Median (interquartile range) follow‐up years were 1.45 (2.77) in Hong Kong, 1.72 (2.39) in Taiwan and 1.45 (2.46) in Korea. Compared to TNFi, the adjusted incidence rate ratios (aIRRs) (95% confidence interval [CI]) of IL‐6i in Hong Kong, Taiwan and Korea are 0.99 (0.25, 3.95), 1.06 (0.57, 1.98) and 1.05 (0.59, 1.86) and corresponding aIRR of JAKi are 1.50 (0.42, 5.41), 0.60 (0.26, 1.41), and 0.81 (0.38, 1.74), respectively. Pooled aIRRs showed no significant risk of cardiovascular events (CVEs) associated with IL‐6i (1.05 [0.70, 1.57]) nor JAKi (0.80 [0.48, 1.35]) compared to TNFi. Conclusion: There was no difference in the risk of CVE among RA patients initiated with IL‐6i, or JAKi compared to TNFi. The finding is consistent in Hong Kong, Taiwan and Korea. [ABSTRACT FROM AUTHOR]

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Abstract Introduction RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment. Methods RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any cause (excluding sustained response) at 24 months, (i.e., the rate of discontinuation of initial baricitinib or ts/bDMARD). Patient profiles of each cohort are described and compared. Post-baseline data are descriptively analyzed. This manuscript presents baseline and interim (6-month) outcomes for European patients with RA participating in the global RA-BE-REAL study. Results Data from 1074 patients (cohort A: 509; cohort B: 565) were analyzed. For cohorts A and B, respectively, the 6-month cumulative incidence (95% confidence interval) of treatment discontinuation was 16.5 (12.9–21.1) and 23.3 (19.1–28.2), and the proportions of patients achieving remission were 25.6% and 18.5%. At baseline, mean patient age was 59.1 and 57.0 years (p = 0.010) and mean disease duration was 10.0 and 8.9 years (p = 0.047), respectively. The proportions of patients exposed to ts/bDMARDs at any time before study entry were 51.9% and 39.1%, and the proportions of patients initiated on monotherapy were 50.9% and 31.2%, respectively. Conclusion In real-world settings, patients with RA initiating treatment with baricitinib were older and had longer disease duration than those initiating treatment with any other tsDMARD or any bDMARD. Initial descriptive data regarding treatment discontinuation (including reasons for discontinuation), effectiveness, and treatment patterns will be enriched as the study progresses.

The advent of biological disease-modifying anti-rheumatic drugs (bDMARDs), and more recently of Janus kinase inhibitors (JAKi), has had a major impact on the herpes zoster (HZ) reactivation, which represents an important clinical challenge in the treatment of inflammatory arthritis (IA) in patients with a complete pharmacological control of peripheral inflammation. In this review, we provide an overview on the effects of conventional DMARDs/ bDMARDs and JAKi on HZ reactivation. Furthermore, we underline the controversial findings and the potential management strategies. We searched PubMed, Medline, and the Cochrane Library for papers published between 1995 and November 2022. The overall data showed a slightly higher risk of HZ in patients treated with bDMARDs, and more pronounced for those treated with JAKi. As management strategies, we suggest an effective vaccination campaign and a focus on early diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to assess the 10‐year prevalence of latent tuberculosis infection (LTBI) among Apulian patients with rheumatic diseases (RDs). Secondary endpoint was to record new cases of active TB disease and LTBI among patients treated with biologic disease‐modifying antirheumatic drugs (bDMARDs). Methods: We analysed the results from the patients included in the BIOPURE registry from 2009 to 2018, who underwent QuantiFERON‐TB Gold In‐tube (QFT‐GIT) test as screening before bDMARDs treatment. Demographic and clinical data were recorded at the time of the first QFT‐GIT test. Administration of preventive therapy and bDMARD treatments were recorded for patients with positive QFT‐GIT test. All new tuberculosis infections were recorded during the follow‐up. Results: The final study population included 3028 patients (855 rheumatoid arthritis, 1001 psoriatic arthritis, 833 spondyloarthritis, 130 connective tissue diseases, 33 systemic vasculitis and 176 other inflammatory rheumatic conditions), more frequently female (67.2%), with a mean age of 52 ± 18 years. Patients with QFT‐GIT‐positive test were elderly people, predominantly male with higher prevalence of diabetes as comorbidity. The 10‐year prevalence of LTBI was 10.8%. Of note, no cases of TB reactivation were recorded in patients who completed preventive therapy treatment. Three thousand and sixteen patients were followed over time (42.6 ± 30 months), and five (.2%) developed active TB, which corresponds to.47 cases per 1000 person‐years. Conclusions: In the 10‐year observation, the use of bDMARDs seems to be safe in rheumatologic patients with positive QFT‐GIT test treated according to current recommendations. Nevertheless, cases of primary TB disease did occur during treatment with biologicals. [ABSTRACT FROM AUTHOR]

Objective We aim to provide real-world evidence on the effectiveness of patient-individual tapering of DMARDs for patients with RA in daily clinical practice using medical records and claims data. Methods We utilize data obtained through a controlled prospective cohort study in Germany conducted from July 2018 to March 2021. Participants consist of RA patients in sustained remission (>6 months) who were eligible for tapering at enrolment. Patients treated with individual tapering based on shared decision making (n  = 200) are compared with patients without any dose reduction (n  = 237). The risk of loss of remission and the risk of flare is assessed with risk-adjusted Kaplan–Meier estimators and Cox regressions. We evaluate differences in costs 1 year before and after baseline based on claims data for the subgroup of patients insured at one major sickness fund in Germany (n  = 76). Results The risk of flare (hazard ratio 0.88, 95% CI 0.59, 1.30) or loss of remission (hazard ratio 1.04, 95% CI 0.73, 1.49) was not statistically different between the individual tapering group and the continuation group. Minor increases of disease activity and decreases of quality of life were observed 12 months after baseline, again with no statistically significant difference. Drug costs decreased by 1017€ in the individual tapering group while they increased by 1151€ in the continuation group (P  < 0.01). Conclusion Individual tapering of DMARDs does not increase the average risk of experiencing flares or loss of remission. Encouraging rheumatologists and patients to apply tapering in shared decision making may be a feasible approach to allow individualization of treatment in RA. [ABSTRACT FROM AUTHOR]

This study aimed to explore the dynamic interactions between 32 cytokines and biomarkers in Psoriatic Arthritis (PsA) patients to compare cytokine signatures of treatment responders and non-responders. Biomarkers were measured before and after four months of treatment in 39 PsA patients initiating either Tumor Necrosis Factor alpha inhibitor (TNFi) or Interleukin-17A inhibitor (IL-17Ai). Response to treatment was defined by the composite measure, Disease Activity in Psoriatic Arthritis (DAPSA). A two-component principal component analysis (PCA) was implemented to describe cytokine signatures comparing DAPSA50 responders and non-responders. The cytokine signature of TNFi responders was driven by the correlated cytokines interferon γ (IFNγ) and IL-6, additionally associated with IL-12/IL-23p40, TNFα, and CRP, while the cytokine signature of TNFi non-responders was driven by the correlated cytokines IL-15, IL-8, and IFNγ. IL-17Ai responders were characterized by contributions of strongly correlated Th17 inflammatory cytokines, IL-17A, IL-12/IL-23p40, IL-22 to the cytokine signature, whereas IL-17A and IL-12/IL-23p40 did not demonstrate significant contribution in IL-17Ai non-responders. Based on PCA results it was possible to differentiate DAPSA50 responders and non-responders to treatment, endorsing additional examination of cytokine interaction models in PsA patients and supporting further PsA patient immune stratification to improve individualized treatment of PsA patients. [ABSTRACT FROM AUTHOR]

Sarcopenia is a syndrome defined by generalized and progressive loss of skeletal muscle mass, strength, and function. Besides affecting elderly population, it is actually common among inflammatory rheumatic diseases (IRD) patients. We performed a systematic literature review with a meta-analysis to investigate the influence of biologic and target synthetic disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) on sarcopenia in IRD. A systematic search has been performed on Pubmed, Scopus, and Web of science. Studies characteristics were collected. Assessment tools were body composition (total lean mass (TLM) and percentage, appendicular skeletal mass (ASM), fat-free mass and index (FFM and FFMI), skeletal mass index (SMI) and segmental lean mass (SLM)), and muscle strength and physical performance tests. Treatment effect defined the difference in change from baseline to the end of follow-up treatment was divided by the pooled SD of the difference. Twenty-two studies on 778 patients receiving bDMARDs/tsDMARDs and 157 controls were reviewed. They investigated rheumatoid arthritis (RA) (N = 14), spondyloarthritis (SpA) (N = 6), psoriatic arthritis (N = 1), and both RA and SpA (N = 1). tsDMARDs were used in one study with no effect on sarcopenia. Ten studies demonstrated that bDMARDs increased significantly muscle measures in 347 patients (44.6%) with a significant increase in TLM (6/15 studies; 57.4%), FFMI (4/6 studies; 59.9%), ASM (2/5 studies; 17.6%), SMI (2/5 studies; 18.1%), and SLM (2/2 studies; 3.6%). bDMARDs showed also a positive effect on handgrip strength in 1/3 of studies (45.2%) and on physical performance in 1/2 of studies (61%). In 1/5 of comparative studies, IRD patients on bDMARDs showed significantly higher increase of TLM in comparison to controls naïve bDMARDs. Regarding diagnosis, positive effect of bDMARDs was seen in 67.4% in SpA versus 49.3% in RA, with a significant increase of TLM, ASM and FFMI in 59.4%, 100%, and 65.2% in SpA versus 54.9%, 24.1%, and 54.8% in RA, respectively. Meta-analysis assessed the effect of bDMARD on TLM in 10 studies. There was no statistically significant difference [SMD − 0.10 (95% Confidence Interval − 0.26 − 0.06; tau2 = 0). Heterogeneity across studies was null, and the 95% confidence interval (index of precision) was equal to the 95% predictive interval. The first systematic literature review showed that bDMARDs have a significant improve effect in nearly half of RA and SpA patients on muscle mass and muscle strength, assessed separately. However, the meta-analysis concluded that bDMARDs have no significant effect on TLM. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies (IIM) are a rare group of disorders that feature progressive immune-mediated skeletal muscle destruction along with skin, lung, and joint involvement. Management of IIMs necessitates glucocorticoid therapy followed by conventional steroid-sparing agents to control disease activity. In the settings of refractory myositis or life-threatening manifestations, e.g. lung involvement or oropharyngeal dysphagia, second-line therapies are needed to minimize disease burden, avoid end-organ damage and steroid toxicity, and decrease mortality. These therapies may include biological disease-modifying antirheumatic drugs (bDMARDs), and to a lesser extent, targeted synthetic disease-modifying antirheumatic drugs (TSD). This article reviews the current use of bDMARDs, e.g. intravenous immunoglobulin and rituximab, and a TSD—Janus kinase inhibitors (JAKI)—along with their indications, efficacy, and safety in managing IIM. [ABSTRACT FROM AUTHOR]

There is increased cardiovascular (CV) morbidity and mortality in rheumatoid arthritis (RA) and other rheumatic and musculoskeletal diseases (RMDs). Systemic inflammation is highly involved in atherogenesis. Non-steroidal anti-inflammatory drugs (NSAIDs), primarily COX-2 inhibitors might increase CV risk. Corticosteroids might act as a double-edged sword as they exert both beneficial and negative effects on the CV system. NSAIDs and corticosteroids are anti-inflammatory, but, on the other hand, they might be potentially atherogenic. Conventional synthetic DMARDs (csDMARDs), such as antimalarials, methotrexate, sulfasalazine, leflunomide and cyclosporine A have good CV safety, however, leflunomide and cyclosporine A might cause hypertension. Biologic DMARDs, by suppressing inflammation and disease activity, might either reduce CV risk or at least not cause any harm in that respect. Recently, tofacitinib and most likely other Janus kinase inhibitors have been associated with increased CV risk, at least in RMD patients with high CV risk at baseline. In clinical practice, EULAR and other recommendations guide the rheumatologist when screening for and managing CV comorbidities. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis (JIA) associated uveitis (JIA-U) is the most common extra-articular manifestation of JIA, affecting 10–15% of patients, especially in oligoarticular JIA where its course may be faint. Therefore, JIA-U is one of the most challenging pediatric uveitis, associated with major ocular morbidity and possibly leading to irreversible structural ocular damage and to vision-threatening complications. Adequate management is crucial for avoiding visual impairment complications. Since the introduction of biologic disease modifying anti-rheumatic drugs (bDMARDS), the visual prognosis of JIA-U has dramatically improved over the decades. Tumor necrosis factor-α (TNF-α) blockers are the most used bDMARDs in treating JIA-U with large evidence of efficacy. However, inadequate response to these agents, either due to intolerance or inefficacy, may be observed, requiring a swap to other classes of immunosuppressive agents, including anti-IL-6, anti-CD20, and, more recently, JAK inhibitors. Tocilizumab is a humanized monoclonal antibody to the interelukin-6 receptor preventing IL-6 from binding to its soluble and membrane-bound receptors. A growing body of literature provides promising results about the efficacy of intravenous and subcutaneous tocilizumab in the treatment of JIA-U. A narrative review of the literature on this topic will improve our knowledge on the potential use of tocilizumab in JIA-U. [ABSTRACT FROM AUTHOR]

Abstract Background Biological treatment and treat-to-target approaches guide the achievement of inactive disease and clinical remission in Autoinflammatory Diseases (AID). However, there is limited evidence addressing optimal tapering strategies and/or discontinuation of biological treatment in AID. This study evaluates available evidence of tapering biological treatment and explores key factors for successful tapering. Methods A systematic literature search was conducted in Embase, MEDLINE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials using the OVID platform (1990-08/2020). Bibliographic search of relevant reviews was also performed. Studies/case series (n ≥ 5) in AID patients aged ≤ 18 years with biological treatment providing information on tapering/treatment discontinuation were included. After quality assessment aggregated data were extracted and synthesized. Tapering strategies were explored. Results A total of 6035 records were identified. Four papers were deemed high quality, all focused on systemic juvenile idiopathic arthritis (sJIA) (1 open-label randomized trial, 2 prospective, 1 retrospective observational study). Biological treatment included anakinra (n = 2), canakinumab (n = 1) and tocilizumab (n = 1). Strategies in anakinra tapering included alternate-day regimen. Canakinumab tapering was performed randomized for dose reduction or interval prolongation, whereas tocilizumab was tapered by interval prolongation. Key factors identified included early start of biological treatment and sustained inactive disease. Conclusion Tapering of biological treatment after sustained inactive disease should be considered. Guidance for optimal strategies is limited. Future studies may leverage therapeutic drug monitoring in combination with pharmacometric modelling to further enhance personalized “taper-to-target” strategies respecting individual patients and diseases aspects.

Aim. To compare the features of the course of the disease and the therapy in rheumatoid arthritis (RA) patients who meet the criteria of difficult-to-treat RA (D2T). Materials and methods. The study included 505 RA patients (ACR/EULAR 2010). Rheumatologist experts discussed all patients, since the treatment of RA ware perceived as problematic and/or insufficient. All patients had at least one of the following signs: the activity of the disease is no lower than moderate; the inability to reduce the dose of glucocorticoids to low; rapid radiological progression; RA symptoms causing a decrease in quality of life. The D2T group included 35 patients with true inefficiency or intolerance of two or more of bDMARDs/tsDMARDs of different mechanism of action. The control group (K) included patients with RA who already had experience of taking at least one class of bDMARDs/tsDMARDs (n=291). Results. On average, every 15 patients (7%) with RA met the EULAR criteria for D2T. The median age of patients in the D2T group was 45 years, which is less than in K (Me 54 [43; 62] years; p=0.046). The duration of RA in both groups was comparable. The severity of articular destruction in D2T was higher than in K (stage IV in 40% and 23%, respectively). Positivity for the RF and ACPA in D2T was less common than in K (60% and 85.9%; 60% and 76.6%, respectively). The presence of systemic manifestations of RA was more typical for K than for D2T (28.6% and 63%, p=0.0001). In the group of D2T patients, the number of previously taken DMARDs was higher than in K (p=0.002). Methotrexate was more often prescribed as the first DMARDs in both groups (in 62.9 and 65.7%, respectively). Initiation of bDMARDs/tsDMARDs therapy in D2T was more often performed by TNF-a inhibitors (OR 2.8; p=0.003) and co-stimulation blocker abatacept (OR 4.6; p=0.004), and in control by B-cell inhibitor rituximab (OR 6.9; p0.0001). Conclusion. The results of this study suggest that in Russia, as well as abroad, the principle of RA treatment treat to target has not yet become widespread, and the development of adequate therapy takes too much time.

• In axial spondyloarthritis, anti-TNF and anti-IL17 do not increase the FIB-4 score after two years. • In psoriatic arthritis, anti-IL17 but not anti-TNF increases the FIB-4 score after two years. [ABSTRACT FROM AUTHOR]

Introduction: RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment. Methods: RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any cause (excluding sustained response) at 24 months, (i.e., the rate of discontinuation of initial baricitinib or ts/bDMARD). Patient profiles of each cohort are described and compared. Post-baseline data are descriptively analyzed. This manuscript presents baseline and interim (6-month) outcomes for European patients with RA participating in the global RA-BE-REAL study. Results: Data from 1074 patients (cohort A: 509; cohort B: 565) were analyzed. For cohorts A and B, respectively, the 6-month cumulative incidence (95% confidence interval) of treatment discontinuation was 16.5 (12.9–21.1) and 23.3 (19.1–28.2), and the proportions of patients achieving remission were 25.6% and 18.5%. At baseline, mean patient age was 59.1 and 57.0 years (p = 0.010) and mean disease duration was 10.0 and 8.9 years (p = 0.047), respectively. The proportions of patients exposed to ts/bDMARDs at any time before study entry were 51.9% and 39.1%, and the proportions of patients initiated on monotherapy were 50.9% and 31.2%, respectively. Conclusion: In real-world settings, patients with RA initiating treatment with baricitinib were older and had longer disease duration than those initiating treatment with any other tsDMARD or any bDMARD. Initial descriptive data regarding treatment discontinuation (including reasons for discontinuation), effectiveness, and treatment patterns will be enriched as the study progresses. [ABSTRACT FROM AUTHOR]

Flare Assessment in Rheumatoid Arthritis (FLARE-RA) is a self-administered tool aiming to capture current or recent flares in rheumatoid arthritis (RA). We aimed to externally validate the FLARE-RA instrument and its existing cutoffs for flare detection within a bDMARD-tapering context in established RA. Data were analyzed from the Tapering Etanercept in Rheumatoid Arthritis (TapERA) trial, which studied the feasibility of tapering etanercept in patients with established RA in sustained remission. The English FLARE-RA was translated and cross-culturally adapted into Dutch, and internal consistency and test–retest reliability were evaluated with Crohnbach's alpha and intraclass correlation coefficient (ICC). Participants completed the FLARE-RA 3-monthly for 12 months. Accuracy and optimal cutoffs of FLARE-RA to detect DAS28-defined flares were assessed using area under the receiver operating characteristic curves (AUC). Association of FLARE-RA scores with current and future flares was studied using logistic generalized estimating equations (GEE). The Dutch FLARE-RA showed excellent internal consistency and test–retest reliability (Cronbach's alpha 0.96; ICC 0.96 [95% CI 0.70–1.00]). Discriminatory capacity of FLARE-RA to detect flares was acceptable (AUC 0.77, 0.80, and 0.72 for global, arthritis, and general symptoms subscales, respectively), with an optimal global score cutoff of 4/10. In GEE-models, higher FLARE-RA scores were associated with increased odds of both current and future flares. We successfully translated and cross-culturally adapted the FLARE-RA into a Dutch version and validated its capacity to detect flares in a bDMARD-tapering context in established RA. Finally, higher FLARE-RA scores might indicate an increased risk of future flares. Trial registration: EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004631-22/BE, EudraCT number 2012–004,631-22. Key Points • Translation and cross-cultural adaptation of the FLARE-RA resulted in a Dutch version with excellent internal consistency and test–retest reliability. • The FLARE-RA is a valid instrument to detect current OMERACT-defined flares within a bDMARD tapering setting, with an optimal global score cutoff of 4/10. • Higher scores on the FLARE-RA are associated with increased risk of future flares, which could be particularly relevant when considering DMARD tapering. [ABSTRACT FROM AUTHOR]

Despite of the availability of several effective bDMARDs, a significant proportion of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients discontinued bDMARDs. The aims of this study were to analyze causes of bDMARDs discontinuation in RA and AS included in the Moroccan registry RBSMR. A historical prospective multicenter cohort study based on the RBSMR database at 12 months of follow-up, which included 225 RA and 170 AS. Using T student, Mann–Whitney U, chi-squared or Fischer exact tests, baseline demographic and clinical features were compared between patients discontinuing bDMARDs and patients remaining on initiated bDMARDs or switching bDMARDs. Logistic regression models were used to identify factors associated with drugs discontinuation. 61 RA discontinued bDMARDs and 47 AS interrupted anti-TNF. The most common reasons for drugs discontinuation were adverse events (7.5%) in RA patients and social security reimbursement problems (16.8%) in AS. RA patients discontinuing bDMARDs were more frequently first-line biological drugs users, more frequently female and had more comorbidities and lower DAS28 CRP than RA patients remaining on initiated bDMARDs or switching bDMARDs (p < 0.001, p = 0.01, p < 0.001 and p < 0.001 respectively). Female sex and comorbidities were the significant predictors of bDMARDs discontinuation in RA patients. Higher baseline BASDAI had a protective role on anti-TNF interruption in AS patients. Adverse events and social security reimbursement problems were the main reasons for drugs discontinuation in RA and AS patients respectively. Female sex and comorbidities in RA patients, baseline BASDAI in AS patients impacted bDMARDs discontinuation in real-life settings. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study was to determine the seasonal changes in the initiation of biological disease-modifying antirheumatic drugs (bDMARDs) and methotrexate (MTX) using big claims data. Methods: We counted the monthly number of initial administrations of each bDMARD and MTX in patients with rheumatoid arthritis (RA) between April 2010 and March 2017. Data were collected from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. This database covers more than 95% of Japanese citizens. Seasonal changes in the number of initiations were determined. Patient claims were also classified according to drugs, districts, gender, and ages. Results: The initiation of bDMARDs and MTX administration varied according to the season in a sine curve shape, with the highest numbers in May to July and the lowest numbers in November to January. The same changing pattern was observed among each bDMARD, district, gender, and age groups particularly when the number was on the higher side. Conclusion: We noted an apparent seasonal change in the number of bDMARDs initiated, with a peak during spring, suggesting an exacerbation of RA in the spring in Japan. These changes are overlooked in daily practice and are only visible using big data. [ABSTRACT FROM AUTHOR]

To assess treatment patterns and initial and maintenance dosing of biologics over 3 years in pediatric patients with ulcerative colitis (UC) or Crohn's disease (CD), utilizing data from the ImproveCareNow registry. Pediatric patients diagnosed with UC or CD and aged 2–17 years were included in the study. Descriptive statistics were employed to summarize baseline demographics. The proportion of patients on medication for UC or CD were analyzed at the baseline visit, 1-year, and 3-year time points (Cohort 1). Biologic maintenance dosage was calculated only for patients who had data for dose and weight at all-time points (Cohort 2). In Cohort 1 (UC = 1784; CD = 4720), baseline treatment in UC included corticosteroid, 5-ASA, and 6-MP/AZA; at 1-year and 3-year time points, treatment with 5-ASA and corticosteroid decreased, whereas 6-MP/AZA and anti-TNFs increased. In CD, baseline treatment included corticosteroid, anti-TNF, 6-MP/AZA, and methotrexate; use of corticosteroids decreased, whereas the use of methotrexate and anti-TNFs increased over 3 years. In Cohort 2 (UC = 350; CD = 1537), at first maintenance dose, UC patients on infliximab received a mean dose of 10.5 mg/kg/8 wk, adalimumab (weight < 40 kg and ≥40 kg) 1.3 mg/kg/2 wk and 0.8 mg/kg/2 wk, and vedolizumab 6.9 mg/kg/8 wks. At the first maintenance dose, CD patients on infliximab received a mean dose of 8.1 mg/kg/8 wk, adalimumab (weight < 40 kg) 1.1 mg/kg/2 wk, adalimumab (weight ≥ 40 kg) 0.8 mg/kg/2 wk, and vedolizumab 10.5 mg/kg/8 wks. The use of corticosteroids was common at the initial visit in patients. Anti-TNFs remain the most used class of biologics, however, reported doses in our study were substantially higher than the standard dosing guidelines. [ABSTRACT FROM AUTHOR]

Introduction: Early psoriatic arthritis (PsA) diagnosis is critical to prescribe timely treatment to prevent the irreversible joint damage and the many other problems that patients with PsA experience. This retrospective study aimed to highlight the benefits of a Rheuma–Derma Clinic focused on the early diagnosis and prompt treatment of PsA with a shared approach among Italian psoriasis patients. Diagnosing PsA early is the main goal to reduce joint damage and disability in the patients affected. Studies describing the results of rheuma–derma clinics aimed to reach this goal emerged in the last decade. This study presents limitations and advantages typical of retrospective designs. Methods: A Rheuma–Derma Clinic was created in 2017 at the Rheumatology Department of the Hospital Policlinico Gaspare Rodolico of the University of Catania in San Marco, Italy. This study compared the number of patients under disease-modifying antirheumatic treatment 5 years before and after the joint clinic was created. A rheumatologist and dermatologist simultaneously assessed patients with psoriasis and/or PsA to obtain a rapid multidisciplinary diagnostic approach and a shared therapeutic strategy. In addition, demographic, clinical, and clinimetrics data were collected. Results: The number of patients with PsA receiving biological disease-modifying antirheumatic drugs increased 47% (from 255 to 374 patients) before and after the joint clinic was implemented. Likewise, those receiving conventional synthetic disease-modifying antirheumatic drugs increased by 47% (from 367 to 539) as well. Additionally, for all the clinimetrics evaluated (DAS28, HAQ, BASDAI, DAPSA, PASI, PGA), there was an improvement over the 12 months under the Rheuma–Derma Clinic care. The measures that improved the most were DAPSA, PGA, PASI, and BASDAI. Conclusion: The implementation of the Rheuma–Derma Clinic was associated with an increase in the number of patients diagnosed, the number of patients with PsA receiving DMARD treatments, and improvements in clinimetrics among the study participants. Plain language summary: Psoriatic arthritis needs to be detected early to treat it correctly and for its consequences in patients with psoriasis to be prevented. This study was carried out to find out if shared clinics where rheumatologists and dermatologists care for patients together helped to control psoriatic arthritis better and improve the life of the patients affected by it. The shared clinic was created in 2017 at the Rheumatology Department of the Hospital Policlinico Gaspare Rodolico of the University of Catania in San Marco, Italy. The study collected information about the number of patients diagnosed with psoriasis and psoriatic arthritis, the number of patients receiving treatments, and the results of quality of life and other standard tests. During the time that the joint clinic was in place, the number of patients receiving treatments specific for diseases such as psoriatic arthritis increased from 622 (before the clinic was started) to 913. The patients treated in this clinic also had improvements in their quality of life and other aspects. This study found that a clinic where rheumatologists and dermatologists work together to care for patients can increase the number of patients treated with drugs that are specific for their disease and improve their overall health. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology that mainly affects the joints, but extra-articular symptoms may also occur. The global prevalence of RA is approximately 5 cases per 1,000 adults[1]. A better understanding of the pathophysiology of the disease in the treatment of RA has led to the development of more effective treatments. Current drugs include glucocorticoids (GCs) and synthetic and biological disease-modifying anti-rheumatic drugs (DMARDs). Apart from these, the most commonly used analgesics are non-steroidal anti-inflammatory drugs (NSAIDs). BLMPs work by targeting specific molecules involved in the inflammatory process, not just symptom relief. Purpose: To review the currently available PubMed data on biologics and exercise for RA and their mechanisms in the context of disease pathophysiology and future prospects. Brief description of the state of knowledge: BLMPs are a necessary alternative in patients who have not achieved the treatment goal for 6 months or have experienced side effects during treatment with conventional disease-modifying drugs. We also analyzed the effect of exercise on the course of RA. Conclusions: The introduction of bDMARDs has opened a new era in the treatment of diseases such as RA. However, due to the difficult access to this form of therapy, side effects, contraindications to currently used drugs, and increasingly well-known mechanisms, there is also a need to constantly search for new solutions. A growing body of evidence in recent years suggests that regular physical activity has a positive effect on various aspects of RA, including disease-related outcomes, mental well-being, and cardiovascular health. Also in this non-pharmacological field, further research is needed to fully understand the mechanisms behind these effects.