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Background Achieving clinical remission is a key therapeutic goal in rheumatoid arthritis (RA). While pivotal trials and early real-world studies have demonstrated the efficacy of upadacitinib (UPA), data on its impact as assessed by imaging remain limited. Here, we report the 48 weeks outcomes from the full cohort of the UPARAREMUS study. Methods UPARAREMUS is a 12-month follow-up, observational study involving RA patients from 9 Italian rheumatology centers initiating UPA. The primary objective was to evaluate the proportion of patients achieving combined clinical and ultrasound (US) remission. Secondary endpoints included the proportion of patients achieving clinical or US remission alone at multiple time points. Results A total of 115 patients were enrolled. Combined clinical and US remission was achieved in 35% of patients at week 12, increasing to 55% at week 24 and 72% at week 48. Younger age, lower baseline CDAI, and higher ESR were associated with higher remission rates, while baseline corticosteroid use was linked to a 65% lower likelihood of achieving remission. More than 60% of patients showed absence of power Doppler (PD) signal at week 24, rising to over 80% by week 48. The majority of patients in clinical remission also achieved US remission. Conclusions After 12 months of UPA treatment, a substantial proportion of RA patients achieved combined clinical and US remission, independent of prior bDMARDs use or monotherapy. These findings highlight UPA's ability to induce and maintain deep disease control in real-world practice.

Rheumatoid arthritis (RA) is an autoimmune disorder in which gut and oral microbiota play a crucial role. Diet is a modifiable factor that can influence both microbiota composition and arthritis outcome; previous studies have suggested associations between dietary habits and RA, with contrasting results. We investigate the protective effect of the Mediterranean diet (MD) on disease activity and the gut microbiota profile in RA patients. Sixty consecutive RA patients were enrolled upon filling a validated 14-item questionnaire for the assessment of adherence to the Mediterranean diet (Prevention with Mediterranean Diet-PREDIMED). Then, 16S analysis was employed to explore the gut microbiota within the two cohorts of patients. Patients with high adherence to MD (20) had a significantly lower C-reactive protein (p < 0.037) and disease activity (p < 0.034) than the 40 patients with low/moderate adherence to MD. An inverse association between MD and disease activity was confirmed by multivariate analysis after adjustments for all the different demographic, clinical and serologic variables. A healthier gut microbiota composition was observed in the high adherence group, with a significant decrease in Lactobacillaceae and an almost complete absence of Prevotella copri with respect to the low/moderate adherence group. In conclusion, our findings support the protective role of MD on disease activity and microbiota composition in RA patients, and suggest the feasibility of shifting the habitual diet to modulate the gut microbiota and promote the benefits associated with MD.

Impressive efforts have been made by researchers worldwide in the development of target vaccines against the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and in improving the management of immunomodulating agents. Currently, different vaccine formulations, such as viral vector, mRNA, and protein-based, almost all directed toward the spike protein that includes the domain for receptor binding, have been approved. Although data are not conclusive, patients affected by autoimmune rheumatic diseases (ARDs) seem to have a slightly higher disease prevalence, risk of hospitalization, and death from coronavirus disease-2019 (COVID-19) than the general population. Therefore, ARD patients, under immunosuppressive agents, have been included among the priority target groups for vaccine administration. However, specific cautions are needed to optimize vaccine safety and effectiveness in these patients, such as modification in some of the ongoing immunosuppressive therapies and the preferential use of mRNA other than vector-based vaccines. Immunomodulating agents can be a therapeutic opportunity for the management of COVID-19 patients; however, their clinical impact depends on how they are handled. To place in therapy immunomodulating agents in the correct window of opportunity throughout the identification of surrogate markers of disease progression and host immune response is mandatory to optimize patient’s outcome.

Patients with autoimmune rheumatic diseases (ARDs) such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are at increased risk of infections due to immune dysregulation and immunosuppressive therapy. Vaccination is a cornerstone of infection prevention, but uptake is still inadequate. We conducted an observational, multicenter study at four Italian rheumatology centers. Adult patients with RA or SLE on immunosuppressive therapy completed a standardized questionnaire assessing demographics, disease activity, treatments, vaccination status for influenza, pneumococcus, varicella-zoster virus [VZV], hepatitis B virus [HBV], human papillomavirus [HPV], adverse events, and reasons for or against vaccination. A total of 325 patients were included (226 RA, 99 SLE; median age 60 years; 84.6% females). Overall vaccine coverage was 68.0%, with influenza being the most frequent (54.2%), followed by pneumococcal (30.8%), HBV (21.2%), VZV (12.9%) and HPV (5.9%). RA patients showed higher influenza and pneumococcal uptake, while HBV vaccine was more common in SLE. Education was associated with higher pneumococcal and HBV coverage in both groups. Major adverse events and disease flares were rare. Physician recommendation was the main motivator, with rheumatologists driving VZV uptake and general practitioners influencing influenza and HBV. Among unvaccinated patients, the leading barrier was not being offered vaccination (42.5%), followed by concerns about efficacy/safety (18.3%) and lack of awareness (15.7%). Cluster analysis identified three subgroups: \"Not offered\" (largest), \"Unaware,\" and \"Skeptical,\" with age distribution differing across clusters. Vaccination coverage among Italian ARD patients remains insufficient. Physician recommendation is pivotal, while lack of physician offer and awareness are major barriers. Targeted educational strategies and proactive physician involvement are needed to improve vaccine uptake in this high-risk population.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that can present different extrarticular manifestations involving heart, lungs and kidneys. In recent years there has been a growing awareness of the central role played by the lungs in the onset and progression of RA. In particular interstitial lung disease (ILD) is a common pulmonary manifestation that may be related to the inflammatory process itself, infectious complications and to the treatments used. Management of patients with ILD/RA is still a challenge for clinicians, both synthetic [mainly methotrexate (MTX), leflunomide] and biologic immunosuppressors [mainly anti-tumor necrosis factor (TNF)α] have in fact been related to the onset or worsening of lung diseases with conflicting data. Here we report the case of a 61-year-old male patient with severely active early RA, previously treated with MTX, who developed subacute ILD, along with a review of ILD/RA topic. Tocilizumab (humanized monoclonal antibody against the interleukin-6 receptor) was introduced on the basis of its effectiveness in RA without concomitant MTX and the ability to overcome the profibrotic effects of interleukin (IL)-6. After 3 months of treatment the clinical condition of the patient strongly improved until it reached low disease activity. He no longer complained of cough and dyspnea and bilateral basal crackles were no more present. Considering its distinctive features, tocilizumab, in such a challenging clinical condition, appears to be a safe and effective therapy, thus it enables RA remission without deteriorating ILD, at 1-year follow up, as confirmed by ultrasonography of the affected joints and chest high-resolution computed tomography (HRCT).

On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient’s clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk.

Introduction: Psoriatic arthritis (PsA) is a complex condition within the Spondyloarthritis (SpA) group. Recent studies have focused on the important role of the intestinal microbiota in maintaining immunological homeostasis, highlighting how intestinal dysbiosis may act as a trigger for autoimmune diseases. Tofacitinib is a Janus kinase inhibitor (JAK-i) with proven efficacy for the treatment of both rheumatoid arthritis and PsA. However, there is a lack of data on its ability to reduce joint remission through ultrasonography (US) and the effects it might have on the composition of the gut microbiota. Methods: Here, we present a case series of seven bio-naïve PsA patients who received tofacitinib treatment and were followed up for 12 months. The clinical response was assessed using validated scores (DAPSA, ASDAS, and BASDAI), laboratory tests, and US assessment of the target joint and enthesis. Finally, we evaluated changes in the composition of the intestinal microbiota using next-generation sequencing analysis of fecal samples. Results: The patients in the study showed a significant improvement in all clinical scores used; this improvement was also confirmed by a significant reduction in the US synovitis scores. The data on the microbiota analysis suggested that the effectiveness of tofacitinib in ameliorating PsA activity was associated with a relevant modification of some gut bacterial lineages. No cases of severe adverse effects were reported. Conclusions: Treatment with tofacitinib proved to be effective, safe and capable of varying the composition of the gut microbiota by selecting bacterial strains considered beneficial in immune modulation.

IntroductionClinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase 1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study.MethodsThis is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week 24. The proportion of patients achieving clinical remission with different composite indexes at week 12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks 12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints.ResultsAfter 12 weeks and 24 weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve.ConclusionsUPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24 weeks, 63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.

Spondyloarthritis (SpA) and inflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by an aberrant immune response and inflammation with a key role for TNF in their pathogenesis. Accordingly, TNF-inhibiting therapy (TNFi) has dramatically improved the management of these diseases. However, about 30% of patients discontinue TNFi for lack of response, loss of response, and side effects and/or adverse events. Thus, the possibility to identify in advance those patients who will have a good response to TNFi would be extremely beneficial. The aim of this study was to investigate differences between males and females with either SpA or IBD in response to TNFi molecules, i.e., infliximab (IFX) and adalimumab (ADA), considering the reasons for TNFi withdraw. Data of 594 patients, 349 with IBD (M/F: 194/155) and 245 with SpA (M/F: 123/122), previously unexposed to TNFi, were collected. In the IBD group, the rate of female patients discontinuing ADA was significantly higher than that of male patients ( = 0.03). No difference emerged according to the distribution of reason for discontinuation. Otherwise, a similar discontinuation rate between female and male patients receiving IFX therapy was observed. In the SpA group, the overall discontinuation rate was not different between males and females both for ADA and IFX. However, in patients treated with ADA, males interrupted therapy more frequently than females due to lack of response ( = 0.03). In conclusion, the assessment of sex differences in TNFi response could help physicians personalize the therapeutic approach in a sex-oriented perspective.

Differential diagnosis in early arthritis is challenging, especially early after symptom onset. Several studies applied musculoskeletal ultrasound in this setting, however, its role in helping diagnosis has yet to be clearly defined. The purpose of this work is to systematically assess the diagnostic applications of ultrasonography in early arthritis in order to summarize the available evidence and highlight possible gaps in knowledge. In December 2017, existing systematic literature reviews (SLR) on rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), polymyalgia rheumatica (PMR), calcium pyrophosphate deposition disease (CPPD), and gout were retrieved. Studies on ultrasound to diagnose the target conditions and detecting elementary lesions (such as synovitis, tenosynovitis, enthesitis, bone erosions, osteophytes) were extracted from the SLRs. The searches of the previous reviews were updated and data from new studies fulfilling the inclusion criteria extracted. Groups of reviewers worked separately for each disease, when possible diagnostic accuracy (sensitivities, specificities) was calculated from primary studies. When available, the reliability of ultrasound to detect elementary lesions was extracted. For all the examined disease, recent SLRs were available. The new searches identified 27 eligible articles, with 87 articles included from the previous SLRs. The diagnostic performance of ultrasound in identifying diseases was addressed by 75 studies; in most of them, a single elementary lesion was used to define diagnosis, except for PMR. Only studies on RA included consecutive patients with new onset of arthritis, while studies on gout and CPPD often focused on subjects with mono-arthritis. Most of the remaining studies enrolled patients with a defined diagnosis. Synovitis was the most frequently detected lesion; clinical diagnosis was the most common reference standard. The diagnostic performance of ultrasound across different conditions was extremely variable. Ultrasound to identify elementary lesions was assessed in 38 studies in OA, gout and CPPD. Its performance in OA was very variable, with better results in CPPD and gout. The reliability of ultrasound was moderate to good for most lesions. Although a consistent amount of literature investigated the diagnostic application of ultrasound, in only a minority of cases its additional value over clinical diagnosis was tested. This SLR underlines the need for studies with a pragmatic design to identify the placement of ultrasound in the diagnostic pathway of new-onset arthritis.