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Rheumatoid arthritis (RA) pathogenesis is driven by a complex network of proinflammatory cytokines, among which interleukin-6 (IL-6) plays a key role in inducing and perpetuating chronic inflammation. Targeting the IL-6 pathway has shown to be an invaluable treatment strategy, as demonstrated by the results accrued in the last decade with the first IL-6 inhibitor, tocilizumab. More recently, a second monoclonal antibody blocking IL-6, sarilumab, has enriched our armamentarium by proving outstanding efficacy in RA treatment.After exploring the IL-6 pathway under physiological conditions and in the RA pathogenesis, in this review we discuss the pharmacologic properties of sarilumab and the clinical trials that constitute the sarilumab development program and have enabled its licensed application.Results from clinical trials confirmed the efficacy and safety of sarilumab for the treatment of RA, similar to its precursor tocilizumab. Blocking IL-6 pathway results in comprehensive control of the disease, from both physician's and patient's perspective, and of RA comorbidities and extra-articular manifestations, which are largely IL-6 driven. Finally, the proven efficacy of sarilumab as monotherapy arises the drug as a required therapeutic alternative considering the large proportion of patients intolerant or inadequate to receive conventional synthetic disease-modifying drugs (csDMARDs).

Introduction: Coronavirus disease 2019 (COVID-19) pandemic raises a great challenge in the management of patients with rheumatoid arthritis (RA), which are generally more susceptible to infection events because of the autoimmune condition itself and the treatment with immunomodulatory drugs. The use of disease-modifying anti-rheumatic drugs (DMARDs), including biologics and targeted-synthetic DMARDs, has aroused particular interest because of both their immunosuppressive effects and their hypothetical potential in COVID-19 treatment.Areas covered: For this narrative review, a literature search was conducted between December 2019 and February 2021 on PubMed including epidemiological studies, gathering the main evidence available to date about the impact of COVID-19 on RA patients and the influence of anti-rheumatic drugs on patients' susceptibility to this infection. We also summarize the recommendations from the international guidelines on the management of rheumatic diseases and treatments in this pandemic context, especially focused on RA.Expert opinion: About a year after the outbreak of the pandemic, we are able to answer some of the most relevant questions regarding patients with RA and their management in this pandemic context. Our efforts must now be directed toward consolidating the currently available data with more rigorous studies and facing new issues and challenges including, foremost, vaccination.

Background:Up to 30% of Psoriasis (PsO) patients are prone to develop Psoriatic Arthritis (PsA). Agreement on how to identify PsO patients at risk of developing PsA is still lacking (1).Objectives:To identify predictors of PsA development in PsO patients through a systematic literature review (SLR) and meta-analyses (MA).Methods:MEDLINE, EMBASE and COCHRANE databases were searched (up to February 22nd, 2020). The PICO framework (population = PsO patients; intervention = clinical, environmental, imaging and genetic features; comparator = not applicable; outcome = PsA development) was used to design searches and define the eligibility of studies for inclusion. The MA focuses on 3 major features as possible predictors: i) PsO skin and nail involvement; ii) musculoskeletal (MSK) complaints; iii) inflammation and structural damage detected by imaging (Table 1). The sample estimates of the relative risk were pooled only when the studies were homogeneous in terms of cohort of patients, follow-up, study design and metrics.Results:4698 articles were screened for eligibility, 110 underwent a full reading and 29 were finally included. Figure 1 shows the study flow-chart for article selection. Though pooling was judge not appropriate, 5/7 prospective studies significantly support a predictive value of PsA development in patients with severe PsO (n=174635). While the predictive value of nail involvement is not well defined (n=2202), the pooled estimate from two cohort studies (n=474) supports nail pitting as predictor of PsA (RR=2.14 [1.32; 3.46]). Moving to the MSK complaints, the risk of developing PsA is about two times greater in PsO with than without arthralgia (pooled RR: 2.15 [1.16, 3.99]) within 2 years. Lastly, PsO patients with inflammation or structural damage detected by imaging are nearly four times more likely to develop PsA within 1-2 years (pooled RR from 4 cohort studies (n=247): 3.72 [2.12; 6.51]) (Table 1). The incidence rate of PsA varies from 1.34 to 5.9/100 p-ys in PsO and from 10.9 to 12.5/100 p-ys in PsOAr.Table 1.Studies reporting the major features as possible predictors of PsA development.PsO skin – severityPsO nail involvementPsO nail lesionsVariablesRelative Risk [95%CI]Follow-upWilson, 2009PsO nail involvementHRadjusted: 2.24 [1.26; 3.98]13.1±8.8 ysFaustini, 2015PASI score + PsO nail involvement/σ= -0.18[-0.84; 0.48] RR: 0.95 [0.37; 2.47]1.2±0.2 ysEder, 2016PASI score PsO nail involvement Type of PsO nail lesionsHR (>20vsHRunadjusted: 1.36 [0.76; 2.45] HRunadjusted: 2.21 [1.24; 3.92]4.1±2.1 ysEder, 2017PASI score + Type of PsO nail lesionsHRunadjusted: 1.05 [1.01; 1.09] HRunadjusted: 1.98 [0.83; 4.74]3.8±2.1 ysLewinson, 2017PsO severity defined from medicationsHRadjusted (moderate/severe vs mild): 5.02 [4.18; 6.04]5.1 ysEgeberg, 2018PsO severity defined from medicationsRR (severe vs mild): 1.31 [1.18; 1.46]18 ysElnady, 2019PASI score + PsO nail Involvement/σ= 0.79[-0.37; 1.95] RR: 1.43 [0.38; 5.31]2 ysGreen, 2020PsO severity defined from medicationRR (severe vs mild): 2.79 [2.49; 3.13]5.8 ysMSK-complaintsVariablesIncident-PsA casesFollow-upFaustini, 2015ArthralgiaRR: 1.98 [0.75; 5.19]1.2±0.2 ysEder, 2017ArthralgiaHRadjusted: 2.59 [1.15; 5.88]3.8±2.1 ysZabotti, 2019ArthralgiaRR: 4.44 [0.54; 36.72]1.6±0.5 ysSimon D, 2020ArthralgiaRR: 2.04 [0.86; 4.86]2.4±1.5 ysSub-clinical inflammation or structural damage detected by imagingVariablesIncident-PsA casesFollow-upFaustini, 2015MRIRR: 2.10 [0.75; 5.90]1.2±0.2 ysElnady, 2019MSK-USRR: 5.38 [1.17; 24.63]2 ysZabotti, 2019MSK-USRR: 6.86 [0.83; 56.63]1.6±0.5 ysSimon D, 2020HR-pQCTRR: 4.32 [1.96; 9.55]2.3±1.4 ysConclusion:Arthralgia and inflammation and/or structural damage detected by imaging are predictive features, likely prodromal, of PsA development. PsO severity and nail pitting are clinical manifestations related to PsA development.Figure 1.References:[1]Zabotti A, et al. Curr Rheumatol Rep. 2020 May 16;22(6):24. doi: 10.1007/s11926-020-00891-x.Disclosure of Interests:Alen Zabotti Speakers bureau: UCB, Novartis, Janssen, Paid instructor for: Amgen, Consultant of: Janssen, Orazio De Lucia Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Garifallia Sakellariou Consultant of: AbbVie, Novartis, Alberto Batticciotto Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Gilberto Cincinelli: None declared, Ivan Giovannini: None declared, Luca Idolazzi Speakers bureau: Eli Lilly, UCB, Celgene, MSD, Abbvie, Novartis, Paid instructor for: UCB, Gabriella Maioli Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Ilaria Tinazzi Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Daniel Aletaha Speakers bureau: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Salvatore De Vita Consultant of: GSK, Roche, Grant/research support from: Not relevant for this type of study, Antonio Marchesoni Speakers bureau: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Josef S. Smolen Speakers bureau: Not relevant for this type of study, Consultant of: Not relevant for this type of study, Grant/research support from: Not relevant for this type of study, Annamaria Iagnocco Speakers bureau: not relevant for this type of study, Paid instructor for: not relevant for this type of study, Consultant of: not relevant for this type of study, Grant/research support from: not relevant for this type of study, Dennis McGonagle Speakers bureau: ABBVIE, CELGENE, PFIZER, MSD, NOVARTIS, JANSSEN, UCB, GILEAD, BMS, LILLY, Grant/research support from: ABBVIE, CELGENE, PFIZER, MSD, NOVARTIS, JANSSEN, UCB, GILEAD, BMS, LILLY, Roberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Galapagos, Gilead, Lilly, Pfizer, Roche, UCB, Sanofi, Fresenius Kabi, Samsung bioepis, MSD, Consultant of: Galapagos, Gilead, Lilly, Janssen, MSD

Background Agreement on how to identify psoriasis (PsO) patients at risk of developing psoriatic arthritis (PsA) is lacking. Objective To identify predictors, risk factors and incidence rate (IR) of PsA development in PsO patients through a systematic literature review (SLR) and meta-analyses (MA). Methods MEDLINE, Embase, and Cochrane databases were searched. Cohort studies were used to assess the predictors, while case–control studies for PsA risk factor determination. Results We screened 4698 articles for eligibility, and 110 underwent a full reading and 26 were finally included. Among skin and nail phenotypes, PsO severity and nail pitting were selected as predictors of PsA development. Furthermore, PsO patients with arthralgia (pooled RR 2.15 [1.16; 3.99]) and/or with imaging-MSK inflammation (pooled RR 3.72 [2.12; 6.51]) were at high risk of PsA. Higher categories of BMI and a family history of PsA were other predictors. In outpatient-based cohort studies, the IR of PsA per 100 patient-years varied from 1.34 to 17.4. Limitations Despite the strength of the overall results, the heterogeneity and the number of the cohort studies could be considered a limitation. Conclusions This study provides a tentative profile of the PsO patient at risk of PsA and will help the design of PsA prevention trials. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00378-w.

The management of a child with juvenile idiopathic arthritis (JIA) requires a combination of pharmacological, physical, and psychosocial therapies in order to induce disease remission, by controlling articular and systemic inflammation. This review aims to provide a comprehensive discussion on the biological therapies currently in use in the treatment of JIA referring to existing recommendations and clinical evidence. We also discuss on the emerging biological drugs actually under consideration.Recent findings on immunological mechanisms involved in the pathogenesis of the disease allowed us to identify several specific targets for biologic therapies. A systematic literature review was conducted between January 1997 and January 2020 on PubMed including national and international guidelines and recommendations, trials and case-control studies.There is now a plethora of therapies that are directed against variable targets, and the physician has to choose the most appropriate available medication in order to achieve early and sustained remission with as few side effects as possible. Research is advancing very fast in order to be more and more specific in suppressing inflammatory pathways without harming natural defenses. Finally, pharmacoeconomic considerations will also be very important to deal with, considering the high cost of most of these molecules.

Antiphospholipid syndrome (APS) is an acquired prothrombotic condition characterized by vascular thrombosis and/or obstetric complications, in the persistent positivity of circulating antiphospholipid antibodies (aPLs). The clinical spectrum of manifestations associated with aPL positivity is progressively expanding, including the description of several lung manifestations. The most common pulmonary involvement related to aPL positivity is pulmonary embolism (PE), which has been reported to occur in 14.1% of APS patients during disease course. PE acknowledges a purely thrombotic etiology and thus might be accounted as a criterion for APS, making imperative to test aPL in young subjects with unprovoked PE. Pulmonary hypertension (PH) can manifest in APS patients, being the second most common lung complication of the syndrome, with a prevalence ranging between 1.8 and 3.5%. aPL-positive patients might present PH following a PE, might develop pulmonary arterial hypertension associated with connective tissue disease, or might present pulmonary venous hypertension due to Libman–Sacks endocarditis. Additional lung manifestations, such as diffuse alveolar hemorrhage, acute respiratory distress syndrome, and pulmonary fibrosis, are rarely described in APS patients; it is still not clear whether in these settings aPLs exert a pathogenic role or is a mere epiphenomenon. Hereby we discuss impact, clinical presentation, histopathologic findings, etiology, and treatment of each aPL-associated lung manifestation.

Background:Emerging observational data have shown that rheumatic patients seem not to be more susceptible to SARS-CoV-2 infection neither to worse outcomes. However, the true prevalence of COVID19 is still unknown due to the high proportion of subclinical infection. In this scenario, measuring the seroprevalence of SARS-CoV-2 may be crucial to improve the knowledge about the impact of COVID19 in rheumatic patients.Objectives:To estimate in a COVID19 high-endemic area (Lombardy, Italy) the prevalence of anti-SARS-CoV-2 antibodies in a large cohort of patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) treated with biologic (b-) or targeted synthetic (ts-) disease modifying drugs (DMARDs).Methods:A seroprevalence cross-sectional study was conducted in the period between 4th May and 16th June 2020, including patients with confirmed RA or SpA treated with b- or tsDMARDs. Patients were tested for anti-SARS-CoV-2 IgG, IgM and IgA antibodies against main viral antigens (nucleoprotein [N], spike 1 [S1], receptor-binding domain [RBD]) using ELISA. These data were compared with those observed in the healthy population in the same period and region. Patients also answered a questionnaire on history of symptoms consistent with COVID19, risk factors and comorbidities. Serological response to RBD was evaluated according to symptom severity (asymptomatic, minor, or major [respiratory and fever >37.5°C] symptoms).Results:The study population included 300 patients (62% females, mean age 53 years, 20% over 65 years old) diagnosed with RA (56%), psoriatic arthritis (23%), or ankylosing spondylitis (21%), treated with anti-TNF (57%), abatacept (20%), anti-IL6 (11%), or JAK inhibitors (5%). Four patients (1.3%) referred a prior diagnosis of COVID19 defined by nasopharyngeal swab. Immunoglobulin titers were evaluated resulting in 9%, 13.6%, and 13.3% positive patients for IgG, IgM and IgA, respectively (Table 1), with no significant difference to the healthy population. Among seropositive patients, 55.3% were asymptomatic, 16% had minor and 19.6% major symptoms, 7.1% were hospitalized. No deaths or admission to intensive care units occurred. IgM, IgG and IgA titers to RBD were higher in patients with both minor and major symptoms compared with asymptomatic ones (Figure 1). No differences were found between seronegative and seropositive patients in relation to age, sex, rheumatic diagnosis, and treatments with b- or tsDMARDs. A relative lower risk of seropositivity was observed in patients receiving concomitant methotrexate (RR 0.49, 95% CI 0.25-0.94; p 0.04), while an increased risk was associated with obesity (RR 2.33, 95% CI 1.26-3.79; p 0.019) and presence of at least 2 comorbidities (RR 1.94, 95% CI 1.11-3.15; p 0.037). Corticosteroids use was numerically more frequent in seropositive than seronegative patients (18% vs 14%).Conclusion:This study confirms that, even in a cohort of rheumatic patients, the spread of SARS-CoV-2 infection is much greater than that observed by capturing only swab-diagnosed COVID19 cases. The underlying rheumatic disease and ongoing therapy with b/ts-DMARDs do not seem to impact SARS-CoV-2 antibody positivity, which conversely seems to be proportional to the intensity of COVID19 symptoms and less frequent in patients receiving concomitant methotrexate. The project was co-financed by Lombardy Region 2014-2020 Regional Operational Programme under the European Regional Development Fund.Table 1.Prevalence of specific anti-SARS-CoV-2 antibodies.AntibodiesPosivite(n)Seroprevalence (%)(95% CI)IgG279%(6.2 – 12.7)IgG anti-N268.6%(5.9 – 12.3)IgG anti-RBD206.6%(4.3 – 10)IgG anti-S1186%(3.8 – 9.2)IgM4113.6%(10.2 – 18)IgM anti-N3511.6%(8.5 – 15.7)IgM anti-RBD258.3%(5.7 – 12)IgA4013.3%(9.9 – 17.6)IgA anti-N3712.3%(9.0 – 16.5)IgA anti-RBD258.3%(5.7 – 12)IgG+IgM237.6%(5.1 – 11.2)IgG+IgM+IgA227.3%(4.9 – 10.5)IgG+IgA248%(5.4 – 11.6)IgG/IgM/IgA5618.6%(14.6 – 23.4)Figure 1.Antibody levels (S/Co) against SARS-CoV-2 RBD.Disclosure of Interests:None declared.