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New evidence for the treatment of rheumatoid arthritis (RA) has emerged during the last year. Specifically, updated guidelines on pharmacological and non-pharmacological management of RA have emphasised the necessity of global patient's care, and have shifted the role of some older drugs, such as glucocorticoids and methotrexate. In addition, the long-term safety of Janus kinase inhibitors was investigated and reinforced. With respect to the coronavirus-19 pandemic, reassuring data on the efficacy and safety of vaccinations in the RA population were acquired, as well as on the potential role of telemedicine in RA management. Machine learning prediction models and biomarkers development have emerged as promising innovations in the area of precision/personalised medicine, appearing to encourage future expansion. In this narrative review, the authors aim to give their specific point of view on the most relevant and potentially impacting novelties published during 2021 and early 2022 in the context of RA management.

Systemic lupus erythematosus (SLE) is characterized by multisystemic clinical manifestations ranging from a relatively mild involvement to potentially life-threatening complications. Due to this complexity, a multidisciplinary (MD) approach is the best strategy for optimizing patients’ care. The main aim of this systematic literature review (SLR) was to scrutinize the published data regarding the MD approach for the management of SLE patients. The secondary objective was to evaluate the outcomes of the MD approach in SLE patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used. We performed an SLR to retrieve articles available in English or Italian listed in PubMed, Embase, Cinahl, and Cochrane Library concerning the MD approach used in observational studies and clinical trials. Four independent reviewers performed the study selection and data collection. Of 5451 abstracts evaluated, 19 studies were included in the SLR. The MD approach was most frequently described in the context of SLE pregnancy, reported in 10 papers. MD teams were composed of a rheumatologist, except for one cohort study; a gynecologist; a psychologist; a nurse; and other health professionals. MD approaches had a positive impact on pregnancy-related complications and disease flares and improved SLE psychological impact. Although international recommendations advise an MD approach for managing SLE, our review highlighted the paucity of data supporting this strategy, with most of the available evidence on the management of SLE during pregnancy.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD −0.85 [95% CI −1.23; −0.47]) and CD68+ macrophages (sublining, sl) (SMD −0.74 [−1.16; −0.32]) in synovial biopsies from patients treated for 4–12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

Background:Fertility is thought to be not reduced in women affected by systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease as well as medication exposure might impair gonadal function.Objectives:The aim of this systematic review was to explore clinical, hormonal, serological, instrumental and management factors associated with fertility outcomes in women of childbearing age with SLE.Methods:This systematic review was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English, published from 1972 to 15th August 2020 in Pubmed, EMBASE, Scopus and Cochrane Library. Study selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. Risk of bias of the included studies was assessed by using the NIH risk-of-bias tool [1].Results:Of 788 abstracts, we included in the review 45 studies of which 1 systematic literature reviews, 16 cross-sectional studies, 15 cohort studies, 12 observational studies and 1 case-series study, with a total of 4656 patients. The mean age was 33.5 ± 5.4 years, while the mean disease duration was 97.4 ± 65.2 months. Figure 1 illustrates the quality of the included studies. Definitions of fertility/premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered. Most studies did not use a hormonally based definition of fertility. Clinical factors associated with the development of POF were older age at the time initiation of therapy and older age at the onset of SLE disease. Cyclophosphamide exposure (CYC) and its cumulative dose influenced gonadal function in SLE women, leading to amenorrhoea and ovarian failure, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids seem to be associated with a lower risk of ovarian failure compared to CYC. 3 studies demonstrated that POF was more frequent in patients treated with CYC not receiving gonadotropin-releasing hormone analogues (GnRH) in comparison to those co-treated with GnRH. 11 studies evaluated the impact of damage and disease activity on ovarian reserve in patients with SLE with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors able to influence fertility outcomes; among others nor Anti-Müllerian Hormone, neither anti-corpus luteum antibodies were associated with POF.Conclusion:The role of disease activity on fertility in SLE patients is contradictory. Regarding management factors associated with fertility in SLE women of childbearing age, the strongest evidence is about the treatment with CYC and its cumulative dose. Hormonal and serological factors did not impact on fertility outcome but might be used as a surrogate of fertility, especially after treatment with disease-specific drugs.References:[1]Study Quality Assessment Tools NIH. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools.[2]Andreoli L. et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017; 76: 476–485.Disclosure of Interests:None declared

BackgroundThe efficacy of Janus Kinase inhibitors (JAKis) in Rheumatoid Arthritis (RA) has been established in the last years through numerous randomized clinical trials. Recently, the safety profile of this drug class has come under the spotlight, questioning the actual use in clinical practice and making real-life data even more crucial.ObjectivesThe purpose of this study is to evaluate the long-term retention rate of JAKis and to estimate the influence of baseline population characteristics on treatment persistence.MethodsData of all RA patients who started a JAKi were prospectively collected in the Italian multicentric GISEA registry. The 3-year retention rate of JAKis was calculated by the Kaplan-Meier method and compared by a log-rank test after stratification according to different baseline population characteristics. A descriptive analysis of reasons for discontinuation was performed.ResultsThe study population included 1361 patients (females 83.5%, mean age [±SD] 57.3 [±12.3] years, over 65 years 30%, mean disease duration 12.7 [±9.7] years, mean baseline SDAI 20.6 [±11.7], ACPA positive 68%, RF positive 66%, current smokers 19%, past smokers 13%) who received a JAKi (baricitinib=763, tofacitinib=321, upadacitinib=151, filgotinib=126) as first (n=491) or subsequent line (n=870) targeted drug. The overall 3-year retention rate was 46%. Drug survival was significantly higher in ACPA positive compared with negative patients (51.6 vs 41.8%, p=0.0051) (Figure 1A) and in first-line versus second or further lines of therapy (50.6 vs 43.3%, p=0.0013) (Figure 1B). No difference was found according to age (< or ≥65 years), concomitant methotrexate, smoke, history of diabetes, or at least one cardiovascular comorbidity (hypertension, stroke, or heart failure). Therapy was discontinued in a total of 523 patients because of ineffectiveness (67.5%), adverse events (25.8%), or compliance/other reasons (0.3%). Of relevance, adverse events included cancer (0.7%), major adverse cardiovascular events (MACE) (0.4%), deep vein thrombosis (DVT) (0.6%), and herpes zoster virus (HZV) infections (1.5%).ConclusionOur data confirmed in a real-life setting a favorable 3-year retention rate of JAKis in RA. ACPA positivity and use as first-line targeted drug significantly improved persistence of JAKis. Discontinuations of JAKis because of adverse events (including MACE, DVT, HZV, and malignancy) were very uncommon, suggesting an overall favorable safety profile.Figure 1.A) Retention rate in ACPA positive versus ACPA negative patients. B) Retention rate in first-line versus second or further lines of therapy.AcknowledgementsWe thank the physicians and patients who participated in these studies.Disclosure of InterestsMartina Biggioggero Speakers bureau: Galapagos, Elisa Gremese: None declared, Serena Bugatti: None declared, Andreina Manfredi: None declared, Simone Parisi: None declared, Chiara Bazzani: None declared, Antonio Carletto: None declared, Carlo Garaffoni: None declared, Angelo Semeraro: None declared, Addolarata Corrado: None declared, Rosario Foti: None declared, Alberto Cauli: None declared, Francesca Romana Spinelli Speakers bureau: Amgen, AbbVie, Eli Lilly, Galapagos, Consultant of: Amgen, AbbVie, Eli Lilly, Galapagos, Florenzo Iannone: None declared, Ennio Giulio Favalli Speakers bureau: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB.

BackgroundCardiovascular disease (CVD) risk in patients with chronic inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), is substantially increased compared to the general population. New evidence strengthens the notion that the excess risk of CVD morbidity and mortality in patients with IA is related to both traditional (e.g. hypertension, diabetes, smoking) and novel CVD risk factors, including chronic inflammation, leading to an accelerated atherosclerosis. How to minimize such increased CVD prevalence is still poorly understood, and whether more intensive traditional risk factor control or disease specific risk factor should be targeted is still matter of debate.ObjectivesThe aim of this systematic review was to identify intervention targeting CVD or inflammatory arthritis associated with improvement of CV risk outcomes (estimated CV risk, CV events, endothelial function, arterial stiffness, subclinical atherosclerosis) in adult patients with diagnosis of inflammatory arthritis (RA, PsA and AS).MethodsTwo independent reviewers retrieved randomized controlled trials of interest from systematic searches of Medline, Embase and Cochrane database (20th April 2020). Data extraction was performed using standard template; the quality of each included trials was assessed with the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) [1]. Systematic review was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement.ResultsOut of total of 4823 articles, 27 met the inclusion criteria. Among these, most (n=22) involved RA patients, one trial was based on mixed IAs patients and the remaining (n=4) were performed on spondylarthritis population. Total number of patients was 8045. Overall risk of bias was high in most of per protocol analysis trials (90%) and in 26.7% of intention-to-treat analysis trials. Four trials evaluated major adverse cardiovascular events (MACE) incidence and one of these demonstrated a significant reduction in incidence of MACE in RA patients underwent a treat-to-target strategy of CV risk factor. The same study also demonstrated a significant reduction in progression of subclinical atherosclerosis (carotid Intima-media thickness, cIMT), while other trials (n= 8) exploring effect of rosuvastatin, enalapril, tocilizumab and TNF-inhibitors failed to reach a similar result. Endothelial dysfunction, predominantly measured as reduce flow mediated dilatation (FMD), was widely used as surrogate outcome of CVD and it appeared to be significantly improved by treatment with statins, ACE-inhibitors, anakinra and tocilizumab. Treatment with pioglitazone, anakinra or tocilizumab in three trials significantly ameliorated arterial stiffness, estimated with pulse wave velocity (PWV), Cardio-ankle vascular index (CAVI) or augmentation index (AI). Two studies explored how a reduction of estimated CV risk could be achieved after treatment with enalapril and tight-control strategy aiming to SDAI ≤ 3.3. Results of both trials didn’t demonstrate any variation in QRISK3-2018 and Framingham risk score, respectively.ConclusionOptimal CVD management in IA patients remains undefined and it should be implemented as stated in international guidelines. Randomized controlled trials exploring efficacy of prevention strategy are few and predominantly focused on surrogate outcome measures of cardiovascular risk.References[1]Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366:l4898. https://doi.org/10.1136/bmj.l4898.Disclosure of InterestsCarlo Garaffoni: None declared, Antonio Marangoni: None declared, Marcello Govoni Speakers bureau: Abbvie, Pfizer, Galapagos, BMS, Eli-Lilly, Paid instructor for: Pfizer, Consultant of: Abbvie, BMS, Novartis, Astrazeneca, Pfizer, Carlo Alberto Scirè Grant/research support from: AbbVie, Lilly

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