Ennio Giulio Favalli

Limited data are available on sex differences in the disease characteristics, burden and treatment outcomes of early psoriatic arthritis (PsA). The "Spondyloarthritis Italian Registry: Evidence from a National Pathway" (SIRENA) study is a prospective, observational, Italian study conducted in 23 Rheumatology sites on patients with recent diagnosis of spondyloarthritis and naïve to any disease-modifying antirheumatic drugs (DMARDs). The study included 203 patients with early PsA, observed per clinical practice, who were studied regarding the influence of sex on the disease presentation and the likelihood of achieving minimal disease activity (MDA). Clinical and patient-reported outcome (PRO) measures were collected at both study entry and each follow-up visit until 24 months. Treatment was assigned by the treating rheumatologist based on standard clinical practice. At baseline, 87% of patients with PsA received systemic treatment, mainly with conventional (49%) or biological (25%) DMARDs. Twenty-three of 158 (15%) patients were already in MDA status at study entry: this percentage increased to 55% (n = 83/150) at 6 months and 75% (n = 73/97) at 24 months. MDA was more frequent in males at baseline (20.0% vs. 8.2% in females, p = 0.036) and throughout the study. Significant improvements in clinical measures and PROs were reported in both sexes at all follow-up visits, but PRO scores were significantly worse in females at baseline and at most endpoints. Increasing age, male sex, new PsA diagnosis, mono-/oligoarticular involvement, low (≤ 14) Disease Activity index for PSoriatic Arthritis (DAPSA) and low Health Assessment Questionnaire Disability Index (HAQ-DI) values showed potential associations with MDA achievement at 6 months in univariate analysis, but this was not significant in the multivariate model. In patients with PsA naïve to DMARDs, sex considerably influences the clinical characteristics and outcomes. NCT03131661.

Current literature regarding cancer risk in rheumatic and musculoskeletal diseases (RMDs) is particularly poor and controversial, even though the incidence of malignancy in some patients with RMDs is considered to be increased compared with the general population. Malignancy may be a major comorbidity in subjects with spondyloarthritis (SpA) as the result of multifactorial mechanisms, from disease pathogenesis to the iatrogenic effect of immunomodulating drugs. Several recommendations for screening and management of cancer risk have been developed in recent years with the aim of improving the different outcomes in these patients. The goal of this narrative review is to provide an overview of the currently available evidence on the risk of malignancy connected with RMDs and examine the association of SpA with cancer and the potential impact of its treatment with biologic and targeted synthetic disease-modifying anti-rheumatic drugs on development of malignancy.

Objective: Some concerns remain about the safety of nintedanib in patients with rheumatoid arthritis–related interstitial lung disease (RA-ILD), such as in the presence of comorbidities or in combination with biologic, targeted synthetic, and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). In this multicenter study, we retrospectively evaluated the safety of nintedanib in a real-world population of patients with RA-ILD from the Italian Group for the Study of Early Arthritis (GISEA) registry and the possible role of comorbidities and DMARDs on drug safety and withdrawal. Our secondary aim was to investigate the causes of nintedanib discontinuation. Methods: Sixty-five patients treated with nintedanib in accordance with the current therapeutic indications were enrolled in the study. Nintedanib was prescribed in combination with DMARDs and/or steroids in 62 patients (95.4%). Results: The 12-month retention rate of nintedanib was 76.7% and the drug was effective in about 80% of patients with ≥ 6 months of follow-up. Adverse events (AEs) were recorded in 36 subjects (55.3%), and these were mainly gastroenteric. Thirty-one subjects required a reduction of the nintedanib dose; among them, a transient or permanent reduction of the daily dose of nintedanib allowed the continuation of the treatment in 22, whereas 15 (23.1%) withdrew from the drug. All reductions and discontinuations were owing to treatment-related AEs. Comorbidities were significantly associated with side effects in multivariate analysis, whereas AEs due to nintedanib were the main cause of discontinuation. Conclusion: Combination therapy with DMARDs did not reduce the safety and effectiveness of nintedanib, and AEs were the main cause of drug withdrawal or dose reduction, mainly owing to comorbidities.

Objective. To provide a comprehensive overview of peripheral spondyloarthritis (pSpA), focusing specifically on its occurrence and management in patients with inflammatory bowel disease (IBD). Methods. An exhaustive literature search was conducted in PubMed, Embase, Cochrane Database of Systematic Reviews, and Google Scholar to identify relevant studies on pSpA in IBD patients. Titles, abstracts, and full-text articles were screened for relevance. Data on study design, patient characteristics, diagnostic criteria, main findings, and conclusions were extracted from selected articles. Study quality was assessed using appropriate checklists. Information was synthesized narratively to summarize current understanding. Results. pSpA is the most common extraintestinal manifestation of IBD, with a median prevalence of 16%. It worsens quality of life and requires collaboration between gastroenterologists and rheumatologists for optimal diagnosis and treatment. Several “red flags” guide appropriate specialist referral of IBD patients with suspected pSpA. Once the diagnosis is confirmed, the choice of therapy depends on IBD phenotype and patterns of articular/axial involvement. Anti-tumor necrosis factor (TNF) drugs are first-line biologics, with interleukin (IL)-12/23 and IL-23 inhibitors as alternatives for anti-TNF failure. Small molecules like apremilast and Janus kinase inhibitors also have utility. Recommended treatment algorithms exist, but more randomized controlled trials are needed. Conclusions. Early identification of pSpA is crucial in IBD patients to enable timely intervention, prevent structural damage, and minimize disability. A multidisciplinary, holistic approach addressing musculoskeletal and extra-musculoskeletal manifestations is key to optimal patient outcomes.

Objectives: Real-world evidence is needed to inform treatment strategies for patients with PsA and axial SpA (axSpA) who have non-musculoskeletal manifestations (NMMs), various risk factors and comorbidities. International collaboration is required to ensure statistical power and to enhance generalizability. The first step forward is identifying which data are currently being collected. Across 17 registries participating in the European Spondyloarthritis Research Collaboration (EuroSpA), we aimed to map recording practices for NMMs, comorbidities and safety outcomes in patients with PsA and axSpA. Methods: Through a survey with 4,420 questionnaire items, we explored the recording practices of 58 pre-defined conditions (i.e. NMMs, comorbidities and safety outcomes) covering 10 disease areas. In all registries we mapped for each condition whether it was recorded, the recording procedure and the potential to identify it through linkage to other national registries. Results: Conditions were generally recorded at entry into the registry and clinical follow-up visits using a pre-specified list or a coding system. Most registries recorded conditions within the following disease areas: NMMs (number of registries, n = 15–16), cardiovascular diseases (n = 10–14), gastrointestinal diseases (n = 12–13), infections (n = 10–13) and death (n = 14). Nordic countries had the potential for data linkage and generally had limited recording of conditions in their registry, while other countries had comprehensive recording practices. Conclusion: A wide range of conditions were consistently recorded across the registries. The recording practices of many conditions and disease areas were comparable across the registries. Our findings support the potential for future collaborative research.

Objective: Treat‐to‐target is recommended in the management of rheumatoid arthritis (RA) but its implementation is suboptimal. We aimed to identify interventional strategies targeted at improving treat‐to‐target implementation in RA by systematically reviewing published evidence on barriers to, facilitators of, and interventions to support treat‐to‐target implementation.Methods: Systematic and scoping literature searches in PubMed/MEDLINE, BIOSIS Previews, Derwent Drug File, Embase, EMCare, International Pharmaceutical Abstracts, and SciSearch were conducted to identify barriers/facilitators and interventions relating to treat‐to‐target implementation in RA. The quality of included studies was assessed using Critical Appraisal Skills Programme (CASP) checklists. Data related to barriers/facilitators and interventions were extracted, grouped, and summarized descriptively, and a narrative synthesis was generated.Results: In total, 146 articles were analyzed, of which 123 (84%) included ≥50% of the items assessed by CASP checklists. Of the 146 studies, 76 evaluated treat‐to‐target barriers and facilitators, from which 329 relevant statements were identified and regrouped into 18 target areas, including health care professional (HCP) or patient knowledge or perceptions; patient‐HCP communication or alignment; and time or resources. Overall, 56 interventions were identified from 70 studies across the 18 target areas; 54% addressed disease activity or patient‐reported outcome assessments. Of the 56 interventions identified, 36 improved treat‐to‐target implementation and/or patient outcomes in RA.Conclusion: Despite long‐established treat‐to‐target recommendations, there remain many barriers to its implementation. Interventions to improve treat‐to‐target should be developed further and assessed, with a particular focus on tailoring them to individual countries, regions, and health care settings.

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease which can induce progressive disability if not properly treated early. Over the last 20 years, the improvement of knowledge on the pathogenesis of the disease has made available several drugs targeting key elements of the pathogenetic process, which now represent the preferred treatment option after the failure of first-line therapy with conventional drugs such as methotrexate (MTX). To this category of targeted drugs belong anti-cytokine or cell-targeted biological agents and more recently also Janus kinase inhibitors (JAKis). In the absence to date of specific biomarkers to guide the therapeutic choice in the context of true precision medicine, the choice of the first targeted drug after MTX failure is guided by treatment cost (especially after the marketing of biosimilar products) and by the clinical characteristics of the patient (age, sex, comorbidities and compliance) and the disease (presence or absence of autoantibodies and systemic or extra-articular manifestations), which may influence the efficacy and safety profile of the available products. This viewpoint focuses on the decision-making process underlying the personalized approach to RA therapy and will analyse the evidence in the literature supporting the choice of individual products and in particular the differential choice between biological drugs and JAKis.

Brief Papers; Authors: G. Maioli, G. Cincinelli, M. Biggioggero, R. Caporali, E.G. Favalli