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BackgroundRecent guidelines for SLE recommend using a hydroxychloroquine (HCQ) dose less than 5.0 mg/kg/day to reduce the risk of retinopathy. To determine if this dose reduction would have an impact on the clinical course of SLE, we compared flare incidence in a cohort of patients with SLE treated with two different oral HCQ dosages (≤5 mg/kg/day or >5 mg/kg/day). As a secondary analysis, we compared HCQ blood levels between the two different oral dosages, and evaluated the frequency of non-adherence in patients with SLE treated with HCQ.MethodsWe identified a cohort of patients with SLE taking HCQ for at least 6 months and followed for 24 months. At study entry and 6 months later, a blood venous sample was taken to measure HCQ blood levels by liquid chromatography. Incidence of new SLE flares after recruitment was put in relation to daily HCQ dose and mean HCQ blood levels. Cox regression analysis served to identify factors associated with SLE flares.Results83 patients were enrolled. We observed 11 (16%) flares that developed in mean 14.8 months of follow-up. The difference in terms of flare rate and mean HCQ blood levels between the two oral dosages was not statistically significant. There was a trend (p=0.08) for high HCQ dose being associated with a lower flare rate. At Cox analysis, higher HCQ blood levels and older age at baseline were protective against flare occurrence, while concomitant immunosuppressant therapy showed significant positive association. HCQ blood levels did not correlate with prescribed HCQ dose.ConclusionPatients with low oral HCQ dosage tend to have more flares, although the difference was not statistically significant. Higher HCQ blood levels were protective against flare occurrence. The risks and benefits must be balanced in choosing HCQ dose.

The effects of biological disease-modifying antirheumatic drugs (bDMARDs) in the clinical course of COVID-19 on children with underlying rheumatologic diseases have not been fully demonstrated. To evaluate the course of COVID-19 infection in patients with rheumatic disease receiving bDMARD treatment. This was a retrospective, multicenter study conducted in pediatric patients infected by SARS-CoV-2 and under bDMARDs therapy. The study population consisted of 113 patients (72 female/41 male). The mean age of the patients was 12.87 ± 4.69 years. The primary diagnosis of the cohort was as follows: 63 juvenile idiopathic arthritis, 35 systemic autoinflammatory diseases, 10 vasculitides, and five cases of connective tissue diseases. The mean duration of the primary disease was 4.62 ± 3.65 years. A total of 19 patients had additional comorbid diseases. Thirty-five patients were treated with canakinumab, 25 with adalimumab, 18 with etanercept, 10 with infliximab, nine with tocilizumab, six with rituximab, four with anakinra, three with tofacitinib, and one with abatacept. The median exposure time of the biological drug was 13.5 months. Seventy-one patients had symptomatic COVID-19, while 42 were asymptomatic. Twenty-four patients required hospitalization. Five patients presented with MIS-C. The hospitalized patients were younger and had a shorter duration of rheumatic disease compared to ambulatory patients, although the difference was not statistically significant. Steroid usage, presence of fever, and dyspnea were more common among the hospitalized patients. A worsening in the course of both COVID-19 and current disease was not noticed under bDMARDs, however, to end with a strong conclusion multicentric international studies are required. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Background/aim: to evaluate treatment adherence and predictors of drug discontinuation among patients with inflammatory arthritis receiving bDMARDs within the first 100 days after the announcement of the COVID-19 pandemic. Materials and methods: a total of 1871 patients recorded in TReasure registry for whom advanced therapy was prescribed for rheumatoid arthritis (RA) or spondyloarthritis (SpA) within the 3 months (6-9 months for rituximab) before the declaration of COVID-19 pandemic were evaluated, and 1394 (74.5%) responded to the phone survey. Patients' data regarding demographic, clinical characteristics and disease activity before the pandemic were recorded. The patients were inquired about the diagnosis of COVID-19, the rate of continuation on bDMARDs, the reasons for treatment discontinuation, if any, and the current general disease activity (visual analog scale, [VAS]). Results: a total of 1394 patients (493 RA [47.3% on anti-TNF] patients and 901 SpA [90.0% on anti-TNF] patients) were included in the study. Overall, 2.8% of the patients had symptoms suggesting COVID-19, and 2 (0.15%) patients had PCR-confirmed COVID-19. Overall, 18.1% of all patients (13.8% of the RA and 20.5% of the SpA; p = 0.003) discontinued their bDMARDs. In the SpA group, the patients who discontinued bDMARDs were younger (40 [21-73] vs. 44 years [20-79]; p = 0.005) and had higher general disease activity; however, no difference was relevant for RA patients. Conclusion: although the COVID-19 was quite uncommon in the first 100 days of the pandemic, nearly one-fifth of the patients discontinued bDMARDs within this period. The long-term effects of the pandemic should be monitored., Hacettepe Rheumatology Society

Objective: Currently, concerning the evaluation of psoriatic arthritis (PsA), there is no agreement on a standardized composite index for disease activity that includes all relevant domains. The present study sought to assess the rates of remission (REM)/low disease activity (LDA) and disease states [minimal disease activity (MDA), very low disease activity (VLDA)] as defined by diverse activity scales (DAPSA, DAS28-ESR) in an attempt to display discrepancies across these assessment tools for peripheral PsA. Methods: The study involved 758 patients (496 females, 262 males; mean age 47,1 years) with peripheral PsA who were registered to the Turkish League Against Rheumatism (TLAR) Network. The patients were assessed using the DAS28-ESR, DAPSA, MDA, and VLDA. The overall yield of each scale was assessed in identifying REM and LDA. The presence or absence of swollen joints was separately analysed. Results: The median disease duration was 4 years (range 0-44 years). According to DAPSA and DAS28-ESR, REM was achieved in 6.9% and 19.5% of the patients, respectively. The rates of MDA and VLDA were 16% and 2.9%, respectively. Despite the absence of swollen joints, a significant portion of patients were not considered to be in REM (296 (39.1%) patients with DAS28-ESR, 364 (48%) with DAPSA, and 394 (52%) with VLDA). Conclusion: Patients with peripheral PsA may be assigned to diverse disease activity levels when assessed with the DAS28-ESR, DAPSA, MDA and VLDA, which would inevitably have clinical implications. In patients with PsA a holistic approach seems to be necessary which includes other domains apart from joint involvement, such as skin involvement, enthesitis, spinal involvement, and patient-reported outcomes. © 2021 Société française de rhumatologie

Background A higher prevalence of celiac disease (CD) has been reported in patients with juvenile idiopathic arthritis (JIA) compared to the general population. Factors related to the increased risk of co-occurrence and associated disease course have not been fully elucidated. Aims of this study were to determine the prevalence of CD in a large Southern Italian cohort of children with JIA, describe their clinical features and disease course and investigate risk factors associated with their co-occurrence. Findings Demographic, clinical and laboratory data of all patients with JIA admitted to our Pediatric Rheumatology Unit from January 2001 to June 2019, who underwent CD screening, were retrospectively extracted from clinical charts and analyzed. Eight of 329 JIA patients were diagnosed with CD, resulting in a prevalence higher than the general Italian population (2.4% vs 0.93%, p p p Conclusion A higher CD prevalence was found in a large JIA cohort, supporting the need for CD screening in all JIA children, especially those with a family history of autoimmunity, found to be associated with the co-occurrence of the two diseases. This is clinically relevant since patients with CD and JIA more often required a step-up therapy, suggesting a more severe JIA clinical course.

ObjectivesTo develop predictive criteria for COVID-19-associated cytokine storm (CS), a severe hyperimmune response that results in organ damage in some patients infected with COVID-19. We hypothesised that criteria for inflammation and cell death would predict this type of CS.MethodsWe analysed 513 hospitalised patients who were positive for COVID-19 reverse transcriptase PCR and for ground-glass opacity by chest high-resolution CT. To achieve an early diagnosis, we analysed the laboratory results of the first 7 days of hospitalisation. We implemented logistic regression and principal component analysis to determine the predictive criteria. We used a ‘genetic algorithm’ to derive the cut-offs for each laboratory result. We validated the criteria with a second cohort of 258 patients.ResultsWe found that the criteria for macrophage activation syndrome, haemophagocytic lymphohistiocytosis and the HScore did not identify the COVID-19 cytokine storm (COVID-CS). We developed new predictive criteria, with sensitivity and specificity of 0.85 and 0.80, respectively, comprising three clusters of laboratory results that involve (1) inflammation, (2) cell death and tissue damage, and (3) prerenal electrolyte imbalance. The criteria identified patients with longer hospitalisation and increased mortality. These results highlight the relevance of hyperinflammation and tissue damage in the COVID-CS.ConclusionsWe propose new early predictive criteria to identify the CS occurring in patients with COVID-19. The criteria can be readily used in clinical practice to determine the need for an early therapeutic regimen, block the hyperimmune response and possibly decrease mortality.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder that primarily affects the joints. One hypothesis for the pathogenesis of RA is that disease begins at mucosal sites as a consequence of interactions between the mucosal immune system and an aberrant local microbiota, and then transitions to involve the synovial joints. Alterations in the composition of the microbial flora in the lungs, mouth and gut in individuals with preclinical and established RA suggest a role for mucosal dysbiosis in the development and perpetuation of RA, although establishing whether these alterations are the specific consequence of intestinal involvement in the setting of a systemic inflammatory process, or whether they represent a specific localization of disease, is an ongoing challenge. Data from mouse models of RA and investigations into the preclinical stages of disease also support the hypothesis that these alterations to the microbiota predate the onset of disease. In addition, several therapeutic options widely used for the treatment of RA are associated with alterations in intestinal microbiota, suggesting that modulation of intestinal microbiota and/or intestinal barrier function might be useful in preventing or treating RA.

Background There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group – KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients’ outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p Conclusion Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay – RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n = 67), adalimumab (ADL; n = 49) or etanercept (ETA; n = 47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is very complex and heterogeneous. If not adequately treated, RA patients are likely to manifest excess of morbidity and disability with an important impact on the quality of life. Pharmacological treatment is based on the administration of the disease-modifying antirheumatic drugs (DMARDs), subdivided into conventional synthetic (csDMARDs), targeted synthetic (tsDMARDs), and biological (bDMARDs). bDMARDs are now frequently administered in patients, both as alternative treatment and together with csDMARDs. Unfortunately, there is a therapeutic response variability both to old and new drugs. Therefore, to identify pre-therapeutic and on-treatment predictors of response is a priority. This review aims to summarize recent advances in understanding the causes of the variability in treatment response in RA, with particular attention to predictive potential of autoantibodies and DMARD pharmacogenetics. In recent years, several biomarkers have been proposed to personalize the therapy. Unfortunately, a magic bullet does not exist, as many factors concur to disease susceptibility and treatment outcomes, acting around the patient’s congenital background. Models integrating demographic, clinical, biochemical, and genetic data are needed to enhance the predictive capacity of specific factors singularly considered to optimize RA treatment in light of multidisciplinary patient management.

Introduction: In recent years, different studies regarding psoriatic arthritis (PsA) have shown the pathogenetic role of dysfunction of signaling pathways involving the phosphodiesterase-4 enzyme and transcription factors or enzymes belonging to the kinase (JAK)–signal family pathway. These also represent the target of several drugs known as targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). Areas covered: The authors performed a systematic literature search using the PubMed database, as well as through retrieving data from randomized controlled trials, their post-hoc analysis, and pooled data analysis on the efficacy and safety profile of the PDE4 inhibitor (PDE4i), apremilast, and the inhibitors of JAK (JAKis), tofacitinib, filgotinib, baricitinib, and upadacitinib, in PsA. Expert opinion: In PsA, the PDE4i, apremilast, and the JAKi, tofacitinib, are effective across multiple clinical domains and have an acceptable tolerability profile, thus expanding the treatment options available for PsA patients. Apremilast and tofacitinib show several advantages mainly represented by their oral administration, a fast onset of action, and a short half-life. Data on tsDMARDs in PsA are still limited, and randomized trials and real-life studies are advocated.

IntroductionCovid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic.MethodThis observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1)definitediagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2)highly suspectedCovid-19 disease: presence of highly suggestive symptoms, in absence of a swab test.ResultsA significantly higher prevalence of patients withdefinitediagnosis of Covid-19 disease,or withhighly suspectedCovid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to “Italian general population” (p = .030,p = .001,p = .000, respectively); and fordefinite + highly suspecteddiagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population).Moreover, significantly higher prevalence ofdefinite + highly suspecteddiagnosis of Covid-19 disease was found either in patients with various “connective tissue diseases” compared to “inflammatory arthritis group” (p p = .011).ConclusionsThe finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases.Key Points• Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients’ increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement.• The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing.• Patients with “connective tissue diseases” show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to “inflammatory arthritis group”.• Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.

Background: Rheumatoid Arthritis (RA) has been associated with insulin resistance (IR), a well-established pathophysiological feature of Type 2 Diabetes (T2DM). Inconsistent literature evidence suggests that IR could be ameliorated by biological medications targeting TNFα. Objective: The aim of this systematic review was to evaluate the effect of TNFα inhibitors (TNFi) on IR in RA patients. Methods: We performed a systematic review in order to identify the available data on the effect of anti- TNFα medications on IR in RA patients. For this purpose, MedLine (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and SCOPUS were searched up to December 2016. Results: The search strategy retrieved 209 individual records. Of these, only 12 articles were included in the systematic review. The pooled analysis under a random-effects model demonstrated a significant improvement of IR after treatment with TNFi quantified with the HOmeostasis Model Assessment of Insulin Resistance (HOMA-IR), with a standardized difference in means (SDM) of -0.847 (95%CI: -1.278 - 0.417, p < 0.0001). Heterogeneity across studies was high (Q = 65.00 with df = 9, p < 0.001, I2 = 89.15%). Conclusion: Our meta-analysis suggests that TNFα blockade might improve IR in RA patients.

Purpose: To correlate rheumatologic with ophthalmic and laboratory findings in patients with rheumatoid arthritis (RA) to identify what effect these have on development of ocular disease. Methods: This is a cross-sectional study of 172 eyes of 86 patients with RA. Patients were examined by a group of rheumatologists. Sociodemographic, clinical, and laboratory data were collected. All patients underwent complete ophthalmologic examination including corneal topography and endothelial cell count. Results: There was no significant correlation between RA-negative prognostic indicators (NPIs) and pathologic corneal findings. Patients using disease-modifying antirheumatic drugs (DMARDs) and antimalarial drugs had greater corneal volumes (mean difference 8.51 mm3, 90% confidence interval [CI], 3.98-13.04, P = 0.004; and 2.24, 90% CI, 0.32-4.54, P = 0.048, respectively). Patients using azathioprine had lower endothelial cell counts compared with those using other drugs (mean difference 180 cells/mm2, 90% CI, 69-291, P = 0.008). Patients using biologic DMARDs had better tear osmolarity values (between 280 and 300 mOsm/L) than patients not using them (mean difference 14.3 mOsm/L, P = 0.022). There was no correlation between NPIs of RA and positive keratoconus screening indices (Spearman correlation OD -0.013, P = 0.91; OS -0.033, P = 0.76). Conclusions: There was no clear correlation between RA-NPIs and pathologic corneal findings in our study. DMARDs treatment may help maintain corneal integrity in our patients and prevented collagenolytic manifestations of RA. Other medications such as azathioprine should be used carefully, as endothelial damage may potentially occur. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Purpose: To describe health care resource utilization (HCRU) and costs among patients with juvenile idiopathic arthritis (JIA) compared to patients without JIA and to describe treatment patterns among JIA patients who initiated biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). Patients and methods: The IBM MarketScan® Commercial Database was used to identify patients aged 2–17 years with a new JIA diagnosis (index date) and 12 months continuous enrollment pre- and post-diagnosis from 2008 to 2016. JIA patients were matched to non-JIA patients on age, gender, region, and health plan type. Patients with other rheumatic or autoimmune conditions were excluded. Receipt of a biologic and/or non-biologic was evaluated on or after the new JIA diagnosis. Results: A total of 3,815 JIA patients were matched to 11,535 non-JIA patients (mean age 10.0 [SD=4.5], 69% female). Average total costs were greater for JIA patients than non-JIA controls ($18,611 [SD=$42,104; median=$8,189] versus $2,203 [SD=$9,309; median=$649], p

Introduction: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-α therapies. However, treatment failure with anti-TNF-α can represent a relevant clinical problem. Areas covered: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. Expert opinion: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocated

We read with interest the article by Gupta et al 1 who reported the management of treatments for rheumatic diseases during COVID-19 pandemic among practitioners in India. In this study, the authors showed that about half of the physicians would reduce the use of biological disease-modifying antirheumatic drugs (bDMARDs) or defer specific drugs such as rituximab.1 Choices were apparently made considering possible relationships between drug mechanism of action and effect on the viral infection.1 During COVID-19 pandemic, telemedicine is emerging as a possible tool for reducing the risk of contagion and viral spread,2–4 and a useful strategy for the management of chronic diseases.5 6 As of 29 April 2020, the outbreak of COVID-19 generated 201 505 confirmed cases in Italy, with 2405 confirmed cases in Naples Metropolitan area. The objective of our study was to evaluate telemedicine when offered as part of routine care for the follow-up of patients …

To describe the baseline characteristics of the patients enrolled in the QUality of life in patients with Axial SpondyloARthritis (QUASAR) study in terms of quality of life (QoL), disease activity, therapy adherence, and work ability in a real-world setting.QUASAR is an Italian multicentre, prospective 12-month observational study, including consecutive adult patients classified as axial spondyloarthritis (axSpA) according to the Assessment of SpondyloArthritis international Society criteria for axSpA.Of 512 patients enrolled in 23 rheumatology centres, 80.7% had ankylosing spondylitis (AS) and 19.3% had non-radiographic axSpA (nr-axSpA). Mean ages were 34.1±13.3 years at axSpA symptoms onset and 39.5±13.0 years at diagnosis. Of the patients, 51.4% presented with ≥1 extra articular manifestation (EAM); the most common were psoriasis (17.8%) and uveitis (16.4%). Patients with nr-axSpA and AS had similar EAM rates, disease activity, and QoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs; 83.2%) were the most commonly received medication, followed by conventional synthetic DMARDs (22.9%) and non-steroidal anti-inflammatory drugs (NSAIDs; 16.6%). At baseline, higher treatment satisfaction was reported with bDMARDs which, together with NSAIDs, were associated with the best overall scores for disease activity, function, and QoL in the overall population and AS subgroup.QUASAR is the first Italian prospective study that comprehensively evaluated a large axSpA patient sample in a real-world setting. This interim analysis at baseline confirmed that i) patients with AS and nr-axSpA have similar QoL and disease burden, ii) nearly all axSpA patients receive treatment, and iii) bDMARDs and NSAIDs, overall, yield better disease activity and QoL.

La artritis reumatoidea es una enfermedad crónica de carácter autoinmunitario caracterizada principalmente por el compromiso inflamatorio de las articulaciones cartilaginosas. Se han desarrollado múltiples tratamientos farmacológicos para controlar el avance de la artritis reumatoidea, entre ellos, los fármacos antirreumáticos modificadores de la enfermedad, además de nuevos esquemas terapéuticos con inhibidores del factor de necrosis tumoral alfa, con resultados clínicos satisfactorios. Sin embargo, el uso de tales medicamentos no resulta inocuo, ya que se los ha asociado con diversos efectos secundarios, especialmente, infecciones como la tuberculosis, lo cual exige la aplicación de pruebas de tamización antes de utilizarlos. Se reporta el caso de una paciente de 58 años de edad con artritis reumatoidea de seis años de evolución, que después de recibir tratamiento con uno de estos fármacos, el infliximab, desarrolló tuberculosis diseminada, cuyo diagnóstico se confirmó mediante radiología e histopatología. No se emplearon pruebas de detección de la tuberculosis latente antes de prescribirle el infliximab. Las pruebas de tamización para tuberculosis deben emplearse de forma rutinaria, con el fin de detectar aquellos pacientes con tuberculosis latente, ya que es la única manera de determinar si se requiere profilaxis antituberculosa antes de administrar dichos fármacos, hecho que marca la diferencia cuando se busca disminuir la incidencia de tuberculosis y la consecuente morbimortalid. Rheumatoid arthritis is an autoimmune systemic disease characterized mainly by inflammatory compromise of diarthrodial joints. Multiple drug therapies have been developed to control the activity of rheumatoid arthritis, among them, the first line of disease-modifying antirheumatic drugs (DMARD), and novel drug therapies such as the anti-TNF alpha therapy, with satisfactory clinical outcomes. Despite this positive fact, the use of this therapy implies the risk of producing negative effects due to its mechanism of action, which has been associated with multiple infections, especially tuberculosis, making it necessary to use screen tests before resorting to this kind of drugs. We present the case of a 58-year-old female patient, with a six-year history of rheumatoid arthritis. The patient developed disseminated tuberculosis with compatible radiological and histological findings after receiving treatment with infliximab (anti-TNF therapy). No test was performed to screen for latent tuberculosis infection prior to the administration of infliximab. The performance of routine screenings tests for tuberculosis prior to anti-TNF alpha therapy plays an essential role in the detection of asymptomatic patients with latent tuberculosis. This is the only way to identify those patients who would benefit from anti-tuberculosis drugs before the initiation of anti-TNF alpha therapy, which makes the difference in the search of a significant reduction in the incidence of tuberculosis and its associated morbidity and mortality. © Biomédica 2018.

Background Although in the past, prevention of the joint destruction and disability was strongly emphasised in Rheumatoid Arthritis (RA), at present, a growing body of evidence is focused at identifying the best management of associated comorbidities, such as Type 2 Diabetes (T2D). Recently, the hypothesis that blocking pro-inflammatory activity may be helpful in the treatment of some comorbidities has been proposed in RA patients. Objective We reviewed the role of IL-1β during RA and T2D, the efficacy of IL-1 blocking agents in controlling both diseases and, possible, decreasing the concomitant enhanced atherosclerotic process. Method After literature search, the available evidence has been selected and commented in the text. Results During RA, it is well known that different inflammatory cytokines, such as interleukin-1β (IL-1β), are pivotal pathogenic mediators and their role has been largely confirmed in clinical settings. Similarly, it has been shown that the excess of nutrients, secondary to over-nutrition, may activate the immune system, leading to an increased production of inflammatory cytokines, including IL-1β, suggesting new possible therapeutic targets. Conclusion Although further studies are needed to fully investigate the pathogenic interplay between inflammation and metabolic disorders, IL-1β has been implicated in both RA and T2D pathogenic mechanisms. Intriguingly, the potential role of anti-IL-1 drugs has been proposed in RA patients affected by T2D.

Rheumatoid arthritis (RA) is an immune-mediated condition which primarily affects the joints, but with critical extra-articular manifestations, including a significantly increased cardiovascular risk. Patients suffering from RA can develop deforming and disabling alterations of the affected joints. Their quality of life can be substantially affected, and their life expectancy is shorter compared to that of healthy subjects. Fortunately, several pathogenic mechanisms characterizing RA have been identified, leading to the development of targeted drugs. Inhibitors of tumor necrosis factor (TNF) were the first developed among biological medications and they dramatically changed the therapeutic perspectives of RA patients. Now, 20 years after the licensing of etanercept (the first anti-TNF drug), more than 10 different biological agents have been approved by the U.S. Food and Drug Administration (FDA). Additionally, more and more drugs are under investigation in clinical trials. This review will focus on the more recently approved monoclonal antibodies and the more promising antibodies under investigation.

Objective We aimed to evaluate the relationship among TNFα, sTNFR1, sTNFR2, sIL2R, IL6, neopterin and disease activity in ankylosing spondylitis (AS). Materials and methods TNFα, sTNFR1, sTNFR2, sIL2R, IL6 and neopterin were measured in patients and controls. Patients were grouped according to disease activity and medication. Results Neopterin and sTNFR1 were not different while TNFα, sTNFR2, sIL2R and IL6 were high in patients than controls. There was no difference between active and inactive patients for TNFα, sIL2R and IL6. sTNFR2 was significantly lower in active patients. There was no relationship between CRP positivity and disease activity. AS patient groups are; 1: TNF blockers, 2: nonsteroidal anti-inflammatory drugs (NSAIDs), 3: disease modifying anti-rheumatic drugs (DMARDs), 4: TNF blockers and NSAIDs, 5: DMARDs and NSAIDs. sTNFR2 was significantly lower in active patients than in inactive, in Group 1. ESR levels were significantly lower in inactive patients compared to active in group 3 and 4. There was no significant association between CRP positivity and disease activity. Conclusion According to our study, CRP is insufficient in evaluating AS disease activity. ESR can be useful in evaluating the disease activity. sTNFR2 might be useful as a biological indicator of disease activity in AS treated with TNF inhibitors alone.

We aim to draw attention to occult, atraumatic fractures of the odontoid process in patients with rheumatoid arthritis (RA) and to underline difficulties encountered during clinical and radiological diagnosis. A forty-seven years old man with RA for 4 years had occipital pain for 1 year without any history of trauma. Later, he developed weakness in the upper extremities, but he did not realize weakness in the lower extremities due to deformities. Contrast magnetic resonance imaging revealed a linear fracture of odontiod process and myelopathy. Cervical computed tomography scan revealed an old fracture border with separated and almost disappeared remnant of the tip of the odontoid without free particles in the cord. It was impossible to evaluate atlantoaxial and vertical subluxations with craniometric measurements due to destruction of the tip of odontoid. Following occipitocervical fusion and decompression and a rehabilitation program, his muscle strength improved; however, functional myelopathy stage did not change. Atraumatic fractures of the odontoid process may be more common than reported and may cause compression of the spinal cord or brain stem. Surgery is the treatment of choice but functional recovery is limited once neuronal damage has occurred. Erosion of the critical landmarks makes it difficult to diagnose and follow up atlantoaxial subluxation and/or vertical subluxation, therefore clinicians should consider radiographical follow-ups during the course of the disease. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

Introduction Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). Objectives To evaluate the efficacy and safety of RTX–MTX combination therapy compared with RTX alone in the treatment of RA. Methods We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. Results We identified 338 RA patients, 162 treated with RTX and 176 with RTX–MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX–MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX + MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX + MTX and RTX, respectively; while 12 patients (4.5% in RTX + MTX, and 2.5% in RTX group) suspended therapy for AE. Conclusions RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.